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Intravitreal injection of methotrexate in persistent diabetic macular edema: a 6-month follow-up study

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the efficacy of intravitreal injection of methotrexate (MTX) in patients with persistent diabetic macular edema (DME) nonresponsive to intravitreal bevacizumab.

Methods

In this prospective, interventional study, intravitreal injection of 400 μg MTX was performed in eyes with persistent center-involving DME unresponsive to at least three consecutive bevacizumab injections or two consecutive bevacizumab injections plus macular photocoagulation. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and maximum retinal thickness (MRT) were recorded before and 1, 3, and 6 months after injections.

Results

Eighteen eyes of 16 patients with a mean age of 61.1 ± 6.7 years were included. Mean number of intravitreal bevacizumab injections was 3.9 ± 1.8 (range 2–8). The mean change in BCVA was −0.09 ± 0.19, −0.1 ± 0.19, and −0.1 ± 0.19 LogMAR at 1, 3, and 6 months after intravitreal MTX injections, respectively (all P = 0.04). Three eyes (16.6 %) had improvement of at least two lines of BCVA and no eye lost visual acuity. Mean change in CST was −23.7 ± 66.7, −28.7 ± 82.2 and 26.5 ± 83.4 μm at 1, 3, and 6 months after MTX injections, respectively (all P = 0.1). A decrease in CST was found in 13 eyes (72.2 %) at 1 and 3 months, and seven eyes (38.8 %) at 6 months of follow-up. Other eyes showed an increase in CST measurements. Mean change in MRT was −35.1 ± 76.4, −40.6 ± 86.3, and 29.8 ± 68.6 μm at 1, 3, and 6 months after MTX injections, respectively (P = 0.06, P = 0.06, and P = 0.08, respectively). No complication attributable to intravitreal MTX occurred.

Conclusion

In this study, intravitreal injection of MTX resulted in anatomical improvement in a significant proportion of eyes with persistent DME. Significant visual improvement was found in 16.6 % of eyes.

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References

  1. Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122:1375–1394

    Article  PubMed  Google Scholar 

  2. Scott IU, Danis RP, Bressler SB, Bressler NM, Browning DJ, Qin H, Diabetic Retinopathy Clinical Research Network (2009) Effect of focal/grid photocoagulation on visual acuity and retinal thickening in eyes with non-center-involved diabetic macular edema. Retina 29(8):613–7

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ho AC, Scott IU, Kim SJ, Brown GC, Brown MM, Ip MS, Recchia FM (2012) Anti-vascular endothelial growth factor pharmacotherapy for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology 119(10):2179–88

    Article  PubMed  Google Scholar 

  4. Jampol L, Bressler NB, Glassman AR (2014) Revolution to a new standard treatment of diabetic macular edema. JAMA 311:2269–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rangasamy S, McGuire PG, Das A (2012) Diabetic retinopathy and inflammation: novel therapeutic targets. Middle East Afr J Ophthalmol 19:52–9

    Article  PubMed  PubMed Central  Google Scholar 

  6. Diabetic Retinopathy Clinical Research Network (DRCR.net), Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C (2009) Three- year follow up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 127:245–251

    Article  Google Scholar 

  7. Chan ES, Cronstein BN (2002) Molecular action of methotrexate in inflammatory diseases. Arthritis Res 4(4):266–73

    Article  PubMed  PubMed Central  Google Scholar 

  8. Samson CM, Waheed N, Baltatzis S, Foster CS (2001) Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology 108:1134–1139

    Article  CAS  PubMed  Google Scholar 

  9. Smith JR, Rosenbaum JT, Wilson DJ, Doolittle ND, Siegal T, Neuwelt EA, Pe’er J (2002) Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology 109:1709–1716

    Article  PubMed  Google Scholar 

  10. Hardwig PW, Pulido JS, Bakri SJ (2008) The safety of intraocular methotrexate in silicone-filled eyes. Retina 28(8):1082–6

    Article  PubMed  Google Scholar 

  11. Falavarjani KG, Modarres M, Hadavankhani A, Moghaddam AK (2015) Intrasilicone oil injection of methotrexate at the end of vitrectomy for advanced proliferative diabetic retinopathy. Eye (Lond) 29(9):1199–203

