Oštrina vida i anatomski ishodi lečenja intravitrealnim afliberceptom kod bolesnika koji imaju centralni dijabetični edem makule – retrospektivna longitudinalna kohortna studija
Sažetak
Uvod/Cilj. Dijabetesni edem makule koji zahvata centar makule (center-involved diabetic macular edema – CI-DME) jedan je od glavnih uzroka gubitka vida kod obolelih od dijabetesa melitusa, a karakteriše ga zadebljanje mrežnjače (1 mm) u centralnoj zoni fovee. Intravitrealni lekovi koji inhibiraju faktor rasta vaskularnog endotela (anti-vascular endothelial growth factor – anti-VEGF), kao što je aflibercept, široko se koriste za lečenje edema mrežnjače i poboljšanje ishoda vidnih funkcija. Cilj rada bio je da se procene anatomske i funkcionalne promene mrežnjače nakon intravitrealne primene aflibercepta kod obolelih od CI-DME. Metode. Retrospektivnom longitudinalnom kohortnom studijom obuhvaćeno je 70 očiju kod 50 bolesnika koji su imali CI-DME, potvrđen pomoću optical coherence tomography – OCT [sa centralnom debljinom fovee ≥ 350 µm i najbolje korigovanom vidnom oštrinom (best-corrected visual acuity – BCVA) ≥ 0,6 po Snellen-u], lečenih primenom tri mesečne injekcije aflibercepta. BCVA, centralna debljina fovee (central foveal thickness – CFT) i makularni volumen (MV) mereni su na početku tretmana i nakon 1, 3 i 6 meseci pomoću Optovue RTVue XR OCT uređaja. Rezultati. Prosečna starost bolesnika iznosila je 64,63 ± 7,79 godina. Hipertenzija je bila najčešća pridružena bolest (72,0%). Tokom šestomesečnog praćenja zabeleženo je značajno smanjenje prosečne vrednosti CFT (sa 459,00 µm na 379,92 µm, p < 0,001) i MV (sa 9,05 mm³ na 8,44 mm³, p < 0,001). Iako je pokazano blago poboljšanje rezultata BCVA, ono nije dostiglo statističku značajnost. Anatomska poboljšanja bila su u skladu sa inhibicijom VEGF-A i faktora rasta posteljice dejstvom aflibercepta, čime je smanjena vaskularna permeabilnost. Zaključak. Intravitrealna primena aflibercepta značajno smanjuje debljinu i MV mrežnjače kod obolelih od CI-DME, potvrđujući njegovu anatomsku efikasnost. Funkcionalno poboljšanje vida bilo je ograničeno, verovatno zbog hroničnog oštećenja mrežnjače. Da bi se razjasnio uticaj intravitrealno primenjenog aflibercepta na ishode vidnih funkcija, potrebne su dugotrajnije studije koje uključuju veći broj bolesnika.
Reference
International Council of Ophthalmology. ICO guidelines for diabet-ic eye care [Internet]. San Francisco (CA): ICO; 2017 [ac-cessed 2025 Oct 15; cited 2026 March 23]. Available from: https://icoph.org/eye-care-delivery/diabetic-eye-care/
American Academy of Ophthalmology. Diabetic macular edema [Internet]. EyeWiki 2010 [accessed 2025 Oct 15; cited 2026 March 23]. Available from: https://eyewiki.org/Diabetic_Macular_Edema
American Academy of Ophthalmology. Preferred Practice Pat-tern® guidelines: Diabetic retinopathy PPP 2024 [Internet]. San Francisco (CA): AAO; 2023 [accessed 2025 Oct 15; cited 2026 March 23]. Available from: https://www.aao.org/education/preferred-practice-pattern/diabetic-retinopathy-ppp
Solomon SD, Chew E, Duh EJ, Sobrin L, Sun JK, VanderBeek BL, et al. Diabetic retinopathy: a position statement by the Ameri-can Diabetes Association. Diabetes Care 2017; 40(3): 412–8. DOI: 10.2337/dc16-2641. Erratum in: Diabetes Care 2017; 40(6): 809. DOI: 10.2337/dc17-er06e. Erratum in: Diabetes Care 2017; 40(9): 1285. DOI: 10.2337/dc17-er09.
