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Review

Anti-VEGF agents in the management of diabetic macular edema

, , &
Pages 285-296 | Received 13 Jan 2020, Accepted 04 Aug 2020, Published online: 29 Sep 2020

References

  • Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124–136.
  • Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.
  • Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17.
  • Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–564.
  • Bahrami B, Hong T, Gilles MC, et al. Anti-VEGF therapy for diabetic eye diseases. Asia Pac J Ophthalmol (Phila). 2017;6(6):535–545.
  • Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984;91(12):1464–1474.
  • Bhagat N, Grigorian RA, Tutela A, et al. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009;54(1):1–32.
  • Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Early treatment diabetic retinopathy study research group. Arch Ophthalmol. 1985;103(12):1796–1806.
  • Mitchell P, Bandello F, Schmidt-Erfurth U, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118(4):615–625.
  • Schmidt-Erfurth U, Lang GE, Holz FG, et al. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014;121(5):1045–1053.
  • Ishibashi T, Li X, Koh A, et al. The REVEAL study: ranibizumab monotherapy or combined with laser versus laser monotherapy in Asian patients with diabetic macular edema. Ophthalmology. 2015;122(7):1402–1415.
  • Mordenti J, Cuthbertson RA, Ferrara N, et al. Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol. 1999;27(5):536–544.
  • Raghavan M, Bjorkman PJ. Fc receptors and their interactions with immunoglobulins. Annu Rev Cell Dev Biol. 1996;12:181–220.
  • Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002;99(17):11393–11398.
  • Diabetic Retinopathy Clinical Research N, Scott IU, Edwards AR, Beck RW, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114(10):1860–1867.••This was a significant phase II randomized clinical trial reporting the efficacy of intravitreal bevacizumab in reducing central subfield thickness and improving visual acuity at 24 weeks in eyes with diabetic macular edema.
  • Rajendram R, Fraser-Bell S, Kaines A, et al. A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol. 2012;130(8):972–979.
  • Nguyen QD, Shah SM, Heier JS, et al. Primary end point (six months) results of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2009;116(11):2175–81 e1.
  • 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.
  • Sepah YJ, Sadiq MA, Boyer D, et al. Twenty-four-month outcomes of the ranibizumab for edema of the macula in diabetes - protocol 3 with high dose (READ-3) study. Ophthalmology. 2016;123(12):2581–2587.
  • 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.••This was a significant paper reporting the 36 month results of the RISE and RIDE studies, which ultimately led to the FDA approval of ranibizumab for treatment of DME. Ranibizumab demonstrated long term visual acuity gains and retinal anatomy improvement in eyes with DME.
  • 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.
  • Ziemssen F, Wachtlin J, Kuehlewein L, et al. Intravitreal ranibizumab therapy for diabetic macular edema in routine practice: two-year real-life data from a non-interventional, multicenter study in Germany. Diabetes Ther. 2018;9(6):2271–2289.
  • Do DV, Schmidt-Erfurth U, Gonzalez VH, et al. The DA VINCI Study: phase 2 primary results of VEGF trap-eye in patients with diabetic macular edema. Ophthalmology. 2011;118(9):1819–1826.
  • Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247–2254.
  • Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122(10):2044–2052. ••This was a significant paper reporting the 100 week results of the VISTA and VIVID studies, which ultimately led to the FDA approval of aflibercept for treatment of DME. Aflibercept demonstrated long term visual acuity gains and retinal anatomy improvement in eyes with DME.
  • Korobelnik JF, Daien V, Faure 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):521–528.
  • Tsapardoni FN, Makri OE, Lagogiannis AP, et al. Functional and anatomic results of up to 24 months aflibercept treatment for diabetic macular edema in real-life setting. Hell J Nucl Med. 2019;22(Suppl 2):47–54.
  • Diabetic Retinopathy Clinical Research N, Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015;372(13):1193–1203.