    Article  Google Scholar 

  12. Soheilian M, Movaseghi M, Ramezani A, Peyman GA (2011) Pilot study of safety and effect of combined intravitreal bevacizumab andmethotrexate for neovascular age-related macular degeneration. Eur J Ophthalmol 21(1):77–82

    Article  PubMed  Google Scholar 

  13. Falavarjani KG, Khadamy J, Safi H, Karimi N, Amirkourjani F (2015) Effect of grid decentration on macular thickness measurements in normal subjects and patients with diabetic macular edema. Eur J Ophthalmol 25(3):218–21

    Article  PubMed  Google Scholar 

  14. Funatsu H, Noma H, Mimura T, Eguchi S, Hori S (2009) Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 116(1):73–79

    Article  PubMed  Google Scholar 

  15. Diabetic Retinopathy Clinical Research Network (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117:1064–77

    Article  Google Scholar 

  16. Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, Li XY, Cui H, Hashad Y, Whitcup SM, Ozurdex MEAD Study Group (2014) Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121:1904–14

    Article  PubMed  Google Scholar 

  17. Campochiaro PA, Brown DM, Pearson A, Ciulla T, Boyer D, Holz FG, Tolentino M, Gupta A, Duarte L, Madreperla S, Gonder J, Kapik B, Billman K, Kane FE, FAME Study Group (2011) Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 118:626–35

    Article  PubMed  Google Scholar 

  18. Velez G, Yuan P, Sung C, Tansey G, Reed GF, Chan CC, Nussenblatt RB, Robinson MR (2001) Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma. Arch Ophthalmol 119(10):1518–24

    Article  CAS  PubMed  Google Scholar 

  19. Ghasemi Falavarjani K, Golabi S, Hadavandkhani A (2016) Effect of Intravitreal injection of Methotrexate on human corneal endothelial cells. Cornea 35(2):217–9

    Article  PubMed  Google Scholar 

  20. Diabetic Retinopathy Clinical Research Network; Writing Committee, Aiello LP, Beck RW, Bressler NM, Browning DJ, Chalam KV, Davis M, Ferris FL 3rd, Glassman AR, Maturi RK, Stockdale CR, Topping TM (2011) Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema. Ophthalmology 118(12):e5–14

    Article  Google Scholar 

  21. Jeon S, Lee WK (2014) Effect of intravitreal triamcinolone in diabetic macular edema unresponsive to intravitreal bevacizumab. Retina 34(8):1606–11

    Article  CAS  PubMed  Google Scholar 

  22. Kim YT, Kang SW, Kim SJ, Kim SM, Chung SE (2012) Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular edema unresponsive to prior treatments; 3-year results. Graefes Arch Clin Exp Ophthalmol 250(5):679–84

    Article  PubMed  Google Scholar 

  23. Zhioua I, Semoun O, Lalloum F, Souied EH (2015) Intravitreal Dexamethasone implant in patients with Ranibizumab persistent diabetic macular edema. Retina 35(7):1429–35

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Eye research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Sattarkhan-Niayesh Street, Tehran, 14456-13131, Iran

    Khalil Ghasemi Falavarjani, Sara Golabi & Mehdi Modarres

Authors
  1. Khalil Ghasemi Falavarjani
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  2. Sara Golabi
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  3. Mehdi Modarres
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Corresponding author

Correspondence to Khalil Ghasemi Falavarjani.

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Funding

Supported by a grant from the Eye Research Center of the Iran University of Medical Sciences (No. 25937).

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional ethics committee and the Helsinki declaration.

Informed consent

Informed consent was obtained from all participants included in the study.

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Falavarjani, K.G., Golabi, S. & Modarres, M. Intravitreal injection of methotrexate in persistent diabetic macular edema: a 6-month follow-up study. Graefes Arch Clin Exp Ophthalmol 254, 2159–2164 (2016). https://doi.org/10.1007/s00417-016-3374-2

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  • DOI: https://doi.org/10.1007/s00417-016-3374-2

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