Effect of retrobulbar prostaglandin analog injection on orbital fat in rats.

PURPOSE: Periorbital fat atrophy is a known side effect of topical prostaglandin analogs (PA). This side effect may have implications in the treatment of diseases like thyroid orbitopathy. In this in vivo study we aimed to evaluate the effects of retrobulbar injection of three different PAs on orbital fat. METHODS: Eighteen adult male Wistar-albino rats were divided into three groups of six animals. 0.1 ml of 0.03% bimatoprost, 0.005% latanoprost, or 0.005% travoprost was injected into the right orbits and saline was injected into the left orbits, as controls. Both orbits were exenterated after 3 weeks. Histological cross-sections were analyzed using ImageJ image analysis software. Intraconal adipocyte density was calculated. RESULTS: There was no significant difference in the adipocyte density between the PA injected orbits and the control side in each of the three groups. When calculations from all three groups were analyzed together, again the difference in the adipocyte density between the PA injected orbits and the control side was not significant. CONCLUSION: No significant fat atrophy was noted in this rat model three weeks after retrobulbar injection of PAs. To evaluate retrobulbar injection of PA as a potential therapy for orbital diseases with fat proliferation, in vivo studies in different animal models, higher concentrations of PA, or longer follow-up duration are required.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

Generic benzalkonium chloride-preserved travoprost eye drops are not identical to the branded polyquarternium-1-preserved travoprost eye drop: Effect on cultured human conjunctival goblet cells and their physicochemical properties.

PURPOSE: To investigate the effect of polyquaternium-1 (PQ)-preserved and benzalkonium chloride (BAK)-preserved travoprost eye drops on viability of primary human conjunctival goblet cell (GC) cultures and on secretion of mucin and cytokines. Furthermore, to evaluate the physicochemical properties of the branded travoprost eye drop Travatan® and available generics. METHODS: The effect of travoprost eye drops was evaluated on GC cultures. Cell viability was assessed through lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin secretion was evaluated by immunohistochemical staining. Secretion of interleukin (IL)-6 and IL-8 was measured using BD Cytometric Bead Arrays. pH, viscosity, droplet mass, osmolality and surface tension were measured for all included eye drops. RESULTS: In the LDH assay, BAK travoprost caused significant GC loss after 2 hrs of incubation compared to the control. PQ travoprost caused no GC loss at any time point. Both PQ- and BAK travoprost caused secretion of mucin to the cytoplasma. No difference in IL-6 and IL-8 secretion was identified compared to controls. The pH values for the generics were lower (pH 6.0) than the pH value for Travatan (pH 6.7; p < 0.0001). The viscosity was lowest for Travatan, while the mean droplet mass was higher for Travatan (35 mg) than the generics (28-30 mg; p ≤ 0.0318). The osmolality and surface tension did not differ between the eye drops investigated. CONCLUSION: BAK travoprost caused GC loss, indicating that PQ preservation may be preferable in treatment of glaucoma. Furthermore, physicochemical properties of branded and generic travoprost eye drops can not be assumed to be identical.

Serous macular detachments associated with topical travoprost.

Here is presented a unique case of bilateral serous macular detachments as a side effect of topical travoprost (0.004%) therapy. Only three other cases in the literature have definitively associated this side effect with other topical prostaglandins. The aetiological and pathophysiological pathways remain to be clearly elucidated but are potentially related to increased choroidal vascular permeability. In this case, the subretinal fluid resolved rapidly and completely after cessation of travoprost drops, showing it to be a reversible pathology similar to prostaglandin-associated cystoid macular oedema. This uncommon association is therefore important to consider in the differential diagnosis of serous macular detachment. Increasing ophthalmic awareness could help to prevent unnecessary investigations in undifferentiated patients without other guiding historical or examination features. This may save time and expense for the patient and health systems.

Effects of topical prostaglandin drops on angiogenesis in an in ovo chick chorioallantoic membrane model.

