UNASSIGNED: 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.
UNASSIGNED: Cross-sectional.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: Cross-sectional observational study (NCT04112667).
UNASSIGNED: Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification.
UNASSIGNED: Cross-sectional study.
UNASSIGNED: Participants from the Northern Ireland Sensory Ageing study (Queen\'s University Belfast).
UNASSIGNED: Complete RMDA (rod-intercept time [RIT]) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT.
UNASSIGNED: Rod-intercept time data (age-corrected).
UNASSIGNED: Data from 459 participants (median [interquartile range] age, 65 [59-71] years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0-3, with 3 being intermediate age-related macular degeneration [iAMD]) groups was 6.0 (4.5-8.7), 6.6 (4.7-10.5), 5.7 (4.4-7.4), and 13.2 (6-21.1) minutes, respectively. OCT classifications OCT0-OCT2 yielded different median (interquartile range) values: 5.8 (4.5-8.5), 8.4 (5.2-13.3), and 11.1 (5.3-20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P < 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P = 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P < 0.01) but not in OCT1 (P = 0.285).
UNASSIGNED: Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.

UNASSIGNED: To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically defined age-related macular degeneration (AMD) and geographic atrophy (GA).
UNASSIGNED: Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866).
UNASSIGNED: Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye.
UNASSIGNED: Participants were assigned to the increasing dose cohorts and received 1 50-μl intravitreal injection of GEM103 at doses of 50 μg/eye, 100 μg/eye, 250 μg/eye, or 500 μg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities.
UNASSIGNED: Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a.
UNASSIGNED: No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 μg or more. Complement activation biomarkers were reduced 7 days after dose administration.
UNASSIGNED: A single intravitreal administration of GEM103 (up to 500 μg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD.

UNASSIGNED: To elucidate the incidence and treatment pattern of active exudative age-related macular degeneration (AMD).
UNASSIGNED: A population-based cohort study conducted using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a national claims database managed by the Japanese Ministry of Health, Labour, and Welfare (MHLW).
UNASSIGNED: The entire Japanese population aged 40 years or older (76 million people).
UNASSIGNED: With the permission of the MHLW, we accessed the complete NDB dataset and identified patients with newly diagnosed active exudative AMD between 2011 and 2018. The incidence of active exudative AMD was categorized by age and sex per year between 2011 and 2018; moreover, details regarding first-line therapy and number of anti-vascular endothelial growth factor (VEGF) injections per elapsed year since initial treatment were obtained and changes in treatment pattern were investigated.
UNASSIGNED: Incidence rate of active exudative AMD.
UNASSIGNED: During the specified 8-year period, 246 064 incident cases of active exudative AMD were identified; 61.4% of these patients were men. The overall incidence rate was 40.66 per 100 000 person-years (95% confidence interval [CI], 40.49-40.82) in the general population aged 40 years or older, 53.22 (95% CI, 52.95-53.49) in men, and 29.78 (95% CI, 29.60-29.98) in women. Mean age of onset was lower in men than in women (72.51 ± 10.50 years vs. 73.90 ± 10.46 years). Among patients with newly diagnosed active exudative AMD, 92.9% received anti-VEGF injections for initial treatments, whereas 1.8% underwent combination therapy with photodynamic therapy. The number of anti-VEGF injections in the first year (0-12 months), second year (13-24 months), and third year (25-36 months) after the initial injection was 3.66 ± 2.30, 1.39 ± 2.20, and 1.23 ± 2.19, respectively. Patients who received fewer injections in the first year received fewer injections in subsequent years and vice versa.
UNASSIGNED: This is a relatively large population-based study on the detailed epidemiology and actual treatment patterns of active exudative AMD in clinical practice. Our results can be a fundamental information source to ensure healthy eyes and promote well-being for all at all ages.

