Vol.13  No. 1,  October 2003

FAMILIAL UVEAL COLOBOMA - A REVIEW ARTICLE

Dr. Satbir Singh, Prof. C. S. Dhull, Dr. Nidhi Garg

INTRODUCTION

Ocular colobomata are caused by defective embryogenesis.  All layers of eye can be involved, including the iris, zonules and ciliary body, choroid, retina and optic nerve.  It is a common malformation which can occur as an isolated finding in an otherwise healthy individual or can be a part of complex malformation syndrome of known or unknown etiology.  The etiologies of colobomata are varied and visual prognosis is related to their location and associated features.

DEFINITION & PATHOGENESIS

Coloboma ( Plural : Colobomata ) is derived from the Greek Koloboma 1, meaning mutilated or curtailed.  the malformation refers to a notch, gap, hole or fissure in any of ocular structures.  The term applies primarily to embryologic defects, although it is occasionally used to describe acquired iris abnormalities.  Coloboma is frequently associated with microphthalmia.  In a prospective study of more than 50,000 pregnancies in the United States, the incidence of anophthalmia or microphthalmia or both was found to be 0.22 / 1000 births and the incidence of coloboma was 0.26 per 1000.  Incidence rates found in an epidemiological study of congenital eye malformation in 131,760 consecutive births were 108 per 10,000 for microphthalmia, 0.3 per 10,000 for anophthalmia and 0.7 per 10,000 for coloboma. 2  The prevalence of coloboma among blind adults has been calculated at 0.6-10%.  among children, it accounts for a greater proportion of blindness3 (3.2-11.2%).  In a family with an autosomal dominant inheritance pattern, it is estimated that any individual with a normal ocular examination has an 8.6% chance of having an affected child.4

Typical coloboma results from a failure of the fetal or choroidal fissure to close during the 5th to 6th week of fetal life, (7-14 mm stage), which is the period between the invagination of the optic vesicle and the closure of the fetal fissure.5

CLASSIFICATION

Coloboma can be classified on the basis of its location as follow:-

                                    Coloboma

Typical                                                                      Atypical

 

Typical Coloboma

  • It involves inferonasal quadrant due to defective closure of the fetal fissure.

  • It is most frequent.

  • It may affect any part of the globe traversed by the fissure from the iris to the optic nerve.

ATYPICAL COLOBOMA

  • It involves other than inferonasal quadrant of the globe.

  • The embryologic basis of this malformation is still unclear.

PHENOTYPIC EXPRESSION

The spectrum of phenotypic expression of colobomatous malformation ranges from iris coloboma to orbital cyst which sometimes appears as clinical anophthalmos.  Intermediate in this range is coloboma of the choroid and retina which may be limited to the quadrant inferonasal to the disc or which may encompass the optic disc with or without sparing of macula.

Typical iris coloboma may be complete thickness defect of the iris stroma and pigment epithelium which extends inferonasally to the corneoscleral limbus producing the characteristic keyhole shaped pupil.  An incomplete coloboma is usually partial thickness involving either the pigment epithelium or the iris stroma.  It tends to be wedge shaped and is best demonstrated by iris transillumination.

Chorioretinal colobomata are usually glistening white defects with distinct margins often rimmed by irregular pigment clumps.  Although occasionally flat and smooth, the margins of the defect usually are uneven and bulges posteriorly.

Coloboma of optic disc results from failure of closure of the most proximal portion of the optic stalk. It presents as enlarged, white , sharply delineated, bowl shaped excavation of the disc, 2-8 diopters in depth.  Usually, a rim of neural tissue is preserved superiorly.  The retinal vessels always have an abnormal origin.  Of special importance is the and congenital forebrain anomalies.  the morning glory disc anomaly appears as a large excavated, funnel shaped disk with a prominent elevated rim or ring of peripapillary tissue.  The emerging vessels characteristically form a radiating pattern as they fan out from the disk.  It usually occurs unilaterally and is associated with either strabismus and or poor visual acuity in the affected eye.

