MRIDULA V AMARNATH

Chinmaya Mission Hospital,Bangalore,Karnataka

*Corresponding author email: [email protected]

ABSTRACT

To analyse the efficacy of topical nepafenac 0.1% eye drops in the treatment of diabetic macular edema(DME). Method: a prospective interventional study  in 14 eyes having centre involving DME were taken into consideration. They were administered topical nepafenac eye drops 0.1% thrice daily for 6 months. Their vision and foveal thickness were recorded systematically at the start of the treatment and then at 2nd ,4th  and 6 th month follow up.Results: The mean baseline and final LogMAR visual acuity were 0.33 and 0.15 respectively and the mean baseline and final foveal thickness were 450 µm and 290 µm respectively. Conclusion: A statistically significant improvement was noticed in the visual acuity and foveal thickness after the administration of 0.1% of topical nepafenac eye drops.

KEYWORDS: centre involving diabetic macular edema, foveal thickness

INTRODUCTION

Diabetic macular edema is one of the common causes of decreased vision in patients having diabetic retinopathy1. Focal laser was the initial modality of treatment for clinically significant macula edema. Early treatment diabetic retinopathy study (ETDRS) showed that focal laser reduced the risk of visual loss by 50%.But however focal laser treatment is associated with various side effects like scotoma, reduced colour vision, vision loss due to the formation of choroidal neovascular membrane, subretinal fibrosis formation, migration of hard exudates into the foveal centre, enlargement of the laser scars towards the foveal centre.

Hence various other treatment modalities were looked into and evaluated which included intravitreal injections of steroids, agents that target vascular endothelial growth factors(VEGF).Intravitreal injection of triamcinolone for DME was effective for a short period and again was associated with adverse effects like development of cataract, increase in the intraocular pressure as was seen in nearly 50% of the patients. Anti VGEF agents were effective in DME2. But it required repeated injections which carried an increased risk of endophthalmitis. And hence a safer alternative modality of treatment became necessary.

It is known that inflammation plays a key role in the pathogenesis of diabetic retinopathy. Cyclo- oxygenase -2(COX-2) is up regulated in the retina in diabetic individuals which in turn leads to increased production of prostaglandins E2(PGE2) which is an important mediator of inflammation. An elevated PGE2 leads to increased VEGF in diabetic retinopathy and also leads to retinal endothelial cell degeneration.

Nepafenac is a non steroidal anti-inflammatory agent. It is a pro-drug and gets converted to Amfenac by intraocular hydrolases, which inhibits both COX1 and 2.

 In a study conducted on a rat model it was shown that topical nepafenac inhibits diabetes induced retinal micro vascular abnormalities .Topical nepafenac reaches its bioactive concentration in the posterior segment.

METHOD

A prospective interventional case study was done on patients who came to the ophthalmology OPD and was confirmed to have a centre involving DME. A written consent was taken from the patients prior to the procedure. The patients were administered topical nepafenac eye drops 0.1% three times a day.

INCLUSION CRITERIA

1. Diabetic retinopathy patients with centre involving DME, as demonstrated by optical coherence tomography (OCT) .

2. Patients who are not willing for anti VGEF or triamcinolone intravitreal injections.

3 . Patients who were willing for a follow up of 6 months.

EXCLUSION CRITERIA

  1. Any patient who was subjected to intravitreal steroid or anti VGEF injection within 6 months period.
  2. Patients who had undergone focal/grid laser treatment in the previous 6 months.

3.  Vision loss not solely attributed to diabetic retinopathy.

The patients’ vision was assessed with the help of Snellen’ s chart and the anterior segment was evaluated by a slit lamp bio microscope and the posterior segment was assessed by a slit lamp bio microscope with 90D lens and indirect ophthalmoscope. OCT was done for all the selected patients and the central macular thickness was evaluated.

The patients were followed up on the 2nd,4th and 6 th month and during each follow up their visual acuity and CMT were recorded. Snellen’s chart was converted into LogMAR for analysis. Wilcoxon signed rank test for visual acuity analysis and paired T test for CMT were used. The software used was STATA 13.

RESULTS.

