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.

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.

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.

Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer.

BACKGROUND: Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be utilized for extended release analgesia in patients undergoing radiation (RT) for head-and-neck cancer (HNC) and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. METHODS AND MATERIALS: We performed a prospective trial that enrolled participants > 18 years with histologically confirmed HNC who were scheduled to receive RT. Analgesia was prescribed in accordance with the WHO pain ladder. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30 mg of morphine sulfate equivalent and was titrated weekly during RT. Pain level and effect on quality of life were assessed using the Brief Pain Inventory. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. RESULTS: Twenty-six eligible patients were enrolled. Microsphere oxycodone was initiated in 16 (61.5%) patients. Six (23.1%) patients utilized a gastrostomy tube to administer microsphere oxycodone during all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy. No patients were discontinued due to toxicity or difficulty with administration. Ratings for average pain was 3.1 (± 3.4) at enrollment, 4.0 (± 2.4) at week 6 of RT, and 1.8 (± 2.2) at 3-month follow-up. CONCLUSIONS: These results support the feasibility and safety of microsphere oxycodone for extended release analgesia among patients with HNC undergoing RT.

Nonexudative Macular Neovascularization Supporting Outer Retina in Age-Related Macular Degeneration: A Clinicopathologic Correlation.

PURPOSE: Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision. DESIGN: Case study and clinicopathologic correlation. PARTICIPANT: A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age. METHODS: The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n = 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps). MAIN OUTCOME MEASURES: Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps. RESULTS: The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV. CONCLUSIONS: Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy.

Smile dimensions in adult African American and Caucasian females and males.

OBJECTIVES: To test smile dimension variations in adult African American and Caucasian females and males. SETTING AND SAMPLE POPULATION: The University of Alabama at Birmingham School of Dentistry and Hospital. Three hundred and ninety-four participants were recruited; African American females and males distributed over five age groups: 20-30, 30-40, 40-50, 50-60 and older than 60. MATERIAL & METHODS: Three-dimensional surface imaging was used to acquire two images of each participant, one at rest and one upon smile. Landmarks were plotted on the lips and linear distances measured to assess the length of the upper and lower lips, mouth width at rest and upon smile, gingival and dental display upon smile. RESULTS: Linear dimensions are larger in males than in females, and in African Americans than in Caucasians, except for the length of the upper lip that does not differ between male African American and Caucasian males, in any given age group. Gingival display and dental display decrease with age in all groups. CONCLUSION: Norms should reflect race, age and sex in order to optimize treatment goals.

CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.

Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm2/m2, P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated these measures with the CCI was associated with improved accuracy for prediction of noncancer death. © RSNA, 2016 Online supplemental material is available for this article.

Laundry pod and non-pod detergent related emergency department visits occurring in children in the USA.

OBJECTIVE: Previous studies have reported that children are at risk of severe injuries from exposure to laundry detergent pods. For the first time, this study sought to compare demographic and exposure characteristics and risk among children exposed to pod and non-pod laundry detergents presenting to emergency departments (EDs). METHODS: Data from the National Electronic Injury Surveillance System (NEISS) from 2012-2014 were used. All observations with injuries involving laundry detergent (NEISS code 0949) were included in this study. The χ2 test was used for bivariate analysis and logistic regression was used to determine the OR and 95% CI of hospitalisation for pod related versus non-pod laundry detergent exposures. RESULTS: From 2012-2014, there were an estimated 26 062 non-pod and 9814 pod laundry detergent related exposures among those aged 18 years and younger. For pod detergent, children aged 0-5 years had the most injuries. Poisoning (71.3%) was the most common diagnosis for pod detergent while contact dermatitis (72.2%) was most common for non-pod detergent. Hospitalisation occurred in 12.5% of pod detergent cases and just 3.0% of non-pod cases. Compared with non-pod detergent, those exposed to pod detergent were 4 times as likely to be hospitalised (OR 4.02; 95% CI 1.96 to 8.24). CONCLUSIONS: A greater effort should be made to appropriately educate the public about the dangers of laundry detergents, specifically pods, so a safe home environment can be established. While new regulations such as childproof containers, opaque packaging, and less appealing and colourful pods could reduce the number of pod related ED visits for children, caregivers should store detergents, along with other chemicals, in a secure location where children cannot easily access them.

