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Purpose: To evaluate the epidemiologic association between visual acuity and other measures of visual function and motor vehicle collisions (MVCs) as well as their performance as screening tests for MVCs., Design: Prospective cohort study., Participants: A total of 2000 licensed drivers aged 70 years and older who resided in the environs of Jefferson County, Alabama., Methods: Visual acuity, contrast sensitivity, useful field of view, Motor-free Visual Perception Test, and visual field sensitivity were measured at a baseline visit. Study participants were followed for up to 4 years for the occurrence of MVC involvement. Area under the curve (AUC), sensitivity, and specificity were calculated to determine the screening performance of each visual function measure with respect to MVC occurrence. Poisson regression was used to estimate rate ratios (RRs) for the association between each visual function measure and MVC occurrence., Main Outcome Measures: Police-reported MVCs., Results: For all visual function measures, the AUC values were only slightly higher than 0.50; additionally, none of the measures exhibited adequate values for both sensitivity and specificity (i.e., > 80%). For all visual function measures except visual acuity, there were statistically significant positive RRs for the association between vision impairment and MVC occurrence, although the magnitude of the associations was weak (i.e., < 2.0)., Conclusions: The negative impact of involuntary driving cessation on mobility and the associated mental health implications likely outweigh the safety benefit of vision screening. Alternative approaches to improving older driver safety should be considered., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD) and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD., Design: Cross-sectional., Participants: Adults 60 years of age or older showing normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease Study 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9)., Methods: Single nucleotide polymorphisms were genotyped in the complement factor H (CFH) and ARMS2 genes using a Taqman assay. Rod-mediated dark adaptation was assessed in 1 eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (in minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking., Main Outcome Measure: Rod intercept time., Results: The sample consisted of 543 participants having both genotype and RIT determination; 408 showed normal macular health and 135 demonstrated AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted P = 0.0001 and P = 0.0023, respectively). For healthy participants, the A69S variant in ARMS2 was associated with higher RIT (adjusted P = 0.0011), whereas the Y402H variant in CFH was not (adjusted P = 0.2175). For AMD patients, the A69S variant of ARMS2 and the Y402H variant of CFH were associated with higher RIT (adjusted P = 0.0182 and P = 0.0222, respectively). Those with a larger number of high-risk ARMS2 and CFH alleles showed higher RIT, in both healthy and AMD groups (adjusted P = 0.0002 and P < 0.0001, respectively)., Conclusions: We report a novel association wherein older adults with high-risk ARMS2 and CFH genotypes are more likely to demonstrate delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those showing normal macular health with the ARMS2 A69S allele demonstrate delayed RMDA. Understanding ARMS2 function is a research priority., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging., Design: Cross-sectional study., Participants: A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics., Methods: Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes., Main Outcome Measures: Prevalence of SDD in participants with and without AMD., Results: Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume., Conclusions: Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later., Design: Prospective cohort., Participants: Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators., Methods: Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD., Main Outcome Measures: Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline., Results: Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline., Conclusions: Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, 2 tissues with prominent age- and AMD-related pathology., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found., Design: A retrospective, population-based study., Participants: A sample of 2000 licensed drivers aged ≥70 years who reside in north central Alabama., Methods: At-fault MVC involvement over the 5 years before enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity (CS), and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RRs) and 95% confidence intervals (CIs)., Main Outcomes Measures: At-fault MVC involvement over the 5 years before enrollment., Results: Drivers with glaucoma (n = 206) had a 1.65 times higher MVC rate (95% CI, 1.20-2.28; P = 0.002) compared with those without glaucoma after adjusting for age, and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR, 2.11; 95% CI, 1.09-4.09; P = 0.027), whereas no association was found among those with impaired visual acuity and CS. When the visual field was subdivided into 6 regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper, or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (3.16; P = 0.001) compared with other regions. However, no association was found in deficits in the right side or along the horizontal or vertical meridian., Conclusions: A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma seems to have an independent association with at-fault MVC involvement, whereas visual acuity and CS impairments do not., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression., Design: Experimental study., Participants and Controls: Ten GA donor eyes (mean age ± standard deviation, 87.1 ± 4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0 ± 7.2 years) without GA., Methods: The 10-micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch's membrane at 0.2-μm intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF])., Main Outcome Measures: Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes., Results: The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades., Conclusions: Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of age and race on optic disc, retinal nerve fiber layer (RNFL), and macular measurements with spectral-domain optical coherence tomography (SD OCT)., Design: Cross-sectional observational study., Participants: Three hundred fifty adult subjects without ocular disease., Methods: Data from SD OCT imaging of the optic nerve head, peripapillary RNFL, and macula of 632 eyes from 350 subjects without ocular disease were imaged with SD OCT. Multivariate models were used to determine the effect of age and race on quantitative measurements of optic disc, RNFL, and macula., Main Outcome Measures: Optic nerve, RNFL, and macular measurements with SD OCT across racial strata and age., Results: For optic nerve parameters, participants of European descent had significantly smaller optic disc area than other groups (P<0.0001), and Indian participants had significantly smaller rim area than other groups (P<0.0001). Indian and Hispanic participants had thicker global RNFL measurements than other groups (P<0.0001). Participants of African descent were associated with thinner inner retinal thickness in the macula (P<0.0001). Age was associated with several parameters, with rim area reducing by 0.005 mm(2)/year, RNFL thickness reducing by 0.18 μm/year, and inner retinal thickness reducing by 0.1 μm/year (P<0.0001 for all age associations)., Conclusions: Optic nerve, RNFL, and macular measurements with SD OCT all varied across racial groups and with age. These differences are important in defining the range of normal variation in differing populations and should be considered in the use of these instruments in the detection of optic nerve and macular disease across these population groups., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine impairment in cone- versus rod-mediated dark adaptation in the parafovea of persons with age-related maculopathy (ARM)., Design: Cross-sectional., Participants: Older adults with ARM at various severity levels from early to advanced (n = 83) and in good retinal health (n = 43), as determined by stereo fundus photographs evaluated with the Age-Related Eye Disease Study severity scale., Methods: Dark adaptation, both cone- and rod-mediated components, was measured with a modified Humphrey Field Analyzer using a target located 12 degrees in the inferior visual field on the vertical meridian, after exposure to a 98% bleach. Information was collected on self-reported problems for activities at night or under dim illumination (Low Luminance Questionnaire [LLQ]) and for activities during daytime conditions (modified National Eye Institute Visual Function Questionnaire [NEI VFQ])., Main Outcome Measures: Cone- and rod-mediated parameters of dark adaptation., Results: Compared with older adults in normal retinal health, ARM patients had significant impairments in rod-mediated parameters of dark adaptation (rod-cone break, rod slope, rod sensitivity) (P<0.0001), which were increasingly abnormal as disease severity increased. Cone-mediated parameters (cone time constant and cone sensitivity) were not impaired. Low Luminance Questionnaire scores and NEI VFQ scores decreased with increased ARM severity (P = 0.0004 and P = 0.0005, respectively); the percent decrease in LLQ scores as a function of disease severity was larger in magnitude than the percent decrease in NEI VFQ scores., Conclusions: Disturbances in rod-mediated but not cone-mediated dark adaptation in the parafovea at 12 degrees in the inferior field on the vertical meridian are characteristic of ARM even in its early phases.

