Longitudinal Ocular Surface Changes in Women with Polycystic Ovary Syndrome Receiving Hormonal or Ovulation-Induction Therapy: A Prospective Cohort Study.

Abstract

Background: Polycystic ovary syndrome (PCOS) is a multisystem endocrine disorder associated with hyperandrogenism, insulin resistance, and chronic low-grade inflammation. These systemic changes may affect ocular surface homeostasis, yet longitudinal data on treatment effects are limited. This study aimed to evaluate different ocular surface parameters in women with PCOS and assess their changes following treatment with cyclical estrogen-progestogen therapy (hormone therapy [HT]) or clomiphene citrate.

Methods: In this prospective cohort study, 60 women with PCOS and 30 age-matched healthy controls underwent ocular surface evaluation using the Dry Eye Diagnostic System (MediWorks), Schirmer's test, tear breakup time (TBUT), and the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. PCOS patients were treated with HT for non-fertility indication (n = 30) or clomiphene citrate for fertility indication (n = 30) and re-evaluated at 3 and 6 months. Laboratory markers included LH/FSH ratio, total testosterone, and neutrophil-to-lymphocyte ratio (NLR).

Results: At baseline, PCOS patients showed significant reductions (p < .001) in tear function (TBUT, Schirmer's test, NIBUT), a significantly higher proportion of meibomian gland loss, and abnormal lipid layer thickness, significantly higher conjunctival redness, and increased central corneal thickness (CCT) compared with controls (p < .001). Over six months, HT therapy was associated with further significant reduction of tear film stability and meibomian gland morphology (p < .001), alongside a continued increase in CCT, reduced best corrected visual acuity (BCVA), and decreased tear functions assessed by tear break up time (TBUT), Schirmer's test (p < .001). Conversely, clomiphene citrate treatment led to significant increase in tear film parameters, meibomian gland function, and significant decrease in ocular surface staining, and CCT (p < .001), with preservation of visual acuity.

Conclusion: PCOS is associated with subclinical ocular surface dysfunction and increased corneal thickness. Treatment modality was associated with differing ocular outcomes: HT use was associated with worsening dry eye parameters, while clomiphene citrate use was associated with improved tear film stability and meibomian gland integrity; this between-group divergence remained significant after adjusting for baseline values and for baseline hormonal/inflammatory covariates (all adjusted p < .001 except IOP). However, because treatment groups were not randomized and differed at baseline, these associations should not be interpreted as causal drug effects. Objective ocular surface assessment should be considered in PCOS management to guide therapy and monitor ocular health.