Use Of Prostaglandin Analogues Research Articles

Conjunctival hyperaemia with the use of latanoprost versus other prostaglandin analogues in patients with ocular hypertension or glaucoma: a meta-analysis of randomised clinical trials

Aim:To conduct a meta-analysis of randomised clinical trials (RCTs) in order to evaluate the development of conjunctival hyperaemia after the use of latanoprost versus travoprost and bimatoprost, in patients with...

Effects of Oxidative Stress in Trabecular Meshwork Cells Are Reduced by Prostaglandin Analogues

The trabecular meshwork (TM) of glaucomatous eyes is characterized by cell loss, increased accumulation of extracellular matrix (ECM), and cellular senescence. One factor increasingly discussed in the pathogenesis of primary open-angle glaucoma (POAG) is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these typical glaucomatous changes in vitro and whether these oxidative stress-induced TM changes can be reduced by the application of prostaglandin analogues. Cultured human TM cells were exposed to 200 to 800 microM hydrogen peroxide (H(2)O(2)) for 1 hour. Cell loss was detected by cell-viability assay. Levels of fibronectin and MMP-2 mRNA were determined by real-time PCR analysis. Senescence-associated beta-galactosidase (SA-beta-Gal) activity was investigated by histochemical staining. The effects of prostaglandin analogues and benzalkonium chloride (BAC) on these glaucoma typical TM changes were investigated by preincubation of nonstressed or H(2)O(2)-treated cells with 1:100 diluted commercial solutions of bimatoprost, travoprost, and latanoprost or their corresponding BAC concentrations. H(2)O(2) induced cell death and fibronectin mRNA expression, but decreased the amount of MMP-2 mRNA. H(2)O(2) increased SA-beta-Gal activity. Additional pretreatment with BAC further increased the typical glaucomatous TM changes in vitro. These effects were reduced by preincubation with prostaglandin analogues in H(2)O(2)-treated and, to a lesser extent, in nonstressed cells. No reduction occurred in the presence of prostaglandin F receptor antagonists in H(2)O(2)-treated cells. Oxidative stress is able to induce characteristic glaucomatous TM changes in vitro, and these oxidative stress-induced TM changes can be minimized by the use of prostaglandin analogues. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.

Influence of topical bimatoprost on macular thickness and volume in glaucoma patients with phakic eyes

Background: In light of concern about the possible relation between the extensive clinical use of prostaglandin analogues and the development of retinal disorders such as cystoid macular edema, this study investigated the influence of topical application of bimatoprost 0.03% on macular thickness and volume in glaucoma patients with phakic eyes. Methods: A total of 40 eyes in 22 patients with primary open-angle glaucoma or normal-tension glaucoma were evaluated in this study. Optical coherence tomography images were taken before initiation of bimatoprost application and after 1, 2, and 3 months of treatment. In addition, best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured, and contrast sensitivity tests and fundus examinations were performed. Changes in various parameters, including macular thickness and volume, were analyzed. Results: BCVA and contrast sensitivity did not change from baseline over the treatment period. IOP declined by 20% to 25% from baseline for 1 month before stabilizing. Macular thickness and volume did not increase significantly during the 3 months. Interpretation: Topical application of bimatoprost does not induce clinical or structural changes in the macula, at least in glaucoma patients with phakic eyes. Moreover, bimatoprost effectively lowered IOP without causing macular disorders such as cystoid macular edema.

Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema?

Aim:A retrospective comparative case series was studied to determine whether the use of prostaglandin (PG) analogues to treat raised intraocular pressure (IOP) in patients with uveitis resulted in an increase...

