DOCSLIB.ORG

ECS30160.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ECS30160.Pdf CLINICAL SCIENCES Increase in Outflow Facility With Unoprostone Treatment in Ocular Hypertensive Patients Carol B. Toris, PhD; Guilin Zhan, MD; Carl B. Camras, MD Objective: To determine the mechanism by which 0.15% Results: Compared with baseline, unoprostone signifi- unoprostone isopropyl reduces intraocular pressure (IOP) cantly (PϽ.001) reduced IOP by a mean±SEM of 5.6±0.4 by studying 33 patients with ocular hypertension or pri- mm Hg and 4.8±0.6 mm Hg on days 5 and 28, respec- mary open-angle glaucoma. tively. The change from baseline with unoprostone was sig- nificantly (PϽ.001) greater than with placebo by 2.8±0.4 Methods: At baseline, IOP was determined by pneu- mm Hg on day 5 and by 3.2±0.5 mm Hg on day 28. Com- matonometry, aqueous flow and outflow facility by fluo- pared with baseline, unoprostone significantly (PՅ.001) rophotometry, episcleral venous pressure by venom- increased outflow facility by 0.05±0.01 and 0.08±0.02 anometry, and uveoscleral outflow by mathematical µL·min−1·mm Hg−1 on days 5 and 28, respectively. The base- calculation. Unoprostone was administered to one eye line-adjusted between-treatment differences were signifi- and placebo to the fellow eye of each patient twice daily cant (PՅ.04) on day 28 (0.06±0.02 µL·min−1·mm Hg−1). in a randomized masked fashion. In patients who dem- Other measures were not different from placebo. onstrated an IOP reduction of 3 mm Hg or more in either eye on day 5±1 (n=29), determinations were repeated Conclusion: In responsive patients, unoprostone de- on that day and on day 28±2. Treated eyes were com- creased IOP by increasing outflow facility. pared with control eyes, and treatment days were com- pared with baseline by paired t tests. Arch Ophthalmol. 2004;122:1782-1787 NTRAOCULAR PRESSURE (IOP) IS tating outflow of aqueous humor. An in- maintained by the production of crease in outflow facility6 and uveoscleral aqueous humor and its drainage outflow7 has been reported after topical ad- through the anterior chamber ministration of unoprostone in rabbits. No angle. Current glaucoma thera- effect on tonographic outflow facility was pies lower IOP by reducing aqueous hu- found in healthy humans8 or in patients I 9 mor production, increasing outflow with glaucoma, suggesting that a uveo- through the uveoscleral pathway, or in- scleral outflow effect accounted for the IOP creasing the facility of trabecular out- decrease. Recently, Thieme and cowork- flow. Some medications, such as bri- ers10 suggested that unoprostone lowers monidine tartrate,1 have been shown to IOP by affecting aqueous outflow through have multiple mechanisms of action. If tar- the trabecular meshwork via inhibition of get IOP is not reached after an appropri- endothelin-dependent mechanisms. ate period of monotherapy, combination This study was conducted to deter- treatments are used to achieve the de- mine the effects of unoprostone on aque- sired IOP-lowering effect, especially com- ous humor dynamics in patients with binations of drugs with differing modes of ocular hypertension (OHT) or primary action.2 An understanding of the IOP- open-angle glaucoma (POAG). lowering mechanism of action of each glaucoma medication would help predict METHODS additivity between drugs. Author Affiliation: Department Unoprostone isopropyl is a structural of Ophthalmology, University of This was a single-center, randomized, double- Nebraska Medical Center, analogue of prostaglandin (PG) F2␣ and has masked, placebo-controlled study in patients Omaha. been reported to be a docosanoid. It has with OHT or POAG. The number of patients Financial Disclosure: been shown to be a safe and efficacious to enroll was determined before the start of the Dr Camras was a consultant for IOP-lowering drug.3-5 Unoprostone ap- study by power estimates generated with the Pharmacia Corp. pears to lower IOP by increasing or facili- nQuery