When to Perform a Treatment Switch in Diabetic Macular Edema in Patients with Inadequate Response to Anti-VEGF
Main Article Content
Abstract
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Multiple therapeutic options are currently available for these patients, including laser photocoagulation; intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs or steroids; or pars plana vitrectomy for tractional DME. The initial treatment for DME is well-defined and widely accepted, with anti-VEGF as first-line option. Nevertheless, between 30 and 40% of patients show partial response or no response whatsoever. There is no consensus on the number of injections needed in order to classify a patient as a non-responder or sub-optimal responder, nor on the definition of the latter. In this study, these concepts are analysed as well as the different therapeutic alternatives at hand, with special interest on the switch between different anti-VEGF and/or steroids. These analyses are performed from an anatomical and functional point of view as well as from an economic, cost-effectiveness perspective. Recent evidence suggests that an early switch to dexamethasone implant in eyes that did not respond adequately to anti-VEGF therapy after 3 injections provides better functional outcomes while alleviating the heavy economic burden of this disease.
Keywords:
macular edema, diabetic retinopathy, dexamethasone, anti-VEGF
Article Details
How to Cite
RUIZ-MEDRANO, Jorge; GONZALEZ-BUENDIA, Lucia; RUIZ-MORENO, José M..
When to Perform a Treatment Switch in Diabetic Macular Edema in Patients with Inadequate Response to Anti-VEGF.
Medical Research Archives, [S.l.], v. 10, n. 5, june 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2741>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i5.2741.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Rowley WR, Bezold C, Arikan Y, Byrne E, Krohe S. Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Popul Health Manag. 2017;20(1):6-12. doi:10.1089/pop.2015.0181
2. Hsia NY, Lin CJ, Chen HS, et al. Short-Term Outcomes of Refractory Diabetic Macular Edema Switch From Ranibizumab to Dexamethasone Implant and the Influential Factors: A Retrospective Real World Experience. Frontiers Medicine. 2021;8:649979. doi:10.3389/fmed.2021.649979
3. Liu Y, Cheng J, Gao Y, Qin L, Min X, Zhang M. Efficacy of switching therapy to aflibercept for patients with persistent diabetic macular edema: a systematic review and meta-analysis. Ann Transl Medicine. 2020;8(6):382. doi:10.21037/atm.2020.02.04
4. Kocur I, Resnikoff S. Visual impairment and blindness in Europe and their prevention. Brit J Ophthalmol. 2002;86(7):716. doi:10.1136/bjo.86.7.716
5. Furino C, Boscia F, Reibaldi M, Alessio G. Intravitreal Therapy for Diabetic Macular Edema: An Update. J Ophthalmol. 2021;2021:1-23. doi:10.1155/2021/6654168
6. Photocoagulation for Diabetic Macular Edema: Early Treatment Diabetic Retinopathy Study Report Number 1 Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol-chic. 1985;103(12):1796-1806. doi:10.1001/archopht.1985.01050120030015
7. Moisseiev E, Loewenstein A. Diabetic Macular Edema: Emerging Strategies and Treatment Algorithms. Dev Ophthalmol. 2017;60:165-174. doi:10.1159/000459706
8. Group ETDRSR. Treatment Techniques and Clinical Guidelines for Photocoagulation of Diabetic Macular Edema Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. 1987;94(7):761-774. doi:10.1016/s0161-6420(87)33527-4
9. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, 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
10. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002;109(5):920-927. doi:10.1016/s0161-6420(02)00975-2
11. Gillies MC, Sutter FKP, Simpson JM, Larsson J, Ali H, Zhu M. Intravitreal Triamcinolone for Refractory Diabetic Macular Edema Two-Year Results of a Double-Masked, Placebo-Controlled, Randomized Clinical Trial. Ophthalmology. 2006;113(9):1533-1538. doi:10.1016/j.ophtha.2006.02.065
12. Network TDRCR, Elman MJ, Aiello LP, et al. Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology. 2010;117(6):1064-1077.e35. doi:10.1016/j.ophtha.2010.02.031
13. Danis RP, Sadda S, Li XY, Cui H, Hashad Y, Whitcup SM. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials. Br J Ophthalmol. 2016;100(6):796-801. doi:10.1136/bjophthalmol-2015-306823
14. Boyer DS, Yoon YH, Belfort R, et al. Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema. Ophthalmology. 2014;121(10):1904-1914. doi:10.1016/j.ophtha.2014.04.024
15. Campochiaro PA, Hafiz G, Shah SM, et al. Sustained Ocular Delivery of Fluocinolone Acetonide by an Intravitreal Insert. Ophthalmology. 2010;117(7):1393-1399.e3. doi:10.1016/j.ophtha.2009.11.024
16. Abreu-Gonzalez R, Gallego-Pinazo R, Abraldes M, Pinilla I, Lopez-Galvez MI. Management of diabetic macular edema patients in clinical practice in Spain. Eur J Ophthalmol. 2018;29(6):664-672. doi:10.1177/1120672118804079
17. Gillies MC, Lim LL, Campain A, et al. A Randomized Clinical Trial of Intravitreal Bevacizumab versus Intravitreal Dexamethasone for Diabetic Macular Edema The BEVORDEX Study. Ophthalmology. 2014;121(12):2473-2481. doi:10.1016/j.ophtha.2014.07.002
18. Nguyen QD, Shah SM, Khwaja AA, et al. Two-Year Outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology. 2010;117(11):2146-2151. doi:10.1016/j.ophtha.2010.08.016
19. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for Diabetic Macular Edema Results from 2 Phase III Randomized Trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. doi:10.1016/j.ophtha.2011.12.039
20. Network DRCR, Elman MJ, Qin H, et al. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment Three-Year Randomized Trial Results. Ophthalmology. 2012;119(11):2312-2318. doi:10.1016/j.ophtha.2012.08.022
21. Prünte C, Fajnkuchen F, Mahmood S, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Brit J Ophthalmol. 2016;100(6):787. doi:10.1136/bjophthalmol-2015-307249
22. Freund KB, Korobelnik JF, Devenyi R, et al. TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES. Retin. 2015;35(8):1489-1506. doi:10.1097/iae.0000000000000627
23. Bressler SB, Ayala AR, Bressler NM, et al. Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment. Jama Ophthalmol. 2016;134(3):1-8. doi:10.1001/jamaophthalmol.2015.5346
24. Gonzalez VH, Campbell J, Holekamp NM, et al. 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. doi:10.1016/j.ajo.2016.09.012
25. Dugel PU, Campbell JH, Kiss S, et al. ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA. Retin. 2019;39(1):88-97. doi:10.1097/iae.0000000000002110
26. Couturier A, Giocanti-Auregan A, Massin P. Les switchs de traitement dans l’œdème maculaire diabétique : revue de la littérature et algorithme de prise en charge. J Français D’ophtalmologie. 2020;43(8):710-717. doi:10.1016/j.jfo.2019.12.006
27. Martínez AH, Delgado EP, Silva GS, et al. Early versus late switch: How long should we extend the anti-vascular endothelial growth factor therapy in unresponsive diabetic macular edema patients? Eur J Ophthalmol. 2019;30(5):1091-1098. doi:10.1177/1120672119848257
