Faculty Bibliography

PURPOSE:: To investigate a relationship between the inner segment-outer segment (IS-OS) junctional layer integrity and the overlying retinal sensitivity assessed by Spectral OCT/SLO (spectral-domain optical coherence tomography) and microperimetry testing in patients with dry and wet forms of age-related macular degeneration (AMD). METHODS:: Spectral-domain optical coherence tomography examination and microperimetry testing were performed in 55 eyes of 43 consecutive patients with AMD. Microperimetry maps were registered onto three-dimensional retinal topography maps, and point-to-point analysis of correlation between microperimetric retinal sensitivities and corresponding status of the underlying IS-OS junctional layer was performed. In addition, the analysis of correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of fovea was also performed. RESULTS:: Retinal sensitivity was inversely and strongly correlated with the integrity of IS-OS layer in both dry and wet forms of AMD (correlation coefficient [r] = -0.75 [95% confidence interval, 0.49-0.88], P < 0.001, and -0.79 [95% confidence interval, 0.61-0.89], P < 0.001, respectively). The correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of fovea was less significant (r = -0.58 [95% confidence interval, 0.19-0.79], P = 0.02, for dry AMD, and r = -0.6 [95% confidence interval, 0.32-0.78], P = 0.015, for wet AMD). CONCLUSION:: Retinal sensitivity consistently correlated with the status of underlying IS-OS junctional layer in both dry and wet forms of AMD. Loss of IS-OS layer is significantly associated with poor retinal sensitivity, assessed by microperimetry. Compared with visual acuity, functional testing with microperimetry appears to more consistently correlate with changes in the outer retina, such as IS-OS junctional integrity, especially, in patients with wet AMD

PURPOSE: To establish normative values for macular light sensitivity and to determine the intrasession fluctuation of perimetric responses using the OPKO/OTI microperimeter. METHODS: A total of 32 visually normal subjects participated in the study. A standardized grid pattern was used for testing, which consisted of 28 points arranged concentrically in three circles that occupied an area of 11 degrees (in diameter) within the central macula. Each subject participated in at least two tests. Parameters evaluated included: overall mean macular sensitivity for test 1 and 2, overall difference in mean macular sensitivity between tests, and the mean sensitivity for each circle. The relationship between sensitivity and age was also examined. RESULTS: The overall median sensitivity for test 1 was 16.8 decibels (dB) and for test 2 was 16.9 dB. The median sensitivities for test 1 and test 2 were not significantly different (P = 0.72). The mean intrasession sensitivity difference was 0.13 dB. The variability of the sensitivity difference between tests decreased as mean sensitivity increased. The sensitivity values averaged across the two tests for inner, middle, and outer circles ranged from 14.3 to 18.8 dB (median value of 16.9 dB), 13.8-18.3 dB (median value of 17.2 dB), and 11.3-18.3 dB (median value of 16.6 dB), respectively. Linear regression analysis showed a 0.5 dB sensitivity loss for each decade of life. CONCLUSION: We documented a narrow range of intrasession fluctuation using the OPKO/OTI microperimeter. The establishment of normative sensitivity values will facilitate monitoring the loss of macular visual function in patients with retinal disease

To investigate the relationship between depression and quantitative measures of visual function, we recruited 18 subjects with central scotomas from macular degeneration who were enrolled in a reading rehabilitation program. Psychological batteries and reading assessments were administered prior to rehabilitation; reading assessments and a measure of adaptation to vision loss were administered following rehabilitation. We investigated relationships between reported levels of depressive symptoms and reading and adaptation outcome measures by using Pearson product moment correlation analysis. Results revealed a significant relationship between depression levels and reading acuity difference scores (r(16) = 0.54, p = 0.02) and changes in adaptation to vision loss levels (r(16) = 0.62, p = 0.01), suggesting that those who reported greater depressive symptoms did not respond as well functionally to reading rehabilitation but reported greater improvement in levels of adaptation to vision loss following rehabilitation. Future research should focus on defining standard methods to assess and remediate depression as part of the rehabilitation process.

