The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 4th Ed.

6. Anterior Chamber

Primary Angle-Closure Glaucoma

Secondary Angle-Closure Glaucoma

Hypotony

Hyphema

Cells and Flare

Hypopyon

Endophthalmitis

Anterior Uveitis

Uveitis–Glaucoma–Hyphema Syndrome

Primary Angle-Closure Glaucoma

Definition

Glaucoma due to obstruction of the trabecular meshwork by peripheral iris; classified as acute, subacute (intermittent), or chronic.

Etiology/mechanism

Pupillary Block

Most common. Lens–iris apposition interferes with aqueous flow and causes the iris to bow forward and occlude the trabecular meshwork.

Plateau Iris Syndrome (Without Pupillary Block)

Peripheral iris occludes the angle in patients with an atypical iris configuration (anteriorly positioned peripheral iris with steep insertion due to anteriorly rotated ciliary processes) (see Chapter 7).

Epidemiology

Approximately 5% of the general population over 60 years old have occludable angles, 0.5% of these develop angle-closure. Usually bilateral (develops in 50% of untreated fellow eyes within 5 years); higher incidence in Asians and Eskimos; female predilection (4 : 1). Associated with hyperopia, nanophthalmos, anterior chamber depth less than 2.5 mm, thicker lens, and lens subluxation.

Symptoms

Acute Angle-Closure

Pain, red eye, photophobia, decreased or blurred vision, halos around lights, headache, nausea, emesis.

Subacute Angle-Closure

May be asymptomatic or have symptoms of acute form but less severe; episodes evolve over the course of days or weeks and resolve spontaneously.

Chronic Angle-Closure

Asymptomatic; may have decreased vision or constricted visual fields in late stages.

Signs

Acute Angle-Closure

Decreased visual acuity, increased intraocular pressure, ciliary injection, corneal edema, anterior chamber cells and flare, shallow anterior chamber, narrow angles on gonioscopy, mid-dilated nonreactive pupil, iris bombé; may have signs of previous attacks including sector iris atrophy, anterior subcapsular lens opacities (glaukomflecken; due to lens epithelial cell ischemia and necrosis from high intraocular pressure), dilated irregular pupil, and peripheral anterior synechiae (PAS).

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FIGURE 6-1 Primary angle-closure glaucoma with very shallow anterior chamber and iridocorneal touch (no space between slit-beam view of cornea and iris).

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FIGURE 6-2 Glaukomflecken appear as dot-like anterior subcapsular lens opacities.

Subacute and Chronic Angle-Closure

Narrow angles; may have increased intraocular pressure, PAS, sector iris atrophy, glaukomflecken, optic nerve cupping, nerve fiber layer defects, and visual field defects.

Evaluation

• Complete ophthalmic history and eye exam with attention to pupils, cornea, tonometry, anterior chamber, indentation gonioscopy (Zeiss lens), iris, lens, and ophthalmoscopy.

• Check visual fields.

• Consider provocative testing (prone test, dark room test, prone dark room test, and pharmacologic dilation; intraocular pressure increase of >8 mmHg is considered positive).

Management

ACUTE ANGLE-CLOSURE

• Topical β-blocker (timolol [Timoptic] 0.5% q 15 min × 2, then bid), α-agonist (apraclonidine [Iopidine] 1% q 15 min × 2), and topical steroid (prednisolone acetate 1% q 15 minutes × 4, then q1h).

• Topical miotic (pilocarpine 1–2% min × 1 initially, then qid if effective; usually not effective if intraocular pressure > 40 mmHg due to iris sphincter ischemia; in 20% of patients pilocarpine will exacerbate the situation due to forward displacement of the lens–iris diaphragm); can also consider topical α-antagonist (thymoxamine 0.5% q 15 min for 2–3 hours).

• Systemic acetazolamide (Diamox 500 mg po STAT, then bid) and hyperosmotic (isosorbide up to 2 g/kg po of 45% solution).

• Laser peripheral iridotomy (LPI) with or without iridoplasty: Definitive treatment after acute attack is broken medically; may require application of topical glycerin (Ophthalgan) to clear corneal edema for adequate visualization of iris.

• Procedure parameters: A contact lens is used to stabilize the eye, focus the beam better, and place laser spots peripherally (in iris valley or crypt); patency of the iridotomy is confirmed by visualization of the lens capsule (often a rush of aqueous fluid through the hole is seen) not by the appearance of a red reflex.

• Argon laser (depends on iris pigmentation):

Dark brown: 0.02–0.05 s duration, 50 μm spot size, 600–1000 mW power; then 0.1 s and 400–600 mW through pigment epithelium.

Medium brown: 0.1–0.2 s duration, 50 μm spot size, 600–1000 mW power.

Blue: 0.05 s duration, 500 μm spot size, 200–500 mW power contraction burns; then 0.1 s duration, 50 μm spot size, 600–1000 mW power through stroma and 400–600 mW through pigment epithelium.

• Nd : YAG laser: 4–10 mJ power.

• Prophylactic laser peripheral iridotomy in fellow eye with narrow angle to prevent an acute attack in the future.

• If unable to perform laser peripheral iridotomy, consider surgical iridectomy.

• Consider goniosynechiolysis for recent peripheral anterior synechiae (< 12 months).

• Plateau iris syndrome may require long-term miotic therapy and peripheral iridectomy to reduce risk of pupillary block; consider argon laser iridoplasty or gonioplasty.

• Procedure parameters: 0.2–0.5 s duration, 200–500 μm spot size, 200–400 mW power, approximately 10 spot applications per quadrant, spots are placed on the iris as peripherally as possible and the power setting is adjusted until movement of the iris is observed.

SUBACUTE AND CHRONIC ANGLE-CLOSURE

• Laser peripheral iridotomy even without evidence of pupillary block.

• Treatment of increased intraocular pressure (see Primary Open-Angle Glaucoma section in Chapter 11); may require trabeculectomy or glaucoma drainage implant to lower pressure adequately.

Prognosis

Good if prompt treatment is initiated for acute attack; poorer for chronic cases but depends on extent of optic nerve damage and subsequent intraocular pressure control.

Secondary Angle-Closure Glaucoma

Definition

Acute or chronic angle-closure glaucoma caused by a variety of ocular disorders.