Cystoid Macular Edema in a Pseudophakic Patient After Switching from Latanoprost to BAK-free Travoprost

The aim of this study was to report a case of cystoid macular edema (CME) in a pseudophakic patient after switching from latanoprost to BAK-free travoprost. This study is presented as an interventional case report. Clinical examination showed the development of CME, proven by ocular coherence tomography, after institution of BAK-free travoprost in a patient that was previously treated with Latanoprost. Ocular signs and symptoms responded to stopping travoprost and treatment with topical prednisolone and non-steroidal anti-inflammatory medicines. The intraocular pressure was successfully controlled with brimonidine tartrate 0.15%. CME is a known adverse effect of all prostaglandin analogs. However, our patient developed this complication after being switched from latanoprost to BAK-free travoprost. This may be due to exacerbation of a previously undiagnosed CME or to the ionic-buffered preservative system (sofZia) alone or in combination with travoprost unique to this product. It is prudent to exercise caution in the use of prostaglandin analogs and prostamides especially in high-risk eyes.

Effect of Topical Prostaglandin Analog Use on Outcome Following Selective Laser Trabeculoplasty

The aim of this study was to determine the effect of prostaglandin analog use on postoperative intraocular pressure (IOP) and treatment success following selective laser trabeculoplasty (SLT). Records from 113 eyes with open angle glaucoma who underwent SLT were reviewed retrospectively. Eyes were categorized as to whether they were receiving a topical prostaglandin analog (n = 78) or other classes of glaucoma medications (n = 35) before and following SLT. IOP was measured before (baseline) and at 1 h, 1 day, 1 week, and 1 month following SLT. Baseline IOP (+/-standard error [SE]) did not differ between prostaglandin analog users (18.0 +/- 0.48 mmHg) and nonusers (17.5 +/- 0.71 mmHg). One (1) month after SLT, average IOP decrease (+/-SE) was greater (P < 0.02) among prostaglandin analog users (3.4 +/- 0.4 mmHg), compared to nonusers (1.6 +/- 0.5 mmHg). Also at 1 month, average percent IOP decrease (+/- SE) was greater (P < 0.015) among prostaglandin analog users (16.5 +/- 2.0%), compared to nonusers (7.9 +/- 2.7%). At 1 h, 1 day, and 1 week after SLT, there were no differences in average IOP decrease or percent IOP decrease between prostaglandin analog users and nonusers. The percentage of eyes with a 20% or greater decrease in IOP was greater (P < 0.015) among prostaglandin analog users (44.9%), compared to nonusers (22.9%), 1 month after SLT. Also, 48.7% of prostaglandin analog users had an IOP decrease of 3 mmHg or greater, compared to 31.4% of nonusers, 1 month after SLT (P < 0.05). Retreatment rate among prostaglandin analog users (11.5%) was less (P < 0.005) than nonusers (34.3%). Prostaglandin analog use during the perioperative period prior to and 1 month after SLT is associated with greater average IOP decrease and percent IOP decrease 1 month postoperatively, compared to eyes not receiving these agents. Prostaglandin analog use is also associated with a greater likelihood of treatment success and a lesser likelihood of requiring retreatment 1 month postoperatively.

Misoprostol for Termination of Mid-trimester Post-Caesarean Pregnancy

Misoprostol, a synthetic prostaglandin analog, has become the leading means of terminating pregnancy, especially in the second trimester. In addition to being effective and safe, it is relatively inexpensive and easy to use. It is not clear, however, whether misoprostol is a safe abortifacient or labor-inducing agent after 20 weeks' gestation in women who have a uterine scar from a previous lower-segment cesarean delivery. This study evaluated the safety of misoprostol when used to terminate mid-trimester pregnancies in women with a history of at least one previous lower-segment cesarean section. The 80 participants underwent termination for an unwanted pregnancy, missed abortion, fetal anomaly, or fetal death between 13 and 26 weeks' gestation. The dose of misoprostol was 400 μg up to 20 weeks' gestation and 200 μg thereafter. Fifty women in each group took misoprostol intravaginally and the other 30 by the sublingual route. The dose was repeated every 6 hours up to a maximum of 24 hours. Woman having termination for similar reasons but lacking a history of cesarean section served as a control group. Women in the study and control groups were similar demographically. Unwanted pregnancy was the most prevalent indication for termination. The median interval from induction to abortion or delivery was 16.4 hours in study women and 15.6 hours in the control group. No scar rupture or dehiscence was observed, and there were no significant group differences in rates of incomplete abortion, blood loss, or sepsis. In 7 women, antibiotics readily controlled mild sepsis. Two women in each group who responded poorly to misoprostol underwent hysterotomy and salpingectomy. The investigators conclude that a scarred uterus from one or more previous lower-segment cesarean deliveries does not preclude the use of a prostaglandin analog such as misoprostol to terminate mid-trimester pregnancies.

