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 Table of Contents    
ORIGINAL ARTICLE
Year : 2018  |  Volume : 11  |  Issue : 3  |  Page : 254-258  

Treatment before macular grid in patients of diabetic macular edema


1 Cornea Services, Medanta Hospital, New Delhi, India
2 Department of Community Ophthalmology, Dr. R P Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
3 Retina and Uvea Services, Dr. R P Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
4 Department of Biostatistics, Dr. R P Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication29-Oct-2018

Correspondence Address:
Dr. Meenakshi Wadhwani
Room No 784, 7th Floor, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ojo.OJO_148_2016

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   Abstract 


AIM: The aim of this study is to compare the efficacy of intravitreal bevacizumab and posterior subtenons triamcinolone acetate in the management of diffuse diabetic macular edema (DME) and to evaluate their efficacy as an adjunct to modified grid laser in management of DME.
DESIGN: This was a prospective, randomized clinical trial of 30 patients.
MATERIALS AND METHODS: A total of 30 patients attending the medical ophthalmology clinic at a tertiary care hospital were included in the study. These 30 patients were divided into two groups. Group I (15 eyes) received intravitreal bevacizumab followed by modified grid photocoagulation 2 weeks after injection. Group II (15 eyes) received posterior subtenons triamcinolone followed by modified grid photocoagulation 2 weeks after injection. Each patient in our study was followed up at 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after the initial injection to record the central macular thickness (CMT) and best-corrected visual acuity (BCVA).
RESULTS: Both the combination therapies have efficacy to reduce the CMT (P = 0.001). The percentage fall in CMT was greater in bevacizumab + laser group, and there was a significant difference in the CMT values at the end of the study in the bevacizumab group (P = 0.013). The mean BCVA improved in both the groups and this difference was statistically significant compared to the baseline (P = 0.005). However, there was no statistically significant difference in BCVA between the two groups at the end of the study.
CONCLUSION: Both intravitreal bevacizumab and posterior subtenons triamcinolone given as an adjuvant therapy along with modified grid laser are equally efficacious in the reduction of the CMT; however, the percentage fall in the CMT was greater in bevacizumab + laser group, and there was a significant difference in the fall in CMT at all the visits as compared to a plateau in the fall of CMT in posterior subtenons triamcinolone group.

Keywords: Diabetic macular edema, diabetic retinopathy, intravitreal avastin, macular grid


How to cite this article:
Srilatha P S, Wadhwani M, Vohra R, Gogia V, Garg S, Pandey V. Treatment before macular grid in patients of diabetic macular edema. Oman J Ophthalmol 2018;11:254-8

How to cite this URL:
Srilatha P S, Wadhwani M, Vohra R, Gogia V, Garg S, Pandey V. Treatment before macular grid in patients of diabetic macular edema. Oman J Ophthalmol [serial online] 2018 [cited 2018 Dec 12];11:254-8. Available from: http://www.ojoonline.org/text.asp?2018/11/3/254/244308




   Introduction Top


Diabetic macular edema (DME) is the most important cause of visual impairment in patients with diabetes mellitus. It occurs mainly as a result of disruption of blood retinal barrier which leads to increased accumulation of fluid within intraretinal layers of macula. DME can occur at any stage of diabetic retinopathy and is caused by excessive vascular permeability resulting in the leakage of fluid and plasma.[1]

Nowadays, the current approach is of combining pharmacotherapy with Laser for the management of diffuse DME (DDME), so this prospective randomized clinical trial of 30 patients was done to compare the efficacy of intravitreal bevacizumab and posterior subtenons triamcinolone acetate in management of DDME and to evaluate their efficacy as an adjunct to modified grid laser in management of DME.


   Materials and Methods Top


A total of 30 patients attending the medical ophthalmology clinic at a tertiary care hospital were included in the study. These 30 patients were divided into two groups randomly according to age and gender. Group I (15 eyes) received 0.05 ml of 1.25 mg of intravitreal bevacizumab using a 30G needle on 1 cc syringe followed by modified grid photocoagulation 2 weeks after injection under full aseptic conditions. Group II (15 eyes) received 0.5 ml of 20 mg of posterior subtenons triamcinolone in a superotemporal quadrant with a 26G needle on a 2 cc syringe followed by modified grid photocoagulation 4 weeks after injection under full aseptic conditions.

