The Acute Effects of Caffeine on OCT and OCTA Parameters: A Systematic Review and Meta-Analysis

Davi Marçola Veiga,1 Yuri Aleksander Ivanov,2 Alexandre Yamada Fujimura Júnior,1 Maria Eduarda Figueiredo Rebolho,1 Beatriz Gonçalves da Silva Miroski Gerente,3 Dillan Cunha Amaral,4 Raíza Jacometti,5 Jaime Guedes,6 Mário Luiz Ribeiro Monteiro,5 Ricardo Noguera Louzada4,5 1Faculty of Medicine, Marilia Medical School, Marília, SP, Brazil; 2Faculty of Medicine, University of the Extreme South of Santa Catarina, Criciúma, SC, Brazil; 3Faculty of Medicine, University of Southern Santa Catarina, Florianópolis, SC, Brazil; 4Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 5Division of Ophthalmology and the Laboratory for Investigation in Ophthalmology (LIM-33), Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil; 6Aran Eye Associates, Coral Gables, FL, USACorrespondence: Jaime Guedes, Aran Eye Associates, 1097 S Lejeune Road, Coral Gables, FL, 33134, USA, Email [email protected]: This systematic review and meta-analysis aimed to comprehensively assess the acute effects of caffeine and caffeinated beverages on ocular microvasculature measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters, explicitly focusing on subfoveal choroidal thickness (SFCT) and superficial capillary vessel density (SVD), and deep capillary vessel density (DVD).Methods: A systematic search was conducted across PubMed, the Cochrane Database, and Embase for trials evaluating the acute effects of caffeine or caffeinated beverages on SFCT, SVD, and DVD, as measured by OCTA. Pooled mean differences (MD) were calculated using random-effects models, with heterogeneity assessed by I2 statistics. Subgroup analyses were performed by study design, intervention type, and refractive status. The protocol was prospectively registered in PROSPERO (CRD420251091123). Statistical analyses were performed using RStudio 2025.05.1+513.Results: 18 studies comprising 630 patients were included. Pooled analysis demonstrated a significant reduction in SFCT after caffeine intake (– 23.79 μm; 95% CI: – 31.43 to – 16.15; p < 0.001), particularly with coffee and caffeine capsules, whereas no effect was observed with energy drinks or in highly myopic eyes. Regarding SVD, caffeine was associated with significant reductions across foveal, parafoveal, and perifoveal regions, mainly driven by coffee and capsule interventions. In DVD analyses, no overall significant effect was found; however, subgroup analyses indicated significant reductions with caffeine capsules and coffee, while energy drinks showed opposite trends.Conclusion: Acute caffeine intake, primarily from capsules or coffee, induces significant SFCT reduction and modest reductions in SVD, while changes in DVD were confined mainly to the caffeine-capsule subgroup, suggesting that energy drink ingredients may counteract caffeine-induced vasoconstriction. These findings offer valuable insights into the acute effects of caffeine on ocular microvasculature; however, the modest effect sizes necessitate caution regarding inherent physiological, measurement, and bioactive components variability. This study establishes a foundation for future investigations into the clinical significance of acute ocular microvascular fluctuations following caffeine intake.Keywords: caffeine, coffee, subfoveal choroidal thickness, optical coherence tomography, optical coherence tomography angiography, systematic review