Microphthalmia and microcornea along with uveal coloboma can occur as an isolated finding in an otherwise healthy individual or a part of complex malformation syndrome. Microphthalmia has been defined as an eye with an axial length atleast two standard deviations below the mean for that age group and / or the volume of the globe is smaller than normal. Simple microphthalmia refers to a globe that is small but otherwise normal, whereas in complex or complicated microphthalmia there are other associated abnormalities including retinochoroidal coloboma.  Clinical anophthalmia is generally applied to extreme microphthalmia in which ocular structures are identifiable only histopathologically.  Microcornea frequently occurs in association with microphthalmia.  The horizontal & vertical diameters may be different in microphthalmia resulting in an oval shaped cornea.

ETIOLOGY AND PATTERNS OF INHERITANCE

Isolated Ocular Monogenic Syndrome

  • Autosomal dominant

  • Autosomal recessive

Multisystem Monogenic Syndrome

  • Autosomal dominant inheritance

  • Autosomal recessive inheritance

  • X-linked inheritance

  • Unknown etiology

  • Chromosomal Aberrations

Environmental causes and Intrauterine Insults

ISOLATED OCULAR MONOGENIC SYNDROME

Autosomal Dominant:-  Autosomal dominant colobomatous microphthalmia without associated systemic malformations have been well established and often results in familial uveal coloboma.  Variable expressivity, from small iris or choroidal coloboma to clinical anophthalmia or orbital cyst can be there.  No extraocular malformations are seen and intelligence is normal.  When one parent is known to carry the gene for autosomal dominant ocular coloboma, there is 50% risk to each offspring of inheriting the altered gene; however, it should be recognized that the risk of having significantly reduced vision in one or both eyes secondary to malformation is less than the actual risk of inheriting the gene.  It is usually unilateral but some cases are bilateral and may be asymmetric.  The penetrance of gene for autosomal dominant coloboma is incomplete; that is the proportion of obligate gene carriers who actually manifest the gene is less than 100%, so the incomplete penetrance reduces the risk that the offspring of an affected individual will have an colobomatous microphthalmia.

AUTOSOMAL RECESSIVE : Pedigrees supporting non syndromal autosomal recessive inheritance of microphthalmia are few, and "sporadic" isolated coloboma with no other affected family members is common.

MULTISYSTEM MONOGENIC SYNDROME:

Autosomal Dominant Inheritance: Ocular coloboma may be one aspect of single gene disorder with multisystem involvement in basal cell nevus syndrome.  It is characterized by multiple basal cell carcinomas, dyskeratotic cysts of the jaw, rib & spinal anomalies and pits of the hands and feet, mental retardation along with colobomatous microphthalmia as well as congenital cataract and strabismus.  The gene has been mapped to the long arm of chromosome 9. Other example of such AD syndrome is congenital contractural arachnodactyly.

Autosomal Recessive:  Various syndromes like Mekel-Gurber syndrome, Sjogren-Larsson Syndrome, Walker-Warburg Syndrome have autosomal recessive type of inheritance.  In these syndromes along with systemic manifestations patients have various ocular findings comparsingof coloboma, microphthalmia etc.

X-linked Inheritance: Lenz microphthalmia syndrome, Aicardi syndrome, MIDAS syndrome, Catel Manzke syndrome are inherited as X-linked recessive disorders.

Chromosomal Aberration:

Multiple chormosomal aberrations have been associated with colobomatous micropthalmia.  Trisomy 13, Triploidy, Cat Eye Synodrome and 4p- are common chromosomal aberrations.  Other rare chromosomal aberrations are : 11q-, 13q-, 18q-,  Trisomy 18 etc. 

Tsisomy 13 has both ocular and systemic manifestations.

a)

 

Ocular  -

 

Microphthalmos, coloboma, mild cataract, presistence of the primary vitreous and hyaloidal vasculature, absence of secondary vitreous and retinal detachment.

b)

 

Systemic  -

 

Microcephaly, Hydrocephalus, Septal defects, Patent foramen ovale, Cleft lip, Cleft palate, Polydactyly etc.

