Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing.

PURPOSE: 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. DESIGN: Prospective observational case series. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.

The application of chromatic dark-adapted kinetic perimetry to retinal diseases.

PURPOSE: To demonstrate the value of a 2-color perimetric procedure for determining cone and rod system contributions to the dark-adapted kinetic visual field (VF). DESIGN: Prospective evaluation of perimetric testing procedure. PARTICIPANTS: Five patients with retinal diseases and 6 visually normal individuals. METHODS: Long- and short-wavelength stimuli were presented under dark-adapted conditions in a Goldmann perimeter. Visual fields were measured for the II and V test target sizes with a long-wavelength filter (cut-on at 600 nm) and a short-wavelength filter (cutoff at 510 nm). Light intensities through these filters were matched scotopically for the rod system by producing equal peripheral boundaries on 6 visually normal individuals. To validate the application of this procedure, we tested a patient with congenital achromatopsia and another patient with congenital stationary night blindness (CSNB). We then tested 2 patients with retinitis pigmentosa (RP) and 1 patient with Usher's syndrome to determine the cone and rod contributions to their VF isopters. MAIN OUTCOME MEASURES: Isopters for long- and short-wavelength test stimuli, and the appearance of the test stimuli, whether reported as chromatic or achromatic. RESULTS: The patient with congenital achromatopsia showed superimposed isopters for the 2 stimuli, which were reported as achromatic, demonstrating that the peripheral field boundaries were rod mediated. The patient with CSNB showed an isopter in response to the long-wavelength stimulus that was considerably larger than that in response to the short-wavelength stimulus, both stimuli reported as chromatic, showing that the cone system determined peripheral thresholds for both stimuli. In 2 patients with RP, we observed a mixed pattern of cone or rod system detection of the chromatic stimuli. The peripheral isopters were rod mediated, whereas the cone system determined the central field isopters. In an Usher's syndrome patient, cones mediated both the peripheral and the central field isopters. CONCLUSIONS: A 2-color dark-adapted Goldmann perimetric procedure was able to determine whether the VF isopters were rod or cone mediated in 5 patients with various forms of retinal disease.