4.1 Superficial Punctate Keratopathy
Symptoms
Pain, photophobia, red eye, foreign body sensation, and mildly decreased vision.
Signs
(See Figure 4.1.1.)
FIGURE 4.1.1 Superficial punctate keratopathy stained with fluorescein.
Critical. Pinpoint locations of corneal epithelial cell damage or breakdown that stain with fluorescein. May be confluent if severe. Staining pattern may allude to etiology. Pain is relieved by the instillation of anesthetic drops. Also referred to as punctate epithelial erosions.
NOTE: Relief of pain with the instillation of anesthetic drops (e.g., proparacaine) strongly suggests corneal epithelial disease as the etiology of pain. Although anesthetic drop instillation is an essential part of the ocular examination, patients should NEVER be prescribed topical anesthetic drops, and the clinician should ensure the patient does not take anesthetic drops from the office. When used chronically, these drops inhibit epithelial healing and may cause corneal ulceration.
Other. Conjunctival injection and watery discharge.
Etiology
Superficial punctate keratopathy (SPK) is nonspecific but is most commonly seen in the following disorders, which may be associated with a specific staining pattern:
• Superior staining
• Contact lens-related disorder (e.g., chemical toxicity, tight lens syndrome, contact lens overwear syndrome, giant papillary conjunctivitis). See 4.20, Contact Lens-Related Problems.
• Foreign body under the upper eyelid: Typically linear SPK, fine epithelial defects arranged vertically.
• Floppy eyelid syndrome: Extremely loose upper eyelids that evert easily. See 6.6, Floppy Eyelid Syndrome.
• Superior limbic keratoconjunctivitis (SLK): Superior bulbar conjunctival inflammation. See 5.4, Superior Limbic Keratoconjunctivitis.
• Vernal conjunctivitis: Atopy, large conjunctival papillae under the upper eyelid and/or limbus. See 5.1, Acute Conjunctivitis.
• Interpalpebral staining
• Dry eye syndrome: Poor tear lake, decreased tear break-up time, decreased Schirmer test. See 4.3, Dry Eye Syndrome.
• Neurotrophic keratopathy: Decreased corneal sensation. May progress to corneal ulceration. See 4.6, Neurotrophic Keratopathy.
• Ultraviolet burn/photokeratopathy: Often in welders or from sunlamps. See 4.7, Ultraviolet Keratopathy.
• Inferior staining
• Blepharitis: Erythema, telangiectasias, or crusting of the eyelid margins, meibomian gland dysfunction. See 5.8, Blepharitis/Meibomitis.
• Exposure keratopathy: Poor eyelid closure with failure of eyelids to cover the entire globe. See 4.5, Exposure Keratopathy.
• Topical drug toxicity (e.g., neomycin, gentamicin, trifluridine, atropine, as well as any drop with preservatives, including artificial tears, or any frequently used drop).
• Conjunctivitis: Discharge, conjunctival injection, and eyelids stuck together on awakening. See 5.1, Acute Conjunctivitis and 5.2, Chronic Conjunctivitis.
• Trichiasis/distichiasis: One or more eyelashes rubbing against the cornea (superior SPK if misdirected lashes from upper eyelid). See 6.5, Trichiasis.
• Entropion or ectropion: Eyelid margin turned in or out (superior SPK if upper eyelid abnormality). See 6.3, Ectropion and 6.4, Entropion.
• Other
• Trauma: SPK can occur from relatively mild trauma, such as chronic eye rubbing.
• Mild chemical injury: See 3.1, Chemical Burn.
• Thygeson superficial punctate keratitis: Bilateral, recurrent epithelial keratitis (raised epithelial staining lesions, not micro erosions) without conjunctival injection. See 4.8, Thygeson Superficial Punctate Keratitis.
Workup
1. History: Trauma? Contact lens wear? Eye drops? Discharge or eyelid matting? Chemical or ultraviolet light exposure? Snoring or sleep apnea? Time of day when worse?
2. Evaluate the cornea, eyelid margin, and tear film with fluorescein. Evert the upper and lower eyelids. Check eyelid closure, position, and laxity. Look for inward-growing or misdirected lashes.
3. Inspect contact lenses for fit (if still in the eye) and for the presence of deposits, sharp edges, and cracks.
NOTE: A soft contact lens should be removed before instillation of fluorescein.
Treatment
See the appropriate section to treat the underlying disorder. SPK is often treated nonspecifically as follows:
1. Noncontact lens wearer with a small amount of SPK
• Artificial tears q.i.d., preferably preservative-free.
• Can add a lubricating gel or ointment q.h.s.
2. Noncontact lens wearer with a large amount of SPK
• Preservative-free artificial tears q2h.
• Ophthalmic antibiotic ointment (e.g., bacitracin/polymyxin B or erythromycin q.i.d. for 3 to 5 days).
• Consider a cycloplegic drop (e.g., cyclopentolate 1% t.i.d.) for relief of pain and photophobia.
3. Contact lens wearer with a small amount of SPK
• Discontinue contact lens wear.
• Artificial tears q.i.d., preferably preservative-free.
• Can add a lubricating gel or ointment q.h.s.
4. Contact lens wearer with a large amount of SPK
• Discontinue contact lens wear.
• Antibiotic: Fluoroquinolone (e.g., ciprofloxacin, gatifloxacin, moxifloxacin, or besifloxacin) or aminoglycoside (e.g., tobramycin) drops four to six times per day as well as ophthalmic ointment q.h.s. (e.g., ciprofloxacin or bacitracin/polymyxin B). If confluent SPK, consider ophthalmic antibiotic ointment four to six times per day.
• Consider a cycloplegic drop (e.g., cyclopentolate 1% t.i.d.) for relief of pain and photophobia.
NOTE: DO NOT patch contact lens-related SPK or epithelial defects because they can quickly develop into severely infected ulcers.
Follow Up
1. Noncontact lens wearers with SPK are not seen again solely for the SPK unless the patient is a child or is unreliable. Reliable patients are told to return if their symptoms worsen or do not improve within 2 to 3 days. When underlying ocular disease is responsible for the SPK, follow up is in accordance with the guidelines for the underlying problem.
2. Contact lens wearers with a large amount of SPK are seen every day or two until significant improvement is demonstrated. Contact lenses are not to be worn until the condition clears. Antibiotics may be discontinued when the SPK resolves. The patient’s contact lens regimen (e.g., wearing time, cleaning routine) must be corrected or the contact lenses changed if either is thought to be responsible (see 4.20, Contact Lens-Related Problems). Contact lens wearers with a small amount of SPK are rechecked in several days to 1 week, depending on symptoms and degree of SPK.
NOTE: Contact lens wearers should be advised not to wear contacts when their eyes feel irritated.
4.2 Recurrent Corneal Erosion
Symptoms
Recurrent attacks of acute ocular pain, photophobia, foreign body sensation, and tearing. The pain may awaken patients from sleep or occur immediately upon eye opening. There is often a history of prior corneal abrasion in the involved eye.
Signs
Critical. Localized irregularity and mobility of the corneal epithelium (fluorescein dye may outline the area with negative or positive staining) or a corneal abrasion. Epithelial changes may resolve within hours of the onset of symptoms so abnormalities may be subtle or absent when the patient is examined.
Other. Corneal epithelial dots or microcysts, a fingerprint pattern, or map-like lines may be seen in both eyes if epithelial basement membrane (map-dot-fingerprint) dystrophy is present. These findings may also be seen unilaterally and focally in any eye that has recurrent erosions.
Etiology
Damage to the corneal epithelium or epithelial basement membrane from one of the following:
• Anterior corneal dystrophy: Epithelial basement membrane (most common), Reis-Bucklers, Thiel-Behnke, and Meesmann dystrophies.
• Previous traumatic corneal abrasion: Injury may have been years before the current presentation.
• Stromal corneal dystrophy: Lattice, granular, and macular dystrophies.
• Corneal degeneration: Band keratopathy, Salzmann nodular degeneration.
• Keratorefractive, corneal transplant, cataract surgery, or any surgery in which the corneal epithelium is removed (either therapeutically or for visualization).
Workup
1. History: History of a corneal abrasion? Ocular surgery? Family history (corneal dystrophy)?
2. Slit lamp examination with fluorescein staining of both the eyes (visualization of abnormal basement membrane lines may be enhanced by instilling fluorescein and looking for areas of rapid tear break-up, referred to as “negative staining”).
Treatment
1. Acute episode: Cycloplegic drop (e.g., cyclopentolate 1%) t.i.d. and ophthalmic antibiotic ointment (e.g., erythromycin, bacitracin) four to six times daily. Can use 5% sodium chloride ointment q.i.d. in addition to antibiotic ointment. If the epithelial defect is large, a bandage soft contact lens and topical antibiotic drops q.i.d. may be placed. Oral analgesics as needed.
2. Never prescribe topical anesthetic drops.
3. After epithelial healing is complete, artificial tears at least q.i.d. and artificial tear ointment q.h.s. for at least 3 to 6 months, or 5% sodium chloride drops q.i.d. and 5% sodium chloride ointment q.h.s. for at least 3 to 6 months.
4. If the corneal epithelium is loose or heaped and is not healing, consider epithelial debridement. Apply a topical anesthetic (e.g., proparacaine) and use a sterile cotton-tipped applicator or cellulose sponge (e.g., Weck-Cel surgical spear) to gently remove all of the loose epithelium.
5. For erosions not responsive to the preceding treatment, consider the following:
• Prophylactic medical treatment with 5% sodium chloride ointment q.h.s.
• Oral doxycycline (matrix metalloproteinase inhibitor) 50 mg b.i.d. with or without a short course of topical steroid drops (e.g., fluorometholone 0.1% b.i.d. to q.i.d. for 2 to 4 weeks).
• Extended-wear bandage soft contact lens for 3 to 6 months with a topical antibiotic and routine changing of the lens.
• Anterior stromal puncture can be applied to localized erosions, such as in traumatic cases, outside the visual axis in cooperative patients. It can be performed with or without an intact epithelium. Stromal puncture may be applied manually with a needle at the slit lamp or with Nd:YAG laser. This treatment may cause small permanent corneal scars that are usually of no visual significance if outside of the visual axis.
• Epithelial debridement with diamond burr polishing of Bowman membrane or excimer laser phototherapeutic keratectomy (PTK). Both are highly effective (up to 90%) for large areas of epithelial irregularity and lesions in the visual axis. Excimer laser ablation of the superficial stroma can be particularly helpful if repeated erosions have created anterior stromal haze or scarring. It is important to keep in mind that excimer laser PTK can lead to a hyperopic refractive shift after treatment if a deep ablation is performed.
Follow Up
Every 1 to 2 days until the epithelium has healed, and then every 1 to 3 months, depending on the severity and frequency of the episodes. It is important to educate patients that persistent use of lubricating ointment (5% sodium chloride or tear ointment) for 3 to 6 months following the initial healing process reduces the chance of recurrence.
4.3 Dry Eye Syndrome
Symptoms
Burning, dryness, foreign body sensation, mildly to moderately decreased vision, and excess tearing. Often exacerbated by smoke, wind, heat, low humidity, or prolonged use of the eye (e.g., when working on a computer that results in decreased blink rate). Usually bilateral and chronic (although patients sometimes are seen with recent onset in one eye). Discomfort often out of proportion to clinical signs.
Signs
Critical
• Scanty or irregular tear meniscus seen at the inferior eyelid margin: The normal meniscus should be at least 0.5 mm in height and have a convex shape.
• Decreased tear break-up time (measured from a blink to the appearance of a tear film defect, by using fluorescein stain): Less than 10 seconds indicates tear film instability.
NOTE: Tear film defects must be randomly located, as isolated areas of repeated early tear break-up may indicate a focal corneal surface irregularity.
Other. Punctate corneal or conjunctival fluorescein, rose bengal, or lissamine green staining; usually inferiorly or in the interpalpebral area. Excess mucus or debris in the tear film and filaments on the cornea may be found in severe cases.
Differential Diagnosis
See 4.1, Superficial Punctate Keratopathy.
Etiology
• Idiopathic: Commonly found in menopausal and postmenopausal women.
• Evaporative: Lipid layer tear deficiency; often associated with blepharitis or meibomian gland dysfunction. Symptoms may be worse in the morning with complaints of visual blurring upon waking.
• Aqueous deficient: Aqueous layer tear deficiency; aqueous production decreases with age. Symptoms frequently worse later in the day or after extensive use of the eyes.
• Combination: Evaporative and aqueous deficiency often occur together. May also include a mucin layer tear deficiency.
• Lifestyle related: Arid climate, allergen exposure, smoking, extended periods of reading/computer work/television viewing.
• Connective tissue diseases (e.g., Sjogren syndrome, rheumatoid arthritis, granulomatosis with polyangiitis [GPA, formerly Wegener granulomatosis], systemic lupus erythematosus).
• Conjunctival scarring (e.g., mucous membrane pemphigoid, Stevens-Johnson syndrome, trachoma, chemical burn).
• Drugs (e.g., oral contraceptives, anticholinergics, antihistamines, antiarrhythmics, antipsychotics, antispasmodics, tricyclic antidepressants, beta blockers, diuretics, retinoids, selective serotonin reuptake inhibitors, chemotherapy).
• Infiltration of the lacrimal glands (e.g., sarcoidosis, tumor).
• Postradiation fibrosis of the lacrimal glands.
• Vitamin A deficiency: Usually from malnutrition, intestinal malabsorption, or bariatric surgery. See 13.7, Vitamin A Deficiency.
• After cataract surgery or corneal refractive surgery such as limbal relaxing incisions, photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE): Likely secondary to disruption of corneal nerves and interference with normal reflex tearing. The size and location of the incision or flap may be correlated to the degree of the patient’s symptoms.
Workup
1. History and external examination to detect underlying etiology.
2. Slit lamp examination with fluorescein stain to evaluate the ocular surface and tear break-up time. May also use rose bengal or lissamine green stain to examine the cornea and conjunctiva. Tear meniscus is best evaluated prior to the instillation of eye drops.
3. Tear secretion testing: Technique: After drying the eyes of excess tears, Schirmer filter paper is placed at the junction of the middle and lateral one-third of the lower eyelid in each eye for 5 minutes. Eyes are to remain open with normal blinking.
• Unanesthetized: Measures basal and reflex tearing. Normal is wetting of at least 15 mm in 5 minutes.
• Anesthetized: Measures basal tearing only. Topical anesthetic (e.g., proparacaine) is applied before drying the eye and placing the filter paper. Abnormal is wetting of 5 mm or less in 5 minutes. Less than 10 mm may be considered borderline. We prefer the less irritating anesthetized method.
4. Other potentially helpful in-office tests include measurement of tear osmolarity and level of matrix metalloproteinase-9 (MMP-9); elevation of these factors suggests dryness and inadequate tear film. Tear lactoferrin can also be measured; low levels suggest aqueous deficient dry eye disease.
5. Consider screening for Sjogren syndrome especially if associated with dry mouth and systemic autoimmune-related symptoms.
Treatment
Mild Dry Eye
Artificial tears q.i.d., preferably preservative-free.
Moderate Dry Eye
1. Increase the frequency of artificial tear application up to q1-2h; use only preservative-free artificial tears.
2. Add a lubricating gel or ointment q.h.s.
3. Lifestyle modification (e.g., humidifiers and smoking cessation).
4. Cyclosporine 0.05% or 0.09% b.i.d. is effective for patients with chronic dry eye and decreased tears secondary to ocular inflammation. Cyclosporine often burns with application for the first several weeks and takes 1 to 3 months for significant clinical improvement. To hasten improvement and lessen side effects, consider treating patients concomitantly with a mild topical steroid drop (e.g., loteprednol 0.5%, fluorometholone 0.1%, or fluorometholone acetate 0.1%) b.i.d. to q.i.d. for 1 month while beginning cyclosporine therapy.
5. Lifitegrast 5% b.i.d. is effective for the signs and symptoms of dry eye disease. Lifitegrast may burn on instillation, may cause blurred vision for several minutes, and may leave a metallic taste in the throat. Symptomatic improvement is often noted within 2 weeks of starting lifitegrast, but can take up to 3 months.
6. If these measures are inadequate or impractical, consider punctal occlusion. Use collagen inserts (temporary) or silicone or acrylic plugs (reversible). Be sure that any inflammatory component including blepharitis is treated prior to punctal occlusion.
Severe Dry Eye
1. Cyclosporine 0.05% or 0.09% or lifitegrast 5% as described earlier.
2. Punctal occlusion, as described earlier (both lower and upper puncta if necessary), and preservative-free artificial tears up to q1-2h. Consider permanent occlusion by thermal cautery if plugs continually fall out.
3. Add lubricating gel to ointment b.i.d. to q.i.d. p.r.n.
4. Moisture chamber (plastic film sealed at orbital rim) or glasses/goggles with lubrication at night.
5. If mucus strands or filaments are present, remove with forceps and consider 10% acetylcysteine q.i.d.
6. Other therapies may include oral flaxseed oil, oral omega-3 fatty acids, autologous serum tears, topical vitamin A, bandage soft contact lens, or a scleral lens.
7. Consider a small permanent lateral tarsorrhaphy if all of the previous measures fail. A temporary adhesive tape tarsorrhaphy (to tape the lateral one-third of the eyelid closed) can also be used, pending a surgical tarsorrhaphy.
NOTE:
1. In addition to treating the dry eye, treatment for contributing disorders (e.g., blepharitis, exposure keratopathy) should be instituted if these conditions are present.
2. Always use preservative-free artificial tears if dosing is more frequent than q.i.d. to prevent preservative toxicity.
3. If the history suggests the presence of a connective tissue disease (e.g., history of arthritic pain, dry mouth), consider blood testing for these conditions and/or referral to an internist or rheumatologist for further evaluation.
Follow Up
In days to months, depending on the severity of symptoms and degree of dryness. Anyone with severe dry eyes caused by an underlying chronic systemic disease (e.g., rheumatoid arthritis, Sjogren syndrome, sarcoidosis, ocular pemphigoid) may need to be monitored more closely.
NOTE: Patients with significant dry eye should be discouraged from contact lens wear and corneal refractive surgery such as PRK, LASIK, and SMILE. However, daily disposable soft contact lenses can be successful if fit loosely and combined with aggressive preservative-free lubrication and plugs, if needed.
Patients with Sjogren syndrome have an increased incidence of lymphoma and mucous membrane problems and may require internal medicine, rheumatologic, dental, and gynecologic follow up.
4.4 Filamentary Keratopathy
Symptoms
Moderate-to-severe pain, red eye, foreign body sensation, tearing, and photophobia.
Signs
Critical. Short fluorescein-staining strands of degenerated epithelial cells surrounding a mucus core adherent to the anterior surface of cornea.
Other. Conjunctival injection, poor tear film, and punctate epithelial defects.
Etiology
• Severe ocular dryness: Most common cause. See 4.3, Dry Eye Syndrome.
• SLK: Filaments are located in the superior cornea, in association with superior conjunctival injection, superior punctate fluorescein staining, and superior corneal pannus. See 5.4, Superior Limbic Keratoconjunctivitis.
• Recurrent corneal erosions: Recurrent spontaneous corneal abrasions often occurring upon waking. See 4.2, Recurrent Corneal Erosion.
• Adjacent to irregular corneal surface (e.g., postoperative, near a surgical wound).
• Patching (e.g., postoperative, after corneal abrasions) or ptosis.
• Neurotrophic keratopathy: See 4.6, Neurotrophic Keratopathy.
Workup
1. History, especially for the previously mentioned conditions.
2. Slit lamp examination with fluorescein staining.
Treatment
1. Treat the underlying condition.
2. Consider debridement of the filaments. After applying topical anesthetic (e.g., proparacaine), gently remove filaments at their base with fine forceps or a cotton-tipped applicator. This gives temporary relief, but the filaments will recur if the underlying etiology is not treated.
3. Treatment with one or more of the following regimens:
• Preservative-free artificial tears six to eight times per day and lubricating gel or ointment q.h.s.
• Punctal occlusion.
• Acetylcysteine 10% q.i.d.
NOTE: Acetylcysteine is not commercially available as a drop but can be made by a compounding pharmacy.
4. If the symptoms are severe or treatment fails, then consider a bandage soft contact lens (unless the patient has severe dry eyes as underlying etiology). Extended-wear bandage soft contact lenses may need to be worn for weeks to months. Concomitant prophylactic or therapeutic topical antibiotics such as fluoroquinolone drops are typically given, especially if associated with a corneal abrasion/epithelial defect. A scleral lens may be helpful in recalcitrant cases.
Follow Up
In 1 to 4 weeks. If the condition is not improved, consider repeating the filament removal or applying a bandage soft contact lens. Longterm lubrication must be maintained if the underlying condition cannot be eliminated.