28. Group F the IR, Busch C, Zur D, et al. Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema. Acta Diabetol. 2018;55(8):789-796. doi:10.1007/s00592-018-1151-x
29. Maturi RK, Glassman AR, Liu D, et al. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. Jama Ophthalmol. 2017;136(1):29. doi:10.1001/jamaophthalmol.2017.4914
30. Shah SU, Harless A, Bleau L, Maturi RK. PROSPECTIVE RANDOMIZED SUBJECT-MASKED STUDY OF INTRAVITREAL BEVACIZUMAB MONOTHERAPY VERSUS DEXAMETHASONE IMPLANT MONOTHERAPY IN THE TREATMENT OF PERSISTENT DIABETIC MACULAR EDEMA. Retin. 2016;36(10):1986-1996. doi:10.1097/iae.0000000000001038
31. Ruiz-Medrano J, Rodríguez-Leor R, Almazán E, et al. Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: Early versus late switch. Eur J Ophthalmol. Published online 2020:112067212092996. doi:10.1177/1120672120929960
32. Ruiz-Moreno JM, Andrés-Nogales F de, Oyagüez I. Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients. Bmc Ophthalmol. 2020;20(1):371. doi:10.1186/s12886-020-01637-0
33. Network DRCR, Wells JA, Glassman AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. New Engl J Medicine. 2015;372(13):1193-1203. doi:10.1056/nejmoa1414264
34. Bressler NM, Beaulieu WT, Glassman AR, et al. Persistent Macular Thickening Following Intravitreous Aflibercept, Bevacizumab, or Ranibizumab for Central-Involved Diabetic Macular Edema With Vision Impairment: A Secondary Analysis of a Randomized Clinical Trial. Jama Ophthalmol. 2018;136(3):257. doi:10.1001/jamaophthalmol.2017.6565
35. Udaondo P, Adan A, Arias-Barquet L, et al. Challenges in Diabetic Macular Edema Management: An Expert Consensus Report. Clin Ophthalmol. 2021;Volume 15:3183-3195. doi:10.2147/opth.s320948
36. Chatziralli I. Editorial - Suboptimal response to intravitreal anti-VEGF treatment for patients with diabetic macular edema: is there any point in switching treatment? Eur Rev Med Pharmaco. 2018;22(15):5047-5050. doi:10.26355/eurrev_201808_15648
37. Torabi H. Management of Refractory Diabetic Macular Edema: A Review Article. Int J Medical Rev. 2018;5(1):27-34. doi:10.29252/ijmr-050105
38. Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G. Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Brit J Ophthalmol. 2017;101(12):1689. doi:10.1136/bjophthalmol-2017-310242
39. Kodjikian L, Baillif S, Couturier A, et al. Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study. Eur J Ophthalmol. Published online 2021:112067212110528. doi:10.1177/11206721211052852
40. Blinder KJ, Dugel PU, Chen S, et al. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1). Clin Ophthalmol. 2017;Volume 11:393-401. doi:10.2147/opth.s128509
41. Shah AR, Yonekawa Y, Todorich B, et al. Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection. J Vitreoretin Dis. 2017;1(3):169-174. doi:10.1177/2474126416682569
42. Bhandari S, Nguyen V, Fraser-Bell S, et al. Ranibizumab or Aflibercept for Diabetic Macular Edema Comparison of 1-Year Outcomes from the Fight Retinal Blindness! Registry. Ophthalmology. 2020;127(5):608-615. doi:10.1016/j.ophtha.2019.11.018
43. Massin P, Creuzot-Garcher C, Kodjikian L, et al. Real-World Outcomes with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema: 12-Month Results from the 36-Month BOREAL-DME Study. Ophthalmic Res. 2019;62(2):101-110. doi:10.1159/000497406
44. Plaza-Ramos P, Borque E, García-Layana A. Evaluation of ranibizumab and aflibercept for the treatment of diabetic macular edema in daily clinical practice. Plos One. 2019;14(10):e0223793. doi:10.1371/journal.pone.0223793
