Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition



Alex V. Levin

Thomas W. Wilson

David Rootman

Jerome Kazdan

The cornea develops from surface ectoderm (corneal epithelium) and neural crest cells (corneal stroma and endothelium). Developmental anomalies can result from inherited or spontaneous genetic mutations and insults during embryogenesis. Acquired disease can result from infection or other environmental or local contiguous processes. Multiple genes are involved in corneal formation. Mutations in these genes may result in isolated corneal malformation or associated abnormalities of the anterior and posterior segment.

As the most important refracting portion of the eye, corneal disease is likely to have a significant effect on vision. In the developing visual system of a child, superimposed amblyopia will almost certainly accompany most corneal disease. As the cornea has afferent neural pain fibers carried by the trigeminal nerve, photophobia and pain are also common symptoms of corneal disease. Its location does allow for topical treatment to be effective in many types of disease, but some corneal problems are not amenable to medical therapy. Corneal transplantation is available to clear the visual axis and relieve symptoms, but this process requires long-term follow-up and treatment, which itself can be uncomfortable and amblyogenic. In the setting of congenital obstruction of the visual axis, the poor success of infantile corneal transplantation has to be carefully weighed against the value of clearing the visual axis as soon as possible.



Figure 5.1 Peters Anomaly

Peters anomaly is due to defective separation of the lens, a surface ectoderm derivative, from the surface ectoderm during the fourth to seventh week of gestation. The resulting corneal opacity (left image), which is usually central, is associated with a defect in the posterior cornea (Descemet membrane and endothelium) to which the iris and/or lens remains attached (right image). The lens is often cataractous. It is bilateral in 80% of patients, and glaucoma is present in 50% of patients. When patients have associated heart defects, cleft palate, and skeletal anomalies, the syndrome is referred to as Peters Plus (Krause-Kivlin syndrome). Although most cases are sporadic, involvement of the PAX6, CYP1B1, and PITX2 has also been occasionally described.


Figure 5.2 Sclerocornea

Sclerocornea is an opacification of the cornea, which is contiguous with the sclera. There is often associated microcornea, microphthalmia, or cornea plana. Visual prognosis is guarded even with early transplantation due to the associated ocular developmental abnormalities. Extensive vascularization may also contribute to corneal graft failure. Although the intraocular pressure may appear to be elevated by tonometry and glaucoma is associated, one must be careful to consider that the increased rigidity and thickness of the cornea may result in artifactitious measured pressure elevation.


Figure 5.3 Corneal Dermoid

Corneal dermoids are round or oval vascular masses attached to the corneal surface. They often protrude, as seen here. They consist of ectodermally derived tissue and may contain hair and sweat glands within the corneal stroma. Therefore, these lesions are classified as choristomas. The lesions are most commonly located at the inferotemporal limbus but may also occur in the conjunctiva or central cornea. Astigmatic or occlusion amblyopia is a concern. Systemic associations include Goldenhar syndrome (Chapter 14: Craniofacial,Figs. 14.18, 14.19, 14.20 and 14.21). Lamellar keratoplasty and penetrating keratoplasty are performed for superficial and deep lesions, respectively. When isolated, this is usually a sporadic nongenetic anomaly.




Figure 5.4 Microcornea

Microcornea is a corneal horizontal diameter of less than 10 mm after 2 years of age. Normative values for younger ages are also available. Microcornea can occur unilaterally or bilaterally and is associated with other ocular disorders including cataract, glaucoma, and coloboma. Note that microcornea can occur in the absence of microphthalmia (shortened axial length). There are numerous syndromic and chromosomal associations. Although vision is usually reduced, mild microcornea can be associated with vision as good as 6/12 in some patients.


Figure 5.5 Megalocornea

Megalocornea is an increased horizontal diameter of greater than 13 mm by age 2 years. The intraocular pressure, cornea thickness, and endothelial density are typically normal. X-linked recessive transmission is typical, with affected males often having bilateral corneal diameters in excess of 14 mm and carrier females having diameters of 12 to 14 mm. Radial iris transillumination may be present. One characteristic sign, pictured here, is the ability to see the iridocorneal angle structures without gonioscopy. This can also be seen in some cases of buphthalmos due to infantile glaucoma, but there is no corneal edema or opacity in X-linked megalocornea. An autosomal recessive form (Neuhauser syndrome) associated with mental retardation is less common.


