Quantitative Autofluorescence at AMD's Beginnings Highlights Retinal Topography and Grading System Differences: ALSTAR2 Baseline.

INTRODUCTION: The aims of the study were to describe baseline quantitative (short-wavelength) autofluorescence (qAF) findings in a large pseudophakic cohort at age-related macular degeneration (AMD)'s beginnings and to assess qAF8 as an outcome measure and evaluate Age-Related Eye Disease Study (AREDS) and Beckman grading systems. METHODS: In the ALSTAR2 baseline cohort (NCT04112667), 346 pseudophakic eyes of 188 persons (74.0 ± 5.5 years) were classified as normal (N = 160 by AREDS, 158 by Beckman), early AMD (eAMD) (N = 104, 66), and intermediate AMD (iAMD) (N = 82, 122). Groups were compared via mean qAF intensities in a 6°-8° annulus (qAF8) and maps of differences between observations and the overall mean, divided by standard deviation (Z-score). RESULTS: qAF8 did not differ significantly among diagnostic groups by either stratification (p = 0.0869 AREDS; p = 0.0569 by Beckman). Notably, 45 eyes considered eAMD by AREDS became iAMD by Beckman. For AREDS-stratified eyes, Z-score maps showed higher centrally located qAF for normal, near the mean in eAMD, and lower values for iAMD. Maps deviated from this pattern for Beckman-stratified eyes. CONCLUSIONS: In a large sample of pseudophakic eyes, qAF8 does not differ overall from normal aging to iAMD but also does not capture the earliest AMD activity in the macula lutea. AREDS classification gives results more consistent with a slow decline in histologic autofluorescence than Beckman classification.

Teprotumumab Related Hearing Loss: A Large-Scale Analysis and Review of Voluntarily Reported Patient Complaints to the Food and Drug Administration (FDA).

PURPOSE: Accumulating case reports and series have suggested that teprotumumab may significantly increase the risk of hearing impairment that, in some cases, does not resolve. This study investigates the association between hearing impairment and teprotumumab use. METHODS: A disproportionality analysis was conducted using the United States Food and Drug Administration Adverse Event Reporting System, a publicly accessible database used for postmarketing surveillance and research. All adverse event reports containing the terms "teprotumumab" or "Tepezza" and a similar comparison group from all patients with the same indications for teprotumumab use (e.g., autoimmune thyroiditis, endocrine ophthalmopathy, and hyperthyroidism) but who had not received the drug were selected. Hearing impairment events were identified using the hearing impairment Standardized MedDRA Query. RESULTS: A total of 940 teprotumumab-associated adverse events were identified, including 84 hearing-related adverse events, with the first reported to the Food and Drug Administration in April 2020. A comparison group of 32,794 nonteprotumumab adverse events was identified with 127 hearing-related adverse events reported. Use of teprotumumab in patients with thyroid conditions was associated with a nearly 24-fold (proportional reporting ratio [PRR] 23.6, 95% confidence interval [CI]: 18.1-30.8) increased likelihood of any hearing disorder (p value <0.0001). The association was specifically elevated for a variety of deafness conditions (e.g., bilateral deafness [PRR: 41.9; 95% CI: 12.8-136.9]), Eustachian tube disorders (PRR: 34.9; 95% CI: 4.9-247.4), hypoacusis (PRR: 10.1; 95% CI: 7.6-13.3), and tinnitus (PRR: 8.7; 95% CI: 6.2-12.1). CONCLUSIONS: Patients treated with teprotumumab should receive warnings regarding the increased risk of hearing-related impairments and receive audiometry before, during, and after treatment.

Telemedicine Screening for Eye Disorders in Federally Qualified Health Centers: Relationship to Vision-Targeted Health-Related Quality of Life.