 

ENVIRONMENTAL CAUSES & INTRAUTERINE INSULTS

Environmental influences would seem plausible in sporadic cases of colobomatous micropathalmia, Various embryopathic agents are thalidomide, benomyl ( fungicide), anticonvulsants and alcohol.  Various infectious agents responsible are CMV, EMV, Varicella zoster and Herpes simplex virus.

COMPLICATIONS

  • Rhegmatogenous and Nonrhegmatogenous Rentinal detachment - It has been reported in 4-40% of cases and it usually seen because of breaks within or adjacent to the coloboma. 6

  • Cataract- A variety of cataracts associated with coloboma include isolated pigment clumping on the lens capsule at the equator, subcapsular and cortical opacification and anterior and posterior polar cataract.

  • Secondary galucoma, amblyopia, anisometropia and sensory strabismus may also occur.

EVALUATION & MANAGEMENT

Meticulous evaluation of patients with colobomata is must.  However, it is typically difficult, given their lack of cooperation, nystagmus and microphthalmos.  Patient is examined in following ways;

  1. Visual Acuity

  2. Proper refraction

  3. Slit lamp examination - Aids in defining anterior segment manifestations.

  4. Direct& indirect ophthalmoscopy- To study choroid, retina and optic nerve involvement.

  5. Ultrasonography - To measure axial length and to define anophthalmia.

  6. CT Scan - For associated CNS malformation.

  7. Genetic Evaluation - It is must in clinically suspected cases.

TREATMENT

Iris Coloboma:- Since the iris defects themselves impose no visual defect, treatment is indicated only for cosmesis.  Surgical repair is not generally performed unless other intra-ocular surgery is indicated.  Cosmetic contact lens is most useful approach that resembles a normal iris and is designed to match the fellow eye in appearance.

Retinochorodial Coloboma:- Since the indicence of retinal detachment is high, so prophylactic laser photocoagulation is applied posteriorly and cryopexy anteriorly along the edge of the coloboma.

Microphthalmia:- Only treatment modality is cosmetic scleral shell fitting and refitting from infancy onwards.

CONCLUSION

Ocular colobomata are often associated with microphthalmia.  These are common congenital malformations which may occur as an isolated ocular anomaly or in association with multisystem anomalies.

Ocular coloboma is a common malformation of diverse etiologies. Each affected individual should have:-

  1. Complete ophthalmologic evaluation of both eyes;

  2. An evaluation to detemine whether the ocular malformation are an isolated finding or part of a multisystem disorder;

  3. A careful pregnancy history looking for possible teratogen exposure;

  4. A family history that includes questioning  for the full spectrum of colobomotous malformations;

  5. Ophthalmologic examination of both parents and siblings.

There is wide variation in severity, ranging from small iris coloboma to a defect that causes profound visual impairment.  Treatment is dependent on location and severity.

REFERENCES

  1. Dorland's Illustrated Medical Dictionary 27th Edition.  Philadelphia. WB Saunders; 1988: p 359.

  2. Stoll C, Alembik Y, Dott B, Roth MP. Epidemiology of congenital eye malformations in 131, 760 consecutive births.  Ophthalmic Paediatr Genet 1992; 13 : 179-86.

  3. Fujiki K, Nakajima A, Yasuda N. Genetic analysis of microphthalmos. Ophthalmic Paediatr Genet 1982; 1 : 139.

  4. Pagon RA. Ocular coloboma. Surv Ophthalmol 1981; 25 : 223-36

  5. Duke-Elder S. System of Ophthalmology 1963; Vol 3, Part 2 St. Louis, CV Mosby pp 456-72.

  6. Schepens CL. Retinal detachment and Allied diseases.  Philadelphia WB Saunders 1983; pp. 58-62, 615-32.

Department of Ophthalmology,
Post Graduate Institute of Medical Sciences, Rohtak.

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