Breast Cancer Therapy Associated with Punctate Epitheliopathy

Given that these findings may be clinically underrecognized, proactive corneal surface evaluation with fluorescein staining may be a reasonable component of ophthalmic assessment in this patient population. (Epitheliopathy in this image is due to BAK exposure in a glaucoma patient, not this study.) Photo: Jacob R. Lang, OD. Click image to enlarge. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, together with endocrine therapy, are standard treatments for a specific type of carcinoma called hormone receptor-positive, HER2-negative breast cancer. However, by blocking a particular phase of cell growth (G1/S cell-cycle transition), these agents may impair renewal of the corneal epithelium, one of the most rapidly proliferating tissues in the body.Researchers based in Turkey hypothesized that CDK4/6 inhibitor exposure would be associated with corneal epithelial disruption independent of tear film abnormalities. Their comparative study determined that CDK4/6 inhibitor–based therapy was associated with significantly higher prevalence and severity of punctate epitheliopathy and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggested a direct cytostatic effect on the corneal epithelium.However, the researchers noted in their paper, which was published in American Journal of Ophthalmology, incomplete Ocular Surface Disease Index (OSDI) data in the sample “limits definitive conclusions regarding symptom burden.” They also advised that routine fluorescein staining may be warranted for patients on CDK4/6 inhibitor therapy.A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor for a minimum of three months, 44 receiving aromatase inhibitor monotherapy for at least three months and 43 age-matched postmenopausal controls without systemic oncologic therapy.Punctate epitheliopathy was present in 44.4% of eyes in the CDK4/6 inhibitor (ribociclib, palbociclib or abemaciclib) combined with an aromatase inhibitor group vs. 4.7% in the aromatase inhibitor alone group and 2.3% in controls. All moderate (13.3%) and severe/complicated (8.9%) punctate epitheliopathy cases occurred exclusively in the combination group. Vortex keratopathy was observed in 13.3% of combination group patients and in none of the other groups. Schirmer values, tear break-up time and OSDI scores did not differ among groups. Within the CDK4/6 inhibitor combined with an aromatase inhibitor group, punctate epitheliopathy was not associated with treatment duration or tear film parameters.The research team suggested in their paper two pragmatic measures grounded in clinical reasoning, while emphasizing that these were not validated screening guidelines. For oncologists, awareness of corneal epithelial toxicity as a possible class effect of CDK4/6 inhibitors may warrant consideration of a targeted ocular history (new-onset foreign body sensation, photophobia, or blurred vision) in routine follow-up, with referral to an eye doctor when symptoms arise.“For eyecare practitioners, patients who are receiving CDK4/6 inhibitor therapy should undergo fluorescein staining as part of any examination—even in the absence of reported symptoms—to identify early epithelial changes that may benefit from supportive management with preservative-free lubricants,” they wrote.Click here for the journal source. Ozbay EK, Ozturk B, Ozbay MF, et al. Corneal epithelial alterations associated with CDK4/6 inhibitor therapy in hormone receptor-positive breast cancer. Am J Ophthalmol. June 24, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.