Evolving Anti-VEGF Therapy For Diabetic Retinopathy: Current Evidence, Durability Strategies, And Future Directions
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Abstract
Diabetic retinopathy (DR) remains one of the leading causes of vision impairment and blindness among working-age adults worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapy has significantly transformed the management of DR by effectively reducing retinal vascular permeability, inhibiting neovascularization, and improving visual outcomes. This article reviews the evolving role of anti-VEGF agents in the treatment of diabetic retinopathy, highlighting current clinical evidence regarding their efficacy, safety, and comparative performance. Particular attention is given to durability strategies designed to reduce treatment burden, including treat-and-extend regimens, high-dose formulations, sustained-release delivery systems, and emerging long-acting therapeutic approaches. The review also discusses the limitations of existing therapies, such as the need for frequent intravitreal injections, patient adherence challenges, and variability in treatment response. Furthermore, future directions are explored, including novel molecular targets, gene-based therapies, combination treatments, and advancements in personalized medicine supported by artificial intelligence and predictive biomarkers. The findings indicate that while anti-VEGF therapy remains the cornerstone of contemporary diabetic retinopathy management, ongoing innovations aimed at enhancing treatment durability and individualized care have the potential to improve long-term outcomes and reduce the global burden of diabetic eye disease.
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References
Agostini H, Abreu F, Baumal CR, Chang DS, Csaky KG, Demetriades AM, et al. Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes. Graefe s Archive for Clinical and Experimental Ophthalmology [Internet]. Springer Science+Business Media; 2024 June 7 [cited 2025 Aug]; Available from: https://doi.org/10.1007/s00417-024-06531-9
Alali NM, Aljahdali A, AlBalawi HB, Jarallah OJA, Zaïd S, Abuallut I, et al. Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review. Pharmaceuticals [Internet]. 2025 Oct 27 [cited 2026 Mar];18(11):1620–1620. Available from: https://doi.org/10.3390/ph18111620
Aldokhail LS, Alhadlaq A, Alaradi LM, Alaradi LM, AlShaikh FY. Outcomes of Anti-VEGF Therapy in Eyes with Diabetic Macular Edema, Vein Occlusion-Related Macular Edema, and Neovascular Age-Related Macular Degeneration: A Systematic Review. Clinical ophthalmology [Internet]. 2024 Dec 1 [cited 2026 Mar];3837–51. Available from: https://doi.org/10.2147/opth.s489114
Amin R, Kaiser PK. Tyrosine kinase inhibitors for wet age-related macular degeneration: The current developmental landscape. Journal of Pharmacology and Experimental Therapeutics [Internet]. 2026 Jan 9 [cited 2026 Mar];393(3):103803–103803. Available from: https://doi.org/10.1016/j.jpet.2026.103803
Anguita R, Tasiopoulou A, Shahid S, Roth J, Sim SY, Patel PJ. A Review of Aflibercept Treatment for Macular Disease. Ophthalmology and Therapy [Internet]. Adis, Springer Healthcare; 2021 June 13 [cited 2025 Aug];10(3):413–28. Available from: https://doi.org/10.1007/s40123-021-00354-1
Antas P, Carvalho C, Cabral-Teixeira J, Lemos L de, Seabra MC. Toward low-cost gene therapy: mRNA-based therapeutics for treatment of inherited retinal diseases. Trends in Molecular Medicine [Internet]. Elsevier BV; 2023 Dec 2 [cited 2025 Aug];30(2):136–46. Available from: https://doi.org/10.1016/j.molmed.2023.11.009
Arabi A, Tadayoni R, Ahmadieh H, Shahraki T, Nikkhah H. Update on Management of Non-proliferative Diabetic Retinopathy without Diabetic Macular Edema; Is There a Paradigm Shift? Journal of Ophthalmic and Vision Research [Internet]. 2022 Jan 21 [cited 2026 Jan];17(1):108–17. Available from: https://doi.org/10.18502/jovr.v17i1.10175
Arevalo JF, Beatson B, (PACORES) for the PACRSG. LESSONS LEARNED FROM PACORES IN PROLIFERATIVE DIABETIC RETINOPATHY MANAGEMENT, DATA FROM LATIN AMERICA AND SPAIN. Retina [Internet]. 2021 June 3 [cited 2026 Jan];42(1):4–10. Available from: https://doi.org/10.1097/iae.0000000000003226
Awh CC, Barteselli G, Makadia S, Chang RT, Stewart JM, Wieland MR, et al. Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Ophthalmology Retina [Internet]. 2022 May 16 [cited 2026 Jan];6(11):1028–43. Available from: https://doi.org/10.1016/j.oret.2022.05.011
Baker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, 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. JAMA [Internet]. 2019 Apr 30 [cited 2026 May];321(19):1880–1880. Available from: https://doi.org/10.1001/jama.2019.5790
