ABSTRACT
Purpose: To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rod-cone dystrophy associated with RLBP1 pathogenic variants in a large cohort comprising children and adults. Design: Retrospective cohort study. Participants: Patients with pathogenic variants in RLBP1 registered in a single French reference center specialized in inherited retinal dystrophies. Methods: Clinical, multimodal imaging, and genetic findings were reviewed. Main Outcome Measures: Age of onset; visual acuity; ellipsoid line length; nasal, temporal, and foveal retinal thickness; and pathogenic variants and related phenotypes, including Newfoundland rod-cone and Bothnia dystrophies (NFRCDs), were reappraised. Results: Twenty-one patients (15 families) were included. The most frequent form was NFRCD with 12 patients (8 families) homozygous for the recurrent deletion of exons 7 through 9 in RLBP1 and 5 patients (4 families) with biallelic protein-truncating variants (2 novel: p.Gln16∗ and p.Tyr251∗). A novel combination of the p.Arg234Trp Bothnia variant with a nonsense variant in trans led to Bothnia dystrophy in 2 sisters. One proband carrying the p.Met266Lys Bothnia variant and in trans p.Arg121Trp and a second, with the p.Arg9Cys and p.Tyr111∗ combination, both demonstrated mild retinitis punctata albescens. Independently of genotype, all patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 µm, and a mean foveal thickness of less than 130 to 150 µm, with loss of both the interdigitation and ellipsoid lines. Conclusions: The eligibility for RLBP1 gene therapy first should be determined according to the biallelic variant combination using a robust classification as proposed herein. An ellipsoid line width of more than 1200 µm and a central thickness of more than 130 to 150 µm with detectable ellipsoid and interdigitation lines should be 2 prerequisite imaging indicators for gene therapy.
ABSTRACT
PURPOSE: To report an intraocular Jarisch-Herxheimer reaction induced by Lemierre syndrome antibiotherapy. METHODS: Case report. RESULTS: A 43-year-old-man presented with an acute onset of bilateral blurred vision few days after intravenous antibiotic administration for Lemierre syndrome. Best-corrected visual acuity was 20/32 in both eyes. Examination revealed bilateral cystoid macular edema and peripheral retinal vasculitis, persisting despite Lemierre syndrome recovery with antibiotics. Intravitreal injection of ranibizumab 0.5 mg (0.05 mL) was performed in both eyes. After 1 month, cystoid macular edema and retinal vasculitis were totally resolved, and best-corrected visual acuity increased to 20/20 in both eyes. The paradoxical worsening of the patient's best-corrected visual acuity after initiating antibiotherapy evokes a Jarisch-Herxheimer reaction. The result of this single intravitreal injection of ranibizumab was sustained; best-corrected visual acuity remained unchanged (20/20 in both eyes), and no recurrence of cystoid macular edema or retinal vasculitis was found after 4-year follow-up. CONCLUSION: To the best of our knowledge, this is the first reported case of an isolated intraocular Jarisch-Herxheimer reaction induced by Lemierre syndrome antibiotherapy and successfully treated with a single intravitreal injection of ranibizumab.