CENTRAL MACULAR THICKNESS REDUCTION AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB COMPARED TO INTRAVITREAL KETOROLAC IN NAIVE DIABETIC MACULAR EDEMA
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Introduction: Diabetic macular edema (DME) is a debilitating complication of the diabetic eye. Vascular Endothelial Growth Factor (VEGF) was found to be responsible for this disease entity, and anti-VEGF remains the main treatment of DME. Inflammatory processes occur in diabetic eye, with some researchers postulates the role of them in the making of DME. This study’s objective is to search for anti-VEGF alternative using Non-Steroid Anti-Inflammatory Drugs (NSAID), ketorolac tromethamine.
Methods: We conducted a double blind, randomized clinical trial in DME patients using intravitreal injection of bevacizumab and ketorolac. Central macular thickness (CMT) was assessed pre-treatment and one-month post-treatment. Best Corrected Visual Acuity (BCVA) and Intraocular Pressure (IOP) were also assessed. Wilcoxon tests were performed to evaluate changes in CMT, visual acuity, and IOP.
Result: We enrolled 50 treatment-naïve DME patients from March 2020 to March 2021. Twenty-five patients were allocated for each group. There is a statistically significant difference in CMT at one-month follow-up between the two groups (p:0.001) and a markedly reduced CMT between the groups (p:0.001), with the reduction higher in bevacizumab group. BCVA changes significantly in bevacizumab group (p:0.01), but there is no statistically significant difference between the two groups (p:0.07). There’s a marked difference of IOP in 1 hour after injection in both groups, with higher transient IOP elevation in ketorolac group (p:0.02), but there is no marked difference in one-month follow-up (p:>0.05). The perceived pain right after intravitreal injection is not different between bevacizumab and ketorolac group.
Conclusion: Intravitreal injection of ketorolac found to be inferior compared to bevacizumab in reducing CMT of DME. Meanwhile, there’s no differences in visual acuity, intraocular pressure (one-month follow-up) and pain after injection between two groups.
Diabetic Macular Edema, Ketorolac, NSAID, Bevacizumab, CMT
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2. Semeraro F, Morescalchi F, Cancarini A, Russo A, Rezzola S, Costagliola C. Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications. Diabetes Metab. 2019;45(6):517–27. DOI: 10.1016/j.diabet.2019.04.002
3. Imazeki M, Noma H, Yasuda K, Motohashi R, Goto H, Shimura M. Anti-VEGF therapy reduces inflammation in diabetic macular edema. Ophthalmic Res. 2021;64(1):43–9. DOI: 10.1159/000508953
4. Virgili G, Parravano M, Jr E, Gordon I, Lucenteforte E. Anti-vascular endothelial growth factor for diabetic macular oedema : a network meta-analysis ( Review ). Cochrane Database Syst Rev. 2017;(6). DOI: 10.1002/14651858.CD007419.pub5
5. Maldonado RM, Vianna RNG, Cardoso GP, De Magalhães AV, Burnier MN. Intravitreal injection of commercially available ketorolac tromethamine in eyes with diabetic macular edema refractory to laser photocoagulation. Curr Eye Res. 2011;36(8):768–73. DOI: 10.3109/02713683.2011.585734
6. Soheilian M, Karimi S, Ramezani A, Montahai T, Yaseri M, Soheilian R, et al. Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial. Int Ophthalmol. 2015;35(3):421–8. DOI: 10.1007/s10792-014-9967-z
7. Ghanbari H, Kianersi F, Sonbolestan SA, Abtahi MA, Akbari M, Abtahi ZA, et al. Intravitreal Diclofenac plus Bevacizumab versus Bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial. Int Ophthalmol. 2017;37(4):867–74. DOI: 10.1007/s10792-016-0335-z
8. Faghihi H, Yahyapour H, Mahmoudzadeh R, Faghihi S. Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up. Med hypothesis, Discov Innov Ophthalmol J. 2017;6(3):67–75. PMCID: PMC5787025
9. Saputro A, Agni AN, Supanji. Changes in Central Macular Thickness in Intravitreal Injection of Ketorolac Compared to Intravitreal Injection of Bevacizumab in Patients with Diabetic Macular Edema (DME). Thesis: 2021.
10. Shimura M, Yasuda K, Yasuda M, Nakazawa T. Visual outcome after intravitreal bevacizumab depends on the optical coherence tomographic patterns of patients with diffuse diabetic macular EDEMA. Retina. 2013;33(4):740–7. DOI: 10.1097/IAE.0b013e31826b6763
11. Kim TK, Shin HY, Kim SY, Lee YC, Lee MY. Factors influencing intravitreal bevacizumab and triamcinolone treatment in patients with diabetic macular edema. Eur J Ophthalmol. 2017;27(6):746–50. DOI: 10.5301/ejo.5000974
12. Usui-Ouchi A, Tamaki A, Sakanishi Y, Tamaki K, Mashimo K, Sakuma T, et al. Factors affecting a short-term response to anti-vegf therapy in diabetic macular edema. Life. 2021;11(2):1–9. doi: 10.3390/life11020083
13. Parravano M, Costanzo E, Querques G. Profile of non-responder and late responder patients treated for diabetic macular edema: systemic and ocular factors. Acta Diabetol. 2020;57(8):911–21. DOI: 10.1007/s00592-020-01496-7
14. Wong WM, Chee C, Bhargava M, Chai C, Lin H, Zhao P, et al. Systemic Factors Associated with Treatment Response in Diabetic Macular Edema. J Ophthalmol. 2020;2020. DOI: 10.1155/2020/1875860
15. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185–222. DOI: 10.1159/000458539
16. Tsilimbaris M, Tsika C, Kymionis GD. Intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery. Ther Clin Risk Manag. 2016;(12):177–82. DOI: 10.2147/TCRM.S97342
17. Kiddee W, Trope GE, Sheng L, Beltran-Agullo L, Smith M, Strungaru MH, et al. Intraocular Pressure Monitoring Post Intravitreal Steroids: A Systematic Review. Surv Ophthalmol. 2013;58(4):291–310. DOI: 10.1016/j.survophthal.2012.08.003
18. Elbendary AM, Shahin MM. Intravitreal diclofenac versus intravitreal triamcinolone acetonide in the treatment of diabetic macular edema. Retina. 2011;31(10):2058–64. DOI: 10.1097/IAE.0b013e31822a042a
19. Bracha P, Moore NA, Ciulla TA, WuDunn D, Cantor LB. The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review. Surv Ophthalmol. 2018;63(3):281–95. DOI: 10.1016/j.survophthal.2017.08.008
20. Shin SH, Park SP, Kim Y-K. Factors associated with pain following intravitreal injections. Korean J Ophthalmol. 2018;32(3):196. doi: 10.3341/kjo.2017.0081