Introduction In this study, we aimed to investigate the incidence of objective and subjective indicators of the prostaglandin-associated periorbital syndrome (PAPS) after continuous instillation of topical prostaglandin analogues (PGAs) in primary open-angle glaucoma or ocular hypertension patients. Methods A self-controlled and prospective study of PGA instillation was performed in patients (n = 55) with primary open-angle glaucoma or ocular hypertension. Bilateral instillation of bimatoprost, travoprost, latanoprost, or tafluprost was conducted (treatment, 3–6 months). The objective indicators recorded included interpupillary distance (IPD) and exophthalmos; subjective indicators were assessed via colour pictures of the periocular area. Data from before the administration of medication served as controls. Posttreatment changes in IPD, exophthalmos, deepening of the upper eyelid sulcus, periorbital hyperpigmentation and eyelash growth were analysed. Results Compared with those before treatment, the interpupillary distance (IPD) differed from the baseline value at 1 month after treatment (P < 0.0001), and the exophthalmos only significantly differed from the baseline value at month 3 (P = 0.0005). Visible periorbital changes at 1, 3, and 6 months after treatment were assessed, and the incidence of eyelash growth and thickening was 7.27%, 45.45% and 66.67%, respectively. The incidence of periorbital hyperpigmentation was 7.2%, 18.18% and 33.33%, respectively. The incidence of upper-eyelid sulcus deepening was 3.64%, 7.27% and 16.27%, respectively. Bimatoprost had the highest incidence of PAPS, followed by travoprost and tafluprost, and latanoprost had the lowest incidence after three months of treatment in the between-group comparison. Conclusion As an objective index to evaluate PAPS, the change of IPD was more obvious than the exophthalmos. Visible periorbital changes gradually appeared after three months of medication. Bimatoprost caused the most severe PAPS, and latanoprost caused the least severe PAPS. Trial registration The study was registered at www.chictr.org.cn on 15 April 2021, under the identifier ChiCTR2100045465.
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