Anophthalmos/Microphthalmos
Anophthalmos and Microphthalmos are major congenital structural ocular malformations that occur as a result of insults to the developing eye during the first 8 weeks of gestation. It could be isolated or associated with other congenital anomalies.
Prevalence
The prevalence of both Anophthalmos and Microphthalmos is estimated to lie between 1 and 3.5 per 10,000 with no predilection to sex or race, however, an increased incidence has been noticed in low socioeconomic societies, and consanguinity is a known predisposing factor.
Anophthalmos is the congenital absence of the globe. True Anophthalmos may be difficult to differentiate both clinically and radiologically from extreme Microphthalmos (clinical Anophthalmos) where a very small globe can only be detected by serial histological sections of the orbital contents.
Mann Classified Anophthalmos into Three Distinct Types
Primary Anophthalmos: caused by failure of development of the optic vesicle from the forebrain before 2 mm stage of embryonic life. It is usually bilateral and sporadic.
Secondary Anophthalmos: an extremely rare and lethal anomaly due to complete suppression or grossly anomalous development of the entire anterior neural tube: the forebrain and its derivatives, the optic vesicles.
Consecutive or degenerative Anophthalmos: occurs when the optic vesicle forms but subsequently degenerates due to insults during the second stage of development: 4-8 weeks of embryonic life.
Anophthalmos is most commonly bilateral, sometimes occurring on one side and Microphthalmos on the opposite side. The orbit and eyelids are formed but small (micro-orbitism and micro-blepharism), the eyelids are shortened in all directions, often with a dystrophic levator muscle, the fornices are shallow, the extraocular muscles are present but may be maldeveloped.
Infants with true bilateral anophthalmia show an absence of the optic nerves and optic chiasma with maldeveloped optic foramina. Lack of properly established connections from the developing eyes to the optic pathways results in hypoplasia or absence of the related white matter tracts and lateral geniculate ganglia. Dysgenesis or absence of the corpus callosum may also be seen suggesting an anomalous formation of the lamina terminalis which is a precursor of the forebrain and the corpus callosum.
Microphthalmos is a condition in which the affected eye is smaller than 15 mm in greatest diameter at birth (normally 16-19 mm), less than 19 mm at 1 year or 22 mm in adulthood.3
Microphthalmos occurs between 7 and 14 mm stages of embryonic development when the primary optic vesicle already has invaginated but the fetal cleft (embryonic neuroectodermal fissure) has not closed. It is due to intrauterine involution of the optic vesicle and interference with the normal fusion of that fissure. Three types of microphthalmia are recognized:
Simple Microphthalmos (nanophthalmos) is a very rare form. The eye is small, but normal, with no other gross abnormalities; however the relative lens/eye volume is high making it susceptible to acute and chronic angle closure glaucoma. Also there is hypermetropia, thick sclera and a tendency towards postoperative or even spontaneous uveal effusion and secondary choroidal or retinal detachment.
Microphthalmos associated with other ocular anomalies or more generalized systemic malformations as in congenital Rubella and Trisomy 13. The eye is reduced in size with a microcornea often an iris, ciliary body, choroidal or optic nerve coloboma, and may be corneal opacities, posterior synechiae, cataract or retinal detachment.
Microphthalmos with a cyst (Colobomatous Microphthalmos) where the sclera is thin and ectatic appearing as a cyst of variable size that may grow to become bigger than and obscuring the microphthalmic globe itself. The microphthalmic eye is usually displaced upwards behind the upper lid by a cyst located inferiorly and presenting as a bulge in the lower eyelid. Rarely the cyst is located posteriorly causing proptosis.
Duke Elder described three categories of cysts associated with Microphthalmos: a relatively normal eye with a small cyst not apparent clinically; an obvious cyst associated with a grossly deformed eye; a large cyst which has pushed the globe backwards so, that it is no longer visible clinically. The condition is usually unilateral but frequently the other eye shows the evidence of a coloboma.
Histologically
Histologically there is an eversion of the retina through the unclosed fissure to form a lining of rudimentary neuroectodermal tissue covered with a fibrous outer coat of variable thickness which may be continuous with the sclera but the choroid is absent. The cavity of the cyst is usually in direct continuity with the vitreous cavity and is filled with a clear fluid.
