Current Treatments for Diabetic Macular Edema
Abstract
:1. Introduction
2. Pathogenesis of Diabetic Retinopathy and DME
3. Treatments for Diabetic Macular Edema
3.1. Anti-VEGF Treatment
3.1.1. Ranibizumab
3.1.2. Aflibercept
3.1.3. Bevacizumab
3.1.4. Faricimab
3.1.5. Brolucizumab
3.2. Topical Corticosteroid Treatment
3.2.1. Intravitreal Injection of Triamcinolone Acetonide (IVTA)
3.2.2. Subtenon Triamcinolone Acetonide Injection (STTA)
3.2.3. Intravitreal Sustained-Release Steroid Implants
3.2.4. Switching to Steroid Treatments from Anti-VEGF Treatments
3.2.5. STTA or IVTA during Cataract Surgery for Eyes with DME
3.3. Laser Photocoagulation
3.3.1. Focal/Grid Laser
3.3.2. Subthreshold Laser Treatments
PASCAL and Endpoint Management (EpM) Algorithm
Micropulse Diode Laser
3.3.3. Navigated Laser
3.3.4. Selective Retina Therapy
3.4. Combination Therapy with Laser Photocoagulation and Anti-VEGF Agents
3.4.1. Grid Laser + Anti-VEGF Combined Treatments
3.4.2. Focal Laser + Anti-VEGF Treatments
3.4.3. Combined Navigated Laser + Anti-VEGF
3.4.4. Subthreshold Laser + Anti-VEGF
3.4.5. Targeted Retinal Photocoagulation (TRP) + Anti-VEGF
3.5. Pars Plana Vitrectomy
3.5.1. Efficacy of Vitrectomy for DME Refractory to Anti-VEGF Treatment
3.5.2. New Surgical Procedures
3.6. Agents for Systemic Treatments
3.6.1. SGLT2 Inhibitor
3.6.2. Fenofibrate
3.6.3. Metformin
3.7. Recommended Treatment for DME
4. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Anti-VEGF Agents | Ranibizumab | Aflibercept | Bevacizumab | Faricimab | Brolucizumab |
---|---|---|---|---|---|
Molecular format | Fab fragment | VEGFR1/2-Fc fusion protein | Full antibody (lgG1) | anti-VEGF/anti-Ang-2 humanized bispecific monoclonal antibody | Single-chain variable fragment |
Molecular weight | ~48 × 103 | 97–115 × 103 | ~149 × 103 | 150 × 103 | 26 × 103 |
Binding molecule | VEGF-A | VEGF-A, VEGF-B, PlGF-1, PlGF-2 | VEGF-A | VEGF-A, Ang-2 | VEGF-A |
Clinical dose | 0.50 mg | 2.0 mg | 1.25 mg | 6.0 mg | 6.0 mg |
Relative number of molecules per injection | 0.5–0.6 | 1.0 | 0.4–0.5 | 1.15 | 11.2–13.3 |
Author/Journal/Year | Material and Protocol Study Period | Retreatment Criteria | Study Design Follow-Up Periods | Patient Inclusion Criteria of CRT and BCVA | CRT (µm) Baseline ⇒ Final * Difference | BCVA (logMAR) Baseline ⇒ Final * Difference | No. of Injections | † p |
---|---|---|---|---|---|---|---|---|
Moisseiev E et al. Eur J Ophthalmol 2018 [136] | IVR + SML vs. IVR Jan 2013–Jun 2015 | Retrospective 12 months | n = 38 (19 vs. matched control 19) All patients had no more than 3 prior IVR | IVR 408.4 ⇒ 335.9 72.5 | 0.41 ⇒ 0.39 0.02 | 5.6/12 months | <0.001 | |
IVR + SML 316.8 ⇒ 282.6 34.2 | 0.29 ⇒ 0.24 0.05 | 1.7/12 months | ||||||
Altınel MG, et al. Lasers Med Sci. 2021 [137] | IVB + SML vs. IVB Sep 2017–Mar 2020 | Retrospective 15 months | n = 80 (40 vs. 40) Excluded intravitreal injections within the preceding 6 months, CRT > 250 µm | IVB 384.7 ⇒ 325.8 58.9 | 0.39 ⇒ 0.32 0.07 | 8.65/15 months | <0.05 | |
