|Year : 2020 | Volume
| Issue : 2 | Page : 574-580
Topical bromfenac vs focal laser photocoagulation in treatment of focal diabetic macular edema
Abd El Khalek Ebrahim Al Saadany1, Sameh M Elgouhary1, Marwa A Zaky1, Eman A Hossam Eldin2
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Menouf Ophthalmology Hospital, El-Gaish Street, Menouf City, Menoufia, Egypt
|Date of Submission||26-Jul-2019|
|Date of Decision||09-Sep-2019|
|Date of Acceptance||14-Sep-2019|
|Date of Web Publication||27-Jun-2020|
Eman A Hossam Eldin
Menouf Ophthalmology Hospital, El-Gaish Street, Menouf City, Menoufia
Source of Support: None, Conflict of Interest: None
The aim was to evaluate the safety and efficacy of topical bromfenac in comparison with focal laser photocoagulation in treatment of focal diabetic macular edema (DME).
DME, a serious eye condition caused primarily by hyperglycemia, is the major cause of visual loss in the working population of developed countries.
Patients and methods
A total of 30 eyes from 30 diabetic patients with previously untreated focal DME were enrolled in this prospective randomized controlled study from October 2017 to October 2018. Patients with central macular thickness (CMT) less than 350 μm were included. Patients were divided into two equal groups, each of 15 eyes. Group 1 patients received focal laser as needed and group 2 patients received topical bromfenac eye drops twice daily for 6 months. Best-corrected visual acuity and CMT were measured initially and at 1, 3, and 6 months of follow-up.
After 6 months, best-corrected visual acuity was stabilized as baseline in 60 and 53.3% of group 1 and group 2 patients, respectively. After 6 months, the mean baseline CMT was significantly reduced from 290.5 ± 10.1 to 266.4 ± 8.6 μm in group 1 (P < 0.001) and from 286.9 ± 10.59 to 265 ± 14.14 μm in group 2 (P < 0.001).
Topical bromfenac showed good results close to that of focal laser on stabilization of vision and reduction of CMT in patients of focal DME with favorable safety and tolerability. Topical bromfenac twice daily for 6 months may play an effective role in treatment of early focal DME.
Keywords: central macular thickness, diabetic retinopathy, focal laser, macular edema, topical bromfenac
|How to cite this article:|
Al Saadany AE, Elgouhary SM, Zaky MA, Eldin EA. Topical bromfenac vs focal laser photocoagulation in treatment of focal diabetic macular edema. Menoufia Med J 2020;33:574-80
|How to cite this URL:|
Al Saadany AE, Elgouhary SM, Zaky MA, Eldin EA. Topical bromfenac vs focal laser photocoagulation in treatment of focal diabetic macular edema. Menoufia Med J [serial online] 2020 [cited 2020 Jul 15];33:574-80. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/574/287761
| Introduction|| |
The global incidence of diabetes has continued to rise significantly over the recent decades and the number of diabetic patients is estimated to increase from 382 million in 2013 to 592 million by 2035. Diabetic macular edema (DME) is the major cause of vision loss associated with diabetic retinopathy. The prevalence of DME is 6.81% (range: 6.74–6.89) in people with diabetes worldwide, accounting for 12% of new cases of blindness annually.
Sustained hyperglycemia, subsequent damage to the microvasculature, and breakdown of the blood-retina barrier are thought to be the key processes in the development of DME.
According to the Early Treatment Diabetic Retinopathy Study reports number 1 and 2 (1985, 1987), focal/grid laser was established as a standard of care for DME. According to the results of this study, focal/grid laser therapy reduced the risk of moderate vision loss by 50% among patients with DME at 3 years of follow-up,.
Bromfenac (bromfenac sodium hydrate 0.9 mg/ml eye drops) is a potent NSAID that provides targeted inhibition of the cyclooxygenase-2 enzyme, thought to be the primary mediator of ocular inflammation. The lipophilicity of bromfenac provides enhanced penetration through the cornea and ocular tissues, rapidly producing physiologically active drug levels to reduce ocular inflammation.
The aim of this study was to evaluate the safety and efficacy of topical bromfenac in comparison with the standard treatment (focal laser photocoagulation) in treatment of newly diagnosed focal DME.
| Patients and Methods|| |
From October 2017 to October 2018, 30 eyes from 30 diabetic patients with newly diagnosed focal DME were prospectively enrolled in our study. Patients were randomly assigned into two equal groups by simple randomization technique (odd and even numbers): group 1 included 15 eyes that received focal laser photocoagulation as needed and group 2 included 15 eyes that received topical bromfenac eye drops twice daily for 6 months. Patients were followed up for 6 months.
