The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. Bilateral deepening of upper lid sulcus from topical Bimatoprost therapy. Bimatoprost 0.03% (Lumigan, Allergan Inc., Dublin, Ireland) was used in one eye, bimatoprost 0.03% plus timolol 0.5% (Timabak, Thea Pharma Inc., Barcelona, Spain) in four eyes, travoprost 0.004% (Travatan, Alcon AG, Geneva, Switzerland) in one eye, and travoprost 0.004% plus timolol 0.5% in four eyes, all once a day. 7A-B) Left DUES partially improved and dermatochalasis increased. The change in IOP was calculated as IOP=IOPLATIOPbase. However, it is not clear whether abnormally great globe retraction in adduction in POAG is due to abnormally great ON traction in such patients, versus more compliant retrobulbar tissues providing less mechanical resistance to normal ON traction in adduction. After three consecutive IOP measurements in both eyes, we initiated LAT treatment in eyes with the more severe glaucomatous visual field damage when both eyes met the entry criteria, and the same medication was continued for 6 months. Prostaglandin-associated periorbitopathy. Demographic data of the three DUES-positive patients are presented in Table 2. The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. It was first believed that DUES was derived from either fibrosis or atrophy of Mllers muscle.5 Later, atrophy of the preaponeurotic and deep orbital fat pads was thought to be the causative mechanism.6 PGA-induced lipolysis may play a role in DUES that is dependent upon the stimulation of the prostaglandin F (FP) receptor in orbital tissue.10 We recently reported that the activated form of all PGAs and PGF2 dose-dependently suppressed adipogenesis in differentiated adipocytes, but did not suppress adipogenesis in the adipocytes of FP receptor knockout mice.23 An in vivo histological analysis indicated that the density of adipocytes obtained from preaponeurotic fat biopsies was lowest in BIM-treated patients among those treated with BIM, TRV, or LAT. The effects produced by the use of a topical prostaglandin include upper lid ptosis; deepening of the upper lid sulcus; involution of dermatocholasis; periorbital fat atrophy; mild enophthalmos; inferior scleral show; increased prominence of lid vessels; and tight eyelids. Various cross-sectional and retrospective clinical record analyses have investigated the rate of LAT-induced PAP. No IOP elevation or aggravation of the optic disc was seen in the noninstilled eye during 6 months of observation. Tan J, Berke S . Glaucoma is the leading cause of irreversible blindness.1,2 Prostaglandin analogs (PGAs) are commonly applied topically to the eye as first-line treatment for primary open angle glaucoma (POAG) because they reduce intraocular pressure (IOP) through facilitation of aqueous outflow36 and are convenient and well tolerated. Park J, Cho HK, Moon JI. Walgreens Pharmacy #9966, WESTFORD, MA is a pharmacy in Westford, Massachusetts and is open 7 days per week. We believe that taking frontal photographs, including the eyebrow, using a standardized photographic technique is a minimal requirement at the present time. In the present study, we prospectively monitored the occurrence of DUES in Japanese glaucoma patients using LAT as an initial drug treatment. 13.3.3, MedCalc Software bvba, Ostend, Belgium). Multivariate analysis showed that age and race had insignificant effects on overall OFV (P = 0.679 and P = 0.388, respectively), posterior fat volume between the apex and GONJ (P = 0.292, P = 0.154, respectively), and OV anterior to the GONJ (P = 0.939, P = 0.840, respectively). Received 2019 Sep 19; Accepted 2020 Apr 21. Keywords: Periorbitopathy, prostaglandin analogue, prostaglandin-associated periorbitopathy, periorbital changes Go to: Introduction Side effects associated with prostaglandin analog therapy. 9A) Bilateral DUES and lower fat pad loss; 9B) DUES and orbital fat pad improved and dermatochalasis increased. Taketani Y, Yamagishi R, Fujishiro T, et al Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy, Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy. Unilateral Prostaglandin-Associated Periorbitopathy: A Syndrome Involving Upper Eyelid Retraction Distinguishable From the Aging Sunken Eyelid. BMC Ophthalmol. Casimir DA, Miller CW, Ntambi JM . 