Baumal CR, Bodaghi B, Singer M, Tanzer DJ, Seres A, Joshi MR, et al. Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment. HAL (Le Centre pour la Communication Scientifique Directe) [Internet]. 2020 Sept 29 [cited 2026 May];5(6):519–27. Available from: https://hal.sorbonne-universite.fr/hal-03510415
Banerjee M, Moharana S, Padhy SK. Systemic Effects of Intravitreal Anti-VEGF Therapy: A Review of Safety across Organ Systems. Ophthalmology and Therapy [Internet]. 2025 June 6 [cited 2026 Jan];14(8):1661–84. Available from: https://doi.org/10.1007/s40123-025-01157-4
Bordbar D, Mukhtar A, Loya A, Alsoudi AF, Muayad J, Chauhan MZ, et al. Peri-Event Intravitreal Anti-VEGF and Systemic Outcomes After Stroke or Myocardial Infarction. JAMA Ophthalmology [Internet]. 2026 Mar 26 [cited 2026 Mar]; Available from: https://doi.org/10.1001/jamaophthalmol.2026.0460
Bodaghi B, Khanani AM, Khoramnia R, Pavésio C, Nguyen QD. Gains in the current understanding of managing neovascular AMD with brolucizumab [Internet]. Vol. 13, Journal of Ophthalmic Inflammation and Infection. Springer Nature; 2023 [cited 2025 Oct]. Available from: https://doi.org/10.1186/s12348-023-00369-8
Bourzac K. How can treatment for eye disease be made easier? Nature [Internet]. 2025 Mar 5 [cited 2025 Aug];639(8053). Available from: https://doi.org/10.1038/d41586-025-00655-6
Brown DM, Boyer DS, Diana V, Wykoff CC, Sakamoto T, Win PH, et al. Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial. The Lancet [Internet]. 2024 Mar 1 [cited 2026 May];403(10432):1153–63. Available from: https://doi.org/10.1016/s0140-6736(23)02577-1
Brown DM, Wykoff CC, Boyer DS, Heier JS, Clark WL, Emanuelli A, et al. Evaluation of Intravitreal Aflibercept for the Treatment of Severe Nonproliferative Diabetic Retinopathy. JAMA Ophthalmology [Internet]. 2021 Aug 5 [cited 2025 Aug];139(9):946–946. Available from: https://doi.org/10.1001/jamaophthalmol.2021.2809
Carlà MM, Savastano MC, Boselli F, Giannuzzi F, Rizzo S. Ranibizumab Port Delivery System in Neovascular Age-Related Macular Degeneration: Where Do We Stand? Overview of Pharmacokinetics, Clinical Results, and Future Directions. Pharmaceutics [Internet]. 2024 Feb 23 [cited 2026 Jan];16(3):314–314. Available from: https://doi.org/10.3390/pharmaceutics16030314
Chakraborty D, Mondal S, Boral S, Das A. Intravitreal Injection of Brolucizumab for Recalcitrant Macular Edema due to Central Retinal Vein Occlusion: A Small Case Series. Case Reports in Ophthalmology [Internet]. 2022 Nov 17 [cited 2025 Sept];13(3):912–9. Available from: https://doi.org/10.1159/000526710
Chakravarthy U, Armendariz BG, Fauser S. 15 years of anti-VEGF treatment for nAMD: success or failure or something in between? Eye [Internet]. 2022 June 25 [cited 2025 Sept];36(12):2232–3. Available from: https://doi.org/10.1038/s41433-022-02153-9
Chang M, Kapre A, Kaufman D, Kardatzke DR, Rabena M, Patel S, et al. Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration. JAMA Ophthalmology [Internet]. 2022 June 16 [cited 2025 Oct];140(8):771–771. Available from: https://doi.org/10.1001/jamaophthalmol.2022.1091
Chang M, Bobbala A, Malhotra V, Latkany P. 435-P: Port Delivery System with Ranibizumab (PDS) in Diabetic Retinopathy (DR) with or without Diabetic Macular Edema (DME). Diabetes [Internet]. 2021 June 1 [cited 2025 Nov];70. Available from: https://doi.org/10.2337/db21-435-p
Chen KS, Chan HC, Chan C. Can Gene Therapy Transform the Treatment Landscape of Posterior Segment Eye Diseases? A Comprehensive Review of Recent Advancements. Drugs [Internet]. Adis, Springer Healthcare; 2025 Oct 25 [cited 2025 Oct]; Available from: https://doi.org/10.1007/s40265-025-02237-2
Choi K, Park SJ, Yoon H, Choi S, Mun Y, Kim S, et al. Patient-Centered Economic Burden of Diabetic Macular Edema: Retrospective Cohort Study (Preprint). JMIR Public Health and Surveillance [Internet]. 2024 July 22 [cited 2025 Aug];10. Available from: https://doi.org/10.2196/56741
Chou JF, Wu J, Chen Y, Chen S. Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan. Scientific Reports [Internet]. 2023 Nov 7 [cited 2025 Aug];13(1). Available from: https://doi.org/10.1038/s41598-023-43931-z
Choudhary A, Gopalakrishnan N, Joshi A, Balakrishnan D, Chhablani J, Yadav NK, et al. Recommendations for diabetic macular edema management by retina specialists and large language model-based artificial intelligence platforms. International Journal of Retina and Vitreous [Internet]. 2024 Feb 28 [cited 2025 Sept];10(1). Available from: https://doi.org/10.1186/s40942-024-00544-6
ClinicalTrials.gov. A study of RGX-314 gene therapy in participants with diabetic retinopathy without center-involved diabetic macular edema (ALTITUDE). National Library of Medicine; 2025.
