Submacular Injection of Ranibizumab as a New Surgical Treatment for Refractory Diabetic Macular Edema

Samir M El-Baha, Ahmed M Abdel Hadi, Mahmoud A Abouhussein, Samir M El-Baha, Ahmed M Abdel Hadi, Mahmoud A Abouhussein

Abstract

Purpose: In this study, we describe a new surgical technique for the treatment of refractory DME. The technique consists of vitrectomy with ILM peeling with a subretinal injection of ranibizumab.

Methods: This is a prospective interventional noncomparative study including patients with refractory DME. Included patients were subjected to the new surgical technique of pars plana vitrectomy with subretinal injection of ranibizumab.

Results: The study included 19 eyes with refractory macular edema, in which this novel technique was attempted. There were 10 males and 9 females. The age of the patients ranged from 17 to 67 years with a mean of 55.58 ± 13.242 years. The duration of diabetes before enrollment in the study ranged from 7 to 25 years with a mean of 16.3 years. Preoperatively, the mean CMT of the eyes ranged from 352 to 883 microns with mean ± SD of 498.58 ± 152.16 microns. Postoperatively, this improved significantly to 373.5 ± 100.3, 355.9 ± 89.8, and 365.74 ± 120.12 microns at 1, 3, and 6 months, respectively (p ≤ 0.001 for all).

Conclusion: This novel surgical procedure of vitrectomy with ILM peeling with a subretinal injection of ranibizumab is effective in cases of refractory DME. The study has been registered in Contact ClinicalTrials.gov PRS Identifier: NCT03975088.

Conflict of interest statement

All authors declare no conflicts of interest.

Copyright © 2019 Samir M. El-Baha et al.

