Efficacy of pars plana vitrectomy combined with intravitreal dexamethasone for proliferative diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Qiu Aowang , Yu Hao , Liu Qinghuai ,  Zhang Weiwei

Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

Corresponding author：

Zhang Weiwei, Email: zhang_weiwei@njmu.edu.cn

Keywords：

Proliferative diabetic retinopathy; Intravitreal dexamethasone implant; Pars plana vitrectomy

DOI：

10.3760/cma.j.cn511434-20240105-00003

Video：

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Objective To observe the clinical efficacy of pars plana vitrectomy (PPV) combined with dexamethasone intravitreal implant (DEX) in the treatment of proliferative diabetic retinopathy (PDR). Methods A prospective randomized controlled study. A total of 57 PDR patients with 79 eyes diagnosed by Department of Ophthalmology of The First Affiliated Hospital of Nanjing Medical University from May 2021 to February 2023 were included in the study. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) were performed in all affected eyes. Central macular thickness (CMT) was measured by OCT. The patients were randomly divided into control group and experimental group, with 27 cases and 35 eyes and 30 cases and 44 eyes, respectively. All eyes were treated with routine 25G PPV and intraoperative whole-retina laser photocoagulation. At the end of the operation, the experimental group was given 0.7 mg DEX intravitreal injection. At 1, 4, 12, and 24 weeks after operation, the same equipment and methods were used for relevant examinations. The improvement after surgery was assessed according to the diabetic retinopathy severity score (DRSS). Mixed analysis of variance was used to compare logarithm of the minimum angle of resolution BCVA and CMT between the two groups and within the two groups before and after operation. Results At 1, 4, 12 and 24 weeks after surgery, BCVA was significantly improved at different time points after surgery, and the differences were statistically significant (P＜0.001). At different time after operation, BCVA in experimental groups was significantly better than that in control group, with statistical significance (P＜0.001). Compared with the CMT before surgery, the CMT at no time point after surgery in experimental group was significantly decreased, and the difference was statistically significant (P ＜0.05). There was no significant difference one week after eye operation in control group (P=0.315). At 4, 12 and 24 weeks after operation, CMT decreased, and the differences were statistically significant (P＜0.05). Compared with before surgery, DRSS increased two steps higher at 1, 4, 12 and 24 weeks after surgery in 20 (45.45%, 20/44), 26 (59.10%, 26/44), 32 (72.73%, 32/44) and 31 (70.45%, 31/44) eyes in the experimental groups, respectively. The control group consisted of 15 (42.86%, 15/35), 15 (42.86%, 15/35), 16 (45.71%, 16/35) and 18 (51.43%, 18/35) eyes, respectively. There was no significant difference in DRSS at 1, 4 and 24 weeks after operation between the control group and the experimental group (P=0.817, 0.178, 0.105). At 12 weeks after surgery, the difference was statistically significant (P=0.020). Conclusion PPV combined with intravitreal injection of DEX in the treatment of PDR can improve postoperative visual acuity, alleviate postoperative macular edema and improve the severity of DR.

