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Contents

21.2.1Anophthalmia  . . . . . . . . . . . .   290

21.2.2Colobomatous Microphthalmia and Typical Uveal Coloboma  . . . . . . . . . . .   290

21.3Congenital Disorders of the Anterior

21.3.3Axenfeld-RiegerAnomaly andAxenfeld-

Rieger Syndrome  . . . . . . . . . .   293

21.3.4Primary Congenital Glaucoma  . . . . .   294

21.3.5 Iridocorneal Endothelial Syndromes  . . .   294

21.3.6Peters’ Anomaly and Peters’ Plus Syndrome    295

21.3.7Aniridia  . . . . . . . . . . . . . . . . . . . . . . . . . . . .   296

21.4Congenital Disorders of the Cornea  . . .   297

21.4.1 Dermoids  . . . . . . . . . . . . .   297

21.4.2Megalocornea  . . . . . . . . . . . .   297

21.4.3Microcornea  . . . . . . . . . . . .   297

21.4.4 Cornea Plana  . . . . . . . . . . . .   297

21.4.5Sclerocornea  . . . . . . . . . . . .   297

21.4.6Corneal Dystrophies  . . . . . . . . .   298

21.6Persistent Hyperplastic Primary Vitreous/ Persistence of the Fetal Vasculature  . . .   299

21.7.1Aplasia of the Optic Nerve  . . . . . . .   300

21.7.2Hypoplasia of the Optic Nerve  . . . . .   300

21.7.3Optic Disk Coloboma  . . . . . . . . .   300

21.7.4 Morning Glory Disk Anomaly  . . . . .   301

21.7.5Peripapillary Staphyloma  . . . . . . .   302

21.9Congenital Disorders of the Lids and Orbits    303

21.9.1 Hypotelorism  . . . . . . . . . . . .   303

21.9.2Hypertelorism  . . . . . . . . . . . .   303

Core Messages

•The embryogenesis of the eye and ocular adnexa is complex and depends on the organized expression and interaction

of a number of developmental genes.

Mutations in such genes or the influence of certain environmental toxins and teratogens cause ocular malformations. A number of ocular developmental genes

have been identified and clinical molecular testing is now available for some.

•Ocular malformations can be isolated or part of complex multisystem

syndromes. Certain ocular malformations are harbingers of serious “hidden” abnormalities in other organs such as

the heart, brain, or vascular system.

•Ocular malformations cause vision loss directly by interfering with media clarity or integrity of ocular structures, or by causing diseases such as amblyopia, glaucoma, or retinal detachment that

in turn result in loss of vision.

•The management of patients with ocular malformations includes making an accurate diagnosis, identifying any potentially associated syndromes or malformations in other organ systems, optimizing visual function, and anticipating the occurrence of other problems such as glaucoma and amblyopia.

21.1 Embryology of the Eye

As a group, congenital malformations of the eye constitute a significant source of visual morbidity and are often a sign of malformation syndromes and of hidden brain or other organ abnormalities. Malformations result from a variety of chromosomal or single gene defects, or they may be caused by in utero exposure to exogenous teratogens.

In order to evaluate congenital malformations, one needs to have an understanding of the embryology of the eye. Here we provide a brief overview of eye development. The reader is referred elsewhere for more detailed discussions [14, 129]. The three embryonic layers include ectoderm, mesoderm, and endoderm. Anterior ectoderm differentiates into neural ectoderm that gives rise to the eye and the brain. The first evidence of the developing eye is observed on day 21 of gestation when the optic sulci, also known as optic

pits, appear. These invaginations can be found on the inner surface of anterior neural folds of neural ectoderm that will later form forebrain (prosencephalon). At the same time, the neural folds start the fusion process that results in neural tube formation. Neural crest cells are found at the junction of the neural ectoderm and overlying surface ectoderm. They play an important role in eye development. These cells migrate beneath the surface ectoderm to different areas of the embryo, and specifically to the area of optic sulci.

There they serve as precursors to many eye structures including corneal stroma, iris stroma, ciliary muscle, choroid, sclera, and orbital cartilage and bone. It is worth mentioning that although throughout the rest of the body the connective tissue and bone structures are derived from mesoderm, the orbital bone and connective tissue are derived from neural crest cells. In the eye the mesoderm is responsible only for the striated muscle of the extraocular muscles and vascular endothelium.

