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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 57  |  Issue : 2  |  Page : 109-112

Topical nepafenac in the treatment of center involving diabetic macular edema


Department of Retina-Vitreous, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Madurai, Tamil Nadu, India

Date of Web Publication10-Sep-2019

Correspondence Address:
Dr. T P Vignesh
Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, No. 1, Anna Nagar, Madurai - 625 020, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjosr.tjosr_12_19

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  Abstract 


Purpose: To assess the efficacy of topical nepafenac 0.1% in the treatment of center-involving diabetic macular edema (DME). Design: A prospective, interventional case series. Methods: Fourteen eyes of thirteen patients with center-involving DME were included in the study, and they were administered topical nepafenac eye drops 0.1% thrice daily, for 6 months. Vision and foveal thickness were recorded at the baseline and 2nd, 4th, and 6th month follow-up visits. Results: The mean baseline and final LogMAR visual acuity were 0.35 and 0.18, respectively, and the mean baseline and final foveal thickness were 463.4 μm and 291.8 μm, respectively, both showing a statistically significant improvement (P < 0.05). Conclusion: Topical nepafenac is effective in the treatment of center-involving DME in this small case series; however, a large randomized study is warranted.

Keywords: Center-involving diabetic macular edema, foveal thickness, nepafenac, prostaglandins


How to cite this article:
Vignesh T P. Topical nepafenac in the treatment of center involving diabetic macular edema. TNOA J Ophthalmic Sci Res 2019;57:109-12

How to cite this URL:
Vignesh T P. Topical nepafenac in the treatment of center involving diabetic macular edema. TNOA J Ophthalmic Sci Res [serial online] 2019 [cited 2019 Nov 19];57:109-12. Available from: http://www.tnoajosr.com/text.asp?2019/57/2/109/266379




  Introduction Top


Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetic retinopathy.[1] Focal laser photocoagulation was thes first treatment introduced, in the treatment of clinically significant macular edema and Early Treatment Diabetic Retinopathy Study (ETDRS) had demonstrated that focal laser treatment reduced the risk of moderate visual loss by 50%.[2] However, focal laser did not improve the vision and also did not prevent visual loss in the majority of patients.[3] Focal laser treatment is associated with adverse effects, which include scotoma, reduced color vision, and vision loss due to the development of choroidal neovascular membrane, subretinal fibrosis, and migration of hard exudates into the foveal center, and laser scars may enlarge into the foveal center.[4] Therefore, other treatment modalities have been evaluated, and they include intravitreal injections of steroids, agents targeting vascular endothelial growth factor (VEGF). Intravitreal injection of triamcinolone for DME was effective only in the short term and also associated with significant adverse effects which include development of cataract and rise in intraocular pressure in approximately about 50% of treated patients.[5] Anti-VEGF agents are effective in the treatment of DME; however, repeated injections are necessary, which carries an increased risk of endophthalmitis.[6] Therefore, a safer alternative treatment modality is necessary in the management of DME.

Inflammation is known to play a role in the pathogenesis of diabetic retinopathy. Cyclooxygenase-2 (COX2) is upregulated in the retina of diabetic animals and humans,[7] which leads to increased production of prostaglandins E2 (PGE2)[8] which is an important mediator of inflammation. Increased PGE2 leads to upregulation of VEGF in diabetic retinopathy and also leads to retinal endothelial cell degeneration in diabetes.[9] Nepafenac is a nonsteroidal anti-inflammatory agent, a prodrug and is converted into amfenac by intraocular hydrolases, which inhibits both COX1 and 2. Topical nepafenac reaches bioactive concentration in the posterior segment.[10],[11],[12] Topical nepafenac has been shown to inhibit diabetes-induced retinal microvascular abnormalities in a rat model.[13] Till date, there is a single small case series which showed a beneficial effect of topical nepafenac in the treatment of DME.[14] We wanted to evaluate the efficacy and safety of topical nepafenac on DME.


  Methods Top


A prospective interventional case series which was conducted on patients with center-involving DME attending the retina services of a tertiary eye care hospital. Patient's with center-involving DME were administered topical nepafenac eye drops 0.1% (Nepaflam, Ajanta Pharma, India) thrice daily, after obtaining informed written consent. The study was done in adherence to the tenets of Declaration of Helsinki.