4.5 Exposure Keratopathy
Symptoms
Ocular irritation, burning, foreign body sensation, tearing, and redness of one or both eyes. Usually worse in the morning.
Signs
Critical. Inadequate blinking or closure of the eyelids, leading to corneal drying. Punctate epithelial defects are found in the lower one- third of the cornea or as a horizontal band in the region of the palpebral fissure (see Figure 4.5.1).
FIGURE 4.5.1 Exposure keratopathy with fluorescein.
Other. Conjunctival injection and chemosis, corneal erosion, infiltrate or ulcer, eyelid deformity, or abnormal eyelid closure.
Etiology
• Seventh cranial nerve palsy: Orbicularis oculi weakness (e.g., Bell palsy). See 10.9, Isolated Seventh Cranial Nerve Palsy.
• Sedation or altered mental status.
• Eyelid deformity (e.g., ectropion or eyelid scarring from trauma, eyelid surgery such as excisional procedure, chemical burn, or herpes zoster ophthalmicus).
• Nocturnal lagophthalmos: Failure to close the eyes during sleep.
• Proptosis (e.g., due to an orbital process such as thyroid eye disease). See 7.1, Orbital Disease.
• After ptosis repair or blepharoplasty procedures.
• Floppy eyelid syndrome. See 6.6, Floppy Eyelid Syndrome.
• Poor blink (e.g., Parkinson disease, neurotrophic cornea).
Workup
1. History: Previous Bell palsy or eyelid surgery? Thyroid disease?
2. Evaluate eyelid closure and corneal exposure. Ask the patient to close his or her eyes gently (as if sleeping). Assess Bell phenomenon (the patient is asked to close the eyelids forcefully against resistance; abnormal when the eyes do not rotate upward). Check for eyelid laxity.
3. Check corneal sensation before instillation of anesthetic drops. If sensation is decreased, there is greater risk for corneal complications and the patient may need further management for neurotrophic keratopathy. See 4.6, Neurotrophic Keratopathy.
4. Slit lamp examination: Evaluate the tear film and corneal integrity with fluorescein dye. Look for signs of secondary infection (e.g., corneal infiltrate, anterior chamber reaction, severe conjunctival injection).
5. Investigate any underlying disorder (e.g., etiology of seventh cranial nerve palsy).
Treatment
Prevention is critical. All patients who are sedated or obtunded are at risk for exposure keratopathy and should receive lubrication according to the following recommendations.
In the presence of secondary corneal infection, see 4.11, Bacterial Keratitis.
1. Correct any underlying disorder.
2. Preservative-free artificial tears q2-6h. Punctal occlusion with plugs may also be considered.
3. Lubricating ointment q.h.s. to q2h.
4. Consider eyelid taping or patching q.h.s. to maintain the eyelids in the closed position. If severe, consider taping the lateral one- third of the eyelids closed (leaving the visual axis open) during the day. Taping is rarely definitive but may be tried when the underlying disorder is thought to be temporary.
5. A potential in-office procedure includes placement of selfretained amniotic membrane tissue (e.g., sterilized, dehydrated amniotic membrane covered by a bandage soft contact lens or frozen, specialized plastic ring-mounted amniotic membrane such as Prokera).
6. When maximal medical therapy fails to prevent progressive corneal deterioration, one of the following surgical procedures may be beneficial:
• Partial tarsorrhaphy (eyelids sewn or glued together).
• Eyelid reconstruction (e.g., for ectropion).
• Eyelid gold or platinum weight implant (e.g., for seventh cranial nerve palsy).
• Orbital decompression (e.g., for proptosis).
• Conjunctival flap or sutured/glued amniotic membrane graft (for severe corneal decompensation if the preceding fail).
Follow Up
Reevaluate every 1 to 2 days in the presence of corneal ulceration. Less frequent examinations (e.g., in weeks to months) are required for less severe corneal disease.
4.6 Neurotrophic Keratopathy
Symptoms
Foggy or blurry vision, red eye, and swollen eyelid. Foreign body sensation or pain is less than expected for the degree of ocular signs.
Signs
Critical. Loss of corneal sensation, interpalpebral SPK, or epithelial defects with fluorescein staining.
Other
• Early: Perilimbal injection and interpalpebral corneal punctate epithelial defects or a frank nonhealing epithelial defect with rolled edges, stromal edema, and Descemet folds. Typically located inferior to the visual axis.
• Late: Corneal ulcer usually without infectious infiltrate, although concomitant infectious keratitis may occur. The ulcer often has a gray, heaped-up epithelial border, tends to be in the lower one- half of the cornea, and is horizontally oval. Progressive thinning may occur rapidly and lead to a descemetocele (corneal stromal loss down to Descemet membrane) or corneal perforation.
Differential Diagnosis
See 4.1. Superficial Punctate Keratopathy.
Etiology
Occurs in eyes with diminished or absent corneal sensation. Denervation causes the corneal epithelium and tear film to become abnormal and unstable. May occur with any of the following conditions:
• Postinfection with varicella zoster virus (VZV) or herpes simplex virus (HSV).
• Following ocular surgery, particularly after corneal incisional or laser surgery (e.g., keratoplasty, LASIK, SMILE, PRK).
• Tumor (especially an acoustic neuroma, where both the fifth and seventh cranial nerves may be affected) or any neurologic insult/disease of the fifth cranial nerve (e.g., brainstem stroke, trauma, multiple sclerosis, Riley-Day syndrome).
• Chronic contact lens wear.
• Diabetic neuropathy.
• Extensive panretinal photocoagulation: May damage the long ciliary nerves (these patients often have concurrent diabetic neuropathy).
• Complication of trigeminal nerve or dental surgery.
• Complication of radiation therapy to the eye or an adnexal structure.
• Chronic topical medications (e.g., nonsteroidal anti-inflammatory agents, timolol).
• Topical anesthetic abuse.
• Crack keratopathy: Often bilateral. Take careful history for crack cocaine smoking or potential exposure. Often helpful to admit patient and remove them from their environment.
• Chemical injury or exposure to hydrogen sulfide or carbon disulfide (used in manufacturing).
Workup
1. History: Previous episodes of a red and painful eye? Prior herpes infection, cold sores, or shingles rash around the eye and/or forehead? Diabetes? History of irradiation, stroke, or hearing problem? Previous refractive procedure or other eye surgery? Chemical exposure? Smoking history? Topical medications?
2. Prior to anesthetic instillation, test corneal sensation bilaterally with a sterile cotton wisp.
3. Slit lamp examination with fluorescein staining of cornea and conjunctiva.
4. Check the skin for herpetic lesions or scars from a previous herpes zoster infection.
5. Look for signs of a corneal exposure problem (e.g., inability to close an eyelid, seventh cranial nerve palsy, absent Bell phenomenon).
6. If suspicious of a central nervous system lesion, obtain a computed tomography (CT) or magnetic resonance imaging (MRI) of the brain.
Treatment
Eyes with neurotrophic keratopathy have impaired healing ability. If not treated in a timely manner, an epithelial defect in an eye with this condition may progress to stromal lysis and possibly perforation.
1. Mild-to-moderate punctate epithelial staining: Preservative-free artificial tears q2-4h and artificial tear ointment q.h.s. Consider punctal plugs and q.h.s. patching.
2. Small corneal epithelial defect: Antibiotic ointment (e.g., erythromycin or bacitracin q.i.d. to q1-2h) until resolved. Usually requires prolonged artificial tear treatment, as described above. Consider placement of a bandage soft contact lens with prophylactic antibiotic drops (e.g., ofloxacin or moxifloxacin t.i.d. to q.i.d.) along with frequent preservative-free artificial tears (q1- 2h) as an alternative to antibiotic ointment.
3. Corneal ulcer: See 4.11, Bacterial Keratitis, for the workup and treatment of a secondarily infected ulceration. Treatment options for a neurotrophic ulceration include antibiotic ointment q2h, tarsorrhaphy, self-retained amniotic membrane tissue, sutured/glued amniotic membrane graft, or conjunctival flap (See treatment in 4.5, Exposure Keratopathy). Oral doxycycline (50 to 100 mg b.i.d.), a collagenase inhibitor, may slow stromal lysis. Systemic ascorbic acid (e.g., vitamin C 1 to 2 g daily) may promote collagen synthesis and reduce the level of ulceration. Autologous serum, albumin, or umbilical cord serum eye drops may also be beneficial.
4. Cenegermin-bkbj 0.002%, recombinant human nerve growth factor, is the first Food and Drug Administration-approved drug for neurotrophic keratopathy and is very effective in many eyes. It is an ophthalmic solution that is applied six times daily for an 8-week treatment course.
5. A scleral lens (e.g., prosthetic replacement of the ocular surface ecosystem [PROSE]) may be helpful long term.
6. Cornea neurotization is a complex surgical procedure whereby nerves are redirected, or more commonly grafted, to reestablish corneal sensation.
NOTE: Patients with neurotrophic keratopathy and corneal exposure often do not respond to treatment unless a tarsorrhaphy is performed. A temporary adhesive tape tarsorrhaphy (the lateral one- third of the eyelid is taped closed) may be beneficial, pending more definitive treatment.
Follow Up
1. Mild-to-moderate epithelial staining: In 3 to 14 days.
2. Corneal epithelial defect: Every 1 to 3 days until improvement demonstrated and then every 5 to 7 days until resolved.
3. Corneal ulcer: Daily until significant improvement is demonstrated. Hospitalization may be required for severe ulcers, especially if there is concern that patient may not be properly administering medication in the setting of decreased corneal sensation or the patient may be abusing anesthetic drops (see 4.11, Bacterial Keratitis).
4.7 Ultraviolet Keratopathy
Symptoms
Moderate-to-severe ocular pain, foreign body sensation, red eye, tearing, photophobia, and blurred vision; often a history of welding or using a sunlamp without adequate protective eyewear. Symptoms typically worsen 6 to 12 hours after the exposure. Usually bilateral.
Signs
Critical. Dense, confluent punctate epithelial defects in an interpalpebral distribution highlighted with fluorescein staining.
Other. Conjunctival injection, mild-to-moderate eyelid edema, mild- to-no corneal edema, relatively miotic pupils that react sluggishly, and mild anterior chamber reaction.
Differential Diagnosis
• Toxic epithelial keratopathy from exposure to a chemical (e.g., solvents, alcohol) or drug (e.g., neomycin, gentamicin, antiviral agents, anesthetic drops).
• Thermal burn/keratopathy: Often from contact with curling iron, boiling fluid, fire ember, or flame. Injury usually limited to corneal epithelium; may have marked superficial corneal opacification or eschar. Treat with possible debridement of involved area and then as for corneal abrasion. See 3.2, Corneal Abrasion.
• See 4.1, Superficial Punctate Keratopathy.
Workup
1. History: Welding? Sunlamp use? Topical medications? Chemical exposure? Prior episodes? Use of protective eyewear?
2. Slit lamp examination: Use fluorescein stain. Evert the eyelids to search for a foreign body.
3. If chemical exposure suspected, check pH of tear lake in upper and lower conjunctival fornices. If not neutral (6.8 to 7.5), treat as chemical burn. See 3.1, Chemical Burn.
Treatment
1. Cycloplegic drop (e.g., cyclopentolate 1%).
2. Antibiotic ointment (e.g., erythromycin or bacitracin) four to eight times per day.
3. Oral analgesics as needed.
NOTE: A bandage soft contact lens with prophylactic topical broad-spectrum antibiotic drop may be used in place of frequent antibiotic ointment.
Follow Up
1. If a bandage soft contact lens was placed, the patient is seen in 1 to 2 days.
2. Reliable patients without a bandage soft contact lens are asked to assess their own symptoms after 24 hours.
• If much improved, the patient continues with topical antibiotics (e.g., erythromycin or bacitracin ointment q.i.d.).
• If still significantly symptomatic, reevaluate. If significant punctate staining is present, retreat with a cycloplegic, antibiotic as discussed previously.
3. Unreliable patients or those with an unclear etiology should not have a bandage soft contact lens placed. Such patients should be reexamined in 1 to 2 days.
4.8 Thygeson Superficial Punctate Keratitis
Symptoms
Mild-to-moderate foreign body sensation, photophobia, and tearing. No history of red eye. Usually bilateral with a chronic course of exacerbations and remissions, but may not be active in both eyes at the same time.
Signs
Critical. Coarse stellate gray-white corneal epithelial opacities that are often central, slightly elevated, and stain lightly with fluorescein. Underlying subepithelial infiltrates may be present (see Figure 4.8.1).
FIGURE 4.8.1 Thygeson superficial punctate keratitis.
Other. Minimal-to-no conjunctival injection, corneal edema, anterior chamber reaction, or eyelid abnormalities.
Differential Diagnosis
See 4.1, Superficial Punctate Keratopathy.
Treatment
Mild
1. Artificial tears, preferably preservative-free, four to eight times per day.
2. Artificial tear ointment q.h.s.
NOTE: Treatment is based more on patient symptoms than corneal appearance.
Moderate to Severe
1. Mild topical steroid (e.g., fluorometholone 0.1%, fluorometholone acetate 0.1%, or loteprednol 0.2% to 0.5% q.i.d.) for 1 to 4 weeks, followed by a very slow taper. May need prolonged low-dose topical steroid therapy.
2. If no improvement with topical steroids, a bandage soft contact lens can be tried.
3. Cyclosporine 0.05% or 0.09% drops daily to q.i.d. or lifitegrast 5% b.i.d. may be an alternative or adjunctive treatment, especially in patients with side effects from steroids.
Follow Up
Weekly during an exacerbation and then every 3 to 6 months. Patients receiving topical steroids require intraocular pressure (IOP) checks every 4 to 12 weeks.
4.9 Pterygium/Pinguecula
Symptoms
Irritation, redness, and decreased vision; may be asymptomatic
FIGURE 4.9.1 Pterygium.
Signs
Critical. One of the following, almost always located at the 3-o'clock or 9-o’clock perilimbal position.
• Pterygium: Wing-shaped fold of fibrovascular tissue arising from the interpalpebral conjunctiva and extending onto the cornea. There is no associated thinning of the cornea below these lesions. Usually nasal in location (see Figure 4.9.1).
• Pinguecula: Yellow-white, flat, or slightly raised conjunctival lesion, usually in the interpalpebral fissure adjacent to the limbus, but not involving the cornea.
Other. Either lesion may be highly vascularized and injected or may be associated with SPK or delle (thinning of the adjacent cornea secondary to drying). An iron line (Stocker line) may be seen in the cornea just beyond the leading edge of a pterygium.
Differential Diagnosis
• Conjunctival intraepithelial neoplasia (CIN): Unilateral papillomatous jelly-like, velvety, or leukoplakic (white) mass, often elevated and vascularized. May not be in a wing-shaped configuration and not necessarily in the typical 3-o’clock or 9- o’clock location of a pterygium or pinguecula. See 5.12, Conjunctival Tumors.
NOTE: Atypical pterygia require biopsy to rule out CIN or melanoma.
• Limbal dermoid: Congenital rounded white lesion, usually at the inferotemporal limbus. See 5.12, Conjunctival Tumors.
• Other conjunctival tumors (e.g., papilloma, nevus, melanoma). See 5.12, Conjunctival Tumors.
• Pseudopterygium: Conjunctival tissue adherent to the peripheral cornea. May appear in location of previous trauma, surgery, corneal ulceration, or cicatrizing conjunctivitis. There is often associated underlying corneal thinning.
• Peripheral hypertrophic subepithelial corneal degeneration: Less common, usually bilateral, occurring mostly in Caucasian women. Elevated peripheral subepithelial opacities with adjacent limbal vascular abnormalities.
• Pannus: Blood vessels growing into the cornea, often secondary to chronic contact lens wear, blepharitis, ocular rosacea, herpes keratitis, phlyctenular keratitis, atopic disease, trachoma, trauma, and others. Usually at the level of Bowman membrane with minimal to no elevation.
• Sclerokeratitis: See 5.7, Scleritis.
Etiology
Elastotic degeneration of deep conjunctival layers resulting in fibrovascular tissue proliferation. Related to sunlight exposure and chronic irritation. More common in individuals from equatorial regions.
Workup
Slit lamp examination to identify the lesion and evaluate the adjacent corneal integrity and thickness. Check for corneal astigmatism, which is often irregular but may be oriented with the rule.
Treatment
1. Protect eyes from sun, dust, and wind (e.g., ultraviolet-blocking sunglasses or goggles if appropriate).
2. Lubrication with artificial tears, preferably preservative-free, four to eight times per day to reduce ocular irritation.
3. For an inflamed pterygium or pinguecula:
• Mild: Artificial tears q.i.d.
• Moderate to severe: A mild topical steroid (e.g., fluorometholone 0.1%, fluorometholone acetate 0.1%, or loteprednol 0.2% to 0.5% q.i.d.), a nonsteroidal antiinflammatory drop (e.g., ketorolac 0.4% to 0.5% q.i.d.), or a topical antihistamine ± mast cell stabilizer (e.g., bepotastine, ketotifen, olopatadine) may be used to decrease symptoms.
4. If a delle is present, then apply artificial tear ointment q2h. See 4.23, Delle.
5. Surgical removal is indicated when:
• The pterygium threatens the visual axis or induces significant astigmatism.
• The patient is experiencing excessive irritation not relieved by the aforementioned treatment.
• The lesion is interfering with contact lens wear.
• The lesion is visually apparent and causing cosmetic concerns.
• Consider removal prior to cataract or refractive surgery.
NOTE: Pterygia can recur after surgical excision. Bare sclera dissection with a conjunctival autograft or amniotic membrane graft reduces the recurrence rate. Intraoperative application of an antimetabolite (e.g., mitomycin C) also reduces recurrence. Antimetabolites are more commonly reserved for excision of recurrent pterygia, as these medications are associated with an increased risk of corneoscleral thinning or necrosis.
Follow Up
1. Asymptomatic, stable patients may be checked every 1 to 2 years.
2. Pterygia should be measured periodically (every 3 to 12 months, initially) to determine the rate at which they are growing toward the visual axis.
3. If treating with a topical steroid, check after a few weeks to monitor inflammation and IOP. Taper and discontinue the steroid drop over several weeks once the inflammation has abated.
4.10 Band Keratopathy
Symptoms
Decreased vision, foreign body sensation, and corneal whitening; may
be asymptomatic.
Signs
Critical. Anterior corneal plaque of calcium at the level of Bowman membrane, typically within the interpalpebral fissure, and separated from the limbus by clear cornea. Lucid spaces may be present in the plaque, giving it a Swiss cheese appearance. The plaque usually begins at the 3-o'clock and 9-o’clock positions, adjacent to the limbus.
(See Figure 4.10.1.)
FIGURE 4.10.1 Band keratopathy.
Other. May have other signs of chronic eye disease.
Etiology
More Common. Chronic uveitis (e.g., juvenile idiopathic arthritis [JIA]), interstitial keratitis (IK), corneal edema, trauma, phthisis bulbi, long-standing glaucoma, dry eye, ocular surgery (especially retinal detachment repair with silicone oil), and idiopathic.
Less Common. Hypercalcemia (may result from hyperparathyroidism, renal failure, sarcoidosis, multiple myeloma, Paget disease of bone, vitamin D excess, etc.), hyperphosphatemia, gout, corneal dystrophy, myotonic dystrophy, long-term exposure to irritants (e.g., mercury fumes), and other causes.
Workup
1. History: Chronic eye disease? Previous ocular surgery? Chronic exposure to environmental irritants or ocular medications? Systemic disease?
2. Slit lamp examination.
3. If no signs of chronic anterior segment disease or long-standing glaucoma are present, and the band keratopathy cannot be accounted for, then consider the following workup:
• Serum calcium, albumin, magnesium, and phosphate levels. Blood urea nitrogen and creatinine. Uric acid level if gout is suspected.
Treatment
Mild (e.g., Foreign Body Sensation)
Artificial tears, preferably preservative-free, four to six times per day and artificial tear ointment q.h.s. to q.i.d. as needed, add antibiotic ointment (e.g., bacitracin, bacitracin-polymyxin or erythromycin) if irregular epitheium or epithelial defects over calcium deposition. Consider a bandage soft contact lens for comfort.
Severe (e.g., Obstruction of Vision, Irritation Not Relieved by Lubricants, Cosmetic Problem)
Removal of the calcium may be performed at the slit lamp or under the operating microscope by chelation using disodium ethylenediamine tetraacetic acid (EDTA):
1. Disodium EDTA 3% to 4% is obtained from a compounding pharmacy.
2. Anesthetize the eye with a topical anesthetic (e.g., proparacaine) and place an eyelid speculum.
3. Debride the corneal epithelium overlying the calcium with a sterile blade or a sterile cotton-tipped applicator.
4. Wipe a cellulose sponge or cotton swab saturated with the EDTA solution over the band keratopathy until the calcium clears (which may take 10 to 60 minutes).