As the neural tube closes anteriorly and the forebrain vesicles are formed, the optic sulci develop as bilateral evaginations of neural ectoderm on the forebrain vesicles. This expansion results in the formation of optic vesicles at gestation day 25. The optic vesicles are connected to the forebrain by the optic stalk, a precursor of the optic nerve. At day 27, the surface ectoderm overlying the evaginating optic vesicles thickens to form the lens placode. Subsequent to lens placode formation, the placode and underlying neural ectoderm start invaginating. The neural ectoderm invaginates on itself forming a double-layered optic cup, the inner layer of which will become the neurosensory retina and the outer the retinal pigment epithelium. The invagination process results in an inferiorly positioned optic fissure, also known as the embryonic or choroidal fissure. The tissue lining the fissure is of neural crest origin and gives rise to the hyaloid artery that courses from the optic stalk to the developing lens derived from the surface ectoderm. The hyaloid artery is a branch of the primitive ophthalmic artery. After the fissure closes at 6 weeks, primitive ciliary epithelium derived from neural ectoderm starts secreting aqueous fluid that creates intraocular pressure (IOP) and aids in expansion of the optic cup [22, 129]. Failure of the fissure to close results in microphthalmia and typical (in location) colobomas.

The lens is formed from the lens placode, which is derived from surface ectoderm. One important step in lens formation is the detachment of the lens vesicle from the surface ectoderm. Anterior lenticonus, anterior capsular cataracts, and anterior segment dysgenesis with keratolenticular adhesions in Peters’ anomaly may result from faulty keratolenticular separation

[129]. The hyaloid vessels form a network around the posterior lens capsule and then anastomose anteriorly with a network of vessels in the pupillary membrane anterior to the lens capsule that contains vessels and connective tissue. The vascular network that is formed around the lens is termed tunica vasculosa lentis and it regresses at 4 months of gestation along with the hyaloid artery. Mittendorf’s dot is a 1- to

2-mm area of fibrosis on the posterior capsule and is likely to represent an incomplete regression of the hyaloid artery at its attachment site. An incompletely regressed pupillary membrane is called persistent pupillary membrane (Fig. 21.1).

The surface ectoderm forms the corneal epithelium, whereas both corneal stroma and endothelium are derived from neural crest cells. In addition, neural crest cells form anterior iris stroma, the ciliary muscle, and most structures of the iridocorneal angle. Aqueous draining is observed by 17–18 weeks of fetal life and gradually increases during development [67]. Increased IOP occurs in many disorders in which the anterior chamber angle structures do not develop properly and in which aqueous drainage is impaired; these conditions include Axenfeld-Rieger syndrome, iridogoniodysgenesis/iris hypoplasia, Peters’ anomaly, primary congenital glaucoma along with cornea plana, sclerocornea, megalocornea, and congenital hereditary endothelial dystrophy [48].

The retina’s cellular differentiation progresses in the form of a wave from inner to outer layers and from central retina to peripheral retina. Ganglion cells appear first. Amacrine, horizontal, and cone cells appear at approximately the same time, but none before the first ganglion cell [16]. Macular differentiation occurs relatively late [45], and it is only after birth that the ganglion and bipolar cells completely vacate the fovea centralis. The central retinal artery is derived from the portion of hyaloid artery within the optic stalk. A benign small tuft of glial cells that emanates from the center of the optic disk is termed Bergmeister’s papilla (Fig. 21.2) and is a remnant of

the hyaloid system of blood vessels and associated tissues. The central retinal artery forms temporal and nasal retinal arcades, with the latter reaching the periphery first. Thus, a newborn can have an immature partially avascular area in the temporal periphery

[129].

The vitreous develops in three stages. The primary vitreous is a highly vascularized gel that is replaced by the avascular secondary vitreous. The tertiary vitreous serves as a precursor of the lens zonule. At birth, most of the posterior vitreous gel is secondary vitreous with the vitreous base and zonule representing tertiary vitreous. Cloquet’s canal is an atrophied primary vitreous that persists as an optically clear zone emanating from the optic nerve to the posterior aspect of the lens [129].