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2.	Arrigo A, Aragona E, Bandello F. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy[J]. Ann Med, 2022, 54(1): 1089-1111. DOI: 10.1080/07853890.2022.2064541.
3.	Zhang J, Zhang J, Zhang C, et al. Diabetic macular edema: current understanding, molecular mechanisms and therapeutic implications[J]. Cells, 2022, 11(21): 3362. DOI: 10.3390/cells11213362.
4.	Forrester JV, Kuffova L, Delibegovic M. The role of inflammation in diabetic retinopathy[J/OL]. Front Immunol, 2020, 11: 583687[2020-11-06]. https://pubmed.ncbi.nlm.nih.gov/33240272/. DOI: 10.3389/fimmu.2020.583687.
5.	Semeraro F, Morescalchi F, Cancarini A, et al. Diabetic retinopathy, a vascular and inflammatory disease: therapeutic implications[J]. Diabetes Metab, 2019, 45(6): 517-527. DOI: 10.1016/j.diabet.2019.04.002.
6.	Kaštelan S, Orešković I, Bišćan F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J/OL]. Biochem Med (Zagreb), 2020, 30(3): 030502[2020-10-15]. https://pubmed.ncbi.nlm.nih.gov/32774120/. DOI: 10.11613/bm.2020.030502.
7.	Liu Y, Li L, Pan N, et al. TNF-α released from retinal Müller cells aggravates retinal pigment epithelium cell apoptosis by upregulating mitophagy during diabetic retinopathy[J]. Biochem Biophys Res Commun, 2021, 561: 143-150. DOI: 10.1016/j.bbrc.2021.05.027.
8.	Pan WW, Lin F, Fort PE. The innate immune system in diabetic retinopathy[J/OL]. Prog Retin Eye Res, 2021, 84: 100940[2021-01-08]. https://pubmed.ncbi.nlm.nih.gov/33429059/. DOI: 10.1016/j.preteyeres.2021.100940.
9.	Chung YR, Kim YH, Ha SJ, et al. Role of inflammation in classification of diabetic macular edema by optical coherence tomography[J/OL]. J Diabetes Res, 2019, 2019: 8164250[2019-12-20]. https://pubmed.ncbi.nlm.nih.gov/31930145/. DOI: 10.1155/2019/8164250.
10.	Liang Y, Yan B, Meng Z, et al. Comparison of inflammatory and angiogenic factors in the aqueous humor of vitrectomized and non-vitrectomized eyes in diabetic macular edema patients[J/OL]. Front Med (Lausanne), 2021, 8: 699254[2021-09-08]. https://pubmed.ncbi.nlm.nih.gov/34568366/. DOI: 10.3389/fmed.2021.699254.
11.	Chen HJ, Ma ZZ, Li Y, et al. Change of vascular endothelial growth factor levels following vitrectomy in eyes with proliferative diabetic retinopathy[J/OL]. J Ophthalmol, 2019, 2019: 6764932[2019-10-23]. https://pubmed.ncbi.nlm.nih.gov/31772768/. DOI: 10.1155/2019/6764932.
12.	Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J]. Ophthalmology, 2014, 121(10): 1904-1914. DOI: 10.1016/j.ophtha.2014.04.024.
13.	Rosenblatt A, Udaondo P, Cunha-Vaz J, et al. A collaborative retrospective study on the efficacy and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: the European DME registry study[J]. Ophthalmology, 2020, 127(3): 377-393. DOI: 10.1016/j.ophtha.2019.10.005.
14.	Flaxel CJ, Adelman RA, Bailey ST, et al. Diabetic retinopathy preferred practice pattern®[J]. Ophthalmology, 2020, 127(1): P66-145. DOI: 10.1016/j.ophtha.2019.09.025.
15.	Ip MS, Zhang J, Ehrlich JS. The clinical importance of changes in diabetic retinopathy severity score[J]. Ophthalmology, 2017, 124(5): 596-603. DOI: 10.1016/j.ophtha.2017.01.003.
16.	Everett LA, Paulus YM. Laser therapy in the treatment of diabetic retinopathy and diabetic macular edema[J]. Curr Diab Rep, 2021, 21(9): 35. DOI: 10.1007/s11892-021-01403-6.
