31.12.13 Role of Bevacizumab (Avastin) in Diabetic Macular Edema

Original Article

 

Role of Bevacizumab in Diabetic

Role of Bevacizumab (Avastin) in Diabetic Macular Edema

Muhammad Awais Ashraf1, Ghulam Abbas1 and Adeel Ahmed Siddiqui2

ABSTRACT

Objective: To evaluate the efficacy of injection Bevacizumab (Intravitreal) in management of diabetic macular edema (DME).

Study Design: Prospective study

Place and Duration of Study: This study was conducted at the completed at Ophthalmology department Nishtar Hospital Multan from March 2019 to March 2020.

Materials and Methods: Study was conducted on 60 eyes of 60 patients presented with diabetic macular edema. Intravitreal bevacizumab injection of 1.25 mg was administered 3.5 mm from the limbus under topical anesthetic drops. Follow up was done at 1st day and at 1 month duration after injection. Macular thickness was measured at every follow ups visit. SPSS version 23 was used for analysis of data. P value ≤ 0.05 was considered as significant.

Results: The mean pre Avastin macular thickness of the patients was 391.43±30.91 µm and after Avastin OCT at one month was 308.66±25.82 µm. Difference was found significant statistically, (p=0.000).

Conclusion: Diabetes leads to macular edema and retinopathy which is a hurdle in macular grid laser in such cases. Intravitreal injection of bevacizumab minimizes the exacerbation of macular edema in diabetic cases.

Key Words: Bevacizumab, Vascular Endothelial Growth Factor (VEGF), Macular thickness, Diabetic macular edema (DME).

Citation of article: Ashraf MA, Abbas G, Siddiqui AA. Role of Bevacizumab (Avastin) in Diabetic Macular Edema. Med Forum 2020;31(12):59-62.

 

 

INTRODUCTION

Angiogenesis either physiological or pathological propagated by vascular endothelial growth factor which is a proangiogenic cytokine1. In condition of hypoxia vascular endothelial growth factor (VEGF) stimulate the endothelial cells which played an important role in pathophysiology of certain opthalmic diseases which may include neurovascular age related degenration, diabetic retinopathy, retinal vein occulusion2,3. This whole procedure results in loss of vision after hemorrhage, edema and retinal detachment after fibro vascular proliferation4.

Anti VGEF therapy brings a revolution in treatment modalities of ocular disease5. First of all Pegaptanib was used and after that bevacizumab, Ranibizumab and Aflibercept were used successfully6.

 

 

1. Department of Ophthalmology, Multan Medical & Dental College (MMDC), Multan.

2. Department of Ophthalmology, Taluka Head Quarter Hospital, Kabirwla.

 

 

Correspondence: Dr. Muhammad Awais Ashraf, Assistant Professor of Ophthalmology, Multan Medical & Dental College, Multan.

Contact No: 03346076030

Email: awaisdr93@yahoo.com

 

 

Received:    July, 2020

Accepted:    August, 2020

Printed:        December, 2020

 

 

 

 

 

 

 

Older therapeutic methods were photo dynamic therapy and neovascularization with laser photocoagulation, although these modalities were non physiologic and destructive in use7. In comparison to these methods, VEGF therapy is more potent and successful to inhibit the level of VEGF.

Now treatment of retinal diseases with anti VEGF is famous worldwide in clinical practice8. Number of injections increasing day by day in united states as in 2001 about 4215 injections were used in 2011 about 2.5 million injections. Similar ratio of increase in injections was noted in United Kingdom and Canada9. After anti VEGF therapy some local complications may occur like intraocular complications, ocular hemorrhage, rhegmatogenous retinal attachment and raised intraocular pressure10.

MATERIALS AND METHODS

This prospective study was conducted at the department of Ophthalmology Nishtar Hospital Multan from March 2019 to March 2020. The hospital's ethics review board approved the all aspects of study. Patients who received anti VEGF therapy during the study period were included in the study. Informed written consents were obtained from patients before the start of procedure. Non probability consecutive sampling technique was used. Sample size was calculated by using an online software Openepi.com. Patients of the presumed or established endopthalmitis were enrolled in the study.

