**Background:** Advanced glycation end products (AGEs) are modified protein derivatives formed via non-enzymatic reactions (Maillard reaction) and are implicated in various inflammatory and degenerative diseases. AGEs have been associated with ocular conditions such as age-related macular degeneration, cataract, glaucoma, and diabetic retinopathy. Previous studies reported higher serum AGE levels in uveitis patients (Behçet's disease, HLA-B27-associated uveitis, sarcoidosis, Vogt–Koyanagi–Harada disease) compared to healthy controls. The receptor for AGEs (RAGE) amplifies inflammatory responses and is found in ocular tissues. This study aimed to investigate whether skin autofluorescence (SAF) AGE levels could serve as a biomarker for uveitis/scleritis activity in systemic immune-related disease patients.
**Methods:** This prospective cross-sectional study was conducted at Siriraj Hospital, Bangkok, Thailand from October 2019 to March 2020. Inclusion criteria: age >18 years, systemic immune-related disease with active non-infectious uveitis/scleritis in at least one eye. Exclusion criteria: infectious ocular inflammation, diabetes, cardiovascular disease. AGEs were measured using the Diagnoptics non-invasive ultraviolet tissue autofluorescence reader on the volar forearm, with results reported in arbitrary units (AU). Active uveitis/scleritis was defined per Standardization of Uveitis Nomenclature and Standardized Grading System for Scleritis criteria (anterior chamber cells ≥1+, vitreous cells ≥1+, vitreous haze ≥grade 2, active retinal/choroidal infiltration, or scleral injection ≥1+). Thirty-one age-matched healthy controls were enrolled. Statistical analysis used Student's t-test, Chi-square/Fisher's exact test, and stepwise backward multivariate logistic regression.
**Key Results:** Thirty-one active uveitis/scleritis patients (mean age 40.0±12.8 years, 55% female) and 31 controls (mean age 40.9±12.8 years) were included. The most common associated systemic disease was VKH disease (n=14), followed by HLA-B27-associated uveitis (n=8), Behçet's disease (n=4), sarcoidosis (n=2), SLE (n=2), and RA (n=1). Most patients had active uveitis (96.8%), with only one RA patient having active scleritis. Anterior uveitis was most common (71.0%), and 71.0% had bilateral disease. Mean SAF AGE level in the study group was 2.38±0.66 AU vs 2.58±0.56 AU in controls (p=0.20). Multivariate analysis showed decreased SAF AGE level was significantly associated with active uveitis/scleritis (OR 0.01, 95% CI 0.00004–0.81; p=0.04). No other variables (age, gender, weight, mean arterial blood pressure, serum creatinine, HbA1c) were independently associated.
**Clinical Implications:** The study found that SAF AGE levels were not significantly different between active uveitis/scleritis patients and healthy controls, and paradoxically lower SAF AGE levels were associated with active inflammation in multivariate analysis. This contradicts previous studies showing higher serum AGEs in uveitis patients. The authors suggest several explanations: differences in measurement methods (SAF vs serum ELISA), potential confounding by diet (patients may consume low-AGE diets), skin tone interference with SAF, and the presence of immunomodulatory therapy in most patients (74.3% on systemic corticosteroids/immunomodulators). The study has limitations including small sample size, cross-sectional design, lack of serum/skin biopsy AGE measurements, and inability to assess pre/post-treatment changes. The authors conclude that SAF AGE level is not a reliable biomarker for uveitis/scleritis activity and recommend larger studies with adjustment for confounders and use of conventional methods (serum/skin biopsy) to identify specific AGE subtypes.