Evaluation of Contrast Sensitivity after Four Different Treatment Modalities Using OPTEC-Functional Vision Analyzer in Primary Open-Angle Glaucoma.

PURPOSE: The purpose of the study is to evaluate the changes in contrast sensitivity (CS) after using the four different types of antiglaucoma eye drops in patients with primary open-angle glaucoma (POAG) by OPTEC-functional vision analyzer (FVA).
METHODS: In this prospective study, eighty patients (80 eyes) with POAG were randomly divided into four groups. The groups were randomly received timolol maleate 0.5%, travoprost 0.004%, dorzolamide 2%, and brimonidine tartrate 0.2%. The medications were used in the eye that was randomly selected. The CS was assessed before and 15 min after the intervention by the FVA. The paired t-test was used to compare the difference between before and after the intervention. P < 0.05 was considered statistically significant.
RESULTS: Fifteen minutes after the instillation of timolol maleate (Group A), the CS in three out of twenty patients at the spatial frequencies of 1.5, and 3 cycles per degree (cpd) was significantly decreased (P = 0.015). However, using travoprost (Group B) and dorzolamide (Group C), the CS in one out of twenty patients at low spatial frequencies (1.5 and 3 cpd) was decreased in the two groups, which was not statistically significant for these medications (P > 0.05). In Group D, after applying brimonidine tartrate, the CS in two out of twenty patients at the spatial frequency of 18 cpd was significantly decreased (P = 0.042).
CONCLUSION: Our study showed that CS values at low and high spatial frequencies after applying timolol and brimonidine eye drops are temporarily reduced in patients with POAG.

RCT Entities:   Population Interventions Outcomes

Introduction

Glaucoma is a worldwide epidemiological challenge affecting approximately 4% of the global population.[1234567] Research shows that by 2010, an estimated 60.5 million people globally will be living with either angle-closure glaucoma or primary open-angle glaucoma (POAG).[8]

Elevated intraocular pressure (IOP) is the most important modifiable risk factor for glaucoma and hence lowering of IOP is the goal of glaucoma therapy.[910] Pharmacotherapy remains the chief management modality for the patients of glaucoma and ocular hypertension.[9]

Topical antiglaucoma medications act either by decreasing aqueous production beta-adrenergic antagonists, carbonic anhydrase inhibitors [CA-I]), increasing aqueous outflow (prostaglandin derivatives, cholinergic agonists) or both (alpha-2 adrenergic agonists).[9] Treatment is started with monotherapy, but in cases where monotherapy fails to attain the target IOP, other drugs are added.[910] Factors that influence the choice of an agent are efficacy, safety profile, ease of administration, and cost.[1112] Dorzolamide is a powerful inhibitor of CA-II that penetrates the sclera and cornea to reach the ciliary process.[1213] CA-II inhibition slows the production of local bicarbonate, reduces the transport of sodium and fluid, and consequently reduces the aqueous humor production and IOP.[14]

Timolol is a nonselective beta-blocker that is eliminated by both hepatic metabolism and renal excretion, and it has little or no local anesthetic, membrane stabilizing, or sympathomimetic properties.[1315] Timolol reduces IOP by inhibiting aqueous humor production.[151617] It has been found that timolol downregulates adenylate cyclase by inhibiting β2-adrenoceptor sites in the ciliary process.[18] Topical beta-blockers and CA inhibitors, such as dorzolamide and latanoprost usually in combination with beta-blockers and brimonidine, may have various side effects on visual acuity. Since their action mechanism is different, they have an additive effect when administered together.[19]

Alpha-adrenergic agonists such as brimonidine decrease the production of aqueous humor, increase aqueous humor outflow, and lower the IOP somewhat. It has a purite preservative (purite is a stabilized oxychloro complex acting as an oxidative preservative that is converted into natural tear components when exposed to light) that breaks down into natural tear components and may be better tolerated in people who have allergic reactions to preservatives in other eye drops.[121319]

Contrast sensitivity (CS) is a parameter used to assess visual performance at different levels of contrast, which usually alters before any severe change in visual acuity.[20] There are various studies correlating the ability of individuals to fulfill complex tasks, such as driving performance, computer task accuracy, or even accomplish everyday activities with their CS function.[2122] Decreasing the quality of life has also been shown in relation to the deterioration of visual performance, including CS.[23] This prospective study was conducted to investigate changes in the CS related to reduction of IOP after starting the treatment of glaucoma with four different formulations of antiglaucoma eye drops.