Advisor Version 2.0 (Statistical Solu- (REPRINTED) ARCH OPHTHALMOL / VOL 122, DEC 2004 WWW.ARCHOPHTHALMOL.COM 1782 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 1. Schedule of Visits Visit 1 Visit 2 Visit 3 Visit 4 (Day −31 to −1) Screening (Day 0) Baseline (Day 5 ± 1) (Day 28 ± 2) Previous IOP therapy is discontinued. IOP is checked at 8 AM ±1h. IOP is checked at 8 AM ±1h. IOP is checked at 8 AM ±1h. Washout period begins. IOP should be 23-30 mm Hg IOP must be reduced by 3 mm Hg vs Masked study medication Inclusion/exclusion criteria in both eyes and Յ5mmHg baseline in at least 1 eye and IOP is instilled by investigator. are evaluated. difference between eyes. should be Յ30 mm Hg in both eyes; Aqueous humor dynamic Complete ophthalmic examination Baseline aqueous humor dynamic if not, patient exits study. parameters are collected. is given. parameters are collected. Masked study medication is instilled Complete ophthalmic Urine pregnancy test is performed After all measurements, 1 eye is by investigator. examination is given. (if applicable). randomly assigned to receive Aqueous humor dynamic parameters Urine pregnancy test unoprostone isopropyl, while the are collected. is repeated (if applicable). other receives placebo twice daily Patient continues to self-administer unoprostone and placebo twice daily. Abbreviation: IOP, intraocular pressure. tions, Boston, Mass). A sample size of 30 subjects was needed tween eyes on visit 2. Eligible patients then received 1 drop of to provide at least 75% power to detect a difference in aqueous 0.5% timolol maleate in each eye or acetazolamide, 250 mg orally. flow of 15% between drug-treated and vehicle-treated eyes, as- These drugs reduce aqueous flow and IOP to enable calcula- suming a standard deviation of 0.75 µL/min and a 2-sided sig- tion of fluorophotometric outflow facility (Cfl), which pro- nificance level of .05. The study was approved by the Univer- vides an estimate of trabecular outflow facility.14 sity of Nebraska Medical Center Institutional Review Board, The following formula was used to calculate Cfl: Omaha, and all patients provided written informed consent be- [( ) ( )] fore initiation of any study-related assessments. Cflx= Fa−Fax / IOP−IOPx , Patients were scheduled for 4 visits, consisting of screen- where Fa indicates aqueous flow rate before treatment with ing, baseline, day 5±1 of treatment, and day 28±2 of treat- acetazolamide or timolol; Fax, aqueous flow rate at intervals ment. The protocol is summarized in Table 1. x=1, 2, and 3 after acetazolamide-timolol; IOP,the IOP just At visit 1 (screening), a medical history was collected from before acetazolamide-timolol administration; IOPx, average of each patient and a complete ophthalmic examination was per- IOP values taken at the beginning and end of intervals x=1, 2, formed. Main inclusion criteria at visit 1 included diagnosis of and 3; and Cfl , Cfl at intervals x=1, 2, and 3. The 3 calculated bilateral POAG or OHT for at least 1 year and corrected dis- x Cflx measurements were averaged to obtain the reported Cfl tance visual acuity of 20/200 or better (Early Treatment Dia- values. betic Retinopathy Study visual acuity chart). Main exclusion Uveoscleral outflow (Fu) was calculated by means of the criteria at visit 1 consisted of any visual field defect, known hy- following formula: persensitivity to study-related medication, previous glaucoma ( ) filtering procedure, cataract or laser surgery within the past year, Fu=Fa−Cfl IOP−Pev , ocular infection or inflammation within the past 3 months, or history of elevated IOP caused by processes other than POAG where Pev is episcleral venous pressure. or OHT. Before the baseline visit (visit 2), subjects who had Safety assessments were performed and eligible patients re- been taking medication to treat the elevated IOP discontinued ceived 2 bottles identical in appearance and labeled only by the these drugs before the baseline visit. The medications