Figure 5.6 Congenital Cornea Ectasia

Congenital corneal ectasia is a thinning and protrusion of the central cornea, if not a descemetocele or frank perforation at birth. Uveal tissue often lines the endothelial surface of the abnormal cornea. There is typically microphthalmia and increased intraocular pressure due to angle anomalies. Ectasia may be a manifestation of Peters anomaly (Fig. 5.1), congenital infections (e.g., cytomegalovirus,Chapter 19: Infectious Diseases, Figs. 19.9, 19.10 and 19.11), or an isolated ocular anomaly. Treatment includes urgent penetrating keratoplasty for tectonic support. Given the young age at which this procedure is required, the success rate is low.


Figure 5.7 Prominent Corneal Nerves

Increased visibility of corneal nerves in children is seen with neurofibromatosis type I, congenital glaucoma, keratoconus, multiple endocrine neoplasia type IIB, ichthyosis, corneal infection with herpes virus or acanthamoeba, leprosy, tuberculosis, and Refsum disease. The visual acuity is not typically affected by the corneal nerves but can be reduced by the associated ocular conditions. Corneal nerves are normally visible up to 2 mm anterior to the limbus.




Figure 5.8 Vertically Oval Cornea

The normal cornea is typically oval with a wider horizontal diameter. When the cornea is vertically oval, it is otherwise normal and the vision is unaffected. Associated conditions include microphthalmia, interstitial keratitis, and Turner syndrome. No treatment is indicated.


Figure 5.9 Cornea Plana

Cornea plana is an abnormally flat anterior corneal surface with corneal curvatures less than 40 diopters and often less than 36. The peripheral cornea is similar to sclera and may be more opaque than usual with features of sclerocornea (Fig. 5.2). Central cornea may also have decreased clarity. Most cases are sporadic, although autosomal dominant and autosomal recessive forms due to mutations in the keratocan gene at 12q also occur, as does association with systemic syndromes such as Ehlers-Danlos and Marfan.


Figure 5.10 Meesman Corneal Dystrophy

Meesman dystropy is an abnormality of the corneal epithelium. Small intraepithelial vesicles can be detected within the first decade. Patients become symptomatic later in life and experience significant photophobia, tearing, and foreign body sensation. Treatment modalities include bandage contact lenses and artificial tears. Patients rarely require keratoplasty. Meesman dystrophy is inherited as an autosomal dominant disorder and is likely due to mutations in genes for the corneal keratins K3 and K12 located at 17q12 and 12q13, respectively. These proteins are involved with corneal epithelial cell cytoskeleton.




Figure 5.11 Reis-Buckler Dystrophy

Reis-Buckler corneal dystrophy, also known as corneal dystrophy of Bowman layer type 1, is an autosomal dominant anterior corneal dystrophy, which is linked, like many other corneal dystrophies, to 5q31. Clinically, this dystrophy is characterized by multiple small discrete opacities with a geographic distribution seen centrally just under the epithelium. The peripheral cornea is usually spared. Secondary involvement of the anterior stroma or overlying epithelium may occur. Patients suffer from recurrent erosions. Histologically, the cornea shows scarring and thickening of collagen in the area of the Bowman membrane with abnormalities of the epithelial cells.


Figure 5.12 Schnyder Crystalline Corneal Dystrophy

Schnyder corneal dystrophy presents in the first few years of life with bilateral central discoid lesions composed of small polychromatic crystals. The needlelike opacities are concentrated in the anterior stroma and can increase in density over time. The condition is autosomal dominant and has been mapped to 1p34.1-36. Histopathology reveals cholesterol and fat deposits within the keratocytes and the extracellular matrix. Phototherapeutic keratoplasty or penetrating keratoplasty may be required to restore visual acuity.


Figure 5.13 Granular Corneal Dystrophy (Groenouw Type I Corneal Dystrophy)

Granular stromal dystrophy is a progressive degeneration of the corneal stroma. It is an autosomal dominant disorder caused by mutations in the keratoepithelin gene at 5q31. Signs typically appear in the first decade of life. The opacities resemble “bread crumbs” and are concentrated in the visual axis. The opacities have sharp borders with clear cornea between the lesions. On pathology, the lesions consist of hyaline degeneration and stain with Masson trichrome stain.