5. Irrigate with normal saline, place an antibiotic ointment (e.g., erythromycin) and a cycloplegic drop (e.g., cyclopentolate 1% to 2%). Consider a bandage soft contact lens and topical antibiotic drop (e.g., moxifloxacin, gatifloxacin q.i.d.).
6. Consider giving the patient a systemic analgesic (e.g., acetaminophen with codeine).
Follow Up
1. If surgical removal has been performed, the patient should be examined every few days until the epithelial defect has healed.
2. Residual anterior stromal scarring may be amenable to excimer laser PTK to improve vision. Excimer laser PTK may also be used to try to improve the ocular surface and prevent recurrent erosions.
3. The patient should be checked every 3 to 12 months, depending on the severity of symptoms. EDTA chelation can be repeated if the band keratopathy recurs.
4.11 Bacterial Keratitis *
Symptoms
Red eye, moderate-to-severe ocular pain, photophobia, decreased vision, discharge, and acute contact lens intolerance.
Signs
(See Figure 4.11.1.)
FIGURE 4.11.1 Bacterial keratitis.
Critical. Focal white opacity (infiltrate) in the corneal stroma associated with an epithelial defect and underlying stromal thinning/tissue loss.
NOTE: An examiner using a slit beam cannot see clearly through an infiltrate or ulcer to the iris, whereas stromal edema or mild anterior stromal scars are more transparent.
Other. Epithelial defect, mucopurulent discharge, stromal edema, folds in Descemet membrane, anterior chamber reaction, endothelial fibrin/cell deposition with or without hypopyon formation (which, in the absence of globe perforation, usually represents sterile inflammation), conjunctival injection, upper eyelid edema. Posterior synechiae, hyphema, and increased IOP may occur in severe cases.
Differential Diagnosis
• Fungal: Must be considered after any traumatic corneal injury, particularly from vegetable matter (e.g., a tree branch), which may lead to filamentous fungal keratitis. Contact lens wear is another risk factor. Infiltrates commonly have feathery borders and/or may be surrounded by satellite lesions. Candida infections more frequently occur in eyes with preexisting ocular surface disease and may mimic the clinical picture of bacterial ulcers. See 4.12, Fungal Keratitis.
• Acanthamoeba: This protozoan classically causes an extremely painful keratitis and/or stromal infiltrate; is associated with perineural invasion. It usually occurs in daily-wear soft contact lens wearers who may or may not practice poor lens hygiene. History of trauma or history of swimming and/or hot tubbing while wearing contact lenses may be elicited. In the early stages, the epithelial abnormality may look more like HSV keratitis than a bacterial ulcer. In the late stages (3 to 8 weeks), the infiltrate often becomes ring shaped. See 4.13, Acanthamoeba Keratitis.
• HSV: May have eyelid vesicles or corneal epithelial dendrites. A history of recurrent unilateral eye disease or known ocular herpes is common. If a staining infiltrate develops in a patient with stromal herpetic keratitis, one needs to rule out bacterial superinfection. See 4.15, Herpes Simplex Virus.
• Atypical mycobacteria: Usually follows ocular injuries with vegetable matter or ocular surgery, such as cataract extraction, corneal grafts, and refractive surgery (especially LASIK). It has a more indolent course. Culture plates (on Lowenstein-Jensen media) must be kept for 8 weeks. An acid-fast bacillus smear may be very helpful.
• Sterile corneal thinning and ulcers: Minimal or no discharge, mild iritis, peripheral stromal infiltration with overlying staining and adjacent vascularization, and negative cultures. Corneal melting may be associated with various systemic diseases. See 4.22, Peripheral Corneal Thinning/Ulceration.
• Staphylococcal hypersensitivity: Peripheral corneal infiltrates, sometimes with an overlying epithelial defect; usually multiple, often bilateral, with a clear space between the infiltrate and the limbus. Conjunctival injection is localized rather than diffuse, and there is less pain. There is minimal-to-no anterior chamber reaction. Often with coexisting blepharitis/meibomitis. See 4.18, Staphylococcal Hypersensitivity.
• Sterile corneal infiltrates: Typically from an immune reaction to contact lens solutions or hypoxia related to contact lens wear. Usually multiple small, often peripheral, subepithelial infiltrates with little overlying staining and minimal anterior chamber reaction. Usually a diagnosis of exclusion after ruling out an infectious process. Similar lesions can occur after adenoviral conjunctivitis, but these tend to be more central and less dense with a preceding history of conjunctivitis. See 5.1, Acute Conjunctivitis.
• Residual corneal foreign body or rust ring: History of foreign body injury. May be accompanied by corneal stromal inflammation, edema, and sometimes, a sterile infiltrate. There may be a mild anterior chamber reaction. The infiltrate and inflammation usually clear after the foreign body and rust ring are removed, but a superinfection may occur.
• Topical anesthetic abuse: A type of neurotrophic ulcer that should be suspected when there is poor response to appropriate therapy. In the late stages of anesthetic abuse, the corneal appearance may mimic an infectious process such as Acanthamoeba or herpes simplex stromal keratitis. A large ring opacity, edema, and anterior chamber reaction are characteristic. Crack cocaine keratopathy has a similar appearance. Healing, with or without scarring, typically occurs after the exposure to anesthetic is stopped.
Etiology
Bacterial organisms are the most common cause of infectious keratitis. In general, corneal infections are assumed to be bacterial until proven otherwise by laboratory studies or until a therapeutic trial of topical antibiotics is unsuccessful. At Wills Eye, the most common causes of bacterial keratitis are Staphylococcus, Pseudomonas, Streptococcus, Moraxella, and Serratia species. Clinical findings vary widely depending on the severity of disease and on the organism involved. The following clinical characteristics may be helpful in predicting the organism involved. However, clinical impression should never take the place of broad-spectrum initial treatment and appropriate laboratory evaluation. See Appendix 8, Corneal Culture Procedure.
FIGURE 4.11.2 Pseudomonas keratitis.
• Staphylococcal ulcers typically have a well-defined, gray-white stromal infiltrate that may enlarge to form a dense stromal abscess.
• Streptococcal infiltrates may be either very purulent or crystalline (see 4.14, Crystalline Keratopathy). Acute fulminant onset with severe anterior chamber reaction and hypopyon formation are common in the former, while the latter tends to have a more indolent course and occurs in patients often on chronic topical steroids (e.g., corneal transplant patients).
• Pseudomonas typically presents as a rapidly progressive, suppurative, necrotic infiltrate associated with a hypopyon and mucopurulent discharge, commonly seen in the setting of soft contact lens wear (see Figure 4.11.2).
• Moraxella may cause infectious keratitis in patients with preexisting ocular surface disease and in patients who are immunocompromised. Infiltrates are typically indolent, located in the inferior portion of the cornea, have a tendency to be fullthickness, and may rarely perforate.
Workup
1. History: Contact lens wear and care regimen should always be discussed. Sleeping in contact lenses? Daily or extended-wear lenses? Conventional, frequent replacement, or single use? Disinfecting solutions used? Recent changes in routine? Water exposure (swimming or hot tub use) with lenses? Trauma or corneal foreign body? Corneal surgery including refractive surgery? Eye care before visit (e.g., antimicrobials or topical steroids)? Previous corneal disease? Systemic illness?
2. Slit lamp examination: Stain with fluorescein to determine if there is epithelial loss overlying the infiltrate; document the size, depth, and location of the corneal infiltrate and epithelial defect. Assess the anterior chamber reaction and document the presence and size of a hypopyon. Measure the IOP, preferably with a TonoPen.
3. Corneal scrapings for smears and cultures if appropriate and if culture media are available. We routinely culture infiltrates if they are larger than 1 to 2 mm, in the visual axis, unresponsive to initial treatment, or if there is suspicion for an unusual organism based on history or examination. See Appendix 8, Corneal Culture Procedure.
4. In contact lens wearers suspected of having an infectious ulcer, the contact lenses and case are cultured, if available. Explain to the patient that the cultured contact lenses will be discarded. A positive culture from a contact lens or contact lens case should be interpreted with clinical judgment. While a contaminant can be misleading, a result that supports the examination findings can be helpful.
Treatment
Ulcers and infiltrates are initially treated as bacterial unless there is a high index of suspicion of another form of infection. Initial therapy should be broad spectrum. Remember that bacterial coinfection may occasionally complicate fungal and Acanthamoeba keratitis. Mixed bacterial infections can also occur.
1. Cycloplegic drop for comfort and to prevent synechiae formation (e.g., cyclopentolate 1% t.i.d.; atropine 1% b.i.d. to t.i.d. recommended if a hypopyon in present). The specific medication depends on severity of anterior chamber inflammation.
2. Topical antibiotics according to the following algorithm:
Low Risk of Visual Loss
Small, nonstaining peripheral infiltrate with at most minimal anterior chamber reaction and no discharge:
• Noncontact lens wearer: Broad-spectrum topical antibiotics (e.g., fluoroquinolone [moxifloxacin, gatifloxacin, besifloxacin, levofloxacin] or polymyxin B/trimethoprim drops q1-2h while awake).
• Contact lens wearer: Fluoroquinolone (e.g., moxifloxacin, gatifloxacin, ciprofloxacin, besifloxacin, levofloxacin) drops q1-2h while awake ± polymyxin B/trimethoprim drops q1-2h while awake; can add tobramycin or ciprofloxacin ointment one to four times a day.
Borderline Risk of Visual Loss
Medium size (1 to 1.5 mm diameter) peripheral infiltrate, or any smaller infiltrate with an associated epithelial defect, mild anterior chamber reaction, or moderate discharge:
• Fluoroquinolone (e.g., moxifloxacin, gatifloxacin, ciprofloxacin, besifloxacin, levofloxacin) q1h around the clock ± polymyxin B/trimethoprim qlh around the clock. Consider starting with a loading dose of q5min for five doses and then q30min until midnight then q1h.
NOTE: Moxifloxacin and besifloxacin have slightly better grampositive coverage. Gatifloxacin and ciprofloxacin have slightly better Pseudomonas and Serratia coverage.
Vision Threatening
Our current practice at Wills Eye is to start fortified antibiotics for most ulcers larger than 1.5 to 2 mm, in the visual axis, or unresponsive to initial treatment. See Appendix 9, Fortified Topical Antibiotics/Antifungals, for directions on making fortified antibiotics. If fortified antibiotics are not immediately available, start with a fluoroquinolone and polymyxin B/trimethoprim until fortified antibiotics can be obtained from a formulating pharmacy.
• Fortified tobramycin or gentamicin (15 mg/mL) q1h, alternating with fortified cefazolin (50 mg/mL) or vancomycin (25 mg/mL) q1h. This means that the patient will be placing a drop in the eye every one-half hour around the clock. Vancomycin drops should be reserved for resistant organisms, patients at risk for resistant organisms (e.g., due to hospital or antibiotic exposure, unresponsive to initial treatment), and for patients who are allergic to penicillin or cephalosporins. An increasing number of methicillin-resistant Staphylococcus aureus (MRSA) infections are now community acquired. If the ulcer is severe and Pseudomonas is suspected, consider starting fortified tobramycin every 30 minutes and fortified cefazolin q1h around the clock; in addition, consider fortified ceftazidime q1h or a fluoroquinolone q1h around the clock.
NOTE: All patients with borderline risk of visual loss or severe vision-threatening ulcers are initially treated with loading doses of antibiotics using the following regimen: One drop every 5 minutes for five doses, then every 30 to 60 minutes around the clock.
1. In some cases, topical steroids are added after the bacterial organism and sensitivities are known, the infection is under control, and severe inflammation persists. Infectious keratitis may worsen significantly with topical steroids, especially when caused by fungus, atypical mycobacteria, Nocardia or Pseudomonas.
2. Eyes with corneal thinning should be protected by a shield without a pressure patch (a patch is never placed over an eye thought to have an infection). The use of a matrix metalloproteinase inhibitor (e.g., doxycycline 100 mg p.o. b.i.d.) and a collagen synthesis promoter such as systemic ascorbic acid (e.g., vitamin C 1 to 2 g daily) may help to suppress connective tissue breakdown and prevent the perforation of the cornea.
3. No contact lens wear.
4. Oral pain medication as needed.
5. Oral fluoroquinolones (e.g., ciprofloxacin 500 mg p.o. b.i.d.; moxifloxacin 400 mg p.o. daily) penetrate the eye well. These may have added benefit for patients with scleral extension or for those with frank or impending perforation. Ciprofloxacin is preferred for Pseudomonas and Serratia.
6. Systemic antibiotics are also necessary for Neisseria infections (e.g., ceftriaxone 1 g intravenously [i.v.] q12-24h if corneal involvement, or a single 1 g intramuscular [i.m.] dose if there is only conjunctival involvement) and for Haemophilus infections (e.g., oral amoxicillin/clavulanate [20 to 40 mg/kg/d in three divided doses]) because of occasional extraocular involvement such as otitis media, pneumonia, and meningitis.
NOTE: Systemic fluoroquinolones were historically used for Neisseria gonorrhoeae, but are no longer recommended to treat gonococcal infections (especially in men who have sex with men, in areas of high endemic resistance, and in patients with a recent foreign travel history) due to increased resistance. Additionally, they are contraindicated in pregnant women and children.
7. Admission to the hospital may be necessary if:
• Infection is sight threatening and/or impending perforation.
• Patient has difficulty administering the antibiotics at the prescribed frequency.
• High likelihood of noncompliance with drops or daily follow up.
• Suspected topical anesthetic abuse.
• Intravenous antibiotics are needed (e.g., gonococcal conjunctivitis with corneal involvement). Often employed in the presence of corneal perforation and/or scleral extension of infection.
8. For atypical mycobacteria, consider prolonged treatment (q1h for 1 week, then gradually tapering) with one or more of the following topical agents: fluoroquinolone (e.g., moxifloxacin or gatifloxacin), fortified amikacin (15 mg/mL), clarithromycin (1% to 4%), or fortified tobramycin (15 mg/mL). Consider oral treatment with clarithromycin 500 mg b.i.d. Previous LASIK has been implicated as a risk factor for atypical mycobacteria infections.
Follow Up
1. Daily evaluation at first, including repeat measurements of the size of the infiltrate, epithelial defect and hypopyon. The most important criteria in evaluating treatment response are the amount of pain, the epithelial defect size (which may initially increase because of scraping for cultures and smears), the size and depth of the infiltrate, and the anterior chamber reaction. The IOP must be checked and treated if elevated (see 9.7, Inflammatory Open Angle Glaucoma). Reduced pain is often the first sign of a positive response to treatment.
2. If improving, the antibiotic regimen is gradually tapered but is never tapered past the minimum dose to inhibit the emergence of resistance (usually t.i.d. to q.i.d. depending on the agent). Otherwise, the antibiotic regimen is adjusted according to the culture and sensitivity results.
3. Consider new or repeat cultures and stains (without stopping treatment) in the setting of non-responsive or worsening infiltrate/ulcer. Treat with fortified antibiotics and modify based on culture results and the clinical course. Hospitalization may be recommended. See Appendix 8, Corneal Culture Procedure.
4. A corneal biopsy may be required if the condition is worsening and infection is still suspected despite negative cultures.
5. For an impending or a complete corneal perforation, a corneal transplant or patch graft is considered. Cyanoacrylate tissue glue may also work in a treated corneal ulcer that has perforated despite infection control. Frequent antibiotics are continued after application of glue to treat the infection.
NOTE: Outpatients are told to return immediately if the pain increases, vision decreases, or they notice an increase in the size of the ulcer when they look in the mirror.
4.12 Fungal Keratitis
Symptoms
Pain, photophobia, redness, tearing, discharge, foreign body sensation. Often history of minor trauma particularly with vegetable matter (e.g., a tree branch), contact lens wear, chronic eye disease, and/or a history of poor response to conventional antibacterial therapy. Usually more indolent than bacterial keratitis.
Signs
Critical
• Filamentous fungi: Corneal stromal gray-white opacity (infiltrate) with a feathery border. The epithelium over the infiltrate may be elevated above the remainder of the corneal surface, or there may be an epithelial defect with stromal thinning (ulcer).
• Nonfilamentous fungi: A gray-white stromal infiltrate similar to a bacterial ulcer.
Other. Satellite lesions surrounding the primary infiltrate, conjunctival injection, mucopurulent discharge, anterior chamber reaction, hypopyon. The infiltrate is more likely to extend beyond the epithelial defect than in bacterial ulcers.
Differential Diagnosis
See 4.11, Bacterial Keratitis.
FIGURE 4.12.1 Candida fungal keratitis.
Etiology
• Filamentous fungi (e.g., Fusarium or Aspergillus species most commonly): Usually from trauma with vegetable matter in previously healthy eyes or associated with contact lens wear.
• Nonfilamentous fungi (e.g., Candida species): Usually in previously diseased eyes (e.g., dry eyes, herpes simplex or varicella zoster keratitis, exposure keratopathy, and chronic use of steroid drops), see Figure 4.12.1.
Workup
See 4.11, Bacterial Keratitis for complete workup and culture procedure.
1. Whenever smears and cultures are done, include a Gram, Giemsa, calcofluor white, or KOH stain for organisms; periodic acid- Schiff, Gomori methenamine silver, and hematoxylin and eosin (H&E) stains can also be used. Scrape deep into the edge of the ulcer for material. See Appendix 8, Corneal Culture Procedure.
2. If an infectious etiology is still suspected despite negative cultures, consider a corneal biopsy to obtain further diagnostic information.
3. Consider cultures and smears of contact lens case and solution.
4. Sometimes all tests are negative, yet the disease continues to progress and therapeutic penetrating keratoplasty (PK) is necessary for diagnosis and treatment.
Treatment
Corneal infiltrates and ulcers of unknown etiology are treated as bacterial until proven otherwise (see 4.11, Bacterial Keratitis). If the stains or cultures indicate a fungal keratitis, institute the following measures:
1. Natamycin 5% drops (especially for filamentous fungi), amphotericin B 0.15% drops (especially for Candida), and/or topical fortified voriconazole 1% initially q1-2h around the clock, then taper over the next several weeks based on response to therapy, (see Appendix 9, Fortified Topical Antibiotics/Antifungals).
NOTE: Natamycin is the only commercially available topical antifungal agent; all others must be compounded.
2. Cycloplegic drop (e.g., cyclopentolate 1% t.i.d.; atropine 1% b.i.d. to t.i.d. is recommended if hypopyon, fibrin or significant anterior chamber reaction is present).
3. No topical steroids. If the patient is currently taking steroids, they should be tapered rapidly and discontinued.
4. Consider adding oral antifungal agents (e.g., fluconazole or itraconazole 200 to 400 mg p.o. loading dose, then 100 to 200 mg p.o. daily, posaconazole 300 mg p.o. b.i.d. for 1 day then 300 mg p.o. q.d., or voriconazole 200 mg p.o. b.i.d.). Oral antifungal agents are often used for deep corneal ulcers or suspected fungal endophthalmitis.
5. Consider epithelial debridement to facilitate the penetration of antifungal medications. Topical antifungals do not penetrate the cornea well, especially through an intact epithelium. When culture results and sensitivities are known, intrastromal depot injections of amphotericin (10 mcg/0.1 mL) or voriconazole (voriconazole 50 mcg/0.1 mL) can also be considered.
6. Measure IOP (preferably with Tono-Pen). Treat elevated IOP if present (see 9.7, Inflammatory Open Angle Glaucoma).
7. Eye shield, without patch, in the presence of corneal thinning.
8. Admission to the hospital may be necessary if patient compliance is an issue. It may take weeks to achieve complete healing.
9. If unable to adequately control the infection despite prolonged treatment, a therapeutic penetrating keratoplasty can be considered, ideally before the infection reaches the limbus. Intracameral antifungal medications (e.g., voriconazole 50 mcg/0.1 mL or amphotericin 10 mcg in 0.1 mL) at the time of therapeutic keratoplasty should be considered. Anterior lamellar keratoplasty is relatively contraindicated because there is a high risk of recurrence of infection.
Follow Up
Patients are reexamined daily at first. However, the initial clinical response to treatment in fungal keratitis is much slower compared to bacterial keratitis. Stability of infection after initiation of treatment is often a favorable sign. Unlike bacterial ulcers, epithelial healing in fungal keratitis is not always a sign of positive response. Fungal infections in deep corneal stroma may be recalcitrant to therapy. These ulcers may require weeks to months of treatment, and therapeutic corneal transplantation may be necessary for infections that progress despite maximal medical therapy or corneal perforation.
4.13 Acanthamoeba Keratitis
Symptoms
Can vary from foreign body sensation to severe ocular pain (often out of proportion to the early clinical findings), redness, and photophobia over a period of several weeks.
Signs
(See Figures 4.13.1 and 4.13.2.)
FIGURE 4.13.1 Acanthamoeba keratitis with radial keratoneuritis.
