Deep-learning automated quantification of longitudinal OCT scans demonstrates reduced RPE loss rate, preservation of intact macular area and predictive value of isolated photoreceptor degeneration in geographic atrophy patients receiving C3 inhibition treatment.

OBJECTIVE: To evaluate the role of automated optical coherence tomography (OCT) segmentation, using a validated deep-learning model, for assessing the effect of C3 inhibition on the area of geographic atrophy (GA); the constituent features of GA on OCT (photoreceptor degeneration (PRD), retinal pigment epithelium (RPE) loss and hypertransmission); and the area of unaffected healthy macula.To identify OCT predictive biomarkers for GA growth. METHODS: Post hoc analysis of the FILLY trial using a deep-learning model for spectral domain OCT (SD-OCT) autosegmentation. 246 patients were randomised 1:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM) and sham treatment (pooled) for 12 months of treatment and 6 months of therapy-free monitoring. Only participants with Heidelberg SD-OCT were included (n=197, single eye per participant).The primary efficacy endpoint was the square root transformed change in area of GA as complete RPE and outer retinal atrophy (cRORA) in each treatment arm at 12 months, with secondary endpoints including RPE loss, hypertransmission, PRD and intact macular area. RESULTS: Eyes treated PM showed significantly slower mean change of cRORA progression at 12 and 18 months (0.151 and 0.277 mm, p=0.0039; 0.251 and 0.396 mm, p=0.039, respectively) and RPE loss (0.147 and 0.287 mm, p=0.0008; 0.242 and 0.410 mm, p=0.00809). PEOM showed significantly slower mean change of RPE loss compared with sham at 12 months (p=0.0313). Intact macular areas were preserved in PM compared with sham at 12 and 18 months (p=0.0095 and p=0.044). PRD in isolation and intact macula areas was predictive of reduced cRORA growth at 12 months (coefficient 0.0195, p=0.01 and 0.00752, p=0.02, respectively) CONCLUSION: The OCT evidence suggests that pegcetacoplan slows progression of cRORA overall and RPE loss specifically while protecting the remaining photoreceptors and slowing the progression of healthy retina to iRORA.

Evaluating the Effects of C3 Inhibition on Geographic Atrophy Progression from Deep-Learning OCT Quantification: A Split-Person Study.

INTRODUCTION: To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification. METHODS: A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12 months. SD-OCT scans of study and fellow eyes taken at baseline and 12 months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye. RESULTS: Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm2; P = 0.003), PRD (0.739 vs. 1.23 mm2; P = 0.015), RPE-loss (0.789 vs. 1.17 mm2; P = 0.007) and intact macula (- 0.735 vs. - 1.29 mm2; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21). CONCLUSIONS: Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF. TRIAL REGISTRATION: Clinical Trials identifier: NCT02503332.

Visual and Anatomical Outcomes of a Single Intravitreal Dexamethasone in Diabetic Macular Edema: An 8 Year Real-World Study.

IMPORTANCE: Diabetic macular edema (DME) is a major cause of vision loss in patients with diabetes mellitus. Intravitreal dexamethasone is a treatment option for patients unsuitable for or non-responsive to anti-angiogenic agents. OBJECTIVE: To quantify visual and anatomical outcomes from an initial intravitreal dexamethasone injection over the expected 6-month period of dexamethasone release by the implant. Design and enrolment: This is a retrospective cohort study using electronic medical records of patients reviewed between 1 January 2012 and 1 April 2022. SETTING: A tertiary eye-care center in London, United Kingdom; Moorfields Eye Hospital National Healthcare System Foundation Trust. PARTICIPANTS: The cohort comprised 418 adult patients with DME who received an initial treatment of 700 µg intravitreal dexamethasone in the study period. Of these, 240 patients met the inclusion criteria of ≥2 hospital visits following initial injection (≥1 beyond 6 months) and no previous ocular corticosteroid treatment or missing assessment at baseline. EXPOSURE(S): Intravitreal dexamethasone implant (700 µg). MAIN OUTCOME(S) AND MEASURE(S): Probability of a positive visual outcome, defined as ≥5 or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS)-letter gain after treatment when compared to baseline (Kaplan-Meier models). RESULTS: From the initial intravitreal dexamethasone injection alone, we observed a >75% chance of gaining ≥5 ETDRS letters and >50% chance of gaining ≥10 ETDRS letters within 6 months. There was less than a 50% chance of sustaining either positive visual outcome beyond 4 months. CONCLUSIONS AND RELEVANCE: Most patients can be expected to have a positive visual outcome following an initial injection of dexamethasone implants that subsides within 4 months. Real-world re-treatment was observed to be delayed until after visual benefits were lost in half of the cohort. Further research will be needed to study the effects of delays in re-treatment.

