Clinical Staging of Prostaglandin-Associated Periorbitopathy Syndrome in Glaucoma: A Review from Asia.

PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.

Eyelash serums: A comprehensive review.

BACKGROUND: Eyelash serums, both prescription and over-the-counter, are gaining popularity for enhancing the appearance of eyelashes through various biologically active molecules. Categorized into prostaglandin analogs and non-prostaglandin analogs, these serums claim increased strength, length, luster, and thickness. Current United States law also requires no efficacy or safety assessments by the Food and Drug Administration before approving products for consumer use, potentially posing health risks for patients seeking over-the-counter eyelash enhancements. AIMS: Our aims include exploring proposed benefits and adverse effects associated with eyelash serums, while providing evidence-based clinical recommendations on their use. We aim to contribute valuable insights to the understanding of eyelash serums and their respective safety considerations. METHODS: The authors conducted a comprehensive electronic search across databases including PubMed, Embase, Cochrane Central, and Google Scholar to evaluate eyelash serum ingredients. Articles were evaluated by two independent researchers for relevance, and the ingredients discussed were analyzed and given clinical recommendations for eyelash serums based off the Oxford Centre for Evidence-Based Medicine. RESULTS: Results highlight bimatoprost's efficacy, supported by numerous studies evaluating safety and adverse effects. Other prostaglandin ingredients show potential benefits, but further studies are encouraged to enhance the understanding of respective safety profiles. While non-prostaglandins ingredients show promising data, more studies are needed due to a lack of formal evidence in eyelash serum use. CONCLUSION: As the cosmeceutical market for eyelash serums is growing, dermatologists need to be knowledgeable about evidence-based information regarding prescription and over-the-counter eyelash serum products before making recommendations to patients.

Prostaglandin-Induced Macular Hole: A Brief Report.

This case series reports on two patients who developed macular holes while on prostaglandin analogs (PGA) therapy. The first case involves a 63-year-old woman with a history of a macular hole of the left eye that had spontaneously closed. After starting PGA therapy for elevated intraocular pressure, cystoid macular edema formed, which resulted in reopening of the macular hole. The second case involves a 64-year-old man with primary open-angle glaucoma, on PGA therapy, with a newly diagnosed small macular hole of the right eye that closed after cessation of the PGA therapy. These cases demonstrate an association between prostaglandin analogs and the formation or reopening of full-thickness macular holes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:112-115.].

Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells.

PURPOSE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. CONCLUSION: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.

Prostaglandin FP receptor agonists in the treatment of glaucoma and ocular hypertension: a literature review.

INTRODUCTION: Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line medical treatment for glaucoma and ocular hypertension. Despite their efficacy, their IOP lowering effect may be insufficient requiring second agents, and poor patient compliance to medical therapy may preclude their full effect. AREAS COVERED: This literature review examines the novel FP receptor drugs and drug delivery devices in clinical phase trials for treatment of glaucoma. Three novel drugs targeting FP receptors were identified, including latanoprostene bunod, NCX 470, and sepetaprost. Additionally, sustained drug delivery devices in early clinical phase trials included intracameral implants, punctal plugs, ocular rings, and contact lenses. EXPERT OPINION: NO hybrid FP receptor agonists and dual FP/EP3 receptor agonists may show promise as novel medical therapies with greater efficacy than approved prostaglandin analogs in clinical use, with a similar safety profile. Alternatively, drug delivery systems may provide a similar IOP lowering effect to existing agonists but overcome issues with patient compliance and convenience. A personalized approach to drug delivery devices may be required to ensure the most appropriate fit for the patient according to the invasiveness and duration of therapy desired.

