Type 1 diabetes mellitus following COVID-19 vaccination: a report of two cases and review of literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00695-9.

Effectiveness of insulin degludec/liraglutide versus insulin degludec/insulin aspart in Japanese patients with type 2 diabetes.

Aims: To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6 months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D). Materials and methods: A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25 kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup. Results: The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (- 0.17 vs - 0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes. Conclusions: Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.

Use of the reliable change index to evaluate the effect of a multicomponent exercise program on physical functions.

AIMS: Using the reliable change index (RCI), we aimed to examine the effect of a multicomponent exercise program on the individual level. METHODS: Overall, 270 adults (mean age, 78 years) completed a multicomponent physical exercise program (strength, aerobic, gait, and balance) for 40 min, 1-2 times per week, continued up to 1 year at a daycare center. Effectiveness was assessed using grip, ankle, knee, and hip strength; Timed Up & Go (TUG); Berg Balance Scale (BBS); gait speed; and 6-min walking distance. These were measured at baseline and every 3 months thereafter. We calculated the RCI using the data between two-time points (baseline and at 3, 6, 9, or 12 months) in each participant and then calculated the mean RCI value across the participants. A paired t-test was also employed to evaluate the effect of the intervention as an average-based statistics. RESULTS: The highest mean RCI values were on ankle plantar-flexion strength, followed by gait speed, hip abduction strength, BBS, knee extensor strength, 6-min walk distance, grip strength, and finally TUG. Paired t-test also revealed significant improvement with moderate effect sizes for ankle plantar-flexion strength (0.504), gait speed (0.413), hip abduction strength (0.374), BBS (0.334), knee extensor strength (0.264), and 6-min walk distance (0.248). Significant but small effect size was seen on TUG (0.183). CONCLUSION: The RCI is a convenient method of comparing the effect between different assessments, especially at an individual level. This index can be applied to the use of personal feedback.

Biometric and refractive changes following the monocular application of peripheral myopic defocus using a novel augmented-reality optical system in adults.

The prevalence of myopia is growing at an alarming rate and is associated with axial elongation of the eye. The cause of this undesirable physiological change involves multiple factors. When the magnitude of myopia approaches high levels, this accompanying mechanical effect increases the risk of developing other clinical conditions associated with permanent vision loss. Prior work has investigated how we may halt or reverse this process of axial elongation associated with myopic progression when we expose the eye to a peripheral myopic defocus stimulus. Specifically, the known, short-term response to myopic defocus stimulation is promising and demonstrates the possibility of establishing more permanent effects by regulating the axial length of the eye with specific defocus stimulation. However, how to directly convert these known, short-term effects into more long-term, permanent changes to effectively prevent these unfavourable physiological and refractive changes over time is yet to be understood. Here, we show for the first time that we can produce sustained, long-term reductions in axial length and refractive endpoints with cumulative short-term exposure to specific myopic defocus stimuli using a novel optical design that incorporates an augmented reality optical system. We believe that this technology will have the potential to improve the quality of vision in mankind.

Longitudinal effects of physical exercise on health-related outcomes based on frailty status in community-dwelling older adults.

AIM: To clarify the difference in the longitudinal effects of physical exercise on health-related outcomes according to the baseline frailty status (frail or non-frail) in community-dwelling older adults. METHODS: Participants included 177 adults aged ≥65 years who carried out multicomponent physical exercises (strength, aerobic, gait and balance) for 40 min, one to three times per week, for 1 year at a day-care center. Bodyweight, comfortable walking speed, 6-min walking distance and Mini-Mental State Examination were measured at baseline and every 3 months. For longitudinal trend, we analyzed the change in scores from baseline for each outcome using the linear mixed effects model. Fixed effects included "group" (frail or non-frail), "time" (4 time points every 3 months, from 3 to 12 months) and "interaction between group and time." RESULTS: The effect sizes from baseline showed almost all positive values for each outcome. The linear mixed effects model showed significant effects on "interaction between group and time" in changes in bodyweight (P = 0.033), "group" in changes in walking speed (P = 0.013) and "time" in changes in the Mini-Mental State Examination (P < 0.001). Bodyweight showed a decreasing trend in the non-frail group after 3 months, unlike in the frail group. For walking speed, moderate effect sizes (d = 0.67-0.74) were sustained over time in the frail group, as did lesser effect sizes (d = 0.26-0.40) in the non-frail group. CONCLUSIONS: Exercise-based multicomponent interventions were effective for both groups. The longitudinal effects on walking speed and bodyweight were greater in the frail group. Geriatr Gerontol Int 2022; 22: 213-218.

