Search

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene associated Stargardt Disease (STGD1). DESIGN: Multicenter prospective cohort study. METHODS: PARTICIPANTS: 127 molecular confirmed STGD1 patients enrolled from 6 centers in the USA and Europe and followed every 6 months for up to 2 years. OBSERVATION PROCEDURES: The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°−10° eccentricity), and the MD for scotopic sensitivity for the extrafovea were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. MAIN OUTCOME MEASURES: Baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (p

Purpose In this study, we describe common demographic and clinical characteristics of the glaucoma patient population attending vision rehabilitation. Design Cross-sectional study. Participants Patients attending a hospital-based vision rehabilitation center with a primary ocular diagnosis of glaucoma. Methods Participants’ charts were retrospectively reviewed. Data extracted from medical records included demographics, referring physician, ocular history, glaucoma diagnosis, past ocular surgery, intraocular pressure, optic nerve findings, results of a functional intake assessing activities of daily living, depression, visual hallucinations, best-corrected visual acuity (BCVA), mean deviation (MD) scores on visual field testing, and log contrast sensitivity (CS). Main Outcome Measures Participant demographic information, ocular history, self-reported difficulty with activities of daily living, depression, visual hallucinations, BCVA, visual field, and CS. Results The mean age of patients in this study was 77 years and ranged from 8 to 103 years. Ninety percent of patients were referred to vision rehabilitation by an ophthalmologist. Median BCVA was 20/50. Fifty-five percent of patients were functionally monocular, and for all patients, there was a median 9-line difference in BCVA between eyes. Median MD score was −13.95 decibels (dB). Median CS was 1.05. Patients reported having the greatest difficulty with reading (88%), writing (72%), and mobility (67%). Seventy-eight percent of patients stopped driving, and 12% reported difficulty driving. Among those experiencing depression, there was a 4:1 ratio of depressed patients having difficulty with mobility. One-third of patients experienced visual hallucinations. Conclusions Most glaucoma patients attending vision rehabilitation are not legally blind, but many are functionally monocular. This may cause greater difficulty performing functions that require the use of binocularity. Increasing the referral of younger glaucoma patients to vision rehabilitation may help patients learn to cope with the loss of visual function that occurs over time.

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

The purpose of the present article is to describe the evaluation and treatment processes for glaucoma patients with functional challenges related to their vision. Studies of glaucoma patients demonstrate a decline in the ability to perform vision-related activities. Low vision therapy has proven to have a positive impact for many of these patients. We review the most recent literature in this area and also report on the characteristics of glaucoma patients enrolled in low vision services. Glaucoma is a significant cause of visual impairment and blindness. Low vision rehabilitation complements traditional medical and surgical care by working with patients to identify losses in and improve functionality. A battery of testing to assess visual acuity, contrast sensitivity, visual field, psychological well-being, and ambulation is performed in order to categorize deficits in vision-related tasks. Training and education on the use of visual aids have helped many patients improve independent function.

Purpose To determine fixation location and fixation stability in Stargardt disease (STGD1) and their association with best-corrected visual acuity (BCVA). Design Cross-sectional analysis within the multicenter, prospective ProgStar study. Participants A total of 238 patients and 440 eyes with ABCA4-related STGD1. Methods Patients underwent testing with the Nidek MP-1 microperimeter (Nidek Technologies Inc., Gamagōri, Japan). Fixation location was expressed as the eccentricity of the preferred retinal locus (PRL) from the anatomic fovea, fixation stability was expressed as the bivariate contour ellipse area (BCEA), and BCVA was expressed as Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Linear models with generalized estimating equations were used for statistical analysis while accounting for between-eye correlations. Main Outcome Measures Fixation location and fixation stability. Results Median PRL eccentricity from the fovea was 6° (mean, 6.3°; range, 0°–25°) and median BCEA was 6.31°2 (mean, 12.31°2; range, 0.03°2–365.63°2). Each year of later onset of symptoms of STGD1 was associated with 0.14° more central fixation location (P Conclusions We provide the first extensive database of continuous fixation parameters in STGD1 and demonstrate their association with vision. These measures allow for a more comprehensive assessment of retinal function and may serve as potential secondary outcome measures for future treatment trials for STGD1 and other macular diseases.

Purpose To examine the extent of visual function abnormality outside the dark lesion on short-wavelength fundus autofluorescence (SW-AF), and its correlation with background SW-AF features and optical coherence tomography (OCT) in recessive Stargardt disease (STGD1). Methods Forty-nine eyes of 25 participants in the ProgStar (the Natural History of the Progression of Atrophy Secondary to Stargardt Disease) study at our center were included. Patients underwent microperimetry (both threshold and dense scotoma mapping), OCT, SW-AF, and visual acuity testing. The Fisher's exact test, the χ2 test, and unpaired t-tests were used to analyze the data. Results Of 40 eyes without central fixation, 33 (82%) placed fixation remote (most ≥5°) from the dense scotoma edge, despite good intervening retinal sensitivity. OCT findings accounted for the remote fixation in 75%. Eighteen (37%) of all 49 eyes had dense scotoma extending past the dark lesion border. OCT was not adequate to define the edge of the scotoma. Of the 49 eyes, 28 (57%) had the mottled background pattern, 10 (20%) had the uniform pattern, and 11 (22%) had the other pattern, with >75% of eyes in each pattern having remote fixation. The dense scotoma exceeded the dark lesion primarily in the mottled pattern. The two eyes of each patient were concordant in all features. Conclusions Functional abnormalities in STGD1 extend past the SW-AF dark lesion. The disruption of the ellipsoid zone shows that photoreceptor abnormality extends peripheral to the dark lesion, and it explains in part the remote fixation pattern and the dense scotoma exceeding the dark lesion. This has implications for clinical trials for STGD1.

Purpose: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. Methods: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). Results: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00–19.88) dB and in sMP 11.25 (±5.26; 0–19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10–21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21–21.46) mm2. Conclusions: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study.