The Use of Prostaglandin Analogues and Cystoid Macular Edema after Uneventful Cataract Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate whether using prostaglandin analogues (PGAs) perioperatively is associated with an increased rate of the development of clinical or subclinical cystoid macular edema (CME) after uneventful cataract surgery. METHODS: The PubMed, Scopus, and ScienceDirect databases were searched to June 2022 for this systematic review and meta-analysis. Two authors independently screened search results. Random-effects meta-analyses were performed to calculate the overall incidence rate and odds ratio (OR). Quality of studies was assessed using the modified Newcastle-Ottawa scale. The incidences of CME for continued vs discontinued use of PGAs perioperatively, continued use of PGAs, discontinued use of PGAs, and PGA users vs non-PGA antiglaucomatous users were main outcomes. RESULTS: Out of 544-articles, 9 studies that met the inclusion criteria were analyzed. The continued use of PGAs was not associated with an increased risk of the development of subclinical macular edema compared with discontinued use (OR = 1.32 [95% Confidence Interval (CI) = 0.49-3.51], p = .582). The overall incidence of CME was 34% (95% CI = 0.17-0.52) for continued use of PGAs and 7% (95% CI = 0.02-0.13) for discontinued use of PGAs. Using PGAs did not increase the risk of CME's development compared with non-PGA antiglaucomatous usage (OR = 2.29 [95% CI = 0.84-6.23], p = .103). CONCLUSIONS: Discontinuing treatment with PGAs during the perioperative period in eyes without any known risk factors for CME has no clinically significant effect on reducing the development of postoperative CME based on the existing studies. Further, well-designed randomized controlled trials need to be performed.

Trends in development and quality assessment of pharmaceutical formulations - F2α analogues in the glaucoma treatment.

The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products.

Association between personality traits and experience of adverse periocular reactions to topical prostaglandin analogues.

BACKGROUND: Aesthetically unappealing adverse periocular reactions to prostaglandin (PG) eye-drops are a major challenge in glaucoma treatment. This study analysed the personality traits of patients with glaucoma based on a five-factor model and examined the associations between these factors and adverse periocular reactions. METHODS: One hundred and forty-seven patients with glaucoma were surveyed anonymously regarding their personality traits and how often adverse periocular reactions were experienced. RESULTS: The analysis included 117 valid responses (71 men and 46 women, age: 61.9±11.5 years). Patients who experienced hypertrichosis of the eyelashes scored significantly higher on extraversion (p<0.05), with no significant differences in the other four personality traits. Patients who experienced eyelid hyperpigmentation and deepening of the upper eyelid sulcus showed no significant differences in any of the personality traits. Younger patients scored significantly higher on hypertrichosis (p<0.05). CONCLUSION: The experience of adverse reactions differed according to patient age and personality traits. Therefore, eye-drops should be chosen based on these factors. TRIAL REGISTRATION NUMBER: UMIN000035155.

Do Prostaglandin Analogue Lash Lengtheners Cause Eyelid Fat and Volume Loss?

BACKGROUND: Prostaglandin analogues (PGAs; a first-line antiglaucoma treatment) have been remarketed as popular eyelash-lengthening serums due to their lash-lengthening and lash-thickening side effects. Periorbital volume loss is now a well-established side effect of topical PGAs used to treat glaucoma (prostaglandin-associated periorbitopathy) but has not, to date, been listed as a potential side effect of lash-lengthening serums containing PGAs. OBJECTIVES: The aim of this study was to identify whether periorbital fat/volume loss is seen in users of PGA lash lengtheners. METHODS: This investigation comprised a case report and an informal randomized controlled study comparing "before-and-after" color photographs displayed on the websites of manufacturers of PGA-containing lash lengtheners (PGALLs) (ie, containing bimatoprost, norbimatoprost, isopropyl cloprostenate, dechloro-dihydroxy-difluoro-ethylcloprostenolamide, or methylamido-dihydro-noralfaprostal) vs 2 control groups: non-PGALLs (NPGALL) and false eyelashes (FLs). Expert and layperson blinded graders used a purpose-designed grading system to identify subtle signs of periorbital fat/volume loss over time. RESULTS: A 35-year-old female developed thin, wrinkled, darker skin, and periorbital hollowing after 10 months of treatment with Lash Boost (Rodan & Fields, San Francisco, CA), containing isopropyl cloprostenate, which reversed 6 months after discontinuation. Fifteen "before-and-after" pairs of photographs (PGALL, n = 10; NPGALL, n = 3; FL, n = 2) were graded by 5 graders (3 expert, 2 layperson). Mean grading score was 8.2 (of 19) in the PGALL group, 2.3 in the NPGALL group, and 3.2 in the FL group. PGALL scores were significantly higher than scores in the NPGALL (P < 0.001) and FL (P = 0.017) groups. CONCLUSIONS: Review of commercial "before-and-after" photographs suggests that PGALL users develop changes compatible with prostaglandin-associated periorbitopathy. Consumers must be aware of the possibility of periorbital volume loss prior to commencing treatment with PGALLs. Often the customer-facing product ingredient list contains no mention of PGAs.