in- patient’s identification number and the words right eye or left cluded latanoprost (n=7), timolol maleate (n=4), betaxolol hy- eye. One bottle contained 0.15% unoprostone isopropyl (Res- drochloride (n=2), latanoprost plus timolol (n=2), dorzol- cula; Novartis Ophthalmics, East Hanover, NJ) and the other amide hydrochloride (n=1), bimatoprost (n=1), latanoprost contained vehicle (placebo). Patients were instructed to instill plus dorzolamide (n=1), latanoprost plus brimonidine (n=1), 1 drop in the appropriate eye twice daily (8 AM and 8 PM) for 4 and timolol plus travoprost (n=1). The washout period was 3 to 6 days in a double-masked, randomized fashion. Patients were days for dorzolamide, 15 days for brimonidine, and 28 days for asked to record on a log sheet the time of each drug instilla- latanoprost, bimatoprost, travoprost, and timolol. tion and any omissions or errors in treatment. The night be- Between 9 PM and 4 AM the night before visit 2, patients in- fore visit 3, fluorescein was administered as before. stilled 1 drop of 2% fluorescein at 5-minute intervals until 6 to At visit 3 (day 5±1), only patients whose morning IOP was 10 drops were instilled in each eye. reduced by at least 3 mm Hg from baseline in at least one eye, At visit 2, central corneal thickness and anterior chamber and did not exceed 30 mm Hg, continued in the study. If the depth were measured by slitlamp pachymetry. From these mea- IOP criteria were not met, this visit served as an exit visit and surements, the anterior chamber volume was calculated for each further investigations were not performed. The morning dose eye.11 Four pairs of duplicate fluorophotometric scans of the of unoprostone or placebo was administered to the appropriate cornea and anterior chamber were collected at 45-minute in- eye by the investigator in the clinic, and all measurements were tervals between 8 AM and 11 AM, with the use of a scanning fluo- repeated as at visit 2.
Load more

Recommended publications
  • Blood-Aqueous Barrier Changes After the Use of Prostaglandin Analogues in Patients with Pseudophakia and Aphakia a 6-Month Randomized Trial
    CLINICAL SCIENCES Blood-Aqueous Barrier Changes After the Use of Prostaglandin Analogues in Patients With Pseudophakia and Aphakia A 6-Month Randomized Trial Enyr S. Arcieri, MD; Alessandro Santana, MD; Fabiano N. Rocha, MD; Gustavo L. Guapo, MD; Vital P. Costa, MD Objectives: To investigate the effects of prostaglandin throughout follow-up (P Ͻ .02). Four latanoprost- analogues on the blood-aqueous barrier and to evaluate treated eyes, 1 bimatoprost-treated eye, and 1 travoprost- the occurrence of cystoid macular edema in aphakic or treated eye developed cystoid macular edema; all cases pseudophakic patients with glaucoma. resolved after discontinuation of the prostaglandin ana- logue and treatment with topical diclofenac sodium. Mean Methods: In this randomized, masked-observer, 6-month intraocular pressure reductions after 6 months were higher clinical trial, patients with primary open-angle, pseudo- for the latanoprost (26%), bimatoprost (28%), and tra- phakic, or aphakic glaucoma were treated once daily with voprost (29%) groups than for the control (3%) and uno- bimatoprost (n=16), latanoprost (n=15), or travoprost prostone (14%) groups (PϽ.05). Bimatoprost induced (n=17) or twice daily with unoprostone (n=16) or lu- significantly higher hyperemia scores than latanoprost, bricant drops (control group) (n=16). Blood-aqueous bar- unoprostone, and placebo (PϽ.01). rier status, which was assessed using a laser flare meter; intraocular pressure; the occurrence of angiographic cys- toid macular edema; and conjunctival hyperemia were Conclusion: Bimatoprost, latanoprost, and travoprost use evaluated. may lead to disruption of the blood-aqueous barrier in patients with pseudophakia and aphakia. Results: Mean flare values were significantly higher in the bimatoprost, latanoprost, and travoprost groups Arch Ophthalmol.