The criteria for inclusion was patients suffering from mild-to-moderate nonproliferative diabetic retinopathy with cystoid macular edema (CSME) with central macular thickness (CMT) >250 μ and BCVA of 6/18 with no previous history of laser photocoagulation. The criteria for exclusion were patients suffering from any other macular or retinal pathology or known glaucoma patients or previous history of laser or intravitreal injection or increased blood pressure and glycated hemoglobin >10%. Descriptive statistics to determine mean, standard deviation, and frequency distribution was performed using SPSS (version 15). The analysis of data between the groups was done by Mann-Whitney tests/unpaired student t-test and within the group was done using paired student t-test/Wilcoxon signed-rank test. The study was done according to Declaration of Helsinki after taking clearance from Institutional Ethic Committee. In the present study, all patients with DDME meeting the inclusion criteria were divided into two groups randomly. The diagnosis of CSME was based on clinical examination (+90D), fundus fluorescein angiography, and spectral domain ocular coherence tomogram (OCT). Group I patients (n = 15) received single intravitreal bevacizumab injection followed by modified macular grid photocoagulation 2 weeks later. Group II patient (n = 15) received single posterior subtenon triamcinolone (PST) injection followed by modified macular grid photocoagulation 4 weeks later. Follow-up laser was done only if CMT was <350 μm. The efficacy of the two treatment modalities was assessed with the OCT by measuring the reduction in the CMT and improvement in early treatment diabetic retinopathy study (ETDRS) BCVA. OCT version 3 (Carl Zeiss, Dublin, California USA) was done using fast macular scan, six radial scans centered on the fixation point (fovea) were performed through a dilated pupil in a spoke pattern, equally spaced angular (30°) orientation through common central axis. Each scan had a length of 6 mm. The macular thickness map was divided into nine sections and displayed as three concentric circles, central circle, inner ring, and outer ring with diameter of 1 mm, 3 mm, and 6 mm, respectively. The reliability of the scan was ensured by proper centration of fovea, signal strength, properly drawn borders of scans. Their safety regarding the occurrence of uveitis, endophthalmitis, intraocular pressure (IOP) rise and occurrence or progression of cataract and other rare ocular and systemic complications known to occur with the treatments were also assessed. Each patient in our study was followed up at 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after the initial injection.


   Results Top


A total of 30 diabetic patients visiting the retina clinic having CSME were divided into two groups of 15 each, Group I included 14 males and 1 female and in Group II, there were 13 males and 2 females. The mean age of patients in Group I was 51.8 ± 14.27 years and in Group II was 58.06 ± 6.29 years (P = 0.13). All the patients in both the groups underwent baseline visual acuity and CMT examination before administration of their respective treatment and were followed for improvement in BCVA and changes in CMT. Group I (15 eyes) received intravitreal bevacizumab followed by modified grid photocoagulation 2 weeks after injection. Group II (15 eyes) received posterior subtenons triamcinolone followed by modified grid photocoagulation 4 weeks after injection. Each patient in our study was followed up at 1 week, 2 week, 1 month, 2 months, 3 months, and 6 months after the initial injection to record the CMT and BCVA.

Change in best-corrected visual acuity

All patients underwent detailed visual acuity examination on ETDRS chart, In Group I patients, the logMAR BCVA showed a significant increase from 0.86 ± 0.51 at baseline to 0.71 ± 0.61 at the end of study (P = 0.005). Eight patients (53.3%) had stabilized vision and 7 patients (46.7%) showed an increase in the BCVA. None of the patients had deterioration in vision from their preinjection visual acuity. The change in the BCVA was noted at 1 month and beyond in all cases.

