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

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.

Unilateral Prostaglandin-Associated Periorbitopathy

“…[32][33][34] Involution of the periorbital fat and deepening of the upper eyelid sulci were statistically confirmed and ptosis, decreased levator function, and lower eyelid retraction were found related to PGA use. Kucukevcilioglu et al 35 reviewed a large series of 105 patients treated with PGA drops in only 1 eye.…”

“…Expert opinions have been supported with interobserver agreement through looking at clinical photographs. [32][33][34][35] Attempts to objectify this measurement have involved measuring the invaginated appearance of a sulcus deformity, the very measurement of which one may argue is subjective. 36 We recommend stratifying SSD into 3 objective groups.…”

A Vector Force Model of Upper Eyelid Position in the Setting of a Trabeculectomy Bleb

“…A potential link between topical prostaglandin analogue use and eyelid malposition, both retraction and ptosis, has been reported. [19][20][21][22][23] Typical ocular and periocular tissue effects associated with topical application of prostaglandin analogues include deepening of the upper eyelid sulcus, loss of the inferior orbital fat pads, enophthalmos, a constellation of symptoms referred to as prostaglandin-associated periorbitopathy, and upper eyelid ptosis. 19,20 A cross-sectional survey of 343 patients found that the use of bimatoprost, travoprost, or latanoprost was associated with an odds ratio of 4.04 (95% confidence interval, 2.43-6.72, p value = 7.37 E-08) for the development of worsening ptosis, defined as a decrease in MRD1 of at least 1 mm.…”

“…19,20 A cross-sectional survey of 343 patients found that the use of bimatoprost, travoprost, or latanoprost was associated with an odds ratio of 4.04 (95% confidence interval, 2.43-6.72, p value = 7.37 E-08) for the development of worsening ptosis, defined as a decrease in MRD1 of at least 1 mm. 21 This has been theorized to result from dehiscence of the levator palpebrae superioris from the superior tarsal plate secondary to increased expression of matrix metalloproteinases. 21 An alternative explanation focuses on eyelid tightening secondary to low-grade dermatitis, erythema, and hyperpigmentation of the eyelid tissues that makes the eyelid stiff and ptotic.…”

“…21 This has been theorized to result from dehiscence of the levator palpebrae superioris from the superior tarsal plate secondary to increased expression of matrix metalloproteinases. 21 An alternative explanation focuses on eyelid tightening secondary to low-grade dermatitis, erythema, and hyperpigmentation of the eyelid tissues that makes the eyelid stiff and ptotic. 21 In terms of the vector force model, dehiscence of the levator palpebrae superioris from the superior tarsal plate would serve to decrease the supero-posterior directed F LPS and inflammatory-mediated eyelid tightening would serve to increase the infero-anterior directed F anchors , both of which would favor ptosis.…”