Paracentral Acute Middle Maculopathy and Risk of Cardiovascular Disease, Stroke, and Death: A Longitudinal Study
July 2026
Danny A. Mammo MD
Cole Eye Institute
Cleveland Clinic
Cleveland, OH
Limoli C, Raja LD, Wagner SK, et al. Paracentral Acute Middle Maculopathy and Risk of Cardiovascular Disease, Stroke, and Death: A Longitudinal Study. American Journal of Ophthalmology. 2024;267:286-292.
Paracentral acute middle maculopathy (PAMM) describes a hyperreflective band observed at the level of the inner nuclear layer on optical coherence tomography (OCT) imaging, attributed to transient macular hypoperfusion. While historically recognized alongside retinal vascular diseases (RVD), growing evidence suggests that isolated PAMM (iPAMM) lesions could serve as a clinical indicator or prognostic biomarker for subclinical systemic vascular disease. A group of researchers released the results of a single-center, retrospective cohort study, published in the American Journal of Ophthalmology, evaluating the long-term risk of developing acute cardiovascular events (CVE), cerebrovascular diseases, and all-cause mortality in patients diagnosed with PAMM.
The longitudinal study reviewed electronic medical records from Moorfields Eye Hospital of patients presenting with OCT-confirmed PAMM between January 2014 and June 2021. Patients with a history of major CVE within the 2 years prior to their PAMM event were excluded. A total of 43 patients met the inclusion criteria with a minimum 6-month follow-up, and were stratified a priori by age ( < 50 and > 50 years) and by whether the PAMM was isolated or associated with a concomitant RVD. Kaplan-Meier analysis and adjusted Cox proportional models were used to estimate CVE risk.
Across the younger cohort (n=23), a wide range of underlying predisposing factors was noted at the time of the PAMM event. In the younger iPAMM group (n=12), 91.6% of patients had a clear underlying systemic cause identified, including sickle cell disease (50%), breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, or amphetamine use. Conversely, young patients with combined PAMM and RVD were generally healthy, outside of oral contraceptive use in four individuals. Over a median follow-up of 20.5 months, no young patients experienced an adverse CVE.
In the older cohort (> 50 years; n=20), 75% of subjects possessed at least one pre-existing coronary risk factor, primarily systemic hypertension. Over a median follow-up of 14 months, a massive divergence in systemic outcomes occurred between the older subgroups. While new CVEs were diagnosed in 54.5% (n=6) of the combined PAMM and RVD group within a median of 36 months, all 100% (n=9) of the older individuals with isolated PAMM developed a new CVE. These events included strokes, coronary heart disease, deaths, carotid artery occlusions, and hypertensive crises. Adjusted for age and sex, older subjects with iPAMM faced a significantly higher hazard ratio of 6.37 (95% CI: 1.68-24.14, P=.017) for developing a CVE compared to those with PAMM + RVD. Notably, the iPAMM cohort exhibited an earlier peak in peri-onset risk, with events occurring at a median of just 1 month following the ocular diagnosis compared to 36 months in the RVD group (P<.001). Visually, both older groups demonstrated a favorable prognosis, though the improvement was only statistically significant in the iPAMM group (0.7 logMAR to 0.2 logMAR, P=.033).
These findings indicate that paracentral acute middle maculopathy acts as a critical sentinel vascular marker for severe, life-threatening systemic events. When PAMM presents as an isolated finding without an obvious local retinal vascular occlusion, it highlights a profound risk of immediate stroke, coronary disease, or death. Clinicians must recognize that “the incidence of CVE was particularly increased in the peri-onset timeframe,” underscoring that an incident iPAMM represents an ocular and systemic emergency. Immediate, comprehensive cardiovascular evaluations to screen for carotid occlusive disease, giant cell arteritis, and uncontrolled atherosclerotic risk factors are required alongside routine ophthalmic care to mitigate secondary mortality and morbidity.