Methods

In this prospective, randomized clinical trial, a total of eighty volunteers (80 eyes) with POAG were randomly assigned for the four different types of antiglaucoma eye drops. All volunteers were recruited from glaucoma patients who were admitted to the private hospital (Bahman Hospital, Tehran, Iran) for ocular examination. The recruitment period started between March 2017 and August 2017. This study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Iran University of Medical Sciences, Tehran, Iran. All patients included in the study were informed about the purpose of the study, and informed consent was obtained from all the participants.

In the study, the patients with POAG had IOP >21 mmHg, typical glaucomatous optic neuropathy (GON) with or without visual field defects, gonioscopy (Goldmann three-mirror lens) disclosing a 360° normal-appearing open-angle, and no apparent ocular or systemic abnormalities that might account for the increased IOP. The exclusion criteria included best-corrected visual acuity of <20/20, any sign of secondary glaucoma, significant media opacities, and a history of using oral or topical steroids.

Visual field standard automated perimetry findings (Humphrey Swedish Interactive Threshold Algorithm Standard 24-2, Carl Zeiss Meditec, Dublin, CA, USA) were considered suggestive of glaucoma when either defect of three or more points in cluster with a probability of <5% in a nonedge localization at the pattern deviation plot were observed, or a pattern standard deviation index with a probability of <5% was found or a normal outside limit result was obtained in the glaucoma Hemifield test.

A closed-system CS testing device, the OPTEC-functional vision analyzer (FVA; Stereo Optical Co., Inc., Chicago, IL, USA) was used to examine CS values under daytime without glare. The FVA has rotating slide packages for other visual functions, including visual acuity, disability glare, and stereo and color vision. The CS testing device contains the Functional Acuity Contrast Test chart, which uses three orientations for the gratings: Oriented vertically or tilted 15° to the right or left. Participants identified the orientation of each grating and were required to guess when they could not determine the orientation of gratings. The CS testing device controls light levels with sensors to achieve consistent conditions for each test. This device supplies at a target luminance level of 85 candela per square meter (cd/m2) for the condition of daytime in compliance with the American National Standards Institute. It evaluates spatial frequencies using sine-wave grating charts of 1.5, 3, 6, 12, and 18 cycles per degree (cpd).

The volunteers with glaucoma were randomly divided into four groups. Each group comprised 20 patients. The mean age in the Groups of A, B, C, and D was 45.34 ± 9.26 years, 44.61 ± 10.05 years, 44.51 ± 9.47 years, and 44.96 ± 9.86 years, respectively. The CS was recorded at baseline examination before the intervention. Then, for each group, a different type of antiglaucoma drops was randomly assigned. Antiglaucoma eye drops were instilled in the eye that was randomly selected. In the group of A from timolol maleate 0.5%, in the group of B from travoprost 0.004%, in the group of C from dorzolamide 2%, and in the group of D from brimonidine tartrate 0.2% eye drops was randomly used. Then, 15 min after the instillation of the medications, the CS test was repeated. The CS measurements were performed by a single operator that was blind to the allocation of treatment for patients in the groups. Allocation was based on computer-generated random numbers and was concealed by using sequentially numbered opaque sealed envelopes. All the patients had done the CS test for the first time during our study, and each test lasted approximately 10 min. All the CS values were converted to logarithmic values.

The data were analyzed using paired-samples t- test to assess the CS changes between prior to and 15 min after the intervention. Statistical analysis was performed using SPSS software (Windows version 19.0; SPSS, Inc., Chicago, IL, USA), and statistical significance was defined as P < 0.05.

Results

The age range of patients in the Groups of A, B, C and D was 40–58 years, 39–60 years, 40–63 years, and 40–59 years, respectively. As presented in Table 1, there was no significant difference in sex (P = 0.133) or age (P = 0.296) among the four groups.

Table 1

Clinical features in the four groups of primary open-angle glaucoma patients after intervention

Variables	Group A (n=20)	Group B (n=20)	Group C (n=20)	Group D (n=20)
Age, mean±SD	45.34±9.26	44.61±10.05	44.51±9.47	44.96±9.86
Male/female	11/9	7/13	8/12	9/11
Contrast sensitivity (cpd)
1.5	*	*	*
3	*	*	*
6
12
18				*

*The altered spatial frequency. Group A: Timolol maleate 0.5%, Group B: Travoprost 0.004%, Group C: Dorzolamide 2%, Group D: Brimonidine tartrate 0.2%, cpd: Cycles per degree, SD: Standard deviation, n: The number of patients

In Group A, the CS was decreased by 0.2 log units in 3 out of 20 patients 15 min after applying timolol maleate 0.5% at the spatial frequencies of 1.5 and 3 cpd, in which this change was statistically significant (P = 0.015) [Tables 1 and 2].