Purpose: To evaluate the association between cholesterol-lowering medications and age-related macular degeneration (AMD)., Design: Case-control study., Participants: The Atherosclerosis Risk in Communities study is a prospective, population-based, cohort study conducted in 4 communities across the United States. A total of 15792 individuals aged 45 to 65 years were enrolled between 1987 and 1989; fundus photographs were added to the study protocol at the 6-year follow-up (1993-1995). Cases were subjects who were identified as having AMD after applying a standard definition to their fundus photographs; controls did not have AMD., Methods: The use of cholesterol-lowering medications at any time during the study was determined and compared between cases and controls, adjusting for the potentially confounding effect of demographic, behavioral, and medical characteristics., Main Outcome Measures: Presence of AMD and the use of cholesterol-lowering medications., Results: A total of 871 AMD cases and 11,717 controls were identified. Of the AMD cases, 11% made use of cholesterol-lowering medications, as compared with 12.3% of controls (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.71-1.11). Adjusting for the confounding influence of age, gender, and race revealed a statistically significant relationship between AMD and use of cholesterol-lowering medications (OR, 0.79; 95% CI, 0.63-0.99)., Conclusions: The results of this study add to the growing body of evidence that cholesterol-lowering medications may reduce the risk of developing AMD. Additional research is needed to document the mechanism responsible for this association. A clinical trial of the impact of statins on AMD deserves consideration.

Purpose: To determine if differences in optic disc topography exist between blacks and whites independent of racial differences in the area of the scleral canal., Design: Cross-sectional observational study., Participants: A cohort of 146 eyes from black subjects and 97 eyes from white subjects without detectable ocular disease., Methods: Reliable bilateral images were obtained using a retinal topographer. Mean values for all topographic parameters were compared both unadjusted and adjusted for differences in optic disc area and/or reference plane height. Comparisons of group differences for parameters and linear discriminant functions were adjusted for interocular dependence and multiple comparisons., Results: Blacks had a significantly greater optic disc area (mean disc area in right eye: black subjects, 2.14 mm(2); white subjects, 1.96 mm(2) [P = 0.02]; mean disc area in left eye: black subjects, 2.18 mm(2); white subjects, 2.02 mm(2) [P = 0.04]). Most racial differences in optic disc parameters were not significant after adjustment for differences in optic disc area and reference plane height. However, eyes of black subjects demonstrated a deeper maximum cup depth than those of whites (P = 0.004), independent of differences in disc area and reference plane height. The values of linear discriminant functions did not differ significantly between racial groups, and the Moorfield classification correctly identified a similar proportion of subjects as normal in each racial group., Conclusions: Most of the normal variation in optic disc topography between blacks and whites seen with a retinal topographer is due to either differences in disc area or differences in reference plane height. However, small residual differences remain in cup depth independent of these parameters. These racial differences in optic disc structure should be considered in the statistical judgment of disease status based on these parameters. The Moorfield classification, which takes disc area into account, performed with similar specificity in each racial group.