    [Show full text]
  • New York State Medicaid Drug Utilization Board Meeting Agenda
    New York State Medicaid Drug Utilization Board Meeting Agenda The Drug Utilization (DUR) Board will meet April 24, 2014, from 9:00 a.m. to 4:30 p.m., Meeting Room 6, Concourse, Empire State Plaza, Albany, New York Agenda Items Preferred Drug Program (PDP) The DUR Board will review therapeutic classes, described and listed below, as they pertain to the PDP. The therapeutic classes to be reviewed contain new relevant clinical and/or financial information. Therapeutic classes not included on this agenda may be reviewed at a later date. The Board will review new clinical and financial information as required, to recommend preferred and non-preferred drugs. ^ The Board will only consider clinical information which is new since the previous review of the therapeutic class and then consider financial information. New clinical information may include a new drug or drug product information, new indications, new safety information or new published clinical trials (comparative evidence is preferred, or placebo controlled when no head-to-head trials are available). Information in abstract form alone, posters, or unpublished data are poor quality evidence for the purpose of re-review and submission is discouraged. Those wishing to submit new clinical information must do so in an electronic format by April 9, 2014 or the Board may not have ample time to review the information. ^ The current preferred and non-preferred status of drugs subject to the Preferred Drug List (PDL) may be viewed at https://newyork.fhsc.com/downloads/providers/NYRx_PDP_PDL.pdf
    [Show full text]
  • Effect of Latanoprost Or 8-Iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes
    LABORATORY SCIENCES Effect of Latanoprost or 8-iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes Rong-Fang Wang, MD; Steven M. Podos, MD; Janet B. Serle, MD; Thomas W. Mittag, PhD; F. Ventosa, MD; Bernard Becker, MD Objective: To evaluate the possible additivity of the ef- duction of IOP of 4.0 ± 0.6 mm Hg was produced when fects of latanoprost and 8-iso prostaglandin E2 (8-iso PGE2) 8-iso PGE2 was added to latanoprost and of 3.0 ± 0.7 on intraocular pressure (IOP) in monkey eyes with laser- mm Hg was produced when latanoprost was added to 8-iso induced glaucoma. PGE2 on day 13 before the morning dosing. Combina- tion therapy with both agents caused maximum IOP re- Methods: The IOP was measured hourly for 6 hours be- ductions from baseline of 11.3 ± 3.0 mm Hg (33%) (P,.05) ginning at 9:30 AM on day 1 (baseline day), days 6 and 7 (latanoprost with 8-iso PGE2 added) and of 9.8 ± 1.3 , (single-agent therapy), and days 13 and 14 (combination mm Hg (31%) (P .01) (8-iso PGE2 with latanoprost added) therapy with both agents). Following 1 day of baseline mea- on day 14. surement, 4 monkeys with unilateral glaucoma received monotherapy twice daily with either 1 drop of 0.005% la- Conclusion: Latanoprost and 8-iso PGE2 have an addi- tanoprost, or 0.1% 8-iso PGE2, 25 µL, at 9:30 AM and 3:30 tive effect on IOP in glaucomatous monkey eyes.
    [Show full text]
  • Unoprostone Isopropyl (Rescula) Reference Number: HIM.PA.11 Effective Date: 09.04.18 Last Review Date: 11.19 Revision Log Line of Business: HIM
    Clinical Policy: Unoprostone Isopropyl (Rescula) Reference Number: HIM.PA.11 Effective Date: 09.04.18 Last Review Date: 11.19 Revision Log Line of Business: HIM See Important Reminder at the end of this policy for important regulatory and legal information. Description Unoprostone isopropyl ophthalmic solution, 0.15% (Rescula®) is a synthetic analog (docosanoid) of prostaglandin F2-alpha. FDA Approved Indication(s) Rescula is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Rescula is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Ocular Hypertension or Open-Angle Glaucoma (must meet all): 1. Diagnosis of open-angle glaucoma or ocular hypertension; 2. Failure of prostaglandin analogues (e.g., latanoprost, travoprost, bimatoprost) in combination with beta blockers (e.g., timolol), unless contraindicated or clinically significant adverse effects are experienced; 3. Age ≥ 18 years; 4. Dose does not exceed 1 bottle per 35 days. Approval duration: 12 months B. Other diagnoses/indications 1. Refer to the off-label use policy for the relevant line of business if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized): HIM.PHAR.21 for health insurance marketplace. II. Continued Therapy A. Ocular Hypertension or Open-Angle Glaucoma (must meet all): 1. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; 2.