Wong TY, Sun J, Kawasaki R, Ruamviboonsuk P, Gupta N, Lan-singh VC, et al. Guidelines on diabetic eye care: the Interna-tional Council of Ophthalmology recommendations for screening, follow-up, referral, and treatment based on resource settings. Ophthalmology 2018; 125(10): 1608–22. DOI: 10.1016/j.ophtha.2018.04.007.
Im JHB, Jin YP, Chow R, Yan P. Prevalence of diabetic macular edema based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Surv Oph-thalmol 2022; 67(4): 1244–51. DOI: 10.1016/j.survophthal.2022.01.009.
Szeto SK, Hui VWK, Tang FY, Yang D, Sun ZH, Mohamed S, et al. OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study. Br J Ophthalmol 2023; 107(4): 525–33. DOI: 10.1136/bjophthalmol-2021-319587.
U.S. Food and Drug Administration. Eylea (aflibercept) injec-tion: approval for diabetic macular edema [Internet]. Silver Spring (MD): FDA; 2014 [accessed 2025 Oct 15; cited 2026 March 23]. Available from: https://newsroom.regeneron.com/news-releases/news-release-details/eylear-aflibercept-injection-receives-fda-approval-treatment/
European Medicines Agency. Eylea: EPAR – product information [Internet]. London (UK): EMA; 2012 [accessed 2025 Oct 15; cited 2026 March 23]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/eylea#product-info
Campos Polo R, Rubio Sánchez C, García Guisado DM, Díaz Luque MJ. Aflibercept for clinically significant diabetic macu-lar edema: 12-month results in daily clinical practice. Clin Ophthalmol 2018; 12: 99−104. DOI: 10.2147/OPTH.S154421.
Lukic M, Williams G, Shalchi Z, Sim D, Patel PJ, Keane PA, et al. Intravitreal aflibercept for diabetic macular oedema: Moor-fields' real-world 12-month visual acuity and anatomical out-comes. Eur J Ophthalmol 2020; 30(3): 557−62. DOI: 10.1177/1120672119833270.
Zhang C, Chen T, Jia R, Gong D, Liu Z, Wu C, et al. Intravitre-al aflibercept for diabetic macular edema: structural and func-tional improvements. Front Med (Lausanne) 2025; 12: 1547977. DOI: 10.3389/fmed.2025.1547977.
Sugimoto M, Chujo S, Kato K, Shimura M, Kitano S, Kusuhara S, et al. Real-World Outcomes of Different Types of Treatment for Diabetic Macular Edema Before and After Approval of Anti-Vascular Endothelium Growth Factor Agents. J Clin Med 2024; 13(23): 7336. DOI: 10.3390/jcm13237336.
Munayco-Guillén F, Vazquez-Membrillo MA, Garcia-Roa MR, De La Cruz-Vargas JA, García-Perdomo HA, Pichardo-Rodriguez R. Effectiveness of the Use of Three-Dose Intravitreal Ziv-Aflibercept in the Management of Diabetic Macular Edema in a Real-Life Setting. Clin Ophthalmol 2023; 17: 1129–35. DOI: 10.2147/OPTH.S398359.
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 Med 2020; 8(6): 382. DOI: 10.21037/atm.2020.02.04.
Kern C, Schiefelbein J, Fu DJ, Schworm B, Sim D, Herold T, et al. Two-year visual acuity and structural outcomes in patients with diabetic macular oedema treated with intravitreal afliber-cept: a retrospective cohort study. Clin Ophthalmol 2020; 14: 533–41. DOI: 10.2147/OPTH.S237586.
Salimi A, Vila N, Modabber M, Kapusta M. One-year outcomes of aflibercept for refractory diabetic macular edema in bevaci-zumab nonresponders. Indian J Ophthalmol 2021; 69(2): 360–7. DOI: 10.4103/ijo.IJO_459_20.
Couturier A, Wykoff CC, Lupidi M, Udaondo P, Peto T, Pintard PJ. Anatomic biomarkers as potential endpoints in diabetic macular edema: a systematic literature review with identifica-tion of macular volume as a key surrogate for visual acuity. Surv Ophthalmol 2025; 70(6): 1090–110. DOI: 10.1016/j.survophthal.2025.04.004.
