Continuing Education Activity

The term coloboma derives from the Greek word koloboma, originally used to indicate a part that was removed by mutilation, missing or cut short. Colobomas are congenital ocular defects that can affect the iris, the lens, the choroid, the retina, and the optic nerve. Optic nerve colobomas have been associated with microphthalmos, iris coloboma, ciliary coloboma, lens notching, retinal detachment, neovascular membranes, and macular holes. Optic nerve colobomas have been associated with microphthalmos, iris coloboma, ciliary coloboma, lens notching, retinal detachment, neovascular membranes, and macular holes. 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 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.Iris colobomas may cause photophobia, visual distortion and double vision. They may also be cosmetically unacceptable. Cosmetic contact lenses with an artificial pupil may be used. Surgical repair of the defect with sutures may be possible. Artificial iris prosthetic devices are being explored in the presence of pseudophakia. Iris-painted intraocular lenses may be implanted after removal of the cataract. Foldable artificial irises may also be inserted through a small incision. This activity reviews the evaluation and treatment of optic nerve coloboma and the role of the interprofessional team in managing this condition.

Objectives:

• Describe the pathophysiology of optic nerve colobomas.
• Review the presentation of a patient with an optic nerve coloboma.
• Summarize the treatment of an optic nerve coloboma.
• Explain interprofessional team strategies for enhancing care coordination and communication to advance the evaluation and management of optic nerve colobomas and improve outcomes.

Introduction

The term coloboma derives from the Greek word koloboma, originally used to indicate a part that was removed by mutilation, missing or cut short. Colobomas are congenital ocular defects that can affect the iris, the lens, the choroid, the retina, and the optic nerve.

Eyelid colobomas result in a full-thickness defect of the eyelid: although the coloboma may occur anywhere on the eyelids, the most common site is at the junction of the medial and middle third of the upper eyelid. Eyelid colobomas are classified as traumatic (accidents, surgery) or congenital. Congenital colobomas may be isolated or may occur in the presence of other facial deformities and syndromes. In eyelid colobomas, corneal protection is paramount. Topical lubricating drops and ointment are applied and moisturizing chambers may be used. Patching is sometimes necessary. Surgical repair to improve corneal coverage is undertaken as necessary. The size and location of the defect will determine the exact surgical procedure used. Direct closure may be performed in defects up to 25% of the eyelid. In defects larger than 25% and up to as much as 60%, lateral mobilization with canthotomy, cantholysis and multiple “Z” plasties allows direct closure of the coloboma. When the defect is larger, lid-sharing procedures like the Hughes procedure for lower lid reconstruction and the Cutler-Beard procedure for upper eyelid closure may be necessary, together with the use of skin grafts.

Iris colobomas affect the infero-nasal quadrant and are caused by failure of the embryologic optic fissure to close during the fifth gestational week. This results in a typical keyhole-shaped pupil. On occasion, a bridge of iris may be present in the coloboma, giving rise to type of coloboma called a "bridge coloboma". Iris colobomas are frequently bilateral and associated with a pyriform corneal shape. When the corneal shape is normal, one must look for a surgical cause of a coloboma. 

Iris colobomas may be associated with colobomas of the ciliary body, choroid, retina or optic nerve. Glaucoma, nystagmus, or strabismus may be seen in the presence of iris colobomas. 

Iris colobomas may cause photophobia, visual distortion and double vision. They may also be cosmetically unacceptable. Cosmetic contact lenses with an artificial pupil may be used. Surgical repair of the defect with sutures may be possible. Artificial iris prosthetic devices are being explored in the presence of pseudophakia. Iris-painted intraocular lenses may be implanted after removal of the cataract. Foldable artificial irises may also be inserted through a small incision

Management of associated findings: limbal dermoids may appear simple but care should be taken as penetration into the globe is a very real risk. No such resection should be undertaken without availability of a lamellar graft (cornea or sclera or both).

The rest of this article discusses optic nerve colobomas.

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]

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.

Postoperative and Rehabilitation Care

Children with severely limited visual prognosis in one eye should be fitted with safety glasses by the time they are independently active and should wear goggles for sports. Although amblyopia may be untreatable, in some cases, a trial of part-time occlusion may help to show the parents the inevitability of poor vision in the affected eye. Strabismus can be treated surgically if necessary. In some cases, spectacle correction of hyperopia in the normal eye may correct accommodative esotropia. Children with nystagmus can be treated surgically, especially if .a compensatory face turn is induced.[10]

Consultations

A PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal-coloboma syndrome. It is characterized by renal hypodysplasia and abnormalities of the optic nerve. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77%. Additional clinical signs are high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity.  Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in associated with PAX2–related disorder. Ophthalmologic abnormalities may cause significant vision loss or individuals may have normal vision.[11]

Deterrence and Patient Education

Patients should be educated about the potential complications of optic nerve colobomas that can cause vision loss such as retinal detachments and choroidal neovascularization.

Enhancing Healthcare Team Outcomes

A broad differential diagnosis should be considered when evaluating children’s optic nerve anomalies. Patients with bilateral optic nerve colobomas, morning glory syndrome, and optic nerve hypoplasia should have head imaging to evaluate for midline brain defects. Patients with bilateral optic nerve colobomas should also be evaluated for developmental delay. CHARGE and other genetic conditions should be on the clinician's radar.