Mihaela-Madalina Timofte-Zorila, Mariana Pavel-Tanasa, Giuseppe Giannaccare, Nicoleta Vlas, Filippo Lixi, Mario Troisi, Daniela Constantinescu, Radu Tanasa, Diana Alecu, Sabina Turcas, Sinziana Istrate, D Brănişteanu, Cristina Preda, Daniel Constantin Branisteanu
Dry eye disease (DED) is a common complication following cataract-surgery, potentially impairing visual recovery. Low-level light therapy (LLLT) has emerged as a noninvasive approach to improve ocular surface status. This study evaluated the perioperative effects of LLLT on ocular surface modulation by correlating clinical outcomes with tear biomarker dynamics and developing predictive models to identify patients most likely to benefit from LLLT. Of the 98 patients initially randomized, 88 were included in the final analysis, with 44 allocated to the LLLT group and 44 to the sham treatment group. Clinical evaluation-including Ocular Surface Disease Index (OSDI) as the primary outcome, and tear breakup time, Schirmer test, and tear osmolarity as secondary endpoints-was performed preoperatively and one month postoperatively to classify patients as preclinical or having DED. Tear levels of biomarkers involved in tissue repair and neurotrophic-signaling (GDF-15,β-NGF, VEGFA, PDGF-AB, PDGF-CC) and inflammation (OPN, OPG, TNF-α) were assessed as exploratory endpoints and quantified using Luminex-FlexMap3D technology. LLLT-treated patients showed significantly higher clinical improvement post-cataract surgery than sham controls (44.2% vs. 4.4%; p < 0.0001). In DED patients, LLLT significantly increased GDF-15 (77.6 ± 7.2 to 95.5 ± 7.4 pg/mL; p = 0.0112) and PDGF-CC (711.4 ± 76.6 to 1024 ± 130.8 pg/mL; p = 0.0473). The LLLT-induced β-NGF increase was more pronounced in preclinical cases than in those with baseline DED (10.1 ± 3.02 vs. 5.8 ± 0.55 pg/mL; p = 0.0271). Biomarker profiles indicated inflammatory resolution post-LLLT, whereas sham-treated eyes showed persistent inflammation. Finally, integrative modeling of clinical and molecular data yielded a LASSO-adjusted AUC of 0.886, underscoring high discriminative performance. LLLT accelerates ocular surface recovery after cataract surgery by modulating reparative, neurotrophic, and inflammatory pathways. Tear biomarkers assessed at baseline and through one-month dynamics (GDF-15, PDGF-CC, β-NGF) and integrated with clinical parameters, may help predict treatment response and guide personalized postoperative management.