Eichenbaum D, Ahmed A, Hiya FE. Ranibizumab port delivery system: a clinical perspective. BMJ Open Ophthalmology [Internet]. 2022 Sept 1 [cited 2025 Nov];7(1). Available from: https://doi.org/10.1136/bmjophth-2022-001104
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 12. Retinopathy, Neuropathy, and Foot Care:Standards of Care in Diabetes—2023. Diabetes Care [Internet]. American Diabetes Association; 2022 Dec 12 [cited 2025 Aug];46. Available from: https://doi.org/10.2337/dc23-s012
ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, et al. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2024. Diabetes Care [Internet]. American Diabetes Association; 2023 Dec 11 [cited 2025 Aug];47. Available from: https://doi.org/10.2337/dc24-s012
ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Cusi K, et al. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes—2024. Diabetes Care [Internet]. American Diabetes Association; 2023 Dec 11 [cited 2025 Aug];47. Available from: https://doi.org/10.2337/dc24-s004
Fabre M. Design, synthesis and optimization of new CXCR1/2 receptors antagonists for the treatment of exudative AMD. HAL (Le Centre pour la Communication Scientifique Directe) [Internet]. 2021 June 25 [cited 2025 Oct]; Available from: https://theses.hal.science/tel-04213493
Fung N, Ho M, Cheung CMG, Kwok AK, Lee GK, Ng DS, et al. Consensus on managing center-involving diabetic macular edema in Hong Kong: perspective. Hong Kong Journal of Ophthalmology [Internet]. 2024 Jan 2 [cited 2025 Oct];27(2):61–9. Available from: https://doi.org/10.12809/hkjo-v27n2-365
Friedman SM, Xu Y, Sherman S, Kuznik A, Mojebi A, Keeping S, et al. Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials. Ophthalmology and Therapy [Internet]. 2025 Sept 25 [cited 2025 Sept]; Available from: https://doi.org/10.1007/s40123-025-01247-3
Gabrielle P, Mehta H, Barthelmes D, Daïen V, Nguyen V, Gillies MC, et al. From randomised controlled trials to real-world data: Clinical evidence to guide management of diabetic macular oedema. Progress in Retinal and Eye Research [Internet]. Elsevier BV; 2023 Oct 27 [cited 2025 Aug];97:101219–101219. Available from: https://doi.org/10.1016/j.preteyeres.2023.101219
Genitsaridi I, Salpea P, Salim A, Sajjadi SF, Tomic D, James S, et al. 11th edition of the IDF Diabetes Atlas: global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050. The Lancet Diabetes & Endocrinology [Internet]. 2025 Dec 16 [cited 2026 May];14(2):149–56. Available from: https://doi.org/10.1016/s2213-8587(25)00299-2
Glassman AR, Wells JA, Josic K, Maguire MG, Antoszyk AN, Baker CW, et al. Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study). Ophthalmology [Internet]. 2020 Mar 28 [cited 2026 May];127(9):1201–10. Available from: https://doi.org/10.1016/j.ophtha.2020.03.021
Garcia JMB de B, Costa G da SF da, Isaac DLC, Ávila MP de. Treat-and-Extend: otimização de desfechos no tratamento da degeneração macular relacionada à idade na forma neovascular. eOftalmo [Internet]. 2021 Jan 1 [cited 2025 Mar];7(2). Available from: https://doi.org/10.17545/eoftalmo/2021.0013
Garweg JG, Blum C, Copt RP, Eandi CM, Hatz K, Prünte C, et al. Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects. Ophthalmology and Therapy [Internet]. 2023 Jan 12 [cited 2025 Oct];12(2):639–55. Available from: https://doi.org/10.1007/s40123-023-00647-7
Giudice GL, Galan A, Gattazzo I. Introductory Chapter: Treatment of Medical Retinal Diseases by Surgical Approaches – Mini-Review of the Latest Advances in the Field of Ophthalmology. In: IntechOpen eBooks [Internet]. IntechOpen; 2023 [cited 2025 Oct]. Available from: https://doi.org/10.5772/intechopen.112174
Heyworth P. Bevacizumab for blinding eye disease – is it time for the PBS to list for off-label use? Australian Health Review [Internet]. 2022 Mar 23 [cited 2025 Nov];46(2):150–2. Available from: https://doi.org/10.1071/ah21379