In our study 14 eyes were taken into consideration. Figure 1 shows the sex distribution of the patients that had 10 male and 4 female patients having an average age distribution of 56 years as seen in figure 2. The mean duration of diabetes among the patients were 7.4 years(figure 3).Nine eyes were phakic and five were pseudophakic who had undergone cataract surgery atleast 1 year ago. Eleven eyes had moderate non proliferative diabetic retinopathy, one eye had severe non proliferative diabetic retinopathy and two eyes had stable proliferative diabetic retinopathy post panretinal photocoagulation(figure 4). Eight eyes had previously received focal laser treatment and two eyes had received intravitreal triamcinolone injection 8 months before the study.

The baseline mean LogMAR visual acuity was 0.34 and was 0.25 at 2 nd month, 0.22 at 4 th month and 0.18 at 6 th month follow up. There was a statistically significant improvement between the baseline and the final visual outcome. (p= 0.025)(Table 1)

The mean baseline CMT was 465.78 µ and it decreased to 353.18µ at the 2 nd month follow up and to 303.07 µ at the 4 th month and to 290 µ at the 6 th month. There was statistically significant improvement in the CMT from the baseline to the final follow up visit(p=0.0014)(Table 1 )

Figure 1 shows the sex distribution of patients.

Figure 2 shows the age distribution of patients.

Figure 3 shows the mean duration of diabetes

Figure 4 shows the diabetic status of the patients

Table 1 showing a comparative study between the initial and final visual acuity(VA) and central macular thickness(CMT)

Baseline VABaseline CMTFinal VAFinal CMT
6/123806/6303
6/64936/6240
6/66356/6321
6/64206/6236
6/64836/6412
6/122896/6297
6/183156/18276
6/125536/12593
6/123406/9312
6/64046/9236
6/244566/12187
6/604786/18254
6/365676/12189
6/365786/12197

DISCUSSIONS

It is seen that the in diabetic retinopathy there is an increase in the production of prostaglandins. Inhibition of PG production helps to prevent diabetic retinal micro vascular abnormalities3. In a study done by Baudoin et al,he said that aspirin which is an anti-inflammatory agent tends to inhibit the mean yearly increase in the number of microaneurysms but it was contrary to the ETDRS study which revealed that aspirin did not have any beneficial effect on diabetic retinopathy. Another study showed that Celecoxib which is a COX- 2 inhibitor only helps to decrease the fluorescein leakage and has no drastic effect on the visual outcome in DME4.

Nepafenac inhibits both COX1  and COX 25 and has an overall effect on the prostaglandin production, which plays a key role in the pathogenesis of diabetic retinopathy. Since there is most of the time a drop in the vision in patients with DME and the necessity to undergo repeated anti VGEF injections for the treatment of DME, topical nepafenac was considered as a therapeutic measurement. In our study the use of topical nepafenac showed a positive result in the visual outcome. The study showed that 7 eyes had an improvement in the vision, 6 eyes maintained the same visison and 1 eye had a drop despite having a reduction in the CMT. 11 eyes had a decrease in the CMT and 3 eyes had an increase in the CMT during the final follow up. It was noted that none of the patients had any side effects due to topical nepafenac.

LIMITATION

Our study had a limitation as the sample size was small and the systemic control status of the patients was not adequate. Considering the beneficial effect of topical nepafenac in the treatment of centre DME, a larger study group could also be taken and assessed.

CONCLUSION.

Topical nepafenac is a safe and a cost effective option in the treatment of DME. It can be used as a therapeutic optic in cases of DME with good vision and in patients who have multiple systemic co-morbidities such as uncontrolled hypertension, diabetes, recent myocardial infarction, stroke. It is also helpful in conditions where the usage of antiVGEF needs to be contraindicated or used with extra caution.

BIBLIOGRAPHY

1. Bhagat N,Grigorian RA. Diabetic macular edema: pathogenesis and treatment. Surv ophthalmol. 2009 ;(54): 1-32

2. Salam A, Da Costa J. Antivascular endothelial growth factor agents for diabetic maculopthy. Br J Ophthalmol. 2010;( 94):821-826

3. Sennlaub F,Valamnsesh F.Cyclooxygenase- 2 in human and ischemic proliferative retinopathy. Ophthalmology .2003;(10): 198-204

4. DuY ,Sarthy T. Interaction between NO and Cyclooxygenase pathways in retinal cells. Am J Physiol.2004;(67 ):23-39

5.Chew KT,Kim J.Preliminary assessment of Celecoxib in diabetic macular edema. 2010;( 30): 456-457