A review of glaucoma treatment in Scotland 1994–2004

This study evaluated the changing trends in glaucoma management in Scotland between 1994 and 2004. A retrospective analysis of national health statistics in Scotland from 1994 to 2004. The Scottish morbidity record was used to collect information on all episodes of trabeculectomy. Data on number of prescriptions were gathered for individual drugs and also for groups of active ingredient. The population likely to have glaucoma (PLG) was calculated from estimates of prevalence in individuals aged 40 years and older, based on published epidemiological studies. The outcome measures were trabeculectomy rates, corrected for population likely to be at risk of glaucoma (PLG), and prescribing volume and cost for glaucoma medications. Trabeculectomy rates have fallen by 67% from 46 per 1,000 PLG in 1994 to 15.4 per 1,000 PLG in 2004. Over the same time period, the population likely to be at risk of glaucoma (PLG) increased by 16.6%. The cost of prescribing has increased by 122% over 11 years compared with an increase in number of items per 1,000 PLG by 27.5%. In 1994, beta-blockers accounted for 65.2% of prescribed drugs but by 2004 this had dropped to 33%. Since their introduction, the prescribing of prostaglandin analogues has increased rapidly and in 2004, they accounted for 39.4% of prescribed drugs. The increasing use of prostaglandin analogues has led to an increase in prescribing rates and a rapid increase in cost. At the same time, prescribing of beta-blockers has declined and trabeculectomy rates have fallen.

Adjunctive glaucoma therapy use associated with travoprost, bimatoprost, and latanoprost

ABSTRACTPurpose: This study contrasts the utilization of adjunctive medication associated with travoprost, bimatoprost, or latanoprost, as primary glaucoma therapies.Methods: Patients in the Medco Health database who initiated prostaglandin analog therapy on travoprost, bimatoprost or latanoprost between January 1, 2002 and July 31, 2002 were selected if they had no prostaglandin analog use in the prior 6 months. Patients were also required to have 12 months of prostaglandin therapy subsequent to the initial prescription. Data were available through July 31, 2003. The t-test and chi-square were used where appropriate to calculate p-values and assess significant differences.Results: A total of 13 171 benefit-eligible subjects were identified of which 8381 (64%), 2637 (20%), and 2153 (16%) patients were treated with latanoprost, bimatoprost, and travoprost, respectively. There were no significant differences in mean age or gender between the three study groups with the exception that latanoprost patients were statistically older than travoprost patients (69.0 vs. 68.0). This was not considered a clinically meaningful difference. Overall, patients using travoprost or bimatoprost had a significantly lower rate of adjunctive medication use compared to patients starting on latanoprost monotherapy (22.5%, 23.2%, and 30.2 %, respectively). Therefore, for every 14 patients treated with latanoprost instead of travoprost or bimatoprost, one additional patient would be expected to need adjunctive therapy with another agent. The difference between travoprost and bimatoprost patients was not significant.Conclusions: The use of adjunctive medications to control intraocular pressure was significantly higher for latanoprost patients compared to travoprost and bimatoprost patients. This finding should be interpreted in the context that this study was based only on prescription claims data. It is important to simplify ophthalmic medical regimen as it is more cost effective, better for the patient, and minimizes the washout effect from administering two eye medications within 5 min. Decreasing the complexity of the patients’ drug regimen may lead to increased adherence to prescribed therapy and a decreased risk of the incidence of blindness.