UNASSIGNED: To report fundamental epidemiologic data for choroidal parameters such as choroidal thickness and index of choroidal vascularity in Japanese individuals and to evaluate their correlations with age, sex, systemic parameters, and other ocular parameters.
UNASSIGNED: Population-based cohort study.
UNASSIGNED: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016.
UNASSIGNED: All participants underwent standardized ophthalmic examinations, including OCT with enhanced depth imaging (EDI; RS-3000 Advance; Nidek). We manually segmented the choroidoscleral interface to measure subfoveal choroidal thickness (SFCT) and calculated the normalized choroidal intensity obtained with EDI (NCIEDI) and choroidal vascularity index (CVI). These are indices of choroidal brightness in OCT and reportedly represent the dilation of choroidal vessels. After summarizing the age-sex stratified distributions of SFCT, NCIEDI, and CVI, their associations with age, sex, axial length (AL), and spherical equivalent (SE) were evaluated using linear regression analysis with adjustments for possible confounders.
UNASSIGNED: Distribution of SFCT, NCIEDI, and CVI in the healthy Japanese population and their characteristics.
UNASSIGNED: Age-sex standardized SFCT, NCIEDI, and CVI were 291.2 μm, 0.653, and 66.88%, respectively. In both men and women, SFCT was associated negatively with age (P < 0.001) and NCIEDI was associated positively with age (P < 0.001). Although both SFCT and NCIEDI did not differ significantly between men and women overall (P = 0.87 and P = 0.21, respectively), among younger participants (35-50 years of age), men showed significantly greater SFCT than women (P < 0.001). Only in men was CVI associated positively with age (P < 0.001). In the multivariable analysis, SFCT was associated significantly with age, sex, AL, SE, and the interaction term of age and sex (P < 0.001). Independent of SFCT, NCIEDI and CVI were associated significantly with age (P < 0.001).
UNASSIGNED: We report normative Japanese SFCT, NCIEDI, and CVI data using a large general Japanese cohort. The association analysis of SFCT with NCIEDI and CVI suggested that younger individuals have a more lumen-rich choroid for their choroidal thickness than older individuals.

UNASSIGNED: To evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes.
UNASSIGNED: Double-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365).
UNASSIGNED: Sixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo.
UNASSIGNED: Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit.
UNASSIGNED: Change in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months.
UNASSIGNED: A mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial.
UNASSIGNED: Macular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.

UNASSIGNED: To assess safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with intermediate age-related macular degeneration (AMD) and high-risk drusen (HRD) and to perform exploratory analyses of change in visual function.
UNASSIGNED: Phase 1, single-center, open-label, 24-week clinical trial with preplanned HRD cohort.
UNASSIGNED: Adult patients ≥55 years of age with intermediate AMD and HRD.
UNASSIGNED: Participants received subcutaneous elamipretide 40 mg daily, with safety and tolerability assessed throughout the study. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance best-corrected visual acuity (LLVA), normal-luminance binocular reading acuity (NLRA), low-luminance binocular reading acuity (LLRA), spectral-domain OCT, fundus autofluorescence (FAF), mesopic microperimetry, dark adaptation, and low-luminance questionnaire (LLQ).
UNASSIGNED: The primary end point was safety and tolerability. Prespecified exploratory end points included changes from baseline in BCVA, LLVA, NLRA, LLRA, retinal pigment epithelium (RPE)-drusen complex (DC) volume by OCT, FAF, mesopic microperimetry, dark adaptation, and LLQ results.
UNASSIGNED: Subcutaneous administration of elamipretide was highly feasible. All participants with HRD (n = 21) experienced 1 or more adverse events (AEs), but all were mild (57%) or moderate (43%), with the most common events related to injection site reactions. No serious systemic AEs occurred. One participant discontinued because of injection site reaction, 1 participant withdrew because they did not wish to continue study visits, and 1 participant withdrew after experiencing transient visual impairment. Among the 18 participants who completed the study, mean change in BCVA from baseline to 24 weeks was +3.6 letters (P = 0.014) and LLVA was +5.6 letters (P = 0.004). Compared with baseline, mean NLRA improved by -0.11 logarithm of the minimum angle of resolution (logMAR) units (P = 0.001), and LLRA by -0.28 logMAR units (P < 0.0001). Significant improvements were found in 6 of 7 subscales of the LLQ (P <0.0015). No significant changes were observed for RPE-DC volume, FAF, mesopic microperimetry, or dark adaptation.
UNASSIGNED: Elamipretide appeared to be generally safe and well tolerated in treating intermediate AMD and HRD. Exploratory analyses demonstrate a positive effect on visual function, particularly under low-luminance conditions. Further study of elamipretide for treatment of intermediate AMD with HRD is warranted.