Objective To present a method of estimating and equating scales across functional assessment instruments that appropriately represents changes in a patient's functional ability and can be meaningfully mapped to changes in Medicare G-code severity modifiers. Design Previously published measures of patients' overall visual ability, estimated from low-vision patient responses to 7 different visual function rating scale questionnaires, are equated and mapped onto Medicare G-code severity modifiers. Setting Outpatient low-vision rehabilitation clinics. Participants The analyses presented in this article were performed on raw or summarized low-vision patient ratings of visual function questionnaire (VFQ) items obtained from previously published research studies. Interventions Previously published visual ability measures from Rasch analysis of low-vision patient ratings of items in different VFQs (National Eye Institute Visual Functioning Questionnaire, Index of Visual Functioning, Activities of Daily Vision Scale, Visual Activities Questionnaire) were equated with the Activity Inventory (AI) scale. The 39 items in the Self-Report Assessment of Functional Visual Performance (SRAFVP) and the 48 items in the Veterans Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ) were paired with similar items in the AI in order to equate the scales. Main Outcome Measures Tests using different observation methods and indicators cannot be directly compared on the same scale. All test results would have to be transformed to measures of the same functional ability variable on a common scale as described here, before a single measure could be estimated from the multiple measures. Results Bivariate regression analysis was performed to linearly transform the SRAFVP and VA LV VFQ item measures to the AI item measure scale. The nonlinear relationship between person measures of visual ability on a logit scale and item response raw scores was approximated with a logistic function, and the 2 regression coefficients were estimated for each of the 7 VFQs. These coefficients can be used with the logistic function to estimate functional ability on the same interval scale for each VFQ and for transforming raw VFQ responses to Medicare's G-code severity modifier categories. Conclusions The principle of using equated interval scales allows for comparison across measurement instruments of low-vision functional status and outcomes, but can be applied to any area of rehabilitation.

Background/purpose Foveal hypoplasia is associated with low vision in a variety of conditions. We report and show imaging studies for a series of five patients with foveal hypoplasia who had visual acuity ranging from 20/25 to 20/60. Methods Observational case series. Patients This series includes five patients aged 5 to 18 years who presented to the Greater Baltimore Medical Center, Hoover Low Vision Clinic. All patients showed a partial or complete absence of the fovea in both eyes on examination. Results Eight eyes exhibited absence of foveal depression on spectral domain optical coherence tomography (Cirrus high-definition OCT; Carl Zeiss Meditec). Four eyes exhibited Grade 3 foveal hypoplasia, two eyes exhibited Grade 4 foveal hypoplasia, and two eyes exhibited Grade 1 foveal hypoplasia. For two eyes (one patient), the optical coherence tomography was no longer available for grading, but was interpreted as foveal hypoplasia in both eyes in the chart. Visual acuities ranged from 20/25 to 20/60. Only two of five patients showed signs of albinism. Conclusion Despite the presence of foveal hypoplasia, patients can retain a high level of visual acuity, which suggests that a foveal depression is not essential for the development of good visual acuity.

PUPOSE To document acute thioridazine toxicity from the symptoms only, through the development of ophthalmoscopic signs and recovery of dark adaptation and electroretinogram responses. These findings support the thesis that visual loss is metabolic and reversible if diagnosed early. METHODS Case Report. RESULTS A case is presented of acute thioridazine toxicity with documentation of the development of symptoms before any ophthalmoscopic evidence of toxicity. This case uniquely shows the time course of dark adaptation, showing both delay in adaptation and elevated final threshold, it includes full electrophysiologic studies from within the first weeks of symptoms and regular follow-up demonstrating marked recovery of dark adaptation in terms of both delay and final threshold, a nearly normal electroretinography and normal color vision within 10 months. CONCLUSION Our findings give support to the thesis that functional visual disturbance is primarily metabolic and reversible if detected early in the course of toxicity.

Purpose To describe the enlargement of the dense scotoma over time in Stargardt disease and to highlight methodologic issues in tracking enlargement. Methods Retrospective study of patients with full mapping of the border of the dense scotoma using the MP-1 for at least two visits. Results 14 eyes of 7 patients met this criterion. Patients had median of 3 visits (range 2-5), with median total follow-up of 4.5 years (range 1.5-8). Mean baseline visual acuity was 20/56 (range 20/25-20/200), mean baseline dense scotoma area was 2.23 mm (range 0.41-5.48), and mean dense scotoma enlargement rate was 1.36 mm/year (range 0.22-2.91). The younger patients tended to have more rapid loss of visual acuity, which tended to plateau when the visual acuity was 20/100 or worse. The patients who developed Stargardt before age 20 years, and the single patient who developed Stargardt disease after age 40 years, had more rapid enlargement rates, with preservation of central vision in the oldest patient. The ability to precisely define the dense scotoma area was dependent on the density location of the points tested; this led to significant variability in the assessment of the scotoma enlargement rate in three of the seven patients. The dense scotoma was not described adequately by the extent of the homogeneous dark area on fundus autofluorescence imaging. Conclusion Microperimetry is necessary for mapping the scotoma in patients with Stargardt disease, because current imaging is not adequate. Standardized grid testing, plus a standardized procedure for refining the border of the dense scotoma, should allow more precise testing and longitudinal assessment of enlargement rates.

Background/aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4) and exudative AMD (n=11). The choroids were excised and incubated for alkaline phosphatase (APase; blood vessels) and non-specific esterase activities (MCs). Degranulated (DG) and non-degranulated MCs in four areas of posterior choroid (nasal, non-macular, paramacular and submacular) were counted in flat mounts (4–6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm 2 ; p=0.0091) and GA (199.08±82.0 cells/mm 2 ; p=0.0019) compared with the aged controls. DG MCs were also increased in paramacular (p=0.001) and submacular choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MCs had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler9s and Haller9s layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity with CC in GA and exudative AMD and in choroidal neovascularisation (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and retinal pigment epithelial and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid.