Diabetic patients with previously untreated focal DME in whom the central macular thickness (CMT) was less than 350 μm by optical coherence tomography (OCT) were included in this study.
We excluded patients with any of the following: CMT more than 350 μm; diffuse DME with multifocal leakage; any media opacity that precludes OCT examination; previous cataract surgery to exclude Irvine–Gass syndrome, glaucoma, and high myopia; and patients who received any previous treatment for DME.
Approval for this study was obtained from the Local University Ethical Committee. Patients included in the study received information about the nature of the study and possible benefits and complications of the treatment and signed an informed consent form.
All included patients underwent best-corrected visual acuity (BCVA) assessments using logarithm of the minimum angle of resolution (logMAR) units, anterior segment examinations using slit lamps, intraocular pressure evaluation using a Goldmann applanation tonometer, and posterior segment examinations using slit lamp biomicroscopy with +90 and +78 D Volk lenses. Fundus fluorescein angiograph and optic coherence tomography (OCT Heidelberg Engineering, Germany) were implemented for all patients before treatment. Follow-up by ophthalmic examination and OCT was employed after 1, 3, and 6 months of treatment.
All eyes in group 1 had undergone focal laser photocoagulation with argon laser (Zeiss-Humphrey Systems, Carl Zeiss, Germany). Focal laser was preceded by pupillary dilation and instillation of topical anesthesia. The laser treatment involved focal treatment to all leaking microaneurysms that were located between 500 and 3000 μm from the center of the macula. The settings used for focal laser were as follows: spot diameter 50 μ, exposure time 0.1 s, and power 50–150 mW. The settings were adjusted as required to create whitening within the wall of the microvascular lesion.
In group 2, all eyes had received topical bromfenac eye drops twice daily. Patients were instructed to put topical bromfenac eye drops BID in the affected eye only and to continue on the eye drops for 6 months.
The primary outcomes of this study were changes in BCVA and CMT reduction, which were measured initially and at 1, 3, and 6 months of follow-up.
Secondary outcome was the need for retreatment in either group. Retreatment with rescue laser was performed in cases that developed new leakage or if the CMT exceeded 300 μm at any point during follow-up.
The collected data were tabulated and statistically analyzed using SPSS software (statistical package for the social sciences, version 19; SPSS Inc., Chicago, Illinois, USA). Discrete variables were presented as numbers (counts) and percentage. Continuous variables were presented as mean and SD. Paired sample t-test was used to compare means from the same group at different times, whereas independent samples t-test was used to compare means for the two groups. Findings with P value less than 0.05 were considered significant.
| Results|| |
In group 1, the mean age was 55.6 ± 8.47 years (range: 41–68 years), there were 10 (66.7%) men and five (33.3%) women, and the mean duration of diabetes mellitus was 9.6 ± 2.19 years (range: 6–14 years). In group 2, the mean age was 57.1 ± 6.06 years (range: 40–65 years), there were six (40%) men and nine (60%) women, and the mean duration of diabetes mellitus was 9.7 ± 1.7 years (range: 7–13 years) [Table 1].
There was no significant difference regarding age, sex, and duration of diabetes between the two groups.
Regarding best-corrected visual acuity
For group 1, the mean BCVA was 0.280 ± 0.0414, 0.287 ± 0.0352, 0.287 ± 0.0743, and 0.273 ± 0.0799 logMAR at baseline, 1, 3, and 6 months, respectively. For group 2, the mean BCVA was 0.280 ± 0.0414, 0.280 ± 0.0561, 0.267 ± 0.0488, and 0.247 ± 0.064 logMAR at baseline, 1, 3, and 6 months, respectively. In both groups, there was no statistically significant difference between the mean baseline BCVA and the mean BCVA at 1, 3, and 6 months of follow-up, where for group 1, P = 0.33, 0.71, and 0.75, respectively, and for group 2, P = 1.0, 0.16, and 0.055, respectively [Table 2].
|Table 2: Comparison between studied groups regarding the best-corrected visual acuity|
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There was no significant difference between the two groups regarding the mean BCVA at baseline, 1, 3, or 6 months of follow-up (P = 1.00, 0.09, 0.90, and 0.86, respectively).