Synthetic Graft Augmentation in Vaginal Prolapse Surgery: Long-Term Objective and Subjective Outcomes.

OBJECTIVE: To report long-term objectives and subjective outcomes in women who underwent prolapse surgery with a synthetic graft augmentation. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: University hospital in the southeastern United States. PATIENTS: Women with symptomatic pelvic organ prolapse who underwent transvaginal graft augmentation using the Prolift mesh system between July 2006 and December 2008 for a minimum 5-year follow-up. INTERVENTIONS: Subjects completed the Pelvic Floor Distress Inventory (PFDI-20), the Pelvic Floor Impact Questionnaire (PFIQ-7), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ), and the Patient Satisfaction Questionnaire. Subjects also underwent postoperative physical examination with Pelvic Organ Prolapse Quantification (POP-Q) and vaginal pain/stricture assessment. Long-term postoperative findings were compared with preoperative baseline data. MEASUREMENTS AND MAIN RESULTS: Of 208 eligible subjects, 70 completed the questionnaires only, and 48 of these 70 provided both postoperative examination and questionnaire data. The mean duration of follow-up was 7.0 ± 0.7 years (range, 5.8-8.1 years). POP-Q measurements of Ba (point B anterior), Bp (B posterior), C (cervix), GH (genital hiatus), PB (perineal body), and overall pelvic organ prolapse stage were significantly improved (all p < .001 except for PB, p = .006). PFIQ-7 (total, Urinary Impact Questionnaire, and Pelvic Organ Prolapse Impact Questionnaire) and PFDI-20 (total, Urinary Distress Inventory, and Pelvic Organ Prolapse Distress Inventory) scores significantly improved (all p < .001). No differences were noted in the colorectal-anal subscales (Colorectal-Anal Impact Questionnaire and Colorectal-Anal Distress Inventory) and PISQ scores at >5-year follow-up (all p > .05). Satisfaction rates were 15.7% for not at all, 35.7% for somewhat, and 48.6% for completely satisfied. Complications included graft exposure (n = 3; 6%) and dyspareunia (n = 25; 36%). CONCLUSION: Women undergoing transvaginal prolapse surgery using a synthetic graft continue to have positive objective and subjective outcomes, leading to significantly improved quality of life at a minimum 5-year follow-up.

Comparison of Glaucoma Diagnosis by Telemedicine, In-Person Ophthalmologist and Optometrist.

PRECIS: Diagnosis of glaucoma via telemedicine demonstrates moderate agreement with in-person ophthalmologist and optometrist diagnosis, providing evidence that telemedicine is a timely, accurate screening method in settings where an in-person visit may not be feasible. PURPOSE: To compare diagnostic agreement of glaucoma between in-person ophthalmologist (MD), in-person optometrist (OD), and a simulated telemedicine program. PATIENTS AND METHODS: Cross-sectional study of patients with normal optic nerve structural and functional imaging and new patients referred for glaucoma evaluation examined in-person by an MD for glaucoma with a dilated exam and structural and functional optic nerve testing (optical coherence tomography (OCT)), photos, and visual field); examined in person by an OD with a dilated exam and optic nerve testing; and structural and functional optic nerve testing reviewed separately by two ophthalmologists (TMD1, TMD2) with masking of prior MD and OD diagnoses. MAIN OUTCOME MEASURES: Inter-rater agreement between each diagnostic method (MD, OD, TMD1, TMD2) of normal vs. disease (open angle glaucoma, normal tension glaucoma, other type of glaucoma, other optic nerve disorders, ocular hypertension, glaucoma suspect) for each eye was calculated (Cohen's unweighted kappa). RESULTS: A total of 100 patients with median age of 66 years (IQR 59-72), male (40%) and White (62%) were analyzed. There was moderate agreement between MD and telemedicine [TMD1 kappa 0.49 (95% CI 0.37-0.61), TMD2 kappa 0.44 (95% CI 0.32-0.56)] and between MD and OD diagnosis [0.41 (95% CI 0.28-0.54)] and fair-moderate agreement between OD and telemedicine (TMD1 0.46 (95% CI 0.34-0.58), TMD2 0.61 (95% CI 0.50-0.72)]. CONCLUSIONS: The simulated telemedicine approach had comparable levels of agreement in glaucoma diagnosis with in-person fellowship-trained ophthalmologist, presenting a crucial complementary role in screening and increasing access to care, particularly in rural or underserved settings.