BACKGROUND: To investigate the effects of bimatoprost, latanoprost and travoprost on angiogenesis in the chick chorioallantoic membrane (CAM) model in ovo. MATERIALS AND METHODS: Fifty fertilized specific-pathogen-free chick eggs were used in this preclinical, prospective, experimental embryo study. Eggs were randomly distributed into 5 groups of ten eggs. Eggs were placed in the incubator after disinfection of their shells with alcohol and monitored appropriate temperature and humidity. On the 3rd day of incubation, a small window was opened on the eggshell. Bimatoprost in group 1, latanoprost in group 2, travoprost in group 3, bevacizumab in group 4, phosphate-buffered-saline (PBS) used in group 5 was applied by injection to CAM. The sterile film was glued onto the broken part of the shell and the eggs were placed in the incubator again. On the 8th day of incubation, eggs were opened and vascular structures on CAMs were examined. Digital photographs were taken, analysed in the ImageJ open source image processing software and differences between groups were evaluated. Thereafter, VEGF (Vascular endothelial growth factor) levels were measured appropriately in the embryo samples. RESULTS: All embryos in the prostaglandin groups and the PBS control group were observed to have life signs confirmed by heart rate. In 8 embryos in the bevacizumab group, no life signs were confirmed, while 2 embryos with life signs showed severe hypoplasia. Vascular density, number of vessels and VEGF levels in the bimatoprost, latanoprost and travoprost groups, there were statistically significantly higher than the PBS control group. CONCLUSION: This study demonstrates that topical prostaglandin drops increase angiogenesis in the chick CAM model in ovo.

Effectiveness of Blepharoptosis Surgery in Patients With Deepening of the Upper Eyelid Sulcus.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ±â€Š0.96 mm before surgery and 3.72 ±â€Š0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Effects of a prostaglandin F2alpha derivative glaucoma drug on EGF expression and E-cadherin expression in a corneal epithelial cell line.

Purpose: We examined the effects of travoprost on cell proliferation-related signals and E-cadherin expression in vitro and in situ in order to obtain evidence to support the hypothesis that topical travoprost impairs the integrity of the corneal epithelium.Methods: A human corneal epithelial cell culture was treated with travoprost (0.4 mg/ml) and/or PD168393 (an EGF receptor inhibitor, 10 µM). The culture was then processed for cell proliferation, an mRNA expression analysis of epidermal growth factor (EGF) and E-cadherin, and protein expression analysis of E-cadherin by immunocytochemistry and Western blotting. The eyes of C57/BL6 mice were incubated in serum-free medium plus travoprost (0.4 mg/ml) and/or PD168393 (10 µM). After being cultured for 24 h, the expression patterns of phospho-EGFR, phospho-ERK, E-cadherin, and Ki67 were immunohistochemically examined in paraffin sections.Results: The addition of travoprost up-regulated EGF mRNA expression and cell proliferation in the corneal epithelial cell culture, and this was cancelled by the addition of PD168393. This FP agonist also decreased E-cadherin expression levels in the cell-cell contact zone, and this was cancelled by the addition of PD168393. In the organ culture, the addition of travoprost to the medium up-regulated the expression of phospho-EGFR and phospho-ERK as well as cell proliferation, and down-regulated the expression of E-cadherin in the corneal epithelium, particularly in basal cells, whereas PD168393 reversed these effects.Conclusions: Travoprost activates epithelial cell proliferation by up-regulating an EGF-related signal in association with the suppression of E-cadherin localization in the cell-cell contact zone. Modulation of the EGF signal may be a strategy to minimize the negative impact of this mitogen on reformation of corneal barrier function during epithelial renewal.

Effect of Topical Hypotensive Medications for Preventing Intraocular Pressure Increase after Cataract Surgery in Eyes with Glaucoma.