The optic stalk that connects the optic vesicle to the forebrain serves as a precursor to the optic nerve. The ganglion cells of the developing retina send their axons through the optic stalk at week 6.The optic chiasm consists first of all crossed fibers and only later do the uncrossed fibers reach the optic chiasm. The first ganglion axons reach the dorsal nucleus of the lateral geniculate body at week 9. At month 5 of gestation, axons start becoming myelinated in the area of lateral geniculate body. It takes about 3 months for the wave of myelinization to reach the globe. Myelinization stops at the lamina cribrosa at 1 month after birth. Anomalous myelination of nerve fibers is clinically obvious as a flat, feathery, glossy sheen on the surface of the retina and has been associated with high myopia and amblyopia in some cases (Fig. 21.3)

[32, 112].

Fig. 21.1  Few strands of remnants of the papillary membrane attach to a small fibrous piece of tissue on the anterior lens capsule

Fig. 21.2  Remnant of the hyaloid system on nasal aspect of optic disk, Bergmeister’s papilla

Fig. 21.3  Extensive myelination of the nerve fiber layer associated with high myopia and amblyopia in this patient

21.2Anophthalmia and Colobomatous Microphthalmia

21.2.1 Anophthalmia

Anophthalmia refers to the unilateral or bilateral apparent absence of the globe in an orbit with normal adnexal elements. Rudiments of optic vesicle-derived structures and structures derived from mesoderm and/or neural crest may be found on histopathologic sectioning of the orbit in consecutive or degenerative anophthalmia (clinical anophthalmia), but not in primary or true anophthalmia. The orbit is shallow and orbital volume remains small with increasing age, presumably because of absence of the trophic action of the globe on the orbit. True or primary anophthalmia is extremely rare and results from failure of the optic vesicle to bud from the cerebral vesicle; the optic nerves and tract are usually absent. In secondary anophthalmia there usually are associated severe forebrain malformations, such as holoprosencephaly, and affected fetuses are usually aborted. Consecutive or degenerative anophthalmia results from regression or degeneration of the optic vesicle. Inherited isolated anophthalmia is usually autosomal recessive. Anophthalmia can be present in a number of syndromes such as the Lenz microphthalmia syndrome and with a variety of chromosomal rearrangements. More re-

cently, mutations in the SOX2 gene on chromosome 3 were found to account for a significant proportion of cases of anophthalmia [35]. Treatment of anophthalmia consists of maintenance of orbital volume and conjunctival forniceal depth by insertion of ocular prostheses of increasing sizes into the orbit.

21.2.2Colobomatous Microphthalmia and Typical Uveal Coloboma

In microphthalmic eyes there is variable reduction in the volume of the eye. The corneal diameter is usually less than 10 mm and the anteroposterior globe diameter is less than 20 mm. The incidence of microphthalmia/clinical anophthalmia is 0.22 per 1,000 births; the incidence of coloboma is 0.26 per 1,000 births. The diagnosis of microphthalmia can generally be made by inspection of the eye. The cornea is small, but may be of normal size in posterior microphthalmos. Microcornea can occur in the absence of microphthalmia as a dominant or recessive trait. There may be a coloboma of the iris (Fig. 21.4), choroid, and/or optic nerve (Fig. 21.5). Cataracts may be present. Microphthalmic eyes usually have high hypermetropic refractive errors but may be myopic. The

Fig. 21.5  Very large typical inferior chorioretinal coloboma that has involved the entirety of the optic nerve head. Note the yellow luteal pigment in the upper right of the figure; this area corresponds to the fovea

Fig. 21.6  Coronal MRI section demonstrating right microphthalmia with cyst. These are typically inferior to the globe and cause a bulge in the lower lid

diagnosis of borderline cases can be confirmed by measuring the diameter of the eye using ultrasonography. The normal adult eye measures between 21.50 and 27.00 mm.

Microphthalmia can be unilateral or bilateral and may or may not be associated with uveal coloboma, hence its general classification into colobomatous and non-colobomatous. Asymmetric reduction of the volume of the eyes is common in bilateral cases. Large colobomas may produce a white reflex from the pupil (leukocoria) and have been confused with retinoblastoma. Rare complications of colobomas include subretinal neovascularization and retinal detachment.

Colobomas result from failure of closure of the embryonic fissure in the invaginated optic vesicle, a process completed by week 6 of gestation. “Typical” colobomas are inferonasal and may involve iris, ciliary body, inferior choroid, and/or optic nerve head.

Eyes with colobomas may be of normal size but are generally microphthalmic. A cyst may form in the area of defective closure, producing microphthalmia with cyst (Fig. 21.6). Patients with this condition usually present with a bulging of the inferior lid and superior displacement of the globe by the cyst.