The risk of uveitis due to prostaglandin analogs in pediatric glaucoma.

PURPOSE: To examine the incidence of uveitis in children prescribed prostaglandin analogs (PGAs) for glaucoma. METHODS: In this dual-center cohort study, the medical records of consecutive patients <18 years old treated with a PGA between January 1, 2012, and December 31, 2018, were reviewed retrospectively. Patients with all forms of glaucoma, including those with a prior history of uveitis, were included. Patients who had been on a PGA prior to their first recorded visit were excluded. Patient charts were reviewed for new or recurrent uveitis during the first year of PGA therapy. RESULTS: A total of 103 children (147 eyes) were included, with a total PGA exposure of 1,352 child-months. Ninety-eight children (142 eyes) tolerated the PGA without an episode of uveitis. Five patients with a documented prior history of uveitis experienced a unilateral episode of uveitis. A review of their medical records identified prescribed or unscheduled decrease in topical steroids or immunosuppressive medication as the most likely cause of uveitis recurrence. CONCLUSIONS: This study provides further evidence that PGAs are unlikely to induce uveitis in children being treated for glaucoma and suggests that this may also be true in those with a history of uveitis. We are unable to evaluate whether PGAs make recurrence more likely or the tapering of steroids more difficult.

Dermatological adverse effects of anti-glaucoma eye drops: a review.

Many patients are treated for glaucoma. Like other drugs, anti-glaucoma eye drops may induce dermatological adverse effects. We aim to review the dermatological adverse effects secondary to the active agents in anti-glaucoma eye drops through a literature review. In January 2020, we queried PubMed using the following MeSH terms: glaucoma/drug therapy or glaucoma, open angle/drug therapy cross-referenced with parasympathomimetics/adverse effects or adrenergic agonists/adverse effects or carbonic anhydrase inhibitors/adverse effects or prostaglandins F, synthetic/adverse effects or adrenergic beta antagonists/adverse effects or ophthalmic solutions/adverse effects. The initial search identified 1128 studies, of which 49 were excluded for being in a foreign language, 15 for not involving eye drops, 968 for not focusing on adverse dermatological effects, and 11 for insufficient documentation or redundancy. After adding 38 linked studies, we finally analyzed 123 studies. The ocular and periocular dermatological adverse effects of eye drops are contact dermatitis, hyperpigmentation, prostaglandin analog periorbitopathy, mucous membrane pemphigoid, eyelash depigmentation, skin hypertrichosis, and rare cases of melanoma and skin depigmentation. The reported distant dermatological adverse effects are psoriasis, excessive sweating, lichen planus, alopecia, toxic epidermal necrolysis, erythema multiforme, erythroderma, subacute cutaneous lupus erythematosus, nail pigmentation, and bullous pemphigoid. Most of the cutaneous adverse effects of anti-glaucoma eye drops are ocular and periocular and induced by prostaglandin analogs. Distant adverse effects are rare and sometimes questionable but should be kept in mind, especially mucous membrane pemphigoid, which could lead to blindness. The role of preservatives, such as benzalkonium chloride, should also be considered.

Topical prostaglandin analogue use and cystoid macular oedema following uneventful cataract surgery: a randomised control trial.