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease.

BACKGROUND/AIMS: Stargardt disease is a rare, inherited, degenerative disease of the retina that is the most common type of hereditary macular dystrophy. Currently, no approved treatments for the disease exist. The purpose of this study was to characterise the pharmacodynamics of emixustat, an orally available small molecule that targets the retinal pigment epithelium-specific 65 kDa protein (RPE65), in subjects with macular atrophy secondary to Stargardt disease. METHODS: In this multicentre study conducted at six study sites in the USA, 23 subjects with macular atrophy secondary to Stargardt disease were randomised to one of three doses of daily emixustat (2.5 mg, 5 mg or 10 mg) and treated for 1 month. The primary outcome was the suppression of the rod b-wave recovery rate on electroretinography after photobleaching, which is an indirect measure of RPE65 inhibition. RESULTS: Subjects who received 10 mg emixustat showed near-complete suppression of the rod b-wave amplitude recovery rate postphotobleaching (mean=91.86%, median=96.69%), whereas those who received 5 mg showed moderate suppression (mean=52.2%, median=68.0%). No effect was observed for subjects who received 2.5 mg emixustat (mean=-3.31%, median=-12.23%). The adverse event profile was consistent with prior studies in other patient populations and consisted primarily of ocular adverse events likely related to RPE65 inhibition. CONCLUSION: This study demonstrated dose-dependent suppression of rod b-wave amplitude recovery postphotobleaching, confirming emixustat's biological activity in patients with Stargardt disease. These findings informed dose selection for a 24-month phase 3 trial (SeaSTAR Study) that is now comparing emixustat to placebo in the treatment of Stargardt disease-associated macular atrophy.

Effect of short-term peripheral myopic defocus on ocular biometrics using Fresnel "press-on" lenses in humans.

This study assessed axial length and choroidal thickness changes following short-term peripheral myopic defocus in normal adult subjects. Twenty subjects underwent defocus sessions by viewing a full-field projected movie 4 m away for 4 h in the morning, while wearing spectacle lenses, corrected for distance vision in both eyes. The right eye, serving as the test eye, was peripherally defocused using a Fresnel lens overlay of + 3.50 D with a central clear aperture of 11.5 mm (correlating to a clear central visual field of approximately 23°), while the left eye served as the control (with no Fresnel lens overlay). A subset of 10 subjects from the same cohort also underwent additional defocus sessions with + 5.00 D of peripheral defocus. Axial length was measured and radial sub-foveal choroidal scans were obtained before and after the defocus sessions. The increase in axial length of the test eyes were significantly less than the control eyes under both peripheral defocus conditions (p < 0.05). The difference in mean change for choroidal thickness between test and control eyes was not significant for either dioptric condition. Our results demonstrated that short-term peripheral myopic defocus significantly inhibited axial elongation in adult humans, without significant changes in choroidal thickness.

Visual Performance as a Function of Clear Central Aperture Diameter with a Defocused Myopic Periphery.