Repeatability of Rod-Mediated Dark Adaptation Testing in Normal Aging and Early and Intermediate Age-Related Macular Degeneration.

PURPOSE: The vulnerability of rod photoreceptors in aging and early and intermediate age-related macular degeneration (AMD) has been well documented. Rod-mediated dark adaptation (RMDA) is a measure of the recovery of light sensitivity in rod photoreceptors following a bright light. Delays in RMDA during early and intermediate AMD have been widely reported. For RMDA's promise as an outcome for trials targeted at early and intermediate AMD to be realized, excellent test-retest reliability, its repeatability, must be established. METHODS: Test-retest performance in a commonly used RMDA test based on the rod intercept time metric (RIT) was evaluated in participants with early and intermediate AMD and with normal retinal aging with testing approximately 2 weeks apart. The test target was placed at 5° eccentricity superior to the foveal center, an area with maximal rod loss in aging and AMD. Disease severity was identified by a trained and masked grader of fundus photographs using both the AREDS 9-step and Beckman classification systems. Bland-Altman plots and intra-class correlation coefficients (ICC) evaluated repeatability. RESULTS: The analysis sample consisted of 37 older adults (mean age 76 years, standard deviation 5), with approximately one-third of the sample in each of three groups - normal aging, early AMD, and intermediate AMD. For the total sample, the ICC was 0.98. For individual AMD groups for both AREDS 9-step and Beckman classifications, the ICCs were also very high ranging from 0.82 to 0.99. CONCLUSION: We demonstrated that RMDA testing using the RIT metric has excellent repeatability when target location is at 5° in studying older adults from normal aging to intermediate AMD, suggesting the reliable use of this functional measure in trials.

Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT): Baseline Results.

PURPOSE: To describe baseline results of the Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT) for patients at federally qualified health centers (FQHCs). Candidates were persons at risk for glaucoma-associated diseases (GAD) based on age, race/ethnicity, current diagnosis of GAD, family history, and diabetes. DESIGN: Baseline screening visit followed by remote diagnosis and referral for follow-up examinations. METHODS: Patients presenting to FQHCs who were at least 18 years of age were enrolled and underwent screening for acuity, autorefraction, intraocular pressure, visual field testing, and fundus imaging. Results were transmitted to an ophthalmologist at University of Alabama at Birmingham for diagnosis who made referrals for follow-up; follow-up attendance was noted. Questionnaires assessed participants' perspectives on screening. Primary outcomes were rates of disease detection, referral for follow-up, follow-up attendance, and participant satisfaction. RESULTS: Of the 500 participants enrolled (mean age 58 years), 45.6% were African American and 51.6% White. Remote diagnostic evaluation of ocular screening by ophthalmologist revealed 30% GAD, 6.8% diabetic retinopathy, 37.6% cataract, 68.4% refractive error, 9.2% other eye conditions. In all, 47.2% of the participants were referred for follow-up examination and for acuity 20/40 or worse or IOP ≥23 mm Hg in one or both eyes. Follow-up examination attendance was 76.7% for those referred. Participants reported being very satisfied with screening (85.8%) and with the convenience of screening in their primary care clinic (92.2%). CONCLUSIONS: The high percentage of patients diagnosed with treatable eye conditions at telemedicine screening suggest these programs in FQHCs can be effective and scalable nationwide. Attendance when referred for follow-up examination was high. Participants welcomed screenings in their communities.

Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.

Purpose: Lack of valid end points impedes developing therapeutic strategies for early age-related macular degeneration (AMD). Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The relationship between RMDA and the status of outer retinal bands on optical coherence tomography (OCT) have not been well defined. This study aims to characterize these relationships in early and intermediate AMD. Methods: Baseline data from 476 participants was assessed including eyes with early AMD (n = 138), intermediate AMD (n = 101), and normal aging (n = 237). Participants underwent volume OCT imaging of the macula and rod intercept time (RIT) was measured. The ellipsoid zone (EZ) and interdigitation zone (IZ) on all OCT B-scans of the volumes were segmented. The area of detectable EZ and IZ, and mean thickness of IZ within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were computed and associations with RIT were assessed by Spearman's correlation coefficient and age adjusted. Results: Delayed RMDA (longer RIT) was most strongly associated with less preserved IZ area (r = -0.591; P < 0.001), followed by decreased IZ thickness (r = -0.434; P < 0.001), and EZ area (r = -0.334; P < 0.001). This correlation between RIT and IZ integrity was not apparent when considering normal eyes alone within 1.5 mm of the fovea. Conclusions: RMDA is correlated with the status of outer retinal bands in early and intermediate AMD eyes, particularly, the status of the IZ. This correlation is consistent with a previous analysis of only foveal B-scans and is biologically plausible given that retinoid availability, involving transfer at the interface attributed to the IZ, is rate-limiting for RMDA.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

