Faculty Bibliography

PURPOSE: To determine whether retinal dysfunction in obligate carriers of the Bardet-Biedl syndrome (BBS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). METHODS: Six obligate carriers of the BBS were examined for the study. Examination of each carrier included an ocular examination and mfERG testing of one eye. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally sighted, age-similar control subjects. RESULTS: Mapping of 103 local electroretinographic response amplitudes within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes in three of six carriers. Implicit time measurements in the 6 carriers were all normal except for those locations associated with abnormal amplitude reductions in 3 of the carriers. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. CONCLUSIONS: Multifocal ERG testing can demonstrate areas of retinal dysfunction in carriers of the BBS. This test may therefore be useful for identifying some heterozygous carriers of this disease

Shinoda and colleagues hypothesized that patients with cone dystrophy (CD) might suffer from a selective ON-system deficit, based on the local nature of the disease [Shinoda, K, Ohde, H, Inoue, R, Ishida, S, Mashima, Y, & Oguchi, Y (2002). ON-pathway disturbance in two siblings. Acta Ophthalmologica Scandinavica, 80, 219-223]. The purpose of the current study was to test this hypothesis by examining onset and offset responses as a function of eccentricity in a group of patients with CD using long-duration LED stimuli. Nine patients with CD participated in this study (mean age of 36.1 years and visual acuity 20/200). For this study, the following measures were obtained: Humphrey threshold visual fields, standard multifocal ERGs (mfERGs) as well as mfERGs to long duration stimuli recorded using the Retiscan stimulator (Roland Instruments). This display contained 61 scaled hexagons and the LEDs were on for 100ms (180cd/m(2)) and off for 100ms. In addition, standard full-field photopic and flicker ERGs using Ganzfeld stimulation were obtained. For the control subjects, the onset responses were larger than the offset responses at all eccentricities; whereas for the patients, there was overlap between the amplitudes of the onset and offset responses. For the patients, the amplitude ratios (relative to the control data) indicated that the difference between the onset and offset responses was greatest for the central-most ring and this difference decreased with increasing eccentricity. For the onset responses, Humphrey thresholds and mfERG amplitudes, performance was poorest for the center ring and best for the most peripheral ring; for the offset responses, the opposite pattern of results was obtained. The differences in the pattern of results in the long duration mfERG data are consistent with a selective loss of the onset responses in our patient population

PURPOSE: To investigate possible adverse effects of a yellow-tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination. SETTING: Departments of Ophthalmology, Columbia University and New York University School of Medicine, New York, New York, USA. METHODS: Nine patients with a yellow-tinted IOL in 1 eye and a colorless ultraviolet IOL in the fellow eye and 9 young phakic subjects with and without a yellow-tinted clip-on lens were tested. Hue discrimination was measured with the Farnsworth-Munsell (FM) 100-hue test. Dark-adapted thresholds to 440 nm, 500 nm, and 650 nm lights were measured at 23 locations using a modified Humphrey perimeter, and dark-adapted thresholds to white light were measured at 15 degrees temporal retina. RESULTS: In the 9 patients, there were no significant differences in dark-adapted sensitivities to 440, 500, 650 nm, or white-light stimuli and no differences in FM 100-hue error scores between eyes with yellow-tinted IOLs and those with colorless IOLs. Similarly, in young phakic subjects, there were no significant differences in FM 100-hue error scores or dark-adapted sensitivity to the white light with and without the yellow-tinted clip-on lens. However, with the clip-on lens, mean sensitivities to the 440 nm, 500 nm, and 650 nm stimuli were significantly decreased by 2.7 to 2.8 dB, 0.7 to 1.0 dB, and 0 to 1.2 dB, respectively. CONCLUSION: Results suggest that implantation of a yellow-tinted IOL has non-significant effect on scotopic sensitivity and hue discrimination

PURPOSE: To determine whether retinal dysfunction in obligate carriers of X-linked retinoschisis (XLRS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). METHODS: Nine obligate carriers of XLRS (mean age, 46.2 years) were examined for the study. Examination of each carrier included an ocular examination and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally-sighted, age-similar control subjects. RESULTS: Mapping of 103 local electroretinographic response amplitudes and implicit times within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes and delayed implicit times in two of nine carriers. CONCLUSIONS: The mfERG demonstrated areas of retinal dysfunction in two carriers of XLRS. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Multifocal ERG testing can be useful for identifying some carriers of XLRS.

PURPOSE: To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. METHODS: Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. RESULTS: Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. CONCLUSIONS: ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation

PURPOSE: To determine whether training oculomotor control, without direct practice in reading sentences, could increase reading speed in patients with age-related macular degeneration (AMD). METHODS: Sixteen patients with AMD participated in the study (age range, 65-87 years; mean, 77). The training program consisted of a series of exercises that were designed to allow the patients to practice eye movements. At the beginning of training, the subjects practiced small horizontal saccades in response to cognitively easy stimuli (e.g., dots). The training then progressed to practicing larger eye movements and then to practicing saccades with single letters, pairs of letters, and three-letter words. Reading of sentences was practiced in only one exercise, during the last session of the 8-week training. RESULTS: The difference between average reading speeds before and after training was 24.7 wpm (difference between medians, 17.9 wpm). The increase in speed was statistically significant (Wilcoxon signed rank test = 124.0, P < 0.001). There was no significant relationship between change in maximum reading speed and ETDRS (Early Treatment Diabetic Retinopathy Study) acuity (r = -0.14, P = 0.76) or between change in maximum reading speed and age (r = 0.25, P = 0.45). CONCLUSIONS: The results indicate that a training curriculum that concentrates on eye-movement control can increase reading speed in patients with AMD. This finding is especially interesting, because the training involved little direct practice in reading sentences but instead concentrated on having subjects practice control of eye positions and eye movements