FIGURE 4.13.2 Acanthamoeba keratitis with a dense ring infiltrate.
Critical. Early: Epitheliitis with pseudodendrites, whorls, epithelial ridges, and/or diffuse subepithelial microcysts. Subepithelial infiltrates (sometimes along corneal nerves, producing a radial keratoneuritis).
Late (3 to 8 weeks): Ring-shaped corneal stromal infiltrate.
NOTE: Acanthamoeba keratitis should be considered in any patient with a history of soft contact lens wear, poor contact lens hygiene (e.g., using tap water to clean lenses, infrequent disinfection), and/or history of trauma or exposure to water (swimming, fishing, hot tub use) while wearing contact lenses. Although most patients with Acanthamoeba have a history of contact lens use, some patients do not and these patients often have a delayed diagnosis. Cultures for bacteria are negative (unless superinfection present). The condition usually does not improve with antibiotic or antiviral medications and commonly follows a chronic, progressive, downhill course. Acanthamoeba is important to consider in patients with seemingly unresponsive HSV keratitis, as HSV keratitis usually responds well to appropriate treatment. The diagnosis of HSV keratitis in a contact lens wearer should always include consideration of Acanthamoeba, as the clinical appearance of these two entities can be similar in the early stages of disease.
Other. Eyelid swelling, conjunctival injection (especially circumcorneal), cells and flare in the anterior chamber. Minimal discharge or corneal vascularization. Coinfection with bacteria or fungi may occur later in the course.
Differential Diagnosis
HSV keratitis is first in the differential. See 4.11, Bacterial Keratitis and 4.15, Herpes Simplex Virus.
Workup
See 4.11, Bacterial Keratitis for a general workup. One or more of the following are obtained when Acanthamoeba is suspected:
1. Corneal scrapings for Gram, Giemsa, calcofluor white, and periodic acid-Schiff stains (Giemsa and periodic acid-Schiff stains may show typical cysts). See Appendix 8, Corneal Culture Procedure.
2. Consider a culture on nonnutrient agar with Escherichia coli overlay.
3. Consider a corneal biopsy if the stains and cultures are negative and the condition is not improving on the current regimen.
4. Consider cultures and smears of contact lens and case.
5. Confocal biomicroscopy may be helpful if available.
Treatment
One or more of the following are usually used in combination, sometimes in the hospital initially:
1. Polyhexamethylene biguanide 0.02% (PHMB) drops q1h or chlorhexidine 0.02% drops q1h.
2. Propamidine isethionate 0.1% drops q1h are typically added in addition to PHMB or chlorhexidine. Dibromopropamidine isethionate 0.15% ointment is also available.
3. Consider an oral antifungal agent (e.g., itraconazole 400 mg p.o. for one loading dose, then 100 to 200 mg p.o. daily, ketoconazole 200 mg p.o. daily, or voriconazole 200 mg p.o. daily to b.i.d.).
All patients:
4. Miltefosine is designated by the FDA as an orphan drug for the treatment of acanthamoeba keratitis and can be considered as an adjunctive treatment to the topical therapy. At Wills, we typically begin this medication upon pathologic identification of acanthamoeba cysts and prescribe 50 mg b.i.d. to t.i.d. for a 4 week course. Basic metabolic panel, liver function tests, and pregnancy test (if applicable) should be obtained prior to starting miltefosine, which is known to cause serious risks in pregnancy. Note that there may be rebound inflammation after the miltefosine is stopped, which can respond to topical steroids.
NOTE: Alternative therapy includes hexamidine 0.1%, clotrimazole 1% drops, miconazole 1% drops, or paromomycin drops q2h. Low-dose steroid drops may be helpful in reducing inflammation after the infection is controlled, but steroid use is controversial.
5. Discontinue contact lens wear in both eyes.
6. Cycloplegic drop (e.g., cyclopentolate 1% t.i.d. or atropine 1% b.i.d.).
7. In presence of inflammation, pain, and/or scleritis, oral nonsteroidal anti-inflammatory agents (e.g., naproxen 250 to 500 mg p.o. b.i.d.) may be used. Additional narcotic oral analgesics are often needed.
NOTE: Corneal transplantation may be indicated for medical failures, but this procedure can be complicated by recurrent infection. It is best delayed for 6 to 12 months after medical treatment is completed.
Follow Up
Every 1 to 4 days until the condition is consistently improving, and then every 1 to 4 weeks. Medication may then be tapered judiciously. Treatment is usually continued for 3 months after resolution of inflammation, which may take up to 6 to 12 months.
NOTE:
1. Propamidine isethionate 0.1% drops are available in the United Kingdom and other countries; it may be compounded in the United States.
2. PHMB is available in the United Kingdom as Cosmocil. It can be prepared by a compounding pharmacy in the United States from Baquacil, a swimming pool disinfectant.
4.14 Crystalline Keratopathy
Symptoms
Decreased vision, photophobia, decreased corneal sensation may occur. May be asymptomatic.
Signs
Crystals seen in subepithelial and/or stromal regions of the cornea. May or may not have an overlying epithelial defect. In the presence of a corneal transplant, the crystalline opacities frequently are localized along an existing suture track.
Etiology
• Infectious crystalline keratopathy: Seen in corneal grafts and chronically inflamed corneas. Streptococcus viridans is the most common organism; other organisms include Staphylococcus epidermidis, Corynebacterium species, Pseudomonas aeruginosa, and fungi. Patients with history of refractive surgery are at a higher risk for atypical mycobacteria and Alternaria species.
• Schnyder corneal dystrophy: Slowly progressive, autosomal dominant. Subepithelial corneal crystals in 50% of patients (cholesterol and phospholipids), central and midperipheral corneal haze, dense arcus, decreased corneal sensation. Local disorder of corneal lipid metabolism but can be associated with hyperlipidemia and hypercholesterolemia. Higher prevalence in patients with Swede-Finn descent. See 4.25, Corneal Dystrophies.
• Bietti crystalline corneoretinal dystrophy: Rare, autosomal recessive. Retinal crystals (decrease with time) and sparkling, yellow-white spots at the corneal limbus in the superficial stroma and subepithelial layers of the cornea.
• Cystinosis: Rare, autosomal recessive, systemic metabolic defect. Infantile form (nephropathic): dwarfism, progressive renal dysfunction, and polychromatic cystine crystals in conjunctiva, corneal stroma (densest in peripheral cornea but present throughout anterior stroma), trabecular meshwork. Intermediate/adolescent form: less severe renal involvement. Adult form: normal life expectancy.
• Lymphoproliferative disorders (e.g., monoclonal gammopathy of undetermined significance, essential cryoglobulinemia, or multiple myeloma): Fine crystalline opacities are diffusely distributed throughout the cornea more commonly in the anterior stroma and peripheral cornea than the posterior stroma and central cornea.
Workup
1. Infectious crystalline keratopathy: Culture as outlined in Appendix 8, Corneal Culture Procedure. Obtain mycobacterial cultures/acid-fast bacillus stain (especially in patients with history of refractive surgery).
2. Fasting lipid profile in patients with Schnyder corneal dystrophy.
3. Electroretinogram may be decreased in later stages of Bietti crystalline dystrophy.
4. Cystinosis: Very high level of suspicion required, especially for infantile form, which can be fatal in the first decade of life without a renal transplant. Conjunctival biopsy, blood or bone marrow smear.
5. If a lymphoproliferative disorder is suspected, consult hematology and consider complete blood count with differential, serum chemistries (including calcium), creatinine, albumin, lactate dehydrogenase, beta-2 microglobulin, C-reactive protein (CRP), serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and peripheral/bone marrow smear.
Treatment
1. Infectious crystalline keratopathy: Treat as outlined in see 4.11, Bacterial Keratitis, and 4.29, Corneal Refractive Surgery Complications. If patient is on topical steroid therapy, decrease frequency or steroid strength rather than stopping the steroid abruptly.
2. Schnyder corneal dystrophy: Excimer laser PTK may be effective for subepithelial crystals. Corneal transplantation for severe cases. Diet and/or medications if associated systemic dyslipidemia.
3. No specific treatment for Bietti crystalline dystrophy.
4. Cystinosis: Topical cysteamine drops reduce the density of crystalline deposits and corneal pain. PK for severe cases (although corneal deposits may recur). Patients must get systemic evaluation by primary care physician and/or geneticist.
5. Lymphoproliferative disorder: Consult a hematologist and/or oncologist.
4.15 Herpes Simplex Virus
Symptoms
Red eye, pain, foreign body sensation, photophobia, tearing, decreased vision, skin (e.g., eyelid) vesicular rash, history of previous episodes; usually unilateral.
Signs
Primary HSV infection is usually not apparent clinically. However, neonatal primary herpes infection is a rare, potentially devastating disease associated with localized skin, eye, or oral infection and severe central nervous system and multiorgan system infection (see 8.9, Ophthalmia Neonatorum [Newborn Conjunctivitis]). Compared to adults, children tend to exhibit more severe disease that may be bilateral, recurrent, and associated with extensive eyelid involvement, multiple corneal/conjunctival dendrites, and a greater degree of secondary corneal scarring and astigmatism. Possible triggers for recurrence include ocular surgery, certain topical medications, fever, stress, menstruation, and upper respiratory tract infection. Infection may be characterized by any or all of the following:
Eyelid/Skin Involvement
Clear vesicles on an erythematous base that progress to crusting, heal without scarring, cross dermatomes, but are typically unilateral (only 10% of primary HSV dermatitis is bilateral).
Conjunctivitis
Conjunctival injection with acute unilateral follicular conjunctivitis, with or without conjunctival dendrites or geographic ulceration.
Epithelial Keratitis
(See Figure 4.15.1.)
FIGURE 4.15.1 Herpes simplex dendritic keratitis.
May be seen as macropunctate keratitis, dendritic keratitis (a thin, linear, branching epithelial ulceration with club-shaped terminal bulbs at the end of each branch), or a geographic ulcer (a large, amoeba-shaped corneal ulcer with a dendritic edge). The edges of herpetic lesions are heaped up with swollen epithelial cells that stain well with rose bengal or lissamine green; the central ulceration stains well with fluorescein. Corneal sensitivity may be decreased. Subepithelial scars and haze (ghost dendrites) may develop as epithelial dendrites resolve. Epithelial keratitis is considered to be live, replicating viral disease, and treatment is directed accordingly.
Differential Diagnosis of Corneal Dendrites
A "true" dendrite (branching epithelial ulceration with terminal endbulbs) is pathognomonic for HSV however there are many similar appearing lesions that should be distinguished:
• VZV: Pseudodendrites in VZV are slightly elevated and are without central ulceration. They do not have true terminal bulbs and do not typically stain well with fluorescein. See 4.16, Herpes Zoster Ophthalmicus/Varicella Zoster Virus.
• Recurrent corneal erosion or any recent corneal abrasion: A healing epithelial defect often has a dendritiform appearance. Recurrent erosions in patients with lattice dystrophy can have a geographic shape. See 4.2, Recurrent Corneal Erosion.
• Acanthamoeba keratitis pseudodendrites: History of soft contact lens wear, pain often out of proportion to inflammation, chronic course. These are raised epithelial lesions, not epithelial ulcerations. See 4.13, Acanthamoeba Keratitis.
• Others: Cornea verticillata from medications or Fabry disease, and rarely tyrosinemia.
Stromal Keratitis
• Stromal keratitis without ulceration (alternate terms: nonnecrotizing keratitis, immune stromal keratitis, interstitial keratitis): Unifocal or multifocal stromal haze or whitening, often with stromal edema, in the absence of epithelial ulceration.
Accompanying stromal vascularization indicates chronicity or prior episodes. The differential of stromal keratitis without ulceration includes any cause of IK (see below). HSV stromal keratitis is considered an immune reaction rather than active infectious process and therefore treatment is directed accordingly.
• Stromal keratitis with ulceration (necrotizing keratitis): Suppurative stromal inflammation, thinning, with an adjacent or overlying epithelial defect. Appearance may be indistinguishable from infectious keratitis (fungal, bacterial, parasitic) and therefore infection should be ruled out. Stromal keratitis may lead to thinning or scarring and therefore must be treated diligently.
• Endothelial keratitis (disciform keratitis): Corneal stromal and epithelial edema in a round or discrete pattern, associated with an area of keratic precipitates often out of proportion to the amount of anterior chamber inflammation.
Neurotrophic Ulcer
• A chronic presentation in a relatively neurotrophic cornea due to fifth cranial nerve sensory damage following prior keratitis. A sterile ulcer with smooth epithelial margins over an area of interpalpebral stromal disease that persists or worsens despite antiviral therapy. May be associated with stromal melting and perforation. Without a known history or HSV keratitis, other causes of neurotrophic keratitis should be considered, including: VZV, diabetes, cranial surgery, or radiation.
Uveitis
• An anterior chamber inflammatory reaction may develop during corneal stromal disease or independently from keratitis. Elevated IOP secondary to trabeculitis is often suggestive of herpetic uveitis. Patchy iris transillumination defects are also characteristic.
Retinitis
Rare. See 12.8, Acute Retinal Necrosis.
Workup
1. History: Previous episodes? History of corneal abrasion; contact lens wear; or previous nasal or oral sores? Recent topical or systemic steroids? Immune deficiency state? Recent fever or sun/UV exposure? History of shingles?
2. External examination: Note the distribution of skin vesicles if present. The lesions are more suggestive of HSV than VZV if concentrated around the eye without extension onto forehead, scalp, and tip of nose. HSV often involves both the upper and lower eyelids.
3. Check corneal sensation (before instillation of topical anesthetic), which may be decreased in HSV and VZV.
4. Slit lamp examination with IOP measurement.
5. DFE: Viral retinitis must be ruled out in all new presentations.
6. Herpes simplex is usually diagnosed clinically and requires no confirmatory laboratory tests. If the diagnosis is in doubt, any of the following tests may be helpful:
• Viral PCR (or culture): A sterile, cotton-tipped applicator is used to swab the cornea, conjunctiva, or skin (after unroofing vesicles with a sterile needle) and is placed in the viral transport medium. Readily available in most laboratory settings with a relatively good sensitivity.
• Scrapings of a corneal or skin lesion (scrape the edge of a corneal ulcer or the base of a skin lesion) for Giemsa stain, which shows multinucleated giant cells (this will not help differentiate HSV from other herpes family viruses). Enzyme-linked immunosorbent assay testing specific to HSV also is available.
• HSV antibody titers are frequently present in patients. They rise after primary but not recurrent infection. The absence of HSV1 antibodies helps rule out HSV as a cause of stromal keratitis. Positive titer is nonspecific as HSV is ubiquitous and exposure rates in the general population are extremely high.
Treatment
Blepharoconjunctivitis: Skin/Eyelid/Conjunctivitis
1. Self-limited, however treatment may shorten course and reduce corneal exposure to live virus. Systemic (acyclovir 400 mg five times daily or valacyclovir 500 mg twice daily or famciclovir 250 mg twice daily for 7 to 10 days) or topical (ganciclovir 0.15% ophthalmic gel five times daily or trifluridine 1% nine times daily for 7 to 10 days) therapy may be helpful.
Epithelial Keratitis
1. Either systemic or topical antiviral therapy may be used. Many cornea specialists now prefer systemic treatment for greater intraocular concentration, ease of use, and reduction of corneal medication toxicity.
• Dendritic: Oral treatment (acyclovir 400 mg five times daily or valacyclovir 500 mg twice to three times daily or famciclovir 250 mg twice to three times daily) for 7 to 10 days or topical ganciclovir 0.15% ophthalmic gel or 3% acyclovir ophthalmic ointment five times per day until healed, then three times per day for 7 days or trifluridine 1% drops nine times per day until healed then five times daily for 7 days (but not exceeding 21 days). Topical ganciclovir gel and acyclovir ointment appear to have a lower incidence of corneal toxicity than trifluridine drops.
• Geographic: Oral treatment (acyclovir 400 to 800 mg five times daily or valacyclovir 500 to 1,000 mg twice to three times daily or famciclovir 250 to 500 mg twice to three times daily) for 14 to 21 days or topical therapy as described above.
2. Consider cycloplegic drop (e.g., cyclopentolate 1% t.i.d.) if an anterior chamber reaction or photophobia is present.
3. Topical antibiotic (drop or ointment) may be given at a prophylaxis dose to prevent bacterial superinfection until epithelium is healed.
4. Patients taking topical steroids should have them tapered rapidly.
5. Limited debridement of infected epithelium can be used as an adjunct to antiviral agents.
• Technique: After topical anesthetic instillation, a sterile, moistened cotton-tipped applicator or semisharp instrument is used carefully to peel off the lesions at the slit lamp. After debridement, antiviral treatment should be instituted or continued as described earlier.
6. For epithelial defects that do not resolve after 1 to 2 weeks, bacterial coinfection or Acanthamoeba keratitis should be suspected. Noncompliance and topical antiviral toxicity should also be considered. At that point, the topical antiviral agent should be discontinued, and a nonpreserved artificial tear ointment or an antibiotic ointment (e.g., erythromycin) should be used four to eight times per day for several days with careful follow up. Smears for Acanthamoeba should be performed whenever the diagnosis is suspected.
Stromal Keratitis Without Epithelial Ulceration
• Therapeutic dose topical steroid: Prednisolone acetate 1% six to eight times daily tapered slowly. Patients may require low dose/potency maintenance therapy indefinitely.
• Prophylactic oral antiviral: Acyclovir 400 mg twice daily or valacyclovir 500 mg once or twice daily or famciclovir 250 mg once or twice daily.
• Microbial superinfections must be ruled out and treated. Tissue adhesive or corneal transplantation may be required if the cornea perforates.
Stromal Keratitis With Epithelial Ulceration
• Limited dose of topical steroid: Prednisolone acetate 1% twice daily.
• Therapeutic dose of oral antiviral for 7 to 10 days: Acyclovir 800 mg three to five times daily or valacyclovir 1 g two to three times daily or famciclovir 500 mg two to three times daily. The oral antiviral agent is reduced to prophylactic dose as long as topical steroids are continued.
Endothelial Keratitis
Therapeutic dose of topical steroid and therapeutic dose of oral antiviral (see dosing above).
Neurotrophic Ulcer
See 4.6, Neurotrophic Keratopathy.
NOTE: Chronic use of prophylactic oral antivirals may help prevent subsequent episodes of HSV keratouveitis.
• Adjunctive medications which may be used include:
• Topical antibiotic (e.g., erythromycin ointment) in the presence of epithelial defects.
• Aqueous suppressants for increased IOP. Avoid prostaglandin analogues due to association with recurrent HSV infections and uveitis.
NOTE:
1. Topical steroids are contraindicated in those with infectious epithelial disease.
2. Rarely, a systemic steroid (e.g., prednisone 40 to 60 mg p.o. daily tapered rapidly) is given to patients with severe stromal disease accompanied by an epithelial defect and hypopyon. Cultures should be done to rule out a superinfection.
3. While oral antivirals (e.g., acyclovir, valacyclovir, and famciclovir) have not been shown to be beneficial in the treatment of stromal disease, they are typically employed, and may be beneficial in the treatment of herpetic uveitis (see 12.1, Anterior Uveitis [Iritis/Iridocyclitis]).
4. Valacyclovir has greater bioavailability than acyclovir. Little has been published on famciclovir for HSV, but it may be better tolerated in patients who have side effects to acyclovir such as headache, fatigue, or gastrointestinal upset.
5. Dosing of antivirals discussed above (e.g., acyclovir, valacyclovir, and famciclovir) needs to be adjusted in patients with renal insufficiency. Checking BUN and creatinine is recommended in patients at risk for renal disease before starting high doses of these medications.
6. Valacyclovir should be used with caution in patients with human immunodeficiency virus due to reports of thrombocytopenic purpura and hemolytic uremic syndrome in this population.
7. The persistence of an ulcer with stromal keratitis is commonly due to the underlying inflammation (requiring cautious steroid therapy); however, it may be due to antiviral toxicity or active HSV epithelial infection. When an ulcer deepens, a new infiltrate develops, or the anterior chamber reaction increases, smears and cultures should be considered for bacteria and fungi. See Appendix 8, Corneal Culture Procedure.
Follow Up
1. Patients are reexamined in 2 to 7 days to evaluate the response to treatment and then every 1 to 2 weeks, depending on the clinical findings. The following clinical parameters are evaluated: the size of the epithelial defect and ulcer, the corneal thickness and the depth of corneal involvement, the anterior chamber reaction, and the IOP (see 9.7, Inflammatory Open Angle Glaucoma, for glaucoma management). Patients with necrotizing keratitis need to be followed daily or admitted if there is threat of perforation.
2. Topical antiviral medications for corneal dendrites and geographic ulcers should not be continued for greater than 14 to 21 days (see dosing above).
