Recurrent Bilateral Macular Edema Linked to NOTCH2NLC GGC Repeat Expansion: A Case Report

BACKGROUND Mutation of NOTCH2NLC may contribute to the development of neuronal intranuclear inclusion disease (NIID), which presents with varieties of clinical manifestations. This report presents a case of a young woman carrying this mutation who presented with refractory bilateral macular edema, which is quite rare. CASE REPORT A 35-year-old young woman with no medical history presented with bilateral blurred vision. The best corrected visual acuity was 20/20 in both eyes and no abnormalities were observed. Optical coherence tomography confirmed the presence of cystoid edema and localized loss of the ellipsoid zone. Autofluorescence showed cystic mottled fluorescence at the fovea, while fluorescein angiography combined with indocyanine-green angiography detected multiple cystic hyperfluorescent areas. The patient received anti-VEGF treatment, which significantly resolved the edema. In the next 5 years, the patient experienced recurrent bilateral macular edema with anti-VEGF therapy (26 injections each eye). Genetic testing of the patient revealed that 1 allele of NOTCH2NLC had a GGC repeat, which was similar to her father's gene mutation, though she lacked confirmatory tests (neurological exam, biopsy, or MRI) for a formal NIID diagnosis. The patient continues to attend regular follow-up visits. CONCLUSIONS Given the single-case design and lack of retinal histopathology, we propose this as a hypothesis-generating report: bilateral refractory macular edema of undetermined etiology may represent a potential early indicator of NOTCH2NLC GGC repeat expansion. Anti-VEGF therapy should be considered when macular edema occurs.