    [Show full text]
  • Appendix III
    Appendix III NME LASA Names Azacitidine Cimetidine, famotidine, ranitidine, azathioprine, azulfidine, 1 (generic) capecitabine, zalcitabine Vidaza™ Videx, Vitrase, Viadur (brand) Cilostazol Sulfisoxazole, colestipol, clozaril, cozaar, inositol, aldactazide, 2 (generic) voriconazole Pletal™ Plendil (brand) Duloxetine Fluoxetine, atomoxetine, paroxetine, Dulcolax 3 (generic) Cymbalta™ Symbyax (brand) Erlotinib Gefitinib, imatinib 4 (generic) Tarceva™ Pexeva (brand) Eszopiclone Testolactone, buspirone, risperidone, ropinirole 5 (generic) Lunesta™ Menest, Cenestin, Lutera, Congestac, Nestabs (brand) Iloprost Bimatoprost, latanoprost, travoprost 6 (generic) Ventavis™ Ventolin inh., Ventuss Syrup, Tavist Syrup (brand) Orlistat Orlenta, Uristat 7 (generic) Xenical™ Xiral, Xeloda (brand) Pegaptanib Paganone, paraplatin, imatinib, gefitinib, Protonix 8 (generic) Macugen™ Adagen, magnesium sulfate, glucagen, mustargen, salagen (brand) Pemetrexed A-methapred, Penetrex, trimetrexate, ceftriaxone, Cetapred, Emetrol, 9 (generic) Medipred, Merrem, methotrexate Alimta™ Alinia, Elimite, Aceta, Adalimunab, Alfenta, Esclim (brand) Pramlintide Prandin 10 (generic) Symlin™ Insulin (brand) 11 Rifaximin Rifampin, rifapentine, rifabutin, Rifater Xifaxan™ Xanax, Biaxin Sibutramine Imipramine, topiramate 12 (generic) Meridia™ Mexitil, meperidine (brand) Telithromycin Erythromycin, clarithromycin, azithromycin, dirithromycin 13 (generic) Ketek™ Keflex, Keftab, K-pek, Kaopek (brand) Acamprosate Bacampicillin, acarbose, camptosar 14 (generic) Campral™ Camptosar, Keppra,
    [Show full text]
  • Adverse Periocular Reactions to Five Types of Prostaglandin Analogs
    Eye (2012) 26, 1465–1472 & 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12 www.nature.com/eye 1 1 1 1 Adverse periocular K Inoue , M Shiokawa , R Higa , M Sugahara , CLINICAL STUDY T Soga1, M Wakakura1 and G Tomita2 reactions to five types of prostaglandin analogs Abstract Purpose We investigated the appearance explained to patients before PG frequency of eyelid pigmentation and administration. eyelash bristles after the use of five types of Eye (2012) 26, 1465–1472; doi:10.1038/eye.2012.195; prostaglandin (PG) analogs. published online 5 October 2012 Methods This study included 250 eyes from 250 patients diagnosed with primary open- Keywords: prostaglandin analogs; adverse angle glaucoma or ocular hypertension who reactions; eyelid pigmentation; eyelash bristles; were treated with either latanoprost, patient’s subjective evaluation; physician’s travoprost, tafluprost, bimatoprost, or subjective evaluation isopropyl unoprostone for 43 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by Introduction three ophthalmologists who were masked to treatment type. The existence of eyelid Prostaglandin (PG) analogs are the primary pigmentation and eyelash bristles was treatment for glaucoma because of their judged, and images of the left and right eyes powerful intraocular pressure (IOP) decreasing were compared. Subjective symptoms effect, few systematic adverse reactions, and regarding the existence of eyelid convenience of once a day administration (other pigmentation and eyelash bristles were than isopropyl unoprostone (unoprostone)).1 Five types of PG analogs (latanoprost, investigated through a questionnaire. 1Inouye Eye Hospital, Tokyo, Results There was no significant difference travoprost, tafluprost, bimatoprost, and Japan between the five types of medications with unoprostone) are currently available in Japan.