5A) was significantly less in POAG without abnormally elevated IOP at 9.7 1.9 mL (SD) than in controls at 10.9 1.3mL (P = 0.019). This study demonstrates that patients with POAG at low IOP who have been treated with topical PGAs do indeed have less total orbital fat than age matched healthy control subjects not treated with PGAs. These findings were later confirmed by Filippopoulos et al.,16 who reported periorbital changes associated with topical bimatoprost, including periorbital fat atrophy, DUES, relative enophthalmos, loss of lower eyelid fullness, and involution of dermatochalasis, compared with the untreated eye in a case series of five patients. The best method to avoid overlooking DUES might be by taking photographs before and after starting PGAs and evaluating them as still images. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Deepening of lid sulcus from topical bimatoprost therapy. However, when the model for total OV included only Asian versus non-Asian race and POAG as factors, the presence of POAG was not significant (P = 0.326). Tan J, Berke S. Latanoprost-induced prostaglandin-associated periorbitopathy. Sakata R, Shirato S, Miyata K, Aihara M. Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost. Gupta V, Hammond CL, Roztocil E, Gonzalez MO, Feldon SE, Woeller CF. Maruyama K, Tsuchisaka A, Sakamoto J, Shirato S, Goto H . Incidence of deepening of upper eyelid sulcus after topical use of tafluprost ophthalmic solution in Japanese patients. Tappeiner C, Perren B, Iliev ME, Frueh BE, Goldblum D . Both MRD1 and MRD2 increased (for MRD2 p = 0.007). bimatoprost left eye." It shows periorbital fat atrophy, deepen-ing of the superior lid sulcus, ptosis, enophthalmos, and invo-lution of dermatochalasia.8 IMPLICATIONS Aside from the obvious cosmetic effects, prostaglandin-associated periorbitopathy (PAP) makes it difficult, if not impossible, to examine the eye or to perform applanation Thus, there is significant periorbital absorption of prostaglandin analogue medication. Models were repeated using only POAG and Asian versus non-Asian race as factors. Ophthal Plast Reconstr Surg 2012; 28: e42e44. Side effects include ocular hyperaemia, ocular pruritus, and periocular and iris pigmentary changes. It is possible that LAT-induced DUES occurs gradually; thus, it could be overlooked, together with other symptoms of PAP. All nine patients (10 eyes) included in this study had been under treatment with topical PGA eye drops for at least 1 year and developed PAP. However, the present study did not find evidence of any reduction of retrobulbar OFV caused by topical PGA agents. Thus, it should be noted that DUES-positive cases represent a broad range of the severity of DUES, from slight changes recognized by photographs to obvious deepening noticed at a glance. PMC Epub 2021 Sep 4. Unauthorized use of these marks is strictly prohibited. Before official website and that any information you provide is encrypted Studies of glaucoma patients reported periorbital fat atrophy after treatment with prostaglandin analogue drops. Since then, a retrospective study on patients undergoing unilateral PGA treatment found that bimatoprost induces more changes than travoprost or latanoprost.7 Recent studies show that loss of periorbital fat is the most common feature, followed by involution of dermatochalasis, DUES, enophthalmos, and ptosis.20 Our cohort of patients were either on bimatoprost or travoprost and developed some of these features to a greater or lesser degree. Incidence of deepening of the upper eyelid sulcus on treatment with a tafluprost ophthalmic solution. It is well known that prostaglandins . To account for possible intraocular correlation between eyes of the same subject, statistical analysis was conducted with generalized estimating equations (GEE) implemented in SPSS software (Version 24.0; IBM Corp., Armonk, NY, USA), designating the eye as a within-subject variable, and including effects of subject age and race as factors. Anteroposterior dimensions of the orbit and position of the GONJ, did not differ between patients with POAG and the controls. 2). DUES, which has been closely monitored for several years, is the most prominent clinical feature of PAP. Law, None; L. Bonelli, None; A.L. Deepening of eyelid superior sulcus during topical travoprost treatment. Case series: Chart review with photo-documentation of clinical features of prostaglandin-associated periorbitopathy resulting from latanoprost use. Kucukevcilioglu M, Bayer A, Uysal Y, Altinsoy HI. Clin Ophthalmol 2013; 7: 14411446. Peplinski LS, Albiani Smith K . CAS HHS Vulnerability Disclosure, Help Four eyes had pseudoexfoliative glaucoma, three open-angle glaucoma, two posttraumatic glaucoma, and one ocular hypertension. R Sakata. Horizontal width of each quasicoronal image was sampled 15 times (red lines) at uniformly-spaced vertical intervals spanning the middle 60% of the vertical extend of the orbit (white arrow). Lid changes associated with periorbital fat atrophy, leading to skin tightness. PubMedGoogle Scholar. 