Differential Diagnosis
Differential diagnosis is from congenital cystic eyeball where there is failure of invagination of the primary optic vesicle occurring between 2 and 7 mm stage of embryonic development. The orbit shows a cystic structure of a bluish color due to contained fluid and uveal pigment. In some instances, invagination occurs but is incomplete leading to a condition known as congenital non-attachment of the retina.5
Etiology
Anophthalmos/Microphthalmos may be due to genetic or non-genetic factors that cause the disease to occur in isolation or as a part of a syndrome. All patterns of inheritance are observed: autosomal dominant, autosomal recessive, X-linked dominant and recessive or sporadic. Chromosomal aberrations commonly in the form of trisomy (Trisomy 13, 18 and 22) and deletions may account for 16% of all cases of anophthalmia and microphthalmia. Non-genetic factors include maternal exposure to infections as Rubella, Toxoplasma and Cytomegalovirus, influenza and fever. A number of potential environmental teratogens have been proposed including: alcohol, drugs such as thalidomide, retinoids, warfarin, and carbamazepine, vitamin A deficiency, hyperthermia and exposure to X-rays or agricultural pesticides; the evidence in their support however is only preliminary and the condition may result from a variety of different exposures alone or in combination. It is also probable that a background of genetic susceptibility is required.
Ocular and Systemic Associations
The condition may be associated with microcornea, sclerocornea, Peter's anomaly, cataract, persistent fetal vasculature (posterior hyperplastic primary vitreous), iris coloboma, aniridia, choroidal, retinal or optic nerve colobomata. Systemic Associations differ according to the syndrome (see table), there may be syndactyly or polydactyly; ear anomalies; nasal anomalies such as a thin pinched nose; orodental anomalies such as thin lips, high arched palate, macrostomia, micrognathia, bifid tongue or delayed eruption of teeth; hypoplastic or ambiguous external genitalia. Also Cardiac anomalies, esophageal atresia and skin defects in the form of hypo or hyperpigmentation. Both cranial and intracranial anomalies may be seen as: microcephaly, hydrocephaly, hemifacial atrophy, facial clefting, hypogenesis of corpus callosum and cerebellar hypoplasia.
CT scan and MRI are of value in:
- Demonstration of anophthalmia or microphthalmia by showing an absent or a small globe
- Assessment of associated craniofacial anomalies, and
- Detection of associated intracranial anomalies.
Management
The management is a challenge especially in cases of anophthalmia and severe microphthalmia. Treatment could be long and complicated with multiple orbital, conjunctival and eyelid reconstruction surgeries required throughout the child's life, and even then results may be disappointing because a perfectly normal-looking orbit will not be achieved. Psychological support for both the parents and the child is necessary.7
Examination and management of other ocular anomalies wherever possible such as associated cataract, exclusion of other system malformations by the pediatrician and genetic counselling when required are all appropriate measures.
The timing of surgery differs according to the severity of the condition: early interference is only required in cases of large orbital cysts protruding through the palpebral fissure and in anophthalmia where the results are much better if treatment is initiated in the first year. Recent studies have confirmed that enucleation in childhood compromises orbital growth, cases with small or medium sized cysts with an associated ocular remnant help stimulate orbital expansion better than any artificial orbital implant so, although parents are often keen to have the microphthalmic eye or the cyst removed to improve cosmoses, elective enucleation is better postponed to school age.8
Syndrome | Ocular associations | Systemic associations |
Trisomy 13 (Patau's syndrome) | Iris or ciliary body colobomata, cataract, persistent fetal vasculature, corneal dysge-nesis, retinal dysplasia | Mental retardation, low set ears, cleft palate, cleft lip, polydactyly, cryptorchidism |
Trisomy 18 (Edward's syndrome | Narrow palpebral aperture, ptosis, epicanthus, hypo- or hypertelorism, proptosis, nystagmus, rarely corneal opacities, colobomata, cataract | Mental retardation, low set ears, micrognathia, prominent occipit, narrow pelvis and maybe hip subluxation, flexed overlapping fingers, cardiac and renal anomalies |
Lenz microphthalmia syndrome | Mental retardation, malformed ears, skeletal anomalies, urogenital anomalies | |
Fryns anophthalmia-plus syndrome | Nasal deformity, choanal atresia, bifid uvula, facial cleft | |
Anophthalmia-esophageal-genital syndrome | Esophageal atresia, cryptorchidism | |