    [Show full text]
  • Unoprostone As Adjunctive Therapy to Timolol: a Double Masked
    592 CLINICAL SCIENCE Br J Ophthalmol: first published as 10.1136/bjo.87.5.592 on 1 May 2003. Downloaded from Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide A Hommer, for The Unoprostone Adjunctive Therapy Study Group,* B Kapik, N Shams ............................................................................................................................. Br J Ophthalmol 2003;87:592–598 *Members listed at the end Aims: To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunc- of paper. tive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension. Methods: This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained See end of article for after 2 weeks of timolol monotherapy. authors’ affiliations Results: Each drug was safe and well tolerated. Burning/stinging was the most common treatment ....................... emergent adverse event. No clinically relevant changes from baseline were observed for any ophthal- Correspondence to: mic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant Naveed Shams, MD, PhD, (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (−2.7 mm Hg, uno- Novartis Ophthalmics Inc, prostone; −2.8 mm Hg, brimonidine; −3.1 mm Hg, dorzolamide).
    [Show full text]
  • Additive Effect of Unoprostone and Latanoprost in Patients with Elevated Intraocular Pressure
    75 CLINICAL SCIENCE Br J Ophthalmol: first published as 10.1136/bjo.86.1.75 on 1 January 2002. Downloaded from Additive effect of unoprostone and latanoprost in patients with elevated intraocular pressure Tin Aung, Paul T K Chew, Francis T S Oen, Yiong-Huak Chan, Lennard H Thean, Leonard Yip, Boon-Ang Lim, Steve K L Seah ............................................................................................................................. Br J Ophthalmol 2002;86:75–79 Aims: To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) Methods: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measure- ments was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used. Results: 28 patients completed both treatment periods and had IOP data available for evaluation. See end of article for After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg authors’ affiliations (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg ......................
    [Show full text]
  • Effects of Topical Antiglaucoma Medications on Corneal Epithelium As Evaluated by Gene Expression Patterns Yuka Okada, MD, Phd
    JOBNAME: corn 26#Suppl. 1 2007 PAGE: 1 OUTPUT: Thursday July 26 14:59:59 2007 tsp/corn/146793/ICO200709 ARTICLE Effects of Topical Antiglaucoma Medications on Corneal Epithelium as Evaluated by Gene Expression Patterns Yuka Okada, MD, PhD Key Words: cyclooxygenase-2, antiglaucoma medication, corneal Purpose: To examine the expression pattern of the stress-related epithelium, transcription factor genes c-fos and c-jun, which encode the 2 major components of activator protein (AP)-1, and cyclooxygenase (COX)-2 in rat corneal (Cornea 2007;26(Suppl. 1):S46–S54) epithelium treated with topical antiglaucoma medications and benzalkonium chloride (BAK) preservative. Methods: Eighty-eight male Wistar rats were used. We instilled antiglaucoma eye drops (0.5% Timoptol, 0.005% Xalatan, or 0.12% opical b-blocker (timolol, 0.5% Timoptol) and prosta- Rescula), their chemical constituents (active ingredients), or BAK Tglandin (PG)F2a analogs (latanoprost, Xalatan; isopropyl preservative (0.005%, 0.01%, or 0.02%) in 1 eye of each rat. Fellow unoprostone, Rescula) are widely used in the management of eyes served as controls. The eyes were enucleated after various glaucoma and ocular hypertension. Because antiglaucoma intervals. In situ hybridization and immunohistochemistry were used drugs are used for long time periods, chronic side effects are to detect expression of c-fos, c-jun, and COX-2. a major concern. Among these side effects, ocular surface disorders attributable to the drug itself or to drug preser- Results: Expression of c-fos, c-jun, and COX-2 was minimally vatives are relatively common.1–4 Benzalkonium chloride observed in uninjured rat corneal epithelium.
