A Systematic Review and Meta-Analysis of Prostaglandin-Associated Periorbitopathy

Authors: Lucas D. D. Foster, Trinad Contram-Seetnah, Monali Malvankar, Cindy M. L. Hutnik.

Author Disclosure Block: L.D.D. Foster: None. T. Contram-Seetnah: None. M. Malvankar: None. C.M.L. Hutnik: None.

  Abstract Body:

Purpose: This systematic review aims to characterize and quantify the incidence of PAP-related side effects. Background Information: Prostaglandin-associated periorbitopathy (PAP) is a general term given to describe the constellation of eyelid and orbital fat changes that accompany the administration of prostaglandin analogue (PGA) eye drops. The first report of PAP was documented in 2004 and since then, this topic has garnered significant interest in the field of glaucoma with over 40 studies published on this topic since 2010. To date, there have not been any attempts to systematically review and synthesize all of the available data as it pertains to PAP. As such, the incidence of PAP and related side effects has not been determined. The study presented herein adds to the growing body of literature as it pertains to PAP and quantifies the long-term effects of topical PGA use. It also provides meaningful insight to clinicians considering Microinvasive Glaucoma Surgery (MIGS) as a first-line treatment for glaucoma.

Study Design: Systematic review and meta-analysis

Methods: This systematic review followed the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-analyses guide. MEDLINE, EMBASE, and BIOSIS databases were searched, identifying 5,842 potentially relevant articles. Aftertitle & abstract screening, full text review, and methodological quality assessments, 43 articles were included for quantitative synthesis and data extraction. Data was analyzed using IHvet MetaXL version 2.0, using a pooled effects model to quantify the incidence of adverse events.

Results: The incidence of PAP-related side effects after six months of exposure to prostaglandin therapies was 37.8% (95% CI, 33.4-42.2), 20.3% (95% CI, 17.6-22.9), 34.2% (95% CI, 25.5 - 42.9), 24.2%

(14.1 - 34.3) for deepening of the upper lid sulcus, ptosis, dermatochalasis involution, and enopthalmos, respectively. There was insufficient data to quantify the rates of lower lid retraction, proptosis, hyperglobus, and hypoglobus. The incidence of palpebral side effects was 25.4% (95% CI, 21.4-29.4), 5.4% (95% CI, 4.2 - 6.6), 6.1% (95% CI, 3.4-8.8), 3.0% (95% CI, 1.5-4.5), 2.4% (95% CI, 1.6-3.2) for

hypertrichosis, periocular hyperpigmentation, eyelid erythema, eyelid edema, and blepharitis. There was insufficient data to quantify the rates of trichomegaly, hordeolum, and chalazions.

Conclusions: PAP is a relatively common phenomenon, occurring in approximately 40% of prostaglandin users after six months of treatment. Symptoms will vary from person to person, but most commonly include DUES (37.8%, 95% CI 33.4-42.2), ptosis (20.3%, 95% CI 17.6-22.9), and dermatochalasis involution (34.2%, 95% CI 25.5 - 42.9). These side effects are underrepresented in clinical studies, and often go unnoticed by patients. Most patients will recover within 3 months upon discontinuation, however, some will develop long-term oculoplastic complications. Other palpebral side effects of long- term PGA use include hypertrichosis, hyperpigmentation of the lids, lid edema, and blepharitis.