Association Between Topical Prostaglandin Analog Use and Development of Choroidal Neovascular Membranes in Patients with Concurrent Glaucoma and Age-Related Macular Degeneration

Matrix metalloproteinases (MMPs) are a family of enzymes that act to degrade extracellular matrix (ECM) molecules, such as collagen, elastin, and gelatin. The glaucoma medication latanoprost, and possibly other topical prostaglandin analogs, increase uveoscleral outflow and lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG) by activating MMPs 1, 2, 3, and 9 in the ciliary body. It has been reported that latanoprost may also gain access to the posterior segment and induce cystoid macular edema, although the mechanism is unknown. In the choroid, activation of some of the same subtypes of MMPs (particularly subtypes 2 and 9) has been implicated in the formation of choroidal neovascular membranes (CNVMs) in age-related macular degeneration (AMD). This study examined whether topical prostaglandin analog use is associated with a greater risk of CNVM formation in patients diagnosed with both AMD and POAG. A retrospective record review was performed to identify patients with a concurrent diagnosis of AMD and POAG between 1998 and 2004. Four hundred and eighty-four (484) eyes were identified and grouped as wet (n = 65) or dry (n = 419) AMD. Prostaglandin usage was compared between the two groups. Usage of other glaucoma medications was also compared. A minimum of 1 year of topical glaucoma medication was required for inclusion in the study. Exclusion criteria included a history of CNVM prior to starting glaucoma medications and a previous history of glaucoma surgery. Fifty-six percent (56%) of dry AMD and 62% of wet AMD eyes were using a topical prostaglandin (P > 0.10; not significant). Analysis of specific topical prostaglandin analog usage in the wet versus dry AMD groups revealed no statistically significant differences in the percentage of eyes treated with latanoprost (37.7% versus 41.5%), bimatoprost (12.9% versus 10.8%), or travoprost (9.2% versus 5.3%), respectively. No significant differences in the use of other glaucoma medications were observed between the two groups. No association between long-term topical prostaglandin use and CNVM development was found in patients with AMD and POAG.

Análogos das prostaglandinas diminuem a sensibilidade do teste provocativo da ibopamina no glaucoma

To evaluate the ibopamine provocative test for the diagnosis of glaucoma in glaucoma patients using antiglaucomatous drugs. Two 2% ibopamine eyedrops were instilled 5 minutes apart in one eye selected at random in both glaucoma and normal subjects. The intraocular pressure (IOP) was assessed prior to the drops and 30, 60 and 180 minutes after instillation. The test was considered positive when there was an intraocular pressure increase of greater than 4 mmHg at any one of the time-points. The amount of intraocular pressure change was compared to the types of medical treatment. Fifty-eight eyes were included (38 glaucoma patients and 20 normal individuals). The intraocular pressure rise was significantly higher in glaucoma patients (p<0.001 at all times). The sensitivity and specificity of the ibopamine test were 68% (87% if we exclude eyes using prostaglandin analogues) and 95%, respectively. Glaucoma patients using prostaglandin analogues did not present a significant intraocular pressure elevation. The ibopamine provocative test may be an auxiliary test in glaucoma diagnosis. Despite the small sample size, concurrent use of prostaglandin analogues apparently reduces the test's sensitivity.

Letter to the Editor: Hypertrichosis of the Eyelashes from Prostaglandin Analog Use: A Blessing or a Bother to the Patient?

<i>Letter to the Editor:</i> Hypertrichosis of the Eyelashes from Prostaglandin Analog Use: A Blessing or a Bother to the Patient?

