Fundus Autofluorescence and Intensity-Response Functions in "Cone Dystrophy With Supernormal Rod Electroretinogram" Consequent Upon Mutation in KCNV2

Abstract

Purpose: : To characterize fundus autofluorescence, full-field electroretinogram (ERG) intensity-response functions and ON-OFF ERGs in genetically confirmed cases of "cone dystrophy with supernormal rod ERG".

Methods: : Sixteen affected individuals aged between 10 and 59 years were ascertained. International-standard full-field ERGs were recorded with additional flashes ranging from 0.001cd.s/m² to 11.5 cd.s/m². The youngest patient was tested using lower eyelid ERG electrodes. ON-OFF ERGs were performed in 10 subjects using an orange stimulus superimposed on a green background. Fundus autofluorescence (AF) imaging was performed on 10 subjects. DNA was available on 14/16 subjects and each was screened for mutation in KCNV2.

Results: : Rod-mediated ERGs had characteristic a and b-wave intensity-response functions in 15/15 cases and a broadened a-wave to the brightest flash in 16/16 cases. Bright flash ERG a-waves were often mildly subnormal and ERG b-waves showed considerable overlap with the normal amplitude range, irrespective of age. Cone-mediated full-field ERGs were reduced and delayed. Photopic ON-OFF ERGs showed delay in some ON responses and most OFF responses. One young patient had normal AF. Seven of the other 9 subjects manifested a high density parafoveal AF ring that in older cases encircled macular RPE atrophy. The AF ring diameter correlated positively with age (r=0.77, p<0.05). Mutation in KCNV2 was confirmed in 14/14 cases.

Conclusions: : Full-field ERGs vary in amplitude but the intensity response functions and bright flash ERG waveforms are pathognomonic and may be demonstrated with either corneal or surface ERG electrodes. Fundus autofluorescence reveals a parafoveal ring-like area of high density in most KCNV2 cases that resembles that seen commonly in cone-rod and other retinal dystrophies. Cross-sectional analysis over a 5-decade age range suggests that the AF rings may progressively expand.

Keywords: electroretinography: clinical • retinal degenerations: hereditary • imaging/image analysis: clinical