Optic Nerve Coloboma

Etiology

In normal eye development, the neuroectoderm approaches the surface ectoderm and forms the optic vesicle. The optic vesicle invaginates to form an optic cup dorsally and proximally and the optic fissure ventrally and distally. The most proximal portion of the vesicle forms the optic stalk. The margins of the optic fissure grow toward each other until they fuse, leaving a small opening, the optic disc, for the hyaloid artery. The optic fissure begins to close in the fifth week of fetal development and is completed by about the seventh week. Partial or complete failure of closure of the optic fissure results in colobomas. Since the optic fissure closes ventrally last, the location of the colobomas is usually ventral. The extent of visual impairment caused by a coloboma ranges from asymptomatic to complete loss of vision, depending on the size and location of the defect. The inheritance pattern can be a defect in any of the 39 genes associated with colobomas or more commonly sporadic.[1]

Epidemiology

The prevalence has been reported to be 0.14% in the general population. Half of the cases are bilateral.[2]

History and Physical

Failure of retinal pigment epithelial development in the area of a retino-choroidal coloboma may lead to hypoplasia of the choroid and sclera with formation of a staphyloma. If the fovea is involved, vision may be significantly affected. On the other hand, even with large choroidoretinal colobomas, if the fovea is not involved, vision is relatively preserved.

Children who have symptomatic unilateral optic disc abnormalities generally present during the preschool years with sensory esotropia. Visual acuity may be unaffected as in optic disc pit, or optic disc drusen. Optic nerve colobomas have been associated with microphthalmos, iris coloboma, ciliary coloboma, lens notching, retinal detachment, neovascular membranes, and macular holes. Rhegmatogenous retinal detachments can develop secondary to breaks in the thin membrane that overlies the coloboma.[3] Pal et al. showed that vitrectomy with silicone oil had a success rate in patients with optic disc coloboma and retinal detachment.[4]

Evaluation

Colobomas are seen in:

• The Treacher Collins syndrome (autosomal dominant with variable penetrance)
• In association with cryptophthalmos (absence of eyelid formation)
• Cat eye syndrome is a chromosome 22 abnormality with vertical iris colobomas
• Patau syndrome (trisomy 13)
• Fraser syndrome
• Manitoba Oculotrichoanal syndrome (seen in Northern Manitoba Aboriginal patients), Goldenhar syndrome
• First arch syndrome.
• Franceschetti syndrome
• Amniotic band syndrome
• The CHARGE syndrome is composed of coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities and ear abnormalities. Microphthalmia may also be seen.
• Other associated conditions include renal coloboma syndrome, Aicardi syndrome, Solomon syndrome, and Noonan syndrome.[4]

In the presence of a congenital coloboma involving any of the eye structures, it is wise to perform a complete ophthalmic examination, looking specifically for the following:

• Eyelids: trichiasis, dermoid, lipodermoid
• Eyebrows: defect
• Conjunctiva: symblepharon, caruncle abnormalities
• Cornea: exposure keratopathy, pyramidal cornea, corneal scarring
• Sclera: epibulbar dermoid
• Lacrimal system: punctal or canalicular obstruction
• Lens: anterior polar cataract, subluxation
• Iris: coloboma
• Choroid: coloboma
• Optic Disc: coloboma

Central visual acuity in children born with colobomas involving the optic nerve correlates with the development of normal foveal anatomy, regardless of the size of the coloboma. Olsen et al. studied optic nerve colobomas of 23 eyes. Two graders masked to patients’ visual acuities were asked to rate coloboma size, optic nerve color, foveal development, and subfoveal retinal pigment epithelial changes. Increased relative coloboma excavation (ratio of coloboma depth to axial length) was significantly associated with an increased risk of retinal detachment. A relative coloboma excavation more than 0.15 was associated with a 52% increased risk of retinal detachment, compared to those with a relative coloboma excavation less than 0.15 (23%, P = 0.014). The presence of any structural abnormality or retrobulbar cyst were associated with an increased risk of retinal detachment and severe visual impairment of worse than 20/200. An increased coloboma depth, width, volume, and relative coloboma excavation were not associated with an increased risk of severe visual impairment.[5]

On a typical funduscopic exam, clinicians see large optic nerve excavations usually inferiorly. Defects occur both unilaterally and bilaterally at equal rates. Patients may have microphthalmia or optic nerve cysts that communicate with the subarachnoid space. Cysts rarely expand to cause compressive optic neuropathy.