IVB + SML 379.2 ⇒ 292.6 86.6 | 0.38 ⇒ 0.25 0.13 | 7.38/15 months | ||||||
El Matri L, et al. Ther Adv Ophthalmol. 2021 [138] | IVB + SML vs. IVB 3 + PRN Jan 2015–Jan 2019 | BCVA ⩽ 20/25 Presence of IRF and/or SRF | Retrospective 12 months | n = 98 eyes (49 vs. 49) (63 patients) Treatment naïve for DME CRT ⩽ 500 µm, BCVA ⩾ 20/400 | IVB 359.9 ⇒ 305.9 54.0 | 0.60 ⇒ 0.49 0.11 | 7.2/12 months | <0.005 |
IVB + SML 479.1 ⇒ 289.6 189.5 | 0.69 ⇒ 0.50 0.19 | 4.1/12 months | ||||||
Khattab AM et al. Graefes Arch Clin Exp Ophthalmol 2019 [139] | IVA + SML vs. IVA 3 + PRN Feb 2017–Dec 2018 | CRT > 250 µm | Prospective 18 months | n = 54 eyes (27 vs. 27) (51 patients) Excluded intravitreal injections within the preceding 6 months, CRT > 250 µm, BCVA: 20/400–20/40 | IVA 462.0 ⇒ 249.5 212.5 | ‡ 31.7 ⇒ 50.6 18.9 (0.378) | 7.3/18 months | <0.005 |
IVA + SML 457.1 ⇒ 244.6 212.5 | ‡ 35.0 ⇒ 54.8 19.8 (0.396) | 4.1/18 months | ||||||
Kanar HS et al. Ind J Ophthalmol 2020 [141] | IVA + SML vs. IVA 3 + PRN Apr 2015–Nov 2017 | 20% increase in CRT 1-line decrease at BCVA | Prospective 12 months | n = 56 (28 vs. 28) Treatment naïve for DME CRT ≧ 300 µm, BCVA: 0.2–0.9 | IVA 451.28 ⇒ 328.8 122.5 | 0.38 ⇒ 0.20 0.18 | 5.39/12 months | <0.001 |
IVA + SML 466.07 ⇒ 312.0 154.1 | 0.40 ⇒ 0.17 0.23 | 3.21/12 months | ||||||
Abouhussein MA et al. Int Ophthalmol 2020 [140] | IVA + SML vs. IVA 3 + PRN period: not stated | CRT ≧ 300 µm | Prospective 15 months | n = 40 (20 vs. 20) Treatment naïve for DME CRT ≧ 300 µm, BCVA > 3/60 | IVA 457.9 ⇒ 290.5 167.4 | 0.70 ⇒ 0.24 0.46 | 8.4/15 months | 0.029 |
IVA + SML 469.6 ⇒ 288.5 181.1 | 0.76 ⇒ 0.20 0.56 | 7.5/15 months | ||||||
Koushan K et al. Clin Ophthalmol 2022 [142] | IVA + SML vs. IVA 1 (Continue until ME resolves) + PRN Mar 2017–Oct 2018 | 10% change in CRT 1-Snellen-line change at BCVA | Prospective 12 months | n = 30 (15 vs. 15) Excluded intravitreal injections within the preceding 120 days, CRT > 310 µm, BCVA: 20/400–20/30 | IVA 433.4 ⇒ 288.3 145.1 | 0.38 ⇒ 0.32 0.06 | 8.5/12 months | 0.61 |
IVA + SL 457.8 ⇒ 289.5 168.3 | 0.36 ⇒ 0.22 0.14 | 7.9/12 months | ||||||
Tatsumi T et al. Sci Rep 2022 [143] | IVA + SL vs. IVA 3 + PRN Sep 2016–Sep 2020 | 100 µm increase in CRT 2-line decrease at BCVA | Prospective 24 months | n = 51 (25 vs. 26) Excluded intravitreal injections within the preceding 90 days, CRT > 300 µm, BCVA: 0.05–0.7 | IVA 442.8 ⇒ 319.5 123.3 | 0.37 ⇒ 0.32 0.05 | 5.86/24 months | 0.86 |
IVA + SL 472.8 ⇒ 329.5 143.3 | 0.48 ⇒ 0.28 0.20 | 6.05/24 months |
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Tatsumi, T. Current Treatments for Diabetic Macular Edema. Int. J. Mol. Sci. 2023, 24, 9591. https://doi.org/10.3390/ijms24119591
Tatsumi T. Current Treatments for Diabetic Macular Edema. International Journal of Molecular Sciences. 2023; 24(11):9591. https://doi.org/10.3390/ijms24119591
Chicago/Turabian StyleTatsumi, Tomoaki. 2023. "Current Treatments for Diabetic Macular Edema" International Journal of Molecular Sciences 24, no. 11: 9591. https://doi.org/10.3390/ijms24119591