Cavitary anomalies of the optic disc: Different entities or part of a single spectrum of disease?

In this edition of Oman Journal of Ophthalmology (OJO), Shenoy et al. reported a rare association of the optic disc pit in one eye and optic nerve head coloboma in the other eye of a child diagnosed with Cornelia de Lange syndrome (CdLS).[1] The diagnosis of CdLS was made on a clinical basis. As is stated by Shenoy et al., the craniofacial features in patients suspected to have this condition are easily recognized and are helpful in making the diagnosis. There are few studies of ophthalmologic findings in CdLS,[234] and optic disc malformations have been reported in this condition, albeit infrequently. They include optic nerve pallor or atrophy,[2] poor macular reflex and foveal hypoplasia,[2] tilted optic discs,[3] optic nerve hypoplasia,[3] optic nerve coloboma,[3] and megalopapilla.[4] Optic pits have not been previously reported in association with CdLS.

Excavated optic disc anomalies include megalopapilla, peripapillary staphyloma, optic disc coloboma, optic pit, and morning glory disk anomaly (MGDA).[5] The optic disc anomaly seen in periventricular leukomalacia (PVL) and papillorenal syndrome are also often considered as cavitary anomalies of the optic disc. One may be tempted to look at these anomalies as part of a disease spectrum, especially as many a time different entities are seen occurring together, as in the patient reported in this issue of OJO.[1] However as one looks at the pathogenesis and embryologic origin of each anomaly, it becomes apparent that each anomaly has a specific etiopathogenesis. Further, ocular and systemic associations with each anomaly often differ, which suggests that each anomaly is better considered as a distinct disease entity.

In the MGDA and peripapillary staphyloma, a congenital excavation of the peripapillary fundus surrounds and incorporates the optic disc. Ipsilateral intracranial vascular dysgenesis is seen in some patients with MGDA suggesting that MGDA results from a primary vascular dysgenesis with resulting mesenchymal abnormality.[6] Peripapillary staphyloma appears to arise as a sequel to a localized disturbance in scleral development.[5]

Optic disc colobomas comprise a clearly demarcated bowl-shaped excavation of the optic disc, generally decentered and deeper inferiorly. Colobomas result from abnormal fusion of the two sides of the proximal end of the optic cup.[7] They may be accompanied by multiple systemic conditions including the CHARGE association, Walker–Warburg syndrome, Goltz’ focal dermal hypoplasia, and Aicardi syndrome.

Optic disc colobomas may be associated with PAX2 gene mutations as part of the papillo-renal or renal-coloboma syndrome (bilateral optic disc anomalies associated with hypoplastic kidneys).[7] However, coloboma seems to be an inappropriate terminology to use in the papillo-renal syndrome as there is no evidence that the optic fissure fails to close. On the contrary, the optic disc anomaly in this condition has been shown to be a form of hypoplasia resulting from hereditary vascular dysgenesis affecting the ocular circulation.[8]

The optic disc cavitation seen with PVL (an abnormally large optic cup and a thin neuroretinal rim contained within a normal-sized optic disc) is also considered by some as a form of segmental optic nerve hypoplasia resulting from retrograde degeneration of axons secondary to injury to optic radiation after the scleral canals have established normal diameter.[9]

Megalopapilla is a generic term for an abnormally large optic disc that does not have the inferior excavation of an optic disc coloboma or the features of a MGDA. It is believed to result from altered optic axonal migration early in embryogenesis. Optic pit consists of a dysplastic retina that has herniated posteriorly into a collagen-lined pocket through a defect in the lamina cribrosa. The pathogenesis of optic pits is unclear. They are unassociated with systemic anomalies.

Congenital anomalies of the optic disc are rare. The visual function is difficult to predict from the appearance of the optic nerve. In many cases, unilateral or asymmetrical involvement means that functional vision is not significantly impaired. Occlusion of the less affected eye to optimize vision in the worse eye is good practice. Optimal refractive correction is mandatory. Retinal detachment is a recognized complication of cavitary optic disc anomalies. In contrast to retinochoroidal colobomas, the detachment is not rhegmatogenous, and spontaneous re-attachment is known to occur. Fluid is believed to enter the subretinal space from surrounding orbital tissue, choriocapillaris, or from the subarachnoid space. Systemic anomalies involving the brain, kidneys, endocrine, and vascular system are common in patients with malformed discs and it is mandatory to perform appropriate investigations to detect and appropriately manage them.

In conclusion, it is not completely clear if the various optic disc anomalies mentioned above represent a spectrum of disease or are unrelated. Molecular genetic studies in the future may help answer this intriguing question.