Figure 5.14 Lattice Stromal Dystrophy

Lattice stromal dystrophy is a progressive deposition of amyloid material within the corneal stroma. It is inherited as an autosomal dominant trait and typically appears within the first decade of life. Patients usually present with decreased vision or pain secondary to recurrent corneal erosions. Clinically the cornea storage diseases, birth trauma with forceps injury, and sclerocornea are also included in the differential diagnoses. Pathologically there is endothelial degeneration with an abnormal Descemet membrane. The anterior banded zone of Descemet is normal; however, the posterior part of Descemet shows increased thickness. Treatment would include corneal transplant.


Figure 5.15 Macular Corneal Dystrophy (MCD)

Macular corneal dystrophy is an autosomal recessive disorder due to mutations in a sulfotransferase gene at 16p22. Onset occurs in the first decade and the disorder is progressive with the development of punctuate gray opacities. Patients experience recurrent attacks of photophobia due to recurrent erosions. Special stains on corneal specimens show acid mucopolysaccharides in corneal fibroblasts. The disorder is divided into two types: MCD type I, which has almost no sulfated keratan sulfate in the serum and cornea; and MCD type II, in which sulfated keratin sulfate is normal.


Figure 5.16 Congenital Hereditary Endothelial Dystrophy (CHED)

Congenital hereditary endothelial dystrophy is an autosomal recessive abnormality of the corneal endothelium. Patients typically present at birth with cloudy cornea. Autosomal recessive and autosomal dominant inheritance patterns have been reported. The autosomal dominant form develops in the first few years of life with increasing photophobia and epiphora. Because the cornea is clear for the first year of life, nystagmus typically is not present. The autosomal recessive form has significant corneal edema at birth, and nystagmus is common. Pathologic examination reveals a normal anterior banded layer of Descemet membrane and an abnormal posterior layer. Treatment includes corneal transplant. Differential diagnoses include sclerocornea, congenital glaucoma, trauma due to forceps injury, corneal ulcer, metabolic diseases, and dermoid.


Figure 5.17 Posterior Polymorphous Dystrophy

Posterior polymorphous dystrophy is an autosomal dominant posterior corneal abnormality. The abnormal gene has been mapped to chromosome 20Q11. It is typically bilateral and presents with irregular blisterlike opacities in the area of the Descemet membrane. Peripheral anterior synechiae can form causing corectopia, iris atrophy, and glaucoma. The pathologic examination of the posterior cornea shows an endothelium with similar morphologic and immunopathologic resemblance to corneal epithelium.




Figure 5.18 Keratoglobus

Keratoglobus is a generalized corneal ectasia secondary to an abnormality of corneal collagen. Keratoglobus is a bilateral condition that presents at birth with myopia and astigmatism. Unlike congenital corneal ectasia (Fig. 5.6), there is a generalized protrusion of the globe with thinning of the corneal stroma and localized absence of the Bowman membrane. The thinning is greatest in the periphery, which makes penetrating keratoplasty difficult. The cornea is usually clear, although edema may result from a progressive break in the Descemet membrane. Corneal diameter is normal. The cornea may be particularly susceptible to rupture from even minor trauma.


Figure 5.19 Keratoconus

Keratoconus is an abnormality in corneal collagen. Keratoconus typically presents in the second decade of life and can be either rapidly or slowly progressive. Clinical signs include a corneal protuberance in the shape of a cone, the apex of which is progressively thin. Keratoconus is an autosomal dominant disorder that has been mapped to multiple loci with one known gene, VSX1 at 20p11.2. Keratoconus is associated with increased visualization of corneal nerves (Fig. 5.7) and iron lines caused by pigment deposition within the epithelial and Bowman layer (Fleischer ring). It is more common in children with Down syndrome, atopy, Leber congenital amaurosis, and perhaps eye rubbing.


Figure 5.20 Keratoconus—Acute Corneal Hydrops and Munson Sign

If the Descemet membrane is ruptured due to progressive thinning at the apex of the cone, the cornea can rapidly fill with fluid, causing a rapid decrease in vision due to corneal edema (left image). This acute corneal hydrops may improve with no treatment but may also require emergency corneal grafting. Subsequent scarring in the visual axis after the acute hydrops resolves is another indication for transplantation. This scarring can be seen in the right image, which also demonstrates a Munson sign: A conical deviation in the lower lid in downgaze due to the corneal cone.




