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The outcome of fluocinolone acetonide intravitreal implant is predicted by the response to dexamethasone implant in diabetic macular oedema

A Correction to this article was published on 01 March 2021

This article has been updated



To investigate if the visual and anatomic response to the first dexamethasone implant (DEX) predicts the 12-month clinical outcome after shifting to fluocinolone acetonide (FAc) implant in patients with diabetic macular oedema (DMO).


Retrospective cohort study including pseudophakic patients with previously treated DMO, undergone one or more DEX injections before FAc. Functional and morphologic response to DEX was defined based on the best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after the first DEX, respectively. Steroid-response was defined as intraocular pressure (IOP) elevation ≥5 mmHg or IOP > 21 mmHg after any previous DEX exposure. Pairwise comparisons for BCVA, CMT, and IOP after FAc were performed with linear mixed models and a repeated-measure design.


Forty-four eyes of 33 patients were included. Patients were shifted to FAc after a mean ± standard deviation of 4.6 ± 3.2 DEX injections. Overall, BCVA and CMT improved during the first 12 months after switching to FAc (p = 0.04 and p < 0.001, respectively). Only eyes with a good morphologic response to DEX had a significant CMT reduction after FAc (p < 0.001), while no significant relationship was found between BCVA improvement after DEX and after FAc. IOP elevation occurred in 9 eyes (20%) following DEX implant. These eyes carried a 20-fold increased risk of having an IOP rise after FAc (p < 0.001), with a non-linear relationship between the IOP increase after DEX and the one after FAc.


The response to previous DEX may anticipate the morphologic response to subsequent FAc. Eyes with steroid-induced IOP elevation after DEX are at a high risk of IOP increase after FAc. The visual response after FAc was not associated with the visual response to previous steroids, indicating that FAc may have a role also in patients refractory to DEX implant.

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Fig. 1: Functional, morphologic, and intraocular pressure (IOP) changes after long-term intravitreal steroids stratifying eyes on the basis of the response to dexamethasone (DEX) implant. For group definition, refer to the methods.
Fig. 2: Intraocular pressure (IOP) changes after long-term intravitreal steroids (fluocinolone acetonide, FA) stratifying eyes on the basis of the response to short-term (dexamethasone, DEX) exposure.

Change history


  1. Bandello F, Cicinelli MV, Parodi MB. Anti-VEGF molecules for the management of diabetic macular edema. Curr Pharm Des. 2015;21:4731–7.

    CAS  Article  Google Scholar 

  2. Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G. Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol. 2017;101:1689–93.

    Article  Google Scholar 

  3. 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;237:185–222.

    Article  Google Scholar 

  4. Whitcup SM, Cidlowski JA, Csaky KG, Ambati J. Pharmacology of corticosteroids for diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59:1–12.

    CAS  Article  Google Scholar 

  5. Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014;121:1904–14.

    Article  Google Scholar 

  6. Rehak M, Busch C, Unterlauft JD, Jochmann C, Wiedemann P. Outcomes in diabetic macular edema switched directly or after a dexamethasone implant to a fluocinolone acetonide intravitreal implant following anti-VEGF treatment. Acta Diabetol. 2020;57:469–78.

    CAS  Article  Google Scholar 

  7. Vaz-Pereira S, Castro-de-Sousa JP, Martins D, Prates Canelas J, Reis P, Sampaio A, et al. The outcomes of switching from short- to long-term intravitreal corticosteroid implant therapy in patients with diabetic macular edema. Ophthalmic Res. 2020;63:114–21.

    CAS  Article  Google Scholar 

  8. Singh P, Chedid A, Deuchler SK, Kohnen T, Muller M, Koch FH. The efficacy and safety outcomes of the 0.19 mg fluocinolone acetonide implant after prior treatment with the 0.7 mg dexamethasone implant in patients with diabetic macular edema. Int Med Case Rep J. 2018;11:265–9.

    CAS  Article  Google Scholar 

  9. Bailey C, Chakravarthy U, Lotery A, Menon G, Talks J, Medisoft Audit G. Real-world experience with 0.2 mug/day fluocinolone acetonide intravitreal implant (ILUVIEN) in the United Kingdom. Eye. 2017;31:1707–15.

    CAS  Article  Google Scholar 

  10. Chakravarthy U, Taylor SR, Koch FHJ, Castro de Sousa JP, Bailey C, Group IRSSI. Changes in intraocular pressure after intravitreal fluocinolone acetonide (ILUVIEN): real-world experience in three European countries. Br J Ophthalmol. 2019;103:1072–7.

    Article  Google Scholar 

  11. Eaton A, Koh SS, Jimenez J, Riemann CD. The USER study: a chart review of patients receiving a 0.2 microg/day fluocinolone acetonide implant for diabetic macular edema. Ophthalmol Ther. 2019;8:51–62.

    Article  Google Scholar 

  12. Riclassificazione del medicinale per uso umano “Iluvien”, ai sensi dell’articolo 8, comma 10, della legge 24 dicembre 1993, n. 537. (Determina n. 33/2017).

  13. Panozzo G, Cicinelli MV, Augustin AJ, Battaglia Parodi M, Cunha-Vaz J, Guarnaccia G, et al. An optical coherence tomography-based grading of diabetic maculopathy proposed by an international expert panel: The European School for Advanced Studies in Ophthalmology classification. Eur J Ophthalmol. 2020;30:8–18.

    Article  Google Scholar 

  14. Framme C, Schweizer P, Imesch M, Wolf S, Wolf-Schnurrbusch U. Behavior of SD-OCT-detected hyperreflective foci in the retina of anti-VEGF-treated patients with diabetic macular edema. Invest Ophthalmol Vis Sci. 2012;53:5814–8.