  • Cai S, Bressler NM. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol. 2017;28(6):636–643.••This study was significant because it was the first multicenter randomized clinical trial comparing intravitreal bevacizumab, ranibizumab, and aflibercept. The study showed that when initial visual acuity loss was mild, all three anti-VEGF agents demonstrated similar efficacy.
  • Ross EL, Hutton DW, Stein JD, et al. Cost-effectiveness of aflibercept, bevacizumab, and ranibizumab for diabetic macular edema treatment: analysis from the diabetic retinopathy clinical research network comparative effectiveness trial. JAMA Ophthalmol. 2016;134(8):888–896.
  • Holekamp N, Duff SB, Rajput Y, et al. Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data. J Med Econ. 2020;23(3):287–296.
  • Sophie R, Lu N, Campochiaro PA. Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab. Ophthalmology. 2015;122(7):1395–1401.
  • Ying GS, Huang J, Maguire MG, et al. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120(1):122–129.
  • Chen YP, Wu AL, Chuang CC, et al. Factors influencing clinical outcomes in patients with diabetic macular edema treated with intravitreal ranibizumab: comparison between responder and non-responder cases. Sci Rep. 2019;9(1):10952.
  • Ciulla TA, Bracha P, Pollack J, et al. Real-world outcomes of anti-vascular endothelial growth factor therapy in diabetic macular edema in the United States. Ophthalmol Retina. 2018;2(12):1179–1187.
  • Bressler SB, Odia I, Maguire MG, et al. Factors associated with visual acuity and central subfield thickness changes when treating diabetic macular edema with anti-vascular endothelial growth factor therapy: an exploratory analysis of the protocol T randomized clinical trial. JAMA Ophthalmol. 2019;137(4):382–389.
  • Udaondo P, Hernandez C, Brianso-Llort L, et al. Usefulness of liquid biopsy biomarkers from aqueous humor in predicting anti-VEGF response in diabetic macular edema: results of a pilot study. J Clin Med. 2019;8:11.
  • Choi MY, Jee D, Kwon JW. Characteristics of diabetic macular edema patients refractory to anti-VEGF treatments and a dexamethasone implant. PLoS One. 2019;14(9):e0222364.
  • Lee H, Jang H, Choi YA, et al. Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59(2):715–721.
  • Korot E, Comer G, Steffens T, et al. Algorithm for the measure of vitreous hyperreflective foci in optical coherence tomographic scans of patients with diabetic macular edema. JAMA Ophthalmol. 2016;134(1):15–20.
  • Framme C, Schweizer P, Imesch M, et al. Behavior of SD-OCT-detected hyperreflective foci in the retina of anti-VEGF-treated patients with diabetic macular edema. Invest Ophthalmol Vis Sci. 2012;53(9):5814–5818.
  • Framme C, Wolf S, Wolf-Schnurrbusch U. Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2010;51(11):5965–5969.
  • Schreur V, Altay L, van Asten F, et al. Hyperreflective foci on optical coherence tomography associate with treatment outcome for anti-VEGF in patients with diabetic macular edema. PLoS One. 2018;13(10):e0206482.
  • Kang JW, Chung H, Chan Kim H. Correlation of optical coherence tomographic hyperreflective foci with visual outcomes in different patterns of diabetic macular edema. Retina. 2016;36(9):1630–1639.
  • Yoshitake T, Murakami T, Suzuma K, et al. Hyperreflective foci in the outer retinal layers as a predictor of the functional efficacy of ranibizumab for diabetic macular edema. Sci Rep. 2020;10(1):873.
  • Rasti R, Allingham MJ, Mettu PS, et al. Deep learning-based single-shot prediction of differential effects of anti-VEGF treatment in patients with diabetic macular edema. Biomed Opt Express. 2020;11(2):1139–1152.
  • Chen SC, Chiu HW, Chen CC, et al. A novel machine learning algorithm to automatically predict visual outcomes in intravitreal ranibizumab-treated patients with diabetic macular edema. J Clin Med. 2018;7:12.