The coordinated expression of a large number of developmental genes is necessary for normal ocular

and optic nerve development and the pathways and interactions between these genes are currently being elucidated. Mutations in any of these genes can theoretically result in microphthalmia and/or coloboma.

Microphthalmia can be isolated or familial, or can occur in a number of single gene, chromosomal, and embryopathic multisystem malformation syndromes. About a quarter of patients with microphthalmia/ coloboma have the CHARGE association (Fig. 21.7)

[10]. There is extreme variable expressivity in familial cases, with some family members exhibiting severe microphthalmia and others only small asymptomatic uveal colobomas in normal-sized eyes; hence the importance of ocular examination of all family members. CHX10 on chromosome 14q24.3 is one of the genes associated with microphthalmia [36].

Errors of refraction should be corrected. Cataract extraction is performed if the retina is attached and the size of the eye is not extremely small. Prostheses are fit over very small blind eyes for cosmetic purposes. Genetic counseling should be provided after examination of all available family members to determine the possible mode of inheritance in familial cases. The empiric risk of recurrence in a sibling is 2% if both parents are unaffected and increases to 14% if one parent is affected. The yield of chromosomal studies is poor for isolated microphthalmia/ coloboma but increases significantly if there is associated mental retardation and at least one other congenital malformation.

21.3Congenital Disorders of the Anterior Segment

Anterior segment anomalies can result from disturbances of neural crest cell, ectoderm, or global ocular development. The anterior segment consists of the cornea, iris, anterior chamber angle, and lens. Research in Drosophila melanogaster and murine and other animal models has identified several transcription factor genes that play a vital role in normal development of the anterior segment. PAX6 has the most panocular expression and has been implicated in aniridia [42], Peters’anomaly [42],Axenfeld’s anomaly [5], keratitis [73], optic nerve malformations [6], and foveal hypoplasia [123]. Foxc1 (Fkhl7), Pitx2

Fig. 21.7  Patient with CHARGE association. Left eye is microphthalmic. Note hearing aid and abnormally shaped ear

(Rieg1), and Lmx1b are some of the developmental genes expressed in neural crest cells. The former two have been implicated in such forms of anterior segment dysgenesis as iridogoniodysgenesis anomaly, iris hypoplasia, Axenfeld-Rieger anomaly, AxenfeldRieger syndrome, and congenital glaucoma [56, 58, 69, 74, 80, 87, 103]. Foxe3 and Maf are expressed within the developing lens and are involved in cataract formation and anterior segment ocular dysgenesis

[49, 102, 120].Additionally, the CYP1B1 gene that is not a transcription factor but encodes an enzyme has been implemented in congenital glaucoma [110].

Abnormalities of neural crest cell development in the eye result in posterior embryotoxon, iris hypoplasia and iridogoniodysgenesis, the Axenfeld-Rieger anomaly and Axenfeld-Rieger syndrome, primary congenital glaucoma, and iridocorneal endothelial syndromes.

21.3.1 Posterior Embryotoxon

Isolated posterior embryotoxon denotes an anteriorly displaced and prominent Schwalbe’s line. It is present in a small percentage of normal individuals and generally does not require treatment. However, it

should be recognized that posterior embryotoxon can be part of the Axenfeld-Rieger anomaly and hence eyes that display it are predisposed to glaucoma. Additionally, it has been associated with Alagille syndrome, a condition characterized by hepatic ductular hypoplasia, with neonatal jaundice, pulmonic valvular stenosis as well as peripheral arterial stenosis, abnormal “butterfly” vertebrae, decrease in interpediculate distance in the lumbar spine, absent deep tendon reflexes, poor school performance, and peculiar facies [1, 95, 127].

21.3.2Iris Hypoplasia

and Iridogoniodysgenesis

First described by Berg in 1932, hypoplastic irides have a gray/brown color that represents the pigmented iris epithelium showing through hypoplastic iris stroma that is derived from neural crest cells. The iris appears flat and lacks the normal crypts and variations in thickness. Iris vessels may be prominent. It may or may not be associated with a prominent Schwalbe’s line. Iris hypoplasia can be associated with angle maldevelopment–iridogoniodysgenesis and thus be part of the autosomal dominant iridogoniodysgenesis anomaly (type I iridogoniodysgenesis) that is characterized by iris hypoplasia and goniodysgenesis with frequent juvenile glaucoma, and that maps to 6p25 [68].Agroup of dominant disorders involving changes in the anterior segment of the eye associated with glaucoma (Axenfeld-Rieger anomaly, iris hypoplasia, and iridogoniodysgenesis) maps to 6p25 and results from mutations in the

FOXC1 gene [80].