45. Udaondo P, Hernández C, Briansó-Llort L, García-Delpech S, Simó-Servat O, Simó R. Usefulness of Liquid Biopsy Biomarkers from Aqueous Humor in Predicting Anti-VEGF Response in Diabetic Macular Edema: Results of a Pilot Study. J Clin Medicine. 2019;8(11):1841. doi:10.3390/jcm8111841
46. Wong TY, Sun J, Kawasaki R, et al. Guidelines on Diabetic Eye Care The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings. Ophthalmology. 2018;125(10):1608-1622. doi:10.1016/j.ophtha.2018.04.007
47. Layana AG, Adán A, Ascaso FJ, et al. Use of intravitreal dexamethasone implants in the treatment of diabetic macular edema: Expert recommendations using a Delphi approach. Eur J Ophthalmol. 2019;30(5):1042-1052. doi:10.1177/1120672119861623
48. Cervera E, Andrés-Nogales FD, Armadá F, Arias L, Oyagüez I, Martínez C. Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema. Farmacia Hosp Organo Oficial De Expresion Cientifica De La Sociedad Espanola De Farmacia Hosp. 2018;42(6):244-250. doi:10.7399/fh.11016
49. Brown DM, Nguyen QD, Marcus DM, et al. Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials RISE and RIDE. Ophthalmology. 2013;120(10):2013-2022. doi:10.1016/j.ophtha.2013.02.034
50. Demir G, Ozkaya A, Yuksel E, et al. Early and Late Switch from Ranibizumab to an Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema in the Event of a Poor Anatomical Response. Clin Drug Invest. 2020;40(2):119-128. doi:10.1007/s40261-019-00865-7
51. Lang KM, Little TD. Principled Missing Data Treatments. Prev Sci. 2018;19(3):284-294. doi:10.1007/s11121-016-0644-5
52. Abraldes MJ, Pareja A, Roura M, group on behalf of the O study. Analysis of costs associated with the management and morbidity of diabetic macular oedema and macular oedema secondary to retinal vein occlusion. Archivos De La Sociedad Española De Oftalmología Engl Ed. 2016;91(6):273-280. doi:10.1016/j.oftale.2015.11.006
53. Romero-Aroca P, Riva-Fernandez S de la, Valls-Mateu A, et al. Cost of diabetic retinopathy and macular oedema in a population, an eight year follow up. Bmc Ophthalmol. 2016;16(1):136. doi:10.1186/s12886-016-0318-x
54. Escobar-Barranco JJ, Pina-Marín B, Fernández-Bonet M. Dexamethasone Implants in Patients with Naïve or Refractory Diffuse Diabetic Macular Edema. Ophthalmologica. 2015;233(3-4):176-185. doi:10.1159/000371770
55. Guigou S, Pommier S, Meyer F, et al. Efficacy and Safety of Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema. Ophthalmologica. 2015;233(3-4):169-175. doi:10.1159/000381356
56. Chhablani J, Bansal P, Veritti D, et al. Dexamethasone implant in diabetic macular edema in real-life situations. Eye. 2016;30(3):426-430. doi:10.1038/eye.2015.246
57. Malclès A, Dot C, Voirin N, et al. REAL-LIFE STUDY IN DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT. Retin. 2017;37(4):753-760. doi:10.1097/iae.0000000000001234
58. Pareja-R¨aos A, Fuente-Rodr¨aguez PR de la, Bonaque-Gonz¨¢lez S, L¨®pez-G¨¢lvez M, Lozano-L¨®pez V, Romero-Aroca P. Intravitreal dexamethasone implants for diabetic macular edema. Int J Ophthalmol-chi. 2018;11(1):77-82. doi:10.18240/ijo.2018.01.14
59. Iglicki M, Busch C, Zur D, et al. DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES. Retin. 2019;39(1):44-51. doi:10.1097/iae.0000000000002196
60. Nagpal M, Mehrotra N, Juneja R, Jain H. Dexamethasone implant (0.7 mg) in Indian patients with macular edema: Real-life scenario. Taiwan J Ophthalmol. 2018;8(3):141-148. doi:10.4103/tjo.tjo_62_17
61. Castro-Navarro V, Cervera-Taulet E, Navarro-Palop C, Monferrer-Adsuara C, Hernández-Bel L, Montero-Hernández J. Intravitreal dexamethasone implant Ozurdex® in naïve and refractory patients with different subtypes of diabetic macular edema. Bmc Ophthalmol. 2019;19(1):15. doi:10.1186/s12886-018-1022-9