Optic coherence tomography (OCT) of the optic nerve can help elucidate the different optic nerve anomalies that look similar on fundoscopy alone. OCT of optic nerve coloboma shows retinochoroidal-scleral excavation of the nerve. On follow up examinations, OCT is used to monitor for peripapillary CNVs. OCT angiography could be used to distinguish between morning glory syndrome, which has a dense peripapillary network, and optic nerve pits and optic nerve colobomas that do not have a radial peripapillary network.[4]

Treatment / Management

Head imaging should be obtained in all patients with bilateral ONC, as they are more likely to have midline brain defects.[6] Additional management in these patients includes the use of sunglasses to reduce the photophobia and treatment for anisometric amblyopia in cases of low visual acuity.[3] Ophthalmologists should assess the possibility of a chromosomal disorder or malformations of the central nervous system (CNS) in patients who have colobomatous microphthalmia along with developmental delay or any other malformations.[7] The literature confirms the finding of systemic anomalies in the CNS, urogenital, skeletal, and other systems in patients with ocular coloboma. Van Dalen et al. found systemic anomalies almost exclusively in patients with bilateral ocular colobomatous changes.[6](B2)

Differential Diagnosis

The differential diagnosis includes other optic nerve head anomalies. Optic nerve pits do not result from deficiencies in fetal closure of the optic fissure. The root cause may be an early developmental defect. Abnormal vitreoretinal adhesions can result in maculopathy. Visual acuity depends mostly on the degree of maculopathy that may develop. In untreated patients, visual acuity can be 20/200 or worse. There are a couple of theories regarding the source of the intraretinal fluid in maculopathy, subarachnoid, or vitreous fluid. It is postulated that cerebrospinal fluid (CSF) travels through the lamina cribrosa defect from the subarachnoid space. Or intravitreous fluid travels into the intraretinal and subretinal spaces.

Morning glory disc anomaly (MGDA) is a clinically distinct condition from optic nerve coloboma. Patients typically have excavated, conical optic disc, central glial tuft, retinal vessels that exit radially from the enlarged posterior scleral opening, and peripapillary pigment. Optic nerve coloboma does not have glial tufts or peripapillary pigment. The pathogenesis of MGDA is not clear. It may be due to the failure of closure of the terminal optic stalk. Patients have poor visual prognosis, strabismus, and are a risk for rhegmatogenous retinal detachments due to retinal breaks at the disc margin. Associated cerebrovascular findings are present in up to 45% of patients, so all patients should undergo neuroimaging for evaluation of basal encephalocele, hypopituitarism, moyamoya, midline cranial defects, and agenesis of corpus callosum.

Optic nerve hypoplasia is a more common cause of visual impairment in children than optic nerve coloboma. Bilateral disease is more common than unilateral disease. The former presents with nystagmus, whereas the latter presents with strabismus. Visual acuity can range from 20/20 to NLP. On examination the optic nerve is small. There is an area of hypopigmentation surrounding the nerve. This is an extension of the retinal and retinal pigment epithelium on the outer lamina cribrosa. This pattern is classically called the “double ring sign.” The defect may be segmental, i.e., maternal DM1 is associated with superior segmental ONH. Binocular complete ONH is more likely to have associated extraocular developmental abnormalities. Septo-optic dysplasia (deMorsier syndrome) can occur in unilateral or bilateral disease and is associated with developmental delay, an absence of septum pellucidum, agenesis of corpus callosum, and pituitary and hypothalamic function abnormalities.[4]

Megalopapilla is defined as increased disc area associated with a normal rim area and normal retinal nerve fiber layer. It may be a physiologic variant of normal optic disc papilla. However, visual acuity may be decreased in patients with megalopapilla.[8]

Complications

The initial effect of optic nerve colobomas on visual acuity is variable, and some patients even have normal visual acuity. However, during the evolution of the disease, they may develop a decrease in visual acuity due to complications such as serous retinal detachment in optic disc pit, atrophy or subretinal neovascularization.

In patients with an optic nerve head coloboma, the extent of abnormal tissue is much greater than it is in optic pits. This papillary defect along with a poorly differentiated retina and retinal pigment epithelium, an abnormal lamina cribrosa, and an enlarged scleral canal potentially allow the vitreous cavity, subretinal space, subarachnoid space, and the orbital space to communicate in these patients. A retinal detachment can develop through a defect.[9] Treatment of retinal detachment in patients with optic nerve colobomas can be trying because of the high propensity for recurrence. The hole cannot be directly closed with laser, diathermy, or cryotherapy due to the proximity of the hole to the optic nerve. If there is vitreous traction on the hole, then induction of a posterior vitreous detachment may alleviate traction and allow the retina to reattach, as described for optic pits.