Etiology/mechanism

With Pupillary Block

Lens-induced (phacomorphic, dislocated lens, microspherophakia), seclusio pupillae, aphakic or pseudophakic pupillary block, silicone oil, nanophthalmos.

Without Pupillary Block

Posterior “pushing” mechanism

Mechanical or anterior displacement of the lens–iris diaphragm.

• Anterior rotation of ciliary body due to:

• Inflammation (scleritis, uveitis, panretinal photocoagulation).

• Congestion (scleral buckling, nanophthalmos).

• Choroidal effusion (hypotony, uveal effusion, medication [topiramate, sulfonamides]).

• Suprachoroidal hemorrhage.

• Aqueous misdirection (malignant glaucoma).

• Pressure from posterior segment (tumor, expanding gas, exudative retinal detachment).

• Developmental abnormalities (persistent hyperplastic primary vitreous, retinopathy of prematurity).

Anterior “pulling” mechanism

Adherence of iris to the trabecular meshwork or membranes over the trabecular meshwork.

• Epithelial (downgrowth or ingrowth).

• Endothelial (iridocorneal endothelial syndrome, posterior polymorphous dystrophy).

• Neovascular (neovascular glaucoma; see Chapter 7).

• Postinflammatory peripheral anterior synechiae.

• Adhesion from trauma.

• Mesodermal dysgenesis syndromes.

Symptoms

Acute Angle-Closure

Pain, red eye, photophobia, decreased or blurred vision, halos around lights, headache, nausea, emesis.

Chronic Angle-Closure

Asymptomatic; may have decreased vision or constricted visual fields in late stages.

Signs

Acute Angle-Closure

Decreased visual acuity, increased intraocular pressure, ciliary injection, corneal edema, anterior chamber cells and flare, shallow anterior chamber, narrow angles on gonioscopy, mid-dilated nonreactive pupil, iris bombé; signs of underlying etiology.

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FIGURE 6-3 Secondary angle-closure due to pseudophakic pupillary block. The intact anterior vitreous face (visible with pigment) is blocking the pupil and superior iridectomy. The slit-beam shows the peripheral iris bowing forward, obstructing the angle and bulging around the anterior chamber intraocular lens.

Chronic Angle-Closure

Narrow angles, increased intraocular pressure, PAS, signs of underlying etiology; may have sector iris atrophy, glaukomflecken, optic nerve cupping, nerve fiber layer defects, and visual field defects.

Evaluation

• Complete ophthalmic history and eye exam with attention to pupils, cornea, tonometry, anterior chamber, indentation gonioscopy, iris, lens, and ophthalmoscopy.

• Check visual fields.

Management

• Treat underlying etiology.

• Laser peripheral iridotomy for pupillary block.

• Topical cycloplegic (scopolamine 0.25% qid or atropine 1% bid) for malignant glaucoma, microspherophakia, after scleral buckle or after panretinal photocoagulation (do not use miotic agents).

• May require pars plana vitrectomy and lens extraction in refractory cases of malignant glaucoma or Nd : YAG laser disruption of the anterior hyaloid face in patient with pseudophakia and aphakia.

• Topical cycloplegic (scopolamine 0.25% qid), steroid (prednisolone acetate 1% qid), and panretinal photocoagulation for neovascular glaucoma.

• Cataract extraction may be necessary in some cases of lens-induced angle-closure glaucoma.

• Treatment of increased intraocular pressure (see Primary Open-Angle Glaucoma section in Chapter 11); may require trabeculectomy or glaucoma drainage implant to lower pressure adequately.

Prognosis

Poorer than primary angle-closure because usually due to chronic process; depends on etiology, extent of optic nerve damage, and subsequent intraocular pressure control.

Hypotony

Definition

Low intraocular pressure (≤ 5 mmHg).

Etiology

Increased Outflow (Excessive Drainage of Aqueous or Vitreous Fluid)

Trauma (cyclodialysis), surgery (wound leak, bleb overfiltration), choroidal effusion, retinal detachment.

Decreased Production (Ciliary Body Shutdown)

Inflammation (uveitis), medication (ciliary body toxicity: 5-fluorouracil, mitomycin-C, cidofovir, mannitol, anesthetic agents [fentanyl, succinylcholine, propofol, sevoflurane]), systemic disorder (bilateral hypotony: dehydration, ketoacidosis, uremia), cyclitic membrane, anterior proliferative vitreoretinopathy, ocular ischemic syndrome, phthisis.

Symptoms

Asymptomatic; may have pain and decreased vision.

Signs

Normal or decreased visual acuity, low intraocular pressure, functional and structural changes usually occur; may have refractive (hyperopic) shift, corneal folds and edema, positive Seidel test, filtering bleb, anterior chamber cells and flare, shallow anterior chamber, cyclodialysis cleft, cataract, cyclitic membrane, choroidal effusion, chorioretinal folds (hypotony maculopathy), cystoid macular edema, retinal detachment, proliferative vitreoretinopathy, optic disc edema, phthisis (end-stage; see Chapter 1).

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FIGURE 6-4 Hypotony maculopathy with choroidal folds after trabeculectomy surgery.

Evaluation

• Complete ophthalmic history with attention to trauma, surgery, medications, and systemic conditions.

• Complete eye exam with attention to cornea, tonometry, anterior chamber, gonioscopy, and ophthalmoscopy.

• Seidel test (see TraumaLaceration section in Chapter 5) to rule out open globe or wound leak in traumatic or postsurgical cases.

• B-scan ultrasonography to evaluate choroidal effusion, retinal detachment, and intraocular foreign body if unable to visualize the fundus.

• Consider ultrasound biomicroscopy (UBM) to identify cyclitic membrane, cyclodialysis cleft, and ciliary body detachment (≥ 2 clock hours).

• Consider fluorescein angiogram or OCT to identify choroidal folds.

Management

• Treat underlying etiology.

• Topical cycloplegic (cyclopentolate 1%, scopolamine 0.25%, atropine 1% bid to tid).

• Topical antibiotic for wound leak (gatifloxacin [Zymaxid] or moxifloxacin [Vigamox] qid).

• Bandage contact lens or pressure patch may work for small wound leaks.

• May require drainage of choroidal effusion or surgical repair of wound leak, retinal detachment, or ciliary body detachment.