After 6 months, in group 1, BCVA was improved in 26.7% of patients, stabilized in 60%, and deteriorated in 13.3% in comparison with baseline. However, in group 2, 40% showed improved BCVA, 53.3% had the same BCVA, and 6.7% had deteriorated BCVA in comparison with baseline.
Regarding central macular thickness
For group 1, the mean CMT was 290.5 ± 10.1 μm (range: 276–315), 286.2 ± 7.32 μm (range: 272–296), 278.5 ± 14.2 μm (range: 264–312), and 266.4 ± 8.6 μm (range: 256–284) at baseline, 1, 3, and 6 months, respectively [Figure 1].
|Figure 1: A 52-year-old female patient with right eye focal DME. The patient was treated with a single session of focal laser. (a) Baseline OCT image.; (b) OCT image, 6 months after laser. DME, diabetic macular edema; OCT, optical coherence tomography.|
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For group 2, the mean CMT was 286.9 ± 10.59 μm (range: 265–304), 280.9 ± 9.87 μm (range: 262–294), 276.2 ± 11.72 μm (range: 257–292), and 265 ± 14.14 μm (range: 246–294) at baseline, 1, 3, and 6 months, respectively [Figure 2].
|Figure 2: A 58-year-old female patient with right eye focal DME. The patient was treated with topical bromfenac eye drops twice daily for 6 months. (a) Baseline OCT image; (b) OCT image, 6 months after topical bromfenac administration. DME, diabetic macular edema; OCT, optical coherence tomography.|
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In comparison with baseline CMT, for group 1, there was no significant CMT reduction after 1 month (P = 0.065), but there was significant CMT reduction after 3 and 6 months (P = 0.016 and <0.001, respectively). For group 2, there was a statistically significant CMT reduction after 1 month (P = 0.022), after 3 months (P = 0.003), and after 6 months (P < 0.001). There was no significant difference between the two groups regarding the mean CMT at baseline, 1, 3, or 6 months of follow-up (P = 0.87, 0.25, 0.75, and 0.16, respectively) [Table 3].
|Table 3: Comparison between studied groups regarding the central macular thickness|
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In group 1, 3 months after focal laser therapy, two (13.3%) patients developed new leakage and had increased CMT greater than 300 μm. So, a second laser session was performed.
In the first patient, the CMT was 282 and 296 μm at baseline and 1 month after laser, respectively. At the third month of follow-up, the CMT was increased to 312 μm, and a second laser session was performed. At the sixth month of follow-up, the CMT was reduced to 284 μm.
In the second patient, the CMT was 280 and 291 μm at baseline and 1 month after laser, respectively. At the third month of follow-up, the CMT was increased to 307 μm, and a second laser session was performed. At the sixth month of follow-up, the CMT was reduced to 281 μm.
In group 2, there was no need for rescue laser as the CMT did not exceed 300 μm in any patient during follow-up.
| Discussion|| |
DME is the major cause of visual loss in the working population of developed countries. The pathogenesis of DME has not been fully elucidated, as it is caused by complex pathological process with many contributing factors.
Multiple clinical data have confirmed that early detection and treatment of DME is an effective strategy to prevent vision loss. Current treatment options for DME include focal/grid laser photocoagulation, intravitreal anti- Vascular Endothelial Growth Factor agents (anti-VEGF) agents, intravitreal steroids, combination therapy with laser photocoagulation, topical NSAIDs drugs, and vitrectomy,.
Because elevated inflammatory markers have been found in patients with diabetic retinopathy, it is likely that inflammation aids in the progression of vascular disease in these patients. For this reason, NSAIDs may be effective against DME.
Clinical evidence suggested that bromfenac is effective in a range of ocular conditions with favorable safety and tolerability. Twice daily topical bromfenac has demonstrated efficacy in reducing postoperative pain and inflammation following cataract surgery in multiple clinical trials,.
We studied the effect of topical bromfenac in comparison with focal laser photocoagulation on stabilization of vision and reduction of CMT, in patients with newly diagnosed focal DME.