Fallberichte

After application of bimatoprost containing eye drops for four weeks, a 72 year-old patient, suffering from glaucoma, developed hyperpigmentation and hypertrichosis of the eyelids. These symptoms can be seen in 1-10% of the patients as side effects in local therapy with bimatoprost, a prostaglandin analogue. The changes persist for varying periods of time but are reversible. Although prostaglandin analogues are sometimes more effective in the reduction of the intraocular pressure than beta-adrenoreceptor blocking agents, they remain second-line choices because of their side effects. This case report is meant to re-stimulate interest in the as yet obscure role of prostaglandins in hair biology, in clarifying the underlying mechanisms, and in exploring the possible therapeutic use of prostaglandin analogues in the management of hair loss (e.g. in androgenetic alopecia) or hair depigmentation (e.g. poliosis, canities).

Effects of progestagens and prostaglandin analogues on ovarian function and embryo viability in sheep

Current study assessed differences in the response of sheep to estrus synchronization either by the administration of two doses of prostaglandin or by the insertion of an intravaginal progestagen sponge. The preovulatory follicular dynamics and estradiol secretion, the ovulatory response and progesterone secretion and the number and quality of embryos were studied in 27 ewes treated with two doses of 100 μg of cloprostenol, 10 days apart, and in 29 sheep treated with progestagen sponges for 14 days. Percentage of sheep responding to the synchronization treatments with signs of estrus behaviour was similar between both groups (81.5% versus 72.4%, respectively). The use of progestagen resulted in a higher diameter of the largest follicle (6.6 ± 0.2 versus 5.9 ± 0.2, P < 0.05), and a lower number of small (6.7 ± 0.3 versus 9.6 ± 0.4, P < 0.005) and total follicles (10.3 ± 0.3 versus 12.9 ± 0.4, P < 0.005). However, mean plasma estradiol concentration during the follicular phase was higher in cloprostenol treated sheep ( P < 0.005). The mean ovulation rate was similar in both treatments (1.7 ± 0.2 versus 1.7 ± 0.3), but progesterone concentration during the early luteal phase was again higher in sheep treated with cloprostenol ( P < 0.05). The mean number of retrieved oocytes/embryos was very similar in both treatments (1.2 ± 0.2 versus 1.4 ± 0.2) and showed similar fertilization rates (70.6% versus 66.7%), but, although differences did not reach statistical significance, final viability rate was higher in cloprostenol than in progestagen treated ewes (58.9% versus 46.1%, P = 0.07). Current results give new evidences supporting the negative effects of progestagens on the functionality of ovulatory follicles and support the development of new protocols for assisted reproduction including the use of prostaglandin analogues.

Latanoprost and Pigmentation

Latanoprost is a prostaglandin analogue with well-established efficacy in the treatment of open-angle glaucoma and ocular hypertension. Once-daily administration of this drug for up to 5 years is generally well tolerated both locally and systemically. While most reported side effects have been classified as mild in intensity, an increase in iris, eyelash, and periocular pigmentation has been associated with prostaglandin analogue use in some patients. Follow-up studies of patients withdrawn from latanoprost treatment suggest that the increased iridial pigmentation is irreversible while changes in eyelash and periocular skin pigmentation are reversible after cessation of therapy. Concern as to whether latanoprost affects proliferation of iridial melanocytes or other cellular components prompted investigation into its mechanism of action. All available evidence from in vitro, in vivo, and clinical studies suggests that latanoprost does not induce melanocyte proliferation. Morphologic study of human peripheral iridectomy specimens did not reveal any significant latanoprost-induced pathologic change in the iris. There was no evidence of melanin granules blocking the outflow pathways in treated patients. Stimulation of melanogenesis in iridial melanocytes, perhaps through an effect on tyrosinase, appears to account for induction of melanin production. Additional studies are in progress to further elucidate the mechanism of latanoprost-induced increased iridial pigmentation.