Fetal rubella syndrome | Corneal opacity, cataract, glaucoma, chorioretinitis, | Deafness, cardiac anomalies |
Fetal alcohol syndrome | Short palpebral fissures, ptosis | Microcephaly, cardiac anomalies |
CHARGE syndrome | Colobomata most commonly retinal | Cardiac anomalies, choanal atresia, ear anomalies, deafness, genital anomalies |
Aicardi syndrome | Chorioretinal lacunae | Infantile spasms, agenesis of corpus callosum |
Focal dermal hypoplasia (Golz syndrome) | Skin anomalies, skeletal anomalies, dental anomalies | |
Microphthalmia and linear skin defect syndrome (MLS) | Sclerocornea, chorioretinal abnormalities | Skin anomalies, agenesis of corpus callosum, hydrocephalus, infantile seizures, mental retardation, cardiac anomalies |
Goldenhar syndrome | Epibulbar dermoids, accessory auricular appendages, | Vertebral anomalies |
Hallermann-Streiff syndrome | Microcornea, cataract | Mandibular hypoplasia, parrot-beak nose, bird-like facies |
Fig. 6: Posterior embryotoxon may not be easily detected clinically, but with the high resolution of UBM, its detection may be easier
(UBM image courtesy of Z El Sanabary, MD, Cairo University)
Management of Anophthalmos
Orbital Surgery
Orbital expansion can be achieved by:
- Progressively increasing the size of a Solid Conformer
- An Inflatable Silicone Expander reconstituted with saline through a tube placed at the lateral orbital rim.
- Osmotic Tissue Expander which is a recently introduced self-inflating Hydrogel or HEMMA expander. Once expansion of the orbit and fornices permits, fitting of an ocular prosthesis improves the appearance. More volume enhancement can be achieved by orbital implants when feasible.
In cases of late referral with severe micro-orbitism or insufficient orbital volume, a three dimensional orbital bone expansion surgery for the bony orbit with or without bone grafts to augment the deficient contours is needed.
Eyelid Surgery
Fitting of the prosthesis is often limited by the palpebral fissure and eyelid shortening. The palpebral fissure may be widened by a lateral and/or a medial canthotomy or canthoplasty. Additional lengthening of eyelids can be accomplished by a combination of skin, mucosal or cartilage grafts, but this is best postponed until maximum expansion has been achieved by conformer therapy as early treatment may lead to cicatricial tissue formation.
Management of Microphthalmos
Patients with poor orbital volume can achieve very good cosmetic results if treated with conformers as early as possible, microphthalmic eyes with some residual vision can be treated with clear conformers that do not obscure the visual axis, cosmetic scleral shells with optical correction have also been recently introduced. Cysts may be aspirated but this is frequently followed by fluid reaccumulation, in this case surgical excision and orbital implantation is indicated. Silicone, acrylic, hydroxyappatite and other implants may be used but the Dermis fat graft has the advantage of being autogenous and with the ability to enlarge as the child grows.
Anterior Segment Dysgenesis
Anterior segment dysgenesis (ASD) constitutes a spectrum of developmental disorders involving the cornea, angle, iris and lens. It most likely represents an abnormal embryonic development of the cranial neural ectoderm. Many theories on the pathogenesis of ASD have been proposed. A developmental arrest, late in gestation, of certain anterior segment structures derived from neural crest cells is the most likely mechanism. First, abnormal retention of the primordial endothelial layer on the surface of the iris and anterior clamber angle, with subsequent contraction, is believed to account for the iris changes and the tissue strands in the anterior clamber angle.11
Fig. 8: Typical Peter's anomaly with defective central Descemet's membrane (down arrow) and iridocorneal synechiae at the edges of the defect (right arrow)
(UBM image courtesy of Z El Sanabary, MD, Cairo University)
Fig. 9: Variant of Peter's anomaly with poorly developed DM
(UBM image courtesy of Z El Sanabary, MD, Cairo University)
Furthermore, deposition of basement membrane by these cells is felt to result in a prominent Schwalbe's line. Secondly, a developmental arrest in the posterior recession of the iris root during the third trimester, results in a high insertion into the posterior aspect of the trabecular meshwork. Lastly, incomplete development of the trabecular meshwork and Schlemm's canal represents further evidence of developmental arrest occurring during the third trimester.
Posterior Embryotoxon
Posterior embryotoxon is a prominent, anteriorly displaced Schwalbe's line. It can be found in up to 15% of normal eyes without any clinical significance or may represent a form fruste of anterior segment dysgenesis.
