Case Report: Histamine-mediated inflammation and mast cell modulation in central serous chorioretinopathy: a two case illustrations.

Introduction: Central serous chorioretinopathy (CSCR) is characterized by retinal pigment epithelium dysfunction and choroidal hyperpermeability. Beyond established associations such as psychosocial stress and corticosteroid exposure, experimental and epidemiological findings raise the possibility that mast cell and histamine-related pathways may contribute to CSCR pathophysiology. This study reviews mechanistic and clinical evidence for the role of histamine in the pathogenesis of CSCR, as well as the role of histamine-targeted therapies in this condition. We also present two cases, highlighting the possible therapeutic role of anti-allergy agents in CSCR. Methods: We searched Ovid MEDLINE, Embase, and Cochrane CENTRAL to October 2025 for studies of antihistamines and/or mast-cell stabilizers, alone or in combination in central serous retinopathy and pachychoroid spectrum diseases. Eligible designs included human observational and controlled studies. Two reviewers independently screened, extracted, and appraised data using ROBINS-I, NOS, and GRADE. Results were narratively synthesized. Results: After screening 316 articles, three studies (430 patients, 390 controls) from India and the United States were included. Direct evidence for anti-allergy therapeutics was limited to a single management series, in which short-course antihistamine treatment showed no meaningful visual or anatomical benefit; however, improvements occurred spontaneously or after focal laser. One case-control study reported a higher prevalence of antihistamine use and allergic disorders among CSCR patients (OR 4.1), suggesting a possible histamine-mediated risk. Another case-control study found no statistically significant association between antihistamine use and CSCR after multivariable adjustment. Conclusion: Analysis of the literature revealed inconsistent associations between antihistamine use and CSCR risk, with a brief therapeutic trial offering no benefit for acute CSCR. However, two illustrative cases demonstrate temporal associations between interruption of anti-allergic therapy and subsequent CSCR activity, followed by anatomical improvement after treatment re-initiation or modification. These observations are hypothesis-generating but cannot establish therapeutic efficacy or causality, particularly given concurrent treatment changes in case 1. Given the inconclusive therapeutic data, further randomized controlled trials are warranted to more rigorously evaluate sustained mast-cell stabilization regimens before drawing clinical conclusions.