Biologically Guided Optimization of Test Target Location for Rod-mediated Dark Adaptation in Age-related Macular Degeneration: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Purpose: We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it. Design: Cross-sectional. Participants: Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems. Methods: In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging. Main Outcome Measures: Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°. Results: In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems. Conclusions: We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression.

Older Drivers' Attitudes and Preferences about Instrument Cluster Designs in Vehicles Revealed by the Dashboard Questionnaire.

Background: Older drivers are a rapidly growing demographic group worldwide; many have visual processing impairments. Little is known about their preferences about vehicle instrument cluster design. Methods: We evaluated the psychometric properties of a questionnaire on "dashboard" design for a population-based sample of 1000 older drivers. Topics included gauges, knobs/switches, and interior lighting; items were statements about their visual design. Response options used a Likert-scale ("Definitely True" to "Definitely False"). Factor and Rasch analyses identified underlying subscales. Results: Driver responses revealed four thematic subscales fitting the Rasch model: cognitive processing, lighting, pattern recognition, and obstructions. Internal consistency of subscales was acceptable (0.70-0.87); all possessed a sufficiently unidimensional structure. Opportunities for improvement were identified (item scope, category ordering, discrimination of respondents' perception levels). Conclusions: Assessment of motor vehicle dashboard preferences indicated cognitive processing, lighting, pattern recognition, and obstructions are areas relevant to older drivers. Future work will examine the relationship between older drivers' visual function (e.g., contrast sensitivity, visual processing speed) and their design preferences as revealed by the Dashboard Questionnaire, with the aim to optimize instrument cluster displays for older drivers.

Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Purpose: Quantification of retinal xanthophyll carotenoids in eyes with and without age-related macular degeneration (AMD) via macular pigment optical volume (MPOV), a metric for xanthophyll abundance from dual wavelength autofluorescence, plus correlations to plasma levels, could clarify the role of lutein (L) and zeaxanthin (Z) in health, AMD progression, and supplementation strategies. Design: Cross-sectional observational study (NCT04112667). Participants: Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD. Methods: Macular health and supplement use was assessed by the Age-related Eye Disease Study (AREDS) 9-step scale and self-report, respectively. Macular pigment optical volume was measured from dual wavelength autofluorescence emissions (Spectralis, Heidelberg Engineering). Non-fasting blood draws were assayed for L and Z using high-performance liquid chromatography. Associations among plasma xanthophylls and MPOV were assessed adjusting for age. Main Outcome Measures: Age-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0° and 9.0°; plasma L and Z (µM/ml). Results: Of 809 eyes from 434 persons (89% aged 60-79, 61% female), 53.3% eyes were normal, 28.2% early AMD, and 18.5% intermediate AMD. Macular pigment optical volume 2° and 9° were similar in phakic and pseudophakic eyes, which were combined for analysis. Macular pigment optical volume 2° and 9° and plasma L and Z were higher in early AMD than normal and higher still in intermediate AMD (P < 0.0001). For all participants, higher plasma L was correlated with higher MPOV 2° (Spearman correlation coefficient [Rs] = 0.49; P < 0.0001). These correlations were significant (P < 0.0001) but lower in normal (Rs = 0.37) than early and intermediate AMD (Rs = 0.52 and 0.51, respectively). Results were similar for MPOV 9°. Plasma Z, MPOV 2°, and MPOV 9° followed this same pattern of associations. Associations were not affected by supplement use or smoking status. Conclusions: A moderate positive correlation of MPOV with plasma L and Z comports with regulated xanthophyll bioavailability and a hypothesized role for xanthophyll transfer in soft drusen biology. An assumption that xanthophylls are low in AMD retina underlies supplementation strategies to reduce progression risk, which our data do not support. Whether higher xanthophyll levels in AMD are due to supplement use cannot be determined in this study.