PURPOSE: To compare the effects of a topical intraocular pressure (IOP)-lowering medication for preventing an IOP increase after cataract surgery in eyes with glaucoma. DESIGN: Randomized clinical study. METHODS: A total of 165 eyes of 165 patients with primary open-angle glaucoma or pseudoexfoliation glaucoma scheduled for phacoemulsification were randomly assigned to 1 of 3 groups to receive each medication immediately postoperatively: 1) prostaglandin F2α analog (travoprost), 2) ß-blocker (timolol maleate), or 3) carbonic anhydrase inhibitor (brinzolamide). Intraocular pressure (IOP) was measured using a rebound tonometer at 1 hour preoperatively, at the end of surgery, and at 2, 4, 6, 8, and 24 hours postoperatively. The incidence of eyes exhibiting a marked IOP increase to greater than 25 mm Hg was compared among the groups. RESULTS: At 1 hour preoperatively and at the end of surgery, mean IOP did not differ significantly among the groups. Mean IOP increased significantly between 4 and 8 hours postoperatively and then decreased at 24 hours postoperatively in all groups (P < .0001). Mean IOP was significantly lower in the brinzolamide group than in the travoprost or timolol group at 4, 6, and 8 hours postoperatively (P ≤ .0374) and did not differ significantly among groups at 2 and 24 hours postoperatively. The incidence of an IOP spike was significantly lower in the brinzolamide group than in the travoprost and timolol groups (P = .0029). CONCLUSIONS: Brinzolamide reduces the short-term IOP increase after cataract surgery more effectively than travoprost or timolol in eyes with glaucoma, suggesting that brinzolamide is preferable for preventing an IOP spike.

Eficácia do travoprosta 0, 004% na redução da pressão intraocular em pacientes com glaucoma / Travoprosta 0, 004% efficacy in intraocular pressure in patients with glaucoma

Resumo Objetivo: avaliar a eficácia do colírio TRAVAMED® (travoprosta 0,004%) (Ofta, Brasil) na redução da pressão intraocular (PIO), em pacientes com glaucoma primário de ângulo aberto (GPAA) ou hipertensão ocular (HO), bem como avaliar os efeitos colaterais decorrentes do uso da droga. Métodos: estudo randomizado, controlado, com 70 olhos de 38 pacientes acima de 18 anos de idade, com diagnóstico de GPAA ou HO. Todos os pacientes receberam o colírio TRAVAMED® como primeira droga a ser introduzida no tratamento, tendo sido utilizada uma gota uma vez ao dia (à noite), e 30 dias após foram submetidos à tonometria de aplanação (Goldmann) para mensuração da PIO, com o mesmo examinador, no mesmo tonômetro e nos mesmos horários. Resultados: A média de redução da PIO após 30 dias de uso do TRAVAMED® foi de 7,46 mmHg. Em relação aos efeitos colaterais, 15,71% (11) dos olhos apresentaram hiperemia conjuntival, 8,57% (6) apresentaram dor, 8,57% (6) apresentaram ardência, 2,86% (2) apresentaram embaçamento visual e em 1,56% (1) dos olhos não houve queda significativa da PIO. Conclusão: A medicação TRAVAMED® foi eficiente na redução da PIO após 30 dias de uso contínuo, na dose de 1x/dia. Acerca dos efeitos colaterais, os mais observados foram hiperemia ocular (15,71%), dor (8,57%) e ardência (8,57%), porém estudos com maior tempo de seguimento se fazem necessários.

Abstract Objective: to evaluate how much decreases intraocular pressure (IOP) with TRAVAMED® (travoprost 0,004%) (Germed, Brazil) in patients with primary open angle glaucoma (POAG) and ocular hypertension (OH) and possible side effects. Methods: controlled and randomized study, it was evaluated 70 eyes of 38 patients with age of 18 years old or more diagnosed with POAG and OH. All the patients had TRAVAMED® as first drop for treatment used once daily (at night) and 30 days later they had IOP measured by Goldmann tonometry, with the same examiner in the same tonometer at the same times. Results: the mean decrease in IOP was 7,46 mmHg after 30 days using the drops. 15.71% (11) of eyes had conjunctival redness, 8.57% (6) had pain, 8.57% (6) had burning, 2.86% (2) had blurring vision and 1.56% (1) of the eyes there wasn't a significant reduction in IOP. Conclusion: TRAVAMED® was efficient when evaluating IOP decrease. The most correlated side effects were conjunctival redness (15.71%), pain (8.57%) and burning (8.57%), but studies with longer follow-up are needed.

Association of Postoperative Topical Prostaglandin Analog or Beta-Blocker Use and Incidence of Pseudophakic Cystoid Macular Edema.