62. Bellocq D, Akesbi J, Matonti F, et al. The Pattern of Recurrence in Diabetic Macular Edema Treated by Dexamethasone Implant: The PREDIAMEX Study. Ophthalmol Retin. 2018;2(6):567-573. doi:10.1016/j.oret.2017.10.016
63. Matonti F, Pommier S, Meyer F, et al. Long-Term Efficacy and Safety of Intravitreal Dexamethasone Implant for the Treatment of Diabetic Macular Edema. Eur J Ophthalmol. 2016;26(5):454-459. doi:10.5301/ejo.5000787
64. Rajesh B, Zarranz-Ventura J, Fung AT, et al. Safety of 6000 intravitreal dexamethasone implants. Brit J Ophthalmol. 2020;104(1):39. doi:10.1136/bjophthalmol-2019-313991
65. Downey L, Acharya N, Devonport H, et al. Treatment choices for diabetic macular oedema: a guideline for when to consider an intravitreal corticosteroid, including adaptations for the COVID-19 era. Bmj Open Ophthalmol. 2021;6(1):e000696. doi:10.1136/bmjophth-2020-000696
2. Hsia NY, Lin CJ, Chen HS, et al. Short-Term Outcomes of Refractory Diabetic Macular Edema Switch From Ranibizumab to Dexamethasone Implant and the Influential Factors: A Retrospective Real World Experience. Frontiers Medicine. 2021;8:649979. doi:10.3389/fmed.2021.649979
3. Liu Y, Cheng J, Gao Y, Qin L, Min X, Zhang M. Efficacy of switching therapy to aflibercept for patients with persistent diabetic macular edema: a systematic review and meta-analysis. Ann Transl Medicine. 2020;8(6):382. doi:10.21037/atm.2020.02.04
4. Kocur I, Resnikoff S. Visual impairment and blindness in Europe and their prevention. Brit J Ophthalmol. 2002;86(7):716. doi:10.1136/bjo.86.7.716
5. Furino C, Boscia F, Reibaldi M, Alessio G. Intravitreal Therapy for Diabetic Macular Edema: An Update. J Ophthalmol. 2021;2021:1-23. doi:10.1155/2021/6654168
6. Photocoagulation for Diabetic Macular Edema: Early Treatment Diabetic Retinopathy Study Report Number 1 Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol-chic. 1985;103(12):1796-1806. doi:10.1001/archopht.1985.01050120030015
7. Moisseiev E, Loewenstein A. Diabetic Macular Edema: Emerging Strategies and Treatment Algorithms. Dev Ophthalmol. 2017;60:165-174. doi:10.1159/000459706
8. Group ETDRSR. Treatment Techniques and Clinical Guidelines for Photocoagulation of Diabetic Macular Edema Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. 1987;94(7):761-774. doi:10.1016/s0161-6420(87)33527-4
9. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, 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
10. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002;109(5):920-927. doi:10.1016/s0161-6420(02)00975-2
11. Gillies MC, Sutter FKP, Simpson JM, Larsson J, Ali H, Zhu M. Intravitreal Triamcinolone for Refractory Diabetic Macular Edema Two-Year Results of a Double-Masked, Placebo-Controlled, Randomized Clinical Trial. Ophthalmology. 2006;113(9):1533-1538. doi:10.1016/j.ophtha.2006.02.065
12. Network TDRCR, Elman MJ, Aiello LP, et al. Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema. Ophthalmology. 2010;117(6):1064-1077.e35. doi:10.1016/j.ophtha.2010.02.031
13. Danis RP, Sadda S, Li XY, Cui H, Hashad Y, Whitcup SM. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials. Br J Ophthalmol. 2016;100(6):796-801. doi:10.1136/bjophthalmol-2015-306823
14. Boyer DS, Yoon YH, Belfort R, et al. Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema. Ophthalmology. 2014;121(10):1904-1914. doi:10.1016/j.ophtha.2014.04.024