PURPOSE. To evaluate the contrast response of the visual system in retinitis pigmentosa ( RP) under conditions designed to emphasize the parvocellular (PC) and magnocellular (MC) pathways. METHOD. Visual evoked potentials (VEPs) were measured in 10 patients with RP and in 10 age-equivalent control subjects with normal visual acuity and color vision, by using an array of isolated checks that were presented against a steady yellow background. The checks were modulated sinusoidally, either in isoluminant chromatic contrast (5.6 Hz), to favor the chromatic PC pathway, or in luminance contrast ( 5.6 and 11.2 Hz), to favor the MC pathway. Response amplitude and phase at the stimulus ( fundamental) frequency were derived from Fourier analysis, and contrast response functions were fit with a Michaelis-Menten equation to derive R-max, the maximum response amplitude, and sigma, the contrast necessary to produce R-max/2. RESULTS. In the control subjects, the mean amplitude function for chromatic modulation increased approximately linearly with increasing contrast, whereas the function for luminance modulation increased sharply at low contrasts and saturated at contrasts above approximately 30% for both temporal frequencies, as expected. The patients with RP showed primarily a reduction in R-max with little change in sigma in all testing conditions. The reduction in R-max was equivalent for chromatic modulation and luminance modulation at 5.6 Hz, but was substantially lower for luminance modulation at 11.2 Hz. CONCLUSION. Contrast processing was impaired within both the MC and PC pathways in these patients with RP, but the degree of impairment within the MC pathway depended on temporal frequency. These VEP results are in general agreement with recent psychophysical studies of contrast sensitivity losses in patients with RP, and further they characterize contrast processing deficits in these patients at suprathreshold levels

Purpose: Previous studies indicated abnormal development of fixation toward the optic nerve head in patients with the inherited retinal disease North Carolina macular dystrophy (NCMD). The implication of this development on functional vision and structural characteristics has not been described. Methods: The anatomical characteristics of five NCMD-affected individuals were assessed by measuring the retinal thickness of the macula using optical coherence tomography. The underlying physiologic health of the retina was assessed using the multifocal ERG. Psychophysical assessment of remaining vision in the affected areas was done with a new microperimetry system that measures functional visual acuity at 27 discrete locations and the Humphrey visual field analyzer. Results: All patients had better areas of visual sensitivity toward the nasal macula. Follow-up examination showed no changes in the clinical appearance of the retina. Visual acuities ranged from -0.10 logMAR (Snellen equivalent, approximately 20/16) to 0.50 logMAR (Snellen equivalent, approximately 20/63) in the better eye. No significant changes in visual acuity were found over time. Local multifocal electroretinogram deficits were found in all patients. Patients with grade 2 or 3 disease had large patches of decreased amplitudes and delayed implicit times. Results of the anatomical, electrophysiological, and psychophysical tests were consistent. Conclusion: The electrophysiological and psychophysical deficits found in patients with more severe disease were consistent with an abnormal development of fixation from the anatomical fovea toward the optic nerve head with the placement of the lesion temporal to fixation (into the nasal visual field)

We examined the effects of inter-modal attention and mental arithmetic on Humphrey visual field sensitivity and multifocal visual evoked potential (mfVEP) amplitude. Four normally sighted subjects (ages ranging from 24 to 58 years) participated in this study. Monocular visual field sensitivity was measured under two conditions: (1) standard testing condition and (2) while the subject performed a Paced Auditory Serial Addition Task (PASAT). Monocular mfVEPs were recorded in response to a 60-sector stimulus. The checkerboard pattern in each sector was contrast reversed according to a binary m-sequence. mfVEPs were recorded under two conditions: (1) standard testing conditions and (2) while the subject performed a PASAT. We found that, when compared to the no-task condition, all subjects had locations of significantly reduced Humphrey visual field sensitivities when performing the PASAT. In contrast, there were no significant decreases in mfVEP amplitude in any sector for any of the subjects while performing the PASAT. Our findings indicate that divided attention and ongoing mental processes did not affect the mfVEP. Therefore, the mfVEP provides an objective measure of visual field function that may be useful for some patients with unreliable automated static perimetry results

PURPOSE/OBJECTIVE:To identify clinical vision measures that are associated with the driving performance of glaucoma patients who have visual field loss and visual acuity better than 20/100 and to compare the driving performance of glaucoma patients with the driving performance of a group of age- and sex-equivalent individuals without eye disease. PATIENTS/METHODS:Forty patients with glaucoma and 17 normally sighted control subjects participated in this study. METHODS:Clinical vision data, consisting of visual acuity, letter contrast sensitivity, and visual fields, were collected. Driving performance was assessed by (1) an interactive driving simulator that measured 7 indices of performance (including number of accidents) and (2) the self-reported accident involvement for the past 5 years. MAIN OUTCOME MEASURES/METHODS:Driving simulator performance and real-world, self-reported accident involvement. RESULTS:The number of accidents as measured on the driving simulator in the glaucoma group was significantly correlated with three Goldmann visual field measures: combined horizontal extent (rho = -0.47, P = 0.01), total horizontal extent (rho = -0.49, P = 0.007), and total peripheral extent (rho = -0.55, P = 0.002). There were no statistically significant correlations between the driving performance of the glaucoma group and the visual acuity or contrast sensitivity measures. When compared with the control group, a significantly greater proportion of the glaucoma group reported having at least one real-world accident within the past 5 years (Fisher exact test, P = 0.005). CONCLUSIONS:Visual field reduced to less than 100 degrees of horizontal extent may place patients with peripheral field loss at greater accident risk. A higher incidence of real-world and simulator accidents was found for the group with glaucoma.