Inclusion criteria

  1. Diabetic retinopathy patients with center-involving DME, demonstrated by optical coherence tomography (OCT) and who are not willing for anti-VEGF or triamcinolone intravitreal injections
  2. At least 6-month follow-up.


Exclusion criteria

  1. Any patient who was given intravitreal steroid or anti-VEGF injection or focal/grid laser treatment in the study eye within the previous 6 months
  2. Any patient who had undergone cataract surgery in the study eye in the past 1 year
  3. Vision loss not solely attributed to diabetic retinopathy.


Patients underwent visual acuity evaluation by Snellen's chart and thorough anterior segment evaluation by slit lamp and posterior segment evaluation by slit lamp biomicroscopy with 90D lens and indirect ophthalmoscopy. All the patients underwent OCT (Stratus OCT 3, Zeiss Meditec, USA) and central macular thickness (CMT) was measured.

Patients were followed up at 2nd, 4th, and 6th months, and at each visit, visual acuity and CMT were recorded. Improvement in vision and change in CMT were the primary and secondary outcome measures. Snellen's visual acuity was converted into LogMAR for analysis. Wilcoxon signed-rank test for visual acuity analysis and paired t-test for CMT analysis were used. The software used was STATA 13 (Texas, USA).


  Results Top


Fourteen eyes of thirteen patients were included in the study. [Table 1] shows the details of demographics of all the patients, with pretreatment and posttreatment visual acuity as well as CMT. Eleven patients were male and two were female. The mean age of the patients was 56.1 years. The mean duration of diabetes mellitus was 7.5 years. Nine eyes were phakic and five were pseudophakic, who had undergone cataract surgery at least 1 year back. Eleven eyes had moderate nonproliferative diabetic retinopathy, one eye had severe nonproliferative diabetic retinopathy, and two eyes had stable proliferative diabetic retinopathy postpanretinal photocoagulation. Eight eyes had previously received focal laser treatment for DME and two eyes had received intravitreal triamcinolone injection, 6 months before enrollment in the study. Five eyes had been treated with focal laser twice, two eyes once, and one eye had been treated with focal laser, 4 times.
Table 1: Demographics and results

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The baseline mean LogMAR visual acuity was 0.35 and was 0.26 at 2nd month, 0.23 at 4th month, and 0.18 at 6th month follow-up. There was a statistically significant improvement between baseline and final visual acuity (P = 0.025).

The mean baseline CMT was 463.43 μ and it decreased to 356.21 μ at the 2nd month follow-up and to 304.07 μ at the 4th month and to 291.86 μ at the 6th month follow-up. There was a statistically significant improvement in CMT from the baseline to the final follow-up (P = 0.0014). [Figure 1]a, [Figure 1]b, [Figure 2]a, [Figure 2]b, [Figure 3]a and [Figure 3]b show a decrease in CMT between baseline and at the final follow-up of 6 months, in three study patients.
Figure 1: (a and b) Right eye of subject No. 1 with a pretreatment vision of 6/36 improving to 6/12 at 6 months. Central macular thickness at baseline was 647 μ which reduced to 199 μ at 6 months

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Figure 2: (a and b) Left eye of subject No. 1 with a pretreatment vision of 6/36 improving to 6/12 at 6 months. Central macular thickness at baseline was 622 μ which reduced to 199 μ at 6 months

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Figure 3: (a and b) Right eye of subject No. 4 with a pretreatment vision of 6/6, decreased to 6/9 at 6 months. Central macular thickness at baseline was 407 μ which reduced to 240 μ at 6 months

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There was no statistically significant difference in CMT, between the treatment-naïve and previously treated groups at the final follow-up of 6 months (P = 0.8).


