Proliferative retinopathy in a patient with mutation in the gene.

Purpose: is a gene that encodes the voltage-gated chloride channel protein 2 in the human brain and eyes. While mutations in this gene have been associated with leukoencephalopathy as well as ocular manifestations including optic neuropathy and choroidopathy, here we report for the first time a case of severe proliferative retinopathy in a patient with mutation.

Observations: A 12-year-old girl with Familial Mediterranean Fever (FMF) was referred due to blurred vision in both eyes. Ophthalmoscopic examination revealed mild vitreous hemorrhage, large neovascularization at the disc (NVD), extensive neovascularization along the arcades (i.e., NVE; neovascularization elsewhere), retinal arteriolar narrowing, silver sheathing of the veins and preretinal hemorrhages. Fluorescein angiography (FA) demonstrated prominent leakage from multiple large NVEs. A thorough and multidisciplinary evaluation ruled out metabolic, thrombotic, infectious, inflammatory, or autoimmune etiologies. Notably, however, brain magnetic resonance imaging (MRI) revealed leukodystrophy yet poorly correlated with her clinical manifestation. Strikingly, whole exome sequencing uncovered a homozygous mutation in the gene. She was treated with intravitreal injections of the anti-vascular endothelial growth factor (VEGF) antibody Bevacizumab and laser pan-retinal photocoagulation (PRP) with partial response.

Conclusions: This case suggests that mutation may possess a key role in an aggressive form of proliferative retinopathy with partial response to anti-VEGF therapy. We hypothesize that the potential underlying mechanism involves astrocyte dysfunction and retinal blood barrier disruption. Noteworthy, a comprehensive approach is unequivocally significant in evaluating such cases of proliferative retinopathy with unclear etiology to establish a diagnosis and management strategy.