Introduction: Federally Qualified Health Centers (FQHCs) play a crucial role as safety-net primary health care clinics in the United States, serving medically underserved areas and populations. However, eye services are rarely offered at FQHCs. We examined how telemedicine-generated ocular diagnoses impacted vision-targeted health-related quality of life at FQHCs in rural Alabama. Methods: We focused on patients who are at risk for glaucoma. Both visual function and retinal imaging were assessed. The telemedicine vision screening protocol performed by a remote ophthalmologist evaluated eyes for glaucoma, diabetic retinopathy, cataract, age-related macular degeneration, and a measurement of habitual visual acuity. The National Eye Institute Visual Function Questionnaire-9 (VFQ-9) was administered. Results: Using stepwise regression, the best-fitting model for predicting VFQ-9 scores incorporated visual acuity 20/40 or worse, a diabetic retinopathy diagnosis, and sociodemographic variables (gender, transportation, insurance type/status, and employment status). Conclusion: Vision-targeted, health-related quality of life in our FQHC settings was related to the visual acuity impairment and the diagnosis of diabetic retinopathy but was also influenced by a variety of sociodemographic factors.

Vision Screening for Motor Vehicle Collision Involvement among Older Drivers.

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.

Visual functions associated with on-road performance by older drivers evaluated by a certified driving rehabilitation specialist.

PURPOSE: To assess associations between visual function and on-road driving performance evaluated by a certified driving rehabilitation specialist (CDRS). METHODS: Adults aged 70 and older enrolled and completed assessments of visual acuity, contrast sensitivity, visual processing speed, visual field sensitivity, motion perception and spatial ability. At follow-up, on-road driving performance was evaluated on a 15-mile route. Age-adjusted odds ratios and 95% confidence intervals (95% CIs) were used to associate worse CDRS composite score and CDRS global rating for those with poorer visual function compared to those with better scores and ratings. RESULTS: For the 144 participants who enrolled, completed vision testing and the on-road driving evaluation, the mean age was 79.2 (5.1) and 45.8% were female. The odds of worse CDRS global rating and composite score were significantly associated with moderately and severely impaired visual processing speed under divided attention (all p < 0.05). Those with poorer motion perception were at greater odds of a worse CDRS composite score (OR: 2.67, 95% CI: 1.14-6.26). CONCLUSIONS: The CDRS composite score of on-road driving performance by older adults was associated with slowed visual processing and impaired motion perception, suggesting that older driver performance, as rated by a CDRS, relies on visual skills. The CDRS global rating was also associated with impaired visual processing speed. The literature suggests impairments in these same visual functions elevate crash risk. While the results provide additional evidence suggesting these functional measures are associated with driving, further work is needed to identify and assess visual measures most closely related to driving safety and performance among older adults to better inform interventions, policy and future research.

Low rates of eye care utilization among visually impaired subsidized senior housing residents.

OBJECTIVE: To examine the rate of self-reported vision impairment, eye disease, and eye care utilization among residents of subsidized senior housing (SSH) communities. METHODS: In this cross-sectional, observational study, residents of 14 SSH communities in Jefferson County, AL, USA self-reported their vision status and eye care utilization as part of vision screening events held in their community. RESULTS: Two hundred and thirty-seven residents self-reported their vision status, presence of eye disease, and eye care utilization. A third of participants (33.3%) reported difficulty with distance vision while 38% reported difficulty with near vision. Rates of eye disease among this sample were as follows: 40.3% reported having cataracts, 13.6% reported having glaucoma, 4.2% reported having age-related macular degeneration, and 5.5% reported having diabetic retinopathy. The majority of participants (52.8%) had not been to see an eye care provider within the last year. Persons with vision impairment were less likely to report having seen an eye care provider within the last year than those without impairment (p = .03). CONCLUSION: This study illuminates the low utilization of eye care among socioeconomically disadvantaged older adults residing in SSH, especially among those with vision impairment and eye disease. Vision-related health care is important in maintaining both physical and mental health in older adults.

Association of Photopic and Mesopic Contrast Sensitivity in older drivers with risk of motor vehicle collision using naturalistic driving data.