BACKGROUND AND AIMS: We correlated retinal sensitivity as determined by scanning laser ophthalmoscope microperimetry (SLO-MP) in glaucomatous eyes with paracentral visual field (VF) defects detected by standard automated perimetry (SAP). METHODS: Twenty eyes with glaucomatous optic neuropathy and a SAP VF defect involving the central 16 test points (at least one point with p<1% in the 24-2 VF) were enrolled. Eyes with diseases other than glaucoma were excluded. All patients underwent SLO-MP and SAP of the central 10 degrees. Results from each eye were divided into 4 quadrants for analysis. Normal and abnormal quadrants by SAP were compared to the corresponding normal and abnormal quadrants by SLO-MP. Regression analysis was used to correlate the mean threshold values (dB) of SLO-MP and SAP in each quadrant. Macular optical coherence tomography (OCT) was performed when there was a disagreement between functional tests. RESULTS: Mean age and VF mean deviation were 60.8+/-13.4 years and -7.3+/-6.1 dB, respectively. There was a significant correlation between SLO-MP and SAP results in all quadrants (r2>/=0.68, p<0.001). All abnormal SAP quadrants had a corresponding abnormal SLO-MP quadrant. However, 21% of the normal SAP quadrants had an abnormal corresponding microperimetry result; a corresponding significant reduction in total macular thickness measured by OCT was present in 75% of these quadrants. CONCLUSIONS: Macular sensitivity evaluated by SLO-MP correlates significantly with SAP paracentral VF defects. SLO-MP detected retinal sensitivity reduction in areas of OCT structural damage with normal SAP and suggests that subtle paracentral functional deficits may be present in many more eyes with established glaucoma than generally assumed

AIMS: To investigate the combination of 3D optical coherence tomography (OCT) retinal thickness measurements and superimposed scanning laser ophthalmoscopy (SLO) microperimetry obtained using a Spectral OCT/SLO and to test the correlation between retinal thickness and retinal sensitivity in retinal diseases grouped according to anatomic locations. METHODS: Patients with various retinal diseases and subjects with normal fundi underwent microperimetry testing and imaging with the Spectral OCT/SLO. Based on the Spectral OCT/SLO findings, the participants were divided into 4 groups: patients with retinal thickening due to the outer retina pathology (group I); patients with retinal thickening due to the cystic changes observed in the inner retina (group II); patients with macular neurosensory retina thinning associated with geographic atrophy or underlying subretinal cicatricial changes (group III), and subjects with unremarkable fundus appearance and normal appearing retina on Spectral OCT/SLO (group IV). The primary outcome was the correlation coefficient (r) between Spectral OCT/SLO-measured macular thickness and microperimetry values. RESULTS: Correlations between retinal thickness and psychophysical thresholds were calculated for each patient, and these values were averaged within groups. The mean correlation values (Pearson product movement) were as follows: for group I (n = 21 eyes) r = 0.04; for group II (n = 24 eyes) r = -0.53; for group III (n = 16 eyes) r = 0.41, and for group IV (n = 15 eyes) r = 0.04. CONCLUSIONS: The combination of 3D OCT images and superimposed SLO microperimetry obtained by Spectral OCT/SLO demonstrated that thickening due to cystic changes of the inner retinal layers or thinning of the neurosensory retina on OCT correlated most significantly with decreases in psychophysical threshold sensitivities

PURPOSE: To examine if vision in subjects with macular heterotopia (MH) secondary to retinopathy of prematurity (ROP) is related to anatomical macular structure. METHODS: Six subjects with MH who were between 18 years and 65 years of age and three age-matched subjects with normal vision were recruited for the study. Vision and macular structure of the better eye of the subjects with MH and the dominant eye of age-matched subjects with normal vision were assessed. High contrast visual acuity and contrast sensitivity were measured using Early Treatment of Diabetic Retinopathy Study and Pelli-Robson charts, respectively. The Micro Perimeter (Nidek Technologies MP-1) was used to assess macular sensitivity and fixation stability. Using optical coherence tomography, macular thickness and relative retinal thickness at fixation were measured. RESULTS: Subjects with MH had significantly reduced visual acuity and macular sensitivity compared with age-matched subjects with normal vision. In comparison with their age-matched counterparts, subjects with MH had significantly increased macular thickness and increased relative retinal thickness at fixation. A normal foveal architecture was absent in three subjects with MH (50%). CONCLUSION: Patients with MH secondary to ROP have increased macular thickness and reduced vision.

PURPOSE:: To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity. METHODS:: Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull's eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter. RESULTS:: Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli. CONCLUSION:: Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function

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

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