Korobelnik JF, Daien V, Faure C, Tadayoni R, Giocanti-Aurégan A, Dot C, et al. Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. Graefes Arch Clin Exp Ophthalmol 2020; 258(3): 521–8. DOI: 10.1007/s00417-019-04592-9.
Donati S, Yang CH, Xu X, Mura M, Giocanti-Aurégan A, Hoerauf H, et al. Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema in Routine Clinical Practice: Results from the 24-Month AURIGA Observational Study. Ophthalmol Ther 2024; 13(1): 161–78. DOI: 10.1007/s40123-023-00829-3.
Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014; 121(11): 2247–54. DOI: 10.1016/j.ophtha.2014.05.006.
Santhakumaran S, Salimi A, Brunetti VC, Galic J. Efficacy and Safety of Aflibercept Therapy for Diabetic Macular Edema: A Systematic Review and Meta-Analysis. J Curr Ophthalmol 2022; 34(2): 133–47. DOI: 10.4103/joco.joco_308_21.
Griffin DR, Richmond PP, Olson JC. Intravitreal Aflibercept Outcomes in Patients with Persistent Macular Exudate Previ-ously Treated with Bevacizumab and/or Ranibizumab for Ne-ovascular Age-Related Macular Degeneration. J Ophthalmol 2014; 2014: 497178. DOI: 10.1155/2014/497178.
Grewal DS, Gill MK, Sarezky D, Lyon AT, Mirza RG. Visual and anatomical outcomes following intravitreal aflibercept in eyes with recalcitrant neovascular age-related macular degen-eration: 12-month results. Eye (Lond) 2014; 28(7): 895–9. DOI: 10.1038/eye.2014.101.
Tran THC, Erginay A, Verdun S, Fourmaux E, Le Rouic JF, Uz-zan J, et al. One-Year Outcome of Aflibercept Intravitreal In-jection in Vitrectomized Eyes with Diabetic Macular Edema. Clin Ophthalmol 2021; 15: 1971–8. DOI: 10.2147/OPTH.S304030.
Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, et al. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Stud-ies. Ophthalmology 2015; 122(10): 2044–52. DOI: 10.1016/j.ophtha.2015.06.017.
Heier JS, Korobelnik JF, Brown DM, Schmidt-Erfurth U, Do DV, Midena E, et al. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Stud-ies. Ophthalmology 2016; 123(11): 2376–85. DOI: 10.1016/j.ophtha.2016.07.032.
Diabetic Retinopathy Clinical Research Network; Wells JA, Glass-man AR, Ayala AR, Jampol LM, Aiello LP, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015; 372(13): 1193–203. DOI: 10.1056/NEJMoa1414264.
Bressler NM, Beaulieu WT, Glassman AR, Blinder KJ, Bressler SB, Jampol LM, et al. Persistent Macular Thickening Following Intravitreous Aflibercept, Bevacizumab, or Ranibizumab for Central-Involved Diabetic Macular Edema With Vision Im-pairment: A Secondary Analysis of a Randomized Clinical Tri-al. JAMA Ophthalmol 2018; 136(3): 257–69. DOI: 10.1001/jamaophthalmol.2017.6565. Erratum in: JAMA Ophthalmol 2018; 136(5): 601. DOI: 10.1001/jamaophthalmol.2018.0795.
National Institute for Health and Care Excellence. Aflibercept for treating diabetic macular oedema [Internet]. Manchester: NICE; 2018 [accessed 2026 Feb 15; cited 2026 March 23]. Available from: www.nice.org.uk/guidance/ta346
Han YE, Jo J, Kim YJ, Lee J. Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study. J Diabetes Res 2023; 2023: 1485059. DOI: 10.1155/2023/1485059.
Tiosano L, Ayalon A, Banin E, Averbukh E, Jaouni T, Chowers I. Correlation of Response between Both Eyes to First- and Second-Line Anti-VEGF Therapy in Diabetic Macular Ede-ma. Curr Eye Res 2021; 46(4): 539−45. DOI: 10.1080/02713683.2020.1812085.