17.	Chatziralli I, Loewenstein A. Intravitreal anti-vascular endothelial growth factor agents for the treatment of diabetic retinopathy: a review of the literature[J]. Pharmaceutics, 2021, 13(8): 1137. DOI: 10.3390/pharmaceutics13081137.
18.	Xu Y, Xie C, Fang Y, et al. Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients[J]. Int J Ophthalmol, 2022, 15(10): 1619-1626. DOI: 10.18240/ijo.2022.10.09.
19.	Prince J, Kumar D, Ghosh A, et al. Surgical management of diabetic macular edema[J]. Curr Diab Rep, 2023, 23(6): 119-125. DOI: 10.1007/s11892-023-01505-3.
20.	Ding Y, Su N, Luan J, et al. Effect of intravitreal Conbercept injection on complications of pars plana vitrectomy in patients with proliferative diabetic retinopathy[J]. J Pers Med, 2023, 13(4): 572. DOI: 10.3390/jpm13040572.
21.	Ozer F, Tokuc EO, Albayrak MGB, et al. Comparison of before versus after intravitreal bevacizumab injection, growth factor levels and fibrotic markers in vitreous samples from patients with proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2022, 260(6): 1899-1906. DOI: 10.1007/s00417-021-05515-3.
22.	Pande GS, Tidake P. Laser treatment modalities for diabetic retinopathy[J/OL]. Cureus, 2022, 14(10): e30024[2022-10-07]. https://pubmed.ncbi.nlm.nih.gov/36348830/. DOI: 10.7759/cureus.30024.
23.	Lima-Fontes M, Leuzinger-Dias M, Barros-Pereira R, et al. Intravitreal Fluocinolone acetonide implant (FAc, 0.19 mg, ILUVIEN®) in the treatment of patients with recurrent cystoid macular edema after pars plana vitrectomy[J]. Ophthalmol Ther, 2023, 12(1): 377-388. DOI: 10.1007/s40123-022-00613-9.
24.	Rodríguez ML, Pérez S, Mena-Mollá S, et al. Oxidative stress and microvascular alterations in diabetic retinopathy: future therapies[J/OL]. Oxid Med Cell Longev, 2019, 2019: 4940825[2019-11-11]. https://pubmed.ncbi.nlm.nih.gov/31814880/. DOI: 10.1155/2019/4940825.
25.	Figueras-Roca M, Sala-Puigdollers A, Zarranz-Ventura J, et al. Anatomic response to intravitreal Dexamethasone implant and baseline aqueous humor cytokine levels in diabetic macular edema[J]. Invest Ophthalmol Vis Sci, 2019, 60(5): 1336-1343. DOI: 10.1167/iovs.18-26215.
26.	Munk MR, Somfai GM, de Smet MD, et al. The role of intravitreal corticosteroids in the treatment of DME: predictive OCT biomarkers[J/OL]. Int J Mol Sci, 2022, 23(14): 7585[2022-07-08]. https://pubmed.ncbi.nlm.nih.gov/35886930/. DOI: 10.3390/ijms23147585.
27.	Chang-Lin JE, Burke JA, Peng Q, et al. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes[J]. Invest Ophthalmol Vis Sci, 2011, 52(7): 4605-4609. DOI: 10.1167/iovs.10-6387.
28.	Iglicki M, Busch C, Lanzetta P, et al. Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? The VITDEX study[J]. Eye (Lond), 2023, 37(2): 280-284. DOI: 10.1038/s41433-022-01931-9.
29.	Iglicki M, Zur D, Busch C, et al. Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'[J]. Acta Diabetol, 2018, 55(6): 541-547. DOI: 10.1007/s00592-018-1117-z.
30.	Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, et al. Randomized trial evaluating Ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema[J]. Ophthalmology, 2010, 117(6): 1064-1077. DOI: 10.1016/j.ophtha.2010.02.031.
31.	Thorne JE, Sugar EA, Holbrook JT, et al. Periocular Triamcinolone vs. intravitreal Triamcinolone vs. intravitreal Dexamethasone implant for the treatment of uveitic macular edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) trial[J]. Ophthalmology, 2019, 126(2): 283-295. DOI: 10.1016/j.ophtha.2018.08.021.

