Purpose To determine if there are sex differences in levels of regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with intermediate age-related macular degeneration (iAMD) and in controls with no AMD. Methods Patients with iAMD and controls defined by multi-modal imaging were recruited into a Colorado AMD registry. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. Results The plasma level of RANTES was significantly higher in the control group in comparison with the iAMD group. When moderated by sex, RANTES was significantly lower ( P = 0.005) in males (median, 4525.6 pg/mL; interquartile range, 2589–7861 pg/mL) compared with females (median, 6686 pg/mL; interquartile range, 3485–12488 pg/mL) within the iAMD cohort. No significant difference was found in levels of RANTES between males and females in the control group. Conclusions We found that levels of RANTES were moderated by sex in cases with iAMD with lower levels in males compared with females. The findings illustrate the importance of including sex as a biological variable in AMD research. There is a need for further studies of RANTES, stratified by sex, in the advanced phenotypes of AMD. Translational Relevance The biomarker RANTES identified in the plasma of patients with iAMD reflects systemic alterations when stratified by sex.

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Background Visual acuity (VA) loss has been associated with depression in patients with age-related macular degeneration (AMD). However, previous studies did not incorporate subgroups of AMD when correlating VA and mental health. The goal of this study was to describe the relationship between VA and mental health questions in patients with different classifications of AMD, and to identify associations of mental health subscale scores. Methods AMD patients classified by multi-modal imaging were recruited into an AMD registry. Habitual VA was obtained by ophthalmic technicians using the Snellen VA at distance. At enrollment, patients completed the NEI-VFQ-25, which includes 25 questions regarding the patient’s visual functionality. Median with interquartile-range (IQR) scores on the mental health subscale of the VFQ were calculated by AMD classification and VA groups. Univariate and multivariable general linear models were used to estimate associations between mental health scores and variables of interest. Results Eight hundred seventy-five patients were included in the study. Patients with bilateral geographic atrophy (GA) or bilateral GA and neovascular (NV) AMD scored lowest on the mental health subscales with a median (IQR) of 58.2 (38–88) and 59.3 (38–88). When stratified by VA, patients with a habitual VA of 20/200 or worse scored the lowest on mental health subscales scores: median of 43.8 (IQR: 31–62). Patients with a VA of 20/20 scored the highest: 87.5 (IQR: 81–94). Habitual VA of the better- and worse-seeing eye and AMD classification were significantly associated with mental health subscale scores (all p < 0.0001 in both the univariate and multivariable analysis, except the VA of the worse-seeing eye in multivariable model p = 0.027). Patients enrolled during the COVID pandemic had mental health scores that were 2.7 points lower than prior to the pandemic, but this difference was not significant in univariate (p = 0.300) or multivariable analysis (p = 0.202). Conclusion There is a significant association between mental health questionnaire scores and AMD classification, as well as VA in both the better and worse-seeing eyes in patients with AMD. It is important for clinicians to recognize feelings of worry/ frustration in these patients, so they can be appropriately referred, screened, and treated for mental health problems.

Purpose A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls. Methods The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. Results The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799–19,554] pg/mL vs. 5435 [3420–9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls. Conclusions We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients. Translational Relevance The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

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