Ocular colobomas result from an arrest of normal ocular development during the 5th to 7th week of fetal life at the 7- to 14-mm stage. The typical coloboma is caused by defective closure of the fetal fissure and is located in die inferonasal quadrant.1,2 Problems related to the embryonal fissure can involve the choroid, retina, optic disc, iris, and ciliary body. There are six types of optic disc involvement: (1) a normal disc outside the fundus coloboma; (2) an abnormal disc outside the fundus coloboma; (3) an independendy colobomatous disc outside the fundus coloboma; (4) a normal disc within the fundus coloboma; (5) a colobomatous disc within the fundus coloboma; and (6) the shape of a disc not identified but blood vessels seen emanating from the superior border of the large fundus coloboma.3
Affected eyes are often microphthalmic. Orbital involvement may occur with cyst formation, reduced orbital volume because of a microphthalmic eye, or both.4"6 Severity varies widely, ranging from a small iris coloboma to a defect that causes profound visual impairment.
Figure 1 . Magnetic resonance imaging showing the retrobulbar cyst in the colobomatous microphthalmic eye (case 1 1 ).
Types of complications and their severity vary depending on the location and size of the coloboma. The retina overlying the choroidal defects remains thin and undifferentiated and therefore is prone to the formation of retinal breaks and detachment.7 On the other hand, colobomas may occur as an isolated ocular anomaly or in association with multisystem anomalies.8,9 In the current small case series, a variety of presentations of optic disc colobomas are reported.
Patients and Methods
We reviewed the records of all patients with a diagnosis of optic disc coloboma during the period from 1994 through 2001 at the Department of Ophthalmology, Pediatric Ophthalmology and Strabismus Unit, Dokuz Eylul University. We included all eyes with either colobomatous defects that involved only the optic nerve or large chorioretinal colobomas including the optic nerve. Age at presentation, length of follow-up, visual acuity, extent of the coloboma, presence of strabismus, nystagmus, microphthalmia, retinal detachment, and systemic findings were noted.
Figure 2. Microcornea, microphthalmia, and an inferior iris coloboma (case 4).
Microcornea was defined as a horizontal corneal diameter of 10 mm or less, measured with corneal calipers. Microphthalmos was diagnosed on the basis of axial length measured by B-scan where possible. The fundus was evaluated with binocular indirect ophthalmoscopy. Fundus findings were documented with either a detailed drawing or a photograph.
Visual acuity was assessed using a Snellen acuity chart or Teller acuity cards according to the age and cooperation of the child. If the child was unable to cooperate, the ability to fix and follow a target was assessed. Cycloplegic refraction was performed.
Neuroimagi ng was performed if there was developmental delay, extreme microphthalmia, dysmorphic features, or all three.
Fifteen patients met the criteria described above. Eight (53%) of the 15 patients were female and 7 (47%) were male. The age at presentation ranged from 1 month to 37 years (average, 66.2 months). Eight (53%) of the patients had bilateral but asymmetric involvement of the optic nerve with the coloboma. One patient (case 6) had an extremely microphthalmic fellow eye and, as a result, the fundus could not be evaluated. Patient characteristics and associated clinical features are documented in the table.
Fourteen eyes of 9 patients were microphthalmic. One patient (case 11) had a retrobulbar cyst with colobomatous microphthalmia (Fig. 1) and another patient (case 6) had an extreme degree of microphthalmia. Additionally, 9 eyes of 6 patients had microcornea (Fig. 2). Of the 30 eyes, the optic disc and choroid were involved in 1 8 (Fig. 3), with the macula being spared in 8 eyes and involved in 10 eyes. An isolated chorioretinal coloboma was seen in 1 eye, an isolated disc coloboma was seen in 5 eyes, and no posterior segment coloboma was seen in 4 eyes. One patient (case 1) had an abnormally shaped disc, but it was not colobomatous. One patient (case 15) had optic nerve hypoplasia and atrophy in the fellow eye. Sixteen (53%) of 30 eyes had a typical iris coloboma. One patient had ectopia pupillae in one eye and a typical iris coloboma in the other. Two patients (cases 8 and 14) had unilateral cortical lens opacities.
