CHAPTER 9
Basic and Clinical Concepts of Congenital Anomalies of the Cornea, Sclera, and Globe
Congenital anomalies are discussed in depth in BCSC Section 6, Pediatric Ophthalmology and Strabismus. See also BCSC Section 2, Fundamentals and Principles of Ophthalmology.
Developmental Anomalies of the Globe and Sclera
Cryptophthalmos
Cryptophthalmos, or “hidden eye,” is a rare, usually bilateral condition in which the eyelids and associated structures of the brows and lashes fail to form (ablepharon). The cornea is merged with the epidermis, and the anterior chamber, iris, and lens are variably formed or are absent (Fig 9-1). The conjunctiva is typically absent. Associated ocular findings include corneal and conjunctival dermoid, absence of the lacrimal glands and canaliculi. Pseudocryptophthalmos occurs when the eyelids and associated structures form but fail to separate (ankyloblepharon).
Figure 9-1 A, Complete cryptophthalmos, both eyes. B, Incomplete cryptophthalmos of the right eye, with eyelid fused to cornea superonasally.
Cryptophthalmos occurs in both an isolated and a recessive syndromic form as Fraser syndrome.
Patients with this syndrome may have a combination of acrofacial and urogenital malformations with or without cryptophthalmos. The disorder results from mutations in the FRAS1 gene located at 4q21, which encodes a putative extracellular matrix (ECM) protein.
Cryptophthalmos requires surgical intervention for cosmesis or relief of pain from absolute glaucoma. Pseudocryptophthalmos may benefit from fornix reconstruction using buccal mucosal and amniotic membrane grafts, with eyelid reconstruction to protect the corneas.
McGregor L, Makela V, Darling SM, et al. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet. 2003;34(2):203–208.
Stewart JM, David S, Seiff SR. Amniotic membrane graft in the surgical management of cryptophthalmos. Ophthal Plast Reconstr Surg. 2002;18(5):378–380.
Microphthalmos
Microphthalmos is a small, disorganized globe (Fig 9-2; Table 9-1). There is often an associated cystic outpouching of the posteroinferior sclera, likely due to a failure of the fetal fissure to close properly, and colobomatous defects of the iris, ciliary body, uvea, and optic nerve are often present.
Figure 9-2 Microphthalmos, right eye. (Courtesy of Jeffrey Nerad, MD.)
Table 9-1
Multiple associations have been found with microphthalmos, including trisomies of almost every
chromosome (typically, trisomy 13), maternal infections, and exposure to toxins and radiation. Most cases of nonsyndromic microphthalmos are sporadic, although autosomal dominant, autosomal recessive, and X-linked forms have been reported. Associated ocular abnormalities may include leukomas, anterior segment disorders, retinal dysplasia, colobomas, cysts, marked internal dysgenesis, persistent fetal vasculature (PFV), small orbit, ptosis, and blepharophimosis. Systemic associations are numerous, including intellectual disability and dwarfism.
Associated conditions should be sought and managed appropriately, and genetic counseling should be considered. A cosmetic shell or contact lens may be indicated in selected patients.
Ferda Percin E, Ploder LA, Yu JJ, et al. Human microphthalmia associated with mutations in the retinal homeobox gene CHX10. Nat Genet. 2000;25(4):397–401.
Li H, Wang JX, Wang CY, et al. Localization of a novel gene for congenital nonsyndromic simple microphthalmia to chromosome 2q11-14. Hum Genet. 2008;122(6):589–593.
Verma AS, FitzPatrick DR. Anophthalmia and microphthalmia. Orphanet J Rare Dis. 2007;2:47.
Nanophthalmos
Nanophthalmos is characterized by a small, functional eye with relatively normal internal organization and proportions. Patients have a high degree of hyperopia (7–15 diopters [D]) due to a short axial length (15–20 mm), and they also have a high lens-to-eye volume ratio that can lead to crowding of the anterior segment and angle-closure glaucoma. In addition, these patients have thickened sclera, steep corneal curvature, narrow palpebral fissures, and crowded anterior segments associated with angle-closure glaucoma. Many patients have strabismus. Choroidal effusions or hemorrhage has been frequently encountered during anterior segment surgery.
Nanophthalmos may be sporadic or hereditary, and both autosomal dominant and autosomal recessive inheritance patterns have been reported. One gene locus for the autosomal dominant form has been mapped to chromosome arm 11p. The recessive form of the disease is caused by a mutation in the gene encoding membrane-type frizzled protein (MFRP).
Laser iridotomy, sometimes combined with peripheral laser iridoplasty, may be effective treatment of the angle-closure component. Cataract surgery may be complicated by uveal effusion or hemorrhage and exudative retinal detachment, although advances in small-incision surgery have reduced the frequency of these complications. Extremely high intraocular lens powers are required to achieve emmetropia.
Faucher A, Hasanee K, Rootman DS. Phacoemulsification and intraocular lens implantation in nanophthalmic eyes: report of a medium-size series. J Cataract Refract Surg. 2002;28(5):837–842.
Traboulsi EI, ed. Genetic Diseases of the Eye. 2nd ed. Cary, NC: Oxford University Press; 2011.
Blue Sclera
The striking clinical picture of blue sclera is related to generalized scleral thinning, with increased visibility of the underlying uvea. This anomaly must be distinguished from the slate-gray appearance of ocular melanosis bulbi and from acquired causes of scleral thinning such as rheumatoid arthritis or staining from minocycline treatment.
Two syndromes associated with blue sclera are osteogenesis imperfecta type I and Ehlers-Danlos syndrome type VI (see Table 9-1). Osteogenesis imperfecta type I is a dominantly inherited generalized connective tissue disorder characterized mainly by bone fragility, in addition to blue sclerae. Ehlers-Danlos syndrome type VI is a rare syndrome with autosomal recessive inheritance. In addition to blue sclera, keratoglobus, and keratoconus, it is characterized by joint hyperextensibility, severe kyphoscoliosis, cardiac anomalies, and skin abnormalities of easy bruisability, abnormal