Purpose Refraction often may be overlooked in low-vision patients, because the main cause of vision decrease is not refractive, but rather is the result of underlying ocular disease. This retrospective study was carried out to determine how frequently and to what extent visual acuity is improved by refraction in a low-vision population. Design Cross-sectional study. Participants Seven hundred thirty-nine low-vision patients seen for the first time. Methods A database with all new low-vision patients seen from November 2005 through June 2008 recorded presenting visual acuity using an Early Treatment Diabetic Retinopathy Study chart; it also recorded the best-corrected visual acuity (BCVA) if it was 2 lines or more better than the presenting visual acuity. Retinoscopy was carried out on all patients, followed by manifest refraction. Main Outcome Measures Improvement in visual acuity. Results Median presenting acuity was 20/80 –2 (interquartile range, 20/50–20/200). There was an improvement of 2 lines or more of visual acuity in 81 patients (11% of all patients), with 22 patients (3% of all patients) improving by 4 lines or more. There was no significant difference in age or in presenting visual acuity between the group that did not improve by refraction and the group that did improve. When stratified by diagnosis, the only 2 diagnoses with a significantly higher rate of improvement than the age-related macular degeneration group were myopic degeneration and progressive myopia (odds ratio, 4.8; 95% confidence interval [CI], 3.0–6.7) and status post–retinal detachment (odds ratio, 7.1; 95% CI, 5.2–9.0). For 5 patients (6% of those with improvement), the eye that was 1 line or more worse than the fellow eye at presentation became the eye that was 1 line or more better than the fellow eye after refraction. Conclusions A significant improvement in visual acuity was attained by refraction in 11% of the new low-vision patients. Improvement was seen across diagnoses and the range of presenting visual acuity. The worse-seeing eye at presentation may become the better-seeing eye after refraction, so that the eye behind a balance lens should be refracted as well. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

PURPOSE: The goal of this study was to see how the availability of ranibizumab affected the referral patterns for low vision (LV) evaluation. METHODS: This study used a retrospective review and a comparison of all patients newly referred from retinal Practice 1 (J.T.T., R.N.S.) for LV consultation, from July 2005 to June 2006 (Year 1, preranibizumab) and from July 2006 to June 2007 (Year 2, ranibizumab available), and a retrospective review of patients referred by retinal Practice 2 (M.J.E.) since February 2007. RESULTS: Practice 1: In Year 1, 24 patients with choroidal neovascularization were referred for LV, and in Year 2, only 12 were referred. There was a trend for those patients referred in Year 2 to have worse visual acuity and Pelli-Robson contrast sensitivity than those in Year 1. In Years 1 and 2, 18 and 11 patients with other conditions were referred for LV consultation, respectively. For these patients without choroidal neovascularization, there was no significant difference between groups for visual acuity or contrast sensitivity. Practice 2: The mean best-corrected visual acuity of patients with bilateral choroidal neovascularization referred was 20/145, and no patient had visual acuity > or =20/100. CONCLUSION: Although the use of antivascular endothelial growth factor agents puts visual acuity in a zone more favorable for successful LV intervention, patients with better acuities may not be referred for LV evaluation despite their residual visual impairments and their scotomas, and despite the fact that without LV intervention, they are having difficulty with reading and other activities of daily living. The frequent visits required for monthly injection, the tendency to wait until a course of therapy is complete before referring patients, and a lesser appreciation for the need for LV intervention in patients with only moderate visual loss may be factors in explaining this.

Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to “fit” within the central spared area.

OBJECTIVE To determine the relationship between reduced retinal autofluorescence and the dense scotomas in Stargardt disease. METHOD Retrospective review of patients with Stargardt disease seen between 2000 and 2004 at a tertiary referral center. PATIENTS All 32 patients with Stargardt who underwent both autofluorescence (AF) imaging and scotoma mapping were included. RESULTS Forty-seven percent of eyes had dense scotomas corresponding to the areas of loss of AF (27% corresponding to the area of uniform loss of AF, and 20% corresponding to the area of uniform plus mottled loss of AF). Fifty-three percent of eyes did not have a good correlation of the dense scotoma with the area of loss of AF. Both eyes were judged to be in the same group in 75% of patients. CONCLUSIONS Areas of reduced AF are measurable, but are not equivalent to the area of dense scotoma in 53% of patients. Measures of retinal sensitivity and scotomas are necessary for defining retinal functional involvement in Stargardt disease.

To describe, in a group of patients with moderately advanced retinitis pigmentosa (RP), the prevalence of cystoid macular edema (CME), the variation in foveal thickness over a 48-week period, the correlation of visual acuity (VA) with retinal thickness, and the lack of response of CME to lutein administration.Optical coherence tomography (OCT) imaging of the macula and clinical examination were evaluated for 77 eyes of 39 patients with RP over 11 months, with a scan done every 6 weeks.The prevalence of CME, defined by cysts visible on OCT, was 49%. Bilateral CME was present in 44% of patients (17 of 39), and an additional two patients had unilateral CME. Central retinal thickness varied little over the 48 weeks. Sixty-six percent of the eyes with CME had VA of 20/40 or better. The eyes with CME with VA worse than 20/40 had either greater degrees of thickening or in fact had lower thickness measures. For the eyes without CME, the eyes with VA worse than 20/40 tended to have lower retinal thickness than the eyes with VA of 20/40 or better. VA was highly concordant between eyes, and did not differ significantly between the groups with and without CME. Lutein did not show a statistically significant effect on retinal thickness in the patients with or without CME, nor was such an effect observed in subgroups of patients with vision better or worse than 20/40.The prevalence rate of CME is higher than in previous reports, perhaps because the patients had some preserved macular vision and because of the use of a definition based on OCT findings. Retinal thickness remains fairly stable over time, both in eyes with CME and in eyes without CME.

PURPOSE To show that the area of atrophy seen on ophthalmoscopy may not correspond with the area of scotoma in some macular diseases. METHODS Three cases are presented, one with geographic atrophy (GA) from age-related macular degeneration, one with Stargardt disease, and one with a macular dystrophy. Nidek MP-1 microperimetry was performed and the correspondence of the dense scotoma to the visible atrophy is reported. RESULTS In the GA patient, the dense scotoma corresponds with the atrophy. In the patient with Stargardt disease, the dense scotoma is larger than the area of visible atrophy. In the patient with a macular dystrophy, the dense scotoma is smaller than the area of visible atrophy. CONCLUSIONS In GA from age-related macular degeneration, the dense scotoma generally corresponds with the atrophy, so that measurement of the enlargement rate of the atrophy is a direct measure of enlargement of the scotoma. This may not be true of other macular diseases.