UNASSIGNED: This study aimed to estimate the incidence and prevalence of neovascular age-related macular degeneration (nAMD) in the French population between 2008 and 2018.
UNASSIGNED: This was a retrospective, longitudinal population study using health care consumption data from the Système National des Données de Santé (SNDS; the French National Health Information Database), which covers approximately 99% of the French population.
UNASSIGNED: We identified individuals treated for nAMD from the French population 50 years of age and older. Identification criteria were nAMD diagnosis or reimbursement of nAMD treatments (anti-vascular endothelial growth factor intravitreal injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and other treatments for macular diseases (dexamethasone implant, laser therapy, etc.).
UNASSIGNED: We calculated incidence and prevalence based on the age-matched general population in France. Adjustment for age and sex was also performed for incidence.
UNASSIGNED: Incidence and prevalence of nAMD in the French population between 2008 and 2018.
UNASSIGNED: Between 2008 and 2018, we identified 342 961 patients with nAMD (67.5% women). Mean ± standard deviation age at nAMD diagnosis or first treatment increased from 78.8 ± 8.1 years in 2008 to 81.2 ± 7.9 years in 2018. In 2018, annual incidence was 0.149% and prevalence was 1.062% for the French population 50 years of age or older. Incidence was stable over the 10-year period. Annual incidence increased with age (0.223%, 0.380%, and 0.603% in those 60 years of age or older, 70 years of age or older, and 80 years of age or older, respectively), with similar trends for prevalence. No major differences were observed among the 14 regions of France for incidence or prevalence. Neovascular age-related macular degeneration incidence in 2018 was not impacted by the availability of primary or ophthalmology care in patients\' localities.
UNASSIGNED: The LANDSCAPE study provides exhaustive nationwide data on incidence and prevalence of nAMD in France over a 10-year period.

UNASSIGNED: Assess the safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with dry age-related macular degeneration (AMD) and noncentral geographic atrophy (NCGA) and to perform exploratory analyses of change in visual function.
UNASSIGNED: Phase 1, single-center, open-label, 24-week clinical trial with preplanned NCGA cohort.
UNASSIGNED: Adults ≥ 55 years of age with dry AMD and NCGA.
UNASSIGNED: Participants received subcutaneous elamipretide 40-mg daily; safety and tolerability assessed throughout. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance BCVA (LLBCVA), normal-luminance binocular reading acuity (NLBRA), low-luminance binocular reading acuity (LLBRA), spectral-domain OCT, fundus autofluorescence (FAF), and patient self-reported function by low-luminance questionnaire (LLQ).
UNASSIGNED: Primary end point was safety and tolerability. Prespecified exploratory end-points included changes in BCVA, LLBCVA, NLBRA, LLBRA, geographic atrophy (GA) area, and LLQ.
UNASSIGNED: Subcutaneous elamipretide was highly feasible. All participants (n = 19) experienced 1 or more nonocular adverse events (AEs), but all AEs were either mild (73.7%) or moderate (26.3%); no serious AEs were noted. Two participants exited the study because of AEs (conversion to neovascular AMD, n = 1; intolerable injection site reaction, n = 1), 1 participant discontinued because of self-perceived lack of efficacy, and 1 participant chose not to continue with study visits. Among participants completing the study (n = 15), mean ± standard deviation (SD) change in BCVA from baseline to week 24 was +4.6 (5.1) letters (P = 0.0032), while mean change (SD) in LLBCVA was +5.4 ± 7.9 letters (P = 0.0245). Although minimal change in NLBRA occurred, mean ± SD change in LLBCVA was -0.52 ± 0.75 logarithm of the minimum angle of resolution units (P = 0.005). Mean ± SD change in GA area (square root transformation) from baseline to week 24 was 0.14 ± 0.08 mm by FAF and 0.13 ± 0.14 mm by OCT. Improvement was observed in LLQ for dim light reading and general dim light vision.
UNASSIGNED: Elamipretide seems to be well tolerated without serious AEs in patients with dry AMD and NCGA. Exploratory analyses demonstrated possible positive effect on visual function, particularly under low luminance. A Phase 2b trial is underway to evaluate elamipretide further in dry AMD and NCGA.