Huang X, Zhang L, Fu Y, Zhang M, Yang Q, Peng J. Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy. Frontiers in Bioengineering and Biotechnology [Internet]. Frontiers Media; 2023 May 23 [cited 2025 Oct];11. Available from: https://doi.org/10.3389/fbioe.2023.1199922
Holekamp NM, Gentile B, Giocanti‐Auregan A, García‐Layana A, Pető T, Viola F, et al. Patient Experience Survey Of Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema. Ophthalmic Research [Internet]. 2024 Apr 29 [cited 2026 Mar];67(1):311–21. Available from: https://doi.org/10.1159/000538975
Hutton DW, Glassman AR, Liu D, Sun JK, Network DR, Sneath M, et al. Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema. JAMA Ophthalmology [Internet]. 2023 Feb 2 [cited 2026 Jan];141(3):268–268. Available from: https://doi.org/10.1001/jamaophthalmol.2022.6142
Işık P, Sızmaz S, Esen E, Uysal A, Demircan N. Comparison of intravitreal ranibizumab and aflibercept for the treatment of diabetic macular edema: a real-world study. International Ophthalmology [Internet]. 2023 July 28 [cited 2025 Oct];43(11):4171–80. Available from: https://doi.org/10.1007/s10792-023-02820-0
Jhaveri C, Glassman AR, Ferris FL, Liu D, Maguire MG, Allen JB, et al. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. New England Journal of Medicine [Internet]. 2022 July 14 [cited 2026 May];387(8):692–703. Available from: https://doi.org/10.1056/nejmoa2204225
Korobelnik J, Diana V, Schmidt‐Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal Aflibercept for Diabetic Macular Edema. Ophthalmology [Internet]. 2014 July 8 [cited 2026 May];121(11):2247–54. Available from: https://doi.org/10.1016/j.ophtha.2014.05.006
Kim YC, Shin JP, Pak KY, Kim HW, Sagong M, Lee SJ, et al. Two-year outcomes of the treat-and-extend regimen using aflibercept for treating diabetic macular oedema. Scientific Reports [Internet]. 2020 Dec 16 [cited 2025 Aug];10(1). Available from: https://doi.org/10.1038/s41598-020-78954-3
Kim JS, Lee S, Kim JY, Seo EJ, Chae JB, Kim DY. Visual/anatomical outcome of diabetic macular edema patients lost to follow-up for more than 1 year. Scientific Reports [Internet]. 2021 Sept 15 [cited 2025 Aug];11(1). Available from: https://doi.org/10.1038/s41598-021-97644-2
Khachigian LM, Liew G, Teo KYC, Wong TY, Mitchell P. Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration. Journal of Translational Medicine [Internet]. BioMed Central; 2023 Feb 21 [cited 2025 Oct];21(1). Available from: https://doi.org/10.1186/s12967-023-03937-7
Khoramnia R, Figueroa MS, Hattenbach L, Pavésio C, Anderesi M, Schmouder R, et al. Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD. Graefe s Archive for Clinical and Experimental Ophthalmology [Internet]. 2021 Dec 21 [cited 2025 July];260(6):1843–56. Available from: https://doi.org/10.1007/s00417-021-05518-0
Kaiser PK, Giani A, Fuchs H, Chong V, Heier JS. Factors That Can Prolong Ocular Treatment Duration in Age-Related Macular Degeneration. Ophthalmic Research [Internet]. Karger Publishers; 2023 Jan 1 [cited 2025 Oct];653–63. Available from: https://doi.org/10.1159/000527815
Khanani AM, Campochiaro PA, Graff JM, Marcus DM, Miller DM, Mittra RA, et al. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema [Internet]. Vol. 143, JAMA Ophthalmology. American Medical Association; 2025 [cited 2025 Dec]. p. 326–326. Available from: https://doi.org/10.1001/jamaophthalmol.2025.0006
Kuznik A, Coughlan A, Pinsent A, Toro‐Díaz H, Sherman S, Patel N. Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US. Ophthalmology and Therapy [Internet]. 2025 Sept 19 [cited 2025 Oct]; Available from: https://doi.org/10.1007/s40123-025-01236-6
Lam LA, Mehta S, Lad EM, Emerson GG, Jumper JM, Awh CC, et al. Intravitreal Injection Therapy: Current Techniques and Supplemental Services. Journal of VitreoRetinal Diseases [Internet]. 2021 July 22 [cited 2025 Nov];5(5):438–47. Available from: https://doi.org/10.1177/24741264211028441