15. Campochiaro PA, Hafiz G, Shah SM, et al. Sustained Ocular Delivery of Fluocinolone Acetonide by an Intravitreal Insert. Ophthalmology. 2010;117(7):1393-1399.e3. doi:10.1016/j.ophtha.2009.11.024
16. Abreu-Gonzalez R, Gallego-Pinazo R, Abraldes M, Pinilla I, Lopez-Galvez MI. Management of diabetic macular edema patients in clinical practice in Spain. Eur J Ophthalmol. 2018;29(6):664-672. doi:10.1177/1120672118804079
17. Gillies MC, Lim LL, Campain A, et al. A Randomized Clinical Trial of Intravitreal Bevacizumab versus Intravitreal Dexamethasone for Diabetic Macular Edema The BEVORDEX Study. Ophthalmology. 2014;121(12):2473-2481. doi:10.1016/j.ophtha.2014.07.002
18. Nguyen QD, Shah SM, Khwaja AA, et al. Two-Year Outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology. 2010;117(11):2146-2151. doi:10.1016/j.ophtha.2010.08.016
19. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for Diabetic Macular Edema Results from 2 Phase III Randomized Trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. doi:10.1016/j.ophtha.2011.12.039
20. Network DRCR, Elman MJ, Qin H, et al. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment Three-Year Randomized Trial Results. Ophthalmology. 2012;119(11):2312-2318. doi:10.1016/j.ophtha.2012.08.022
21. Prünte C, Fajnkuchen F, Mahmood S, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Brit J Ophthalmol. 2016;100(6):787. doi:10.1136/bjophthalmol-2015-307249
22. Freund KB, Korobelnik JF, Devenyi R, et al. TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES. Retin. 2015;35(8):1489-1506. doi:10.1097/iae.0000000000000627
23. Bressler SB, Ayala AR, Bressler NM, et al. Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment. Jama Ophthalmol. 2016;134(3):1-8. doi:10.1001/jamaophthalmol.2015.5346
24. Gonzalez VH, Campbell J, Holekamp NM, et al. 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. doi:10.1016/j.ajo.2016.09.012
25. Dugel PU, Campbell JH, Kiss S, et al. ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA. Retin. 2019;39(1):88-97. doi:10.1097/iae.0000000000002110
26. Couturier A, Giocanti-Auregan A, Massin P. Les switchs de traitement dans l’œdème maculaire diabétique : revue de la littérature et algorithme de prise en charge. J Français D’ophtalmologie. 2020;43(8):710-717. doi:10.1016/j.jfo.2019.12.006
27. Martínez AH, Delgado EP, Silva GS, et al. Early versus late switch: How long should we extend the anti-vascular endothelial growth factor therapy in unresponsive diabetic macular edema patients? Eur J Ophthalmol. 2019;30(5):1091-1098. doi:10.1177/1120672119848257
28. Group F the IR, Busch C, Zur D, et al. Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema. Acta Diabetol. 2018;55(8):789-796. doi:10.1007/s00592-018-1151-x
29. Maturi RK, Glassman AR, Liu D, et al. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. Jama Ophthalmol. 2017;136(1):29. doi:10.1001/jamaophthalmol.2017.4914
30. Shah SU, Harless A, Bleau L, Maturi RK. PROSPECTIVE RANDOMIZED SUBJECT-MASKED STUDY OF INTRAVITREAL BEVACIZUMAB MONOTHERAPY VERSUS DEXAMETHASONE IMPLANT MONOTHERAPY IN THE TREATMENT OF PERSISTENT DIABETIC MACULAR EDEMA. Retin. 2016;36(10):1986-1996. doi:10.1097/iae.0000000000001038
31. Ruiz-Medrano J, Rodríguez-Leor R, Almazán E, et al. Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: Early versus late switch. Eur J Ophthalmol. Published online 2020:112067212092996. doi:10.1177/1120672120929960
32. Ruiz-Moreno JM, Andrés-Nogales F de, Oyagüez I. Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients. Bmc Ophthalmol. 2020;20(1):371. doi:10.1186/s12886-020-01637-0