To derive information from the Geographic Atrophy (GA) Natural History Study that is relevant to recruiting patients and designing clinical trials for GA.A prospective natural history study with annual follow-up enrolled patients with GA and no choroidal neovascularization (CNV) in at least one eye. Characteristics of recruited and enrolled patients are analyzed, in the context of progression data from the study.The data show that GA from age-related macular degeneration (AMD) was seen in 82% of the referred patients, there was an attrition rate of 14%, and 60% of the patients with GA from AMD had bilateral GA without CNV. Within the 83 patients in the bilateral GA group with follow-up, 50 patients (60%) met both the proposed visual acuity and the proposed GA area criteria for a treatment trial in one or both eyes.These data should be helpful in planning future treatment trials for GA.

Purpose To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. Design Prospective natural history study of GA resulting from age-related macular degeneration. Participants Two hundred twelve eyes of 131 patients were included in the analysis. Methods Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. Main Outcome Measure Rate of enlargement of the atrophy. Results The median overall enlargement rate was 2.1 mm 2 /year (mean, 2.6 mm 2 /year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (α, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. Conclusions Treatment trials for GA with an outcome variable of change in enlargement rate are feasible.

To study whether fixation patterns changed over time in patients with central scotomas from geographic atrophy from age-related macular degeneration.Prospective cohort study.setting: Institutional. patient or study population: Prospective natural history study of geographic atrophy included 34 eyes of 25 patients with baseline acuity between 20/80 and 20/200 and with subsequent follow-up. observation procedures: Baseline and annual follow-up visits included best-corrected visual acuity, scanning laser ophthalmoscope macular perimetry, reading rate, and clinical evaluation. main outcome measures: Location of eccentric preferred retinal locus for fixation (PRL).At baseline, 77% of study eyes had a PRL. At the final visit (median follow-up, 5.3 years), 91% of study eyes had a PRL, with 81% of the eyes retaining the baseline PRL location. Fixation with the scotoma to the right and fixation with the scotoma superior were the first and second most common fixation patterns, respectively. Reading rates of50 words/min were present in 54% of eyes. Eyes fixating with the scotoma to the left tended to have lower reading rates than eyes fixating with right or superior patterns.Fixation with right pattern remained the most common fixation pattern, both in patients with a PRL at baseline and in patients who had a PRL during follow-up. Eyes with a PRL at baseline generally retained this pattern. The reading rate data suggest an advantage of fixation with right or superior pattern, rather than left. Reading rate declined further during follow-up in most patients.

Purpose To describe retinotopic mapping of the visual cortex when a central scotoma is present. Design Single observational case report. Methods Scanning laser ophthalmoscope perimetry was used to define the site and stability of fixation and the area of dense scotoma. Functional magnetic resonance imaging of the visual cortex was performed while the patient viewed an expanding annular stimulus. Results Retinotopic mapping of the visual cortex for a patient with a horseshoe scotoma from geographic atrophy involving the macular region showed a loss of stimulation to the cortical areas representing the site of the atrophic lesion. Conclusions Cortical retinotopic mapping can be performed successfully in patients with central scotomas from macular disease. This study can serve as a basis for the future investigation of cortical plasticity in visual cortex.

Purpose To compare different metrics and acquisition modes of fixation stability as a new visual function biomarker in a large cohort of patients with ABCA4-related Stargardt disease from the multicenter prospective ProgStar study. Methods Fixation was tested during a separate fixation exam and also dynamically during a sensitivity exam, using fundus-tracking microperimetry (Nidek MP-1). Fixation data were analyzed using the bivariate contour ellipse area (BCEA), the 2/4 degree method, and the Fujii classification. Results In a total of 235 patients, the mean BCEA was larger when measured during the sensitivity exam (418 eyes; 12.5 vs. 4.6 deg2 during the fixation task in 427 eyes). Correlations between the two tests were generally weak. Fixation stability during the sensitivity test was significantly correlated with visual acuity. Comparing the BCEA values and the corresponding Fujii categories for these eyes revealed ranges of overlap where an eye with one defined BCEA value can fall into each of the three Fujii categories. Conclusions Patients may have limited ability to fixate over defined time periods, which leads to significant differences between shorter and longer measurements of fixation stability. The most appropriate way to use this functional biomarker appears to be using continuous metrics for fixation stability, such as the BCEA, during a macular sensitivity test.

IMPORTANCE: New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity. OBJECTIVE: To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as “normal,” “relative,” or “deep” scotoma. MAIN OUTCOMES AND MEASURES: Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas. RESULTS: Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, −0.13 to −0.041; P

To illustrate the confounding factors when assessing visual acuity and color vision in a patient with a bullseye macular scotoma in one eye and a horseshoe of atrophy sparing the fovea in the fellow eye. Case report. Visual acuity, color vision, and scanning laser ophthalmoscope analysis. The patient with geographic atrophy from age-related macular degeneration in both eyes had visual acuity of 20/40– in the right eye and 20/40+ in the left eye. She reported that she could read newsprint but not news headlines. She could not identify any color plates, but had only minor errors using a color cap (large D-15) test. She had a macular ring scotoma (bullseye scotoma) in the right eye, and a horseshoe-shaped area of atrophy surrounding the fovea in the fellow eye. Scotomas surrounding but sparing the fovea can lead to difficulty reading large letters, because these letters do not fit in the spared foveal region. Care must be taken in measuring visual acuity in these patients so that the testing does not stop when the patient cannot read the largest letters. The presence of scotomas in the central field may not allow the whole figure on color plate testing to be integrated and identified, leading to a possible misdiagnosis of cone dystrophy. Color cap testing avoids this problem.

PURPOSE To study the improvement in visual acuity over time in patients with central scotomas. METHODS In a prospective natural history study of geographic atrophy (GA) from age-related macular degeneration (ARMD) with annual follow-up, 36 patients with bilateral GA completed 3 years of follow-up. Protocol visual acuity (VA) measurements were performed. Scanning laser ophthalmoscopy (SLO) was performed, and the areas of GA were measured from fundus photographs. RESULTS Six eyes of six patients with VA ranging from 20/80 to 20/500 had a VA improvement of two or more lines (mean, 3.2 lines). This was found only in the worse-seeing eyes of the patients and was contemporaneous with the deterioration in VA of the better-seeing eyes. Four of six eyes that improved in acuity had an improvement in the ability to find and hold the fixation target in an area of seeing retina, as assessed by SLO at follow-up, and a fifth eye changed from one fixation site that had little functional retina to another site. CONCLUSIONS Spontaneous improvement in VA in eyes with bilateral GA and central scotomas may occur. It appears to be related to deterioration in VA of the better-seeing fellow eye and is associated with improvement of fixation in the worse-seeing eye. The worse-seeing eye of a patient with bilateral ARMD may have the potential for better vision than measured VA indicates. This finding may have implications for the choice of patients in treatment trials, for interpretation of long-term results, and for planning and assessment of low vision intervention.