3. Topical steroids used for corneal stromal disease are tapered slowly (often over months to years). The initial concentration of the steroid (e.g., prednisolone acetate 1%) is eventually reduced (e.g., loteprednol 0.5% or prednisolone acetate 0.125%). Extended taper includes dosing q.o.d., twice weekly, once weekly, etc., especially with a history of flare-ups when steroids are stopped. Prophylactic systemic antiviral agents (see dosing above) are used until steroids are used once daily or less, at which point they can be continued or stopped.
4. Corneal transplantation may eventually be necessary if inactive postherpetic scars significantly affect vision, though a rigid gas permeable (RGP) contact lens and maximization of the ocular surface with aggressive lubrication should be tried first. The eye should be quiet for at least 3 to 6 months prior to surgery. Systemic antiviral prophylaxis is typically continued for at least 1 year (often indefinitely) following surgery.
5. Recommend long-term oral antiviral prophylaxis (e.g., acyclovir 400 mg b.i.d.) if a patient has had multiple episodes of epithelial disease or stromal disease.
4.16 Herpes Zoster Ophthalmicus/Varicella Zoster Virus
Symptoms
Dermatomal pain, paresthesias, and skin rash or discomfort. May be preceded by headache, fever, or malaise, and accompanied or followed by blurred vision, eye pain, and red eye.
Signs
Critical. Acute vesicular dermatomal skin rash along the first division of the fifth cranial nerve. Characteristically, the rash is unilateral and typically spares the lower eyelid. Hutchinson sign (tip of the nose involved in the distribution of the nasociliary branch of V1) predicts higher risk of ocular involvement. While the associated edema of the vesicular rash may extend bilaterally, the lesions always respect the midline.
Other. Less commonly, the lower eyelid and cheek on one side (V2), and, rarely, one side of the jaw (V3) are involved. Conjunctivitis, corneal involvement (e.g., multiple small epithelial dendritiform lesions early, followed by larger pseudodendrites [raised mucous plaques which may be present on cornea or conjunctiva, see Figure 4.16.1], SPK, immune stromal keratitis, neurotrophic keratitis), uveitis, sectoral iris atrophy, scleritis, retinitis, choroiditis, optic neuritis, cranial nerve palsies, and elevated IOP can occur. Late postherpetic neuralgia also may occur.
FIGURE 4.16.1 Herpes zoster keratitis with pseudodendrites.
NOTE: Corneal disease may follow the acute skin rash by several days, weeks, or months and can last for years. Occasionally, the diagnosis can be more difficult to determine in cases where a clinical rash never develops or cases where corneal disease precedes the skin rash. There is a rise in VZV titers after zoster.
Differential Diagnosis
• HSV: Patients are often younger; rash is not dermatomal. See 4.15, Herpes Simplex Virus.
Workup
1. History: Duration of rash and pain? Immunocompromised or risk factors for HIV/AIDS? Hearing changes, facial pain or weakness, vertigo (cranial nerve VII involvement [Ramsay Hunt syndrome])? Rashes elsewhere?
2. Complete ocular examination, including a slit lamp evaluation with fluorescein or rose bengal staining, IOP check, and dilated fundus examination with careful evaluation for acute retinal necrosis (ARN) in immunocompetent patients and progressive outer retinal necrosis (PORN) in patients with immunodeficiency. See 12.8, Acute Retinal Necrosis (ARN).
3. Consider medical evaluation for immunocompromised status if immunodeficiency is suspected from the history.
4. If patient is >60 years old (especially if systemic steroid therapy is to be initiated), or if any other organ systems or nonophthalmic sites are involved, evaluation by the patient’s primary medical doctor or other subspecialist(s) is warranted.
Treatment
See Table 4.16.1.
NOTE: Immunocompromised patients should not receive systemic steroids.
TABLE 4.16.1
Antiviral Therapy Guidelines for Varicella Zoster Virus
Skin Involvement
1. In adults with a moderate-to-severe skin rash for <4 days in which active skin lesions are present and consider if the patient presents later in the first week with active lesions:
• Oral antiviral agent (e.g., acyclovir 800 mg p.o. five times per day, valacyclovir 1,000 mg p.o. t.i.d., or famciclovir 500 mg p.o. t.i.d.) for 7 to 10 days. If the condition is severe, as manifested by orbital, optic nerve, or cranial nerve involvement, or the patient is systemically ill, hospitalize and prescribe acyclovir 5 to 10 mg/kg i.v. q8h for 5 to 10 days.
• Ophthalmic antibiotic ointment (e.g., bacitracin or erythromycin) to skin lesions b.i.d.
• Warm compresses to periocular skin t.i.d.
2. Adults with a skin rash of more than 1-week duration or without active skin lesions:
• Ophthalmic antibiotic ointment (e.g., bacitracin or erythromycin) to skin lesions b.i.d.
• Warm compresses to periocular skin t.i.d.
3. Children: Discuss with a pediatrician and consider weight-based acyclovir dosing (20 mg/kg q8h) for children <12 years of age or under 40 kg, otherwise use adult dosage above. For systemic spread, hospitalize and prescribe intravenous acyclovir in conjunction with pediatric and infectious disease comanagement.
Ocular Involvement
NOTE: It is common clinical practice at Wills Eye for all patients with VZV ocular findings to receive 7 to 10 days of systemic oral antivirals (e.g., acyclovir 800 mg p.o. five times per day, valacyclovir 1,000 mg p.o. t.i.d., or famciclovir 500 mg p.o. t.i.d.) usually in conjunction with the following therapies.
1. Conjunctival involvement: Cool compresses and ophthalmic ointment (e.g., bacitracin or erythromycin) to the eye b.i.d.
2. SPK: Lubrication with preservative-free artificial tears q1-2h and ointment q.h.s.
3. Corneal or conjunctival mucous plaque pseudodendrites: Lubrication with preservative-free artificial tears q1-2h and ointment q.h.s. Consider antibiotic ointment to prevent bacterial superinfection. Topical antivirals (e.g., ganiciclovir gel four to five times daily) may be helpful for recalcitrant corneal mucous plaque pseudodendrites.
4. Immune stromal keratitis: Topical steroid (e.g., prednisolone acetate 1%) started at a frequency of four to eight times per day and adjusted according to clinical response. Topical steroids are tapered over months to years using weaker steroids with a goal of less than daily dosing (e.g., q.o.d., twice weekly, once weekly, etc.).
5. Uveitis (with or without immune stromal keratitis): Topical steroid (e.g., prednisolone acetate 1%) four to eight times per day and cycloplegic drop (e.g., cyclopentolate 1% t.i.d.). See 12.1, Anterior Uveitis (Iritis/Iridocyclitis). Treat increased IOP with aggressive aqueous suppression; avoid prostaglandin analogues.
6. Neurotrophic keratitis: Treat mild epithelial defects with ophthalmic antibiotic ointment (e.g., erythromycin) four to eight times per day. If a corneal infiltrate occurs, obtain appropriate smears and cultures to rule out infection (see 4.11, Bacterial Keratitis).
If the infiltrate is sterile, and there is no response to ointment, consider punctal plugs, bandage soft contact lens, tarsorrhaphy, amniotic membrane tissue, autologous serum tears, recombinant nerve growth factor, or conjunctival flap along with prophylactic topical antibiotics (see 4.6, Neurotrophic Keratopathy).
7. Scleritis: See 5.7, Scleritis.
8. Retinitis, choroiditis, optic neuritis, or cranial nerve palsy: Acyclovir 10 mg/kg i.v. q8h for 1 week and prednisone 60 mg p.o. for 3 days, then taper over 1 week. Management of ARN or PORN may require intraocular antivirals (see 12.8, Acute Retinal Necrosis). Infectious disease and neurologic consultation to rule out central nervous system involvement should be considered. Patients with severe disease can develop a large vessel cranial arteritis resulting in a massive cerebrovascular accident.
9. Increased IOP: May be steroid response or secondary to inflammation. If uveitis is present, increase the frequency of the steroid administration for a few days and use topical aqueous suppressants (e.g., timolol 0.5% daily or b.i.d., brimonidine 0.2% t.i.d., or dorzolamide 2% t.i.d.; see 9.7, Inflammatory Open Angle Glaucoma, and 9.9, Steroid-Response Glaucoma). Oral carbonic anhydrase inhibitors may be necessary if the IOP is >30 mm Hg. If IOP remains increased and the inflammation is controlled, substitute fluorometholone 0.1% or loteprednol 0.5% drops for prednisolone acetate and attempt to taper the dose.
NOTE: Pain may be severe during the first 2 weeks, and narcotic analgesics may be required. An antidepressant (e.g., amitriptyline 25 mg p.o. t.i.d.) may be beneficial for both postherpetic neuralgia and depression that can develop in VZV. Capsaicin 0.025% or doxepin ointment may be applied to the skin t.i.d. to q.i.d. after the rash heals (not around the eyes) for postherpetic neuralgia. Oral gabapentin or pregabalin can be helpful for acute pain and for postherpetic neuralgia. Management of postherpetic neuralgia should involve the patient’s primary medical doctor or a pain management specialist.
Follow Up
If ocular involvement is present, examine the patient every 1 to 7 days, depending on the severity. Patients without ocular involvement can be followed every 1 to 4 weeks. After the acute episode resolves, check the patient every 3 to 6 months (3 if on steroids) because relapses may occur months to years later, particularly as steroids are tapered. Systemic steroid use is controversial.
NOTE: VZV is contagious for children and adults who have not had chickenpox or the chickenpox vaccine and is spread by inhalation. Varicella-naive pregnant women must be especially careful to avoid contact with a VZV-infected patient. A vaccine for shingles is recommended for people aged 50 years or older.
VARICELLA ZOSTER VIRUS (CHICKENPOX)
Symptoms
Facial rash, red eye, foreign body sensation.
Signs
Early: Acute conjunctivitis with vesicles or papules at the limbus, on the eyelid, or on the conjunctiva. Pseudodendritic corneal epithelial lesions, stromal keratitis, anterior uveitis, optic neuritis, retinitis, and ophthalmoplegia occur rarely.
Late: Immune stromal or neurotrophic keratitis.
Treatment
1. Conjunctival involvement and/or corneal epithelial lesions: Cool compresses and ophthalmic antibiotic ointment (e.g., erythromycin t.i.d.) to the eye and periorbital lesions.
2. Stromal keratitis with uveitis: Topical steroid (e.g., prednisolone acetate 1% q.i.d.), cycloplegic drop (e.g., cyclopentolate 1% t.i.d.)
3. Neurotrophic keratitis: Uncommon; see 4.6, Neurotrophic Keratopathy.
4. Canalicular obstruction: Uncommon. Managed by intubation of puncta.
NOTE:
1. Aspirin is contraindicated in children because of the risk of Reye syndrome.
2. Immunocompromised children with chickenpox may require i.v. acyclovir.
Follow Up
1. Follow up in 1 to 7 days, depending on the severity of ocular disease. Taper the topical steroids slowly.
2. Watch for stromal or neurotrophic keratitis approximately 4 to 6 weeks after the chicken pox infection resolves.
4.17 Interstitial Keratitis
IK is broadly defined as any non-ulcerating inflammation of the corneal stroma without epithelial or endothelial involvement, but often with neovascularization. IK is the common end-point of many corneal diseases.
Signs
Acute Phase
Critical. Marked corneal stromal blood vessels and edema.
Other. Anterior chamber cells and flare, fine keratic precipitates on the corneal endothelium, conjunctival injection.
Chronic Phase
(See Figure 4.17.1.)
FIGURE 4.17.1 Interstitial keratitis.
Deep corneal haze or scarring, corneal stromal blood vessels containing minimal or no blood (ghost vessels), stromal thinning.
Etiology
Most Common. HSV is the most common cause of IK (see 4.15, Herpes Simplex Virus). Other common causes include: VZV, congenital syphilis (bilateral in 80% of cases, often occurs in the first or second decade of life, rare in first years of life. Affects both eyes within 1 year of each other, more commonly occurs as late inactive/immune-mediated disease and less often as acute/infectious disease), acquired syphilis, and tuberculosis (TB, unilateral and often sectoral).
Less Common. Epstein-Barr virus (EBV) Lyme disease, leprosy, and Cogan syndrome (autoimmune disorder characterized by bilateral IK, vertigo, tinnitus, hearing loss, and negative syphilis serologies; also associated with systemic vasculitis [e.g., polyarteritis nodosa] and typically occurs in young adults).
Workup
For active IK or old, previously untreated IK:
1. History: Venereal disease in the mother during pregnancy or in the patient? Hearing loss or tinnitus? Prior HSV or shingles infections?
2. External examination: Look for saddle-nose deformity, Hutchinson teeth, frontal bossing, or other signs of congenital syphilis. Look for hypopigmented or anesthetic skin lesions and thickened skin folds, loss of the temporal eyebrow, and loss of eyelashes, as in leprosy.
3. Slit lamp examination: Examine corneal nerves for segmental thickening, like beads on a string (leprosy). Examine the iris for nodules (leprosy) and hyperemia with fleshy, pink nodules (syphilis). Check IOP.
4. Dilated fundus examination: Look for classic salt-and-pepper chorioretinitis or optic atrophy of syphilis.
5. Laboratory evaluation: Fluorescent treponemal antibody absorption (FTA-ABS) or treponemal-specific assay (e.g., microhemagglutination-Trcpoftcma pallidum [MHA-TP]) for prior exposure; Venereal Disease Research Laboratory test (VDRL) or rapid plasma reagin (RPR) for disease activity. See 12.12, Syphilis.
6. Purified protein derivative (PPD) or interferon-gamma release assay (IGRA) (e.g., QuantiFERON-TB Gold)
7. Lyme serology if in endemic region.
8. Chest radiograph or chest CT if negative FTA-ABS (or MHA-TP) or positive PPD or IGRA.
9. Consider erythrocyte sedimentation rate, rheumatoid factor, complete blood count, and EBV antibody.
Treatment
1. Acute disease:
• Topical cycloplegic drop (e.g., cyclopentolate 1% t.i.d. or atropine 1% b.i.d.).
• Topical steroid (e.g., prednisolone acetate 1% q2-6h depending on the degree of inflammation).
• Treat any underlying disease.
2. Old inactive disease with central scarring:
• RGP or scleral contact lens if vision decreased from irregular astigmatism
• Corneal transplantation may improve vision if minimal amblyopia is present.
3. Recently inactive or old inactive disease:
• If the treponemal-specific assay or FTA-ABS is positive and the patient has active or untreated syphilis, or if the VDRL or RPR titer is positive and has not declined the expected amount after treatment, then treatment for syphilis is indicated. See 12.12, Syphilis.
• If PPD or IGRA is positive and the patient is <35 years and has not been treated for TB in the past, or there is evidence of active systemic TB (e.g., positive finding on chest radiograph), then refer the patient to an internist and infectious disease specialist for TB treatment.
• If Cogan syndrome is present, refer the patient to an otolaryngologist and rheumatologist.
• If Lyme antibody and titers are positive, treat per 13.4, Lyme Disease.
Follow Up
1. Acute disease: Every 3 to 7 days initially, and then every 2 to 4 weeks. The frequency of steroid administration is slowly reduced as the inflammation subsides over the course of months (may take years). IOP is monitored closely and reduced with medications based on the degree of IOP elevation and overall health of the optic nerve (see 9.7, Inflammatory Open Angle Glaucoma).
2. Old inactive disease: Yearly follow up, unless treatment is required for underlying etiology.
4.18 Staphylococcal Hypersensitivity
Symptoms
Mild photophobia, mild pain, localized red eye, chronic eyelid crusting, foreign body sensation or dryness. History of recurrent acute episodes, chalazia, or styes.
Signs
(See Figure 4.18.1.)
FIGURE 4.18.1 Staphylococcal hypersensitivity.
Critical. Singular or multiple, unilateral or bilateral, peripheral corneal stromal infiltrates often with a clear space between the infiltrates and the limbus. Variable staining with fluorescein. Minimal anterior chamber inflammation. Sectoral conjunctival injection typically occurs.
Other. Blepharitis, inferior SPK, phlyctenule (a wedge-shaped, raised, vascularized sterile infiltrate near the limbus, usually in children). Peripheral scarring and corneal neovascularization. Findings often present in the contralateral eye or elsewhere in the affected eye.
Differential Diagnosis
• Infectious corneal infiltrates: Often round, painful, and associated with an anterior chamber reaction. Not usually multiple and recurrent. See 4.11, Bacterial Keratitis.
• Other causes of marginal thinning/infiltrates: See 4.22, Peripheral Corneal Thinning/Ulceration.
Etiology
Infiltrates are believed to be a cell-mediated, or delayed, type IV hypersensitivity reaction to bacterial antigens in the setting of staphylococcal blepharitis.
NOTE: Patients with ocular rosacea (e.g., meibomian gland inflammation and telangiectasias of the eyelids) are especially susceptible to this condition.
Workup
1. History: Recurrent episodes? Contact lens wearer (a risk factor for infection)?
2. Slit lamp examination with fluorescein staining and IOP measurement.
3. If an infectious infiltrate is suspected, then corneal scrapings for cultures and smears should be obtained. See Appendix 8, Corneal Culture Procedure.
Treatment
Mild
Warm compresses, eyelid hygiene, and an antibiotic drop q.i.d. (e.g., fluoroquinolone or trimethoprim/polymyxin B) and antibiotic ophthalmic ointment q.h.s. (e.g., bacitracin, erythromycin, bacitracin/polymyxin B). See 5.8, Blepharitis/Meibomitis.
Moderate to Severe
• Treat as described for mild, but add a low-dose topical steroid (e.g., loteprednol 0.5%, fluorometholone 0.1%, fluorometholone acetate 0.1% or prednisolone acetate 0.125% q.i.d.) with an antibiotic (e.g., fluoroquinolone or trimethoprim/polymyxin B q.i.d.). A combination antibiotic/steroid can also be used q.i.d. (e.g., loteprednol 0.5%/tobramycin 0.3%, dexamethasone 0.1%/tobramycin 0.3% or dexamethasone 0.05%/tobramycin 0.3%). Steroid use without antibiotic coverage is not recommended. Maintain until the symptoms improve and then slowly taper.
• If episodes recur despite eyelid hygiene, add systemic doxycycline (100 mg p.o. b.i.d., for 2 weeks, and then daily for 1 month, and then 50 to 100 mg daily titrated as necessary) until the ocular disease is controlled for several months. This medication has an anti-inflammatory effect on the sebaceous glands in addition to its antimicrobial action. Topical azithromycin q.h.s., erythromycin q.h.s. or cyclosporine b.i.d. may be helpful in controlling eyelid inflammation.
• Low-dose antibiotics (e.g., bacitracin or erythromycin ointment q.h.s.) may have to be maintained indefinitely.
NOTE: Tetracyclines such as doxycycline are contraindicated in children <8 years old, pregnant women, and breast feeding mothers. Erythromycin 200 mg p.o. one to two times per day can be used in children to decrease recurrent disease.
Follow Up
In 2 to 7 days, depending on the clinical picture. IOP is monitored while patients are taking topical steroids.
4.19 Phlyctenulosis
Symptoms
Tearing, irritation, pain, mild-to-severe photophobia. History of similar episodes or chalazia. Corneal phlyctenules are more symptomatic than conjunctival phlyctenules.
Signs
Critical
FIGURE 4.19.1 Corneal phlyctenule.
• Conjunctival phlyctenule: A small, rounded, white inflammatory nodule on the bulbar conjunctiva, often at or near the limbus, in the center of a hyperemic area.
• Corneal phlyctenule: A small, white nodule, initially at the limbus, with dilated conjunctival blood vessels approaching it. Often associated with epithelial ulceration and central corneal migration, producing wedge-shaped corneal neovascularization and scarring behind the leading edge of the lesion. Can be bilateral and recurrent (see Figure 4.19.1).
Other. Conjunctival injection, blepharitis, corneal scarring.
Differential Diagnosis
• Inflamed pinguecula: Uncommon in children. Located in the palpebral fissure. Connective tissue often seen from lesion to the limbus. Often bilateral. See 4.9, Pterygium/Pinguecula.
• Infectious corneal ulcer: With migration, corneal phlyctenules produce a sterile ulcer surrounded by a white infiltrate. When an infectious ulcer is suspected (e.g., increased pain, anterior chamber reaction), appropriate antibiotic treatment and diagnostic smears and cultures are necessary. See Appendix 8, Corneal Culture Procedure.
• Staphylococcal hypersensitivity: Peripheral corneal infiltrates, sometimes with an overlying epithelial defect; usually multiple, often bilateral, with a clear space between the infiltrate and the limbus. Minimal anterior chamber reaction. See 4.18, Staphylococcal Hypersensitivity.
• Ocular rosacea: Corneal neovascularization with thinning and subepithelial infiltration may develop in an eye with rosacea. See 5.9, Ocular Rosacea.