  • Mori K, Yoshida S, Kobayashi Y, et al. Decrease in the number of microaneurysms in diabetic macular edema after anti-vascular endothelial growth factor therapy: implications for indocyanine green angiography-guided detection of refractory microaneurysms. Graefes Arch Clin Exp Ophthalmol. 2020;258:735–741.
  • Couturier A, Rey PA, Erginay A, et al. Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti-vascular endothelial growth factor. Ophthalmology. 2019;126(12):1685–1694.
  • Hodzic-Hadzibegovic D, Sander BA, Valerius M, et al. Diabetic macular edema treated with anti-vascular endothelial growth factor: considerations related to nonimprovers. Ophthalmol Retina. 2018;2(11):1133–1142.
  • Scholz P, Altay L, Fauser S. A review of subthreshold micropulse laser for treatment of macular disorders. Adv Ther. 2017;34(7):1528–1555.
  • Moisseiev E, Abbassi S, Thinda S, et al. Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema. Eur J Ophthalmol. 2018;28(1):68–73.
  • Mansouri A, Sampat KM, Malik KJ, et al. Medscape. Efficacy of subthreshold micropulse laser in the treatment of diabetic macular edema is influenced by pre-treatment central foveal thickness. Eye (Lond). 2014;28(12):1418–1424.
  • Kanar HS, Arsan A, Altun A, et al. Can subthreshold micropulse yellow laser treatment change the anti-vascular endothelial growth factor algorithm in diabetic macular edema? A randomized clinical trial. Indian J Ophthalmol. 2020;68(1):145–151.
  • Khattab AM, Hagras SM, AbdElhamid A, et al. Aflibercept with adjuvant micropulsed yellow laser versus aflibercept monotherapy in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2019;257(7):1373–1380.
  • Abouhussein MA, Gomaa AR. Aflibercept plus micropulse laser versus aflibercept monotherapy for diabetic macular edema: 1-year results of a randomized clinical trial. Int Ophthalmol. 2020;40:1147–1154.
  • Zhang X, Wang N, Schachat AP, et al. Glucocorticoids: structure, signaling and molecular mechanisms in the treatment of diabetic retinopathy and diabetic macular edema. Curr Mol Med. 2014;14(3):376–384.
  • Urbancic M, Gardasevic Topcic I. Dexamethasone implant in the management of diabetic macular edema from clinician’s perspective. Clin Ophthalmol. 2019;13:829–840.
  • Urias EA, Urias GA, Monickaraj F, et al. Novel therapeutic targets in diabetic macular edema: beyond VEGF. Vision Res. 2017;139:221–227.
  • Bandello F, Preziosa C, Querques G, et al. Update of intravitreal steroids for the treatment of diabetic macular edema. Ophthalmic Res. 2014;52(2):89–96.
  • 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. 2018;136(1):29–38.
  • Chen YY, Chang PY, Wang JK. Intravitreal aflibercept for patients with diabetic macular edema refractory to bevacizumab or ranibizumab: analysis of response to aflibercept. Asia Pac J Ophthalmol (Phila). 2017;6(3):250–255.
  • Ibrahim WS, Eldaly ZH, Saleh MG, et al. Switching to aflibercept in diabetic macular edema after unsatisfactory response to other anti-vascular endothelial growth factor drugs. Korean J Ophthalmol. 2019;33(2):122–130.
  • Xiao K, Li FZ, Liang SZ, et al. Efficacy of conversion to aflibercept for diabetic macular edema previously refractory to bevacizumab or ranibizumab: a meta-analysis of high-quality nonrandomized studies. Ann Pharmacother. 2020;1060028020904358.
  • Baker CW, Glassman AR, Beaulieu WT, et al. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical Trial. JAMA. 2019;321(19):1880–1894.