Patients with any degree of intraocular inflammation who required Intravitreal antibiotics were labeled as presumed endopthalmitis. Positive gram stain and culture was used to approve the endopthalmitis. Patients in which endopthalmitis develops secondary to some other etiology or who did not fulfill the criteria of endopthalmitis were excluded from the study. All Intravitreal injections were performed in well designed operating rooms with standard protocols. A 29 gauge needle was used for administration in infra temporal quadrant. It was about 4mm distance from the limbus. Conjuctival anaesthesia was given with 4% lidocaine and 0.5% proparacaine. 5% povidone iodine solution was used to prepare eyelashes and eyelids. Patient's mouth and nose covered with surgical self adhesive drape. Sterile lid speculum was also used. Injections were administered by an ophthalmologist having 5 years experience in this procedure. Every patient was dealt after changing surgical sterile gloves and complete hand sepsis. Use of face masks and cessation of conversation at the time of injection administration was assured. A vitreous fluid of all patients sent to laboratory for microbial culture. Empiric treatment was started. Treatment modified according to the culture results.

SPSS version 23 was used for data analysis. Mean and standard deviation was calculated for categorical data. P value less than or equal to 0.05 was considered as significant.

RESULTS

Sixty patients were included, in this study. Intravitreal Injection of Bevacizumab was given to these sixty patients’ sixty eyes. There were more males than females i.e. n=35 (58.3%) and n=25 (41.7%), respectively. The mean age of the patients was 52.91±3.25 years. The mean duration of diabetes of the patients was 12.61±4.15 years. n=11 (18.3%) eyes insulin dependent patients’ and n=49 (81.7%) eyes were non-insulin dependent patients’. n=39 (65.0%) patients were controlled diabetes on medicine where as n=21 (35.0%) patients were found to be uncontrolled diabetes by medicine. (Table. I).

Table No.1: Baseline Characteristics of the Patients

Variable

Presence

Gender

Male

n=35 (58.3%)

Female

n=25 (41.7%)

Age (years)

52.91±3.25

duration of diabetes (years)

12.61±4.15

Insulin dependent patient

n=11 (18.3%)

Insulin independent patient

n=49 (81.7%)

Controlled diabetes patient

n=39 (65.0%)

Un- controlled diabetes patient

n=21 (35.0%)

The mean pre Avastin macular thickness of the patients was 391.43±30.91 micrometers and post Avastin OCT after one month was 308.66±25.82 micrometers. The difference was statistically significant, (p=0.000). (Figure. I). It was seen that macular thickness after one month of injection was decreased in n=55 (91.7%) cases and increased in n=5 (8.3%) cases. Reduction in macular thickness was found as > 10% in n=46 (76.7%) cases, < 10% in n=9 (15.0%) cases and increased in n=5 (8.3%) cases. (Table. 2).

Table No.2: Reduction in Macular Thickness

Reduction in macular thickness

Presence

Yes > 10%

n=46 (76.7%)

Yes < 10%

n=9 (15.0%)

Increased

n=5 (8.3%)

Figure No.1: Mean Avastin mascular thickness.

DISCUSSION

In patients of vitreous hemorrhage or media opacity it is difficult to perform laser therapy. Patients with neovascular glaucoma or iris neovascularization often present corneal edema or hyphema which is a hurdle in laser treatment11. Despite grid laser therapy in some cases macular thickness continue to increase in size. But in such cases Bevacizumab shows rapid and dramatic results and observed very effective that resolve complete macular edema in couple of days. Better outcomes associated with good diabetic control and compliance towards follow ups12.

The mean age of the patients in our study was 52.91±3.25 years. A similar study was conducted by Mason et al13 on 30 patients having mean age of 47.7 ± 12.5 years; another study was conducted by Avery et al14 and observed mean age of 58 years which much higher than our study. Arevalo JF et al15 reported a close enough observation of 53.2 years mean age in his study. Patients of these studies having diabetic retinopathy show variation in age limits may be due to geographical settings.

In our study mean duration of diabetes was 12.61±4.15 years. In a study by EI Haddad et al16 reported that age of patient and duration of diabetes also associated with retinopathy but by logistic regression model lost the significance of diabetic duration which proves that it is not an independent risk factor. In a study by Ateeq A et al17 reported mean duration of diabetes was 10.15 ± 3.2 years. This study also reveals that prevalence rate of diabetic maculopathy is higher in cases with prolonged duration of diabetes.

In our study 18.3% eyes were insulin dependent and 81.7% eyes were non insulin dependent. In a study by Ateeq A et al17 reported 18.5% were insulin dependent and 81.5% patients were noninsulin dependent. Regarding outcomes of study macular thickness after Bevacizumab a significant decrease in macular thickness (91.7%) was observed. Another similar study was conducted by Haritoglou et al18 on diabetic macular edema treated with Bevacizumab 1.25mg and observed a significant decrease in macular edema (33%). Baseline macular thickness was 498.96±123.99 micrometers and after 1 month of injection thickness was 334.40±121.76 µm.