• Herpes simplex keratitis: May produce corneal neovascularization associated with a stromal infiltrate. Usually unilateral. See 4.15, Herpes Simplex Virus.
Etiology
Delayed hypersensitivity reaction usually as a result of one of the following:
• Staphylococcus: Usually related to blepharitis. See 4.18, Staphylococcal Hypersensitivity.
• Rarely TB or another infectious agent (e.g., Coccidiomycosis, Candidiasis, lymphogranuloma venereum).
Workup
1. History: TB or recent infection?
2. Slit lamp examination: Inspect the eyelid margin for signs of Staphylococcal anterior blepharitis and rosacea.
3. PPD and/or IGRA in patients without blepharitis and those at high risk for TB.
4. Chest radiograph or chest CT if high suspicion for TB or positive PPD or IGRA.
Treatment
Indicated for symptomatic patients.
1. Topical steroid (e.g., loteprednol 0.5% or prednisolone acetate 1% q.i.d., depending on the severity of symptoms). A combination antibiotic/steroid can also be used q.i.d. (e.g., loteprednol 0.5%/tobramycin 0.3% or dexamethasone 0.1%/tobramycin 0.3%).
2. Topical ophthalmic antibiotic regimen in the presence of corneal ulcer. See 4.11, Bacterial Keratitis. Otherwise antibiotic ointment (e.g., erythromycin, bacitracin) q.h.s.
3. Eyelid hygiene b.i.d. to t.i.d. for blepharitis. See 5.8, Blepharitis/Meibomitis.
4. Preservative-free artificial tears four to six times per day.
5. In severe cases of blepharitis or acne rosacea, use doxycycline 100 mg p.o. daily. to b.i.d., or erythromycin 200 mg p.o. daily to b.i.d. See 5.8, Blepharitis/Meibomitis.
6. If the PPD, IGRA, or chest radiograph is positive for TB, refer the patient to an internist or infectious disease specialist for management.
Follow Up
Recheck in several days. Healing usually occurs over a 10- to 14-day period, with a residual stromal scar. When the symptoms have significantly improved, slowly taper the steroid. Maintain the antibiotic ointment and eyelid hygiene indefinitely. Continue oral antibiotics for 3 to 6 months. Topical cyclosporine may be a beneficial steroid-sparing agent in patients with recurrent inflammation.
4.20 Contact Lens-Related Problems
Symptoms
Pain, photophobia, foreign body sensation, decreased vision, red eye, itching, discharge, burning, and contact lens intolerance.
NOTE: Any contact lens wearer with pain or redness should remove the lens immediately and have a thorough ophthalmic examination as soon as possible if symptoms persist or worsen.
Signs
See the distinguishing characteristics of each etiology.
Etiology
• Infectious corneal infiltrate/ulcer (bacterial, fungal, Acanthamoeba): White corneal lesion that may stain with fluorescein. Must always be ruled out in contact lens patients with eye pain. See 4.11, Bacterial Keratitis, 4.12, Fungal Keratitis, and 4.13, Acanthamoeba Keratitis.
• Giant papillary conjunctivitis: Itching, mucous discharge, and lens intolerance in a patient with large superior tarsal conjunctival papillae. See 4.21, Contact Lens-Induced Giant Papillary Conjunctivitis.
• Hypersensitivity/toxicity reactions to preservatives in solutions: Conjunctival injection and ocular irritation typically develop shortly after lens cleaning and insertion, but can be present chronically. A recent change from one type or brand of solution is common. It not only occurs more often in patients using older preserved solutions (e.g., thimerosal or chlorhexidine as a component) but also is seen with newer “all-purpose” solutions. May be due to inadequate rinsing of lenses after enzyme use. Signs include SPK, conjunctival injection, bulbar conjunctival follicles, subepithelial or stromal corneal infiltrates, superior epithelial irregularities, and superficial scarring.
• Contact lens deposits: Multiple small deposits on the contact lens, leading to corneal and conjunctival irritation. The contact lens is often old and may not have been cleaned or enzyme-treated properly in the past.
• Tight lens syndrome: Symptoms may be severe and often develop within 1 or 2 days of contact lens fitting (usually a soft lens), especially if patient sleeps overnight with daily-wear lenses. No lens movement with blinking and lens appears “sucked-on" to the cornea (this can occur after rewearing a soft lens that has dried out and then been rehydrated). An imprint in the conjunctiva is often observed after the lens is removed. Central corneal edema, SPK, anterior chamber reaction, and sometimes a sterile hypopyon may develop.
• Contact lens-associated red eye (CLARE): Red eye, corneal edema, iritis with or without hypopyon, hypoxic subepithelial, or stromal infiltrates (often multiple) may be present.
• Corneal warpage: Seen predominantly in long-term polymethylmethacrylate hard contact lens wearers. Initially, the vision becomes blurred with glasses (“spectacle blur") but remains good with contact lenses. Keratometry reveals distorted mires and corneal topography shows irregular astigmatism that usually eventually resolves after lens discontinuation.
• Corneal neovascularization: Patients are often asymptomatic until the visual axis is involved. Superficial corneal neovascularization for 1 mm is common and usually not a concern in aphakic contact lens wearers. With any sign of chronic hypoxia, the goal is to increase oxygen permeability, increase movement, and discontinue extended-wear lenses.
• Limbal stem cell deficiency: Early signs include punctate staining in a whorl-like pattern of the epithelium near the limbus, often superiorly. If untreated, the epitheliopathy can extend to involve the entire cornea. Neovascularization and haze can develop.
• Contact lens keratopathy (pseudo-SLK): Hyperemia and fluorescein staining of the superior bulbar conjunctiva, particularly at the limbus. SPK, subepithelial infiltrates, stromal haze, and irregularity may be found on the superior cornea. This may represent a hypersensitivity or toxicity reaction to preservatives in contact lens solutions (classically thimerosal, but newer preservatives as well). No corneal filaments, papillary reaction, or association with thyroid disease.
• Displaced contact lens: Most commonly the lens has actually fallen out of the eye and been lost. If retained, the lens is usually found in the superior fornix and may require double eversion of the upper eyelid to remove. Fluorescein will stain a soft lens to aid in finding it.
• Others: Contact lens inside out, corneal abrasion (see 3.2, Corneal Abrasion), poor lens fit, damaged contact lens, and change in refractive error.
Workup
1. History: Main complaint (mild-to-severe pain, discomfort, itching)? Type of contact lens (soft, hard, gas-permeable, extended wear, frequent replacement, or single-use daily disposable)? Age of lens? When lens last worn? Continuous time lens are worn? Sleeping in lenses? How are the lenses cleaned and disinfected? Are enzyme tablets used? Preservative-free products? Recent changes in contact lens habits or solutions? How is the pain related to wearing time? Is pain relieved by removal of the lens?
2. In noninfectious conditions, while the contact lens is still in the eye, evaluate its fit and examine its surface for deposits, irregularities, and defects at the slit lamp.
3. Remove lens and examine the eye with fluorescein. Evert the upper eyelids of both eyes and inspect the superior tarsal conjunctiva for papillae.
4. Smears and cultures are taken when an infectious corneal ulcer is suspected with infiltrate >1 mm, involvement of visual axis, or when an unusual organism is suspected (e.g., Acanthamoeba or fungus). See 4.11, Bacterial Keratitis, 4.12, Fungal Keratitis, 4.13, Acanthamoeba keratitis, and Appendix 8, Corneal Culture Procedure.
5. The contact lenses and lens case are also cultured occasionally.
Treatment
When the diagnosis of infection is suspected:
1. Discontinue contact lens wear.
2. Antibiotic treatment regimen varies with diagnosis as follows:
Possible Corneal Ulcer (Corneal Infiltrate, Epithelial Defect, Anterior Chamber Reaction, Pain)
a. Obtain appropriate smears and cultures. See Appendix 8, Corneal Culture Procedure.
b. Start intensive topical antibiotics, See 4.11, Bacterial Keratitis.
Small Subepithelial Infiltrates, Corneal Abrasion, or Diffuse SPK
a. Topical antibiotic (e.g., fluoroquinolone) drops four to eight times per day and a cycloplegic drop.
b. Can also add fluoroquinolone or bacitracin/polymyxin B ointment q.h.s. Beware of toxicity with long-term use.
c. See 3.2, Corneal Abrasion or 4.1, Superficial Punctate Keratopathy for specific details.
NOTE: Never pressure patch a contact lens wearer because of the risk of rapid development of infection.
When a specific contact lens problem is suspected, it may be treated as follows:
Giant Papillary Conjunctivitis
(See 4.21, Contact Lens-Induced Giant Papillary Conjunctivitis)
Hypersensitivity/Toxicity Reaction
a. Discontinue contact lens wear.
b. Preservative-free artificial tears four to six times per day.
c. On resolution of the condition, the patient may return to new contact lenses, preferably daily disposable lenses. If the patient desires frequent-replacement or conventional lenses, hydrogen peroxide-based systems are recommended, and appropriate lens hygiene is reviewed.
Contact Lens Deposits
a. Discontinue contact lens wear.
b. Replace with a new contact lens once the symptoms resolve. Consider changing the brand of contact lens, or change to daily disposable or frequent replacement lens.
c. Teach proper contact lens care, stressing weekly enzyme treatments for lenses replaced less frequently than every 2 weeks.
Tight Lens Syndrome and CLARE
a. Discontinue contact lens wear.
b. Consider a topical cycloplegic drop (e.g., cyclopentolate 1% t.i.d.) in the presence of an anterior chamber reaction.
c. Once resolved, refit patients with a flatter and more oxygen- permeable contact lens. Discontinue extended-wear contact lenses.
d. If a soft lens has dried out, discard and refit.
NOTE: Patients with small hypopyon do not need to be cultured when tight lens syndrome is highly suspected (i.e., if epithelium intact, with edema but no infiltrate).
Corneal Warpage
a. Discontinue contact lens wear. Explain to patients that vision may be poor for the following 2 to 6 weeks, and they may require a change in spectacle prescription. May need to discontinue lenses one eye at a time so patient can function.
b. A gas-permeable hard contact lens should be refitted when the refraction and keratometric readings have stabilized.
Corneal Neovascularization
a. Discontinue contact lens wear.
b. Consider a topical steroid (e.g., prednisolone 1% q.i.d. or loteprednol 0.5% q.i.d.) for extensive deep neovascularization (rarely necessary).
c. Refit carefully with a highly oxygen-transmissible, daily-wear disposable contact lens that moves adequately over the cornea.
Limbal Stem Cell Deficiency
a. Discontinue contact lens wear.
b. Use preservative-free artificial tears and lubricating ointment.
c. Consider punctal occlusion.
d. Consider a short course of topical steroids (e.g., loteprednol 0.5%, fluorometholone 0.1% or fluorometholone acetate 0.1%).
e. Consider autologous serum drops (e.g. 20% q.i.d.).
f. In more advanced cases surgical considerations including selective epithelial debridement for partial limbal stem cell deficiency or limbal stem cell grafting in complete limbal stem cell deficiency may be indicated.
Pseudo-Superior Limbic Keratoconjunctivitis
a. Treat as described for hypersensitivity/toxicity reactions. Use preservative-free artificial tears. When a large subepithelial opacity extends toward the visual axis, topical steroids may be added cautiously (e.g., loteprednol 0.5% q.i.d.), but they are often ineffective. Steroid use in contact lens-related problems should have concomitant antibiotic coverage.
Displaced Lens
a. Inspect lens carefully for damage. If lens is undamaged, clean and disinfect it; if damaged, discard and replace. Recheck fit when symptoms have resolved.
Follow Up
1. Next day if infection cannot be ruled out. Treatment is maintained until the condition clears.
2. In noninfectious conditions, reevaluate in 1 to 4 weeks, depending on the clinical situation. Contact lens wear is resumed when the condition resolves. Patients using topical steroids should be followed more closely with attention to IOP monitoring.
3. The following regimen for contact lens care is one we recommend if single-use daily disposable lenses are not possible:
a. Daily cleaning and disinfection with removal of lenses while sleeping for all lens types, including those approved for "extended wear" and "overnight wear." We prefer standard rather than hyperoxygen-transmissible lenses for frequent replacement, as the latter may allow greater adherence for organisms.
b. Daily cleaning regimen for soft contact lenses:
• Preservative-free daily cleaner.
• Preservative-free saline.
• Disinfectant, preferably hydrogen peroxide type.
• Disinfection solutions must be used for recommended time (hours) prior to lens reinsertion.
• Weekly treatment with enzyme tablets (not necessary in disposable lenses replaced every 2 to 4 weeks or less).
c. RGP lenses: Cleaning/soaking/rinsing all in one solution. Lenses can be reinserted soon after the removal from disinfecting solution.
4.21 Contact Lens-Induced Giant Papillary Conjunctivitis
Symptoms
Itching, mucous discharge, contact lens intolerance, increased contact lens awareness, and excessive lens movement.
Signs
Critical. Giant papillae on the superior tarsal conjunctiva (see Figure 4.21.1).
FIGURE 4.21.1 Giant papillary conjunctivitis.
NOTE: The upper eyelid must be everted to make the diagnosis. Upper eyelid eversion should be part of the routine eye examination in any patient who wears contact lenses.
Other. Contact lens coatings, high-riding lens, mild conjunctival injection, ptosis (usually a late sign).
Differential Diagnosis
• Vernal keratoconjunctivitis: Bilateral allergic conjunctivitis more commonly seen in younger patients. Seasonal variation (spring and summer tend to be the worst). Gelatinous limbal papillae (Horner-Trantas Dots) and shield ulcer may be present.
• Atopic keratoconjunctivitis: History of atopy, dermatitis, and/or asthma. Giant papillae occasionally seen in both superior and inferior conjunctiva.
NOTE: Consider alternative etiology if no improvement of papillae with discontinuation of contact lens wear or if systemic symptoms present.
Workup
1. History: Details of contact lens use, including the age of lenses, daily or extended wear, the frequency of replacement, and the cleaning and enzyme treatment regimen.
2. Slit lamp examination: Evert the upper eyelids and examine for large papillae (>1 mm).
Treatment
1. Modify contact lens regimen as follows:
Mild-to-Moderate Giant Papillary Conjunctivitis
a. Replace and refit the contact lens. Consider planned replacement or daily disposable lenses (daily disposable lenses preferred).
b. Reduce contact lens wearing time (switch from extended-wear contact lens to daily-wear).
c. Have the patient clean the lenses more thoroughly, preferably by using preservative-free solutions, preservative-free saline, and a hydrogen peroxide-based disinfection system.
d. Increase enzyme use (use at least every week).
Severe Giant Papillary Conjunctivitis
a. Suspend contact lens wear.
b. Restart with a new contact lens when the symptoms and signs clear (usually 1 to 4 months), preferably with daily disposable soft contact lenses.
c. Careful lens hygiene as described earlier.
d. Start a topical mast cell stabilizer or combination antihistamine/mast cell stabilizer (e.g., pemirolast, nedocromil, lodoxamide, cromolyn, alcaftadine, olopatadine, bepotastine, or epinastine).
e. In unusually severe cases, short-term use of a low-dose topical steroid may be considered (e.g., loteprednol 0.5%, fluorometholone 0.1% or fluorometholone acetate 0.1% q.i.d.). Contact lenses should not be worn while using a topical steroid.
f. Steroid sparring topical anti-inflammatory agents such as cyclosporine 0.05% or 0.09% or lifitegrast 5% may be beneficial if long-term treatment is needed.
Follow Up
In 2 to 4 weeks. The patient may resume contact lens wear once the symptoms are resolved. Symptoms may improve before papillae resolve. Mast cell stabilizers are continued while the signs remain, and they may need to be used chronically to maintain contact lens tolerance. If topical steroids are used, they are usually slowly tapered and patients need to be monitored for steroid side effects.
NOTE: Giant papillary conjunctivitis can result not only from contact lens wear and atopic/vernal conjunctivitis, but also an exposed suture or an ocular prosthesis. Exposed sutures are removed. Prostheses should undergo routine cleaning and polishing. A coating can be placed on the prosthesis to reduce giant papillary conjunctivitis. Otherwise, these entities are treated as described earlier.
4.22 Peripheral Corneal Thinning/Ulceration
Symptoms
Pain, photophobia, red eye; may be asymptomatic.
Signs
Peripheral corneal thinning (best seen with a narrow slit beam); may be associated with sterile infiltrate or ulcer.
Differential Diagnosis
Infectious infiltrate or ulcer. Lesions are often treated as infectious until cultures come back negative. See 4.11, Bacterial Keratitis.
FIGURE 4.22.1 Peripheral ulcerative keratitis.
Etiology
• Peripheral ulcerative keratitis (PUK), idiopathic or related to systemic connective tissue disease: Rheumatoid arthritis, GPA, relapsing polychondritis, polyarteritis nodosa, systemic lupus erythematosus, others. Peripheral (unilateral or bilateral) corneal thinning/ulcers may be associated with sterile inflammatory infiltrates. The sclera may be involved. May progress circumferentially to involve the entire peripheral cornea. Perforation may occur. This may be the first manifestation of systemic disease (see Figure 4.22.1).
• Terrien marginal degeneration: Usually bilateral, often asymptomatic. Slowly progressive thinning of the peripheral cornea; typically superior; more often in men. The anterior chamber is quiet, and the eye is typically not injected although may be associated with inflammatory signs and symptoms secondary to epithelial breakdown and inflammatory or infectious infiltrates. A yellow line (lipid) may appear, with a fine pannus along the central edge of the thinning. The thinning may slowly spread circumferentially. Refractive changes, including irregular and against-the-rule astigmatism are often present. The epithelium usually remains intact, but perforation may occur with minor trauma.
• Mooren ulcer: Unilateral or bilateral. Painful corneal thinning and ulceration with inflammation. Initially starts as a focal area in the peripheral cornea, nasally or temporally with involvement of the limbus; later extends circumferentially or centrally. Unlike PUK, Mooren ulcer usually does not involve the sclera. An epithelial defect, stromal infiltrate/thinning, and an undermined leading edge are typically present. Limbal blood vessels may grow into the ulcer, and perforation can occur. Idiopathic (autoimmunity may play a key role); diagnosis of exclusion after ruling out the aforementioned systemic causes of PUK. Mooren-like ulcer has been associated with systemic hepatitis C virus infection. Bilateral cases are more resistant to treatment than unilateral cases.
• Pellucid marginal degeneration: Painless, non-inflammatory bilateral asymmetric corneal thinning of the inferior peripheral cornea (usually from the 4- to 8-o’clock portions). There is no anterior chamber reaction, conjunctival injection, lipid deposition, or vascularization. The epithelium is intact. Corneal protrusion may be seen above the area of thinning. The thinning may slowly progress.
• Furrow degeneration: Painless corneal thinning just peripheral to an arcus senilis, typically in the elderly. Noninflammatory without vascularization. Perforation is rare. Usually nonprogressive and does not require treatment.
• Delle: Painless oval corneal thinning resulting from corneal drying and stromal dehydration adjacent to an abnormal conjunctival or corneal elevation. The overlying epithelium may be compromised but is often intact. See 4.23, Delle.
• Staphylococcal hypersensitivity/marginal keratitis: Peripheral, white corneal infiltrate(s) with limbal clearing that may have an epithelial defect and mild thinning. See 4.18, Staphylococcal Hypersensitivity.
• Dry eye syndrome: Peripheral (or central) sterile corneal melts may result from severe cases of dry eye. See 4.3, Dry Eye Syndrome.
• Exposure/neurotrophic keratopathy: In severe cases, a sterile oval ulcer may develop in the inferior interpalpebral portion of the cornea without signs of significant inflammation. May be associated with an eyelid abnormality, a fifth or seventh cranial nerve defect, or proptosis. The ulcer may become superinfected. See 4.5, Exposure Keratopathy and 4.6, Neurotrophic Keratopathy.
• Sclerokeratitis: Corneal ulceration may be associated with scleritis. Scleral edema with or without nodules develops, scleral vessels become engorged, and the sclera may develop a blue hue. An underlying connective tissue disease, especially GPA, must be ruled out. See 5.7, Scleritis.
• Ocular rosacea: Typically affects the inferior cornea in middleaged patients. Erythema and telangiectasia of the eyelid margins, corneal neovascularization. See 5.9, Ocular Rosacea.
• Others: Cataract surgery, inflammatory bowel disease, previous HSV or VZV infections, and leukemia can rarely cause peripheral corneal thinning/ulceration.
Workup
1. History: Contact lens wearer or previous HSV or VZV keratitis? Connective tissue disease or inflammatory bowel disease? Other systemic symptoms? Seasonal conjunctivitis with itching (vernal)? Prior ocular surgery?
2. External examination: Old facial scars of VZV? Lagophthalmos or other eyelid closure problem causing exposure? Blue tinge to the sclera? Rosacea facies?