Group II patients, the logMAR BCVA showed a significant increase from 0.86 ± 0.53 at baseline to 0.60 ± 0.43 at the end of 6 months (P = 0.005) [Table 1] and [Table 2]. 6 patients (40%) had stabilized vision, and 9 patients (60%) showed an increase in BCVA. None of the patients had a decrease in vision. The change in the BCVA was noted at 1 month and beyond in all cases [Figure 1].
Table 1: Changes in best-corrected visual acuity from preinjection to follow-up between the two groups

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Table 2: Changes in best-corrected visual acuity from preinjection to follow-up within the two groups

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Figure 1: Line diagram showing changes in best-corrected visual acuity preinjection to 6 months

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Change in mean central macular thickness

All the patients underwent measurement of CMT on Zeiss OCT. In Group I, the pretreatment mean CMT was 427.8 ± 125 μm. After intravitreal injection of bevacizumab and modified macular grid at 2 weeks, a mean reduction of 130 μm from baseline was noted at the end of 1 month. Further, progressive reduction in the CMT was noted on consecutive follow-ups. The mean CMT at 2, 3 and 6 months follow-up were 267 ± 55.10 μm, 245 ± 47.42 μm and 225.6 ± 45.8 μm, respectively. Thus, there was a statistically significant decrease in CMT (P = 0.001) at the end of 6 months. The mean percentage fall of CMT reduction at the end of 6 months from the baseline was 43.62 ± 19.36.

In Group II, the pretreatment mean CMT was 469.4 ± 197.7 μm. After posterior subtenons triamcinolone injection and modified macular grid photocoagulation at the end of 4 weeks, a mean reduction of 128 μm from baseline was noted at the end of 1 month. The mean CMT at 2, 3, and 6 months follow-up were 321 ± 98.65, 338 ± 137.20, and 291 ± 88.48 μm, respectively [Figure 2].
Figure 2: Representation of central macular thickness outcomes through line diagram between both the groups

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There was a statistically significant decrease in CMT (P = 0.001) at the end of 6 months. The mean percentage fall of CMT reduction at the end of 6 months from the baseline was 31.94 ± 20.08 [Table 3].
Table 3: Percentage change in central macular thickness from baseline

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Although there was a statistical significance both for BCVA and CMT within the groups, on comparing the treatment efficacy between the two groups, it was statistically significant only for CMT P = 0.013 and not for BCVA (P = 0.806) [Table 1], [Table 2], [Table 3]. IOP rise was seen only in two patients in the PST + laser group at 1st and 2nd week follow-up (maximum 25 mmHg) and was controlled with topical antiglaucoma therapy. None of the patients showed significant development of cataract to hamper in the Ll.


   Discussion Top


In a typical grid treatment, 100–200 mm gray-white spots are placed around the fovea.[2] This conventional photocoagulation protocol is effective for treating DDME; however, it causes visible laser scars that can enlarge postoperatively, leading to decreased vision.[3],[4],[10] Even when carefully performed in conventional technique, it is difficult to minimize the laser power for grid photocoagulation against “edematous” retina. Grid laser photocoagulation is beneficial for reducing vision loss in patients with DDME.[5],[6],[7],[8] Despite its effectiveness, some problems remain because laser photocoagulation irreversibly damages the focal retina, which leads to a decreased visual field.[5],[6] Various hypothesis has been given on the mechanism of grid photocoagulation including opening of new pathways in the retinal pigment epithelium barrier for fluid transportation and/or a decrease in the photoreceptor population, thereby reducing oxygen demand leading to reduced blood flow and resolution of macular edema.

However, with conventional techniques, it is difficult to make enough (gray-color) laser burns under these conditions against ''edematous'' retina before grid treatment. Laser absorption and thermal injury are focused on the retinal pigment epithelium located on the most outer part of the retina, and the laser energy reaches this area via retinal tissue.[8],[9],[10] Therefore, the thicker the retina, the more laser power required for retinal photocoagulation. In addition, some cytokines related to tissue inflammation, such as interleukin-6 and interleukin-8, are induced by laser photocoagulation, which aggravate the existing macular edema.[11]