Lowater SJ, Grauslund J, Subhi Y, Vergmann AS. Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review. Ophthalmology and Therapy [Internet]. Adis, Springer Healthcare; 2023 Dec 6 [cited 2025 Aug];13(1):51–69. Available from: https://doi.org/10.1007/s40123-023-00843-5
Liu Z, Chen H, Zheng L, Sun L, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduction and Targeted Therapy [Internet]. Springer Nature; 2023 May 11 [cited 2025 Oct];8(1). Available from: https://doi.org/10.1038/s41392-023-01460-1
Leroy BP, Fischer MD, Flannery JG, MacLaren RE, Dalkara D, Scholl HPN, et al. Gene Therapy for Inherited Retinal Disease: Long-Term Durability of Effect. Ophthalmic Research [Internet]. Karger Publishers; 2022 Sept 14 [cited 2025 Oct];66(1):179–96. Available from: https://doi.org/10.1159/000526317
Lee B, Josic K, Nittala MG, Velaga SB, Karamat A, Srinivas S, et al. Long-Term Effects of Intravitreal Ranibizumab Compared With Panretinal Photocoagulation on Optical Coherence Tomography Measured Choroidal Thickness and Vascularity. Translational Vision Science & Technology [Internet]. 2024 July 26 [cited 2025 July];13(7):19–19. Available from: https://doi.org/10.1167/tvst.13.7.19
Liu Z, Han J, Li X. Integrative Management of High-Risk Proliferative Diabetic Retinopathy: Precision Diagnostics via Ultra-Widefield Imaging and Therapeutic Strategies. Diabetes Metabolic Syndrome and Obesity [Internet]. 2025 Oct 1 [cited 2025 Oct];3813–32. Available from: https://doi.org/10.2147/dmso.s535338
Li S, Tang J, Han X, Wang Z, Zhang L, Zhao M, et al. Prospective Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients. Ophthalmology and Therapy [Internet]. 2022 July 29 [cited 2025 Oct];11(5):1833–45. Available from: https://doi.org/10.1007/s40123-022-00550-7
Luckham K, Tebbs H, Dadswell C, Yosef AH, Claxton L, Kelley K, et al. Cost-effectiveness of anti-vascular endothelial growth factor and macular laser treatments for people with centre-involving diabetic macular oedema and central retinal thickness of at least 400 micrometres. Eye [Internet]. 2025 Sept 19 [cited 2025 Oct]; Available from: https://doi.org/10.1038/s41433-025-04015-6
M. B David, Quan DN, M. M Dennis, S. B David, Sunil P, Leonard F, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Graduate Medical Education Research Journal [Internet]. 2013 Oct 1 [cited 2026 Feb]; Available from: https://digitalcommons.unmc.edu/com_eye_articles/41
Mayor R. Are We Overusing Anti-vascular Endothelial Growth Factor? – Reflections on Treatment Burden and Real-World Outcomes. Delhi Journal of Ophthalmology [Internet]. 2025 Oct 1 [cited 2025 Dec];35(4):247–247. Available from: https://doi.org/10.4103/dljo.dljo_225_25
Manders EA, Wel V van der, Schlingemann RO, Hollak CEM, Visser SJ de. Repurposing biosimilars, rethinking costs: a framework for sustainable drug pricing for repurposed bevacizumab for intravitreal injections. The European Journal of Health Economics [Internet]. 2026 Feb 7 [cited 2026 Mar]; Available from: https://doi.org/10.1007/s10198-025-01891-3
Montesel A, Bucolo C, Sallo FB, Eandi CM. Short-Term Efficacy and Safety Outcomes of Brolucizumab in the Real-Life Clinical Practice. Frontiers in Pharmacology [Internet]. 2021 Nov 4 [cited 2025 Sept];12. Available from: https://doi.org/10.3389/fphar.2021.720345
Moret E, Ambresin A, Gianniou C, Bijon J, Besse-Hayat C, Bogiatzi S, et al. Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors. Graefe s Archive for Clinical and Experimental Ophthalmology [Internet]. 2021 Sept 16 [cited 2025 Sept];260(3):1005–14. Available from: https://doi.org/10.1007/s00417-021-05353-3
Nagy A, Börzsei D, Hoffmann A, Török S, Veszelka M, Almási N, et al. A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms. Cardiovascular Drugs and Therapy [Internet]. 2024 Mar 16 [cited 2025 Sept]; Available from: https://doi.org/10.1007/s10557-024-07574-0