1. Stitt AW, Curtis TM, Chen M, et al. The progress in understanding and treatment of diabetic retinopathy[J]. Prog Retin Eye Res, 2016, 51: 156-186. DOI: 10.1016/j.preteyeres.2015.08.001.
2. Arrigo A, Aragona E, Bandello F. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy[J]. Ann Med, 2022, 54(1): 1089-1111. DOI: 10.1080/07853890.2022.2064541.
3. Zhang J, Zhang J, Zhang C, et al. Diabetic macular edema: current understanding, molecular mechanisms and therapeutic implications[J]. Cells, 2022, 11(21): 3362. DOI: 10.3390/cells11213362.
4. Forrester JV, Kuffova L, Delibegovic M. The role of inflammation in diabetic retinopathy[J/OL]. Front Immunol, 2020, 11: 583687[2020-11-06]. https://pubmed.ncbi.nlm.nih.gov/33240272/. DOI: 10.3389/fimmu.2020.583687.
5. Semeraro F, Morescalchi F, Cancarini A, et al. Diabetic retinopathy, a vascular and inflammatory disease: therapeutic implications[J]. Diabetes Metab, 2019, 45(6): 517-527. DOI: 10.1016/j.diabet.2019.04.002.
6. Kaštelan S, Orešković I, Bišćan F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J/OL]. Biochem Med (Zagreb), 2020, 30(3): 030502[2020-10-15]. https://pubmed.ncbi.nlm.nih.gov/32774120/. DOI: 10.11613/bm.2020.030502.
7. Liu Y, Li L, Pan N, et al. TNF-α released from retinal Müller cells aggravates retinal pigment epithelium cell apoptosis by upregulating mitophagy during diabetic retinopathy[J]. Biochem Biophys Res Commun, 2021, 561: 143-150. DOI: 10.1016/j.bbrc.2021.05.027.
8. Pan WW, Lin F, Fort PE. The innate immune system in diabetic retinopathy[J/OL]. Prog Retin Eye Res, 2021, 84: 100940[2021-01-08]. https://pubmed.ncbi.nlm.nih.gov/33429059/. DOI: 10.1016/j.preteyeres.2021.100940.
9. Chung YR, Kim YH, Ha SJ, et al. Role of inflammation in classification of diabetic macular edema by optical coherence tomography[J/OL]. J Diabetes Res, 2019, 2019: 8164250[2019-12-20]. https://pubmed.ncbi.nlm.nih.gov/31930145/. DOI: 10.1155/2019/8164250.
10. Liang Y, Yan B, Meng Z, et al. Comparison of inflammatory and angiogenic factors in the aqueous humor of vitrectomized and non-vitrectomized eyes in diabetic macular edema patients[J/OL]. Front Med (Lausanne), 2021, 8: 699254[2021-09-08]. https://pubmed.ncbi.nlm.nih.gov/34568366/. DOI: 10.3389/fmed.2021.699254.
11. Chen HJ, Ma ZZ, Li Y, et al. Change of vascular endothelial growth factor levels following vitrectomy in eyes with proliferative diabetic retinopathy[J/OL]. J Ophthalmol, 2019, 2019: 6764932[2019-10-23]. https://pubmed.ncbi.nlm.nih.gov/31772768/. DOI: 10.1155/2019/6764932.
12. Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J]. Ophthalmology, 2014, 121(10): 1904-1914. DOI: 10.1016/j.ophtha.2014.04.024.
13. Rosenblatt A, Udaondo P, Cunha-Vaz J, et al. A collaborative retrospective study on the efficacy and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: the European DME registry study[J]. Ophthalmology, 2020, 127(3): 377-393. DOI: 10.1016/j.ophtha.2019.10.005.
14. Flaxel CJ, Adelman RA, Bailey ST, et al. Diabetic retinopathy preferred practice pattern®[J]. Ophthalmology, 2020, 127(1): P66-145. DOI: 10.1016/j.ophtha.2019.09.025.
15. Ip MS, Zhang J, Ehrlich JS. The clinical importance of changes in diabetic retinopathy severity score[J]. Ophthalmology, 2017, 124(5): 596-603. DOI: 10.1016/j.ophtha.2017.01.003.
16. Everett LA, Paulus YM. Laser therapy in the treatment of diabetic retinopathy and diabetic macular edema[J]. Curr Diab Rep, 2021, 21(9): 35. DOI: 10.1007/s11892-021-01403-6.
