Inner retinal cavitations in three cases of NR2E3-associated retinopathy

To describe previously unrecognized inner retinal cavitations in patients with Enhanced S-cone syndrome (ESCS) carrying specific NR2E3 mutations, and to evaluate their structural characteristics using multimodal imaging.

Three patients with molecularly confirmed ESCS, each harboring homozygous NR2E3 variants (c.290G > A [p.Arg97His] and c.229C > T [p.Arg77Trp]), were evaluated. Detailed clinical assessments included fundus examination, full-field electroretinography (ERG), and multimodal retinal imaging, including swept-source optical coherence tomography (SS-OCT), fundus autofluorescence (FAF), and red-free photography.

All patients exhibited classical ESCS functional features: nyctalopia, hyperopia with full-field ISCEV-standard ERGs demonstrating pathognomonic changes consistent with ESCS and additional S-cone ERGs of greater amplitude than standard light-adapted (LA 3.0) ERGs. Bilateral, perhaps oblong like, hypopigmented retinal cavitations were observed along the vascular arcades and nasal to the optic disc. SS-OCT localized these lesions primarily to the ganglion cell and inner plexiform layers, occasionally extending to the outer plexiform layer. Red-free imaging delineated cavitations more clearly than FAF. Hyperautofluorescent foci partially overlapped with the cavitations but did not match their shape.

In this case series, inner retinal cavitations were observed in NR2E3-associated enhanced S-cone syndrome and may represent a previously underrecognized structural feature. Larger studies are needed to establish the broader prevalence of this finding across NR2E3 genotypes.