Objective To describe the progression of geographic atrophy (GA) from age-related macular degeneration (AMD) with respect to visual acuity (VA) loss and enlargement of atrophy. Design A prospectively observed case series. Setting Tertiary retinal referral center. Participants One hundred twenty-three patients with GA due to AMD who completed at least 1 year of follow-up (median follow-up, 3 years) were examined annually. Methods At each examination, a protocol best-corrected VA of each eye was measured, a clinical examination was performed, and color fundus photographs were taken. The areas of atrophy were drawn and measured. Main outcome measures Visual acuity loss and enlargement of total and central atrophy. Results At baseline, median VA was poorer with larger areas of atrophy, but there was wide variation related to sparing of the fovea. Thirty-one percent of all study eyes suffered a three-line VA loss from baseline by 2 years, and 53% had a three-line loss by 4 years. Those eyes with VA better than 20/50 had the highest rate of acuity loss; 27% of these eyes had acuities of 20/200 or worse at 4 years. Visual acuity loss in the GA study eye was similar in patients with bilateral GA and in those with choroidal neovascularization in the fellow eye. Total atrophy enlarged a median of 1.8 Macular Photocoagulation Study disc areas (DA) at 2 years; atrophy within a 4-DA circle centered on the fovea enlarged a median of 0.9 DA. Two (22%) of nine patients with GA in one eye and only drusen without advanced AMD in the fellow eye developed GA in the fellow eye at 2 years. Conclusions Geographic atrophy is associated with a significant decline in VA over time in many eyes. Areas of atrophy continue to enlarge over time, even when already large at baseline. The combination of reduced VA with enlargement of atrophy, occurring bilaterally in most patients, can lead to significant impairment of visual function.

Objective To determine the rate of developing choroidal neovascularization (CNV) in eyes with geographic atrophy (GA) from age-related macular degeneration (AMD) and the characteristics of the CNV in these eyes. Design Prospective natural history study with cohort analysis. Participants One hundred fifty-two patients with GA and no CNV by fluorescein angiography in at least 1 eye, with annual follow-up. Main outcome measures The development of CNV. Results Thirteen eyes with GA developed CNV. For patients with bilateral GA and no CNV at baseline, 2% developed CNV by 2 years and 11% by 4 years. For patients with CNV in the fellow eye, 18% developed CNV in the study eye with GA by 2 years and 34% by 4 years. The eyes that developed CNV experienced more acuity loss than did the eyes with only GA. Within the fellow eye CNV group, those study eyes with GA that had less central atrophy (and better acuity) at baseline were more likely to develop CNV. The CNV developed at a peripheral border of GA in nine eyes, in the spared foveal region in two eyes, and in both center and border in one eye. No eye developed CNV in the area of atrophy itself. The appearance of CNV was evanescent in some cases and had a final appearance of an enlarged area of GA. Twelve other eyes had hemorrhages without definite evidence of CNV; three were thought to be suspicious for CNV and the remainder were thought to be hemorrhages that may be seen in elderly patients. Conclusion An eye with GA whose fellow eye has CNV is at significant risk for the development of CNV in the GA eye. A patient with bilateral GA and no evidence of CNV is at relatively low risk for developing CNV. The CNV may be evanescent and may not be detected. Intraretinal hemorrhages unrelated to CNV are relatively common in this older population.

Purpose: To study fixation patterns and reading rates in eyes with central scotomas from geographic atrophy (GA) of age-related macular degeneration and to compare fixation patterns with those of patients with Stargardt disease. Methods: Scanning laser ophthalmoscope analysis of fixation patterns in eyes with 20/80 to 20/200 visual acuity. Included were 41 eyes of 35 patients with GA and 10 eyes of 5 patients with Stargardt disease. The patients with GA also were tested for maximum reading rate, and the size of the areas of atrophy were measured by fundus photograph analysis. Results: Sixty-three percent of GA eyes fixating outside the atrophy placed the scotoma to the right of fixation in visual field space, 22% placed the scotoma above fixation, and 15% placed it to the left, regardless of the laterality of the GA eye. Fixation was stable in subsequent years of testing for scotoma placement to the right of or above fixation. All GA eyes fixated immediately adjacent to the atrophy. In contrast, seven of ten eyes with Stargardt disease fixated at a considerable distance from the scotoma border, with the dense scotoma far above the fixation site in visual field space. For the patients with GA, the maximum reading rate was highly correlated with size of the atrophic area, but not with age or visual acuity within the limited visual acuity range tested. There was a trend to more rapid reading with the scotoma above fixation and slower reading with the scotoma to the left. Conclusion: There is a preference for fixation with the scotoma to the right in eyes with GA. Patients with Stargardt disease use different strategies for fixation, perhaps due to subdinical pathology adjacent to the atrophic regions. The size of the atrophic area in GA plays the predominant role in reading rate for eyes that have already lost foveal vision.

This chapter focuses on the changes in vision experienced by patients with RP and AMD. The specific aspects of vision that are reviewed include progressive changes in central acuity, contrast sensitivity, visual field, color vision, night vision, glare, and light and dark adaptation. Emphasis is on patients’ perspectives, including the impact on functioning and performance of activities of daily living, as well as rates, patterns of vision loss, and day-to-day visual fluctuations experienced by those with retinal degenerative diseases. Several types of visual phenomena are presented, including Charles Bonnet Syndrome hallucinations in AMD, perceptual completion or filling-in of scotomas in AMD, remapping visual cortex in AMD, the preferred retinal locus in AMD, and photopsias or light show type flashes in RP. The proposed implications of these visual changes and phenomena as they apply to retinal prosthetic vision are discussed.