Clinical Features of the Patients
Clinical Features of the Patients
Figure 3. The optic disc coloboma involved by the inferior chorioretinal coloboma (case 9).
One patient (case 12) had a nonrhegmatogenous retinal detachment at the time of diagnosis. She had only a optic disc coloboma without a chorioretinal coloboma. She underwent classic detachment surgery that was unsuccessful.
Eight (53%) of the patients had sensory strabismus. Four patients were esotropie and 4 patients were exotropic. Overaction of the inferior oblique muscle accompanied the horizontal deviation in two patients. All patients with bilateral involvement had nystagmus. The results of cycloplegic refraction were available for 10 of the patients and are listed in the table.
Systemic malformations were documented in 6 (40%) of the 15 patients. Three patients (cases 6, 7, and 1 5) had malformations of the central nervous system. One patient (case 11) had a cleft lip and palate with hypertelorism, and another (case 8) had moderate joint contracture in her digits. One patient (case 13) had mental retardation; neuroimaging could not be performed because she was lost to follow-up.
Congenital anomalies of the eye are localized structural defects resulting from disruption of ocular development during the embryonic stage.1'2 This study shows the wide variety of presentations of ocular colobomas, ranging from iris colobomas to various degrees of optic disc and chorioretinal colobomas to clinical anophthalmos.9
Colobomas can be unilateral or bilateral; when bilateral, they are often asymmetric. The prognosis for vision depends on the amount of ocular malformation and the degree of microphthalmia. Colobomas of the optic nerve are usually associated with some decrease in visual acuity, even when the fovea is spared. Given the wide variation in severity of optic disc colobomas, classification is helpful for predicting the degree of visual impairment, particularly in infants and young children.
Gopal et al.3 categorized and described the type of optic disc involvement and blood vessel patterns seen in 67 eyes of 40 patients with a choroidal coloboma. In their study, 6 types of disc involvement were identified. The mildest form was a normal disc outside the chorioretinal coloboma. The most severe form was an unidentifiable disc shape with blood vessels emerging from the superior border of a large chorioretinal coloboma. Visual acuity was better when the disc was outside the fundus coloboma and independently colobomatous, compared with when the disc was within the coloboma. Macular involvement by die coloboma positively correlated with the severity of disc involvement, and this has a direct effect on visual acuity. Our study further confirmed the outcome of poorer visual acuity if there is macular involvement in addition to an optic disc coloboma. Also, the presence of microphthalmia, microcornea, or both results in poorer visual acuity.
In a study by Olsen et al.,9 the only ophthalmoscopic feature that was predictive of visual acuity was the degree of foveal involvement by die optic nerve coloboma. Color, size, and involvement of the subfoveal retinal pigment epithelium were not predictive of visual acuity.
Hornby et al.10 proposed a phenotypic classification of colobomas to give information on the likely visual outcome. The classification system was based on axial length and corneal diameter. Microphthalmos with a cyst had the worst prognosis, a cornea with microcornea and microphthalmos had a poor prognosis, a coloboma with only microcornea had an intermediate prognosis, and a simple coloboma had the best prognosis. However, meticulous evaluation of infants with colobomas is typically difficult, given their lack of cooperation, nystagmus, and microphthalmos.