Figure 5.21 Corneal Forceps Injury

A corneal injury can occur when forceps are inadvertently applied to the face, with the edge of a forceps blade across the open or closed lid, during delivery. Breaks in the Descemet membrane are the direct result of pressure placed on the cornea and are typically linear. They appear as parallel lines representing the two edges of the scrolled Descemet membrane. Corneal edema and permanent scarring can lead to photophobia, astigmatism, and vision loss. However, improvement usually occurs over time and transplantation is rarely needed. There may be associated injury to the periocular tissues such as ecchymosis and laceration, and/or facial nerve palsy. The lesion is virtually always unilateral.


Figure 5.22 Band Keratopathy

Band keratopathy is caused by deposition of calcium within the Bowman layer of the cornea. The deposits are grayish-white and are concentrated within the interpalpebral area. The absence of the Bowman layer in the peripheral cornea creates a clear zone at the corneal–limbal junction. As seen in the photo, pinpoint clear areas can be seen throughout the opacity and represent areas where the corneal nerves pass through the Bowman layer. Potential causes include chronic inflammation (e.g., uveitis, keratitis), hypercalcemia, toxins, and skin diseases. Treatment modalities include chelation with ethylenediaminetetraacetic acid and/or mechanical scraping.




Figure 5.23 Exposure Keratopathy

Corneal exposure can occur with reduced corneal lubrication or inadequate eyelid closure. Decreased lubrication can be secondary to inadequate tear quality or quantity (e.g., blepharitis, damage to the lacrimal gland from radiation, tumor or trauma, and Sjögren syndrome). Inadequate eyelid closure can be the result of lower lid ectropion, proptosis, lagophthalmos, or facial nerve palsy. A neurotrophic/anesthetic cornea will be more susceptible to changes secondary to exposure. The cornea in the photo has chronic exposure with keratinization of the corneal surface and vascularization. Progressive damage can ultimately lead to perforation. Treatment modalities include aggressive tear replacement with drops and ointment, elimination of eyelid apposition abnormalities, tarsorrhaphy, and nighttime closure with tape.


Figure 5.24 Thygeson Superficial Punctate Keratitis

Thygeson superficial punctate keratitis is a focal keratitis without conjunctival or stromal involvement. It is usually recurrent and bilateral. Patients typically present with foreign body sensation with photophobia and increased tearing. On slit-lamp examination there are multiple slightly raised, white/gray dots. They are concentrated centrally and may stain with fluorescein during the acute attack (Fig. 5.25). There is no associated conjunctivitis or subepithelial infiltrate. The episode lasts 4 to 6 weeks and then typically recurs several times a year. Treatment options include topical steroids and a bandage contact lens.


Figure 5.25 Thygeson Superficial Punctate Keratopathy

The cause of this remarkably asymptomatic disorder is largely unknown. It is characterized by mild foreign body sensation and multiple elevated white or gray-white round intraepithelial opacities that stain with fluorescein. The remainder of the eye examination is normal. The lesions usually resolve spontaneously, but recurrences and chronicity are common. Artificial lubrication, and in more severe cases topical steroids, are used as treatment.


Figure 5.26 Staphylococcal Hypersensitivity Immune Keratitis

Staphylococcal hypersensitivity immune keratitis is a type IV immune response on the periphery of the cornea. The small raised white dots located near the limbus will often stain with fluorescein. Excessive amounts of staphylococcal species, usually coagulase negative and otherwise nonpathogenic, are the causative agent. Blepharitis and meibomian plugging are commonly found (Chapter 2: Lids and Adnexa, Fig. 2.23). Treatment includes lid hygiene, warm compresses, and topical antibiotics to address the lid margin disease, but a short course of topical steroids will rapidly resolve the keratitis.




Figure 5.27 Corneal Phlyctenule

Corneal phlyctenules are inflammatory lesions located just anterior to the limbus. A type IV hypersensitivity reaction to staphylococcus species is the most common cause and may also be associated with conjunctival phlyctenule (Chapter 4: Conjunctiva, Fig. 4.15). Corneal phlyctenule may also be due to tuberculosis or, in immunocompromised patients, sporotrichosis. The lesions can become ulcerated on the surface and result in scarring of the peripheral cornea. Treatment of the underlying blepharitis (Chapter 2: Lids and Adnexa, Fig. 2.23) with lid hygiene and topical antibiotics is essential. Topical steroids are indicated for severely inflamed lesions or lesions not responding to conservative therapy.