SIGNIFICANCE: Visual performance is affected least by a 15° radial aperture surrounded by peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs and myopia control optimization. PURPOSE: The purpose of this study was to assess the effect of clear central apertures of different diameters with a defocused retinal periphery, using a range of visual performance tasks. METHODS: Thirty visually normal subjects (mean age, 24.4 ± 3.3 years; 20 females; mean spherical equivalent of -1.28 D) were enrolled. Subjects wore five different spectacles during testing, all corrected for distance refraction, in random order: three single-vision spectacles with clear central apertures of 10, 12.5, and 15° radii with the periphery defocused using Fresnel "press-on" lenses (+3.5 D sphere), progressive addition lens (PAL) spectacles with a +3.5 D addition, and single-vision lens (SVL) spectacles with no peripheral defocus. Static and kinetic visual field sensitivities, reading rate and comprehension, head movements, global saccadic tracking, and saccadic visual search were evaluated. RESULTS: Reading rate and comprehension did not differ across the five test conditions; however, increased head movement was found with the smallest aperture compared with the PAL condition with adjusted P < .05. Static visual field sensitivity was reduced for all three apertures in eccentric regions when compared with the SVL and PAL conditions with adjusted P < .05, whereas kinetic sensitivity did not differ for any lens condition. The 15° aperture was superior to the 10 and 12.5° apertures based on its similarity to the SVL and PAL spectacle conditions in head movement during reading, the Michigan Tracking Test, and the vertical results of the Developmental Eye Movement Test. CONCLUSIONS: Visual performance is least affected adversely by a 15° aperture surrounded by a peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs to optimize myopia treatment with minimal impact on visual performance.

The correlation of salivary telomere length and single nucleotide polymorphisms of the ADIPOQ, SIRT1 and FOXO3A genes with lifestyle-related diseases in a Japanese population.

BACKGROUND: It has been reported that genetic factors are associated with risk factors and onset of lifestyle-related diseases, but this finding is still the subject of much debate. OBJECTIVE: The aim of the present study was to investigate the correlation of genetic factors, including salivary telomere length and three single nucleotide polymorphisms (SNPs) that may influence lifestyle-related diseases, with lifestyle-related diseases themselves. METHODS: In one year at a single facility, relative telomere length and SNPs were determined by using monochrome multiplex quantitative polymerase chain reaction and TaqMan SNP Genotyping Assays, respectively, and were compared with lifestyle-related diseases in 120 Japanese individuals near our university. RESULTS: In men and all participants, age was inversely correlated with relative telomere length with respective p values of 0.049 and 0.034. In men, the frequency of hypertension was significantly higher in the short relative telomere length group than in the long group with unadjusted p value of 0.039, and the difference in the frequency of hypertension between the two groups was of borderline statistical significance after adjustment for age (p = 0.057). Furthermore, in men and all participants, the sum of the number of affected lifestyle-related diseases, including hypertension, was significantly higher in the short relative telomere length group than in the long group, with p values of 0.004 and 0.029, respectively. For ADIPOQ rs1501299, men's ankle brachial index was higher in the T/T genotype than in the G/G and G/T genotypes, with p values of 0.001 and 0.000, respectively. For SIRT1 rs7895833, men's body mass index and waist circumference and all participants' brachial-ankle pulse wave velocity were higher in the A/G genotype than in the G/G genotype, with respective p values of 0.048, 0.032 and 0.035. For FOXO3A rs2802292, women's body temperature and all participants' saturation of peripheral oxygen were lower in the G/T genotype than in the T/T genotype, with respective p values of 0.039 and 0.032. However, relative telomere length was not associated with physiological or anthropometric measurements except for height in men (p = 0.016). ADIPOQ rs1501299 in men, but not the other two SNPs, was significantly associated with the sum of the number of affected lifestyle-related diseases (p = 0.013), by genotype. For each SNPs, there was no significant difference in the frequency of hypertension or relative telomere length by genotype. CONCLUSION: Relative telomere length and the three types of SNPs determined using saliva have been shown to be differentially associated with onset of and measured risk factors for lifestyle-related diseases consisting mainly of cardiovascular diseases and cancer.

A Cross-Sectional Study on the Association between Body Mass Index and Frailty According to Sex in Elderly Patients with Disabilities from an Elderly Day-Care Center.

The association between body mass index (BMI) and frailty in elderly patients with disabilities is unclear. We aimed to investigate the association between BMI and frailty in the elderly with disabilities according to sex. This cross-sectional study included 280 elderly patients with disabilities from an elderly daycare center. BMI classification for the Asian population was used to categorize the patients into four groups: underweight, normal, overweight, and obese. Frailty score was based on the phenotypic definition of frailty and consisted of five criteria derived from the revised Japanese version of the Cardiovascular Health Study. Those who had three or more criteria were considered frail. Logistic regression models were constructed to investigate the associations between frailty and BMI in each group (males and females). In females, being underweight was significantly associated with frailty after adjusting for confounders (age and Mini-Mental State Examination score); after adding medical history as a confounder, the aforementioned association was not significant. In males, BMI was not significantly associated with frailty. The association between BMI and frailty differed according to sex among the elderly with disabilities. This finding provides important information regarding frailty risk to workers in daycare facilities.

