Retinal nerve fiber layer thickness as a biomarker of uveitis activity: A systematic review

Optical coherence tomography (OCT)-derived peripapillary retinal nerve fiber layer thickness (pRNFL) has emerged as a promising surrogate for inflammatory activity in uveitis. We conducted a PRISMA-compliant systematic search of PubMed and Embase to identify studies that measured pRNFL in infectious and noninfectious uveitis. Twenty-three studies comprising 2632 eyes met our criteria. Risk of bias was appraised with the ROBINS-I tool and ranged from low to serious, predominantly moderate (13/23) and serious (9/23). Between study heterogeneity was substantial across OCT platforms, anatomic locations, and etiologies. In cross-sectional cohorts, eyes with active uveitis demonstrated an average pRNFL thickening ranging from + 12 to + 44 µm in adults and 8-25 µm in children, when compared with inactive, fellow, or healthy control eyes. Optic discs with angiographic leakage had greater pRNFL thickness, and in one pediatric series, a pRNFL threshold of 130 µm achieved 79 % sensitivity and 85 % specificity for detecting optic disc leakage. Longitudinal analyses demonstrated reversibility of pRNFL thickening, with reductions ranging from approximately 6-47 % of baseline values as inflammation subsided over 1-12 months. Thickening was most pronounced in intermediate, posterior, and panuveitic eyes and least pronounced in isolated anterior uveitis, whereas Fuchs uveitis syndrome showed little or no change. These findings indicate that pRNFL thickening may reflect uveitic activity and warrant further validation.