Intense Pulsed Light for Perennial Allergic Conjunctivitis: A Prospective Interventional Study with Untargeted Tear Metabolomics

Abstract

Objective:

To evaluate the clinical efficacy of an intense pulsed light (IPL)-augmented regimen for moderate-to-severe perennial allergic conjunctivitis (PAC) and to elucidate its potential mechanisms through tear inflammatory factor profiling and untargeted metabolomics.

Methods:

In this prospective, single-arm, interventional study, 18 patients underwent two IPL sessions at two-week intervals. Outcomes included symptom visual analog scale (VAS) scores and sign scores, bulbar redness index (BRI), tear breakup time (TBUT), and tear inflammatory factors, including immunoglobulin E (IgE), matrix metalloproteinase-9 (MMP-9), and lymphotoxin-alpha (LTA). Untargeted metabolomics of tear fluid was performed using LC–MS/MS to identify differential metabolites and pathways.

Results:

Symptom VAS [median difference: –25.0 (95% CI: –31.0, –21.0); p < 0.01] and sign [–4.0 (–6.0, –4.0); p < 0.01] scores improved significantly, with 79.4% symptom reduction, a shift from frequent to occasional itching, and large effect sizes (Cohen’s d: 2.18 symptoms, 2.70 signs). TBUT and BRI showed no significant changes. Tear IgE and MMP-9 tended to decrease and LTA to increase (nonsignificant). MMP-9 positively correlated with posttreatment BRI (r = 0.570, p < 0.05), while LTA negatively correlated with baseline BRI (r = –0.573, p < 0.05). Untargeted metabolomics identified 65 differential metabolites: purine-related compounds (e.g., adenine, guanine) and stearic acid were downregulated; oleic acid, 9-OxoODE, etc., were upregulated. Purine metabolism was significantly altered (Raw p = 0.0013, false discovery rate [FDR] = 0.104), while unsaturated fatty acid biosynthesis changes were not significant (Raw p = 0.49, FDR = 1). No serious adverse events occurred.

Conclusion:

An IPL-augmented regimen may alleviate moderate-to-severe PAC, which is consistent with the modulation of purine and unsaturated fatty acid metabolism. This modulation is characterized by suppressed purine activity and proinflammatory lipids while enhancing anti-inflammatory and antioxidant unsaturated fatty acids. These changes collectively dampen inflammation and promote immune homeostasis.