  • Zafar S, Smith K, Boland MV, et al. Real-world outcomes among eyes with center-involving diabetic macular edema and good visual acuity. Curr Eye Res. 2019;1–9. ••This study was significant because it demonstrated that observation without treatment unless visual acuity worsens is reasonable treatment strategy in eyes with center-involving DME. The study considered eyes with center involving DME and good visual acuity, and compared aflibercept vs. laser photocoagulation vs. observation intervention strategies at 2 years.
  • An MM, Zou Z, Shen H, et al. Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis. Eur J Clin Pharmacol. 2010;66(8):813–821.
  • Ranpura V, Hapani S, Chuang J, et al. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol. 2010;49(3):287–297.
  • Zarbin MA, Dunger-Baldauf C, Haskova Z, et al. Vascular safety of ranibizumab in patients with diabetic macular edema: a pooled analysis of patient-level data from randomized clinical trials. JAMA Ophthalmol. 2017;135(5):424–431.
  • Etminan M, Maberley DA, Babiuk DW, et al. Risk of myocardial infarction and stroke with single or repeated doses of intravitreal bevacizumab in age-related macular degeneration. Am J Ophthalmol. 2016;166:205.
  • Reibaldi M, Fallico M, Avitabile T, et al. Risk of death associated with intravitreal anti-vascular endothelial growth factor therapy: a systematic review and meta-analysis. JAMA Ophthalmol. 2019.
  • Zarbin MA. Extending our knowledge on systemic adverse events associated with intravitreal anti-vascular endothelial growth factor therapy. Ophthalmology. 2019;126(7):1016–1017.
  • Maloney MH, Schilz SR, Herrin J, et al. Risk of systemic adverse events associated with intravitreal anti-VEGF therapy for diabetic macular edema in routine clinical practice. Ophthalmology. 2019;126(7):1007–1015.
  • McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011;31(4):654–661.
  • Meyer CH, Michels S, Rodrigues EB, et al. Incidence of rhegmatogenous retinal detachments after intravitreal antivascular endothelial factor injections. Acta Ophthalmol. 2011;89(1):70–75.
  • Hoang QV, Mendonca LS, Della Torre KE, et al. Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections. Ophthalmology. 2012;119(2):321–326.
  • Xu Y, Rong A, Bi Y, et al. Intravitreal conbercept injection with and without grid laser photocoagulation in the treatment of diffuse diabetic macular edema in real-life clinical practice. J Ophthalmol. 2016;2016:2143082.
  • Li F, Zhang L, Wang Y, et al. One-year outcome of conbercept therapy for diabetic macular edema. Curr Eye Res. 2018;43(2):218–223.
  • Xu Y, Qu Y, Suo Y, et al. Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment. BMC Ophthalmol. 2019;19(1):123.
  • Sahni J, Patel SS, Dugel PU, et al. Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-A with faricimab in diabetic macular edema: BOULEVARD phase 2 randomized trial. Ophthalmology. 2019;126(8):1155–1170.
  • Holz FG, Dugel PU, Weissgerber G, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology. 2016;123(5):1080–1089.
  • Dugel PU, Jaffe GJ, Sallstig P, et al. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: a randomized trial. Ophthalmology. 2017;124(9):1296–1304.
  • Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2019.
  • Do DV Update on phase 1b and phase 2 studies of KSI-301: a novel anti-VEGF antibody biopolymer conjugate with potential for extended durability in wet AMD. Presented February 2020 at the Angiogenesis, Exudation, and Degeneration Conference.
  • Conti FF, Alezzandrini A, Rasendran C, et al. An international comparison of baseline characteristics of patients undergoing initiation of anti-VEGF therapy for DME. Ophthalmic Surg Lasers Imaging Retina. 2019;50(11):e300–e10.
  • Stewart MW. Extended duration vascular endothelial growth factor inhibition in the eye: failures, successes, and future possibilities. Pharmaceutics. 2018;10(1):21.

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