Visual increment thresholds measured on backgrounds flashed on simultaneously with the test flash exhibit saturation rather than following Weber’s law. These flash-on-flash thresholds have been modeled with saturating nonlinearities similar to those used to describe intensity-response functions of retinal neurons. Recently, the flash-on-flash technique has been used to assess the mechanisms of threshold elevations in visual system diseases. However, the results were interpreted in a qualitative way. This paper extends the clinical application of flash-on-flash threshold measures by providing a theoretically derived algorithm for estimating nonlinear model parameters from flash-on-flash threshold data. The performance of the algorithm is evaluated with Monte Carlo techniques, and the theoretical interpretations of the model parameters are tested experimentally. Published clinical flash-on-flash threshold data are reanalyzed using the algorithm. A previously unappreciated decrease in the half-saturation constant of retinitis pigmentosa patients was revealed by this analysis.

Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to “fit” within the central spared area.

Objective To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD). Design Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute. Participants Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination. Methods Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm 2 circle centered on the fovea. Main Outcome Measures Visual acuity loss at 2 years and risk factors for visual loss. Results Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13–7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39–12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11–5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm 2 than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm 2 . The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate. Conclusions Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To demonstrate the potential and limits of autofluorescence imaging in identifying and delineating areas of atrophy. Methods: Fundus photographs and infrared scanning laser ophthalmoscope (SLO) imaging, SLO macular perimetry, and SLO autofluorescence imaging results were compared for two patients with geographic atrophy (GA) from age-related macular degeneration, one patient with pigmentary alteration of the retina, and two patients with Stargardt disease. The main outcome measure in this case series was the presence of reduced autofluorescence. Results: Drusen may become undetectable during autofluorescence imaging for some patients, allowing simple identification of areas of GA with areas of reduced autofluorescence. In other patients, drusen themselves have decreased autofluorescence, despite having intact retinal function in the retina overlying them. Some patients may have areas of reduced autofluorescence that persist for many years, without evidence of the development of atrophy. In Stargardt disease, decreased autofluorescence can easily detect and delineate areas of scotoma. Areas with mottled autofluorescence may have overlying function, but the function may not be adequate to support a fixation locus in that area. Conclusions: Using decreased autofluorescence to delineate areas of atrophy may be helpful in atrophic macular disorders. For GA, correlation with fundus photographs or macular perimetry findings may be necessary to differentiate between drusen and atrophy. For Stargardt disease, the nature of areas of decreased autofluorescence may help explain visual function of those areas.

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP , a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.

Purpose To evaluate the effects of subfoveal choroidal neovascularization secondary to age-related macular degeneration on functional parameters obtained by scanning laser ophthalmoscope microperimetry. Design Retrospective observational case series and cross-sectional study. Methods At the Doheny Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration was studied. The onset of visual symptoms, best-corrected visual acuity, fluorescein angiography, evaluation of fundus microperimetry and fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained for each patient. The main outcome measures were central retinal sensitivity and fixation pattern (fixation location and fixation stability) in eyes with subfoveal choroidal neovascularization and their relationship to the length of disease, type and characteristics of choroidal neovascularization, and visual acuity. Results Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor central fixation, and 17 (9%) had predominantly eccentric fixation. Seventy-six eyes (42%) had stable fixation, 70 eyes (39%) had relatively unstable fixation, and 33 eyes (18%) had unstable fixation. In 50 eyes (28%) a dense central scotoma was noted. Eighty-nine of 100 eyes (89%) with length of symptoms of less than 3 months had predominantly central fixation and 58 (58%) had stable fixation; 14 of 34 eyes (41%) with length of symptoms of more than 6 months had predominantly central fixation, and 5 eyes (15%) had stable fixation. In 15 eyes of patients who elected not to receive treatment, successive scanning laser ophthalmoscope microperimetry were obtained over time (follow-up of 18 months after onset of symptoms). Three months or less after the onset of symptoms, 13 eyes (87.7%) had predominantly central fixation and 9 eyes (60%) had stable fixation. More than 3 months and 6 months or less after the onset of symptoms, 10 eyes (66.7%) had predominantly central fixation and 7 eyes (46.7%) had stable fixation. This trend was further demonstrated in eyes more than 6 months after the onset of symptoms. Conclusions We conclude that the sequence of events leading to visual function deterioration appears to involve an initial mild decrease in central retinal sensitivity and visual acuity followed by progressive fixation instability and, ultimately, development of an absolute central scotoma with totally eccentric fixation. Increased length of disease is associated with worse fixation pattern and retinal sensitivity deterioration as assessed by scanning laser ophthalmoscope microperimetry. A better understanding of the characteristics of visual loss assessed by fixation pattern evaluation and microperimetry in age-related macular degeneration may help optimize timing, patient selection, and treatment options in eyes with this condition.

Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5-61), representing four families with known VMD2 mutations, were included. OCT scans were recorded in the central retina and longitudinal reflectivity profiles were analysed. The central retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep retinal band termed the outer retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory retina, such as in central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner retina and central vision.

Objectives To evaluate the use of the scanning laser ophthalmoscope (SLO) as a predictor for potential visual improvement in eyes with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) undergoing limited macular translocation. Design Retrospective noncomparative case series. Participants Consecutive series of 71 eyes of 70 patients with subfoveal CNV secondary to AMD that underwent effective and uncomplicated limited macular translocation at the Wilmer Ophthalmological Institute. Methods Evaluation of the fundus microperimetry and fixation pattern was conducted on all patients using the Rodenstock scanning laser ophthalmoscope (G. Rodenstock Instrument GmbH, Munich, Germany) within 72 hours before surgery. Main outcome measures Sensitivity and specificity in addition to positive and negative predictive values of SLO findings for visual outcome after macular translocation. Results Stable fixation presented the highest positive predictive value for visual acuity equal to or better than 20/100 (30 of 33=0.91), and predominantly eccentric fixation had the highest negative predictive value for visual acuity worse than 20/100 (7 of 9=0.78). Sensitivity was higher for the presence of predominantly central fixation (42 of 48=0.87), and specificity was higher for relatively unstable/unstable fixation (20 of 23=0.87). Conclusions Eyes with stable and central fixation (without dense central scotoma) good preoperative visual acuity, and short length of symptoms are those with the greatest chance to achieve good vision after macular translocation. The knowledge of the fixation and microperimetry pattern enables better understanding of the macular function in eyes with AMD and may be useful for evaluation of baseline retinal cell viability. Incorporation of these testing modalities may help to optimize patient selection for macular translocation or other future techniques aimed at rescuing photoreceptors.