BACKGROUND: Older drivers have a crash rate nearly equal to that of young drivers whose crash rate is the highest among all age groups. Contrast sensitivity impairment is common in older adults. The purpose of this study is to examine whether parameters from the photopic and mesopic contrast sensitivity functions (CSF) are associated with incident motor vehicle crash involvement by older drivers. METHODS: This study utilized data from older drivers (ages ≥60 years) who participated in the Strategic Highway Research Program Naturalistic Driving Study, a prospective, population-based study. At baseline participants underwent photopic and mesopic contrast sensitivity testing for targets from 1.5-18 cycles per degree. Model fitting generated area under the log CSF (AULCSF) and peak log sensitivity. Participant vehicles were instrumented with sensors that captured continuous driving data when the vehicle was operating (accelerometers, global positioning system, forward radar, 4-channel video). They participated for 1-2 years. Crashes were coded from the video and other data streams by trained analysts. RESULTS: The photopic analysis was based on 844 drivers, and the mesopic on 854 drivers. Photopic AULCSF and peak log contrast sensitivity were not associated with crash rate, whether defined as all crashes or at-fault crashes only (all p > 0.05). Mesopic AULCSF and peak log sensitivity were associated with an increased crash rate when considered for all crashes (rate ratio (RR): 1.36, 95% CI: 1.06-1.72; RR: 1.28, 95% CI: 1.01-1.63, respectively) and at-fault crashes only (RR: 1.50, 95% CI: 1.16-1.93; RR: 1.38, 95% CI: 1.07-1.78, respectively). CONCLUSIONS: Results suggest that photopic contrast sensitivity testing may not help us understand future crash risk at the older-driver population level. Results highlight a previously unappreciated association between older adults' mesopic contrast sensitivity deficits and crash involvement regardless of the time of day. Given the wide variability of light levels encountered in both day and night driving, mesopic vision tests, with their reliance on both cone and rod vision, may be a more comprehensive assessment of the visual system's ability to process the roadway environment.

Functionally validated imaging endpoints in the Alabama study on early age-related macular degeneration 2 (ALSTAR2): design and methods.

BACKGROUND: Age-related macular degeneration (AMD), a leading cause of irreversible vision impairment in the United States and globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris in the setting of characteristic extracellular deposits between outer retinal cells and their blood supply. Research has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision in early AMD, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light and pattern sensitivity. The unifying hypothesis of the Alabama Study on Early Macular Degeneration (ALSTAR2) is that early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors. Functionally this is manifest as delayed rod-mediated dark adaptation and eventually as rod-mediated visual dysfunction in general. METHODS: A cohort of 480 older adults either in normal macular health or with early AMD will be enrolled and followed for 3 years to examine cross-sectional and longitudinal associations between structural and functional characteristics of AMD. Using spectral domain optical coherence tomography, the association between (1) subretinal drusenoid deposits and drusen, (2) RPE cell bodies, and (3) the choriocapillaris' vascular density and rod- and cone-mediated vision will be examined. An accurate map and timeline of structure-function relationships in aging and early AMD gained from ALSTAR2, especially the critical transition from aging to disease, will identify major characteristics relevant to future treatments and preventative measures. DISCUSSION: A major barrier to developing treatments and prevention strategies for early AMD is a limited understanding of the temporal interrelationships among structural and functional characteristics while transitioning from aging to early AMD. ALSTAR2 will enable the development of functionally valid, structural biomarkers for early AMD, suitable for use in forthcoming clinical trials as endpoint/outcome measures. The comprehensive dataset will also allow hypothesis-testing for mechanisms that underlie the transition from aging to AMD, one of which is a newly developed Center-Surround model of cone resilience and rod vulnerability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04112667, October 7, 2019.

The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration.

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.

DYNAMISM OF DOT SUBRETINAL DRUSENOID DEPOSITS IN AGE-RELATED MACULAR DEGENERATION DEMONSTRATED WITH ADAPTIVE OPTICS IMAGING.