• Consider Simmons’ shell or anterior chamber injection of viscoelastic or gas for bleb overfiltration.

• Steroids (topical, sub-Tenon’s, intravitreal, or oral), especially in cases due to uveitis.

• Consider topical ibopamine 2%.

Prognosis

Depends on etiology and duration.

Hyphema

Definition

Blood in the anterior chamber. Hyphema forms a layer of blood, whereas a microhyphema cannot be visualized with the naked eye (can only see red blood cells floating in the anterior chamber on slit-lamp examination).

Etiology

Usually traumatic (60% also have angle recession); may be spontaneous when associated with neovascularization of the iris or angle, iris lesions, or a malpositioned or loose intraocular lens (IOL).

Symptoms

Decreased vision; may have pain, photophobia, red eye.

Signs

Normal or decreased visual acuity, red blood cells in the anterior chamber (layer or clot); may have subconjunctival hemorrhage, increased intraocular pressure, rubeosis, iris sphincter tears, unusually deep anterior chamber, angle recession, iridodonesis, iridodialysis, cyclodialysis, and other signs of ocular trauma; may have iris lesion or pseudophacodonesis of IOL implant.

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FIGURE 6-5 Hyphema demonstrating layered blood inferiorly and suspended red blood cells and clot.

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FIGURE 6-6 Hyphema with active bleeding from the pupil margin.

Differential Diagnosis

Trauma, uveitis–glaucoma–hyphema (UGH) syndrome, juvenile xanthogranuloma, leukemia, child abuse, postoperative, Fuchs’ heterochromic iridocyclitis, rubeosis irides.

Evaluation

• Complete ophthalmic history and eye exam with attention to cornea, tonometry, anterior chamber, iris, and ophthalmoscopy; wait 2–4 weeks to perform gonioscopy and scleral depression in traumatic cases.

• B-scan ultrasonography to rule out open globe if unable to visualize the fundus.

• Consider UBM to evaluate angle structures.

• Lab tests: Sickle cell prep and hemoglobin electrophoresis to rule out sickle cell disease.

Management

• Topical steroid (prednisolone acetate 1% up to q1h initially, then taper over 3–4 weeks as hyphema and inflammation resolve).

• Topical cycloplegic (scopolamine 0.25% or atropine 1% bid to tid).

• Consider aminocaproic acid ([Amicar] 50–100 mg / kg q4h).

• May require treatment of increased intraocular pressure (see Primary Open-Angle Glaucoma section in Chapter 11; do not use carbonic anhydrase inhibitors in patients with sickle cell disease; do not use miotic agents or prostaglandin analogues).

• Instruct patient to avoid aspirin-containing products, sleep with head of bed elevated at 30° angle, protect eye with metal shield at all times, and remain at bed rest.

• Daily examination for first 5 days (when risk of recurrent bleed is highest) then slowly space out visits.

• May require anterior chamber washout for corneal blood staining, uncontrolled elevated intraocular pressure, persistent clot, rebleed (8-ball hyphema).

• IOL removal or exchange for UGH syndrome.

Prognosis

Good in traumatic cases if intraocular pressure is controlled and there is no rebleed; may be at risk for angle recession glaucoma in the future.

Cells and Flare

Definition

Extravasated leukocytes (cells) and protein and fibrin (flare) in the anterior chamber due to breakdown of the blood–aqueous barrier by inflammation.

Cells

Appear as small white particles floating in the aqueous. Other types of cells can sometimes be present in the aqueous: red blood cells (microhyphema), pigment cells (from iris after dilation and in pigment dispersion syndrome), and tumor cells. Large quantities of cells can settle inferiorly in the anterior chamber and form a layer (hypopyon [WBCs], hyphema [RBCs], or pseudohypopyon [pigment, ghost, or tumor cells]).

Flare

Appears as hazy or cloudy aqueous; severe fibrinous exudate produces a jelly-like plasmoid aqueous appearance with strands of fibrin (4+ flare).

Etiology

Exudation from blood vessels due to anterior segment inflammation; usually uveitis, trauma, postoperative, scleritis, and keratitis.

Symptoms

Variable pain, photophobia, tearing, red eye, decreased vision; may be asymptomatic.

Signs

Normal or decreased visual acuity, ciliary injection, miosis, anterior chamber cells and flare (best seen when viewed with a short narrow (1 × 1 mm) slit-lamp beam directed at a 30–45° angle through the pupil producing an effect similar to shining a flashlight through a dark room; cells demonstrate brownian motion and flare looks like smoke in the light beam; graded on a 0 to 4 scale [i.e., Cells: 0 = 0 cells; 1+ = 5–10 cells; 2+ = 11–20 cells; 3+ = 21–50 cells; 4+ = > 50 cells; often trace or minimal refers to 1–4 cells. Flare: 0 = empty; 1+ = faint; 2+ = moderate (iris / lens clear); 3+ = marked (iris / lens hazy); 4+ = severe (fibrin, fixed aqueous, no motion of cells [termed fibrinoid or “plastic” anterior chamber reaction]).]) May have scleritis, keratic precipitates, keratitis, iris nodules, posterior synechiae, increased or decreased intraocular pressure, hypopyon, hyphema, pseudohypopyon, cataract, vitritis, vitreous hemorrhage, or retinal or choroidal lesions.

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FIGURE 6-7 Grade 4+ anterior chamber cells and flare visible with fine slit-beam between the cornea and iris.

Differential Diagnosis

See above.

Evaluation

• Complete ophthalmic history and eye exam with attention to sclera, cornea, tonometry, anterior chamber, gonioscopy, iris, lens, and ophthalmoscopy.

• Consider uveitis workup (see Anterior Uveitis section).

Management

• Treat underlying etiology.

• Topical steroid (prednisolone acetate 1% [Pred Forte] or difluprednate 0.05% [Durezol] up to q1h initially, then taper slowly) and cycloplegic (cyclopentolate 1%, scopolamine 0.25%, or atropine 1% bid to tid).

• Consider sub-Tenon’s steroid injection (triamcinolone acetonide 40 mg / mL), oral steroids (prednisone 60–100 mg po qd), or cytotoxic agents for severe inflammation after ruling out infectious etiologies (see Anterior Uveitis section).

