Long-Term Clinical Outcomes and Genotype–phenotype Correlation in Familial Exudative Vitreoretinopathy in a Tertiary Referral Center

Abstract

Background/Purpose: To evaluate clinical outcomes and assess genotype–phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR). Methods: Clinical charts of 40 patients with FEVR were reviewed. FEVR was staged per Pendergast and Trese, and retinal dragging and folds further classified per Yaguchi et al. We performed whole-exome sequencing and compared clinical characteristics between genetic-positive and genetic-negative groups. Results: The mean duration of follow-up was 5.4 years (range: 0.33, 15) for genetic-positive and 6.9 (range: 1, 20) for genetic-negative patients. The mean age at diagnosis was 5.6 years (0.25, 27) for genetic-positive and 6.0 (0, 32) for genetic-negative patients. Genetic-positive patients reported 100% full-term births and genetic-negative patients reported 45% full-term births (P = 0.0012). There were more patients with retinal folds with all major vessels affected (Yaguchi's Group 4) in genetic-positive compared with genetic-negative patients (21.4% vs. 2.6%, P = 0.045). TSPAN12 was the most common (57.1%) genetic mutation in our population of which 50% exhibited asymmetric presentation. Conclusion: Patients who test positive for a typical FEVR gene mutation reported more term births and had more severe disease by Yaguchi's classification. TSPAN12 was the most common genetic mutation in our population and had highly asymmetrical disease.

Early-onset of Familial Exudative Vitreoretinopathy: clinical characteristics, management and outcomes

“…Interestingly, the overall surgical success rate was similar to a previous study published by our team on surgical management of FEVR, which included all the patients followed in our department and who underwent surgery before 2017, irrespective of age. 10 It also appears similar to the 83% anatomical stability reported by Tsai et al 5 Failure rate was the highest in stage 5 eyes.…”

“…Notably, only about 12.5% to 45% of cases have a family history of the disease. [5][6][7] The Wnt signaling pathway, crucial in angiogenesis, is frequently implicated in FEVR, with NDP, FZD4, LRP5, and TSPAN12 genes accounting for most molecular diagnoses. However, approximately 50% of cases remain without a molecular diagnosis.…”

“…However, approximately 50% of cases remain without a molecular diagnosis. 5,8 The mean age at diagnosis of FEVR ranges from 6 to 23.6 years old, and the course of the disease can vary widely, from nonprogressive or slowly progressive to rapidly progressive disease with early-onset retinal detachment (RD). 6,9 Clinical features include avascular peripheral retina, neovascularization, radial retinal folds (most often temporal), dragging of retinal vessels, ectopia maculae, epiretinal membranes, and tractional or rhegmatogenous RD.…”