17. Chatziralli I, Loewenstein A. Intravitreal anti-vascular endothelial growth factor agents for the treatment of diabetic retinopathy: a review of the literature[J]. Pharmaceutics, 2021, 13(8): 1137. DOI: 10.3390/pharmaceutics13081137.
18. Xu Y, Xie C, Fang Y, et al. Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients[J]. Int J Ophthalmol, 2022, 15(10): 1619-1626. DOI: 10.18240/ijo.2022.10.09.
19. Prince J, Kumar D, Ghosh A, et al. Surgical management of diabetic macular edema[J]. Curr Diab Rep, 2023, 23(6): 119-125. DOI: 10.1007/s11892-023-01505-3.
20. Ding Y, Su N, Luan J, et al. Effect of intravitreal Conbercept injection on complications of pars plana vitrectomy in patients with proliferative diabetic retinopathy[J]. J Pers Med, 2023, 13(4): 572. DOI: 10.3390/jpm13040572.
21. Ozer F, Tokuc EO, Albayrak MGB, et al. Comparison of before versus after intravitreal bevacizumab injection, growth factor levels and fibrotic markers in vitreous samples from patients with proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2022, 260(6): 1899-1906. DOI: 10.1007/s00417-021-05515-3.
22. Pande GS, Tidake P. Laser treatment modalities for diabetic retinopathy[J/OL]. Cureus, 2022, 14(10): e30024[2022-10-07]. https://pubmed.ncbi.nlm.nih.gov/36348830/. DOI: 10.7759/cureus.30024.
23. Lima-Fontes M, Leuzinger-Dias M, Barros-Pereira R, et al. Intravitreal Fluocinolone acetonide implant (FAc, 0.19 mg, ILUVIEN®) in the treatment of patients with recurrent cystoid macular edema after pars plana vitrectomy[J]. Ophthalmol Ther, 2023, 12(1): 377-388. DOI: 10.1007/s40123-022-00613-9.
24. Rodríguez ML, Pérez S, Mena-Mollá S, et al. Oxidative stress and microvascular alterations in diabetic retinopathy: future therapies[J/OL]. Oxid Med Cell Longev, 2019, 2019: 4940825[2019-11-11]. https://pubmed.ncbi.nlm.nih.gov/31814880/. DOI: 10.1155/2019/4940825.
25. Figueras-Roca M, Sala-Puigdollers A, Zarranz-Ventura J, et al. Anatomic response to intravitreal Dexamethasone implant and baseline aqueous humor cytokine levels in diabetic macular edema[J]. Invest Ophthalmol Vis Sci, 2019, 60(5): 1336-1343. DOI: 10.1167/iovs.18-26215.
26. Munk MR, Somfai GM, de Smet MD, et al. The role of intravitreal corticosteroids in the treatment of DME: predictive OCT biomarkers[J/OL]. Int J Mol Sci, 2022, 23(14): 7585[2022-07-08]. https://pubmed.ncbi.nlm.nih.gov/35886930/. DOI: 10.3390/ijms23147585.
27. Chang-Lin JE, Burke JA, Peng Q, et al. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes[J]. Invest Ophthalmol Vis Sci, 2011, 52(7): 4605-4609. DOI: 10.1167/iovs.10-6387.
28. Iglicki M, Busch C, Lanzetta P, et al. Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? The VITDEX study[J]. Eye (Lond), 2023, 37(2): 280-284. DOI: 10.1038/s41433-022-01931-9.
29. Iglicki M, Zur D, Busch C, et al. Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'[J]. Acta Diabetol, 2018, 55(6): 541-547. DOI: 10.1007/s00592-018-1117-z.
30. Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, et al. Randomized trial evaluating Ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema[J]. Ophthalmology, 2010, 117(6): 1064-1077. DOI: 10.1016/j.ophtha.2010.02.031.
31. Thorne JE, Sugar EA, Holbrook JT, et al. Periocular Triamcinolone vs. intravitreal Triamcinolone vs. intravitreal Dexamethasone implant for the treatment of uveitic macular edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) trial[J]. Ophthalmology, 2019, 126(2): 283-295. DOI: 10.1016/j.ophtha.2018.08.021.

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