Abstract
Purpose of Review
Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention.
Recent Findings
Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement.
Summary
Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis [Internet]. 2015;2(1):1–25. Available from: https://doi.org/10.1186/s40662-015-0026-2
•• 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: a randomized clinical trial. JAMA - J Am Med Assoc. 2019;321(19):1880–94. This study provided evidence that patients with DME with good visual acuity can be treated with either intravitreal injections or laser photocoagulation or continued observation with similar outcomes.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology [Internet]. 2011;118(4):615–25. Available from: https://doi.org/10.1016/j.ophtha.2011.01.031
Chew EY, Clemons TE, Harrington M, Bressler SB, Elman MJ, Kim JE, et al. Effectiveness of different monitoring modalities in the detection of neovascular age-related macular degeneration. Retina [Internet]. 2016 Aug [cited 2018 Mar 1];36(8):1542–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27243927
Shah SU, Maturi RK. Therapeutic options in refractory diabetic macular oedema. Drugs. 2017;77(5):481–92.
Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185–222.
Santos AR, Costa MA, Schwartz C, Alves D, Figueira J, Silva R, et al. Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema: the CHARTRES study. Retina. 2018;38(6):1110–9.
Radwan SH, Soliman AZ, Tokarev J, Zhang L, Van Kuijk FJ, Koozekanani DD. Association of disorganization of retinal inner layers with vision after resolution of center-involved diabetic macular edema. JAMA Ophthalmol. 2015;133(7):820–5.
Das R, Spence G, Hogg RE, Stevenson M, Chakravarthy U. Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol. 2018;136(2):202–8.
Maheshwary AS, Oster SF, Yuson RMS, Cheng L, Mojana F, Freeman WR. The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema. Am J Ophthalmol [Internet]. 2010;150(1):63–67.e1. Available from: https://doi.org/10.1016/j.ajo.2010.01.039
Otani T, Yamaguchi Y, Kishi S. Correlation between visual acuity and foveal microstructural changes in diabetic macular edema. Retina. 2010;30(5):774–80.
Shen Y, Liu K, Xu X. Correlation between visual function and photoreceptor integrity in diabetic macular edema: spectral-domain optical coherence tomography. Curr Eye Res. 2016;41(3):391–9.
Ercalik NY, Imamoglu S, Kumral ET, Yenerel NM, Bardak H, Bardak Y. Influence of the epiretinal membrane on ranibizumab therapy outcomes in patients with diabetic macular edema. Arq Bras Oftalmol. 2016;79(6):373–5.
Maryam AK, Tafgeh M, Mahmoud M, Pasha A, Ahad S, Khalil GF. Short term effect of intravitreal bevacizumab for diabetic macular edema associated with epiretinal membrane. Rom J Ophthalmol. 2018;62(3):212–6.
Figueroa M, Contreras I, Noval S. Surgical and anatomical outcomes of pars plana vitrectomy for diffuse nontractional diabetic macular edema. Retina. 2008;28(3):420–6.
Dillinger P, Mester U. Vitrectomy with removal of the internal limiting membrane in chronic diabetic macular oedema. Graefe’s Arch Clin Exp Ophthalmol. 2004;242(8):630–7.
Nasrallah FP, Jalkh AE, Van Coppenolle F, Kado C, Trempe L, McMeel JW, et al. The role of the vitreous in diabetic macular edema. Ophthalmology. 1988;95(10):1335–9.
Stolba U, Binder S, Gruber D, Krebs I, Aggermann T, Neumaier B. Vitrectomy for persistent diffuse diabetic macular edema. Am J Ophthalmol. 2005;140(2):295.e1-295.e9.
Kumagai K, Hangai M, Ogino N, Larson E. Effect of internal limiting membrane peeling on long-term visual outcomes for diabetic macular edema. Retina. 2015;35(7):1422–8.
Yanyali A, Nohutcu AF, Horozoglu F, Celik E. Modified grid laser photocoagulation versus pars plana vitrectomy with internal limiting membrane removal in diabetic macular edema. Am J Ophthalmol. 2005;139(5):795–801.
Browning D, Lee C, Stewart M, Landers M. Vitrectomy for center-involved diabetic macular edema. Clin Ophthalmol. 2016;10:735–42.
Ulrich JN. Pars plana vitrectomy with internal limiting membrane peeling for nontractional diabetic macular edema. Open Ophthalmol J. 2017;11(1):5–10.
