Prospective observational study of the association between tear and serum CHI3L1 and PTX3 levels and the severity and prognosis of retinopathy of prematurity.

BACKGROUND

To investigate the independent and combined associations of tear-fluid and serum chitinase-3-like protein 1 (CHI3L1) and pentraxin-3 (PTX3) with retinopathy of prematurity (ROP) severity and long-term neurovascular outcomes, and to evaluate their incremental predictive value beyond conventional risk factors.

METHODS

This prospective cohort study enrolled 235 premature infants with ROP (diagnosed January 2024-May 2025) and 110 gestational-age-matched controls. ROP infants were stratified into poor-outcome (n = 34) and favorable-outcome (n = 201) subgroups based on treatment response and longitudinal neurovascular findings. Poor outcome was defined as posterior pole retinal fold involving the macula, retinal detachment, or posterior pole obscuration by fibrous tissue or a "white mass" at ≥6 months after intravitreal anti-VEGF therapy. Tear fluid and venous blood were collected within 24 h of the first ROP diagnosis; CHI3L1 and PTX3 were measured by enzyme-linked immunosorbent assay. Spearman correlation, multivariable logistic regression, and receiver operating characteristic (ROC) curves were employed to examine the associations.

RESULTS

Tear and serum CHI3L1 and PTX3 concentrations increased stepwise across control, mild-ROP, and severe-ROP groups (all p < 0.05), correlating positively with fundus stage (Spearman r = 0.610-0.779). Infants with unfavorable neurovascular outcomes had higher baseline levels than those with favorable outcomes (p < 0.05). Multivariable analysis identified gestational age, birth weight, severe ROP, bronchopulmonary dysplasia, tear CHI3L1, tear PTX3, serum CHI3L1, and serum PTX3 as independent predictors of poor outcome (p < 0.05). The four-biomarker panel predicted progression with an area under the curve of 0.847 (95% CI 0.775-0.919), outperforming individual markers (p < 0.05).

CONCLUSION

Tear and serum CHI3L1 and PTX3 are associated with ROP severity and may serve as a noninvasive early biomarker panel for risk assessment.