Type II iridogoniodysgenesis is also an autosomal dominant disorder characterized by iris hypoplasia, goniodysgenesis, and increased IOP, but is caused by mutations in the PITX2 gene on chromosome 4q2 25-q26, the same gene that causes classic AxenfeldRieger syndrome indicating that iridogoniodysgenesis andAxenfeld-Rieger syndrome are allelic variants of the same disorder [3, 56].

An autosomal recessive form of iridogoniodysgenesis has been reported to be associated with congenital glaucoma, skeletal anomalies, and peculiar facial appearance [93].

Ophthalmologists caring for patients with iridogoniodysgenesis should be acutely aware of the glaucomatous component of the disorder, and IOP should be periodically checked in these patients.

21.3.3Axenfeld-Rieger Anomaly

and Axenfeld-Rieger Syndrome

Axenfeld-Rieger anomaly (ARA) clinically is characterized by posterior embryotoxon with iris strands, corectopia, iris hypoplasia, and abnormalities of the anterior chamber angle. Iridocorneal adhesions cause pupil displacement or corectopia and iris atrophy can be so severe that it results in pseudopolycoria (Fig. 21.8). The anterior angle abnormalities include high insertion of the iris root on the trabecular meshwork, resultant adhesions over the angle, and excessive connective tissue deposition [61]. The consequence of these ocular abnormalities is a 50% lifetime risk of glaucoma [61].

The systemic manifestations of Axenfeld-Rieger syndrome (ARS) are extremely variable. They include cranio-dento-facial findings such dental hypoplasia, anterior teeth crowding, and underdevel-

Fig. 21.8  Anterior segment of patient with Rieger’s syndrome. The pupil is displaced inferiorly. The superior part of the iris is thin. There is an anteriorly displaced Schwalbe’s line (mostly in the inferior part of the cornea in this patient) with strands of iris adherent to it in some locations

oped maxilla [50]. Patients often have failure of the periumbilical skin to involute, sensory hearing loss, congenital heart defects, skeletal abnormalities, and rarely anal stenosis [23, 52, 61].

Currently there are two genes associated with ARS and at least two more incompletely defined genetic loci [61]. PITX2 (RIEG1) is located on chromosome 4q25 and FOXC1 maps to 6p25. The genes for loci 13q14 and 16q24 have not been identified.

Treatment depends on the patient’s presenting symptoms. Pupilloplasty might be required for patients with severe pupillary stenosis. Glaucoma should be treated medically first; surgery appears to have a lower success rate than that in primary congenital glaucoma. If medical treatment fail, enhanced filtering surgery is recommended [113]. It is important to remember that glaucoma drugs have a higher risk of systemic effects in pediatric patients. Parasympathomimetics and β-blockers can be used. Carbonic anhydrase inhibitors, prostaglandin agonists, and sympathomimetics are usually used as secondline pharmacologic interventions [113].

21.3.4 Primary Congenital Glaucoma

Glaucoma in an infant can be part of a syndrome. For instance, patients with ARS have greater chance of developing glaucoma [104], as do children with neurofibromatosis type 1, Sturge-Weber syndrome, Lowe syndrome, and Peters’ anomaly [7, 65]. Primary congenital glaucoma (PCG) arises as an independent entity with evidence of isolated trabeculodysgenesis. It usually presents bilaterally with buphthalmos (ocular enlargement), photophobia, epiphora, and blepharospasm and can be associated with corneal edema [7].

Untreated or poorly responsive cases go on to develop significant corneal opacification (Fig. 21.9). Formerly believed to be caused by the persistence of a membrane (Barkan’s membrane) over the angle structures, it is now considered to be due to developmental arrest of the trabecular meshwork. The trabecular meshwork has been shown to have thickened trabecular beams and uveal cords with narrow trabecular spaces [7].An examination under sedation or general anesthesia is frequently required for establishment of definitive diagnosis. Since PCG responds poorly to medical treatment, surgical intervention is often required [7]. A

Fig. 21.9  Bilateral total opacification of enlarged corneas in a young boy with congenital glaucoma

technique combining trabeculotomy with trabeculectomy has been reported to be a successful for treatment of PCG with corneal opacity [64]. Goniotomy surgery can be attempted if corneal clarity is preserved, but often a repeat procedure is needed [96]. The use of adjunctive mitomycin C in trabeculectomy is controversial for, although it results in higher number of successful outcomes, it has been associated with increased incidence of late-onset endophthalmitis [8, 38, 106]. Aqueous shunt devices should be used with caution [20, 33] and cyclodestruction is generally reserved to be the last option [7].