Marriage contributes to higher obesity risk in China: findings from the China Health and Nutrition Survey.

BACKGROUND: To investigate the association between marriage and the prevalence of overweight and obesity in China. METHODS: We conducted cross-sectional and retrospective cohort analyses using a nationwide sample of 36,310 individuals from the China Health and Nutrition Survey [2004-2015]. RESULTS: The prevalence of overweight and obesity increased from 28.7% to 36.7% and from 8.0% to 14.5% between 2004 and 2015, respectively. The cross-sectional analysis showed that married individuals were at a higher risk of being overweight (OR =2.18; 95% CI, 1.90-2.51) or obese (OR =1.95; 1.57-2.43) than never-married individuals. Divorced/widowed individuals were also at a greater risk of being overweight (OR =1.80; 1.51-2.13) or obese (OR =1.67; 1.28-2.17) than never-married individuals. Retrospective cohort analysis showed that individuals who married during the study were 1.55 (1.13-2.11) times more likely to be overweight than those who remained never-married. Compared to those who remained never-married, individuals who remained married were 1.71 (1.42-2.07) and 1.45 (1.11-1.89) times more likely to be overweight and obese. Individuals who became divorced or widowed were more likely to be overweight (RR =1.59; 1.18-2.15) or obese (RR =1.63; 1.08-2.46) than those who remained never-married. However, the risk of being overweight or obese among those who became divorced or widowed did not differ significantly from the risk among those who remained married. CONCLUSIONS: Marriage contributes to an increased risk of overweight and obesity in China; however, this risk is not significantly reduced by exiting a marriage.

Evaluation of work resumption strategies after COVID-19 reopening in the Chinese city of Shenzhen: a mathematical modeling study.

OBJECTIVES: As China is facing a potential second wave of the epidemic, we reviewed and evaluated the intervention measures implemented in a major metropolitan city, Shenzhen, during the early phase of Wuhan lockdown. STUDY DESIGN: Based on the classic SEITR model and combined with population mobility, a compartmental model was constructed to simulate the transmission of COVID-19 and disease progression in the Shenzhen population. METHODS: Based on published epidemiological data on COVID-19 and population mobility data from Baidu Qianxi, we constructed a compartmental model to evaluate the impact of work and traffic resumption on the epidemic in Shenzhen in various scenarios. RESULTS: Imported cases account for most (58.6%) of the early reported cases in Shenzhen. We demonstrated that with strict inflow population control and a high level of mask usage after work resumption, various resumptions resulted in only an insignificant difference in the number of cumulative infections. Shenzhen may experience this second wave of infections approximately two weeks after the traffic resumption if the incidence risk in Hubei is high at the moment of resumption. CONCLUSION: Regardless of the work resumption strategy adopted in Shenzhen, the risk of a resurgence of COVID-19 after its reopening was limited. The strict control of imported cases and extensive use of facial masks play a key role in COVID-19 prevention.

A systematic review, and meta-analysis, examining the prevalence of price promotions on foods and whether they are more likely to be found on less-healthy foods.

OBJECTIVE: There are concerns that price promotions encourage unhealthy dietary choices. This review aims to answer the following research questions (RQ1) what is the prevalence of price promotions on foods in high-income settings, and (RQ2) are price promotions more likely to be found on unhealthy foods? DESIGN: Systematic review of articles published in English, in peer-review journals, after 1 January 2000. SETTING: Included studies measured the prevalence of price promotions (i.e. percentage of foods carrying a price promotion out of the total number of foods available to purchase) in retail settings, in upper-mid to high-income countries. PARTICIPANTS: 'Price promotion' was defined as a consumer-facing temporary price reduction or discount available to all customers. The control group/comparator was the equivalent products without promotions. The primary outcome for this review was the prevalence of price promotions, and the secondary outcome was the difference between the proportions of price promotions on healthy and unhealthy foods. RESULTS: Nine studies (239 344 observations) were included for the meta-analysis for RQ1, the prevalence of price promotions ranged from 6 % (95 % CI 2 %, 15 %) for energy-dense nutrient-poor foods to 15 % (95 % CI 9 %, 25 %) for cereals, grains, breads and other starchy carbohydrates. However, the I-squared statistic was 99 % suggesting a very high level of heterogeneity. Four studies were included for the analysis of RQ2, of which two supported the hypothesis that price promotions were more likely to be found on unhealthy foods. CONCLUSIONS: The prevalence of price promotions is very context specific, and any proposed regulations should be supported by studies conducted within the proposed setting(s).