Lateral gain is impaired in macular degeneration and can be targeted to restore vision in mice.

Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3-/- mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.

Visual and medical risk factors for motor vehicle collision involvement among older drivers.

AIMS: To identify visual and medical risk factors for motor vehicle collisions (MVCs). METHODS: Data from four cohorts of older drivers from three states were pooled (n = 3158). Health information was collected at baseline, and MVC data were obtained prospectively. Cox proportional hazards regression was used to estimate rate ratios (RRs) and 95% CIs for associations between medical characteristics and MVCs. RESULTS: A total of 363 MVCs were observed during the study period (1990-1997), of which 145 were at fault, and 62 were injurious. Falls and impaired useful field of view (UFOV) were positively associated with overall MVCs. At-fault MVCs were also positively associated with falls and UFOV impairment, and inversely with cancer. Injurious MVCs were positively associated with arthritis and neurological disease, and inversely with hypertension. CONCLUSIONS: These findings show similarities and differences across the risk factors for all, at-fault and injurious MVCs, and point to the need for verification and possible interventions.

The effect of retinal image slip on peripheral visual acuity.

Retinal image slip promoted by fixational eye movements prevents image fading in central vision. However, in the periphery a higher amount of movement is necessary to prevent this fading. We assessed the effect of different levels of retinal image slip in peripheral vision by measuring peripheral visual acuity (VA), with and without crowding, while modulating retinal image slip by using gaze-linked stimuli. Measurements were carried out at four isoeccentric positions at 5 and at 10 degrees eccentricity. Gaze position was monitored throughout using an infrared eyetracker. The target was presented for up to 500 msec, either with no retinal image slip, with reduced retinal slip, or with increased retinal image slip. Without crowding, peripheral visual acuity improved with increased retinal image slip compared with the other two conditions. In contrast to the previous result, under crowded conditions, peripheral visual acuity decreased markedly with increased retinal image slip. Therefore, the effects of increased retinal image slip are different for simple (noncrowded) and more complex (crowded) visual tasks. These results provide further evidence for the importance of fixation stability on complex visual tasks when using the peripheral retina.

Visual function and quality of life following vitrectomy and epiretinal membrane peel surgery.

AIM: To investigate the effect of epiretinal membrane (ERM) peel on patients' health related quality of life (HR-QOL) and to explore the association between self reported HR-QOL and conventional measures of visual function. METHODS: The National Eye Institute 25 Item Visual Function Questionnaire (VFQ-25) and the 36 Item Short-Form Health Survey (SF-36) were self administered by 20 patients before and 4 months following surgery. Preoperative and postoperative data collected included logMAR near and distant visual acuity (VA), contrast sensitivity, and metamorphopsia. Questionnaire scores were compared preoperatively and postoperatively and their correlation with traditional methods of visual function evaluation analysed. RESULTS: Postoperatively there was no significant improvement in mean logMAR VA. However, eight (40%) subjects improved by two or more ETDRS lines and nine eyes (45%) reached a final VA of 6/18 or better. Metamorphopsia decreased significantly (p = 0.019) and there was significant improvement in VFQ-25 mean scores for the general vision (p = 0.03), distance activities (p = 0.05), and composite score (p = 0.03). Baseline binocular VA was significantly correlated with baseline VFQ-25 composite score (r = 0.631, p = 0.004). CONCLUSIONS: ERM surgery appears to improve patients' subjective perception of visual function as indicated by higher composite scores in VFQ-25 and improved metamorphopsia in the absence of significant improvement in mean logMAR VA.

Contrast sensitivity as an outcome measure in patients with subfoveal choroidal neovascularisation due to age-related macular degeneration.