Comparing Rod-Mediated Dark Adaptation in Older Adults before and after Cataract Surgery.

PURPOSE: Studies on age-related macular degeneration often use rod-mediated dark adaptation (RMDA) to evaluate macular functional health, studying eyes with cataract and pseudophakic eyes within the same sample. We examine a poorly understood issue-whether rod intercept time (RIT), a measure of RMDA, changes after cataract surgery and intraocular lens (IOL) insertion as compared to RIT before cataract surgery. Cataract may serve as a filter reducing photo-bleach magnitude prior to surgery, biasing RMDA interpretation. METHODS: A pre-/post-cataract surgery design was used. Persons with nuclear sclerotic and/or cortical cataract per the electronic health record were enrolled. Prior to cataract surgery, visual acuity, RMDA, and the LOCS III classification documenting cataract presence/severity were measured. Thirty days after surgery (mean), visual acuity and RMDA were repeated, followed by fundus photos to document macular health. RESULTS: Twenty-four participants (mean age 72.7 years, standard deviation 5.6) enrolled. All eyes had nuclear sclerotic and nuclear color cataract; 68% had cortical cataract. All IOLs were monofocal with 21 having blue blocking characteristics and 3 had clear IOLs. Most eyes had higher RIT post-surgery (15.6 min, SD 6.7) as compared to pre-surgery (13.7 min, SD 6.4), p = 0.0006, meaning that RMDA was slower post-surgery. Eyes with moderate cataract (<4 on any LOCS III grade) had RIT that increased on average by 0.7 min; those with more advanced cataract (≥4) had RIT that increased by 3.1 min (p = 0.0116). Results were unchanged when clear IOLs were removed from analysis. CONCLUSION: RMDA was significantly slower (RIT was greater) following cataract surgery, with the greatest impact on RIT in older eyes after surgery for more advanced cataract. These findings suggest that persons with more advanced cataract may bias results when evaluating RMDA using RIT.

Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.

Purpose: Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD. Methods: One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging. Results: In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001). Conclusions: Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.

Discernibility of the Interdigitation Zone (IZ), a Potential Optical Coherence Tomography (OCT) Biomarker for Visual Dysfunction in Aging.

PURPOSE: Photoreceptor (PR) outer segments, retinal pigment epithelium apical processes, and inter-PR matrix contribute to the interdigitation zone (IZ) of optical coherence tomography (OCT). We hypothesize that this interface degrades over adulthood, in concert with a delay of rod mediated dark adaptation (RMDA). To explore this idea, we determined IZ discernibility and RMDA in younger and older adults. METHODS: For this cross-sectional study, eyes of 20 young (20-30 years) and 40 older (≥60 years) participants with normal maculas according to the AREDS 9-step grading system underwent OCT imaging and RMDA testing at 5° superior to the fovea. Custom FIJI plugins enabled analysis for IZ discernibility at 9 eccentricities in 0.5 mm steps on one single horizontal B-scan through the fovea. Locations with discernible IZ met two criteria: visibility on B-scans and a distinct peak on a longitudinal reflectivity profile. The frequency of sites meeting both criteria was compared between both age groups and correlated with rod intercept time (RIT). RESULTS: The median number of locations with discernible IZ was significantly higher (foveal, 4 vs. 0, p = 0.0099; extra-foveal 6 vs. 0, p < 0.001) in eyes of young (26 ± 3 years) compared to older (73 ± 5 years) participants. For the combined young and older sample, the higher frequency of discernible IZ was correlated with shorter RIT (faster dark adaptation) (rs = -0.56, p < 0.0001). This association was significant within young eyes (rs = -0.54; p = 0.0134) and not within older eyes (rs = -0.29, p = 0.706). CONCLUSIONS: Results suggest that the interface between outer segments and apical processes degrades in normal aging, potentially contributing to delayed rod-mediated dark adaptation. More research is needed to verify an age-related association between IZ discernibility and rod-mediated dark adaptation. If confirmed in a large sample, IZ discernibility might prove to be a valuable biomarker and predictor for visual function in aging.