33. Network DRCR, Wells JA, Glassman AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. New Engl J Medicine. 2015;372(13):1193-1203. doi:10.1056/nejmoa1414264
34. Bressler NM, Beaulieu WT, Glassman AR, et al. Persistent Macular Thickening Following Intravitreous Aflibercept, Bevacizumab, or Ranibizumab for Central-Involved Diabetic Macular Edema With Vision Impairment: A Secondary Analysis of a Randomized Clinical Trial. Jama Ophthalmol. 2018;136(3):257. doi:10.1001/jamaophthalmol.2017.6565
35. Udaondo P, Adan A, Arias-Barquet L, et al. Challenges in Diabetic Macular Edema Management: An Expert Consensus Report. Clin Ophthalmol. 2021;Volume 15:3183-3195. doi:10.2147/opth.s320948
36. Chatziralli I. Editorial - Suboptimal response to intravitreal anti-VEGF treatment for patients with diabetic macular edema: is there any point in switching treatment? Eur Rev Med Pharmaco. 2018;22(15):5047-5050. doi:10.26355/eurrev_201808_15648
37. Torabi H. Management of Refractory Diabetic Macular Edema: A Review Article. Int J Medical Rev. 2018;5(1):27-34. doi:10.29252/ijmr-050105
38. Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G. Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Brit J Ophthalmol. 2017;101(12):1689. doi:10.1136/bjophthalmol-2017-310242
39. Kodjikian L, Baillif S, Couturier A, et al. Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study. Eur J Ophthalmol. Published online 2021:112067212110528. doi:10.1177/11206721211052852
40. Blinder KJ, Dugel PU, Chen S, et al. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1). Clin Ophthalmol. 2017;Volume 11:393-401. doi:10.2147/opth.s128509
41. Shah AR, Yonekawa Y, Todorich B, et al. Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection. J Vitreoretin Dis. 2017;1(3):169-174. doi:10.1177/2474126416682569
42. Bhandari S, Nguyen V, Fraser-Bell S, et al. Ranibizumab or Aflibercept for Diabetic Macular Edema Comparison of 1-Year Outcomes from the Fight Retinal Blindness! Registry. Ophthalmology. 2020;127(5):608-615. doi:10.1016/j.ophtha.2019.11.018
43. Massin P, Creuzot-Garcher C, Kodjikian L, et al. Real-World Outcomes with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema: 12-Month Results from the 36-Month BOREAL-DME Study. Ophthalmic Res. 2019;62(2):101-110. doi:10.1159/000497406
44. Plaza-Ramos P, Borque E, García-Layana A. Evaluation of ranibizumab and aflibercept for the treatment of diabetic macular edema in daily clinical practice. Plos One. 2019;14(10):e0223793. doi:10.1371/journal.pone.0223793
45. Udaondo P, Hernández C, Briansó-Llort L, García-Delpech S, Simó-Servat O, Simó R. Usefulness of Liquid Biopsy Biomarkers from Aqueous Humor in Predicting Anti-VEGF Response in Diabetic Macular Edema: Results of a Pilot Study. J Clin Medicine. 2019;8(11):1841. doi:10.3390/jcm8111841
46. Wong TY, Sun J, Kawasaki R, et al. Guidelines on Diabetic Eye Care The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings. Ophthalmology. 2018;125(10):1608-1622. doi:10.1016/j.ophtha.2018.04.007
47. Layana AG, Adán A, Ascaso FJ, et al. Use of intravitreal dexamethasone implants in the treatment of diabetic macular edema: Expert recommendations using a Delphi approach. Eur J Ophthalmol. 2019;30(5):1042-1052. doi:10.1177/1120672119861623
48. Cervera E, Andrés-Nogales FD, Armadá F, Arias L, Oyagüez I, Martínez C. Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema. Farmacia Hosp Organo Oficial De Expresion Cientifica De La Sociedad Espanola De Farmacia Hosp. 2018;42(6):244-250. doi:10.7399/fh.11016