Objectives To report visual improvement following bilateral limited macular translocation for a patient with atrophic macular disease, and to discuss issues related to the selection of potential candidates for this technique. Design Case report. Results A 78-year-old woman with bilateral atrophic maculopathy and no choroidal neovascularization had slowly progressive loss of visual acuity for at least 17 months in the right eye and 25 months in the left eye. She underwent bilateral limited macular translocation, using scleral infolding in the right eye and scleral outpouching in the left eye. Following translocation of her maculae, her best-corrected visual acuity improved from 20/200 to 20/30 OD and from 20/180 to 20/100 OS. She remained stable during 30 months of follow-up for the right eye and 22 months of follow-up for the left eye. Conclusion Macular translocation may allow visual recovery in selected patients with atrophic maculopathy, even after a prolonged period of poor vision.

PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a previously unreported kindred of eight siblings, four of whom had mutations in both of their ABCR alleles. A previously described G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr substitution, were identified. These mutations co-segregated with the affected members of this family. Three of the siblings demonstrated clinical features characteristic of classic Stargardt disease, with bilateral regions of macular atrophy associated with yellow-white "flavimaculatus" flecks in the posterior pole at the level of the retinal pigment epithelium. The fourth affected sibling showed features of early Stargardt disease, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a characteristic peripheral dark choroid. CONCLUSIONS: We have identified both a previously described and a novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. In-depth knowledge of the ABCR mutation spectrum in patients with Stargardt disease will provide for more efficient screening and may provide potential therapies for Stargardt disease and other retinal diseases.

Purpose: Submacular surgery is under investigation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis syndrome, and other causes. The aims of this study were to determine whether the macular area from which choroidal neovascularization was removed surgically remained functional and whether there was any qualitative difference between eyes with different disease conditions or between eyes of younger and older patients. Methods: Our study included 19 patients (19 eyes) with choroidal neovascularization, seven cases caused by age-related macular degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia, or idiopathic causes. All tests were performed at least 6 months after surgical removal of choroidal neovascularization. All patients underwent fundus perimetry with the scanning laser ophthalmoscope for evaluation of dense and relative scotomas and fixation site. Results: After submacular surgery in 19 patients, 10 patients (one with age-related macular degeneration and nine with pathologic myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal neovascularization) fixated within an area that ophthalmoscopically and angiographically was an area of retinal pigment epithelial disturbance occupied by choroidal neovascularization preoperatively. Of 12 patients without age-related macular degeneration, seven of eight patients younger than 50 years of age compared with two of four patients 50 years or older fixated within the area of retinal pigment epithelial disturbance. Conclusions: Our data suggest that in patients without age-related macular degeneration who undergo submacular surgery, the surgically disturbed area previously occupied by choroidal neovascularization can remain functional postoperatively. Furthermore, occasionally a patient with age-related macular degeneration undergoing submacular surgery still can fixate in the area from which the choroidal neovascularization was removed.

Purpose: Geographic atrophy (GA) may cause significant compromise of visual function, even when there still is good visual acuity (VA), because of parafoveal scotomas and foveal function abnormalities antedating visible atrophy. This study evaluates the visual function abnormalities at baseline and the 2-year worsening of VA and reading rate for eyes with GA compared with a group of eyes with drusen only. Methods: Seventy-four eyes with GA and VA greater than or equal to 20/50 from a prospective natural history study of GA were included, as were 13 eyes with only drusen. Baseline visual function testing and 2-year VA and maximum reading rate are reported. Results: The worsening of VA in decreased luminance and foveal dark-adapted sensitivity showed severe abnormalities for the GA group. Contrast sensitivity was significantly reduced for the eyes with GA. Half the eyes with GA, but none of the drusen eyes, had maximum reading rates below 100 words per minute. A scanning laser ophthalmoscope (SLO) measure of the scotoma near fixation combined with a measure of residual foveal function accounted for 54% of the variability in maximum reading rate in the eyes with GA. Of 40 eyes with GA observed for 2 years, half lost greater than or equal to 3 lines of VA and one quarter lost greater than or equal to 6 lines. The nine eyes with drusen with follow-up had no significant change in VA. Low foveal dark-adapted sensitivity, SLO measures of the scotoma within 1° of fixation, and low maximum reading rate were statistically significant risk factors for doubling of the visual angle. Significant reduction in maximum reading rates at 2 years was present for the eyes with GA. Conclusions: The eyes with GA with good VA have profound decreases in visual function, particularly in dim lighting and in reading. Half the eyes with GA had doubling in visual angle at 2 years after the baseline examination, whereas the drusen eyes remained essentially unchanged. Impaired visual function at baseline was predictive of an adverse outcome for the eyes with GA.

Purpose To describe the use of red contact lenses to alleviate photophobia in patients with cone disorders. Design Retrospective interventional case series. Methods Twenty-three patients with achromatopsia or an acquired cone disorder with complaints of severe photophobia were fit with absorptive red soft contact lenses to alleviate photophobia and improve their ability to use their remaining vision more effectively Results The contact lenses immediately resolved the aversion to light, with dramatic improvement in visual function in all patients (determined by observation of the patient and by patient report). It allowed eight patients to become eligible to drive. Conclusions Red contact lenses successfully alleviate photophobia in patients with cone disorders.