BACKGROUND/AIMS: The association between the development of cystoid macular oedema (CMO) following uneventful cataract surgery and prostaglandin analogue (PGA) therapy has not been fully determined. The study aim was to investigate whether discontinuation of PGA therapy following uneventful cataract surgery affected the incidence of postoperative CMO. METHODS: A prospective randomised controlled trial of 62 eyes of 62 participants with ocular hypertension (OH) or primary open angle glaucoma (POAG) treated with PGAs prior to cataract surgery. Participants were randomised to continue with PGA therapy after cataract surgery (CPGA) (n=31) or to discontinue PGA therapy (n=31). The primary outcome measure was the development of CMO at 1-month postoperatively, determined by a masked observer assessment of optical coherence tomography scans. The secondary outcome measure was change from baseline intraocular pressure (IOP). RESULTS: The incidence of CMO was identical in both groups at 12.9% (4 of 31 eyes) at the 1-month postoperative visit (OR 1.000; 95% CI 0.227 to 4.415). At 1-month postoperatively, the IOP was significantly lower in the CPGA group compared with baseline IOP. CONCLUSION: Continuation of PGA therapy following uneventful cataract surgery in eyes with normal macular morphology did not increase the incidence of CMO. Continuation of PGA therapy significantly reduced IOP at 1-month postoperatively suggesting that, when indicated, it might be beneficial to continue PGA therapy in patients with POAG or OH after uneventful cataract surgery in the absence of other risk factors for developing CMO.

A new look at the safety and tolerability of prostaglandin analogue eyedrops in glaucoma and ocular hypertension.

INTRODUCTION: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. AREAS COVERED: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. EXPERT OPINION: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy.

ABSTRACT: The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ±â€Šstandard deviation, 69.9 ±â€Š14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ±â€Š5.4 mm Hg) than grades 0 (15.0 ±â€Š5.1 mm Hg, P = .032) and 1 (14.5 ±â€Š4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ±â€Š3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ±â€Š0.8) and bimatoprost (2.0 ±â€Š0.7) than latanoprost (1.0 ±â€Š0.8, P < .001 for both comparisons) and tafluprost (1.0 ±â€Š0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ±â€Š0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard ß = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.

Revisiting the Safety of Prostaglandin Analog Eyelash Growth Products.

BACKGROUND: The FDA approved bimatoprost ophthalmic solution 0.03% for treatment of eyelash hypotrichosis in 2008. Consumer concern persists regarding potential side effects of this product. OBJECTIVE: To identify gaps in the safety information associated with the use of prostaglandin eyelash growth products. MATERIALS AND METHODS: Literature searches were performed using PubMed, Embase, and Nexis Uni databases without restriction to publication date, language, or study setting. RESULTS: The literature pertaining to bimatoprost for treatment of eyelash hypotrichosis is dominated by industry-sponsored clinical trials. Study design choices create gaps in our understanding of the clinical safety of these products. CONCLUSION: Because of study design choice, clinical trials of bimatoprost for eyelash growth may have systematically underreported the incidence of drug application discomfort and prostaglandin-associated periorbitopathy. The risk of increased iris pigmentation remains inadequately investigated. Consequently, there is an ongoing need to educate and monitor patients who choose to use these products.

Prostaglandin analogues: A double-edged sword in orbital glaucoma disease management.

INTRODUCTION: The authors describe benefits of the recognised adverse effects of prostaglandin analogues on periocular structures in patients with unilateral proptosis and intraocular pressure rise. This case points to intentional consideration of prostaglandin analogue therapy in this selected cohort of patients with secondary ocular hypertension and proptosis. CASE DESCRIPTION: A 70-year-old gentleman who presented with a 1-week history of a red and painful right eye associated with tortuous and dilated episcleral blood vessels. Visual acuity was unaffected. A diagnosis of idiopathic orbital inflammatory disease was made by extraocular muscle biopsy. Two weeks later, the patient presented with worsening pain, reduced vision and raised intraocular pressure. The secondary ocular hypertension was successfully treated with topical preserved eye drops, including latanoprost, a prostaglandin analogue. Over 6 months, the patient developed drop intolerance and punctate keratopathy leading to therapy non-adherence. Interestingly, the patient reported improvement in periocular appearance related to prostaglandin-associated periorbitopathy. Ocular surface disease and intraocular pressures were subsequently managed with preservative-free eye drops. CONCLUSION: Secondary ocular hypertension is not an uncommon consequence of orbital disease. Prostaglandin analogue can act as a double-edged sword in the management of raised intraocular pressure by reducing eye pressure at the cost of developing adverse effects of prostaglandin-associated periorbitopathy. These adverse effects however can be beneficial in the aesthetic rehabilitation of proptosis and associated exposure keratopathy in patients with unilateral orbital disease and probably should be sought as first line treatment in those with proptosis and raised intraocular pressure.