• May require treatment of increased intraocular pressure (see Primary Open-Angle Glaucoma section in Chapter 11; do not use miotic agents or prostaglandin analogues).

Prognosis

Depends on etiology.

Hypopyon

Definition

Layer of white blood cells in the anterior chamber.

Etiology

Usually due to inflammation (uveitis, especially HLA-B27 associated and Behçet’s disease) or infection (corneal ulcer, endophthalmitis).

Symptoms

Pain, red eye, and decreased vision.

Signs

Normal or decreased visual acuity, conjunctival injection, hypopyon, and anterior chamber cells and flare; may have scleritis, corneal infiltrate, keratic precipitates, iris nodules, cataract, vitritis, or retinal or choroidal lesions.

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FIGURE 6-8 Hypopyon demonstrating layered white blood cells inferiorly.

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FIGURE 6-9 Pseudohypopyon composed of khaki-colored ghost cells layered inferiorly.

Differential Diagnosis

Pseudohypopyon (layer of other cells in the anterior chamber including pigment cells, ghost cells, tumor cells, or macrophages).

Evaluation

• Complete ophthalmic history and eye exam with attention to sclera, cornea, tonometry, anterior chamber, iris, lens, and ophthalmoscopy.

• B-scan ultrasonography if unable to visualize the fundus.

• Lab tests: Cultures and smears for infectious keratitis (see Chapter 5) or endophthalmitis (see Endophthalmitis section).

• Consider uveitis workup (see Anterior Uveitis section).

Management

• Treat underlying etiology.

• Antimicrobial medications if infectious (see Infectious Keratitis section in Chapter 5 and Endophthalmitis section below).

• Topical steroid (prednisolone acetate 1% up to q1–2 h initially) and cycloplegic (cyclopentolate 1%, scopolamine 0.25%, or atropine 1% bid to tid).

• Monitor treatment response by hypopyon resorption.

• Rarely requires surgery, except in cases of endophthalmitis.

Prognosis

Depends on etiology and treatment response.

Endophthalmitis

Definition

Intraocular infection; may be acute, subacute, or chronic; localized or involving anterior and posterior segments.

Etiology

Postoperative (70%)

Acute postoperative (< 6 weeks after surgery)

Ninety-four percent Gram-positive bacteria including coagulase-negative staphylococci (70%), Staphylococcus aureus (10%), Streptococcus spp. (11%); only 6% Gram-negative organisms.

Delayed postoperative (> 6 weeks after surgery)

Propionibacterium acnes, coagulase-negative staphylococci, and fungi (Candida spp.).

Conjunctival filtering bleb associated

Streptococcus spp. (47%), coagulase-negative staphylococci (22%), Haemophilus influenzae (16%).

Posttraumatic (20%)

Bacillus (B. cereus) spp. (24%), Staphylococcus spp. (39%), and Gram-negative organisms (7%).

Endogenous (2–15%)

Rare, usually fungal (Candida spp.); bacterial endogenous is usually due to S. aureus and Gram-negative bacteria. Occurs in debilitated, septicemic, or immunocompromised patients, especially after surgical procedures.

Epidemiology

Incidence following cataract surgery is less than 0.1%; risk factors include loss of vitreous, disrupted posterior capsule, poor wound closure, and prolonged surgery. Incidence following penetrating trauma is 4–13%, may be as high as 30% after injuries in rural settings; risk factors include retained intraocular foreign body, delayed surgery (> 24 hours), rural setting (soil contamination), disrupted crystalline lens.

Symptoms

Pain, photophobia, discharge, red eye, decreased vision; may be asymptomatic or have chronic uveitis appearance in delayed onset and endogenous cases.

Signs

Decreased visual acuity (usually severe; only 14% of patients in the Endophthalmitis Vitrectomy Study (EVS) had better than 5 / 200 vision), lid edema, proptosis, conjunctival injection, chemosis, wound abscess, corneal edema, keratic precipitates, anterior chamber cells and flare, hypopyon, vitritis, poor red reflex; may have positive Seidel test and other signs of an open globe (see Chapter 4).

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FIGURE 6-10 Endophthalmitis with large hypopyon (almost 50% of anterior chamber height). There is severe inflammation with 4+ conjunctival injection and a white ring corneal infiltrate at the limbus.

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FIGURE 6-11 Staphylococcus endophthalmitis with ring infiltrate. There is marked corneal edema and the corneal sutures across the surgical wound are visible at the superior limbus.

Differential Diagnosis

Uveitis, sterile inflammation (usually from prolonged intraoperative manipulations, especially involving vitreous; retained lens material; rebound inflammation after sudden decrease in postoperative steroids; or toxic anterior segment syndrome [TASS; acute postoperative anterior chamber reaction and corneal edema due to contaminants from surgical instruments, intraocular solutions, or intraocular lens (IOL) implant]), blebitis (infection of filtering bleb), intraocular foreign body, intraocular tumor, sympathetic ophthalmia, anterior segment ischemia (from carotid artery disease [ocular ischemic syndrome] or following muscle surgery [usually on three or more rectus muscles in same eye at the same surgery]).

Evaluation

• Complete ophthalmic history with attention to surgery and trauma.

• Complete eye exam with attention to visual acuity, conjunctiva, sclera, cornea, tonometry, anterior chamber, vitreous cells, red reflex, and ophthalmoscopy.

• Seidel test (see TraumaLaceration section in Chapter 5) to rule out wound leak or open globe in postsurgical or traumatic cases.

• B-scan ultrasonography if unable to visualize the fundus.

• Lab tests: STAT evaluation of intraocular fluid cultures and smears; conjunctival and nasal swabs can also be collected for culture but have low yield.

• Medical consultation for endogenous endophthalmitis.

Ophthalmic Emergency

ACUTE POSTOPERATIVE ENDOPHTHALMITIS

• If vision is better than light perception (> LP), then anterior chamber and vitreous tap to collect specimens for culture, and intravitreal antibiotics (see below).

• If vision is LP only, then anterior chamber tap, pars plana vitrectomy, and intravitreal antibiotics (EVS conclusion); should be performed by a vitreoretinal specialist.

• Intravitreal antibiotics ± steroid:

Vancomycin (1 mg/0.1 mL).