To reduce intrinsic damage from visible end-point laser photocoagulation, treatment with posterior subtenon triamcinolone acetonide injection and bevacizumab before grid treatment against DDME has been proposed. Triamcinolone acts by increasing the tight junction proteins and local vasoconstriction, as well as it abolishes the induction of vascular endothelial cell growth factor (VEGF) by pro-inflammatory mediators (pigment derived growth factor and platelet activating factor). They can be administered by subtenon, peribulbar or intravitreal route. Intravitreal anti-VEGF inhibitors play an important role by not only decreasing the release of vascular endothelial growth factors but also causing regression of neovascularization.[4],[5] Various studies in the past have evaluated the efficacy of intravitreal bevacizumab and PST independently and both have been found to be effective.[10],[11],[12],[13]

Verma et al.[14] evaluated the adjunctive role of PST in DDME. A total of 31 eyes with DDME were divided into an interventional group subjected to grid laser photocoagulation along with 0.5 mL of 40 mg/mL PST and a noninterventional group subjected to grid laser photocoagulation only. The interventional group showed a statistically significant (P < 0.05) change in both mean BCVA and mean contrast sensitivity, at the end of 24 weeks. A significant rise in IOP was not described in any of the patients in either group. However, CMT evaluation by OCT was not done in their study and also role of intravitreal bevacizumab was not compared.

Shimura et al.[15] also evaluated the efficacy of PST before laser grid photocoagulation in 37 patients suffering from DDME. 42 eyes of these 37 patients, 21 eyes received PST 1 week before grid photocoagulation, and the other eyes served as control. After PST, CMT, and BCVA were improved, and subsequent grid photocoagulation maintained the improvement for up to 24 weeks without recurrence of DDME. In a recent study by Kim et al.[16] to compare the efficacy of intravitreal bevacizumab with PST in patients with DME, found decreased CMT in triamcinolone group as compared to bevacizumab group. Bhayana et al.[17] conducted a similar study to compare the role of PST and intravitreal bevacizumab as an adjunct to modified grid laser in DDME patients, they concluded that improvement in visual acuity was better in bevacizumab group though the reduction in CMT was significantly better than baseline and comparable in both the groups though mean visual acuity was better in bevacizumab group as compared to triamcinolone group.

Current guidelines for the management of DME in some countries have no place for grid photocoagulation and have been completely replaced by intravitreal Anti-VEGFs or intravitreal steroid implants. Their treatment protocol includes monthly injections of ranibizumab or bevacizumab or aflibercept for the management of diabetic macular edema. Recently, Soheilian et al.[18] have documented superiority of intravitreal bevacizumab and triamcinolone over grid photocoagulation alone. This was similar to the study done by Arevalo et al.[19] in PACORES, they evaluated the anatomic and functional (BCVA) response to primary intravitreal bevacizumab in patients with diffuse DME and followed these patients for 24 months and concluded that intravitreal bevacizumab provided stability or improvement in OCT, BCVA, and angiography at the end of 24 months and a mean of 5 injections were required. Similarly Kumar et al.[20] conducted a study on 20 eyes with diffuse diabetic macular edema already treated with laser photocoagulation of some type (focal or grid), all these eyes were injected with intravitreal bevacizumab twice at an interval of six weeks. All these eyes showed significant improvement in visual acuity and decrease in macular edema even after six months. In country like India and other SAARC nations where patients are unable to afford monthly dosing regimen of Anti VEGF, grid photocoagulation is still not out of vogue. Hence, adjunctive intravitreal bevacizumab or PST help in reducing the side effects of photocoagulation apart from their direct effect on macular edema.


   Conclusion Top


Thus from our study, we conclude that both intravitreal bevacizumab and posterior subtenons triamcinolone given as an adjunct therapy along with modified grid laser are equally efficacious in the reduction of the CMT and visual acuity within the two groups; however, it was statistically significant only for CMT and not for BCVA between the groups.