Prostaglandin-Associated Periorbitopathy in Children and Young Adults with Glaucoma.

OBJECTIVE: To evaluate for relative palpebral and orbital changes after long-term unilateral exposure to prostaglandin analogues (PGAs) in patients with childhood glaucoma. DESIGN: Prospective cross-sectional cohort study. PARTICIPANTS: A total of 29 patients with history of childhood glaucoma, who were treated unilaterally with PGAs for at least 12 months. METHODS: Based on 4 standardized clinical photographs (en face with eyes open, right and left side views with eyes open, and en face with eyes closed), 3 masked expert graders each independently selected the eye they perceived to have received unilateral PGA treatment by physical appearance alone and graded the following features relative to the other eye: (1) ocular (e.g., conjunctival hyperemia, iris heterochromia, and buphthalmos), (2) palpebral (e.g., eyelash trichomegaly, eyelash hypertrichosis, eyelid erythema, eyelid edema, eyelid hyperpigmentation, high upper eyelid crease, upper eyelid ptosis, upper and/or lower eyelid retraction, and eyelid skin atrophy with presence of telangiectasias), and (3) periorbital (e.g., superior sulcus hollowing, proptosis, enophthalmos, hypoglobus, and hyperglobus). An interrater reliability analysis was performed using the Fleiss kappa (κ) statistic to determine consistency among raters. MAIN OUTCOME MEASURES: Frequencies of each feature of prostaglandin-associated periorbitopathy (PAP); group consensus; interrater reliability of selected PGA-treatment laterality. RESULTS: Median unilateral PGA exposure time was 31.7 months (interquartile range: 18.8-44.3 months). Eyelash trichomegaly and hypertrichosis (n = 22, 76%), high upper eyelid crease (n = 20, 69%), upper eyelid ptosis (n = 14, 52%), and superior sulcus hollowing (n = 15, 52%) were the most frequently observed features of PAP in PGA-treated eyes compared with untreated fellow eyes. Most of these changes were mild, but 20% to 30% of patients exhibited moderate eyelash and/or eyelid changes. One patient had severe PAP after long-term unilateral PGA exposure. Group consensus with correctly selected laterality was achieved in all patients. The inter-rater reliability was excellent (κ = 0.815, P < 0.001, 95% confidence interval [0.605, 1.000]). CONCLUSIONS: Mild-to-moderate changes in the ocular adnexa can develop in children and young adults with long-term PGA exposure. Patients and their families should be educated on the possibility of PAP, especially when initiating monocular PGA therapy.

Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma.

BACKGROUND: Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence. METHODS: Preferred Reporting Items for Systematic review and Meta-Analyses guidelines were followed. Studies evaluating topical PGAs in patients with ocular hypertension or open angle glaucoma were included. MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, LILACS and ClinicalTrials.gov were searched between 1946 and 2019. Experimental studies, animal studies and randomised studies with other intraocular pressure-lowering eye drops were excluded. RESULTS: 214 studies (28 232 patients) met the inclusion criteria. Using prospective data, the incidence of uveitis and CME among PGA users were 62/28 232 (0.22%) and 25/28 232 (0.09%), respectively. A higher frequency of both uveitis and CME were found among latanoprost users compared with bimatoprost. There were 21 case studies reporting CME including 48 eyes in 43 patients. 47 of 48 eyes (97.9%) had previous incisional ocular surgery. 8 eyes were re-challenged, of which 7 (87.5%) recurred. 7 case studies reported uveitis in 15 eyes of 10 patients. 7 of 15 eyes (46.7%) were either pseudophakic or aphakic. 6 eyes were re-challenged, and all 6 (100%) recurred. CONCLUSIONS: Cases of uveitis or CME revealed a confounding effect of ocular surgery, aphakia or subluxed intraocular lens. PGAs may be used in non-surgical patients without concern of causing CME or uveitis. The incidences of PGA-associated CME and uveitis are rare with limited prospective studies on the cause-effect relationship.

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists.

Purpose: Topical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV). Methods: We studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging. Results: Subjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls. Conclusions: Patients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.