Ceftazidime (2.25 mg/0.1 mL) or amikacin (0.4 mg/0.1 mL).

Dexamethasone (0.4 mg/0.1 mL; controversial, because intravitreal steroids were not evaluated in the EVS, which included only cataract surgery and secondary IOL cases).

• Subconjunctival antibiotics ± steroid:

Vancomycin (25 mg).

Ceftazidime (100 mg) or gentamicin (20 mg).

Dexamethasone (12–24 mg).

• Topical broad-spectrum fortified antibiotics (alternate every 30 minutes):

Vancomycin (50 mg/mL q1h).

Ceftazidime (50 mg/mL q1h).

• Topical steroid (prednisolone acetate 1% q1–2 h initially) and cycloplegic (atropine 1% tid or scopolamine 0.25% qid).

• Systemic intravenous antibiotics for marked inflammation, severe cases, or rapid onset (controversial, because EVS found no benefit with systemic antibiotics):

Vancomycin (1 g IV q12h).

Ceftazidime (1 g IV q12h).

DELAYED, FILTERING BLEB ASSOCIATED, POSTTRAUMATIC, AND ENDOGENOUS

• EVS guidelines do not apply and treatment should be based on the clinical situation.

• Intravitreal antibiotics or steroids similar to acute postoperative guidelines (see above); amphotericin B (0.005 mg/0.1 mL) if endogenous fungal or delayed onset with presumed fungal etiology.

• Subconjunctival antibiotics or steroids similar to acute postoperative guidelines (see above).

• Topical broad-spectrum fortified antibiotics similar to acute postoperative guidelines (see above); amphotericin B (1.0–2.5 mg / mL q1h) or natamycin (50 mg / mL q1h) if fungal.

• Topical steroid (prednisolone acetate 1% q1–2 h initially) and cycloplegic (atropine 1% tid).

• Systemic intravenous antibiotics for marked inflammation similar to acute postoperative guidelines (see above); amphotericin B (0.25–1.0 mg/kg IV divided equally q6h) if disseminated fungal disease exists.

• Delayed postoperative endophthalmitis may require partial or total capsulectomy, pars plana vitrectomy, or IOL removal or exchange.

• Consider repeat tap (or pars plana vitrectomy) and intravitreal injections if clinical worsening after 48–72 hours.

• Adjust antibiotics based on culture results.

• Vitreous tap and injection: This procedure is performed under controlled aseptic conditions with sterile gloves and sterile field (or equivalent). The eye is anesthetized with either sterile cotton swabs soaked in 2% lidocaine, or a subconjunctival injection of 2% lidocaine in the quadrant of the procedure; some patients may require a peribulbar or even retrobulbar block. The eye and lids are prepped with providone iodine, chlorhexidine, or betadine, and a sterile wire lid speculum is placed. A 27-gauge needle on a 1 mL syringe is used to enter the anterior chamber at the limbus, avoiding the iris, and approximately 0.1 mL of aqueous humor and hypopyon is withdrawn. The appropriate distance posterior to the limbus for the vitreous tap and injection sites is measured with sterile calipers (3 mm for pseudophakic patients or 4 mm for phakic patients or use the hub of a 1 mL syringe). Then a 27-gauge needle on a 1 mL syringe is used to enter the posterior chamber at the preplaced mark so that the needle is in the midvitreous cavity, and approximately 0.1 mL of vitreous is withdrawn. Intravitreal injections with a 30-gauge needle attached to the syringes containing the antibiotics are immediately performed, and the injection sites are covered with a sterile cotton-tipped applicator to avoid vitreous exit. Subconjunctival injections should then be performed in the anesthetized quadrant. The aqueous and vitreous samples are immediately plated or sent to the microbiology lab for appropriate smears and cultures. Following the intravitreal injections, patients should be evaluated for possible increased intraocular pressure; this consists of ophthalmoscopy of the optic nerve head for ocular perfusion (if the view is clear) or tonometry.

Prognosis

Depends on etiology, duration, and organism; usually poor, especially for traumatic cases.

Anterior Uveitis (Iritis, Iridocyclitis)

Definition

Inflammation of the anterior uvea (iris [iritis] and ciliary body [cyclitis]) with exudation of white blood cells and protein into the anterior chamber secondary to breakdown of the blood–aqueous barrier and increased vascular permeability from a variety of disorders. Minimal spill-over into the retrolental space can be present. Classified by pathology (nongranulomatous [lymphocyte and plasma cell infiltrates] or granulomatous [epithelioid and giant cell infiltrates]), location (keratouveitis, sclerouveitis, anterior uveitis, intermediate uveitis, posterior uveitis, endophthalmitis, panuveitis), course (acute, chronic, recurrent), or etiology.

Etiology

Most commonly idiopathic or associated with HLA-B27, but it is critical to rule out other causes such as infection, malignancy, medication, and trauma.

Infectious Anterior Uveitis

Herpes Simplex and Herpes Zoster Ophthalmicus

Acute or chronic, recurrent iritis, especially herpes zoster ophthalmicus (HZO); often with keratic precipitates underlying areas of dendritic or stromal keratitis; elevated intraocular pressure common; may have sector iris atrophy, corneal scarring, and decreased corneal sensation.

Lyme Disease

Patients have classic cutaneous erythema chronicum migrans at the site of a tick bite; due to Borrelia burgdorferi transmitted by Ixodes dammini or I. pacificus tick; 1–3 months later can develop neurologic involvement including encephalitis and meningitis. In addition to iritis, may also have conjunctivitis, keratitis, vitritis, and optic neuritis; may develop chronic skin changes, chronic arthritis, and cardiac manifestations.

Syphilis

Chronic or recurrent nongranulomatous or granulomatous anterior uveitis can be an ocular manifestation of acquired secondary syphilis; may also have interstitial keratitis, dilated iris vascular tufts (iris roseola), vitritis, chorioretinitis, papillitis, and mucocutaneous manifestations (see Chapters 5 and 10). This infection must be ruled out in every patient with persistent iritis, because systemic antibiotics are necessary to prevent significant morbidity.