Table 2

Results of contrast sensitivity after using antiglaucoma eye drops in patients with primary open-angle glaucoma

Groups	Patients with CS impairments/total number of patients	P
A	3/20	0.015
B	1/20	0.61
C	1/20	0.72
D	2/20	0.042

Group A: Timolol maleate 0.5%, Group B: Travoprost 0.004%, Group C: Dorzolamide 2%, Group D: Brimonidine tartrate 0.2%, CS: Contrast sensitivity, P value: The significant level of paired t-test within A, B, C, or D groups between baseline and 15 min after intervention

In Groups B and C, only one patient showed a decrease in the CS by 0.2 log units 15 min after the intervention at the spatial frequencies of 1.5 and 3 cpd, which was not statistically significant (P > 0.05).

In Group D, 15 min after the instillation of brimonidine tartrate 0.2%, the CS in 2 out of 20 patients with POAG at the spatial frequency of 18 cpd decreased by 0.2 log units, which was statistically significant (P = 0.042).

Discussion

In this study, the changes of CS between before and after the use of the four different antiglaucoma eye drops in patients with POAG were studied. Various studies have been conducted on the effect of the antiglaucoma medications on CS after a period of 4 weeks or many months, but in this study, the evaluation of CS using OPTEC-FVA was performed 15 min after the instillation of the four different types of antiglaucoma eye drops. The CS function has been used to evaluate the quality of vision in several conditions, including various forms of retinopathy, cataract surgery/IOL implantation, and glaucoma.[242526]

Most studies have focused on the long term effects of the antiglaucoma eye drops on visual function.[272829] Their results are controversial, although there are great numbers of reports outlining an improvement in CS four or more weeks after the drug administration, especially at intermediate spatial frequencies (6 and 12 cpd).[28] This improvement can be attributed to a recovery of the damaged ganglion cells and their microenvironment due to the lowering of the IOP and an increase in the ocular perfusion and hemodynamics.[30]

In the study performed by Hiraoka et al.[31] found that there is a substantial reduction in the CS function for at least 5 min after the instillation of timolol gel-forming solution and brinzolamide, and this temporary decrease was fully restored 15 min after the instillation of drugs. But in our study, the reduction of CS was detected 15 min after the intervention.

In the study performed by Chatzibalis et al.[32] found that the value of CS is reduced 20 min after the instillation of diclofenac sodium, dorzolamide/timolol, and brimonidine. West et al.[33] showed that the CS level of = 1.40 log units and = 1.30 log units after the use of diclofenac sodium is associated with disability in reading and recognition of faces in people older than 65 years. In the present study, the value of CS at low spatial frequencies (1.5 and 3 cpd) after applying timolol maleate 0.5%, travoprost 0.004%, and dorzolamide 2% decreased that this the reduction of CS, 15 min after the instillation of the antiglaucoma eye drops was 0.20 log units. Furthermore, the reduction of CS at the levels of 1.5 and 3 cpd after applying timolol was statistically significant.

In contrast, Evans et al.[30] was evaluated the CS of 16 patients with POAG using brimonidine and timolol. In their study reported an improvement at the spatial frequencies of 6 and 12 cpd with using brimonidine but found no significant changes in the group tested with timolol. In our study, 15 min after the instillation of brimonidine, the CS at high spatial frequency (18 cpd) decreased by 0.20 log units, which was statistically significant. The differences in baseline measurements, and the follow-up time between the previous study and the present study, may be responsible for the various outcomes in the two studies. In our study, 15 min after using travoprost and dorzolamide, there was no significant difference in the CS changes compared to patients who used the two other antiglaucoma drops.

Conclusion

Our study showed that the CS of POAG patients at high- and low-spatial frequencies (1.5, 3, and 18 cpd) may be temporarily changed 15 min after the use of timolol and brimonidine. Therefore, before starting treatment with these the two types of antiglaucoma medications, it should be sufficiently explained to patients. Since, according to our experience, it is mandatory to customize medical therapy for any patient with glaucoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.