Context: Although topical prostaglandin analogs (PGAs) have been previously associated with periocular skin hyperpigmentation, studies using objective clinical methods are lacking. Furthermore changes in periocular skin erythema indexes associated with topical PGAs have not been reported previously.Objective: The purpose of the present study was to evaluate periocular melanin and erythema indexes in patients treated with topical PGA using an objective clinical method - Mexameter.Methods: About 45 glaucoma patients treated with topical PGA therapy, and 30 age-, and sex-matched controls were enrolled in the study. Demographic data, medical history including duration of therapy, PGA type, involved eye (unilateral, bilateral) were noted, and skin phototypes were evaluated. Melanin and erythema indexes on medial and lateral upper and lower eyelids, and normal skin from the upper cheeks were measured using Mexameter MX-18. The index of difference for lower/upper eyelid was calculated. Reading results of patients and controls were compared.Results: Melanin and erythema indexes of upper/lower eyelids, and the index of differences for upper/lower eyelids were significantly higher in patients despite similar clinical findings (p<0.05). Duration of therapy and type of PGA were not associated with skin changes (p>0.05).Conclusions: Both periocular melanin and erythema indexes increased in both upper and lower eyelids due to PGA therapy compared to controls, despite similar clinical findings. Mexametric evaluation is more sensitive than clinical evaluation, and may be used as an objective, sensitive clinical method to evaluate periocular skin changes, even smallest changes, in such patients.