Iglicki M, Lavaque A, Ozimek M, Negri HP, Okada M, Chhablani J, et al. Biomarkers and predictors for functional and anatomic outcomes for small gauge pars plana vitrectomy and peeling of the internal limiting membrane in naïve diabetic macular edema: the vital study. PLoS ONE. 2018;13(7):1–12.
Michalewska Z, Stewart M, Landers M, Bednarski M, Adelman RA, Nawrocki J. Vitrectomy in the management of diabetic macular edema in treatment-naïve patients. Can J Ophthalmol. 2018;53(4):402–7.
•• Pessoa B, Afonso Dias D, Baptista P, Coelho C, Beirão JNM, Meireles A. Vitrectomy outcomes in eyes with tractional diabetic macular edema. Ophthalmic Res. 2019;61(2):94–9. This retrospective study demonstrated that PPV for tractional DME showed a reduction in central foveal thickness and increase in visual acuity in more than 50% of cases with low recurrence and postoperative complications, suggesting it could be a reasonable surgical management option for tractional DME.
Thomas D, Bunce C, Moorman C, Laidlaw DAH. A randomised controlled feasibility trial of vitrectomy versus laser for diabetic macular oedema. Br J Ophthalmol. 2005;89(1):81–6.
Patel JI, Hykin PG, Schadt M, Luong V, Bunce C, Fitzke F, et al. Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation. Eye. 2006;20(8):873–81.
Kumar A, Sinha S, Azad R, Sharma YR, Vohra R. Comparative evaluation of vitrectomy and dye-enhanced ILM peel with grid laser in diffuse diabetic macular edema. Graefe’s Arch Clin Exp Ophthalmol. 2007;245(3):360–8.
Jackson TL, Nicod E, Angelis A, Grimaccia F, Pringle E, Kanavos P. Pars plana vitrectomy for diabetic macular edema: a systematic review, meta-analysis, and synthesis of safety literature. Retina. 2017;37(5):886–95.
Doi N, Sakamoto T, Sonoda Y, Yasuda M, Yonemoto K, Arimura N, et al. Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic macular edema on randomized paired-eyes. Graefe’s Arch Clin Exp Ophthalmol. 2012;250(1):71–8.
Nakajima T, Roggia MF, Noda Y, Ueta T. Effect of internal limiting membrane peeling during vitrectomy for diabetic macular edema: systematic review and meta-analysis. Retina. 2015;35(9):1719–25.
Hoerauf H, Brüggemann A, Muecke M, Lüke J, Müller M, Stefánsson E, et al. Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial. Graefe’s Arch Clin Exp Ophthalmol. 2011;249(7):997–1008.
Bardak Y, Çekiç O, Tiǧ ŞU. Comparison of ICG-assisted ILM peeling and triamcinolone-assisted posterior vitreous removal in diffuse diabetic macular oedema. Eye. 2006;20(12):1357–9.
Yamamoto T, Hitani K, Sato Y, Yamashita H, Takeuchi S. Vitrectomy for diabetic macular edema with and without internal limiting membrane removal. Ophthalmologica. 2005;219(4):206–13.
Chhablani JK, Kim JS, Cheng L, Kozak I, Freeman W. External limiting membrane as a predictor of visual improvement in diabetic macular edema after pars plana vitrectomy. Graefe’s Arch Clin Exp Ophthalmol. 2012;250(10):1415–20.
Hagenau F, Vogt D, Ziada J, Guenther SR, Haritoglou C, Wolf A, et al. Vitrectomy for diabetic macular edema: optical coherence tomography criteria and pathology of the vitreomacular interface. Am J Ophthalmol [Internet]. 2019;200:34–46. Available from: https://doi.org/10.1016/j.ajo.2018.12.004
Yanyali A, Horozoglu F, Celik E, Ercalik Y, Nohutcu AF. Pars plana vitrectomy and removal of the internal limiting membrane in diabetic macular edema unresponsive to grid laser photocoagulation. Eur J Ophthalmol. 2006;16(4):573–81.
Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008;28(3):410–9.
Ichiyama Y, Sawada O, Mori T, Fujikawa M, Kawamura H, Ohji M. The effectiveness of vitrectomy for diffuse diabetic macular edema may depend on its preoperative optical coherence tomography pattern. Graefe’s Arch Clin Exp Ophthalmol [Internet]. 2016;254(8):1545–51. Available from: https://doi.org/10.1007/s00417-015-3251-4
Simunovic MP, Hunyor AP, Ho I-V. Vitrectomy for diabetic macular edema: a systematic review and meta-analysis. Can J Ophthalmol. 2014;49(2):188–95.