In the current study, a strong association of colobomatous defects with microphthalmic eyes also confirms previous data from the literature. Microcornea frequently occurs in association with microphthalmia. Microphthalmia can be associated with either a small, clinically undetectable cyst or a large, typically inferior cyst that deforms the eye and its surrounding area.5,6,9 In our case, the cyst was seen on computed tomography and ultrasonography, although it was clinically undetectable. The usual location of the cyst is inferior or posterior to the globe, with which it is always in contact. A posteriorly located colobomatous cyst may or may not cause proptosis, depending on the sizes of the globe and the cyst. Microphthalmos with a cyst is composed of tissues that originate from the eye wall of a malformed globe with a posterior segment coloboma.5 Most fundus colobomas show some degree of scleral ectasia, resulting from a deficiency of tissue in the region where apposing edges of the embryonic neuroectodermal fissure have failed to fuse properly. Animal studies and pedigree analyses of human families support the concept that retinochoroidal colobomas and orbital cysts result from the same mechanism.11'12 Both are considered part of the clinical spectrum, which includes anophthalmia and microphthalmia.
Severe microphthalmia with a coloboma may also occur with multisystem involvement in a variety of single gene disorders or chromosomal syndromes, or as an element of a variety of dysmorphic syndromes. Other craniofacial associations include cleft lip and palate, agenesis of the corpus callosum, defects in the sella turcica, and endocrine dysfunction.7"9'13 Ophthalmologists should consider the possibility of a chromosomal disorder or malformations of the central nervous system in individuals who have colobomatous microphthalmia with developmental delay or any other malformations. Forty percent of the patients in our series had associated systemic abnormalities. Because of the high frequency of associated anomalies, we suggest that neuroimaging be considered in the initial diagnostic evaluation of these patients, particularly if there is developmental delay and severe microphthalmia.
Nine (60%) of the 15 children in this study had nystagmus. The origin of nystagmus appears to be visual deprivation. Theoretically, nystagmus induced by visual deprivation should not occur unless both eyes have a serious problem that interferes with visual development.
Sensory strabismus was frequently found in this study. Impaired visual acuity in one or both of the eyes is a severe obstacle to sensory fusion and may result in strabismus. Any type of esotropia or exotropia, whether diagnosed early in life or at an older age, may be sensory in origin and can be the first clinical sign of poor visual acuity or even blindness in one eye.14 Clinicians should rehabilitate the involved eye as the presence of an organic abnormality does not exclude the presence of functional additional amblyopia. The refractive errors of our patients ranged from -10.0 D to +6.0 D, which is consistent with the literature.10·15 Additionally, accompanying astigmatism and anisometropia also have amblyogenic potential. After spectacle correction, a trial of occlusion therapy is warranted in infants and small children.
Retinal detachment is the most common complication associated with retinochoroidal colobomas. Retinal detachment has been reported in 2.4% to 43% of cases, usually because of breaks within or adjacent to the coloboma.3,7,13,16 The most likely reasons for such discrepant prevalence figures are referral bias and the age of the patient population in each series. Excavated defects of the optic disc, including congenital pits, optic nerve colobomas, and morning glory syndrome, have been associated with retinal detachment. A nonrhegmatogenous retinal detachment occurs in two-thirds of those individuals with autosomal dominant, isolated optic nerve colobomas, and the incidence varies with the type of optic nerve coloboma.17 In the current study, one patient had an isolated optic disc coloboma and a nonrhegmatogenous retinal detachment at the time of diagnosis. Detachments in an already visually impaired child may remain undiagnosed for a long time and this would make subsequent retinal detachment surgery less likely to be successful. For this reason, periodic examination of such patients is warranted.
This study has shown the wide variety of presentations of eyes affected by the colobomatous process of the fundus. An isolated optic disc coloboma had a better visual prognosis than did a large chorioretinal coloboma that involved both the optic nerve and the macula. Microphthalmia was the most common associated ocular anomaly and a strong indicator of a poorer prognosis for visual acuity. Parents of these children must be made aware of the potential significance of a change in visual behavior or a new onset of strabismus, as retinal detachment is not a remote possibility. Functional amblyopia should be taken into consideration because a wide range of refractive errors accompanied this clinical entity.
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Clinical Features of the Patients
Clinical Features of the Patients