Based on the study, although the percentage fall in the CMT was greater in bevacizumab with laser group, there are many side effects related to intravitreal bevacizumab such as endophthalmitis also its cost makes its usage more precarious than triamcinolone which is more dependable in developing countries with of course, risk of associated side effects such as increase in IOP and cataract. The major limitation of our study is small sample size and shorter duration of follow-up; hence, a study with larger sample size and longer duration of follow-up is required for further deciding on the role of intravitreal bevacizumab and posterior subtenon injection as an adjunct to laser in DDME patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Moss SE, Klein R, Klein BE. The incidence of vision loss in a diabetic population. Ophthalmology 1988;95:1340-8.  Back to cited text no. 1
    
2.
Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Early treatment diabetic retinopathy study research group. Arch Ophthalmol 1995;113:1144-55.  Back to cited text no. 2
    
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Bandello F, Lanzetta P, Menchini U. When and how to do a grid laser for diabetic macular edema. Doc Ophthalmol 1999;97:415-9.  Back to cited text no. 3
    
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Morgan CM, Schatz H. Atrophic creep of the retinal pigment epithelium after focal macular photocoagulation. Ophthalmology 1989;96:96-103.  Back to cited text no. 4
    
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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. 5
    
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Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology 2005;112:806-16.  Back to cited text no. 6
    
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Olk RJ. Argon green (514 nm) versus krypton red (647 nm) modified grid laser photocoagulation for diffuse diabetic macular edema. Ophthalmology 1990;97:1101-12.  Back to cited text no. 7
    
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Striph GG, Hart WM Jr., Olk RJ. Modified grid laser photocoagulation for diabetic macular edema. The effect on the central visual field. Ophthalmology 1988;95:1673-9.  Back to cited text no. 8
    
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Ferrara N. Vascular endothelial growth factor: Basic science and clinical progress. Endocr Rev 2004;25:581-611.  Back to cited text no. 9
    
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Laursen ML, Moeller F, Sander B, Sjoelie AK. Subthreshold micropulse diode laser treatment in diabetic macular oedema. Br J Ophthalmol 2004;88:1173-9.  Back to cited text no. 10
    
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Aroca PR, Salvat M, Fernández J, Méndez I. Risk factors for diffuse and focal macular edema. J Diabetes Complications 2004;18:211-5.  Back to cited text no. 11
    
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Antcliff RJ, Marshall J. The pathogenesis of edema in diabetic maculopathy. Semin Ophthalmol 1999;14:223-32.  Back to cited text no. 12
    
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Sutter FK, Simpson JM, Gillies MC. Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: Three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial. Ophthalmology 2004;111:2044-9.  Back to cited text no. 13
    
14.
Verma LK, Vivek MB, Kumar A, Tewari HK, Venkatesh P. A prospective controlled trial to evaluate the adjunctive role of posterior subtenon triamcinolone in the treatment of diffuse diabetic macular edema. J Ocul Pharmacol Ther 2004;20:277-84.  Back to cited text no. 14
    
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Shimura M, Nakazawa T, Yasuda K, Shiono T, Nishida K. Pretreatment of posterior subtenon injection of triamcinolone acetonide has beneficial effects for grid pattern photocoagulation against diffuse diabetic macular oedema. Br J Ophthalmol 2007;91:449-54.  Back to cited text no. 15
    
16.
Kim HD, Kang KD, Choi KS, Rhee MR, Lee SJ. Combined therapy with intravitreal bevacizumab and posterior subtenon triamcinolone acetonide injection in diabetic macular oedema. Acta Ophthalmol 2014;92:e589-90.  Back to cited text no. 16
    
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Bhayana S, Sood S, Narang S, Sethi NK. Intravitreal bevacizumab versus posterior subtenon triamcinolone in diffuse diabetic macular edema. Int Ophthalmol 2015;35:519-25.  Back to cited text no. 17
    
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Soheilian M, Ramezani A, Obudi A, Bijanzadeh B, Salehipour M, Yaseri M, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology 2009;116:1142-50.  Back to cited text no. 18
    
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Arevalo JF, Sanchez JG, Wu L, Maia M, Alezzandrini AA, Brito M, et al. Primary intravitreal bevacizumab for diffuse diabetic macular edema: The Pan-American collaborative retina study group at 24 months. Ophthalmology 2009;116:1488-97, 1497.e1.  Back to cited text no. 19
    
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Kumar A, Sinha S. Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in an Indian population. Indian J Ophthalmol 2007;55:451-5.  Back to cited text no. 20
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