PURPOSE: Although visual acuity is the most frequently used primary outcome measure in clinical trials of treatments for choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD), contrast sensitivity may provide valuable additional information. This paper reviews the evidence for using contrast sensitivity as a measure of visual function and as an outcome measure in clinical trials in patients with subfoveal CNV due to AMD. METHODS: Medline database searches were performed to retrieve relevant articles on contrast sensitivity. In addition, articles were included from the authors' knowledge of the literature and from the reference lists of retrieved articles. RESULTS: The published literature demonstrates that contrast sensitivity is an important measure of visual function in patients with subfoveal CNV due to AMD. Most clinical trials of treatments for CNV due to AMD have reported visual acuity as the primary outcome. However, there is evidence that treatment (such as verteporfin therapy) may also provide additional benefits in terms of contrast sensitivity. These benefits may not be completely characterised by measurement of visual acuity alone. CONCLUSIONS: The inclusion of contrast sensitivity as an outcome measure in studies of patients with CNV due to AMD may provide a more complete understanding of the effects of treatment on visual function and the likely benefits for patients.

Evaluation of a new quantitative technique to assess the number and extent of preferred retinal loci in macular disease.

Patients with scotomas due to macular disease may use more than one preferred retinal locus (PRL) for fixation. We have developed and evaluated an objective, quantitative technique to determine the number of PRLs used during an episode of fixation and the extent of each locus. In five of eight adults with macular disease our techniques consistently indicated the presence of multiple PRLs. Patients with multiple PRLs were more likely to have suffered recent vision loss in the tested eye. Our technique describes fixation more fully than the traditional method of calculating a single bivariate contour ellipse area.

Fundus autofluorescence imaging compared with different confocal scanning laser ophthalmoscopes.

BACKGROUND: With the advent of confocal scanning laser ophthalmoscopes (cSLO), fundus autofluorescence (FAF) resulting mainly from lipofuscin accumulation on the level of the retinal pigment epithelium can be visualised in vivo. Various cSLOs are available to document FAF. The authors analysed and compared results of FAF using three different instruments. METHODS: Eight eyes of eight normal volunteers and 18 eyes of 12 patients with different retinal diseases (age related macular degeneration, macular dystrophy, central serous retinopathy) were examined. FAF images were recorded from each subject with the Heidelberg retina angiograph (HRA), the Rodenstock cSLO (RcSLO) and the Zeiss Prototype SM 30-4024 (ZcSLO). For excitation an argon laser (488 nm) was used (barrier filter: HRA 500 nm; RcSLO 515 nm; ZcSLO 521 nm). 32 FAF images were aligned and averaged using the same software for all cSLOs. FAF distribution was measured and grey scale values as well as root mean square (RMS) contrast were compared. RESULTS: Mean age of all subjects was 55.5 (SD 21.4) years. The maximum grey scale value averaged across all eyes was 76.19 (39.34) for the HRA, 61.44 (22.12) for the ZcSLO and 37.0 (9.97) for the RcSLO. The RMS contrast was 0.46 (0.20) for the ZcSLO, 0.40 (0.12) for the HRA, and 0.13 (0.05) for the RcSLO. The differences between the cSLOs were statistically significant with higher grey scale levels and more contrast for the HRA and ZcSLO than the RcSLO (repeated measures ANOVA; p<0.0001). The differences between the HRA and the ZcSLO were not significant (post hoc comparisons; p<0.05). CONCLUSIONS: All cSLOs allow clinically useful FAF imaging in retinal diseases. However, grey scale levels and contrast were much lower on the RcSLO. Therefore, RcSLO images appear much darker than HRA or ZcSLO images. Furthermore, not all cSLOs have a fixed photodetector gain and a standardised value for the argon laser amplification, which is mandatory for an absolute comparison of FAF imaging results.

Visual function assessment questionnaires.

With increased emphasis on functional outcomes in ophthalmology, third-party health care payers and research funding agencies have turned their attention to the development and use of visual function questionnaires. Since 1980, more than a dozen such self-report visual function questionnaires have been developed. All of these instruments include items that ask about specific daily activities; patients must respond with a rating that represents the level of difficulty that they experience with the activity described. This article reviews all of the known instruments, with special attention paid to their validity and reliability. Most validation studies have reported high response consistency across items and significant correlations of instrument scores with visual impairment measures. Only two studies have measured test-retest reliability. The developers of visual function questionnaires typically divide the items into several different subscales, suggesting that different variables are being measured. Although the items are very similar for the different instruments, there is little agreement among instruments on the definition of subscales. All instruments are scored as the average of the ordinal patient ratings across items for each subscale and/or for the total instrument. Measurement issues underlying the scoring of ordinal patient ratings are discussed. It is argued that unless the instruments can be converted to interval scales, the averaging of patient ratings does not yield true measurements. The three visual function questionnaires that were calibrated with a statistical item response model, which estimates interval scales, are reviewed. It is concluded that future research and development should devote additional attention to the measurement properties of functional assessment instruments.

The association of multiple visual impairments with self-reported visual disability: SEE project.

PURPOSE: This report examines the relationship between psychophysical measures of visual impairment and self-reported difficulty with everyday visual tasks in a population-based sample of individuals 65 years of age and older. METHODS: Community-dwelling residents (n = 2520) of Salisbury, MD, between the ages of 65 and 84 were recruited for the study. Visual acuity under normal and low luminance, contrast and glare sensitivity, stereoacuity, and visual fields were measured. Subjective physical disability was assessed with the Activities of Daily Vision Scale (ADVS). RESULTS: In multiple regression analyses adjusted for demographic factors, cognitive status, depression, and number of comorbid medical conditions, each of the vision tests except low luminance acuity was independently associated with lower ADVS scores. The analyses indicate that a factor of 2 reduction in visual acuity or contrast sensitivity, comparable with that observed in mild to moderate lens opacity, was associated with a three- to fivefold odds of reporting difficulty with daily tasks. Although age alone was a significant risk factor for disability, it was not associated with overall ADVS score, once visual impairment and other chronic medical conditions were taken into account. CONCLUSIONS: Visual acuity, contrast and glare sensitivity, stereoacuity, and visual fields are significant independent risk factors for self-reported visual disability in an older population. Visual impairment defined by acuity alone is not the only dimension of the association with subjective disability. Additional vision measures are required to understand the impact of vision loss on everyday life.

Monocular versus binocular visual acuity as measures of vision impairment and predictors of visual disability.

PURPOSE: To examine the relationship between monocular and binocular visual acuities as predictors of visual disability in a population-based sample of individuals 65 years of age and older. METHODS: Two thousand five hundred twenty community-dwelling residents of Salisbury, Maryland, between the ages of 65 and 84 years of age were recruited for the study. Corrected visual acuity was measured monocularly and binocularly using ETDRS charts. Reading speed, face discrimination, and self-reported difficulty with visual tasks were also determined. RESULTS: Binocular acuity is predicted with reasonable accuracy by acuity in the better eye alone, but not by the widely used American Medical Association (AMA) weighted-average algorithm. The AMA algorithm significantly underestimates binocular acuity when the interocular acuity difference exceeds one line. Monocular acuity and binocular acuity were significantly better predictors of reading speed than the AMA weighted score or a recently proposed Functional Vision Score (FVS). Monocular acuity in the better eye, binocular acuity, and the AMA and FVS algorithms were equally good predictors of self-reported vision disability. None of the acuity measures were good predictors of face recognition ability. CONCLUSIONS: The binocular acuities of older individuals can be inferred from measures of monocular acuity. There is little evidence for binocular inhibition when the monocular acuities in the two eyes are unequal, as opposed to the widely used AMA algorithm for computing binocular visual impairment. For tasks that are strongly associated with visual acuity, such as reading, this association can be captured from measures of monocular acuity and does not require separate assessment of binocular acuity.

Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study.

OBJECTIVE: To determine the causes of blindness and visual impairment in a population-based sample of older Americans. METHODS: A random sample of 3821 residents of Salisbury, Md, between the ages of 65 and 84 years was identified from Medicare records. Sixty-six percent (2520 persons) agreed to undergo an eye examination; 26% of the participants were African American. The clinical examination included acuity testing with an Early Treatment Diabetic Retinopathy Study chart and standardized refraction testing for those with a visual acuity worse than 20/30, slitlamp and dilated retinal examination by an ophthalmologist, tonometry, lens and fundus photography, and a suprathreshold visual field test. Visual impairment was defined as a best-corrected acuity in the better-seeing eye worse than 20/40 and better than 20/200, while blindness was acuity in the better-seeing eye of 20/200 or worse. For those with a visual acuity worse than 20/40 in either eye, one or more causes were assigned by an ophthalmologist and a final cause for each eye was confirmed by a panel of 3 subspecialty ophthalmologists (O.D.S., H.A.Q., and S.B.B.) based on all available evidence. RESULTS: Bilateral presenting acuity worse than 20/40 increased from 4% in the 65- to 74-year age group to 16% in the 80- to 84-year age group. One third of those with presenting acuity worse than 20/40 improved to 20/40 or better with refraction. Overall, 4.5% had a best-corrected acuity worse than 20/40. African Americans were more likely to remain visually impaired than were whites despite refraction (odds ratio [95% confidence interval], 1.7 [1.1-2.6]). Whites were most often impaired or blind from age-related macular degeneration (1.2% vs 0.5%; P=.09). African Americans had higher rates of impairment and blindness from cataract or posterior capsular opacification (2.7% vs 1.1%; P=.006), glaucoma (0.9% vs 0.1%; P=.006), and diabetic retinopathy (1.2% vs 0.2%; P=. 004). CONCLUSIONS: More than half of those with visual impairment or blindness had conditions that were either surgically treatable or potentially preventable. African Americans had a disproportionate number of blinding diseases, particularly those amenable to eye care intervention. Targeted interventions for specific populations to increase appropriate eye care use would greatly improve vision and function in older Americans. Arch Ophthalmol. 2000;118:819-825

Mixed lens opacities and subsequent mortality.

BACKGROUND: Previous studies have found an association between cataract or lens opacity and increased risk of mortality. Further work on determining explanatory factors for this association is needed. OBJECTIVES: To determine, in a population-based cohort of older persons, the 2-year risk of death associated with different types of lens opacities; whether an association of mortality and lens opacity is explained by confounding risk factors such as smoking, diabetes, age, race, and sex, which are known to be related to opacity and mortality; whether lens opacity is a marker for health status; and whether there are differences in cause-specific mortality for persons with and without lens opacity. MAIN OUTCOME MEASURE: Two-year mortality rate. METHODS: The Salisbury Eye Evaluation Project consists of a random sample of 2520 residents of Salisbury, Md, aged 65 to 84 years. At baseline, lens photographs were taken to document nuclear, cortical, posterior subcapsular cataract, and mixed opacities. Data on education, smoking, alcohol use, hypertension, diabetes and other comorbid conditions, handgrip strength, and body mass index were also collected. Two-year follow-up was conducted for mortality and cause of death. RESULTS: Nuclear opacity, particularly severe nuclear opacity, and mixed opacities with nuclear were significant predictors of mortality independent of body mass index, comorbid conditions, smoking, age, race, and sex (mixed nuclear: odds ratio, 2.23; 95% confidence interval, 1.26-3.95). CONCLUSION: Lens opacity status is an independent predictor of 2-year mortality, an association that could not be explained by potential confounders.

Reading with eccentric fixation is faster in inferior visual field than in left visual field.

PURPOSE: People with central field loss tend to fixate so that information falls in the inferior or left visual field. Studies of reading from a page of text suggest that using inferior field is advantageous relative to using left visual field. In this study, we investigated whether reading without eye movements in normal peripheral vision is better when text is presented in inferior or left visual field. METHODS: Reading rates were determined for retinally stabilized rapid serial visual presentation sentences of seven letter sizes, presented at 5 degrees in inferior and left visual field of six normal observers. RESULTS: When print size is appropriately magnified for peripheral viewing, reading speed in inferior field is faster than in left visual field. There is no significant difference between inferior and left visual field in the print size required to reach maximum reading speed. CONCLUSIONS: For reading tasks not involving eye movements, there is an advantage in eccentrically fixating such that text falls in inferior rather than left visual field.

Determination of risk factor associations with questionnaire outcomes: a methods case study.

Increasingly in biomedical studies, health status is inferred through a series of questionnaire item responses. Challenges for analyzing associations between such responses and risk factors include multiplicity-many indicators must be combined to derive summary statements about health status, and measurement error-persons' self-report fluctuates due to causes other than substantive health changes. In order to deal with these challenges, the authors propose a strategy which comprises three methods: 1) score the item responses, then regress the score on predictors; 2) regress each item response on predictors, accounting for within-person associations; and 3) summarize and analyze the item responses jointly, using a latent variable model. The authors develop modeling and diagnostic procedures for method 3. They then show how the three-method analytic strategy can be used to solve the problem of determining which aspects of vision are associated with self-reported functioning in activities that require seeing at a distance. They demonstrate that methods 2 and 3 illuminate basic findings from method 1 by adding specificity, describing patterns as well as severities of health impairments, and identifying isolated items that relate to risk factors differentially than others. They conclude that the three-method strategy specifies how risk factors determine questionnaire-based health outcomes substantially better than any of the methods in isolation.

Are the benefits of sentence context different in central and peripheral vision?

BACKGROUND: Sentence context increases reading speed relative to reading unrelated words. Previous studies of normal peripheral retina and in patients with central field loss (CFL) have come to different conclusions regarding the benefits of sentence context for reading in peripheral retina. Studies of normal peripheral vision presented the text to inferior visual field; it is presumed that most of the patients fixated using retina lateral to their scotoma. The goal of the current study was to determine whether the location of the text on the retina interacts with the usefulness of sentence context. METHODS: Normally sighted subjects read sentences and random lists of words presented at the fovea and at 50 to the left of and 50 inferior to fixation in visual field space. Texts were presented using rapid serial visual presentation (RSVP). RESULTS: The ratio of reading rates for sentences to random words (context gain) was the same in the inferior field (2.7 +/- 0.20) and at the fovea (2.6 +/- 0.26); context gain was greater in the left field (7.2 +/- 1.22). CONCLUSIONS: Sentence context increases reading speed regardless of the position of the text on the retina. Reading rates in peripheral retina are not decreased because of an inability to use sentence context.

Mobility performance in glaucoma.

PURPOSE: To determine whether glaucoma affects mobility performance and whether there is a relationship between mobility performance and stage of disease as estimated from vision-function measures. METHODS: The mobility performance of 47 glaucoma subjects was compared with that of 47 normal-vision subjects who were of similar age. Mobility performance was assessed by the time required to complete an established travel path and the number of mobility incidents. The subjective assessment of falling and fear of falling were also compared. Vision function was assessed by measures of visual acuity, contrast sensitivity, monocular automated threshold perimetry, and suprathreshold; binocular visual fields were assessed with the Esterman test. RESULTS: The glaucoma subjects walked on average 10% more slowly than did the normal-vision subjects. The number of people who experienced bumps, stumbles, or orientation problems was almost twice as high in the glaucoma group than the normal-vision group, but the difference did not reach statistical significance. The difference between groups also was not significant with respect to the number of people who reported falling in the past year (38% for the glaucoma group and 30% for the normal-vision group) or a fear of falling (28% for the glaucoma group and 23% for the normal-vision group). The visual fields assessed with a Humphrey 24-2 test were more highly correlated with walking speed in glaucoma than the visual fields scored by the Esterman scale or than visual acuity or contrast sensitivity. CONCLUSIONS: Glaucoma is associated with a modest decrease in mobility performance. Walking speed decreases with severity of the disease as estimated by threshold perimetry.