On slit-lamp examination, it appears as a whitish, irregular arcuate ridge located 0.5 to 2 mm central to the limbus. The majority of posterior embryotoxon is seen temporally and limited to a few clock hours, but in some patients it can be seen for 360 degrees.
Alagille syndrome or arteriohepatic dysplasia is an autosomal dominant condition involving jaundice caused by a developmental scarcity of intrahepatic bile ducts. It has characteristic cardiovascular, skeletal, facial and ocular features. A prominent Schwalbe line occurs in 90% of cases of Alagille's syndrome and is identified as an important marker. Early recognition of the syndrome is helpful in establishing the proper diagnosis to avoid unnecessary abdominal surgery and institute vitamin therapy.
Axenfeld-Rieger Syndrome
The presence of posterior embryotoxon in association with numerous iris processes is known as Axenfeld's anomaly. If there is iris hypoplasia in addition to Axenfeld's anomaly, then the condition is referred to as Rieger's anomaly. If systemic features are present it is referred to as Rieger's syndrome. Many eponyms exist for Axenfeld-Rieger syndrome (ARS) including anterior cleavage syndrome and anterior segment mesodermal dysgenesis disorders.
The historical classification of ARS based on phenotypes has been challenged with the advent of the Human Genome Project and more of the molecular biology mechanisms underlying development are being unravelled. It has now become apparent that ARS shares genotypic and phenotypic overlap with other anterior segment dysgenesis such as iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia and familial glaucoma iridogoniodysplasia. It has been proposed that all these overlapping groups of conditions should be classified under the umbrella term of ARS to eliminate the confusing sub-classification and to facilitate communication between clinicians.13
Fig. 11: Sclerocornea with different lenticulo-corneal relationships
(UBM image courtesy of Z El Sanabary, MD, Cairo University)
Axenfeld-Rieger syndrome is inherited in an autosomal dominant pattern. Three chromosomal loci (4q 25, 6p 25, 13q 14) have recently been demonstrated to link to ARS and related phenotypes. The PITX2 gene, on chromosome 4q 25, and the FOXC1 gene, on chromosome 6p 25, have been implicated. These are genes coding for paired-like homeodomain and forkhead/winged-helix transcription-factor families. Mutation in DNA binding domain of these genes can cause a wide variety of phenotypes that share features with ARS. Mutation resulting in increased PITX2 activity has been found to correlate with more severe ARS ocular phenotype. A plyomorphism in the GJA1 gene has been recently identified in association with ARS and raises the possibility of its participation as a modifier gene.
In ARS, gonioscopic examination reveals that the anterior chamber angle is open and the trabecular meshwork is visible, but the scleral spur is obscured by the more anterior insertion of the peripheral iris into the posterior portion of the trabecular meshwork.
In Rieger's anomaly, iris pathology can range from mild stromal thinning (iris hypoplasia) to marked atrophy with hole formation, corectopia and ectropion uvea. When corectopia is present, the pupil is displaced towards a prominent peripheral iridocorneal adhesion; the atrophy and hole formation occurs in the quadrant away from the direction of the pupil.
Abnormalities of the anterior chamber angle do not appear to progress after birth except for occasional thickening of iris strands. Abnormalities of the central iris are usually stable, but have been observed to progress during the first years of life. These changes consist of distortion or displacement of the pupil and occasional thinning and hole formation of the iris. Other associated ocular anomalies include sclerocornea, persistent pupillary membrane, microphthalmus and typical iris coloboma.
Glaucoma develops in 50 to 60% of patients with ARS. It may manifest itself during infancy but more commonly appears in childhood or young adulthood. Glaucoma is felt to occur more often in patients with centric iridic changes and in those with more pronounced anterior peripheral iris insertion into the trabecular meshwork.
Rieger's syndrome is associated with many systemic anomalies, in particular, those involving developmental defects of the teeth and facial bones. Dental defects may include a reduction in crown size (microdontia), a decreased but evenly spaced number of teeth (hypodontia), and a focal absence of teeth (oligodontia or anodontia). Facial anomalies may include maxillary hypoplasia with flattening of the midface and a receding upper lip and prominent lower lip. Hypertelorism, telecanthus, and broad flat nose have also been described.
Other non-ocular associations of ARS include congenital lip abnormalities, hydrocephalus, empty sella syndrome, middle ear deafness, kidney abnormalities, hypospadias, umbilical skin folds and heart defects. There is 15considerable variation in non-ocular features, even among family members with ARS.