Effects of emixustat hydrochloride in patients with proliferative diabetic retinopathy: a randomized, placebo-controlled phase 2 study.

PURPOSE: To evaluate the effects of oral emixustat hydrochloride on pro-angiogenic and inflammatory cytokines in the aqueous humor, as well as other ophthalmic parameters, in subjects with proliferative diabetic retinopathy (PDR). METHODS: Twenty-three patients with PDR, with or without diabetic macular edema (DME), were assigned to emixustat or placebo in daily oral doses ranging from 5 to 40 mg over a step-up titration period, for 84 days. The main outcome measures included levels of IL-1ß, IL-6, IL-8, TGFß-1, and VEGF in the aqueous humor. RESULTS: Seven of 12 subjects (58%) who were randomized to emixustat and 11 of 12 subjects (92%) who were randomized to placebo completed the study. No statistically significant differences between treatment groups were observed for changes in any of the aqueous humor cytokines tested. However, median VEGF levels were slightly reduced in the emixustat but not the placebo group (- 70.0 pg/mL versus + 42.7 pg/mL, or - 11.8% versus + 6.7%). In a post hoc analysis of all subjects (with or without DME), statistically significant differences between treatment arms in mean changes from baseline in central subfield thickness (CST; emixustat - 11.9 µm, placebo + 36.2 µm; P = 0.076) and total macular volume (TMV; emixustat - 0.13 mm3, placebo + 0.23 mm3; P = 0.026) were observed, both favoring emixustat. Emixustat's safety profile was consistent with prior studies (i.e., the adverse events of delayed dark adaptation and visual impairment were more common in subjects treated with emixustat). CONCLUSION: Although this pilot study did not demonstrate statistically significant differences in changes in aqueous humor cytokine levels between the emixustat and placebo groups, VEGF levels were slightly reduced in the emixustat but not in the placebo group. In addition, statistically significant differences favoring the emixustat group were observed in CST and TMV among all subjects. These data warrant further investigation of emixustat's potential therapeutic effects in diabetic retinopathy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02753400 (April 2016).

Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1.

Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that functions as a copper-containing amine oxidase and is involved in leukocyte adhesion at sites of inflammation. Inhibition of VAP-1 oxidative deamination has become an attractive target for anti-inflammatory therapy with demonstrated efficacy in rodent models of inflammation. A previous comparison of purified recombinant VAP-1 from mouse, rat, monkey, and human gene sequences predicted that rodent VAP-1 would have higher affinity for smaller hydrophilic substrates/inhibitors because of its narrower and more hydrophilic active site channel. An optimized in vitro oxidative deamination fluorescence assay with benzylamine (BA) was used to compare inhibition of five known inhibitors in recombinant mouse, rat, and human VAP-1. Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC50 concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207. Hydralazine had a lower IC50 in rats compared to humans, although not significant. However, the IC50 of hydralazine was significantly higher in the rat compared to mouse VAP-1. The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1. Although the sensitivity of these two inhibitors was the lowest in the mouse enzyme, we found no significant differences between mouse, rat, and human VAP-1. Michaelis-Menten kinetics of the small primary amines phenylethylamine and tyramine were also compared to the common marker substrate BA demonstrating that BA had the highest affinity among the substrates. Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models.

Pharmacotherapy for metabolic and cellular stress in degenerative retinal diseases.