Nanegrungsunk O, Bressler NM. Prevention of vision-threatening complications in diabetic retinopathy: two perspectives based on results from the DRCR Retina Network Protocol W and the Regeneron-sponsored PANORAMA. Current Opinion in Ophthalmology [Internet]. 2021 Aug 20 [cited 2025 Nov];32(6):590–8. Available from: https://doi.org/10.1097/icu.0000000000000799
Network TDRCR. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. New England Journal of Medicine [Internet]. 2015 Feb 18 [cited 2026 May];372(13):1193–203. Available from: https://doi.org/10.1056/nejmoa1414264
Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Ranibizumab for Diabetic Macular Edema. Ophthalmology [Internet]. 2012 Feb 11 [cited 2026 May];119(4):789–801. Available from: https://doi.org/10.1016/j.ophtha.2011.12.039
Odio-Herrera M, Orozco-Loaiza G, Wu L. Gene Therapy in Diabetic Retinopathy and Diabetic Macular Edema: An Update. Journal of Clinical Medicine [Internet]. 2025 May 6 [cited 2026 Mar];14(9):3205–3205. Available from: https://doi.org/10.3390/jcm14093205 Patel AJ, Pieramici DJ, Bagheri N. Evaluation of Port Delivery System With Ranibizumab for the Treatment of Neovascular age-related Macular Degeneration. Therapeutic Delivery [Internet]. 2021 Mar 1 [cited 2025 Nov];12(3):191–200. Available from: https://doi.org/10.4155/tde-2020-0132
Pichi F, Abdi AM, Aljneibi S, Ghrably IE, Agarwal A, Ghazi NG. Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema. International Ophthalmology [Internet]. 2024 June 25 [cited 2025 July];44(1). Available from: https://doi.org/10.1007/s10792-024-03226-2
Pieramici DJ, Campochiaro PA, Chang M, Pearce I, Regillo CD, Gune S, et al. Structural Updates to the Implant and Refill Needle of the Port Delivery Platform. Translational Vision Science & Technology [Internet]. 2025 Apr 7 [cited 2025 Nov];14(4):8–8. Available from: https://doi.org/10.1167/tvst.14.4.8
Pramanik S, Mondal LK, Paine SK, Jain SS, Chowdhury S, Ganguly U, et al. Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population. Clinical ophthalmology [Internet]. 2021 Aug 1 [cited 2026 Jan];3341–50. Available from: https://doi.org/10.2147/opth.s317771
Panos GD, Lakshmanan A, Dadoukis P, Ripa M, Motta L, Amoaku WMK. Faricimab: Transforming the Future of Macular Diseases Treatment - A Comprehensive Review of Clinical Studies. Drug Design Development and Therapy [Internet]. Dove Medical Press; 2023 Sept 1 [cited 2025 Aug];2861–73. Available from: https://doi.org/10.2147/dddt.s427416
Pető T, Vujosevic S, Sheth V, Downey AE, Gibson K, Pollreisz A. Does the Efficacy, Durability, and Safety of Faricimab for Diabetic Macular Edema in Randomized Trials Translate into Real-World Settings? Ophthalmology and Therapy [Internet]. 2025 Sept 19 [cited 2025 Oct]; Available from: https://doi.org/10.1007/s40123-025-01233-9
Pollreisz A, Gasser‐Steiner V, Gerendas BS, Mennel S, Radda S, Sacu S, et al. Diagnosis, treatment and monitoring of diabetic eye disease (Update 2023). Wiener klinische Wochenschrift [Internet]. 2023 Jan 1 [cited 2025 Oct];135:195–200. Available from: https://doi.org/10.1007/s00508-022-02119-7
Perais J, Agarwal R, Evans J, Loveman E, Colquitt JL, Owens DR, et al. Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane library [Internet]. Elsevier BV; 2023 Feb 22 [cited 2025 Oct];2023(2). Available from: https://doi.org/10.1002/14651858.cd013775.pub2
Pieramici DJ, Wieland MR, Stewart JM, Chang RT, Gune S, Malhotra VK, et al. Implant Insertion Procedure of the Port Delivery System With Ranibizumab: Overview and Clinical Pearls. Ophthalmic surgery, lasers & imaging retina [Internet]. 2022 May 1 [cited 2025 Nov];53(5):249–56. Available from: https://doi.org/10.3928/23258160-20220408-01