Tuberculosis

Chronic granulomatous iritis; may also have conjunctival nodules, phlyctenules, interstitial keratitis, scleritis, iris nodules, vitritis, and choroiditis (see Chapter 10). It is rarely caused by direct ocular infection of Mycobacterium tuberculosis and most of the time is an immune response directed toward the organism. Patients with a chronic granulomatous iritis who are immunocompromised or come from endemic areas should be evaluated for tuberculosis.

Noninfectious Anterior Uveitis

Nongranulomatous

Idiopathic (acute)

Most common cause of anterior uveitis (50%).

HLA-B27 associated (acute)

Recurrent iritis with alternating involvement of both eyes (~ 75%), usually severe inflammation with fibrinoid anterior chamber reaction, posterior synechiae, and hypopyon. Accounts for up to 50% of anterior uveitis; often male (3 : 1) and tend to develop iritis as young or middle-aged adults; may be chronic or bilateral in women and children; distinct entity from the idiopathic form. Up to 90% have or develop signs related to a seronegative spondyloarthropathy.

Seronegative spondyloarthropathies (acute)

Group of conditions sharing common features that include: radiographic sacroiliitis (with or without spondylitis), asymmetric peripheral arthritis without rheumatoid nodules, negative rheumatoid factor (RF) and antinuclear antibody (ANA), HLA-B27 association, variable mucocutaneous lesions, and anterior uveitis.

Ankylosing spondylitis

Thirty percent develop anterior uveitis, recurrent in 40%, also episcleritis and scleritis. Patients develop lower back pain and stiffness after inactivity; also associated with aortitis and pulmonary apical fibrosis; arthritis less severe in women, but eye disease can still be severe. Sacroiliac radiographs often show sclerosis and narrowing of joint spaces; untreated patients will progress to debilitating spinal fusion; 90% have positive HLA-B27 test results.

Reiter’s syndrome (reactive arthritis)

Triad of nonspecific urethritis, polyarthritis (80%), and mucopurulent, papillary conjunctivitis with iritis; arthritis starts within 30 days of infection; also associated with keratoderma blennorrhagicum, circinate balanitis, plantar fasciitis, Achilles tendonitis, sacroiliitis, palate or tongue ulcers, nail pitting, prostatitis, and cystitis. Occurs in males age 15–40 years old (90%); may be triggered by diarrhea or infectious organism (ChlamydiaUreaplasmaYersiniaShigellaSalmonella); 85–95% have positive HLA-B27 test results.

Inflammatory bowel disease

In contrast to the unilateral iritis associated with ankylosing spondylitis and Reiter’s syndrome, the iritis associated with inflammatory bowel disease is usually bilateral and has a posterior component; may also develop dry eyes, conjunctivitis, episcleritis, scleritis, orbital cellulitis, and optic neuritis. Occurs in 5–10% of patients with ulcerative colitis, more common in Crohn’s disease; associated with sacroiliitis, erythema nodosum, pyoderma gangrenosum, hepatitis, and sclerosing cholangitis; 60% of patients with sacroiliitis have positive HLA-B27 test results.

Psoriatic arthritis

Twenty percent develop iritis; also conjunctivitis and dry eyes. Patients have “sausage” digits from terminal phalangeal joint arthritic involvement, subungual hyperkeratosis, erythematous rash, nail pitting, and onycholysis; associated with sacroiliitis; iritis rarely occurs when psoriasis appears without arthritis; associated with HLA-B27.

Whipple’s disease

Rare systemic disorder associated with Tropheryma whippelii infection, characterized by chronic diarrhea (due to malabsorption), joint inflammation, central nervous system manifestations, and anterior uveitis; associated with sacroiliitis, spondylitis, and HLA-B27.

Behçet’s disease (acute)

Triad of recurrent hypopyon iritis, aphthous stomatitis, and genital ulcers; also develop arthritis, thromboembolism, and central nervous system problems; iritis is usually bilateral with posterior involvement, the hallmark is occlusive retinal vasculitis (see Chapter 10). More common in Asians and Middle Easterners; associated with HLA-B5 (subtypes Bw51 and B52) and HLA-B12.

Glaucomatocyclitic crisis (Posner–Schlossman syndrome) (acute)

Unilateral, mild, recurrent iritis with markedly elevated intraocular pressure, corneal edema, fine keratic precipitates, and a mid-dilated pupil; no synechiae; self-limited episodes (hours to days); associated with HLA-Bw54.

Kawasaki’s disease (acute)

Exanthematous disease with bilateral conjunctivitis and anterior uveitis in children (see Chapter 4); may be fatal.

Drugs (acute)

Certain medications may cause anterior uveitis, specifically rifabutin, cidofovir, sulfonamides, bisphosphonates, diethylcarbamazine, and metipranolol.

Interstitial nephritis (acute)

Usually bilateral, anterior uveitis that occurs more frequently in children, may have posterior involvement; female predilection. Patients have fever, malaise, arthralgias; urinalysis shows white blood cells without infection. May be due to allergic reaction to a nonsteroidal anti-inflammatory or antibiotic; can progress to renal failure if not treated with oral steroids.

Other autoimmune disease (acute and chronic)

Systemic lupus erythematosus, relapsing polychondritis, and Wegener’s granulomatosis.

Juvenile rheumatoid arthritis (JRA, acute and chronic)

Most common cause of uveitis in children, typically bilateral, anterior uveitis with minimal redness and pain. Type I is pauciarticular (90%), RF negative, ANA positive, female predilection (4 : 1), no sacroiliitis, and earlier onset (by age 4 years); type II is pauciarticular, RF negative, ANA negative, HLA-B27 positive, male predilection, sacroiliitis common, and later onset (by age 8 years); both have a chronic course with poor prognosis. Another subset is childhood spondyloarthropathy, which causes an acute, unilateral, self-limited, anterior uveitis; usually in males, older than 12 years, and HLA-B27 positive. Iritis is rare in polyarticular RF-negative JRA and Still’s disease.

Fuchs’ heterochromic iridocyclitis (chronic)

Accounts for 2% of anterior uveitis. Usually unilateral (90%), low-grade iritis with small, white, stellate keratic precipitates, abnormal anterior chamber angle vessels (friable and bleed easily with rapid surgical lowering of intraocular pressure [i.e., during paracentesis]), diffuse iris atrophy may cause heterochromia (for lightly pigmented irides involved iris appears darker; for darkly pigmented irides involved iris appears lighter), and no synechiae; predilection for blue-eyed patients; associated with glaucoma (15%) and cataracts (70%). Good prognosis; poor response to topical steroids (therefore, not indicated).