Ibopamine provocative test and glaucoma: Consideration of factors that may influence the examination

Purpose. To evaluate factors that may influence the ibopamine provocative test for the diagnosis of glaucoma. Methods. Two Ibopamine (3,4 di-isobutyrylester of N-methyldopamine) 2% eyedrops were instilled 5 minutes apart in one eye selected at random in both glaucoma and normal subjects. The intraocular pressure (IOP) was assessed prior to the drops and 30, 60 and 180 minutes after instillation. The test was considered positive when there was an IOP increase of greater than 4 mmHg at any one of the timepoints. The amount of IOP change was compared to the severity of glaucomatous visual field loss and to the types of medical treatment. Results. The sensitivity (glaucoma patients with a positive result) and specificity (normal individuals with a negative result) of the Ibopamine test was 87 and 95%, respectively. Glaucoma patients using prostaglandin analogues did not have a significant IOP elevation. Conclusion. The Ibopamine provocative test may be an auxiliary test in glaucoma diagnosis. Concurrent use of prostaglandin analogues reduces the test’s sensitivity.

Putative Side Effects of Prostaglandin Analogs

Anecdotal case reports describe the occurrence of cystoid macular edema, iritis, herpes simplex keratitis, periocular skin darkening, and headaches in patients treated with prostaglandin analogs for glaucoma. The purpose of this article is to critically analyze these anecdotal case reports in light of a few well-controlled, randomized clinical studies to determine whether conclusions can be made about a causal relationship between the use of prostaglandin analogs and the occurrence of these side effects. None of these putative side effects has been proven to be causally related to latanoprost therapy using valid scientific methodology. These possible side effects occur rarely. Cystoid macular edema, iritis, and herpes simplex keratitis occur in eyes with risk factors. To scientifically establish a causal relationship between drug therapy and rare side effects, repeated rechallenging with masked controls is required. With rare exception, such methodology has not been used with any of these putative side effects. Nevertheless, even without firm establishment of a causal relationship, caution is advised with the use of prostaglandin analogs in eyes with risk factors for cystoid macular edema, iritis, and herpes simplex keratitis until properly designed, large, controlled studies provide more definitive information.

Prostaglandin analog treatment of glaucoma and ocular hypertension.

To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma. Primary and review articles were identified from a MEDLINE search (1966-May 2001) and requested information from product manufacturers. All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date. The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with beta-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes. Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.

Cystoid macular edema in aphakia and pseudophakia after use of prostaglandin analogs

Prostaglandin analogs are powerful ocular hypotensive agents that may also be associated with a breakdown of the blood-retinal barrier and cystoid macular edema. The association is evident in pseudophakic or aphakic patients. This paper presents a case of unilateral latanoprost-associated clinical cystoid macular edema in a bilaterally pseudophakic patient; the only difference between the two eyes was the presence of a capsulotomy in the affected eye. We review the literature concerning prostaglandin analog-associated cystoid macular edema, as well as the evidence for prostaglandin analog-associated breakdown of the bloodretinal barrier. Although some evidence is suggestive of a connection between prostaglandin analogs and cystoid macular edema, many questions concerning the complex physiology of prostanoids remain. Until our understanding of these issues is more advanced, judicious use of prostaglandin analogs in patients at risk for cystoid macular edema would be prudent.

The pros and cons of different prostanoids in the medical management of glaucoma

The prostaglandin analogs are new exciting drugs added to the therapeutic armamentarium for patients with glaucoma. Several studies have evaluated the ocular hypotensive properties and side effects of latanoprost in different forms of glaucoma. This drug, seems to be the most effective intraocular pressure (IOP)-reducing agent currently available, and has a low incidence of ocular and systemic side effects. Fewer data are available regarding unoprostone, but the IOP-reducing effect of this drug seems to be comparable or slightly inferior to that of timolol and it produces fewer side effects. When compared with unoprostone, latanoprost has been shown to effect a greater reduction in IOP. A major drawback to the use of prostaglandin analogues is the lack of long-term experience such as that currently available for other classes of agents.