Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing.
OBJECTIVE
To test whether choroideremia carriers have a mosaic pattern of retinal dysfunction, as noted in carriers of X-linked recessive retinitis pigmentosa and X-linked retinoschisis.


METHODS
Prospective observational case series.


METHODS
Seven obligate choroideremia carriers (age range, 18-72) with visual acuity (VA) of 20/25 or better were recruited into the study.


METHODS
The carriers underwent VA testing (Snellen chart), ophthalmic examination, Humphrey visual field (VF), and multifocal electroretinographic testing. The amplitude and implicit time scales were measured by the algorithm of Hood and Li. The amplitude measures (a scales) and implicit time measures (t scales) were reported abnormal when they were >2 standard deviations above the mean of age-similar normally sighted control subjects.


METHODS
Mapping of local 103 electroretinographic response amplitudes and implicit times.


RESULTS
Only 1 of the 7 carriers showed abnormal Humphrey VF thresholds, whereas 6 of the 7 carriers showed a mosaic pattern of retinal dysfunction measured by multifocal electroretinographic testing. All 6 carriers showed statistically significant implicit time delays, whereas 4 carriers showed statistically significant amplitude reductions and implicit time delays (P<0.05 to P<0.0006). One carrier with a normal-appearing macula and normal Humphrey VF showed a cluster of statistically significant implicit time delays within the macula (P<0.05 to P<0.0006). The overall extent of local electroretinographic abnormalities corresponded to the severity of ophthalmoscopically apparent pigmentary changes. The one carrier with mild threshold elevation on Humphrey VF testing showed the most ophthalmoscopically apparent extensive fundus pigmentary changes.


CONCLUSIONS
We demonstrated a mosaic pattern of retinal cone dysfunction in carriers of choroideremia. Our findings are consistent with the Lyon hypothesis of random X-chromosome inactivation. Multifocal electroretinographic testing is potentially sensitive to detect local retinal dysfunction in choroideremia carriers even in those with a normal-appearing macula and good VA.
Vajaranant
Thasarat S
TS
Department of Ophthalmology and Visual Science, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Fishman
Gerald A
GA
Szlyk
Janet P
JP
Grant-Jordan
Patricia
P
Lindeman
Marty
M
Seiple
William
W
D000328:Adult; D000368:Aged; D015794:Choroideremia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D015331:Cohort Studies; D004596:Electroretinography; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009030:Mosaicism; D011446:Prospective Studies; D011601:Psychophysics / Q000379:methods; D012160:Retina / Q000503:physiopathology*; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology; D014794:Visual Fields