Paracentral acute middle maculopathy and risk of cardiovascular disease, stroke, and death: a longitudinal study

Purpose: To evaluate the risk of acute cardiovascular events (CVE), including cardiovascular diseases, cerebrovascular diseases, and all-cause mortality in patients with paracentral acute middle maculopathy (PAMM). Design: Retrospective cohort study METHODS: We studied 43 individuals with optical coherence tomography -documented PAMM attending Moorfields Eye Hospital between January 2014 and June 2021. We excluded patients with preceding (< 2 years) major adverse cardiac events. We stratified patients by age (<50 years & ≥50 years) and whether associated with retinal vascular diseases (RVD) or isolated (iPAMM). We assessed risk factors, clinical characteristics, and visual prognosis of the patients. CVE risk was estimated using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression. Results: In young patients with iPAMM patients (n=12), underlying predisposing factors included six (50%) sickle cell disease and five (41.6%) others, including breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, amphetamine use; among those with PAMM+RVD (n=12) one (9%) had a vascular disorder, and four (44.4%) oral contraceptive use. In the older group of 20 patients, 15 (75%) had at least one coronary risk factor. During a median follow-up of 14 months (range 12-54), older subjects with iPAMM had a higher risk of developing CVE than those with PAMM+RVD (p<0.001). Notably, iPAMM displayed a significantly earlier peak in peri-PAMM CVE risk compared to PAMM+RVD (median: 1 month, range 1-40 months vs. 36 months, range 12-54 months). Relative to those with PAMM+RVD, risk of CVE was significantly higher in patients with iPAMM, adjusted for age and sex (hazard ratio: 6.37, 95% Confidence Interval 1.68-24.14, p=0.017). No young patients experienced adverse CVE. At baseline, older iPAMM patients mean best corrected visual acuity of 0.7 (0-1.8) LogMAR, which improved significantly to 0.2 (0-1.30) LogMAR at the latest visit (p=0.033). Conclusion: Young individuals with iPAMM have a higher prevalence of predisposing factors compared to those presenting with combined PAMM+RVD. Older patients with iPAMM had a higher risk of CVE than those with PAMM+RVD, especially in the peri-onset timeframe. This suggests the need for a prompt cardiovascular assessment to rule out systemic etiologies and optimize cardiovascular risk factors, in addition to ongoing ophthalmology input.