Figure 5.28 Radiation Keratitis

Radiation keratitis occurs when the eye is in the field of radiation for ocular, orbital, sinus, or brain tumors. In addition to corneal dysfunction, there is contributing meibomian gland dysfunction and loss of conjunctival goblet cells with or without lacrimal gland hyposecretion, all of which lead to dry eye and corneal vascularization. The inferior third of the cornea is usually the most affected site. Artificial lubrication is essential to prevent progression. Left untreated, severe corneal vascularization, scarring, and even perforation may result.


Figure 5.29 Filamentary Keratitis

Corneal filaments are strands of mucus and corneal epithelium attached to the surface of the cornea. Filamentary keratitis is a clinical finding caused by dry eye, recurrent erosion, exposure keratopathy, radiation keratopathy, neurotrophic keratopathy, and herpes simplex virus. Treatment includes debridement, tear supplements, bandage contact lenses, and mucolytic agents (N-acetylcysteine). The filaments can be quite prominent despite minimal symptoms.




Figure 5.30 Herpes Simplex Virus—Primary Infection

The left image shows a patient with primary herpes simplex virus (HSV) infection of the periocular structures. The vesicular lesions on the face are most commonly the result of direct exposure to an infected individual. Clinical features may include vesicular dermatitis, blepharoconjunctivitis, and keratitis. Conjunctival follicles and pseudomembranes (Chapter 4: Conjunctiva, Fig. 4.11) are common. Keratitis occurs in 50% of patients with primary HSV. In the right image, the corneal findings are different from recurrent HSV and include a diffuse epitheliopathy without branching dendrites (as shown in the image). Treatment with antiviral agents is indicated for blepharitis, conjunctivitis, and keratitis. Ocular surface medication is not needed if the eye is not red.


Figure 5.31 Herpes Simplex Virus— Recurrent Infection

Recurrent herpes simplex virus is a reactivation of the latent virus stored within the trigeminal ganglion. The primary disease could have previously involved the periocular structures or the mouth. A diffuse epithelial punctuate keratopathy is the first sign of corneal involvement that may progress into corneal dendrites, as demonstrated here with topical fluorescein staining. The lesions may be painful, but after recurrent infections, corneal sensation is reduced. Treatment includes debridement, topical antivirals, and, in infants or vision-threatening lesions, systemic antivirals.


Figure 5.32 Varicella Zoster

Herpes zoster is caused by reactivation of the varicella virus following earlier chickenpox. The photograph demonstrates the typical vesicular lesions respecting the distribution of the trigeminal nerve. Children with zoster should undergo an evaluation for underlying immunosuppression. Ocular manifestations include keratitis, uveitis, scleritis, conjunctivitis, and chorioretinitis. Treatment includes topical steroids and systemic acyclovir. Postzoster neuralgia can also occur in children.




Figure 5.33 Acanthamoeba Keratitis

Radial keratitis is pathognomonic for acanthamoeba keratitis. Acanthamoeba keratitis is caused by protozoa and is seen most commonly in contact lens wearers. Patients present with severe photophobia and pain. Clinical findings include a follicular conjunctivitis, preauricular node, ring corneal infiltrate, and radial keratitis (enlarged corneal nerves with surrounding infiltrates). Diagnosis is made by culturing the acanthamoeba on Escherichia coli nonnutrient agar. Cysts and trophozoites can be identified on smears with calcofluor white. Treatment includes neomycin, the antifungal agents containing imidazole and triazole, the antiseptic solution chlorhexidine, the swimming pool cleaner Brolene, and polymyxin B.


Figure 5.34 Bacterial

Bacterial corneal ulcers in children can be caused by trauma, contact lens overwear, exposure keratopathy, and congenital malformations. Aphakic children in silicone contact lenses rarely get ulcers. Teenagers with poor cosmetic soft contact lens hygiene are particularly susceptible. Corneal cultures and stains should be obtained to isolate the organism, even if examination under anesthesia is needed. Broad-spectrum antibiotics should be started topically and then tailored to cover the identified organisms. The white corneal infiltrate is usually surrounded by stromal edema and overlying corneal epithelial defects.