All associated ocular and systemic anomalies appear to arise from the maldevelopment of the neural crest cells. Patients with ARS should be examined for the presence of anomalies in the tissues of neural crest origin.
Management of glaucoma in patients with Axenfeld-Rieger syndrome is difficult. Medications, particularly aqueous humor suppressants may be effective, although many patients will require surgery. Goniotomy is reported to be effective in some younger patients, but this procedure can be complicated by extensive iris processes and should probably be avoided in patients with large areas of contact between the iris and cornea. Trabeculotomy, too has a high risk for substantial bleeding, endothelial cell damage, and inflammation in eyes with thick iridocorneal adhesions. Some authors believe that filtering surgery with anti-metabolites is the best surgical procedure for these patients. Eyes that fail trabeculectomy may require an aqueous shunt, or ultimately diode cyclophotocoagulation.
Peters Anomaly
Peter's anomaly is a congenital, mostly bilateral condition in which a central corneal opacity is present with corresponding defects in the posterior corneal stroma, Descemet's membrane and endothelium. The condition is usually sporadic, although autosomal recessive and autosomal dominant transmission both have been reported. Approximately, 50% of patients will have associated glaucoma. Some cases can have the peripheral anterior chamber angle abnormalities of Axenfeld-Rieger syndrome since they are both defects of neural crest cell origin which may lead to diagnostic confusion.
Peter's anomaly is often classified into three groups: (i) posterior corneal defect with leucoma alone; (ii) posterior corneal defect with leucoma and adherent iris strands and (iii) posterior corneal defect with leucoma, adherent iris strands, and keratolenticular contact or cataract.
The corneal opacity in Peter's anomaly is usually central, oval and well-defined, but it may sectorial and have diffuse margins. The affected cornea is rarely vascularized and the peripheral cornea is usually clear although scleralization of the limbus may occur in Peter's anomaly type II, the lens either lies in juxtaposition to the corneal surface or is in normal position with an intact surface but cataract is present. In contrast to the first two forms of Peter's anomaly, the last variant may occur in eyes with microphthalmia, persistent hyperplastic primary vitreous (PHPV) and retinal dysplasia.
Peter's plus syndrome is a multiple malformation syndrome characterized by a combination of Peter's anomaly of the eye and other extraocular defects, including short-limb dwarfism, a thin upper lip, hypoplastic columella, and a 16round face. Hypothyroidism, multiple midline defects such as cleft lip and palate, cardiac anomalies, an atretic cranial meningocele as well as malformations of the ear have also been reported.
Histopathology
Histopathology in Peter's anomaly shows an abnormal, immature or absent Descemet's membrane and attenuated, endothelial cells in the area of the corneal opacity, in addition to thinning or even complete absence of Bowman's membrane. It has been suggested that there is failure of the normal differentiation of the mesoderm into normal endothelium and trabecular meshwork.
Differential Diagnosis
Differential diagnosis of Peters anomaly includes causes of corneal opacities that may be seen in children. These include sclerocornea, where the entire cornea is opacified, aniridia, trauma associated with forceps delivery during birth, congenital glaucoma, mucopolysacharidoses, congenital hereditary endothelial dystrophy (CHED) and a perforated corneal ulcer.
Ultrasound Biomicroscopy
Ultrasound biomicroscopy (UBM) has proved to be useful in confirming the diagnosis of Peter's anomaly. It also acts as a preoperative guide in cases undergoing penetrating keratoplasty by detecting keratolenticular and iridocorneal adhesions.
Management of Peter's anomaly primarily relies on controlling glaucoma, when present and preventing amblyopia. Detection of glaucoma is complicated by the corneal opacity, which affects the accuracy of tonometry and obscures the clinician's view of the anterior chamber angle and optic nerve head. Although some cases may respond to medical management, many cases ultimately may require filtering surgery. Multiple procedures and adjunctive medical therapy are often required to achieve and maintain adequate IOP control. Visual results are poor due to uncontrolled glaucoma, amblyopia, and other anterior and posterior segment anomalies that may accompany Peter's anomaly. Patients undergoing keratoplasty after adequate pressure control are reported to have long-term graft clarity in 36% of cases.