49. Brown DM, Nguyen QD, Marcus DM, et al. Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials RISE and RIDE. Ophthalmology. 2013;120(10):2013-2022. doi:10.1016/j.ophtha.2013.02.034
50. Demir G, Ozkaya A, Yuksel E, et al. Early and Late Switch from Ranibizumab to an Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema in the Event of a Poor Anatomical Response. Clin Drug Invest. 2020;40(2):119-128. doi:10.1007/s40261-019-00865-7
51. Lang KM, Little TD. Principled Missing Data Treatments. Prev Sci. 2018;19(3):284-294. doi:10.1007/s11121-016-0644-5
52. Abraldes MJ, Pareja A, Roura M, group on behalf of the O study. Analysis of costs associated with the management and morbidity of diabetic macular oedema and macular oedema secondary to retinal vein occlusion. Archivos De La Sociedad Española De Oftalmología Engl Ed. 2016;91(6):273-280. doi:10.1016/j.oftale.2015.11.006
53. Romero-Aroca P, Riva-Fernandez S de la, Valls-Mateu A, et al. Cost of diabetic retinopathy and macular oedema in a population, an eight year follow up. Bmc Ophthalmol. 2016;16(1):136. doi:10.1186/s12886-016-0318-x
54. Escobar-Barranco JJ, Pina-Marín B, Fernández-Bonet M. Dexamethasone Implants in Patients with Naïve or Refractory Diffuse Diabetic Macular Edema. Ophthalmologica. 2015;233(3-4):176-185. doi:10.1159/000371770
55. Guigou S, Pommier S, Meyer F, et al. Efficacy and Safety of Intravitreal Dexamethasone Implant in Patients with Diabetic Macular Edema. Ophthalmologica. 2015;233(3-4):169-175. doi:10.1159/000381356
56. Chhablani J, Bansal P, Veritti D, et al. Dexamethasone implant in diabetic macular edema in real-life situations. Eye. 2016;30(3):426-430. doi:10.1038/eye.2015.246
57. Malclès A, Dot C, Voirin N, et al. REAL-LIFE STUDY IN DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT. Retin. 2017;37(4):753-760. doi:10.1097/iae.0000000000001234
58. Pareja-R¨aos A, Fuente-Rodr¨aguez PR de la, Bonaque-Gonz¨¢lez S, L¨®pez-G¨¢lvez M, Lozano-L¨®pez V, Romero-Aroca P. Intravitreal dexamethasone implants for diabetic macular edema. Int J Ophthalmol-chi. 2018;11(1):77-82. doi:10.18240/ijo.2018.01.14
59. Iglicki M, Busch C, Zur D, et al. DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES. Retin. 2019;39(1):44-51. doi:10.1097/iae.0000000000002196
60. Nagpal M, Mehrotra N, Juneja R, Jain H. Dexamethasone implant (0.7 mg) in Indian patients with macular edema: Real-life scenario. Taiwan J Ophthalmol. 2018;8(3):141-148. doi:10.4103/tjo.tjo_62_17
61. Castro-Navarro V, Cervera-Taulet E, Navarro-Palop C, Monferrer-Adsuara C, Hernández-Bel L, Montero-Hernández J. Intravitreal dexamethasone implant Ozurdex® in naïve and refractory patients with different subtypes of diabetic macular edema. Bmc Ophthalmol. 2019;19(1):15. doi:10.1186/s12886-018-1022-9
62. Bellocq D, Akesbi J, Matonti F, et al. The Pattern of Recurrence in Diabetic Macular Edema Treated by Dexamethasone Implant: The PREDIAMEX Study. Ophthalmol Retin. 2018;2(6):567-573. doi:10.1016/j.oret.2017.10.016
63. Matonti F, Pommier S, Meyer F, et al. Long-Term Efficacy and Safety of Intravitreal Dexamethasone Implant for the Treatment of Diabetic Macular Edema. Eur J Ophthalmol. 2016;26(5):454-459. doi:10.5301/ejo.5000787
64. Rajesh B, Zarranz-Ventura J, Fung AT, et al. Safety of 6000 intravitreal dexamethasone implants. Brit J Ophthalmol. 2020;104(1):39. doi:10.1136/bjophthalmol-2019-313991
65. Downey L, Acharya N, Devonport H, et al. Treatment choices for diabetic macular oedema: a guideline for when to consider an intravitreal corticosteroid, including adaptations for the COVID-19 era. Bmj Open Ophthalmol. 2021;6(1):e000696. doi:10.1136/bmjophth-2020-000696