Qassimi NA, Kozak I, Karam MA, Neri P, Aduriz-Lorenzo PM, Attawan A, et al. Management of Diabetic Macular Edema: Guidelines from the Emirates Society of Ophthalmology. Ophthalmology and Therapy [Internet]. 2022 July 27 [cited 2025 Oct];11(5):1937–50. Available from: https://doi.org/10.1007/s40123-022-00547-2
Quist SW, Paulissen J, Lunk I, Carrasco J, Woudstra M, Pochopień M, et al. Anti-VEGFs for Diabetic Macular Oedema: Analysis of Efficacy, Safety, and Cost of More Durable Therapies from a Dutch Societal Perspective. Advances in Therapy [Internet]. 2025 June 7 [cited 2026 Jan];42(8):3774–94. Available from: https://doi.org/10.1007/s12325-025-03233-4
Ranade SV, Wieland MR, Tam T, Rea JC, Horvath J, Hieb AR, et al. The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery. Drug Delivery [Internet]. 2022 May 2 [cited 2026 Mar];29(1):1326–34. Available from: https://doi.org/10.1080/10717544.2022.2069301
Ratra D. Commentary [Internet]. Vol. 69, Indian Journal of Ophthalmology. Medknow; 2021 [cited 2026 Jan]. p. 367–8. Available from: https://doi.org/10.4103/ijo.ijo_2611_20
R R, S FB, A K, M M, RD H, SD E, 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. UCL Discovery (University College London) [Internet]. 2012 Aug 1 [cited 2025 Nov]; Available from: http://discovery.ucl.ac.uk/1344640/
Sharma A, Khanani AM, Parachuri N, Kumar N, Bandello F, Kuppermann BD. Port delivery system with ranibizumab (Susvimo) recall- What does it mean to the retina specialists. International Journal of Retina and Vitreous [Internet]. 2023 Jan 30 [cited 2025 Oct];9(1). Available from: https://doi.org/10.1186/s40942-023-00446-z
Shimura M, Oh H, Ueda T, Kitano S, Mitamura Y, Sato J, et al. Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial. Japanese Journal of Ophthalmology [Internet]. 2024 July 31 [cited 2025 Aug];68(5):511–22. Available from: https://doi.org/10.1007/s10384-024-01078-y
Schmidt‐Erfurth U, García‐Arumí J, Bandello F, Berg KM, Chakravarthy U, Gerendas BS, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica [Internet]. 2017 Jan 1 [cited 2026 May];237(4):185–222. Available from: https://doi.org/10.1159/000458539
Singh RP, Welch L, Longo NL, Frese M. Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change. Research Square (Research Square) [Internet]. 2023 Mar 17 [cited 2025 Aug]; Available from: https://doi.org/10.21203/rs.3.rs-2565067/v1
Sheng X, Zhang C, Zhao J, Xu J, Zhang P, Ding Q, et al. Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components. Cell & Bioscience [Internet]. 2024 June 27 [cited 2025 Oct];14(1). Available from: https://doi.org/10.1186/s13578-024-01269-7
Shen L, Zheng Y, Gao Z, Li Q, Dai M, Yang W, et al. Efficacy and safety of intravitreal injection of conbercept for moderate to severe nonproliferative diabetic retinopathy. Frontiers in Medicine [Internet]. 2024 May 23 [cited 2025 Oct];11. Available from: https://doi.org/10.3389/fmed.2024.1394358
Song JR, Park KH, Kang SW, Chin HS, Yu SY, Park YH, et al. Consensus of Expert Recommendations for the Safe Administration of Brolucizumab in Neovascular Age-related Macular Degeneration. Korean Journal of Ophthalmology [Internet]. 2025 Aug 5 [cited 2026 Jan];39(4):362–8. Available from: https://doi.org/10.3341/kjo.2025.0010
Sheth VS, Schlottmann P, Lai TYY, Abreu F, Chang A, Eter N, et al. Four-Year Outcomes of Faricimab in Diabetic Macular Edema. Ophthalmology [Internet]. 2026 Jan 1 [cited 2026 Mar]; Available from: https://doi.org/10.1016/j.ophtha.2026.01.001
Stanga P, Valentín-Bravo FJ, Stanga S, Reinstein UI, Pastor‐Idoate S, Downes SM. Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic. Eye [Internet]. 2023 Mar 23 [cited 2025 Oct];37(15):3282–9. Available from: https://doi.org/10.1038/s41433-023-02505-z
Sivaprasad S, Reed K, Morgan-Warren P, Leal S, Berliner AJ. Infographic: Efficacy and safety of high-dose intravitreal aflibercept 8 mg in patients with diabetic macular oedema: Week 48 results from the phase 2/3 PHOTON trial. Eye [Internet]. 2025 Jan 31 [cited 2026 Mar]; Available from: https://doi.org/10.1038/s41433-024-03564-6