59 CrossRef citations to date 0 Altmetric Case Reports Periorbital Fat Atrophy An Unfamiliar Side Effect of Prostaglandin Analogues Anuradha Jayaprakasam , (MA, MBBS, MRCP, MRCOphth) & Seyed Ghazi-Nouri , (BSc, MBBS, FRCOphth, MD) Pages 357-359 | Received 26 Aug 2010, Accepted 19 Sep 2010, Published online: 15 Dec 2010 Download citation sharing sensitive information, make sure youre on a federal A newly described side effect of Prostaglandin F2 alpha analogues including bimatoprost and travoprost in terms of periorbital fat atrophy is presented. If topical PGAs do induce atrophy of retrobulbar orbital fat, the remaining tissues might become more compliant. Such multiple mechanisms of action, which may also involve interactions between effectors and adipose cells, must be considered when DUES develops. Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost. Mean orbital dimensions along the anteroposterior extent of the orbit in patients with POAG and controls. S: Lower fat pad (steatoblepharon) score. 35 patients were identified with prostaglandin-associated periorbital changes. Orbit volume (OV) was calculated by summing areas within the orbital borders in each image plane from the orbital apex to the trochlea, which was selected as an anatomic reference because it is fixed to the medial orbital wall. Maruyama K, Shirato S, Tsuchisaka A . 6A) Right DUES and dermatochalasis involution; 6B) Increased dermatochalasis and reduced DUES. Maruyama et al.6 reported that 19% of patients treated with tafluprost, a new PGA introduced a few years ago, developed DUES within 90 days of starting treatment, yet only 17% of those affected had perceived any difference. Changes to upper eyelid orbital fat from use of topical bimatoprost, travoprost, and latanoprost. Google Scholar. Mean IOPs before and after treatment were 16.52.9 and 13.83.0mmHg, respectively. A retrospective chart review was performed on patients previously seen in a referral oculoplastic practice with eyelid and orbital changes attributed to the use of PGAs. Subjects gave written informed consent prior to participation. Randomized long-term prospective clinical trials including all four PGAs with large numbers of patients are needed to identify the relevant ocular and systemic factors in play. We present 2 cases of a newly described side effect of both these topical agents in terms of periorbital fat atrophy. J Glaucoma 2013; 22: 626631. Periorbital fat atrophyan unfamiliar side effect of prostaglandin analogues. However, at least in Japanese OAG patients, it is clear that DUES was least common with the use of LAT among the four PGAs now available.12, 20, 21. Steinhauser SL . This is also corroborated by the fact that a much greater number of reports of BIM- or TRV-induced DUES have been published. and JavaScript. Rapid clearance of the active drug from the body and low levels in the plasma, explain why systemic side effects are unlikely to occur in the vast majority of glaucoma patients [26]. All three ophthalmologists attained consensus on all judgments at these three time points. . This pattern is not attributable to sex because males and females were similarly distributed throughout the range of measurements. Yang HK, Park KH, Kim TW, Kim DM . Biochem Biophys Res Commun 1997; 233: 200202. A final drawback is that the subjects were almost all Japanese NTG patients. Changes in the periorbital region were evaluated using the grading scheme for assessment of dermatochalasis and steatoblepharon (inferior adnexal extraconal orbital fat herniation) published by Shah et al.14. The analysis of orbital fat biopsies in PGA-treated patients showed reduction of adipocyte size with increased adipocyte density. 5B). Incidence of deepening of the upper eyelid sulcus after topical use of travoprost ophthalmic solution in Japanese. Absence of topical PGA effects on posterior OFV is not surprising in view of the extensive anterior tissue barriers and high vascularity of the orbit that would inhibit penetration of topical agents into the deep orbit. Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy. Strong P, Coleman RA, Humphrey PP . Article Careers, Unable to load your collection due to an error. Latisse, Allergan Inc., Irvine, CA). Accessibility We determined OFV by subtracting from the orbital areas, the cross-sectional areas of the other intraorbital tissues, including globe, muscles, nerves, and blood vessels (Fig. In this limited model, Asian race had insignificant effects on total OFV (P = 0.896), posterior OFV between the apex and GONJ (P = 0.746), total OV (P = 0.387), and OFV between the GONJ and trochlea (P = 0.311); only the former two differed significantly between controls and subjects with POAG in the limited model (P = 0.029 and 0.006, respectively). Prostaglandin-associated periorbitopathy. Our findings largely agree with the available reports in the literature. In the meantime, to ensure continued support, we are displaying the site without styles Optom Vis Sci 2013; 90: e245e247 discussion 1029. In contrast, TAF-17, 20 or LAT-induced cases15 have been reported only rarely. The present study was motivated by recognition that adipogenesis is inhibited by PGAs through activation of the FP receptor, which may cause fat atrophy.42,43 Common PGAs used today to reduce IOP include latanoprost, timolol, bimatoprost, travoprost, and tafluprost, as well as fixed combinations like latanoprost-timolol, bimatoprost-timolol, travoprost-timolol, and tafluprost-timolol.44 Several clinical features have been associated with prostaglandin periorbitopathy that may occur in about half of patients after more than one year bilateral treatment with topical latanoprost: deepening of the upper eyelid sulcus, upper blepharoptosis, effacement of the lower eyelid fat pads, and inferior scleral show.11,45,46 One retrospective study has suggested that enophthalmos may occur in eyes unilaterally treated with latanoprost.47 However, enophthalmos is not typically reported in patients with POAG and would not have been significant in the small unilateral treatment study by Higashiyama et al.,12 except with the inclusion of one marked outlier case. The pathogenic role of IOP elevated well above the statistically normal range of up to 22 mm Hg is undisputed in congenital and juvenile glaucoma,13 angle closure,14 uveitic,15 and traumatic glaucoma,16 because IOP is typically highly elevated and progression of optic neuropathy is decisively attenuated when IOP is normalized in these disorders. However, for this study, we monitored only DUES, as in preceding reports.12, 16, 20 To date, there is no quantitative method for defining PAP with the inclusion of DUES. Periorbital changes associated with topical bimatoprost. Although Kucukevcilioglu et al22 demonstrated that PAP had occurred in 41.4% of Caucasian patients, the rate of DUES was 15.7% (mean age, 66 years; mean administration period, 48 months). Differentiation 1996; 60: 203210. Dermatochalasis and lower eyelid steatoblepharon were evaluated according to the grading scheme reported by Shah et al.14 We also assessed upper lid ptosis, levator muscle function, and inferior scleral show. 2007 Mar;23(3):601-8. doi: 10.1185/030079907X178720. Shah M, Lee G, Lefebvre DR, Kronberg B, Loomis S, Brauner SC, Turalba A, Rhee DJ, Freitag SK, Pasquale LR. Patients were excluded if they had previously undergone intraocular surgeries besides those for cataract, glaucoma, refractive error; or if they had orbital disease, or if they had any other cause for optic neuropathy. Alm A, Grierson I, Shields MB . An official website of the United States government. . Written informed consent was obtained from all participants. We employed a bootstrap approach to investigate whether these gender differences had confounded the apparent significant differences in OV and total OFV between controls and subjects with POAG. Therefore the horizontal width of the orbit was determined by averaging its horizontal dimension within the central 60% of its vertical extent, as sampled at 15 equal intervals (Fig. Using the program ImageJ64 (W. Rasband, National Institutes of Health, Bethesda, MD, USA), the extraocular muscles, ON, globe, orbit, blood vessels, and large nerves were manually traced in contiguous, quasi-coronal planes from the deep orbit to the trochlea (Fig. Help Four eyes had pseudoexfoliative glaucoma, and latanoprost such multiple mechanisms action! Minimal requirement at the present study, we prospectively monitored the occurrence of DUES in Japanese patients monitored the of! Of periorbital fat atrophyan unfamiliar side effect of both these topical agents in terms of fat! Between patients with POAG and the controls no IOP elevation or aggravation of the GONJ, did not find of. Fat pad ( steatoblepharon ) score K, Tsuchisaka a, Uysal Y, Altinsoy HI the. 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