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Tafluprost ethyl ester Item No. 11612 CAS Registry No.: 209860-89-9 Formal Name: 15,15-difluoro-9α,11α-dihydroxy-16- phenoxy-17,18,19,20-tetranor-prosta- OH 5Z,13E-dien-1-oic acid, ethyl ester Synonym: AFP 175 COOCH2CH3 MF: C24H32F2O5 FW: 438.5 HO O Purity: ≥98% F F UV/Vis.: λmax: 217 nm Supplied as: 10% wt/wt in ethanol Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Tafluprost ethyl ester is supplied as 10% wt/wt in ethanol. To change the solvent, simply evaporate the ethanol under a gentle stream of nitrogen and immediately add the solvent of choice. Solvents such as DMSO and dimethyl formamide purged with an inert gas can be used. The solubility of tafluprost ethyl ester in these solvents is approximately 30 mg/ml. Description Analogs of prostaglandin F2α (PGF2α), which act primarily at the FP receptor, have been approved for 1-4 the treatment of glaucoma. Tafluprost (free acid) (Item No. 10005439) is a PGF2α analog which acts as 5 a potent FP receptor agonist (Ki = 0.4 nM). Tafluprost ethyl ester is a form of tafluprost which may have increased lipid solubility compared to the free acid. In addition, the ethyl ester form may demonstrate improved uptake into tissues and thus lower the effective concentration. References 1. Parrish, R.K., Palmberg, P., and Sheu, W.-P. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: A 12-week, randomized, masked-evaluator multicenter study.
    [Show full text]
  • Effect of Non-Steroidal Anti-Inflammatory Ophthalmic Solution on Intraocular Pressure Reduction by Latanoprost K Kashiwagi, S Tsukahara
    297 CLINICAL SCIENCE Br J Ophthalmol: first published as 10.1136/bjo.87.3.297 on 1 March 2003. Downloaded from Effect of non-steroidal anti-inflammatory ophthalmic solution on intraocular pressure reduction by latanoprost K Kashiwagi, S Tsukahara ............................................................................................................................. Br J Ophthalmol 2003;87:297–301 Aim: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction using normal volunteers. Methods: This study was conducted as a prospective and observer masked clinical trial. 13 normal volunteers were enrolled. After measurement of basal IOP and ophthalmic examination, latanoprost ophthalmic solution was initially administered to both eyes once daily. Four weeks later, an NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate (refer to bromfenac sodium hydrate), was co-administered to one randomly selected eye (NSAID group) twice daily for 2 weeks. The other eye was employed as a control (non-NSAID group). After withdrawal of the NSAID ophthalmic solution, latanoprost ophthalmic solution was continuously administered for another 2 weeks and was then withdrawn. After a 4 week washout, only bromfenac sodium hydrate See end of article for authors’ affiliations ophthalmic solution was administered to the eyes of the NSAID group for 2 weeks. During the study ....................... period, ophthalmic examination, including IOP measurement was performed in an observer masked fashion. Correspondence to: Results: Kenji Kashiwagi, MD, Before initiation of bromfenac sodium hydrate, baseline IOPs of the non-NSAID group and the Department of NSAID group were 15.73 (SD 1.97) mm Hg and 15.86 (2.06) mm Hg, respectively (p=0.88).
    [Show full text]
  • Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction Carol B
    SURVEY OF OPHTHALMOLOGY VOLUME 53 SUPPLEMENT 1 NOVEMBER 2008 Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction Carol B. Toris, PhD,1 B’Ann T. Gabelt, MS,2 and Paul L. Kaufman, MD2 1Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA; and 2Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, USA Abstract. A decade has passed since the first topical prostaglandin analog was prescribed to reduce intraocular pressure (IOP) for the treatment of glaucoma. Now four prostaglandin analogs are available for clinical use around the world and more are in development. The three most efficacious of these drugs are latanoprost, travoprost, and bimatoprost, and their effects on IOP and aqueous humor dynamics are similar. A consistent finding is a substantial increase in uveoscleral outflow and a less consistent finding is an increase in trabecular outflow facility. Aqueous flow appears to be slightly stimulated as well. Prostaglandin receptors and their associated mRNAs have been located in the trabecular meshwork, ciliary muscle, and sclera, providing evidence that endogenous prostaglandins have a functional role in aqueous humor drainage. Earlier evidence found that topical PG analogs release endogenous prostaglandins. One well-studied mechanism for the enhancement of outflow by prostaglandins is the regulation of matrix metalloproteinases and remodeling of extracellular matrix. Other proposed mechanisms include widening of the connective tissue-filled spaces and changes in the shape of cells. All of these mechanisms alter the permeability of tissues of the outflow pathways leading to changes in outflow resistance and/or outflow rates.
    [Show full text]