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FIGURE 6-12 Fuchs’ heterochromic iridocyclitis with fine, white, stellate keratic precipitates.

Postoperative or trauma (acute or chronic)

Ocular injury including surgery produces variable anterior chamber inflammation, and must be distinguished from: exacerbation of preexisting uveitis, TASS, retained lens fragments, UGH syndrome, endophthalmitis, and sympathetic ophthalmia.

Granulomatous

Autoimmune

Sarcoidosis (see Chapter 10), Vogt–Koyanagi–Harada syndrome (see Chapter 10), sympathetic ophthalmia (see Chapter 10), Wegener’s granulomatosis, multiple sclerosis, and lens-induced (phacoanaphylactic endophthalmitis [phacoantigenic uveitis]; an immune-mediated [type 3] hypersensitivity reaction to lens particles after trauma or surgery causing a zonal granulomatous reaction after a latent period).

HLA associations (located on chromosome 6)

A11 Sympathetic ophthalmia.

A29 Bird-shot retinochoroidopathy.

B5 Behçet’s disease (also B12).

B7 Presumed ocular histoplasmosis syndrome, serpiginous choroidopathy, ankylosing spondylitis.

B8 Sjögren’s syndrome.

B12 Ocular cicatricial pemphigoid.

B27 Ankylosing spondylitis (88%), Reiter’s syndrome (85–95%), inflammatory bowel disease (60%), psoriatic arthritis (also B17).

Bw54 Posner–Schlossman syndrome.

DR4 Vogt–Koyanagi–Harada syndrome, ocular cicatricial pemphigoid.

Symptoms

Pain, photophobia, tearing, red eye; may have decreased vision or floaters. JRA can produce severe anterior uveitis without significant pain or redness.

Signs

Normal or decreased visual acuity, ciliary injection, miosis, anterior chamber cells and flare; may have fine (nongranulomatous) or mutton fat (granulomatous) keratic precipitates, keratitis, decreased corneal sensation, iris nodules (Koeppe, Busacca, Berlin; see Figures 7-42 and 7-43), iris atrophy, usually decreased intraocular pressure but may be increased (especially in HSV, HZV, Posner–Schlossman syndrome, sarcoidosis, toxoplasmosis), peripheral anterior synechiae, posterior synechiae, hypopyon (especially HLA-B27 associated and Behçet’s disease), cataract, vitritis, retinal or choroidal lesions, cystoid macular edema, optic disc edema.

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FIGURE 6-13 Granulomatous uveitis demonstrating keratic precipitates and posterior synechiae.

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FIGURE 6-14 Close-up of granulomatous keratic precipitates.

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FIGURE 6-15 Anterior vitreous cells are visible with fine slit-beam behind the lens. The cells are seen here as small white specks among vitreous strands.

Differential Diagnosis

Masquerade syndromes include retinal detachment, retinoblastoma, malignant melanoma, leukemia, large cell lymphoma (reticulum cell sarcoma), juvenile xanthogranuloma, intraocular foreign body, anterior segment ischemia, ocular ischemic syndrome, and spill-over syndromes from any posterior uveitis (most commonly toxoplasmosis) (see Chapter 10).

Evaluation

• Complete history with attention to past ocular history of herpetic keratitis and trauma, past medical history of associated diseases (i.e., collagen vascular diseases, autoimmune disorders, infections), medications, diet (consumption of raw or poorly cooked meat or unpasteurized milk), geography (living in indigenous areas, travel to third world countries), social history (unprotected sex, IV drug use), other exposures (cats and dogs, and individuals with infectious disease [i.e., tuberculosis, syphilis]), and review of systems particularly for constitutional, skin, joint, respiratory, gastrointestinal (GI), and neurologic symptoms.

• Complete eye exam with attention to corneal sensation, character and location of keratic precipitates, tonometry, anterior chamber, iris (nodules and atrophy), vitreous cells, and ophthalmoscopy.

• Lab testing according to following general principles: Defer testing if first episode of mild, unilateral, nongranulomatous anterior uveitis not associated with systemic symptoms or signs suggestive of an underlying etiology (usually idiopathic), or if diagnosis is known.

Test if uveitis is moderate or severe, bilateral, recurrent, granulomatous, involves posterior segment, or associated with systemic symptoms or signs suggestive of an underlying etiology. Purpose of testing is to eliminate a diagnosis, rule out systemic infections that cause uveitis (i.e., syphilis, tuberculosis), and to confirm a diagnosis already suspected. Consider retesting when initial test results do not match a strong clinical suspicion, and if uveitis changes (becomes more severe, bilateral, diffuse, or new symptoms or signs appear). Workup should be tailored as examination and history dictate.

• Basic testing recommended for nongranulomatous anterior uveitis with a negative history, review of systems, and medical examination: complete blood count (CBC), erythrocyte sedimentation rate (ESR), Venereal Disease Research Laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test or microhemagglutination for Treponema pallidum (MHA-TP) (syphilis), HLA-B27.

• Other lab tests that should be ordered according to history and / or evidence of granulomatous inflammation: ANA, RF (juvenile rheumatoid arthritis), serum lysozyme, angiotensin converting enzyme (ACE) (sarcoidosis), purified protein derivative (PPD) and controls (tuberculosis), herpes simplex and herpes zoster titers, enzyme-linked immunosorbent assay (ELISA) for Lyme immunoglobulin M and immunoglobulin G, human immunodeficiency virus (HIV) antibody test, chest radiographs (sarcoidosis, tuberculosis), chest CT scan (sarcoidosis), sacroiliac radiographs (ankylosing spondylitis), knee radiographs (JRA, Reiter’s syndrome), gallium scan (sarcoidosis), urinalysis (interstitial nephritis), and urethral cultures (Reiter’s syndrome).

• Special diagnostic lab tests: HLA typing, antineutrophil cytoplasmic antibodies (ANCA) (Wegener’s granulomatosis, polyarteritis nodosa), Raji cell and C1q binding assays for circulating immune complexes (systemic lupus erythematosus, systemic vasculitides), complement proteins: C3, C4, total complement (systemic lupus erythematosus, cryoglobulinemia, glomerulonephritis), soluble interleukin-2 receptor.

