Dexamethasone implant as an adjuvant therapy to ranibizumab loading dose in persistent diabetic macular edema

Abstract

Purpose

This study evaluates the effectiveness of a single-dose dexamethasone implant (DI) as an auxiliary therapy to continued intravitreal ranibizumab (IVR) treatment in patients with persistent diabetic macular edema (DME).

Methods

Twenty-five pseudophakic eyes of 25 patients with DME who underwent a single injection of DI as an adjuvant therapy following an IVR loading dose were examined retrospectively. All patients were treatment naive and had a poor response to a loading dose of three consecutive monthly IVR injections. IVR treatments were continued pro re nata after the DI. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 1, 3, 6 and 8 months post-DI treatment.

Results

After the IVR loading dose, the mean BCVA and CMT were 0.9 ± 0.6 LogMAR and 478.2 ± 107.8 µm, respectively. One month after the DI, the mean BCVA and CMT had improved to 0.6 ± 0.4 LogMAR (p = 0.005) and 313.8 ± 62.7 µm (p < 0.001), respectively. This improvement was maintained with mean 0.8 ± 0.8 IVR injections throughout the follow-up period. The final mean BCVA and CMT were 0.5 ± 0.5 LogMAR and 298.4 ± 71.5 µm. Subgroup analyses revealed that different DME types did not have any effect on CMT or BCVA improvement (p = 0.188, p = 0.136; respectively).

Conclusion

Adding DI results in rapid anatomical and visual improvement in patients who respond poorly to an IVR loading dose. Improvements may be maintained with additional IVR in follow-up.

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References

  1. 1.

    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 91:1464–1474

    CAS  Article  Google Scholar 

  2. 2.

    Do DV, Schmidt-Erfurth U, Gonzalez VH et al (2011) The DA VINCI study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 118:1819–1826

    Article  Google Scholar 

  3. 3.

    Cunningham ET Jr, Adamis AP, Altaweel M et al (2005) Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112:1747–1757

    Article  Google Scholar 

  4. 4.

    Cheung N, Wong IY, Wong TY (2014) Ocular anti-VEGF therapy for diabetic retinopathy: over-view of clinical efficacy and evolving applications. Diabetes Care 37:900–905

    CAS  Article  Google Scholar 

  5. 5.

    Nguyen QD, Brown DM, Marcus DM et al (2012) RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 119:789–801

    Article  Google Scholar 

  6. 6.

    Ho AC, Scott IU, Kim SJ et al (2012) Anti-vascular endothelial growth factor pharmacotherapy for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology 119:2179–2188

    Article  Google Scholar 

  7. 7.

    Tamura H, Miyamoto K, Kiryu J et al (2005) Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci 46:1440–1444

    Article  Google Scholar 

  8. 8.

    Grover D, Li TJ, Chong CC (2008) Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 1:CD005656

    Google Scholar 

  9. 9.

    Elman MJ, Aiello LP, Beck RW et al (2010) Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117:1064–1077

    Article  Google Scholar 

  10. 10.

    Smithen LM, Ober MD, Maranan L, Spaide RF (2004) Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol 138:740–743

    CAS  Article  Google Scholar 

  11. 11.

    Pacella E, Vestri AR, Muscella R et al (2013) Preliminary results of an intravitreal dexamethasone implant (Ozurdex) in patients with persistent diabetic macular edema. Clin Ophthalmol 7:1423–1428

    CAS  Article  Google Scholar 

  12. 12.

    Boyer DS, Yoon YH, Belfort R Jr et al (2014) Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121:1904–1914

    Article  Google Scholar 

  13. 13.

    Ferris FL III, Maguire MG, Glassman AR, Ying GS, Martin DF (2016) Evaluating effects of switching anti-vascular endothelial growth factor drugs for age-related macular degeneration and diabetic macular edema. JAMA Ophthalmol 1:22. https://doi.org/10.1001/jamaophthalmol.2016.4820

    Article  Google Scholar 

  14. 14.

    Chatziralli I, Santarelli M, Patrao N et al (2017) Identification of time point to best define ‘sub-optimal response’ following intravitreal ranibizumab therapy for diabetic macular edema based on real-life data. Eye (Lond) 31(11):1594–1599

    CAS  Article  Google Scholar 

  15. 15.

    Maturi RK, Glassman AR, Liu D et al (2017) Diabetic Retinopathy Clinical Research Network. Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR Network Phase 2 randomized clinical trial. JAMA Ophthalmol Nov:11. https://doi.org/10.1001/jamaophthalmol.2017.4914

    Article  Google Scholar 

  16. 16.

    Ying GS, Maguire MG, Daniel E et al (2015) Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group. Association of baseline characteristics and early vision response with 2-year outcomes in the Comparison of AMD Treatments Trials (CATT). Ophthalmology 122(12):2523.e1–2531.e1

    Article  Google Scholar 

  17. 17.

    Elman MJ, Aiello LP, Beck RW et al (2010) Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117(6):1064.e35–1077.e35

    Article  Google Scholar 

  18. 18.

    Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G (2017) Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol 101(12):1689–1693

    Article  Google Scholar 

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Acknowledgements

The authors have no financial interest in any materials used in the study.

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Correspondence to Akin Cakir.

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Cakir, A., Erden, B., Bolukbasi, S. et al. Dexamethasone implant as an adjuvant therapy to ranibizumab loading dose in persistent diabetic macular edema. Int Ophthalmol 39, 2179–2185 (2019). https://doi.org/10.1007/s10792-018-1053-5

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Keywords

  • Dexamethasone
  • Diabetic macular edema
  • Adjuvant therapy