Berrocal MH, Acaba LA, Chenworth ML. Surgical innovations in the treatment of diabetic macular edema and diabetic retinopathy. Curr Diab Rep. 2019;19(10):106.
Currie CJ, Peyrot M, Morgan CLL, Poole CD, Jenkins-Jones S, Rubin RR, et al. The impact of treatment noncompliance on mortality in people with type 2 diabetes. Diabetes Care. 2012;35(6):1279–84.
Tolentino M. Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease. Surv Ophthalmol [Internet]. 2011;56(2):95–113. Available from: https://doi.org/10.1016/j.survophthal.2010.08.006
Singerman LJ, Masonson H, Patel M, Adamis AP, Buggage R, Cunningham E, et al. Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF inhibition study in ocular neovascularisation (VISION) trial. Br J Ophthalmol. 2008;92(12):1606–11.
Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology [Internet]. 2006;116(1):57–65.e5. Available from: https://doi.org/10.1016/j.ophtha.2008.10.018
Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002;109(5):920–7.
Boyle J, Vukicevic M, Koklanis K, Itsiopoulos C, Rees G. Experiences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration. Psychol Heal Med. 2018;23(2):127–40.
Campochiaro PA, Marcus DM, Awh CC, Regillo C, Adamis AP, Bantseev V, et al. The port delivery system with ranibizumab for neovascular age-related macular degeneration: results from the randomized phase 2 ladder clinical trial. Ophthalmology [Internet]. 2019;126(8):1141–54. Available from: https://doi.org/10.1016/j.ophtha.2019.03.036
Genentech’s Susvimo earns FDA approval [Internet]. Modern Retina. [cited 2022 Apr 24]. Available from: https://www.modernretina.com/view/genentech-s-susvimo-earns-fda-approval
Genentech voluntarily recalls Susvimo ocular implant for wet AMD [Internet]. Eyewire+. 2022 [cited 2022 Feb 10]. Available from: https://eyewire.news/news/genentech-voluntarily-recalls-susvimo-ocular-implant-for-wet-amd?c4src=article:infinite-scroll
Genentech: Press Releases | Wednesday, Jul 25, 2018 [Internet]. [cited 2022 Apr 24]. Available from: https://www.gene.com/media/press-releases/14739/2018-07-25/genentech-unveils-positive-phase-ii-resu
•• Holekamp NM, Campochiaro PA, Chang MA, Miller D, Pieramici D, Adamis AP, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology [Internet]. 2022;129(3):295–307. Available from: https://doi.org/10.1016/j.ophtha.2021.09.016. Results of the phase 3 clinical trial of Port Delivery System with Ranibizumab for wet AMD showed equivalent treatment as the current standard of monthly injections. Success in his trial has led to the phase 3 trail of the same system in patients with DME.
This study will evaluate the efficacy, safety, and pharmacokinetics of the port delivery system with ranibizumab in participants with diabetic macular edema compared with intravitreal ranibizumab [Internet]. [cited 2022 Apr 24]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT04108156
Chandrasekaran, Priya R Madanagopalan VG. Ranibizumab port delivery system in neovascular age-related macular degeneration. Ther Adv Ophthalmol. 2022;7(14).
El-Mollayess GM, Saadeh JS, Salti HI. Exogenous endophthalmitis in diabetic patients: a systemic review. ISRN Ophthalmol. 2012;2012(456209).
Mukkamala L, Bhagat N, Zarbin MA. Practical lessons from protocol I for the management of diabetic macular edema. Dev Ophthalmol. 2017;60:91–108.
Maturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, et al. Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol W randomized clinical trial. JAMA Ophthalmol. 2021;139(7):701–12.
Campbell J, Cole AL, Almony A, Ingraham H, Holekamp NM, Marks S, et al. Real world vision outcomes in DME treated with anti-VEGF injections-an analysis of EMR data from a large health system. Invest Ophthalmol Vis Sci. 2014;55(13):3065–3065.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Jamie Prince, Dipen Kumar, Arko Ghosh, Alice Yang Zhang, declare that they have no conflict of interest.
J. Fernando Arevalo received research funding from Topcon Medical Systems Inc. and royalties from Springer SBM LLC and Elsevier. He has received consulting fees from Abbvie, Genentech, THEA laboratories, DORC, EyePoint Pharmaceuticals and Alimera Sciences, Inc.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Prince, J., Kumar, D., Ghosh, A. et al. Surgical Management of Diabetic Macular Edema. Curr Diab Rep 23, 119–125 (2023). https://doi.org/10.1007/s11892-023-01505-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11892-023-01505-3