• Medical or rheumatology consultation.

Management

• Topical steroid (prednisolone acetate 1% [Pred Forte] or difluprednate 0.05% [Durezol] up to q1h initially, then taper very slowly over weeks to months depending on etiology and response; do not begin taper until inflammation is grade 1 + or less). Monitor intraocular pressure closely for steroid response. Patients who are steroid responsive should still be treated with topical steroids initially and the intraocular pressure treated with ocular hypotensive agents, then consider switching to a steroid with less IOP-elevating potential (i.e., Lotemax, Alrex, Vexol, Pred Mild, FML). Some patients with HZO uveitis may require indefinite topical steroid treatment to prevent recurrence.

• Topical cycloplegic (scopolamine 0.25% or homatropine 2% or 5% bid to qid for moderate to severe inflammation; cyclopentolate 1% or tropicamide 1% can be used for mild inflammation).

• May require treatment of increased intraocular pressure, especially glaucomatocyclitic crisis (see Primary Open-Angle Glaucoma section in Chapter 11; do not use miotic agents or prostaglandin analogues).

• Systemic antibiotics for Lyme disease, tuberculosis, syphilis, Whipple’s disease, and toxoplasmosis (see Chapter 10).

• Topical antiviral (ganciclovir gel 0.15% [Zirgan] 5 times/day or trifluridine 1% [Viroptic] 9 times/day) for herpes simplex infections with concomitant corneal epithelial involvement.

• Systemic antiviral (acyclovir [Zovirax] 800 mg 5 times/day for 7–10 days or famciclovir [Famvir] 500 mg po or valacyclovir [Valtrex] 1 g po tid for 7 days) for acute herpes zoster infection (see Chapter 3).

• Consider oral steroids (prednisone 60–100 mg po qd for 1 week, then taper according to response) or orbital steroid injection (triamcinolone acetonide 40 mg / mL peribulbar q 2 weeks prn) for severe cases; check purified protein derivative (PPD) and controls, blood glucose, and chest radiographs before starting systemic steroids.

• Add H2-blocker (ranitidine [Zantac] 150 mg po bid) or proton pump inhibitor when administering systemic steroids.

• Consider sub-Tenon’s steroid injection (triamcinolone acetonide 40 mg / mL) or intravitreal steroid injection (triamcinolone acetonide 4 mg / 0.1 mL) for resistant cases with associated cystoid macular edema. Biodegradable and nonerodable sustained-release steroid implants may also be an option. Use with caution because of possible steroid response.

• If the uveitis becomes steroid-dependent, does not respond or becomes refractory to steroids, or is vision-threatening then consider alternate agents:

• NSAIDs: Diclofenac (Voltaren) 75 mg po bid or diflunisal (Dolobid) 250 mg po bid. Other nonselective NSAIDs that can be used as a second line of therapy include indometacin (Indocin SR) 75 mg po bid or naproxen (Naprosyn) 250 mg po bid. In patients with a known history of gastritis or peptic ulceration, the use of cyclo-oxygenase-2 (COX-2) selective inhibitors should be considered (celecoxib [Celebrex] 100 mg po bid).

• Immunosuppressive chemotherapy: Should be managed by a uveitis specialist or in coordination with a medical specialist familiar with these agents; indications include Behçet’s disease, sympathetic ophthalmia, Vogt–Koyanagi–Harada syndrome, serpiginous choroidopathy, rheumatoid necrotizing scleritis or peripheral ulcerative keratitis, Wegener’s granulomatosis, polyarteritis nodosa, relapsing polychondritis, JRA, or sarcoidosis unresponsive to conventional therapy. Methotrexate is most commonly used first.

Antimetabolites: Azathioprine 1–3 mg / kg/day, methotrexate 0.15 mg / kg/day, mycophenolate mofetil (CellCept) 1–2 g po qd (“off-label” use for autoimmune ocular inflammatory diseases).

Inhibitors of leukocyte signaling: Cyclosporine 2.5–5.0 mg / kg/day, tacrolimus (Prograf) 0.1–0.15 mg / kg/day.

Alkylating agents: Cyclophosphamide 1–3 mg / kg / day, chlorambucil 0.1 mg / kg / day.

Biologic agents: Tumor necrosis factor alpha (TNF-α) inhibitors (infliximab [Remicade], etanercept [Enbrel], adalimumab [Humira]).

Other agents: Dapsone 25–50 mg bid or tid, colchicine 0.6 mg po bid for Behçet’s disease is controversial.

• Lens extraction for phacoanaphylactic endophthalmitis.

Prognosis

Depends on etiology; usually good if inflammation controlled. Poor if sequelae of chronic inflammation exist including cataract, glaucoma, posterior synechiae, band keratopathy, iris atrophy, cystoid macular edema, retinal detachment, retinal vasculitis, optic neuritis, neovascularization, hypotony, phthisis.

Uveitis–Glaucoma–Hyphema Syndrome

Definition

Triad of findings in patients with closed-loop and rigid anterior chamber, iris-supported, or loose sulcus IOLs secondary to trauma to angle structures, iris, or ciliary body.

Symptoms

Pain, photophobia, red eye, and decreased vision; may have constricted visual fields in late stages.

Signs

Decreased visual acuity, increased intraocular pressure, anterior chamber cells and flare, hyphema, IOL implant; may have corneal edema, optic nerve cupping, retinal nerve fiber layer defects, and visual field defects.

Differential Diagnosis

Neovascular glaucoma, trauma.

Evaluation

• Complete ophthalmic history and eye exam with attention to cornea, tonometry, anterior chamber, gonioscopy, iris, and ophthalmoscopy.

• Check visual fields.

Management

• Treatment of increased intraocular pressure (see Primary Open-Angle Glaucoma section in Chapter 11; do not use miotic agents or prostaglandin analogues).

• Topical steroid (prednisolone acetate 1% up to q1h then taper slowly over weeks to months) and cycloplegic (scopolamine 0.25% tid or atropine 1% bid).

• Usually requires surgery for IOL removal or exchange; may require glaucoma surgery.

Prognosis

Variable; depends on duration and extent of ocular damage; visual loss is permanent.