PURPOSE: To investigate the natural history of dot subretinal drusenoid deposits (SDD) in age-related macular degeneration, using high-resolution adaptive optics scanning laser ophthalmoscopy. METHODS: Six eyes of four patients with intermediate age-related macular degeneration were studied at baseline and 1 year later. Individual dot SDD within the central 30° retina were examined with adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. RESULTS: A total of 269 solitary SDD were identified at baseline. Over 12.25 ± 1.18 months, all 35 Stage 1 SDD progressed to advanced stages. Eighteen (60%) Stage 2 lesions progressed to Stage 3 and 12 (40%) remained at Stage 2. Of 204 Stage 3 SDD, 12 (6.4%) disappeared and the rest remained. Twelve new SDD were identified, including 6 (50%) at Stage 1, 2 (16.7%) at Stage 2, and 4 (33.3%) at Stage 3. The mean percentage of the retina affected by dot SDD, measured by the adaptive optics scanning laser ophthalmoscopy, increased in 5/6 eyes (from 2.31% to 5.08% in the most changed eye) and decreased slightly in 1/6 eye (from 10.67% to 10.54%). Dynamism, the absolute value of the areas affected by new and regressed lesions, ranged from 0.7% to 9.3%. CONCLUSION: Adaptive optics scanning laser ophthalmoscopy reveals that dot SDD, like drusen, are dynamic.

The Alabama VIP older driver study rationale and design: examining the relationship between vision impairment and driving using naturalistic driving techniques.

BACKGROUND: Older drivers aged ≥70 years old have among the highest rates of motor vehicle collisions (MVC) compared to other age groups. Driving is a highly visual task, and older adults have a high prevalence of vision impairment compared to other ages. Most studies addressing visual risk factors for MVCs by older drivers utilize vehicle accident reports as the primary outcome, an approach with several methodological limitations. Naturalistic driving research methods overcome these challenges and involve installing a high-tech, unobtrusive data acquisition system (DAS) in an older driver's own vehicle. The DAS continuously records multi-channel video of driver and roadway, sensor-based kinematics, GPS location, and presence of nearby objects in front of the vehicle, providing an objective measure of driving exposure. In this naturalistic driving study, the purpose is to examine the relationship between vision and crashes and near-crashes, lane-keeping, turning at intersections, driving performance during secondary tasks demands, and the role of front-seat passengers. An additional aim is to compare results of the on-road driving evaluation by a certified driving rehabilitation specialist to objective indicators of driving performance derived from the naturalistic data. METHODS: Drivers ≥70 years old are recruited from ophthalmology clinics and a previous population-based study of older drivers, with the goal of recruiting persons with wide ranging visual function. Target samples size is 195 drivers. At a baseline visit, the DAS is installed in the participant's vehicle and a battery of health and functional assessments are administered to the driver including visual-sensory and visual-cognitive tests. The DAS remains installed in the vehicle for six months while the participant goes about his/her normal driving with no imposed study restrictions. After six months, the driver returns for DAS de-installation, repeat vision testing, and an on-road driving evaluation by a certified driving rehabilitation specialist (CDRS). The data streams recorded by the DAS are uploaded to the data coordinating center for analysis. DISCUSSION: The Alabama VIP Older Driver Study is the first naturalistic older driver study specifically focused on the enrollment of drivers with vision impairment in order to study the relationship between visual dysfunction and driver safety and performance.

EXPLORING PHOTORECEPTOR REFLECTIVITY THROUGH MULTIMODAL IMAGING OF OUTER RETINAL TUBULATION IN ADVANCED AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy. METHODS: Four eyes of four subjects with advanced age-related macular degeneration underwent color fundus photography, infrared reflectance imaging, SD-OCT, and adaptive optics scanning laser ophthalmoscopy with a high-resolution research instrument. Outer retinal tubulation was identified in closely spaced (11 µm) SD-OCT volume scans. RESULTS: Outer retinal tubulation in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by adaptive optics scanning laser ophthalmoscopy was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. CONCLUSION: Lack of ORT cone reflectivity by adaptive optics scanning laser ophthalmoscopy indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in optical coherence tomography.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PURPOSE: To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). METHODS: Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). RESULTS: The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. CONCLUSION: In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Association between Glaucoma and At-fault Motor Vehicle Collision Involvement among Older Drivers: A Population-based Study.