In group 1 of our study, treated with focal laser, there was no statistically significant difference between the mean baseline BCVA and the mean BCVA at 1, 3, and 6 months of follow-up. This is consistent with the results of Farhad et al. and Dinesh et al., who reported that there was no significant difference between the mean pretreatment and post-treatment BCVA after laser photocoagulation. On the contrary, our results were different from that of Mohammad et al. who reported a statistically significant decrease in visual acuity (VA), 3 months following laser.
Furthermore, regarding the visual outcome in patients of group 1, the BCVA was stabilized at the pre-laser level in 60%, improved in 26.7%, and deteriorated in 13.3% in comparison with baseline BCVA. These findings were consistent with the results of the Early Treatment Diabetic Retinopathy Study report number 1, where focal macular laser treatment was demonstrated to reduce the risk of moderate visual loss in eyes with clinically significant DME from 28 to 11% at 36 months of follow-up. Our results were close to that of the study by Keshav et al., where VA was stabilized at the pre-laser level in 55.75% and improved in 27.2%. In the study by Mohammad et al., the VA remained stable in 55.88% and improved in 8.8%. Dinesh et al. reported visual stabilization in 57.2% and VA improvement in 42.8% with no visual deterioration following laser photocoagulation. Many studies reported a percentage of visual improvement following focal laser for focal DME between 8.3 and 25% after 2–3 years of follow-up,,.
In group 2 of our study, treated with topical bromfenac, there was no significant difference between the mean BCVA pretreatment and 1 month after treatment. These results were consistent with the work of Antonio et al. where the mean BCVA was 0.49 ± 0.22 and 0.5 ± 0.18 logMAR at baseline and after 30 days of topical bromfenac administration, respectively, with no significant difference.
Moreover, in topical bromfenac group, there was no statistically significant visual improvement after 3 and 6 months of treatment. To our knowledge, no previously reported studies had addressed the long-term use of topical bromfenac in the treatment of DME.
Regarding CMT reduction in group 1 patients, there was no statistically significant CMT reduction 1 month after laser but there was significant CMT reduction after 3 and 6 months following laser therapy in comparison with baseline. These results were similar to that of Diabetic Retinopathy Clinical Research Network, where a significant reduction of CMT from baseline to 2 years was noted in the laser treatment group. Our results were also close to that of Farhad et al. where the mean CMT was significantly reduced from 354.8 to 349.8 μm, 4 months after laser treatment. Kareem et al. reported significant CMT reduction in focal laser group where the mean baseline CMT was reduced from 375.92 ± 65.69 to 314.44 ± 85.938 μm, 3 months after laser.
In group 2, there was significant CMT reduction 1 month following topical bromfenac, where the mean CMT was reduced from 286.9 ± 10.59 μm before treatment to 280.9 ± 9.87 μm, 1 month after treatment. Our results agreed with that of Antonio et al. who stated that topical bromfenac significantly reduced the mean CMT from 465.41 ± 118.47 μm at baseline to 388.88 ± 152.63 μm after 30 days of treatment.
Moreover, in group 2 of our study, there was a significant CMT reduction after 3 and 6 months of topical bromfenac administration, in comparison with baseline.
In this study, CMT reduction was not associated with improvement in BCVA. Although a modest correlation between CMT and VA in patients with DME has been found in some studies, more recent research suggested that other mechanisms may influence visual function, and the relationship between CMT and VA is complex and not yet fully understood.
Our study showed that topical bromfenac was well tolerated, with no corneal complications (as corneal edema or epitheliopathy) during full treatment period. These findings match the experience with bromfenac in other studies, which have demonstrated a generally favorable tolerability profile.
Limitations of this study
First, small number of patients and relatively short period of follow-up are a limitation. Second, bromfenac treatment was continued for whole 6 months of follow-up, whereas focal laser was performed once at the start of treatment then rescue laser was performed as needed, and this might carry some bias toward bromfenac treatment.
| Conclusion|| |
Topical bromfenac showed good results close to that of focal laser photocoagulation on stabilization of vision and reduction of CMT in patients with focal DME, with favorable safety and tolerability. Topical bromfenac twice daily for 6 months may provide an effective and tolerable treatment option for newly diagnosed focal DME. More studies are needed on a large scale of patients for better evaluation of the safety and efficacy of topical bromfenac as a single treatment for focal DME for long period.
The study was performed in Menoufia University Hospital. This article has been read and approved by all authors. This work was self-funded by the authors.
This study was approved by the clinical research committee of the Menoufia University Hospital and it followed the tenets of the Declaration of Helsinki.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]