Another study was conducted by Ozkiriş et al19 and concluded that Intravitreal administered of bevacizumab improves the thickness of macular edema and visual acuity, that why bevacizumab labeled as primary treatment of macular edema in diabetic cases. Joshi et al20 observed in his study that hypertension and previous history of laser treatment are two main contributing predictor of Intravitreal injection of bevacizumab. But improvement in macular thickness reduction is observed.

CONCLUSION

Diabetes leads to macular edema and retinopathy which is a hurdle in macular grid laser in such cases. Intravitreal injection of bevacizumab minimizes the exacerbation of macular edema in diabetic cases.

Author’s Contribution:

Concept & Design of Study:

Muhammad Awais Ashraf

Drafting:

Ghulam Abbas

Data Analysis:

Adeel Ahmed Siddiqui

Revisiting Critically:

Muhammad Awais Ashraf, Ghulam Abbas

Final Approval of version:

Muhammad Awais Ashraf

Conflict of Interest: The study has no conflict of interest to declare by any author.

REFERENCES

1.      Bahrami B, Hong T, Zhu M. Switching therapy from bevacizumab to aflibercept for the management of persistent diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2017; 255, 1133–1140.

2.      Ross EL, Hutton DW, Stein JD. Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema TreatmentAnalysis From the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness TrialJAMA Ophthalmol 2016;134(8):888–896.

3.      Bressler NM, Beaulieu WT, Glassman AR. Persistent Macular Thickening Following Intravitreous Aflibercept, Bevacizumab, or Ranibizumab for Central-Involved Diabetic Macular Edema With Vision ImpairmentA Secondary Analysis of a Randomized Clinical TrialJAMA Ophthalmol 2018;136(3):257–269.

4.      Solomon  SD, Chew  E, Duh  EJ.  Diabetic retinopathy: a position statement by the American Diabetes Association.  Diabetes Care. 2017; 40(3):412-418.

5.      Ferris  FL  III, Maguire  MG, Glassman  AR, Ying  G-s, Martin  DF.  Evaluating effects of switching anti–vascular endothelial growth factor drugs for age-related macular degeneration and diabetic macular edema.  JAMA Ophthalmol 2017; 135(2):145-149.

6.      Gonzalez  VH, Campbell  J, Holekamp  NM.  Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of Protocol I data.  Am J Ophthalmol 2016;172:72-79.

7.      Wells  JA, Glassman  AR, Ayala  AR. Diabetic Retinopathy Clinical Research Network.  Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial.  Ophthalmol 2016;123(6):1351-1359.

8.      Laiginhas R, Silva MI, Rosas V. Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success. Graefes Arch Clin Exp Ophthalmol  2018;256, 83–89.

9.      Brown  DM, Schmidt-Erfurth  U, Do  DV.  Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies.  Ophthalmol 2015;122(10):2044-2052.

10.  Elman MJ, Bressler NM, Qin H. Diabetic Retinopathy Clinical Research Network.  Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmol 2011;118(4):609-614.

11.  Nguyen QD, Tatlipinar S, Shah SM. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol 2006; 142:961–969.

12.  Ferris FL, Patz A. Macular edema: a complication of diabetic retinopathy. Surv Ophthalmol 1984; 28:452–461.

13.  Mason OJ, Yunker JJ, Vail R, McGwin G. Intravitreal bevacizumab (Avastin) Prevention of panretinal Photocoagulation-induced complications in patients with severe proliferative diabetic retinopathy. Retina 2008;28:1319-1324.

14.  Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, et al. Intravitreal bevacizumab in the treatment of proliferative diabetic retinopathy. Ophthalmol 2006;113:
1695-1705.

15.  Arevalo JF, Wu L, Sanchez JG, Maia M, Saravia MJ, Fernandez CF, et al. Intravitrealbevacizumab (Avastin) for proliferative diabetic retinopathy: 6-months follow-up. Eye 2009;23:117-123.

16.  El Haddad OAW, Saad MK. Prevalence and risk factors for diabetic retinopathy among Omani diabetics. Br J Ophthalmol 1998;82:901–906.

17.  Ateeq A, Tahir MA, Cheema A, Dahri A, Tareen S. Intravitreal injection of Bevacizumab in diabetic macular edema. Pak J Med Sci 2014;30(6):1383-1387.  

18.  Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999–1005

19.  Özkiriş, A. Intravitreal bevacizumab (Avastin) for primary treatment of diabetic macular oedemaEye 2009;23; 616–620 (2009).

20.  Joshi L, Bar A, Tomkins-Netzer O, et al. Intravitreal bevacizumab injections for diabetic macular edema - predictors of response: a retrospective study. Clin Ophthalmol 2016;10: 2093-2098.