PURPOSE: The purpose of this article is to determine the association of postoperative topical prostaglandin analog (PGA) or topical beta-blocker use and the incidence of pseudophakic cystoid macular edema (CME). METHODS: This was a nested case-control study. All adult patients who underwent cataract surgery between January 1, 2006 and December 31, 2016 and who were enrolled in the PharMetrics Plus database were eligible for inclusion. The association between postoperative topical PGAs (bimatoprost, latanoprost, and travoprost/travoprost-z) or beta-blocker (betaxolol, levobunolol, and timolol) use and the incidence of pseudophakic CME was assessed by conditional logistic regression. RESULTS: Five hundred eight cases and 5080 controls were included in the analyses. Incidence of pseudophakic CME was found to be statistically significantly associated with the current postoperative use of both topical PGAs [relative risk (RR), 1.86; 95% confidence interval (CI), 1.04-3.32] and topical beta-blockers (RR, 2.64; 95% CI, 1.08-6.49). Postoperative use of each of bimatoprost (RR, 2.73; 95% CI, 1.35%-5.53%) and travoprost/travoprost-z (RR, 3.16; 95% CI, 1.42-7.03) in the year before diagnosis was demonstrated to be statistically significantly associated with the incidence of pseudophakic CME. This association was not observed to be statistically significant with the postoperative use of latanoprost (RR, 1.55; 95% CI, 0.84-2.88). CONCLUSIONS: To the best of our knowledge this is the largest study that has investigated the association between postoperative topical PGA or topical beta-blocker use and the incidence of pseudophakic CME. Postoperative use of both topical PGAs and topical beta-blockers was found to be associated with the incidence of pseudophakic CME.

Prospective Evaluation of Two iStent® Trabecular Stents, One iStent Supra® Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes.

INTRODUCTION: This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG). METHODS: Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1-3 glaucoma medications. Subjects received two iStent® trabecular micro-bypass stents, one iStent Supra® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations. RESULTS: Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. CONCLUSION: IOP control was achieved safely with two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin. This microinvasive, ab interno approach introduces a possible new treatment option for refractory disease. TRIAL REGISTRATION: NCT01456390. FUNDING: Glaukos Corporation.

Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy.

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, ß-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

Factors Related to Prostaglandin-Associated Periorbitopathy in Glaucoma Patients.

PURPOSE: To determine factors related to prostaglandin-associated periorbitopathy (PAP) and its prevalence in glaucoma or ocular hypertension (OHT) patients using prostaglandins analogs (PGAs). DESIGN: A cross-sectional study. METHODS: A study of glaucoma or OHT patients, using topical PGAs for at least 3 months, was performed. Eyes treated with PGAs were photoraphed and independently evaluated for PAP by 2 glaucoma specialists using at least 4 out of 7 clinical appearances. The factors of interest were sex, age, body mass index (BMI), types of glaucoma, types of PGAs, duration of PGA use, and concurrent 0.5% timolol. Univariate (χ2 test) and multivariate (multiple logistic regression) analyses assessing risk factors for PAP were performed to estimate the odds ratios (OR) with 95% conidence intervals (CIs). RESULTS: One hundred thirty-four eyes from 134 patients were included. Seventy (52.2%), 21 (15.7%), and 43 (32%) eyes received components of latanoprost, travoprost, and bimatoprost, respectively. Prevalence of PAP was 44.8% (95% CI, 36.3 to 53.3). Older age >60 years (OR, 3.0; 95% CI, 1.2 to 7.8), bimatoprost (OR, 4.0; 95% CI, 1.6 to 9.5), travoprost (OR, 3.3; 95% CI, 1.1 to 10.1), and timolol (OR, 2.9; 95% CI, 1.3 to 6.8) were at risk of PAP development. In addition, BMI ≥23 kg/㎡ (OR, 0.3; 95% CI, 0.1 to 0.7) was reversely associated with PAP. CONCLUSIONS: Older age, bimatoprost, or travoprost were associated with PAP, whereas high BMI was found as a protective factor. Interestingly, timolol possibly precipitated periorbital change when in use with prostaglandins.

Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits / Efeitos dos análogos da prostaglandina na velocidade do fluxo sanguíneo e resistência na artéria oftálmica de coelhos

ABSTRACT Purpose: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. Methods: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. Results: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. Conclusion: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

RESUMO Objetivo: O objetivo deste estudo foi investigar os efeitos dos análogos da prostaglandina (PGAs) no fluxo sanguíneo da artéria oftálmica em coelhos. Métodos: Cinquenta e cinco coelhos da raça Nova Zelândia clinicamente saudáveis foram divididos em seis grupos para tratamento com formulação tópica de diferentes APGs (bimatoprosta BAK, tafluprosta BAK-free, travoprosta BAK, travoprosta POLYQUAD e latanoprosta BAK) e formulações contendo apenas o conservante cloreto de benzalcônio (BAK). Foi realizada ultrassonografia com Doppler antes e após os tratamentos. Os valores do pico da velocidade sistólica (PSV) e da velocidade diastólica final foram obtidos e o índice de resistência (RI) foi então calculado. A análise estatística foi realizada para comparar as diferenças entre cada droga no pré e pós-tratamento, além das diferenças no pós-tratamento entre as drogas. Resultados: Estes colírios PGAs não afetaram o PSV. A bimatoprosta com o conservante BAK, travoprosta com o conservante POLYQUAD e latanoprosta com o conservante BAK não alteraram o RI. Já o tratamento com tafluprosta sem conservante (BAK-free) e travoprosta com o conservante BAK promoveram redução similar dos valores do RI. Não houve diferença significativa na comparação entre valores pré e pós-tratamento quando BAK foi administrado isoladamente. Conclusão: Os PGAs tafluprosta BAK-free e travoprosta BAK melhoraram o fluxo sanguíneo na artéria oftálmica em coelhos da raça Nova Zelândia sugerindo que estes medicamentos possam contribuir na prevenção da progressão do glaucoma.

Reversible Conjunctival Pigmentation Associated With Prostaglandin Use.

A 54-year-old Indian male with a diagnosis of ocular hypertension was started on a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six years later, he developed progressively increasing bilateral limbal conjunctival hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and over the next year, the patient's conjunctival pigmentation improved significantly in both the eyes. This case report documents with slit-lamp photography the first case of conjunctival pigmentation associated with PGA use that has been shown to have reversal with discontinuation of the PGA. Because of the widespread use of PGAs, and the evolving nature of the conjunctival pigmentation, clinicians should be aware of this reversible condition when considering biopsy or removal of conjunctival melanocytic lesions.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Prostaglandin agonist effect on matrix metalloproteinase aqueous levels in glaucoma patients.

OBJECTIVE: To determine whether the aqueous levels of matrix metalloproteinases (MMPs) differ between patients with glaucoma treated with topical prostaglandin analogues and normal, nonglaucomatous control patients. Also, to note any difference in MMP levels between latanoprost, travoprost, and bimatoprost that might suggest a difference in efficacy or mechanism of action between these drugs. DESIGN: Prospective, observational study. PARTICIPANTS: Patients who were scheduled to undergo routine intraocular surgery (phacoemulsification or combined phacotrabeculectomy) as part of their standard clinical care were included. Eighteen eyes of 18 patients with glaucoma using any 1 prostaglandin analogue (latanoprost, travoprost, or bimatoprost) were compared with 8 normal control patients. METHODS: This was a multicentre study. Aqueous humour (0.2 mL) was aspirated at the beginning of the intraocular surgery through a clear corneal paracentesis. MMP-2 and -9 were quantified in the aqueous of all participants using enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in the levels of either MMP-2 (p = 0.216) or MMP-9 (p = 0.552) between the control patients and the patients with glaucoma on prostaglandins. There was no difference in the levels of MMP-2 or -9 between the latanoprost, travoprost, or bimatoprost groups. CONCLUSIONS: The levels of MMP-2 and -9 in aqueous of glaucomatous eyes on topical prostaglandin analogues were the same as those of normal age-matched control patients. This could reflect either a return to normal levels with efficacious treatment or a lack of difference between disease and nondisease states.

Efficacy of selective laser trabeculoplasty in primary angle-closure glaucoma: a randomized clinical trial.