Sclerocornea
Sclerocornea is one of the common causes of corneal clouding or opacification in the newborn. It presents at birth by non-progressive, non-inflammatory opacification of the peripheral and to a lesser degree the central cornea with vascularisation. Despite its characteristic presentation it should be differentiated from other pathologies such as congenital glaucoma, trauma, infectious diseases, dystrophies, metabolic causes and other forms of ocular dysgenesis.
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The sclera and choroid develop from mesenchymal tissue of neural crest origin. Sclerocornea results from mesenchymal dysgenesis leading to anomalous development of this portion of the anterior segment. It has been suggested that the wave of mesenchymal tissue that normally forms the corneal stroma fails to form the clear cornea and forms tissue resembling sclera instead. This wave of tissue remains as homogenous sheets throughout the 7th–10th week of gestation until the limbal anlage develops. Failure of the limbal anlage to develop or its central displacement may be responsible for various forms of sclerocornea.
Most cases are sporadic however inheritance patterns have been demonstrated. Autosomal dominant patterns as well as autosomal recessive traits have been reported. Cases with an autosomal dominant pattern are invariably less severe.
Sclerocornea is usually bilateral and affects male and female newborns equally. Sclerocornea presents in a newborn with opacification of the peripheral cornea with vasculariziation. Although the axial portion of the cornea may also be involved to a varying degree, the peripheral opacification is usually denser. The limbus is indistinct and blends with the surrounding sclera. Some cases may present with involvement of only a small arc at the periphery. Where relatively clear cornea is present it is invariably flatter than normal. Accurate visualization of the anterior segment is often hindered by the opaque cornea. It should be noted that in cases of total sclerocornea the relative clarity of the central cornea as compared to the periphery can be important in differentiating sclerocornea from Peter's anomaly.
Histologically
Histologically there is thickened collagen fibers in the superficial stroma of the cornea as compared to the posterior stroma. This is a pattern similar to that seen in the sclera. Recent evidence however suggests that sulphation patterns of interfibrillar keratan sulphate proteoglycan within the tissue matrix may resemble cornea rather than sclera as previously postulated.
Ultrasound Biomicroscopy
Ultrasound Biomicroscopy (UBM) has proven to be a vital tool in assessing the nature and extent of structural defects as well as confirming the presence of associated anterior segment anomalies in cases of sclerocornea thus aiding in the surgical decision making process.
Differential Diagnosis
Differential diagnosis of sclerocornea is that of causes of a cloudy cornea in a newborn, this includes infantile glaucoma, forceps injury, congenital hereditary endothelial dystrophy, congenital rubella, and congenital syphilis. Other conditions presenting with corneal opacities such as Peter's anomaly, congenital 18hereditary stromal dystrophy, mucopolysaccharidosis, mucolipidosis and cystinosis may also be confused with sclerocornea.
Laterality, intraocular pressure and associated findings will usually aid in determining the pathology underlying the corneal opacification. However, although many of these entities may seem quite different, the various degrees of affection in sclerocornea may sometimes make an accurate diagnosis difficult. UBM is a useful tool in such cases.
Ocular associations may commonly be encountered in cases of sclerocornea. microphthalmia, iris anomalies, anterior chamber irregularities have been documented in cases of sclerocornea. UBM has dramatically improved the clinician's ability to diagnose associated ocular anomalies which may not be readily diagnosed by routine anterior segment examination.
Systemic associations may be encountered in cases of sclerocornea such as skeletal anomalies, various cerebellar, cranial and cardiac anomalies.
Sclerocornea may also present as part of the a documented syndrome such as the MIDAS (microphthalmia-dermal aplasia-sclerocornea) syndrome. This syndrome is synonymous with the microphthalmia with linear skin defects (MLS) syndrome. This syndrome includes linear areas of erythematous skin dysplasia involving the chin, neck, and head, occurring in association with microphthalmia, corneal opacities, and orbital cysts. Additional findings may include agenesis of corpus callosum, sclerocornea, chorioretinal abnormalities, hydrocephalus, seizures, mental retardation, and nail dystrophy. Some features of the phenotype of this syndrome overlap those of Aicardi and Goltz syndromes.
As with the majority of congenital corneal opacities the ultimate aim in the absence of extensive associated ocular anomalies is to clear the visual axis by performing a penetrating keratoplasty. Associated conditions such as anterior segment anomalies and glaucoma must also be addressed. The timing of this intervention is a debatable issue however in most cases a single or sometimes multiple keratoplasties are indicated to prevent deprivation amblyopia.