Blood-aqueous Barrier Changes After the Use of Timolol and Prostaglandin Analogues Fixed Combination in Pseudophakic Patients With POAG

Cystoid Macular Edema Clinical Trial

Official title:

Blood-aqueous Barrier Changes After the Use of Timolol and Prostaglandin Analogues Fixed Combination in Pseudophakic Patients With Primary Open Angle Glaucoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01978015
• Other study ID #: CEP424/2010
• Secondary ID: CAAE031901460001
• Status: Completed
• Phase: Phase 4
• First received: October 25, 2013
• Last updated: October 31, 2013
• Start date: October 2011
• Est. completion date: January 2013

Study information

• Verified date: October 2013
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee-UNICAMP
• Study type: Interventional

Clinical Trial Summary

Glaucoma, a progressive optic disc neuropathy causing visual field reduction, is the second leading cause of world blindness. The treatment of glaucoma is mainly based in reducing intraocular pressure (IOP) with topical medications. Many patients required two or more medications to achieve a target IOP. Combinations of B-blockers and prostaglandin analogs (PGA) are frequently used in clinical practice because their additive effect in lowering IOP levels. The aim of this study was to investigate the effects of fixed combinations of timolol maleate and PGA on the blood-aqueous barrier and evaluate the measurement of foveal thickness in pseudophakic patients with primary open-angle glaucoma (POAG).

Description:

Most studies found a lower incidence of systemic and ocular adverse events with fixed combinations than with the unfixed combinations. Fixed combinations are better tolerated than their respective prostaglandin analogue. However, among the most serious side effects induced by PGA are the breaking down of the blood-aqueous barrier (BAB) and the development of cystoids macular edema (CME). Also, timolol maleate drops increase protein concentration in the human and benzalkonium chloride, eye drops preservative induces anterior chamber inflammation. This randomized, masked-observer, prospective clinical trial was approved by the Ethics Committee of the University of Campinas, and it adhered to the tenets of the Declaration Of Helsinki. Written informed consent was obtained from each patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: January 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• Patients were eligible for participation if they met the following inclusion criteria: age older than 18 years, pseudophakia and diagnosis of primary open angle glaucoma (an untreated IOP levels of more then 21 mmHg, specific changes in the optic disc or specific visual fields changes. Optic disc changes were focal notching, optic disc haemorrhage, retinal nerve fiber layer (RNFL)defects, overpass-blood vessel crossing over an area of neuroretinal rim loss.Visual fields changes were the glaucoma hemifield test outside normal limits or a cluster of three or more non-edge points in a typical location of glaucoma or a corrected pattern standard deviation that occurs in less than 5% of normal visual fields

Exclusion Criteria:

• Exclusion criteria included history of uveitis or CME, substantial ocular irritation at baseline, or a history of intraocular surgery or a laser procedure within 6 months of baseline, the presence of systemic disorders that could be associated with uveitis or CME (ie, diabetes mellitus and rheumatologic diseases), presence of age-related macular degeneration and other macular diseases, pregnancy, breastfeeding, and inadequate contraception (in females), treatment with systemic beta-blocker, history of bronchial asthma, chronic obstructive pulmonary disease , sinus bradycardia, second and third degree atrioventricular block , sinoatrial block and functionally significant visual field loss

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystoid Macular Edema
• Iridocyclitis
• Iritis
• Macular Edema
• Uveitis, Anterior

Intervention

Drug:
• travoprost and timolol maleate fixed combination
travoprost 0.004% and timolol maleate 0,5%, 1 eye drop at 8p.m. for 6 months
• latanoprost and maleate timolol fixed combination
Latanoprost 0.005% and timolol maleate 0,5%, 1 eye drop at 8 p.m for 6 months
• bimatoprost and timolol maleate fixed combination
bimatoprost0.03% and timolol maleate 0,5%, 1 eye drop at 8 p.m for 6 months
• dextran and hypromellose
Dextran 70 and hypromellose, lubricant eye drop at 8 a.m and 8 p.m for 6 months

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas, UNICAMP	Campinas	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Campinas, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of mean flare values from baseline at 6 months	A flare measure of a laser flare meter (FM 500; Kowa Co Ltd, Tokyo, Japan) was used to determine the status of the blood-aqueous barrier at all follow-up visits. According to information provided by the manufacturer, flare readings greater than 26 photon counts per millisecond (p/ms) are indicative of a disruption in the blood-aqueous barrier.	Flare measurements occurred at baseline; after 15 days; and after 1, 2, 3, 4, 5, and 6 months of treatment	Yes
Secondary	Change of mean macular thickness values from baseline at 6 months	Foveal macular thickness wiht Spectral Domain Optical Coherence Tomography (Cirrus Model 4000; Carl Zeiss Meditec, Dublin, California, USA) examination was conducted to investigate the occurrence of cystoid macular edema (CME). If CME was detected, the patient was instructed to discontinue taking the medication and a nonsteroidal anti-inflammatory drug was prescribed.	Macular optical coherence tomography images were taken at baseline, after one month and six months of treatment, or if a patient has reduced visual acuity during follow-up	Yes