References

    1. Klein R., Klein B. E. K., Moss S. E., Cruickshanks K. J. The Wisconsin epidemiologic study of diabetic retinopathy XV. Ophthalmology. 1995;102(1):7–16. doi: 10.1016/s0161-6420(95)31052-4.
    1. ETDRS Research Group. Early photocoagulation for diabetic retinopathy: ETDRS number 9. Ophthalmology. 1991;98:766–785.
    1. Nguyen Q. D., Brown D. M., Marcus D. M., et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2002;119(4):789–801. doi: 10.1016/j.ophtha.2011.12.039.
    1. Massin P., Bandello F., Garweg J. G., et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care. 2010;33(11):2399–2405. doi: 10.2337/dc10-0493.
    1. Bressler S. B., Ayala A. R., Bressler N. M., et al. Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmology. 2016;134(3):278–285. doi: 10.1001/jamaophthalmol.2015.5346.
    1. Elman M. J., Aiello L. P., Beck R. W., et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064–1077.e35. doi: 10.1016/j.ophtha.2010.02.031.
    1. Elman M. J., Bressler N. M., Qin H., et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118(4):609–614. doi: 10.1016/j.ophtha.2010.12.033.
    1. Uji A., Murakami T., Nishijima K., et al. Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema. American Journal of Ophthalmology. 2012;153(4):710–717. doi: 10.1016/j.ajo.2011.08.041.
    1. Brown D. M., Nguyen Q. D., Marcus D. M., et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials. Ophthalmology. 2013;120(10):2013–2022. doi: 10.1016/j.ophtha.2013.02.034.
    1. Smiddy W. E. Economic Considerations of macular edema therapies. Ophthalmology. 2011;118(9):1827–1833. doi: 10.1016/j.ophtha.2010.12.034.
    1. Laidlaw D. A. H. Vitrectomy for diabetic macular oedema. Eye. 2008;22(10):1337–1341. doi: 10.1038/eye.2008.84.
    1. Haller J. A., Qin H., Apte R. S., et al. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117:1087–1093. doi: 10.1016/j.ophtha.2009.10.040.
    1. Stefánsson E. Physiology of vitreous surgery. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2009;247(2):147–163. doi: 10.1007/s00417-008-0980-7.
    1. Bonnin S., Sandali O., Bonnel S., Monin C., El Sanharawi M. Vitrectomy with internal limiting membrane peeling for tractional and nontractional diabetic macular edema. Retina. 2015;35(5):921–928. doi: 10.1097/iae.0000000000000433.
    1. Sebag J., Buckingham B., Charles M. A., et al. Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. Archives of Ophthalmology. 1992;110(10):1472–1476. doi: 10.1001/archopht.1992.01080220134035.
    1. Bhagat N., Grigorian R. A., Tutela A., Zarbin M. A. Diabetic macular edema: pathogenesis and treatment. Survey of Ophthalmology. 2009;54(1):1–32. doi: 10.1016/j.survophthal.2008.10.001.
    1. Kent D., Vinores S. A., Campochiaro P. A. Macular oedema: the role of soluble mediators. British Journal of Ophthalmology. 2000;84(5):542–545. doi: 10.1136/bjo.84.5.542.
    1. Funatsu H., Yamashita H., Ikeda T., Mimura T., Shimizu E., Hori S. Relation of diabetic macular edema to cytokines and posterior vitreous detachment. American Journal of Ophthalmology. 2003;135(3):321–327. doi: 10.1016/s0002-9394(02)01971-2.
    1. Gandorfer A., Messmer E. M., Ulbig M. W., Kampik A. Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane. Retina. 2000;20(2):126–133. doi: 10.1097/00006982-200002000-00004.
    1. Doi N., Sakamoto T., Sonoda Y., et al. Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic macular edema on randomized paired-eyes. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2011;250(1):71–78. doi: 10.1007/s00417-011-1777-7.
    1. Yamamoto T., Hitani K., Tsukahara I., et al. Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. American Journal of Ophthalmology. 2003;135(1):14–19. doi: 10.1016/s0002-9394(02)01819-6.
    1. Stolba U., Binder S., Gruber D., Krebs I., Aggermann T., Neumaier B. Vitrectomy for persistent diffuse diabetic macular edema. American Journal of Ophthalmology. 2005;140:295.e1–295.e9. doi: 10.1016/j.ajo.2005.03.045.
    1. Yanyali A., Horozoglu F., Celik E., Nohutcu A. F. Long-term outcomes of pars plana vitrectomy with internal limiting membrane removal in diabetic macular edema. Retina. 2007;27(5):557–566. doi: 10.1097/01.iae.0000249390.61854.d5.
    1. Song S. J., Sohn J. H., Park K. H. Evaluation of the efficacy of vitrectomy for persistent diabetic macular edema and associated factors predicting outcome. Korean Journal of Ophthalmology. 2007;21(3):146–150. doi: 10.3341/kjo.2007.21.3.146.
    1. Morizane Y., Kimura S., Hosokawa M., et al. Planned foveal detachment technique for the resolution of diffuse diabetic macular edema. Japanese Journal of Ophthalmology. 2015;59(5):279–287. doi: 10.1007/s10384-015-0390-4.
    1. Martel J. N., Mahmoud T. H. Subretinal pneumatic displacement of subretinal hemorrhage. JAMA Ophthalmology. 2013;131(12):1632–1635. doi: 10.1001/jamaophthalmol.2013.5464.
    1. González-López J. J., McGowan G., Chapman E., Yorston D. Vitrectomy with subretinal tissue plasminogen activator and ranibizumab for submacular haemorrhages secondary to age-related macular degeneration: retrospective case series of 45 consecutive cases. Eye. 2016;30(7):929–935. doi: 10.1038/eye.2016.65.
    1. Peng Y., Tang L., Zhou Y. Subretinal injection: a review on the novel route of therapeutic delivery for vitreoretinal diseases. Ophthalmic Research. 2017;58(4):217–226. doi: 10.1159/000479157.
    1. MacLaren R. E., Groppe M., Barnard A. R., et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. The Lancet. 2014;383(9923):1129–1137. doi: 10.1016/s0140-6736(13)62117-0.
    1. Hillenkamp J., Surguch V., Framme C., Gabel V.-P., Sachs H. G. Management of submacular hemorrhage with intravitreal versus subretinal injection of recombinant tissue plasminogen activator. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2010;248(1):5–11. doi: 10.1007/s00417-009-1158-7.
    1. Machemer R. Macular translocation. American Journal of Ophthalmology. 1998;125(5):698–700. doi: 10.1016/s0002-9394(98)00020-8.
    1. Takagi H., Otani A., Kiryu J., Ogura Y. New surgical approach for removing massive foveal hard exudates in diabetic macular edema11The authors have no financial interest in any aspect of this study. Ophthalmology. 1999;106(2):249–257. doi: 10.1016/s0161-6420(99)90054-4.
    1. Ternant D., Paintaud G. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins. Expert Opinion on Biological Therapy. 2005;5(sup1):S37–S47. doi: 10.1517/14712598.5.1.s37.
    1. Avery R. L., Castellarin A. A., Steinle N. C., et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. British Journal of Ophthalmology. 2014;98(12):1636–1641. doi: 10.1136/bjophthalmol-2014-305252.
    1. Tachi N., Ogino N. Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. American Journal of Ophthalmology. 1996;122(2):258–260. doi: 10.1016/s0002-9394(14)72018-5.
    1. Heij E. C. L., Hendrikse F., Kessels A. G. H., Derhaag P. J. F. M. Vitrectomy results in diabetic macular oedema without evident vitreomacular traction. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2001;239(4):264–270.
    1. Yanyali A., Bozkurt K. T., Macin A., Horozoglu F., Nohutcu A. F. Quantitative assessment of photoreceptor layer in eyes with resolved edema after pars plana vitrectomy with internal limiting membrane removal for diabetic macular edema. Ophthalmologica. 2011;226(2):57–63. doi: 10.1159/000327597.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa