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Gary S. Rubin

Bio: Gary S. Rubin is an academic researcher from University College London. The author has contributed to research in topics: Visual acuity & Macular degeneration. The author has an hindex of 72, co-authored 287 publications receiving 18905 citations. Previous affiliations of Gary S. Rubin include Johns Hopkins University School of Medicine & National Institutes of Health.


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Journal ArticleDOI
TL;DR: Three young adult patients with early-onset, severe retinal dystrophy were administered subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human R PE65 promoter.
Abstract: Early-onset, severe retinal dystrophy caused by mutations in the gene encoding reti- nal pigment epithelium-specific 65-kDa protein (RPE65) is associated with poor vi- sion at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Gold- mann perimetry in any of the three patients. We detected no change in retinal re- sponses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)

1,912 citations

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TL;DR: The objective was to determine the temporal relationship between falls and fear of falling, and to see whether these two outcomes share predictors.
Abstract: OBJECTIVES: Previous cross-sectional studies have shown a correlation between falls and fear of falling, but it is unclear which comes first. Our objectives were to determine the temporal relationship between falls and fear of falling, and to see whether these two outcomes share predictors. DESIGN: A 20-month, population-based, prospective, observational study. SETTING: Salisbury, Maryland. Each evaluation consisted of a home-administered questionnaire, followed by a 4- to 5-hour clinic evaluation. PARTICIPANTS: The 2,212 participants in the Salisbury Eye Evaluation project who had baseline and 20-month follow-up clinic evaluations. At baseline, subjects were aged 65 to 84 and community dwelling and had a Mini-Mental State Examination score of 18 or higher. MEASUREMENTS: Demographics, visual function, comorbidities, neuropsychiatric status, medication use, and physical performance–based measures were assessed. Stepwise logistic regression analyses were performed to evaluate independent predictors of falls and fear of falling at the follow-up evaluation, first predicting incident outcomes and then predicting fall or fear-of-falling status at 20 months with baseline falling and fear of falling as predictors. RESULTS: Falls at baseline were an independent predictor of developing fear of falling 20 months later (odds ratio (OR) = 1.75; P < .0005), and fear of falling at baseline was a predictor of falling at 20 months (OR = 1.79; P < .0005). Women with a history of stroke were at risk of falls and fear of falling at follow-up. In addition, Parkinson's disease, comorbidity, and white race predicted falls, whereas General Health Questionnaire score, age, and taking four or more medications predicted fear of falling. CONCLUSION: Individuals who develop one of these outcomes are at risk for developing the other, with a resulting spiraling risk of falls, fear of falling, and functional decline. Because falls and fear of falling share predictors, individuals who are at a high risk of developing these endpoints can be identified.

956 citations

Journal ArticleDOI
TL;DR: In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG, and comparison with the results obtained in the dog model indicates that there is a species difference in the amount of R PE65 required to drive the visual cycle.
Abstract: BackgroundMutations in RPE65 cause Leber’s congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. MethodsWe performed a phase 1–2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. ResultsImprovements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was d...

599 citations

Journal ArticleDOI
TL;DR: The results provide estimates of the stimulus parameters required for optimal reading of scanned text by measuring reading rates for text scanned across the face of a TV monitor while varying parameters that are important in current theories of pattern vision.

580 citations

Journal ArticleDOI
TL;DR: In this article, the causes of blindness and visual impairment in a population-based sample of older Americans were identified from Medicare records and a panel of three subspecialty ophthalmologists (O.D.S., H.A.Q., and S.B.B.) based on all available evidence.
Abstract: 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.

505 citations


Cited by
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TL;DR: The basic theme of the review is that eye movement data reflect moment-to-moment cognitive processes in the various tasks examined.
Abstract: Recent studies of eye movements in reading and other information processing tasks, such as music reading, typing, visual search, and scene perception, are reviewed. The major emphasis of the review is on reading as a specific example of cognitive processing. Basic topics discussed with respect to reading are (a) the characteristics of eye movements, (b) the perceptual span, (c) integration of information across saccades, (d) eye movement control, and (e) individual differences (including dyslexia). Similar topics are discussed with respect to the other tasks examined. The basic theme of the review is that eye movement data reflect moment-to-moment cognitive processes in the various tasks examined. Theoretical and practical considerations concerning the use of eye movement data are also discussed.

6,656 citations

Journal Article
TL;DR: Prospect Theory led cognitive psychology in a new direction that began to uncover other human biases in thinking that are probably not learned but are part of the authors' brain’s wiring.
Abstract: In 1974 an article appeared in Science magazine with the dry-sounding title “Judgment Under Uncertainty: Heuristics and Biases” by a pair of psychologists who were not well known outside their discipline of decision theory. In it Amos Tversky and Daniel Kahneman introduced the world to Prospect Theory, which mapped out how humans actually behave when faced with decisions about gains and losses, in contrast to how economists assumed that people behave. Prospect Theory turned Economics on its head by demonstrating through a series of ingenious experiments that people are much more concerned with losses than they are with gains, and that framing a choice from one perspective or the other will result in decisions that are exactly the opposite of each other, even if the outcomes are monetarily the same. Prospect Theory led cognitive psychology in a new direction that began to uncover other human biases in thinking that are probably not learned but are part of our brain’s wiring.

4,351 citations

Journal ArticleDOI
TL;DR: Among nondisabled older persons living in the community, objective measures of lower-extremity function were highly predictive of subsequent disability.
Abstract: Background Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons. Methods This prospective cohort study included men and women 71 years of age or older who were living in the community, who reported no disability in the activities of daily living, and who reported that they were able to walk one-half mile (0.8 km) and climb stairs without assistance. The subjects completed a short battery of physical-performance tests and participated in a follow-up interview four years later. The tests included an assessment of standing balance, a timed 8-ft (2.4-m) walk at a normal pace, and a timed test of five repetitions of rising from a chair and sitting down. Results Among the 1122 subjects who were not disabled at base line and who participated in the four-year follow-up, lower scores on the base-line performance tests were associated with a statisticall...

3,388 citations

Journal ArticleDOI
TL;DR: The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.
Abstract: Objectives To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. Methods Summary prevalence estimates of blindness (both according to the US definition of Results Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. Conclusions Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.

2,446 citations