Sambhara D, Vakharia P, Eichenbaum D. Real-world efficacy and safety of 8 mg aflibercept in neovascular AMD: a case series. BMJ Open Ophthalmology [Internet]. 2025 Feb 1 [cited 2026 Mar];10(1). Available from: https://doi.org/10.1136/bmjophth-2024-002091
Tan T, Wong TY. Diabetic retinopathy: Looking forward to 2030. Frontiers in Endocrinology [Internet]. Frontiers Media; 2023 Jan 9 [cited 2025 Oct];13. Available from: https://doi.org/10.3389/fendo.2022.1077669
Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045. Ophthalmology [Internet]. 2021 May 1 [cited 2026 May];128(11):1580–91. Available from: https://doi.org/10.1016/j.ophtha.2021.04.027
Wang L, Liu W, Broussy S, Han B, Fang H. Recent advances of anti-angiogenic inhibitors targeting VEGF/VEGFR axis. Frontiers in Pharmacology [Internet]. 2024 Jan 4 [cited 2025 Oct];14. Available from: https://doi.org/10.3389/fphar.2023.1307860
Watkins C, Paulo T, Bührer C, Holekamp NM, Bagijn M. Comparative Efficacy, Durability and Safety of Faricimab in the Treatment of Diabetic Macular Edema: A Systematic Literature Review and Network Meta-Analysis. Advances in Therapy [Internet]. 2023 Sept 26 [cited 2026 May];40(12):5204–21. Available from: https://doi.org/10.1007/s12325-023-02675-y
Wong TY, Hašková Z, Asik K, Baumal CR, Csaky KG, Eter N, et al. Faricimab Treat-and-Extend for Diabetic Macular Edema. Ophthalmology [Internet]. 2023 Dec 28 [cited 2025 Aug];131(6):708–23. Available from: https://doi.org/10.1016/j.ophtha.2023.12.026
Wong TY, Wykoff CC, Heier JS, Eichenbaum DA, Clark WL, Androudi S. Faricimab treat-and-extend for diabetic macular edema: Two-year results from the randomized phase 3 YOSEMITE and RHINE trials. Ophthalmology. 2024;131(6):708–23.
Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. Ophthalmology [Internet]. 2016 Feb 27 [cited 2026 May];123(6):1351–9. Available from: https://doi.org/10.1016/j.ophtha.2016.02.022
Wong HL, Fung N, Kwok AKH. Brolucizumab and faricimab as new treatment options for diabetic macular edema: perspective. Hong Kong Journal of Ophthalmology [Internet]. 2022 Dec 29 [cited 2025 Oct];26(2):53–7. Available from: https://doi.org/10.12809/hkjo-v26n2-327
Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. The Lancet [Internet]. 2022 Jan 24 [cited 2026 May];399(10326):741–55. Available from: https://doi.org/10.1016/s0140-6736(22)00018-6
Wykoff CC, Campochiaro PA, Pieramici DJ, Khanani AM, Gune S, Maia M, et al. Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration. Ophthalmology and Therapy [Internet]. 2022 June 27 [cited 2025 Oct];11(5):1705–17. Available from: https://doi.org/10.1007/s40123-022-00532-9
Xu D, Khan M, Ho AC. Creating an Ocular Biofactory: Surgical Approaches in Gene Therapy for Acquired Retinal Diseases. Asia-Pacific Journal of Ophthalmology [Internet]. 2021 Jan 1 [cited 2025 Nov];10(1):5–11. Available from: https://doi.org/10.1097/apo.0000000000000362
Yılmaz M, Çıtırık M, Rahmanlar H, Alkan A, Gürsöz H. Off-label uses of Aflibercept, Ranibizumab and Dexamethasone implant for diabetic retinopathy in Turkey. Romanian Journal of Ophthalmology [Internet]. 2022 Dec 15 [cited 2025 Aug];66(4). Available from: https://doi.org/10.22336/rjo.2022.56
Zhai G, Liu N, Wang S, Zhang X. Comparative efficacy of intravitreal aflibercept biosimilar QL1207 versus reference aflibercept in the treatment of diabetic macular edema. Frontiers in Medicine [Internet]. 2025 Oct 21 [cited 2025 Oct];12. Available from: https://doi.org/10.3389/fmed.2025.1662735
Zhao M, Chandra A, Liu L, Zhang L, Xu J, Li J. Investigation of the reasons for delayed presentation in proliferative diabetic retinopathy patients. medRxiv (Cold Spring Harbor Laboratory) [Internet]. 2023 Aug 28 [cited 2025 June]; Available from: https://doi.org/10.1101/2023.08.27.23294689