Case Report: Ribociclib-associated bilateral neurotrophic keratitis requiring amniotic membrane transplantation during adjuvant treatment of early breast cancer

Background Cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy are standard of care for hormone receptor (HR)-positive, HER2-negative breast cancer in metastatic and adjuvant settings. The ribociclib label lists dry eye and increased lacrimation among ocular reactions in under 10% of patients, and isolated vortex keratopathy, epithelial keratopathy, and palinopsia are described. To our knowledge, neither neurotrophic keratitis (NK) nor management of an ocular adverse event with amniotic membrane transplantation (AMT) has been reported with any CDK4/6 inhibitor. Case A 42-year-old premenopausal woman with stage IIB (cT2N1) HR-positive/HER2-negative invasive ductal carcinoma achieved a pathologic complete response after neoadjuvant chemotherapy and bilateral mastectomy. Adjuvant abemaciclib was discontinued after one month for refractory gastrointestinal toxicity, without ocular complaints. Ribociclib 400 mg/day was initiated. After approximately four months she developed bilateral blurred vision; optometry identified bilateral inferior superficial punctate keratitis (SPK), and preservative-free lubrication was started. At the fifth-month visit, bilaterally reduced corneal sensitivity, a feature of early neurotrophic keratopathy, was documented, and prednisolone acetate 1% was begun. With symptoms failing to improve, ribociclib was held. At the six-month visit, with central SPK, tear-film instability, and further visual decline despite corticosteroid, amniotic membrane grafts with bandage contact lenses were placed sequentially in each eye, and topical cyclosporine 0.05% was started. Ribociclib was permanently discontinued. Right-eye vision normalized within five months; the left eye recovered over fifteen months. Anastrozole and all other concomitant medications were continued without recurrence. Conclusion To our knowledge, this appears to be the first reported case of bilateral neurotrophic keratitis during CDK4/6 inhibitor therapy and the first ribociclib-associated ocular adverse event refractory to standard topical therapy that improved after procedural intervention. A Naranjo score of 5 indicates a probable association, supported by a documented normal ocular baseline on the same concomitant medications, absence of ocular toxicity during brief prior abemaciclib exposure, and improvement after dechallenge with continued anastrozole. As a single, signal-generating case, causality cannot be established; additional reports and pharmacovigilance analyses are needed. As adjuvant use expands, clinicians should watch for corneal nerve toxicity beyond dry eye, ask routinely about visual symptoms, and refer early for eye care.