Purpose We explored the clinical impression that geographic atrophy of the retinal pigment epithelium, a form of advanced age-related macular degeneration, is perceived by the patient as progressing gradually, even when fixation switches from foveal to extrafoveal. Methods We analyzed the responses of 60 patients with geographic atrophy to a questionnaire administered as part of a five-year study of the natural course of geographic atrophy, funded by the National Eye Institute. We performed scanning laser ophthalmoscope perimetry on all patients. We examined two additional patients with geographic atrophy who reported abrupt visual loss. Results No eye with geographic atrophy was reported by any patient to have had sudden visual loss. Although most patients with geographic atrophy show foveal fixation until the fovea is atrophic and then show extrafoveal fixation, scanning laser ophthalmoscope perimetry in three patients with geographic atrophy showed alternation between a foveal and an extrafoveal retinal locus for fixation. Two patients with geographic atrophy who complained of abrupt visual loss were found to have occult choroidal neovascularization, which evolved in one patient to classic choroidal neovascularization. The neovascularization was difficult to detect because of the presence of geographic atrophy and its associated ophthalmoscopic and fluorescein angiographic features. Conclusions Visual loss in geographic atrophy is nearly always perceived by the patient as being gradual, even when considerable decreases in visual acuity occur and when foveal vision and fixation are lost. A possible explanation for this perception is that there is a transitional period during which a patient uses both a foveal and extrafoveal site for fixation. The complaint of abrupt visual loss in a patient with geographic atrophy should raise the suspicion of choroidal neovascularization, which may be occult and difficult to detect.

OBJECTIVE: To characterize the traits of low vision patients who seek outpatient low vision rehabilitation (LVR) services in the United States. METHODS: In a prospective observational study, we enrolled 764 new low vision patients seeking outpatient LVR services from 28 clinical centers in the United States. Before their initial appointment, multiple questionnaires assessing daily living and vision, physical, psychological, and cognitive health states were administered by telephone. Baseline clinical visual impairment measures and disorder diagnoses were recorded. RESULTS: Patients had a median age of 77 years, were primarily female (66%), and had macular disease (55%), most of which was nonneovascular age-related macular degeneration. More than one-third of the patients (37%) had mild vision impairment with habitual visual acuity (VA) of 20/60 or greater. The VA correlated well with contrast sensitivity (r=−0.52) but poorly with self-reported vision quality. The intake survey revealed self-reported physical health limitations, including decreased endurance (68%) and mobility problems (52%). Many patients reported increased levels of frustration (42%) and depressed mood (22%); memory and cognitive impairment (11%) were less frequently endorsed. Patients relied on others for daily living support (87%), but many (31%) still drove. CONCLUSIONS: Most patients seeking LVR are geriatric and have macular disease with relatively preserved VA. The disparity between VA and subjective quality of vision suggests that LVR referrals are based on symptoms rather than on VA alone. Patients seen for LVR services have significant physical, psychological, and cognitive disorders that can amplify vision disabilities and decrease rehabilitation potential.

• We describe two patients with spontaneous retinal pigment epithelial tears through the fovea who have maintained at least 20/40 visual acuity for 1 year and 3 years following the rip. Both patients had long-standing serous detachments of the retinal pigment epithelium associated with age-related macular degeneration prior to the development of the tear. Each tear was at least five disc areas in size and centered on the fovea. Foveal fixation was documented despite the presumed absence of pigment epithelium. This observation suggests either that there may be remaining or redundant pigment epithelium or that pigment epithelium directly beneath the central macula is not required for maintenance of 20/40 visual acuity.

A posterior staphyloma is characterised by scleral ectasia and is pathognomonic for pathological myopia.1,2 Posterior staphylomas are classified in to five types based on the anatomic location.1 Type 1 staphylomas extend from the nasal border of the optic nerve into the macular region and are the most frequent staphyloma seen in myopes.1 Type 2 staphylomas are centred on the macula while type 3 staphylomas are centred on the optic disc without macular extension.1 Type 4 staphylomas are located nasal to the optic disc and type 5 staphylomas develop inferior to the optic disc.1 Staphylomas can be associated with multiple complications including retinal pigment epithelial atrophy, lacquer cracks, retinal and subretinal haemorrhages, and choroidal neovascularisation.1,3 This report describes a patient with undiagnosed, bilateral type 2 macular staphylomas compounded by cone dystrophy. To the best of our knowledge, this is a novel association not reported in the literature and with potential therapeutic implications. A 32 year old white woman presented to the Wilmer Ophthalmological Institute, Baltimore, MD, for a second opinion. She …

Background: Leber congenital amaurosis (LCA) is an infrequently encountered congenital form of retinitis pigmentosa with marked genetic and clinical heterogeneity. Thus far, 10 genes have been identified in this disorder since 1996. In the future, LCA may become treatable by gene and/or pharmacological intervention, and these therapies will likely be gene specific, giving major significance to rapid gene identification and genephenotype studies. Objective: To test the hypothesis that parents of patients with LCA have identifiable electroretinographic and psychophysical changes. Subjects, Materials, and Methods: Complete eye examinations and electroretinographic studies were performed on 2 sets of parents whose offspring were diagnosed as having LCA and who were found to carry a mutation in 1 of the 10 LCA genes - GUCY2D. One set of parents also underwent static perimetry threshold measurements. Results: We found that single flash-light-adapted a- and b-wave amplitudes, 30-Hz flicker, or both cone signals were significantly decreased in amplitude in 4 heterozygotes, while 2 parents showed delayed 30-Hz flicker implicit times. Electroretinographic rod-mediated signals were normal in 2 of the heterozygotes, but subnormal in 2. Static perimetry testing showed normal thresholds in the 2 heterozygotes tested. Main Outcome Measures: Single flash-light-adapted a- and b- wave amplitudes and implicit times, 30- or 32-Hz flicker amplitudes and implicit times, rod-mediated signals, and dark-adapted, rod-mediated thresholds. Conclusions: Some carrier parents of patients with LCA and a GUCY2D mutation develop measurable, cone and possibly rod abnormalities most consistent with a mild conerod dysfunction. This correlates well with the known retinal expression pattern of GUCY2D, which is considerably higher in cone compared with rod photoreceptor cells.

PURPOSE To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

The effects of pregnancy on the eye fall into three categories. Nonpathological physiologic changes in pressures, corneal sensitivity and thickness, and visual function can occur. Pathologic conditions reported to develop during pregnancy include central serous chorioretinopathy, hypertensive and vascular disorders, and uveal melanoma. Pregnancy also can affect pre-existing ocular conditions, such as diabetic retinopathy, tumors, and a variety of immunological disorders and can have beneficial effects on such pre-existing conditions as glaucoma. This review covers ocular disorders in these three categories, and summarizes the systemic changes of pregnancy and the effects of ocular medications on the fetus.