IMPORTANCE: Selective laser trabeculoplasty (SLT) should be explored as a therapeutic option in eyes with angle closure. OBJECTIVE: To assess the intraocular pressure (IOP)-lowering efficacy of SLT in eyes with primary angle closure (PAC) and PAC glaucoma (PACG). DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at tertiary eye care institutions of 100 patients diagnosed as having PAC or PAC glaucoma in which the angles had opened at least 180° (visible posterior trabecular meshwork on gonioscopy) after laser iridotomy. Recruitment and baseline were completed from June 2009 to April 2012 and 6-month follow-up was completed from December 2009 to November 2012. INTERVENTIONS: Eligible patients with a baseline IOP greater than 21 mm Hg were randomized to either SLT or prostaglandin analog (PGA; travoprost, 0.004%). The SLT was repeated if the IOP reduction was less than 20.0% from baseline at the 1- or 3-month follow-up visit. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in IOP from baseline to the final follow-up visit (at 6 months). The frequency of additional postoperative treatments and complications were secondary outcomes. RESULTS: Fifty patients (96 eyes) were randomized to SLT and 50 patients (99 eyes) to PGA medical therapy. At 6 months, 49 patients in the SLT group and 47 in the PGA group completed follow-up. Analysis was based on intent to treat. At 6 months, IOP decreased by 4.0 mm Hg (95% CI, 3.2-4.8) in the SLT group (P < .001) and by 4.2 mm Hg (95% CI, 3.5-4.9) in the PGA group (P < .001). There were no differences between the SLT and PGA groups in the absolute mean reduction of IOP (4.0 vs 4.2 mm Hg, respectively; P = .78) or in the percentage of reduction in IOP (16.9% vs 18.5%, respectively; P = .52). Complete success (IOP ≤21 mm Hg without medications) was achieved in 60.0% eyes of the SLT group, compared with 84.0% of eyes in the PGA group (P = .008). No patients required glaucoma surgery. Additional medications were required in 22.0% of patients in the SLT group compared with 8.0% in the PGA group (P = .05). One patient in the SLT group (2.0%) had a transient posttreatment IOP spike greater than 5 mm Hg. The mean endothelial cell count showed a significant decrease from baseline in the SLT arm (4.8% decrease; P = .001). No other events such as persistent uveitis or increase in peripheral anterior synechiae were noted in eyes that underwent SLT. Two patients in the PGA group exited owing to drug-related complications (1 patient with uveitis and 1 with allergic conjunctivitis). CONCLUSIONS AND RELEVANCE: Eyes with PAC or PACG respond to SLT in the short term, but the overall long-term therapeutic effectiveness needs further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004900.

Unilateral Prostaglandin-Associated Periorbitopathy: A Syndrome Involving Upper Eyelid Retraction Distinguishable From the Aging Sunken Eyelid.

PURPOSE: To study the effects of prostaglandin analogue drops on the eyelids and adnexa in unilaterally treated subjects with the intention of qualifying, quantifying, and categorizing the characteristics of prostaglandin-associated periorbitopathy (PAP). METHODS: Patients using prostaglandin analogue drops in only 1 eye for at least 1 year were evaluated by masked examiners. Orbital and eyelid measurements were obtained for each patient, and adnexal photographs were taken. PAP was divided into 3 grades based on the presence and severity of fat atrophy and the existence and depth of superior sulcus deformity. Statistical analysis was performed comparing data between treated and untreated eyes. RESULTS: Thirty-three patients meeting eligibility criteria were enrolled, with equal numbers of subjects using latanoprost, travoprost, and bimatoprost. Treated eyes had a statistically significant increase in lagophthalmos (0.62 mm, p < 0.001), superior sulcus deformity/PAP grade (0.72, p < 0.001), and eyelid redness (1.08, p < 0.001). Treated eyes had significantly greater marginal reflex distance 1 measurements (0.89 mm, p = 0.02), highest with bimatoprost and moderate PAP. Treated eyes had relatively greater enophthalmos than untreated eyes. Very few patients noticed or complained about eyelid changes. CONCLUSION: Prostaglandin analogue drops cause adnexal changes and orbital fat atrophy leading to eyelid redness, superior sulcus deformity, higher eyelid crease, and enophthalmos. In contrast to previous studies showing ptosis in PAP, relative upper eyelid retraction was seen in most of our treated eyes. Our novel PAP grading scale may help objectify and categorize this syndrome. Awareness of these signs is critical, as the eyelids and eyes may be affected even in the absence of patient recognition.