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.

Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration.

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.

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging.

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.

Vision-targeted health related quality of life in older adults: patient-reported visibility problems in low luminance activities are more likely to decline than daytime activities.

BACKGROUND: Commonly used vision-targeted health-related quality of life questionnaires almost exclusively focus items on vision under daytime conditions. Older adults even when in good eye health frequently report experiencing vision problems at night and under low environmental light levels, and psychophysical studies also document these visibility problems. Here we compare the progression of self-reported low luminance visibility problems and self-reported visibility problems under daytime conditions in older adults. METHODS: Trained interviewers administered two questionnaires to older adults in normal eye health: the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) where items are almost entirely focused on difficulties in daytime activities, and the Low Luminance Questionnaire (LLQ) where items are focused on difficulties seeing at night and under low luminance conditions. The following visual functions were also measured: visual acuity, low luminance visual acuity, low luminance deficit, contrast sensitivity, light sensitivity in the macula, and rod-mediated dark adaptation. The protocol was repeated 3 years later. RESULTS: Scores on the NEI VFQ-25 composite and its subscales were unchanged between baseline and 3-year follow-up, whereas scores on the LLQ composite and 5 of 6 subscales significantly decreased (corresponding to less functionality) at the 3-year follow-up. Participants were more likely to display a ≥ 5 point decrease on the LLQ composite than on the NEI VFQ-25 over 3 years. Visual functional tests were largely unrelated to changes in NEI VFQ-25 and LLQ scores from baseline to follow-up. CONCLUSIONS: Older adults' vision-targeted quality of life as measured by questionnaire is more likely to exhibit a practically significant decrease over 3 years using a questionnaire that focused on low luminance activities (LLQ) than one focused on daytime activities (NEI VFQ-25). That the results of visual functional testing did not correspond to older adults' decline in self-reported problems in low luminance activities emphasizes the importance of questionnaires in understanding visual difficulties from the patients' own perspective.

ADHD and Vision Problems in the National Survey of Children's Health.

PURPOSE: To compare the prevalence of attention deficit/hyperactivity disorder (ADHD) in children with normal vision and with vision problems not correctable with glasses or contact lenses (vision problems) as determined by parent report in a nationwide telephone survey. METHODS: This cross-sectional study included 75,171 children without intellectual impairment aged 4 to 17 years participating in the 2011 to 2012 National Survey of Children's Health, conducted by the U.S. Centers for Disease Control and Prevention. Demographic information and information regarding vision and ADHD status were obtained by parent interview. Questions asked whether they had ever been told by a doctor or health care provider that the child had a vision problem not correctable with glasses or contact lenses, ADHD, intellectual impairment, or one of 13 other common chronic conditions of childhood. A follow-up question asked about condition severity. The main outcome measure was current ADHD. RESULTS: The prevalence of current ADHD was greater (p < 0.0001) among children with vision problems (15.6%) compared with those with normal vision (8.3%). The odds of ADHD compared with those of children with normal vision were greatest for those with moderate vision problems (odds ratio [OR], 2.6; 95% confidence interval [95% CI], 1.7 to 4.4) and mild vision problems (OR, 1.8; 95% CI, 1.1 to 2.9). Children with severe vision problems had similar odds of ADHD to those of children with normal vision perhaps because of the small numbers in this group (OR, 1.6; 95% CI, 0.8 to 3.1). In multivariable analysis adjusting for confounding variables, vision problems remained independently associated with current ADHD (OR, 1.8; 95% CI, 1.2 to 2.7). CONCLUSIONS: In this large nationally representative sample, the prevalence of ADHD was greater among children with vision problems not correctable with glasses or contacts. The association between vision problems and ADHD remains even after adjusting for other factors known to be associated with ADHD.