3. Slit lamp examination: Look for infiltrate, corneal ulcer, hypopyon, uveitis, scleritis, old herpetic corneal scarring, poor tear lake, SPK, blepharitis. Check corneal sensation prior to instilling anesthetic. Look for giant papillae on the superior tarsal conjunctiva or limbal papillae. Measure IOP.
4. Schirmer test (see 4.3, Dry Eye Syndrome).
5. Dilated fundus examination: Look for cotton-wool spots consistent with connective tissue disease or evidence of posterior scleritis (e.g., vitritis, subretinal fluid, chorioretinal folds, exudative retinal detachment).
6. Corneal scrapings and cultures when infection is suspected. See Appendix 8, Corneal Culture Procedure.
7. Consider systemic workup including serum erythrocyte sedimentation rate, complete blood count with differential, rheumatoid factor, antinuclear antibody, antineutrophilic cytoplasmic antibody levels, angiotensin-converting enzyme, and chest x-ray or CT to rule out connective tissue disease and leukemia.
8. Scleritis workup, when present (see 5.7, Scleritis).
9. Refer to an internist (and/or rheumatologist) when connective tissue disease is suspected.
Treatment
See sections on delle, staphylococcal hypersensitivity, dry eye syndrome, exposure and neurotrophic keratopathies, scleritis, vernal conjunctivitis, and ocular rosacea.
1. PUK associated systemic immune-mediated disease: Management is usually coordinated with an internist or rheumatologist.
• Ophthalmic antibiotic ointment (e.g., erythromycin ointment) or preservative-free artificial tear ointment q2h.
• Cycloplegic drop (e.g., cylopentolate 1% or atropine 1% b.i.d. to t.i.d.) when an anterior chamber reaction or pain is present.
• Consider doxycycline 100 mg p.o. b.i.d. for its metalloproteinase inhibition properties and ascorbic acid (vitamin C 1 to 2 g daily) as a collagen synthesis promoter.
• Systemic steroids (e.g., prednisone 60 to 100 mg p.o. daily; dosage is adjusted according to the response) and antiulcer prophylaxis (e.g., ranitidine 150 mg p.o. b.i.d. or pantoprazole 40 mg daily) are used for significant and progressive corneal thinning, but not for perforation.
• An immunosuppressive agent (e.g., methotrexate, mycophenolate mofetil, infliximab, azathioprine, cyclophosphamide) is often required, especially for GPA. This should be done in coordination with the patient’s internist or rheumatologist.
• Excision or recession of adjacent inflamed conjunctiva is occasionally helpful when the condition progresses despite treatment.
• Punctal occlusion if dry eye syndrome is present. Topical cyclosporine 0.05% to 2% b.i.d. to q.i.d. or lifitegrast 5% b.i.d. may also be helpful. See 4.3, Dry Eye Syndrome.
• Consider cyanoacrylate tissue adhesive or corneal transplantation surgery for an impending or actual corneal perforation. A conjunctival flap or amniotic membrane graft can also be used for an impending corneal perforation.
• Patients with significant corneal thinning should wear their glasses (or protective glasses [e.g., polycarbonate lens]) during the day and an eye shield at night.
NOTE: Topical steroids should be used with caution in the presence of significant corneal thinning because of the risk of perforation. Gradually taper topical steroids if the patient is already taking them. Notably, corneal thinning due to relapsing polychondritis may improve with topical steroids (e.g., prednisolone acetate 1% q1-2h).
2. Terrien marginal degeneration: Correct astigmatism with glasses or contact lenses if possible. Protective eyewear should be worn if significant thinning is present. Lamellar grafts can be performed if thinning is extreme.
3. Mooren ulcer: Underlying systemic diseases must be ruled out before this diagnosis can be made. Topical steroids, topical cyclosporine 0.05% to 2%, limbal conjunctival excision, corneal gluing, and lamellar or penetrating keratoplasty may be beneficial. Systemic immunosuppression (e.g., oral steroids, methotrexate, cyclophosphamide, and cyclosporine) has been described.
4. Pellucid marginal degeneration: See 4.24, Keratoconus.
5. Furrow degeneration: No treatment is required.
Follow Up
Patients with severe disease are examined daily; those with milder conditions are checked less frequently. Watch carefully for signs of superinfection (e.g., increased pain, stromal infiltration, anterior chamber cells and flare, conjunctival injection), increased IOP, and progressive corneal thinning. Treatment is maintained until the epithelial defect over the ulcer heals and is then gradually tapered. As long as an epithelial defect is present, there is risk of progressive thinning and perforation.
4.23 Delle
Symptoms
Irritation and foreign body sensation or may be asymptomatic.
Signs
Critical. Corneal thinning, usually at the limbus, often in the shape of an ellipse, accompanied by an adjacent focal conjunctival or corneal elevation.
Other. Fluorescein pooling in the area but can stain. No infiltrate, no anterior chamber reaction, mild-to-moderate hyperemia.
Differential Diagnosis
See 4.22, Peripheral Corneal Thinning/Ulceration.
Etiology
Poor spread of the tear film over a focal area of cornea (with resultant stromal dehydration) due to an adjacent surface elevation (e.g., chemosis, conjunctival hemorrhage, filtering bleb, pterygium, tumor, and poststrabismus surgery).
Workup
1. History: Previous eye surgery?
2. Slit lamp examination with fluorescein staining: Look for an adjacent area of elevation.
Treatment
1. Lubricating or antibiotic ophthalmic ointment every 2 to 4 hours and q.h.s. Temporary patching can be helpful in promoting corneal stromal rehydration in presence of excessive thinning.
2. Treat the causative elevated lesion according to etiology. Surgical excision may be necessary.
3. If the cause cannot be removed (e.g., filtering bleb), lubricating ointment should be applied nightly, and viscous artificial tear drops should be used four to eight times per day. If drops are needed more than four times per day, a preservative-free drop should be used.
Follow Up
Unless there is severe thinning, reexamination can be performed in 1 to 7 days, at which time the cornea can be expected to be of normal thickness. If it is not, continue aggressive lubrication.
4.24 Keratoconus
Symptoms
Progressive decrease in vision, starbursts and halos, usually beginning in adolescence and continuing into middle age. Acute corneal hydrops can cause a sudden decrease in acuity, pain, red eye, photophobia, and profuse tearing.
Signs
(See Figure 4.24.1.)
FIGURE 4.24.1 Keratoconus.
Critical. Non-inflammatory ectasia of corneal stroma seen as slowly progressive irregular astigmatism resulting from paracentral (usually inferior) thinning and bulging of the cornea (maximal thinning near the apex of the protrusion), vertical tension lines in the posterior cornea (Vogt striae), an irregular corneal retinoscopic reflex (scissor reflex), and egg-shaped mires on keratometry. Inferior steepening is seen on corneal topographic evaluation, and inferocentral posterior elevation and thinning are seen on tomographic evaluation. Almost always bilateral but often asymmetric.
Other. Fleischer ring (epithelial iron deposits at the base of the cone), bulging of the lower eyelid when looking downward (Munson sign), superficial apical scarring. Corneal hydrops (sudden development of corneal edema) results from a rupture in Descemet membrane (see Figure 4.24.2).
FIGURE 4.24.2 Acute corneal hydrops.
Associations
Keratoconus is associated with sleep apnea, floppy eyelid syndrome, Down syndrome, atopic disease, Turner syndrome, Leber congenital amaurosis, mitral valve prolapse, retinitis pigmentosa, and Marfan syndrome. It frequently is related to chronic eye rubbing. Family history of keratoconus is also a risk factor.
Differential Diagnosis
• Pellucid marginal degeneration: Uncommon, nonhereditary. Corneal thinning in the inferior periphery from 4 to 8 o’clock, 1 to 2 mm from the limbus. Absence of inflammation. The cornea protrudes superior to the band of thinning manifesting in high irregular against the rule astigmatism.
NOTE: Treatment for pellucid marginal degeneration is the same as for keratoconus, except corneal transplantation (penetrating or lamellar) is technically more difficult due to peripheral thinning and has a higher failure rate because larger grafts are necessary.
• Keratoglobus: Rare, congenital, nonhereditary, nonprogressive. Uniform globular-shaped cornea with thinning from limbus to limbus. Associated with Ehlers-Danlos syndrome and blue sclera.
• Post-refractive surgery ectasia: After lamellar refractive surgery such as LASIK and SMILE, and rarely surface ablation, a condition very similar to keratoconus can develop. It is treated in the same manner as keratoconus.
Workup
1. History: Duration and rate of decreased vision? Frequent change in eyeglass prescriptions? History of eye rubbing? Allergies? Medical problems? Family history? Previous refractive surgery?
2. Slit lamp examination with close attention to location and characteristics of corneal thinning, Vogt striae, and a Fleischer ring (may be best appreciated with cobalt blue light).
3. Retinoscopy and refraction. Look for irregular astigmatism and a waterdrop or scissors red reflex.
4. Corneal topography (can show central and inferior steepening), tomography (can show posterior corneal elevation, thinning, and inferior displacement of the thinnest location), and keratometry (irregular mires and steepening).
Treatment
1. Patients are instructed not to rub their eyes.
2. Correct refractive errors with glasses or soft contact lenses (for mild cases) or RGP or scleral contact lenses (successful in most cases). Hybrid or piggyback contact lenses are other options.
3. Partial-thickness (deep anterior lamellar keratoplasty) or fullthickness corneal transplantation surgery is usually indicated when contact lenses cannot be tolerated or no longer produce satisfactory vision.
4. Intracorneal ring segments have been successful in getting some patients back into contact lenses, especially in mild-to-moderate keratoconus.
5. Corneal cross-linking (CXL) is a procedure performed to slow or arrest actively progressive disease by strengthening molecular bonds between collagen fibrils. The currently FDA approved protocol involves creation of a 9 mm corneal epithelial defect after which riboflavin drops are placed on the cornea for at least 30 minutes and then ultraviolet light is applied to the cornea for another 30 minutes. While FDA approved for ages 14 years and older, it can be performed off-label for younger children.
Acute corneal hydrops:
• Descemet membrane usually heals and edema resolves by 3 months. However, treatment may be helpful.
• Cycloplegic agent (e.g., cyclopentolate 1% t.i.d) may be beneficial for relief of pain if there is an associated anterior chamber reaction. In some patients, dilating the pupil can exacerbate photosensitivity,
• Consider an aqueous suppressant such as brimonidine 0.1% b.i.d. to t.i.d.
• Start sodium chloride 5% ointment b.i.d. to q.i.d. until resolved (usually several weeks to months).
• Consider topical steroids to suppress corneal neovascularization and/or enhance ocular comfort.
• Glasses or a shield should be worn by patients at risk for trauma or by those who rub their eyes.
• Intracameral air, SF6, or C3F8 may help edema resolve more quickly, but may be equivalent to conservative management in final BCVA. Such intervention can cause cataract and pupillary block glaucoma. Rarely, full thickness corneal suturing of the cleft may speed resolution but may also cause aqueous leakage.
NOTE: Acute hydrops is not an indication for emergency corneal transplantation, except in the extremely rare case of corneal perforation (which is first treated medically and sometimes with tissue adhesives). Slow aqueous leakage through the stromal fluid cleft and edematous epithelium can occur and usually resolves on its own.
Follow Up
Every 3 to 12 months, depending on the progression of symptoms. After an episode of hydrops, examine the patient every 1 to 4 weeks until resolved (which can take several months).
4.25 Corneal Dystrophies
Typically bilateral, progressive corneal disorders without inflammation or corneal neovascularization. No relationship to environmental or systemic factors. Most are autosomal dominant disorders except for macular dystrophy, type 3 lattice dystrophy, and congenital hereditary endothelial dystrophy (autosomal recessive).
NOTE: The IC3D (International Committee for Classification of Corneal Dystrophies) system of corneal dystrophy classification has described dystrophies according to the layer chiefly affected; epithelial and subepithelial, epithelial-stromal, stromal, and those affecting Descemet membrane and the endothelium. Dystrophies with a known common genetic basis (TGFBI) are also grouped together.
EPITHELIAL AND SUBEPITHELIAL DYSTROPHIES
Epithelial Basement Membrane Dystrophy (Map-Dot- Fingerprint Dystrophy)
Most common anterior dystrophy. Diffuse gray patches (maps), creamy white cysts (dots), or fine refractile lines (fingerprints) in the corneal epithelium, best seen with retroillumination or a broad slit lamp beam angled from the side (see Figures 4.25.1 and 4.25.2). Spontaneous painful corneal erosions may develop, particularly on opening the eyes after sleep. May cause decreased vision, monocular diplopia, and shadow images. See 4.2, Recurrent Corneal Erosion, for treatment.
FIGURE 4.25.1 Epithelial basement membrane dystrophy with multiple “maps and dots” centrally.
FIGURE 4.25.2 Epithelial basement membrane dystrophy depicting multiple “fingerprint” lines.
Meesmann Dystrophy
Rare, epithelial dystrophy that is seen in the first years of life, but is usually asymptomatic until middle age. Retroillumination shows discrete, tiny epithelial vesicles involving the whole cornea but can be segmental (see Figures 4.25.3 and 4.25.4). Although treatment is usually not required, bandage soft contact lenses or superficial keratectomy may be beneficial if significant photophobia is present or if visual acuity is severely affected.
FIGURE 4.25.3 Meesmann corneal dystrophy demonstrating multiple tiny discrete vesicles in direct illumination.
FIGURE 4.25.4 Meesmann corneal dystrophy demonstrating multiple tiny discrete vesicles in retroillumination.
Epithelial-Stromal TGFBI Dystrophies: Reis-Bucklers and Thiel-Behnke
Appears early in life. Subepithelial, gray reticular opacities are seen primarily in the central cornea (see Figure 4.25.5). Painful episodes from recurrent erosions are relatively common and require treatment. Corneal transplantation surgery may be necessary to improve vision, but the dystrophy often recurs in the graft. Excimer laser PTK or superficial lamellar keratectomy may be adequate treatment in many cases.
FIGURE 4.25.5 Reis-Bucklers corneal dystrophy.
CORNEAL STROMAL DYSTROPHIES
When these conditions cause reduced vision, patients usually benefit from a corneal transplant (lamellar or penetrating) or excimer laser PTK.
FIGURE 4.25.6 Lattice dystrophy with branching lines.
Lattice Dystrophy
Four clinical forms:
• Type 1 (most common): Refractile branching lines, white subepithelial dots, and scarring of the corneal stroma centrally, best seen with retroillumination. Recurrent erosions are common (see 4.2, Recurrent Corneal Erosion). The corneal periphery is typically clear (see Figure 4.25.6). Tends to recur within 5 years after excimer laser PTK or corneal transplantation.
• Type 2 (Meretoja syndrome): Associated with systemic amyloidosis, mask-like facies, ear abnormalities, cranial and peripheral nerve palsies, dry and lax skin.
• Types 3 and 4: Symptoms delayed until fifth to seventh decades.
Granular Dystrophy, Type I
Classic granular dystrophy. White anterior stromal deposits in the central cornea, separated by discrete clear intervening spaces (“bread crumb-like” opacities) (see Figure 4.25.7). The corneal periphery is spared. Appears in the first decade of life but rarely becomes symptomatic before adulthood. Recurrent erosions can occur. Also may recur after excimer laser PTK or corneal transplantation within 5 years.
FIGURE 4.25.7 Granular dystrophy with discrete opacities.
Granular Dystrophy, Type II
Also known as combined granular-lattice dystrophy or Avellino dystrophy. Similar to granular dystrophy type I but with significant amyloid deposition consistent with lattice dystrophy.
Macular Dystrophy
Gray-white stromal opacities with ill-defined edges extending from limbus to limbus with cloudy intervening spaces (see Figure 4.25.8). Can involve the full thickness of the stroma, more superficial centrally and deeper peripherally. Corneas tend to be flatter and thinner than normal. Causes late decreased vision more commonly than recurrent erosions. May recur many years after corneal transplantation. Autosomal recessive.
FIGURE 4.25.8 Macular dystrophy showing opacities with ill-defined borders.
Schnyder Corneal Dystrophy
Fine, yellow-white anterior stromal crystals located in the central cornea are seen in half of the patients (see Figure 4.25.9). Later develop full-thickness central haze and a dense arcus senilis. Workup includes fasting serum cholesterol and triglyceride levels due to association with systemic lipid abnormalities. Can compromise vision enough to require excimer laser PTK or corneal transplantation. See 4.14, Crystalline Keratopathy.
FIGURE 4.25.9 Anterior stromal crystals in Schnyder corneal dystrophy.
DESCEMET MEMBRANE AND ENDOTHELIAL DYSTROPHIES
Fuchs Dystrophy
See 4.26, Fuchs Endothelial Dystrophy.
Posterior Polymorphous Corneal Dystrophy
Changes at the level of Descemet membrane, including vesicles arranged in a linear or grouped pattern, diffuse blotchy gray haze, or broad bands with irregular, scalloped edges (see Figure 4.25.10). Iris abnormalities, including iridocorneal adhesions and corectopia (a decentered pupil), may be present and are occasionally associated with corneal edema. Glaucoma may occur. See 8.12, Developmental Anterior Segment and Lens Anomalies/Dysgenesis, for Differential Diagnosis. Treatment includes management of corneal edema and corneal transplantation for severe cases.
FIGURE 4.25.10 Posterior polymorphous corneal dystrophy with linear bands.
Congenital Hereditary Endothelial Dystrophy
Bilateral corneal edema (often asymmetric), normal corneal diameter, normal IOP, and no cornea guttae. Present at birth, nonprogressive, associated with nystagmus. Pain or photophobia uncommon. Rare. Autosomal recessive. (See 8.11, Congenital/Infantile Glaucoma, for differential diagnosis.)
Treatment
Some patients may benefit from a corneal transplant (endothelial or penetrating keratoplasty).
4.26 Fuchs Endothelial Dystrophy
Symptoms
Glare and blurred vision, worse on awakening. May progress to severe pain due to ruptured bullae. Symptoms usually develop in the fifth and sixth decades.
Signs
Critical. Cornea guttae with stromal +/- epithelial edema (see Figure 4.26.1). Bilateral, but may be asymmetric.
FIGURE 4.26.1 Corneal edema secondary to Fuchs endothelial dystrophy.
FIGURE 4.26.2 Corneal guttae in endothelial dystrophy.
NOTE: Central cornea guttae without stromal edema is called endothelial dystrophy (see Figure 4.26.2). This condition may progress to Fuchs dystrophy over years.
Other. Fine pigment dusting on the endothelium, central epithelial edema and bullae, folds in Descemet membrane, stromal edema, subepithelial haze, or scarring.
Differential Diagnosis
• Postsurgical corneal edema (also known as aphakic or pseudophakic bullous keratopathy): History of cataract surgery or other anterior segment surgery (e.g., tube shunt). See 4.27, Aphakic Bullous Keratopathy/Pseudophakic Bullous Keratopathy.
• Congenital hereditary endothelial dystrophy: Bilateral corneal edema at birth. See 4.25, Corneal Dystrophies.
• Posterior polymorphous corneal dystrophy: Seen early in life. Corneal endothelium shows grouped vesicles, geographic gray lesions, or broad bands. Occasionally corneal edema. See 4.25, Corneal Dystrophies.
• Iridocorneal endothelial syndrome: “Beaten metal” corneal endothelial appearance, with corneal edema, peripheral anterior synechiae, increased IOP, variable iris thinning, corectopia, and polycoria. Typically unilateral, in young to middle-aged adults. See 9.15, Iridocorneal Endothelial Syndrome.
Workup
1. History: Previous surgery?
2. Slit lamp examination: Cornea guttae are best seen with retroillumination. Fluorescein staining may demonstrate intact or ruptured bullae.
3. Measure IOP.
4. Corneal pachymetry to determine the central corneal thickness.
5. Consider specular microscopy to evaluate the endothelial cells although may be difficult to image the endothelial layer through an edematous cornea and in between guttate changes.
6. Consider corneal tomography to help monitor progression of disease.
Treatment
1. Topical sodium chloride 5% drops q.i.d. and ointment q.h.s.
2. May gently blow warm air from a hair dryer at arm’s length toward the eyes for a few minutes every morning to dehydrate the cornea.
3. IOP reduction if indicated; also may help with corneal edema.
4. Ruptured corneal bullae are painful and should be treated as recurrent erosions (see 4.2, Recurrent Corneal Erosion).
5. Surgery: Endothelial keratoplasty (Descemet membrane endothelial keratoplasty [DMEK] or Descemet stripping endothelial keratoplasty [DSEK]) is usually indicated when visual acuity decreases due to corneal edema; PK is indicated if significant anterior stromal scarring is present. Descemet stripping only (DSO) may be an option for milder forms of Fuchs endothelial dystrophy.
