Cone Vision Changes in the Enhanced S-Cone Syndrome Caused byNR2E3Gene Mutations

Abstract

PURPOSE. To determine the progression of cone vision loss in patients with recessive disease from NR2E3 gene mutations. METHODS.Patients with NR2E3 mutations (n ¼ 37) were studied as a retrospective observational case series clinically and with chromatic static perimetry. Patients were investigated cross-sectionally, and a subset was followed longitudinally. RESULTS.Patients showed a range of visual acuities; there was no clear relationship to age. With kinetic perimetry (V4e target), a full field could be retained over many years. Other patients showed progression from a full field, with or without pericentral scotomas, to a small central island. Three patterns of S-cone function were defined, based on percentage of hypersensitive S-cone loci in the field. From occupying most of the visual field, hyperfunctioning S-cone loci could diminish in percent, remaining largely in the periphery. Normal S-cone functioning then dominates, followed by the appearance of an annular region of abnormal S-cone loci approximately 108 to 408 from the fovea. Overall, S-cone sensitivity declined 2.6 times faster than L/M-cone sensitivity.CONCLUSIONS. Murine proof-of-concept studies suggest that clinical trials of patients with NR2E3 mutations may be forthcoming. Patterns of S-cone hyperfunction across the field would serve as a means to categorize patients as entry criteria or cohort selection in clinical trials. S-cone perimetry can be measured in the clinic and would be the logical efficacy monitor for therapeutic strategies. Given further understanding of the natural history of the disease, targeting the annular region of S-cone dysfunction for a focal therapy or for monitoring in a retina-wide intervention warrants consideration.

Rod function deficit in retained photoreceptors of patients with class B Rhodopsin mutations

“…Vulnerable retina at the transition zones. Disease progression in IRDs occurs in a complex spatiotemporal pattern 3,12,30,48,[70][71][72][73][74] . One approach in quantifying progression is to follow the boundaries of TZ between disease and health over time in order to define either the expansion of retinal area of disease or constriction of area of health.…”

Wavelength of light and photophobia in inherited retinal dystrophy

“…Several previous reports have proposed the hypothesis that photophobia is primarily caused by cells that respond to short-middle wavelength light including S-cones 10 , intrinsically photosensitive retinal ganglion cells (ipRGCs) 5 , and rods 11 . The fact that patients with S-cone related diseases such as enhanced S-cone syndrome 12 , and blue cone monochromacy 8 often complain of photophobia also supports the S-cone theory. However, patients with achromatopsia may complain photophobia, and the theory is still controversial.…”

Enhanced S-cone syndrome: Clinical spectrum in Indian population

“…Hence, it is postulated that there is failure of the photoreceptors to differentiate properly and are replaced by S cones. [16] This results in visual field loss in the mid-peripheral region. The retinal degeneration is thought to be because of abnormal photoreceptor maintenance, disturbed phagocytosis, microglial proliferation, and complex gene interactions.…”

“…The retinal degeneration is thought to be because of abnormal photoreceptor maintenance, disturbed phagocytosis, microglial proliferation, and complex gene interactions. [16]…”