Genetic studies have identified CYP1B1 as the gene associated with the GLC3A locus on chromosome 2p22-p21, and the gene responsible for the majority of cases of primary infantile glaucoma. The CYP1B1 protein belongs to the cytochrome P450 superfamily of enzymes that have the ability to metabolize a variety of substrates. It has been hypothesized that this form of cytochrome P450 might be responsible for producing a compound necessary for normal development or for removing a substrate that might inhibit development of the trabecular meshwork [98].

21.3.5Iridocorneal Endothelial Syndromes

Iridocorneal endothelial (ICE) syndromes include three clinical entities such as progressive iris atrophy, Chandler’s syndrome, and iris-nevus syndrome

(Cogan-Reese syndrome). All three share the characteristic findings of the iridocorneal adhesions and the corneal endothelial abnormality. The iris findings differentiate the three syndromes for progressive iris atrophy presents with marked corectopia, ectropion uvea, iris atrophy, and hole formation [105]. On the other hand, Chandler’s syndrome has normal iris or mild to moderate degrees of corectopia, ectropion uvea, and iris atrophy with no hole formation [17].

A Cogan-Reese syndrome iris can range from normal to severely affected. This syndrome is characterized by pigmented nodules on the iris stroma [18]. ICE syndromes are usually unilateral, affect women more commonly than men and present in early to middle adulthood. The corneal endothelium abnormality presents as a beaten silver appearance by slit-lamp biomicroscopy, and by specular microscopy the endothelial cells are pleomorphic in size and shape with virtually pathognomonic intracellular dark spots. On electron microscopy one sees areas of multilayered endothelium as well as areas of scant endothelium and abnormal accumulation of connective tissue under the intact Descemet’s membrane [104].

Pediatric patients usually do not require corneal grafting, but might need it as adults. Complications of glaucoma are treated first medically and then surgically.

21.3.6Peters’ Anomaly

and Peters’ Plus Syndrome

Peters’ anomaly is characterized by a central corneal leukoma (Fig. 21.10), lack of the posterior corneal stroma and Descemet’s membrane, and a variable degree of iridocorneal and keratolenticular attachments, with the most severe being of a lens adherent to the corneal stroma. Eighty percent of cases are bilateral, 50–70% are associated with glaucoma, and 25–50% with microphthalmia [130]. Other ocular features include cataracts, colobomas, and aniridia [42, 117, 128].

A variety of genes have been associated with Peters’ anomaly including PAX6, FOXC1, PITX2, and

CYP1B1 [30, 42, 47, 122]. However, the disease pathogenesis remains unclear. Recently, a study identified biallelic truncating mutations in the β1,3-

Fig. 21.10  Bilateral Peters’ anomaly, more severe in the right than the left eye in this young girl with no other malformations

galactosyltransferase-like gene (B3GALTL) in patients with Peters’ plus syndrome. This would implicate glycosylation defects in the pathogenesis of the disorder [60]. Peters’plus syndrome is autosomal recessive and includes short stature, brachymorphism, cupid bow of the upper lip, broad hands and feet, round face, abnormal ears, and developmental delay in addition to ocular findings [63].

The management of patients with Peters’ anomaly is focused on the provision of sufficient clear cornea to allow vision and the early detection and treatment of glaucoma. Depending on the size of the opacity, the treatment varies from observation to optical iridectomy to penetrating keratoplasty. Postoperatively refractive correction and occlusion therapy are almost always needed [130]. The rate of graft survival is the greatest among the initial grafts as compared to the second, third, or fourth grafts. The initial grafts are most likely to fail during the first two postoperative years, with more than half of all failures occurring within the first three postoperative months [131]. Glaucoma represents a major comorbidity of

Peters’ anomaly and its treatment is usually surgical. The commonly performed surgeries to lower IOP include cyclocryotherapy, trabeculectomy, goniotomy, and valve implantation [130]. Visual outcome is guarded.