Retinal photoreceptors continually endure stresses associated with prolonged light exposure and the metabolic demands of dark adaptation. Although healthy photoreceptors are able to withstand these stresses for several decades, the disease-affected retina functions at a reduced capacity and is at an increased risk for dysfunction. To alleviate cellular and metabolic stressors in degenerative retinal diseases, a new class of drugs that modulate the metabolic activity of the retina have been developed. A clinical candidate in this class (emixustat) has been shown to reduce retinal pathology in various animal models of human retinal disease and is currently under clinical study. Here, we describe the pharmacological properties of emixustat, its mechanisms of action, and potential for use in the treatment of specific retinal diseases.

Emixustat Reduces Metabolic Demand of Dark Activity in the Retina.

Purpose: In the dark, photoreceptor outer segments contain high levels of cyclic guanosine 3'-5' monophosphate (cGMP), which binds to ion channels, holding them open and allowing an influx of cations. Ion pumping activity, which balances cation influx, uses considerable amounts of adenosine triphosphate (ATP) and oxygen. Light reduces cation influx and thereby lowers metabolic demand. Blood vessels are compromised in the diabetic retina and may not be able to meet the higher metabolic demand in darkness. Emixustat is a visual cycle modulator (VCM) that reduces chromophore levels and, therefore, may mimic light conditions. We evaluated the effect of emixustat on oxygen consumption and cation influx in dark conditions. Methods: Cation influx was measured in rats using Mn2+-magnetic resonance imaging (MEMRI). Retinal oxygen profiles were recorded to evaluate oxygen consumption. In the MEMRI protocol, animals were treated with either emixustat or vehicle. In the oxygen protocol, animals were untreated or treated with emixustat. Results: In vehicle-treated animals, cation channel activity increased in the dark. Emixustat treatment reduced cation channel activity; activity was comparable to vehicle-treated controls in light conditions. In vehicle-treated animals, minimum retinal oxygen tension decreased as the retina recovered from a photobleach, indicating that more oxygen was being consumed. Emixustat treatment prevented the decrease in oxygen pressure after photobleach. Conclusions: Emixustat reduced the cation influx and retinal oxygen consumption associated with dark conditions. VCMs are a promising potential treatment for ischemic retinal neovascularization, such as that in diabetic retinopathy.

Association among endometrial hyperemia, uterine bacterial infection, and characteristics of large ovarian follicles in dairy cows.

We investigated the association among endometrial hyperemia, uterine bacterial infection, and features of the large ovarian follicles in dairy cows. Genital organs were collected in a complete set at a slaughterhouse, and the degree of endometrial hyperemia was examined for the direct evaluation of uterine inflammation. The rate of bacterial infection in the uterus was higher in cows with endometrial hyperemia regardless of the severity of hyperemia, compared with cows without hyperemia. Moreover, the characteristics of the follicular fluid were changed in cows with uterine bacterial infection and included high concentrations of lipopolysaccharide and malondialdehyde (lipid peroxidation marker). These findings can be utilized as the basic information for the direct evaluation of the uterine inflammatory status in dairy cows.

Potential of muscles to accelerate the body during late-stance forward progression in individuals with knee osteoarthritis.

Many individuals with knee osteoarthritis (OA) generate low forward center of mass (COM) acceleration during the late stance phase, consequently making it difficult to walk fast. This study analyzed individual muscle contributions to forward COM acceleration and the muscle potential (i.e., acceleration by unit force) to clarify whether reduced acceleration was related to decreased muscle potential of forward progression by the triceps sure. Twelve individuals with knee OA and 12 healthy age-matched individuals participated in this study. All participants underwent kinetic measurements during normal gait. The simulation involved 92 Hill-type muscle-tendon units with 23 degrees of freedom. We analyzed how each muscle contributed to forward COM acceleration during the 70-100% stance phase using an induced acceleration analysis. Next, the muscle potential of forward COM acceleration was calculated. Our results showed that individuals with knee OA had significantly lower forward COM acceleration with the soleus, gastrocnemius, and iliopsoas muscles compared with controls. Lower muscle potential in the soleus was found in those with knee OA. These findings implied that improving the contribution of the soleus to forward body progression would be effective for increasing the gait speed of those with knee OA during the late stance phase.

Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment. DESIGN: Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial. PARTICIPANTS: Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2 were enrolled. METHODS: Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point. RESULTS: Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%). CONCLUSIONS: Emixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug's mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.