Follow Up
Every 3 to 12 months to check IOP and assess corneal edema. The condition progresses very slowly, and visual acuity typically remains good until stromal edema, epithelial edema, and/or corneal scarring develop.
4.27 Aphakic Bullous
Keratopathy/Pseudophakic Bullous Keratopathy
Symptoms
Decreased vision, pain, tearing, foreign body sensation, photophobia, and redness. History of cataract surgery in the involved eye.
Signs
(See Figure 4.27.1.)
FIGURE 4.27.1 Pseudophakic bullous keratopathy.
Critical. Corneal edema in an eye in which the native lens has been removed.
Other. Corneal bullae, Descemet folds, subepithelial haze or scarring, corneal neovascularization, with or without preexisting guttae. Cystoid macular edema (CME) may be present.
Etiology
Multifactorial: Corneal endothelial damage, intraocular inflammation, vitreous or subluxed intraocular lens or tube shunt touching (or intermittently touching) the cornea, preexisting endothelial dysfunction, and glaucoma.
Workup
1. Slit lamp examination: Stain the cornea with fluorescein to check for denuded epithelium. Check the position of the intraocular lens if present, determine whether vitreous is touching the corneal endothelium, and evaluate the eye for inflammation. Check for subepithelial haze or scarring. Evaluate the fellow eye for endothelial dystrophy.
2. Check IOP.
3. Dilated fundus examination: Look for CME.
4. Consider a fluorescein angiogram or optical coherence tomography to help detect CME, although evaluation may be limited by corneal opacification.
Treatment
1. Topical sodium chloride 5% drops q.i.d. and ointment q.h.s., if epithelial edema is present.
2. Reduce IOP with medications if needed. Avoid epinephrine derivatives and prostaglandin analogs, if possible, because of the risk of CME (see 9.1, Primary Open Angle Glaucoma).
3. Ruptured epithelial bullae (producing corneal epithelial defects) may be treated with the following:
• An ophthalmic antibiotic drops or ointment (e.g., erythromycin or bacitracin) and a cycloplegic (e.g., cyclopentolate 1% t.i.d.). The topical antibiotic can be used frequently (e.g., q2h) without patching.
• Alternatively, sodium chloride 5% drops or ointment q.i.d., a bandage soft contact lens, or, in patients with limited visual potential, anterior stromal micropuncture or excimer laser PTK can be used for recurrent ruptured epithelial bullae (see 4.2, Recurrent Corneal Erosion).
4. Full-thickness corneal transplant or endothelial keratoplasty (DMEK or DSEK) combined with possible intraocular lens repositioning, replacement, or removal and/or vitrectomy may be indicated when vision fails or when the disease becomes advanced and painful. Anterior stromal micropuncture, excimer laser PTK, conjunctival flap, or amniotic membrane graft surgery may be considered for a painful eye with poor visual potential.
5. See 11.14, Cystoid Macular Edema, for treatment of CME.
NOTE: Although both CME and corneal disease may contribute to decreased vision, the precise role of each is often difficult to determine preoperatively. CME is less likely with posterior chamber or open-loop anterior chamber intraocular lenses than closed-loop anterior chamber intraocular lenses, which are no longer used.
Follow Up
If ruptured bullae, every 1 to 3 days until improvement demonstrated, and then every 5 to 7 days until the epithelial defect heals. Otherwise, every 1 to 6 months, depending on symptoms.
4.28 Corneal Graft Rejection
Symptoms
Decreased vision, mild pain, redness, and photophobia with history of prior corneal transplantation, usually months to years beforehand. Often asymptomatic and diagnosed on routine follow-up examination.
Signs
(See Figure 4.28.1.)
FIGURE 4.28.1 Corneal graft rejection with endothelial rejection line and keratic precipitates.
Critical. New keratic precipitates are localized to the donor endothelium. May be associated with stromal and/or epithelial edema, a line of keratic precipitates on the corneal endothelium (endothelial rejection line or Khodadoust line), subepithelial infiltrates (Krachmer spots), an irregularly elevated epithelial line (epithelial rejection line), or localized stromal neovascularization.
Other. Conjunctival injection (particularly circumcorneal), anterior chamber inflammation, neovascularization growing up to or extending onto the graft, and broken graft suture. Tearing may occur, but a mucoid discharge is not present.
Differential Diagnosis
• Suture abscess or corneal infection: May have a corneal infiltrate, hypopyon, or a purulent discharge. Remove the suture (by pulling the contaminated portion through the shortest track possible) and obtain smears and cultures, including a culture of the suture. Steroid frequency is usually reduced. Treat with intensive topical fluoroquinolone or fortified antibiotics and monitor closely, sometimes in the hospital. See 4.11, Bacterial Keratitis.
• Uveitis: Anterior chamber cells and flare with keratic precipitates that are not limited to the graft endothelium. Often, a previous history of uveitis is obtained, but it is best to treat as if it were a graft rejection. If known history of HSV, add suppressive antiviral therapy if not on it already. HSV iritis is frequently associated with elevated IOP. See Chapter 12, Uveitis.
• Epithelial downgrowth: May present as an advancing line with smooth or scalloped borders on the endothelial surface. Can be present on the donor and/or the recipient endothelium. Will not respond to steroids and is associated with less corneal edema.
• Increased IOP: A markedly increased IOP may produce epithelial corneal edema without other graft rejection signs. Edema clears after the IOP is reduced.
• Other causes of graft failure: Non-immune-mediated late corneal graft endothelial decompensation or recurrent disease in the graft (e.g., herpes keratitis, corneal dystrophy).
Workup
1. History: Time since corneal transplantation? Current eye medications? Compliance with eye medications and postoperative follow up. Recent change in topical steroid regimen? Indication for corneal transplantation (e.g., HSV)?
2. Slit lamp examination, with careful inspection for endothelial rejection line, keratic precipitates, subepithelial infiltrates, and other signs listed above.
Treatment
Endothelial Rejection (Endothelial Rejection Line, Corneal Edema, and/or Keratic Precipitates)
1. Topical steroids (e.g., prednisolone acetate 1% q1h or difluprednate 0.05% q2h while awake; can add dexamethasone 0.1% ointment q.h.s.).
2. If rejection is severe, recurrent, or recalcitrant, consider systemic steroids (e.g., prednisone 40 to 80 mg p.o. daily) or, rarely, subconjunctival steroids (e.g., betamethasone 3 mg per 0.5 mL). In high-risk patients with severe rejection, consider hospitalization and methylprednisolone 500 mg i.v. for a total of one to three doses.
3. In select cases, other systemic immunosuppressives may be considered including cyclosporine and tacrolimus.
4. Cycloplegic agent (e.g., cyclopentolate 1% t.i.d.).
5. Control IOP if increased. See 9.7, Inflammatory Open Angle Glaucoma.
6. Topical cyclosporine 0.05% to 2% b.i.d. to q.i.d. may be helpful in the treatment and prevention of graft rejection.
Epithelial and Stromal Rejection (Subepithelial Infiltrates or Epithelial Rejection Line)
1. Double the current level of topical steroids or use prednisolone acetate 1% q.i.d. (whichever is more).
2. Cycloplegic agent, topical cyclosporine, and IOP control as above.
Follow Up
Institute treatment immediately to maximize the likelihood of graft survival. Examine the patient every 3 to 7 days. Once improvement is noted, the steroids are tapered very slowly and may need to be maintained at low doses for months to years. IOP must be checked regularly in patients taking topical steroids.
4.29 Corneal Refractive Surgery Complications
The basic principle of corneal refractive surgery is to induce a change in the curvature of the cornea to correct a preexisting refractive error.
COMPLICATIONS OF SURFACE ABLATION
PROCEDURES (PHOTOREFRACTIVE KERATECTOMY, LASER SUBEPITHELIAL KERATECTOMY, AND EPITHELIAL LASER IN SITU KERATOMILEUSIS)
In PRK, the corneal epithelium is removed and the corneal stroma is ablated using an argon-fluoride excimer laser (193 nm, ultraviolet) to correct a refractive error. In laser subepithelial keratomileusis (LASEK), the epithelium is chemically separated from the Bowman layer, moved to the side before laser ablation of the stroma, and then repositioned centrally. In epithelial laser in situ keratomileusis (epi- LASIK), the epithelium is mechanically separated from the Bowman layer, moved to the side before laser ablation of the stroma, and then repositioned centrally or discarded (see Table 4.29.1).
TABLE 4.29.1
Refractive Surgery Characteristics
Symptoms
Early (1 to 14 Days). Decreasing visual acuity and increased pain.
NOTE: The induced epithelial defect at surgery, which usually takes a few days to heal, normally will cause postoperative pain. A bandage soft contact lens is used to minimize this discomfort.
Later (2 Weeks to Several Months). Decreasing visual acuity, severe glare, and monocular diplopia.
Signs
Corneal infiltrate and central corneal scar.
Etiology
Early
• Dislocated or poorly fit bandage soft contact lens (see 4.20, Contact Lens-Related Problems).
• Nonhealing epithelial defect (see 3.2, Corneal Abrasion). Must also consider HSV keratitis.
• Corneal ulcer (see 4.11, Bacterial Keratitis).
• Medication allergy (see 5.1, Acute Conjunctivitis).
Later
• Undercorrection or overcorrection.
• Corneal haze (scarring) noted in anterior corneal stroma.
• Irregular astigmatism (e.g., central island, decentered ablation).
• Regression or progression of refractive error.
• Steroid-induced glaucoma or ocular hypertension (see 9.9, Steroid- Response Glaucoma).
Workup
1. Complete ophthalmic examination, including IOP measurement by Tonopen and applanation. IOP may be underestimated given decreased corneal thickness.
2. Refraction if change in refractive error suspected. Hard contact lens overrefraction corrects irregular astigmatism.
3. Corneal topography and/or tomography if irregular astigmatism is suspected.
Treatment and Follow Up
1. Epithelial defect (see 3.2, Corneal Abrasion).
2. Infectious keratitis (see 4.15, Herpes Simplex Keratitis and 4.11, Bacterial Keratitis).
3. Corneal haze: Increase steroid drop frequency. Follow up in 1 to 2 weeks. Cases of severe haze may respond to excimer laser PTK with mitomycin C.
4. Refractive error or irregular astigmatism: Consider surface ablation enhancement. If irregular astigmatism present, topography-guided surface ablation, excimer laser PTK, or hard contact lens may be needed.
5. Steroid-induced glaucoma. See 9.9, Steroid-Response Glaucoma.
COMPLICATIONS OF LASER IN SITU KERATOMILEUSIS
In LASIK, a hinged, partial-thickness corneal flap is created using a microkeratome or femtosecond laser, and then the underlying stroma is ablated with an excimer laser to correct refractive error. The corneal flap is repositioned over the stromal bed without sutures.
Symptoms
Early (1 to 14 Days). Decreasing visual acuity and increased pain.
Later (2 Weeks to Several Months). Decreasing visual acuity, severe glare, monocular diplopia, and dry eye symptoms.
Signs
Severe conjunctival injection, corneal infiltrate, large fluorescein- staining epithelial defect, dislocated corneal flap, interface inflammation, epithelial ingrowth under the flap, central corneal scar, SPK, scissoring of the light reflex or retinoscopy, and irregular corneal thinning or steepening
FIGURE 4.29.1 Diffuse lamellar keratitis.
Etiology
Early
• Dry eye/neurotrophic keratopathy. By far the most common early complication.
• Folding, dislocation, or loss of corneal flap.
• Large epithelial defect.
• Diffuse lamellar keratitis (DLK). Also known as “sands of the Sahara” because of its appearance (multiple fine inflammatory infiltrates in the flap interface). Usually occurs within 5 days of surgery (see Figure 4.29.1).
• Corneal ulcer and/or infection in flap interface. See 4.11, Bacterial Keratitis.
• Central toxic keratopathy (CTK). Central corneal stromal opacification and consolidation of unknown etiology, causing corneal thinning and flattening. It tends to improve over 6 to 12 months.
• Medication allergy. See 5.1, Acute Conjunctivitis.
NOTE: Patients after LASIK have reduced corneal sensation in the area of the flap for at least 3 months (returns to essentially normal in 6 to 12 months).
Later
• Epithelial ingrowth into flap interface.
• Corneal haze (scarring): Less common than after surface ablation procedures.
• Irregular astigmatism (e.g., decentered ablation, central island, flap irregularity, ectasia).
• Regression or progression of refractive error.
• Dry eye syndrome/neurotrophic keratopathy.
• DLK can occur weeks to years after LASIK in response to a corneal insult such as corneal abrasion, recurrent erosion, or viral keratitis.
• Pressure-induced stromal keratitis (PISK). High IOP (often secondary to steroid response) can cause the development of fluid in the interface with a clinical appearance similar to DLK. IOP measurements are falsely low due to the fluid cleft, and pressure should be measured with a Tonopen or other handheld tonometer both on the central cornea and peripheral to the LASIK flap.
Workup
1. Complete slit lamp examination, including fluorescein staining and IOP measurement by Tono-Pen and applanation. IOP may be underestimated given flap creation and decreased corneal thickness. Check IOP peripheral to the flap edge if suspect PISK.
2. Schirmer test, as needed.
3. Refraction on all patients who do not have uncorrected vision of 20/20. Refraction with hard contact lens for irregular astigmatism.
4. Corneal topography and/or tomography for suspected irregular astigmatism.
Treatment and Follow Up
1. Flap abnormalities:
• Visually significant stromal folds: Lift flap and refloat within 24 hours.
• Flap dislocation: Requires urgent surgical repositioning.
• Persistent symptomatic flap striae may require flap lifting and suturing.
2. Lost corneal flap: Treat as epithelial defect. See 3.2, Corneal Abrasion.
3. Epithelial defect. See 3.2, Corneal Abrasion.
4. SPK and dry eye. See 4.1, Superficial Punctate Keratopathy and 4.3, Dry Eye Syndrome.
5. DLK: Aggressive treatment with frequent topical steroids (e.g., prednisolone acetate 1% q1h). If severe, may also require lifting of flap and irrigation of interface. Treat any underlying cause, such as an epithelial defect.
6. CTK: No proven treatment. Lubrication and observation.
7. PISK: Ocular hypotensive medications and rapid tapering of steroids.
8. Corneal infiltrate. See 4.11, Bacterial Keratitis and Appendix 8, Corneal Culture Procedure. The flap may need to be lifted to obtain the best culture results.
9. Epithelial ingrowth: Observation if very peripheral and not affecting vision. Surgical debridement if dense, affecting the health of flap, approaching visual axis, or affecting vision. Small pockets may also be treated with a YAG laser.
10. Corneal haze: Increase steroid drop frequency. Follow up in 1 to 2 weeks.
11. Refractive error or irregular astigmatism: Appropriate refraction. Consider PRK or LASIK enhancement. If irregular astigmatism, consider flap repositioning, custom or topography guided enhancement, or contact lens fitting.
12. Consider CXL for ectasia.
COMPLICATIONS OF SMALL INCISION LENTICULE EXTRACTION
In SMILE, a femtosecond laser is used to create a thin disc of tissue (lenticule) inside the corneal stroma, which is then mechanically dissected and extracted through a small peripheral incision.
Symptoms
Early (1 to 14 days). Decreasing visual acuity and increased pain.
Later (2 weeks to Several Months). Decreasing visual acuity, severe glare, monocular diplopia, and dry eye symptoms.
Signs
Severe conjunctival injection, corneal infiltrate, large epithelial defect, interface inflammation, epithelial ingrowth into interface, central corneal scar, scissoring of the light reflex or retinoscopy, and irregular corneal thinning or steepening.
Etiology
Early
• Cap microstriae.
• Large epithelial defect.
• DLK: Also known as “sands of the Sahara” because of its appearance (multiple fine inflammatory infiltrates in the interface). Usually occurs within 5 days of surgery.
• Corneal ulcer and/or infection in interface. See 4.11, Bacterial Keratitis.
• Dry eye/neurotrophic keratopathy.
• Medication allergy. See 5.1, Acute Conjunctivitis.
NOTE: Early postoperative dry eye symptoms of SMILE are comparable to LASIK but often with faster recovery.
Later
• Epithelial ingrowth into stromal pocket (interface).
• Corneal haze (scarring): Less common than after surface ablation procedures.
• Irregular astigmatism (e.g., retained lenticule fragments, decentered treatment, ectasia).
• Regression or progression of refractive error.
• Dry eye syndrome/neurotrophic keratopathy.
• DLK can occur weeks to years after SMILE in response to a corneal insult such as corneal abrasion, recurrent erosion, or viral keratitis.
• PISK: High IOP (often secondary to steroid response) can cause the development of fluid in the interface with a clinical appearance similar to DLK. IOP measurements are falsely low by the fluid cleft, and pressure should be measured with a Tono-Pen or other handheld tonometer both on the central cornea and peripheral to the SMILE cap.
Workup
1. Complete slit lamp examination, including fluorescein staining and IOP measurement by Tono-Pen and applanation. IOP may be underestimated given lenticule extraction and decreased corneal thickness. Check IOP peripheral to the cap edge if suspect PISK.
2. Schirmer test, as needed.
3. Refraction on all patients who do not have uncorrected vision of 20/20. Refraction with hard contact lens for irregular astigmatism.
4. Corneal topography and/or tomography for suspected irregular astigmatism.
Treatment and Follow Up
1. Cap microstriae: Gentle cap massage, frequent topical steroids.
2. Epithelial defect. See 3.2, Corneal Abrasion.
3. SPK and dry eye. See 4.1, Superficial Punctate Keratopathy and 4.3, Dry Eye Syndrome.
4. DLK: Aggressive treatment with frequent topical steroids (e.g., prednisolone acetate 1% q1h). If severe, may also require lifting of flap and irrigation of interface. Treat any underlying cause, such as an epithelial defect.
5. PISK: Ocular hypotensive medications and rapid tapering of steroids.
6. Corneal infiltrate. See 4.11, Bacterial Keratitis and Appendix 8, Corneal Culture Procedure.
7. Epithelial ingrowth: Observation if very peripheral and not affecting vision. Conversion of cap into a flap and surgical debridement if dense, affecting the health of cap, approaching visual axis, or affecting vision. Small pockets can also be treated with a YAG laser.
8. Corneal haze: Increase steroid drop frequency. Follow up in 1 to 2 weeks.
9. Refractive error or irregular astigmatism: Appropriate refraction. Consider PRK enhancement. If irregular astigmatism, consider custom or topography guided enhancement or contact lens fitting.
10. Consider CXL for ectasia.
COMPLICATIONS OF RADIAL KERATOTOMY
In radial keratotomy (RK), partial-thickness, spoke-like cuts are made in the peripheral cornea using a diamond blade (often 90% to 95% depth), which results in a flattening of the central cornea and correction of myopia. Astigmatic keratotomy (AK) is a similar procedure in which arcuate or tangential relaxing incisions are made to correct astigmatism. Now rarely used given complication rate and advancement of technology.
Symptoms
Early (1 to 14 Days). Decreasing visual acuity and increased pain.
Later (2 Weeks to Years). Decreasing visual acuity, severe glare, and monocular diplopia.
NOTE: RK weakens the corneal integrity placing patients at higher risk for rupture after trauma.
Signs
Corneal infiltrate, large fluorescein-staining epithelial defect, rupture at RK incision site after trauma, and anterior chamber reaction.
Etiology
Early
• Large epithelial defect. See 3.2, Corneal Abrasion.
• Corneal ulcer/infection in RK incision. See 4.11, Bacterial Keratitis.
• Medication allergy. See 5.1, Acute Conjunctivitis.
• Very rarely, endophthalmitis. See 12.13, Postoperative Endophthalmitis.
Later
• RK incisions approaching the visual axis causing glare and starbursts.
• Irregular astigmatism.
• Regression of refractive error; common in first few months after surgery.
• Progression of refractive effect (consecutive hyperopia); common after first few years after surgery.
• Ruptured globe at RK incision site after trauma. See 3.14, Ruptured Globe and Penetrating Ocular Injury.
Workup
1. Complete slit lamp examination, including IOP measurement and fluorescein staining.
2. Refraction on all patients who do not have uncorrected vision of 20/20. Refraction with hard contact lens for irregular astigmatism.
3. Corneal topography and/or tomography if irregular astigmatism suspected.
Treatment and Follow Up
1. Corneal infiltrate: See 4.11, Bacterial Keratitis and Appendix 8, Corneal Culture Procedure.
2. Epithelial defect: See 3.2, Corneal Abrasion.
3. Endophthalmitis: See 12.13, Postoperative Endophthalmitis.
4. Refractive error or irregular astigmatism: Appropriate refraction. Consider enhancement of RK incisions or AK. Rarely, surface laser ablation with mitomycin C can be used. Irregular astigmatism may require a hard contact lens.
5. Ruptured globe at RK incision: Requires surgical repair. See 3.14,
Ruptured Globe and Penetrating Ocular Injury.