  Discussion Top


Prostaglandin (PG) production is upregulated in diabetic retinopathy and inhibition of PG production may prevent the development of diabetic retinal microvascular abnormalities.[13] Various anti-inflammatory therapies had been tried before in diabetic retinopathy; aspirin treatment was found to inhibit the mean yearly increase in the number of microaneurysms in a trial by Baudoin et al.[15] whereas ETDRS[16] revealed aspirin did not have any beneficial effect on any aspect of retinopathy. Celecoxib which is COX2 inhibitor was found to only decrease the fluorescein leakage and had no effect in visual improvement in DME.[17]

Nepafenac inhibits both COX1 and 2 and thereby inhibits the production of PGs, which plays an important role in the pathogenesis of diabetic retinopathy and topical nepafenac had inhibited the development of diabetes-induced retinal microvascular abnormalities in an animal model.[13] Considering the fact that failure of vision improvement in majority of patients with DME and the need for repeated intravitreal anti-VEGF injections in the treatment of DME, we opted for topical nepafenac a s a therapeutic measure in center-involving DME. Our study revealed a positive effect of topical nepafenac in the treatment of center-involving DME, and the results are comparable to the previous small case series.[14] In our study, seven eyes had improvement in vision, six eyes maintained vision, and one eye had a drop in vision despite having reduction in CMT. Eleven eyes had decrease in CMT, while three eyes had increase in the CMT at the final follow-up. None of the patients had any side effects due to topical nepafenac.

Our study has some limitations such as a small sample size and incomplete data on the systemic control status of the patients. However, considering the beneficial effect of topical nepafenac in the treatment of center-involving DME in our study, a larger randomized study is warranted.


  Conclusion Top


Topical nepafenac is safe as well as cost-effective in the treatment of DME as shown in our study and can be used as an therapeutic option in cases of DME with good vision as well as in patients with multiple systemic comorbidities such as uncontrolled hypertension, recent myocardial infarction, or stroke, where anti-VEGFs have to be used with caution or contraindicated.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: Pathogenesis and treatment. Surv Ophthalmol 2009;54:1-32.  Back to cited text no. 1
    
2.
Photocoagulation for diabetic macular edema: Early treatment diabetic retinopathy study report no 4. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin 1987;27:265-72.  Back to cited text no. 2
    
3.
Early Treatment Diabetic Retinopathy Study Group. Photocoagulation forDME: Early treatment diabetic retinopathy study report number 1. Arch Ophthalmol 1985;103:1796-806.  Back to cited text no. 3
    
4.
Schatz H, Madeira D, McDonald HR, Johnson RN. Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. Arch Ophthalmol 1991;109:1549-51.  Back to cited text no. 4
    
5.
Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 2008;115:1447-9, 1449.e1-10.  Back to cited text no. 5
    
6.
Salam A, DaCosta J, Sivaprasad S. Anti-vascular endothelial growth factor agents for diabetic maculopathy. Br J Ophthalmol 2010;94:821-6.  Back to cited text no. 6
    
7.
Sennlaub F, Valamanesh F, Vazquez-Tello A, El-Asrar AM, Checchin D, Brault S, et al. Cyclooxygenase-2 in human and experimental ischemic proliferative retinopathy. Circulation 2003;108:198-204.  Back to cited text no. 7
    
8.
Ayalasomayajula SP, Kompella UB. Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 2003;458:283-9.  Back to cited text no. 8
    
9.
Du Y, Sarthy VP, Kern TS. Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am J Physiol Regul Integr Comp Physiol 2004;287:R735-41.  Back to cited text no. 9
    
10.
Kapin MA, Yanni JM, Brady MT, McDonough TJ, Flanagan JG, Rawji MH, et al. Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation 2003;27:281-91.  Back to cited text no. 10
    
11.
Ke TL, Graff G, Spellman JM, Yanni JM. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II.In vitro bioactivation and permeation of external ocular barriers. Inflammation 2000;24:371-84.  Back to cited text no. 11
    
12.
Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation 2000;24:357-70.  Back to cited text no. 12
    
13.
Kern TS, Miller CM, Du Y, Zheng L, Mohr S, Ball SL, et al. Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. Diabetes 2007;56:373-9.  Back to cited text no. 13
    
14.
Callanan D, Williams P. Topical nepafenac in the treatment of diabetic macular edema. Clin Ophthalmol 2008;2:689-92.  Back to cited text no. 14
    
15.
Baudoin C, Passa P, Sharp P, Kohner E. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy: A multicenter randomized controlled clinical trial. Diabetes 1989;38:491-8.  Back to cited text no. 15
    
16.
Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:757-65.  Back to cited text no. 16
    
17.
Chew EY, Kim J, Coleman HR, Aiello LP, Fish G, Ip M, et al. Preliminary assessment of celecoxib and microdiode pulse laser treatment of diabetic macular edema. Retina 2010;30:459-67.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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