Purpose: To examine the impact of depression in older adults on responses to the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) independent of demographics, vision, and general health., Design: Cross-sectional., Participants: We took the opportunity of an ongoing study on older drivers to address the specific aim stated above. The recruitment population consisted of 6342 older adults (> or =60 years) who were licensed drivers residing in Birmingham, Alabama; who had been involved in a crash in the prior year, as identified by Alabama Department of Public Safety records; and whose phone numbers could be located. Additional eligibility criteria were visual acuity impairment, slowed visual processing speed, or both, and a Mini-Mental State Examination score of > or =23. Persons in the recruitment population who met these eligibility criteria and agreed to enroll in a study on driver safety (purpose of the main study) numbered 403., Methods: The following questionnaires were interviewer administered in person and scored per standard procedures: the NEI VFQ-25, the Center for Epidemiological Studies Depression Scale (CES-D), a general health questionnaire, and a review of demographic information. Depressed persons were defined as those with CES-D scores of > or =16. There were complete data on 397 persons., Main Outcome Measure: Reduced score on the NEI VFQ-25 (defined by a score of <87.5) on the total questionnaire and 12 subscales., Results: After adjusting for demographics, vision, mental status, and general health, depression was significantly associated with a reduced NEI VFQ-25 score for total score and the subscales of distance vision, peripheral vision, role difficulties, dependencies, and mental health. Odds ratio point estimates in these adjusted associations ranged from 2.9 to 4.6., Conclusions: The results imply that older persons who are depressed may have reduced scores on the NEI VFQ-25 independent of the impact of vision problems. Depression in the elderly could be influencing their self-perception of the burden of eye disease and treatment effectiveness in clinical and epidemiologic studies.

Purpose: To determine if hypothyroidism is associated with an increased risk of glaucoma using a large cohort of patients., Design: Nested case-control study., Participants: Patients seen at the Veterans Affairs Medical Center in Birmingham, Alabama with newly diagnosed glaucoma between 1997 and 2001 were selected (n = 590) and age-matched to nonglaucoma controls (n = 5897)., Methods: Patient information was extracted from the Birmingham Veterans Affairs Medical Center data files containing demographic, clinical, and medication information. An index date was assigned to the glaucoma subjects corresponding to the time of diagnosis. Patients who had a glaucoma diagnosis before the observation period of the study were excluded. Ten controls were randomly selected for each patient and matched on age (+/-1 year) and an encounter on or before the index date of the matched case., Main Outcome Measures: Odds ratios (ORs) for the association between the prior diagnosis of hypothyroidism and the risk of developing glaucoma with adjustment for the presence of diabetes, lipid metabolism disorders, hypertension, cardiovascular disease, cerebrovascular disease, arterial disease, and migraines., Results: After adjustment for the other potential risk factors, patients were significantly more likely to have prior hypothyroidism than controls (OR, 1.40; 95% confidence interval, 1.01-1.97)., Conclusions: Our study has demonstrated a significantly greater risk of subjects with a preexisting diagnosis of hypothyroidism developing glaucoma, compared with controls, in a large Veterans Affairs Medical Center population.

Purpose: To evaluate the efficacy and safety of arteriovenous sheathotomy surgery to decompress branch retinal vein occlusion (BRVO)., Design: Prospective, nonrandomized, comparative interventional trial with concurrent control group., Participants: Twenty eyes with decreased visual acuity secondary to BRVO who underwent vitrectomy and surgical decompression by means of arteriovenous sheathotomy were compared with 20 control eyes (10 observation and 10 laser treated)., Intervention: The 20 surgical eyes underwent pars plana vitrectomy and arteriovenous sheathotomy with a microvitreoretinal blade. Of the 20 control eyes, 10 had no intervention (observation), and 10 had grid laser photocoagulation a mean of 9 months after diagnosis., Results: The mean preoperative visual acuity was 20/250 in the surgical group and 20/180 in the control group (statistically similar in the observation group and laser-treated group). The mean 14-month visual acuity was 20/63 in the surgical group and 20/125 in the control group (P = 0.02). Seventy-five percent of the surgical group halved their visual angle compared with 40% of the control group (40% observation vs. 40% laser; P = 0.025). Average lines of visual acuity gained were 4.55 in the surgical group and 1.55 in the control group (P = 0.0226; 1.1 lines in observation group and 2.0 lines in laser group)., Conclusions: Surgical arteriovenous sheathotomy to decompress BRVO results in significantly better visual outcomes than a matched control group of observation and laser-treated eyes. A randomized multicenter clinical trial is warranted to determine the efficacy of this procedure.