A Cross-Sectional Survey of the Association between Bilateral Topical Prostaglandin Analogue Use and Ocular Adnexal Features

Mamta Shah,Stacey C Brauner,Suzanne K Freitag,Douglas J Rhee,Grace Lee,Louis R Pasquale,Angela Turalba,Stephanie Loomis,Benjamin Kronberg,Daniel R Lefebvre,Michael E Boulton

doi:10.1371/journal.pone.0061638

Abstract

We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43–3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54–4.03; p = 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43–6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39–16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58–4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent significant side effects that could impact visual function in glaucoma patients.

Highlights

Prostaglandin analogues (PGAs) are a class of ocular hypotensive agents that lower intraocular pressure (IOP) predominantly by enhancing uveoscleral outflow [1]
Previous studies reported loss of dermatochalasis and inferior orbital fat pads, the findings of ptosis and levator muscle dysfunction associated with use of all members of the PGA class have not been previously emphasized
The mechanism by which PGAs produce the deepening of the upper eyelid sulcus and loss of inferior orbital fat pads seems to involve effects on periorbital adipocytes as first suggested by Filippopoulous et al [5]

Summary

Introduction

Prostaglandin analogues (PGAs) are a class of ocular hypotensive agents that lower intraocular pressure (IOP) predominantly by enhancing uveoscleral outflow [1]. PAP, which can be dismissed as age-related adnexal findings in bilateral users, has been recognized in several small case series involving both unilateral [6] and bilateral PGA users [7]. These series demonstrate that PAP was not an antecedent finding and that the adnexal changes partially reversed when the PGA was withdrawn. Evidence exists that all three members of the PGA class can be associated with PAP [8,9]

Methods

Results

Conclusion