    CAS  Article  Google Scholar 

  15. Song YY, Lu Y. Decision tree methods: applications for classification and prediction. Shanghai Arch Psychiatry. 2015;27:130–5.

    PubMed  PubMed Central  Google Scholar 

  16. Pieramici DJ, Wang PW, Ding B, Gune S. Visual and anatomic outcomes in patients with diabetic macular edema with limited initial anatomic response to ranibizumab in RIDE and RISE. Ophthalmology. 2016;123:1345–50.

    Article  Google Scholar 

  17. R Development Core Team. R: a language and enviroment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2010.

  18. Campochiaro PA, Brown DM, Pearson A, Ciulla T, Boyer D, Holz FG, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118:626–35 e2.

    Article  Google Scholar 

  19. Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119:2125–32.

    Article  Google Scholar 

  20. Alfaqawi F, Lip PL, Elsherbiny S, Chavan R, Mitra A, Mushtaq B. Report of 12-months efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: a real-world result in the United Kingdom. Eye. 2017;31:650–6.

    CAS  Article  Google Scholar 

  21. Fusi-Rubiano W, Mukherjee C, Lane M, Tsaloumas MD, Glover N, Kidess A, et al. Treating Diabetic Macular Oedema (DMO): real world UK clinical outcomes for the 0.19 mg Fluocinolone Acetonide intravitreal implant (Iluvien) at 2 years. BMC Ophthalmol. 2018;18:62.

    Article  Google Scholar 

  22. Coelho J, Malheiro L, Melo Beirao J, Meireles A, Pessoa B. Real-world retrospective comparison of 0.19 mg fluocinolone acetonide and 0.7 mg dexamethasone intravitreal implants for the treatment of diabetic macular edema in vitrectomized eyes. Clin Ophthalmol. 2019;13:1751–9.

    CAS  Article  Google Scholar 

  23. Carneiro A, Meireles A, Castro Sousa J, Teixeira C. Clinical impact of the 0.2 µg/day fluocinolone acetonide intravitreal implant: outcomes from the ILUVIEN® clinical evidence study in Portugal. Ther Adv Ophthalmol. 2020;12:2515841420917768.

    PubMed  PubMed Central  Google Scholar 

  24. Augustin AJ, Bopp S, Fechner M, Holz F, Sandner D, Winkgen AM, et al. Three-year results from the retro-IDEAL study: real-world data from diabetic macular edema (DME) patients treated with ILUVIEN((R)) (0.19 mg fluocinolone acetonide implant). Eur J Ophthalmol. 2020;30:382–91.

    Article  Google Scholar 

  25. Chakravarthy U, Yang Y, Lotery A, Ghanchi F, Bailey C, Holz FG, et al. Clinical evidence of the multifactorial nature of diabetic macular edema. Retina. 2018;38:343–51.

    Article  Google Scholar 

  26. Schechet SA, Adams OE, Eichenbaum DA, Hariprasad SM. Macular thickness amplitude changes when switching from discontinuous to continuous therapy for diabetic macular oedema. BMJ Open Ophthalmol. 2019;4:e000271.

    Article  Google Scholar 

  27. Riemann CD, Eaton AM, Cutino A. Reduction in retinal thickness fluctuations after treatment with fluocinolone acetonide implant for DME: a post-hoc analysis of the USER Study. Ophthalmic Surg Lasers Imaging. Ophthalmic Surg Lasers Imaging Retina. 2020;51:298–306.

    Article  Google Scholar 

  28. Danis RP, Sadda S, Li XY, Cui H, Hashad Y, Whitcup SM. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials. Br J Ophthalmol. 2016;100:796–801.

    Article  Google Scholar 

  29. Adams OE, Schechet SA, Hariprasad SM. Discontinuous to continuous therapy for persistent diabetic macular edema leads to reduction in treatment frequency. Eur J Ophthalmol. 2020;1120672120901691.

  30. Busch C, Fraser-Bell S, Iglicki M, Lupidi M, Couturier A, Chaikitmongkol V, et al. Real-world outcomes of non-responding diabetic macular edema treated with continued anti-VEGF therapy versus early switch to dexamethasone implant: 2-year results. Acta Diabetol. 2019;56:1341–50.

    CAS  Article  Google Scholar 

  31. Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol. 2002;47:S253–62.

    Article  Google Scholar 

  32. Lopes de Faria JM, Jalkh AE, Trempe CL, McMeel JW. Diabetic macular edema: risk factors and concomitants. Acta Ophthalmol Scand. 1999;77:170–5.

    CAS  Article  Google Scholar 

  33. Chatziralli I, Dimitriou E, Theodossiadis G, Chatzirallis A, Kazantzis D, Theodossiadis P. Treatment of macular edema after pars plana vitrectomy for idiopathic epiretinal membrane using intravitreal dexamethasone implant: long-term outcomes. Ophthalmologica. 2019;242:16–21.

    CAS  Article  Google Scholar 

  34. Moein HR, Novais EA, Rebhun CB, Cole ED, Louzada RN, Witkin AJ, et al. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic macular edema. Retina. 2018;38:2277–84.

    Article  Google Scholar 

  35. Sadda SR, Campbell J, Dugel PU, Holekamp NM, Kiss S, Loewenstein A, et al. Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: a post hoc analysis of Protocol I data. Eye. 2020;34:480–90.

    CAS  Article  Google Scholar 

  36. Dugel PU, Hillenkamp J, Sivaprasad S, Vogeler J, Mousseau MC, Wenzel A, et al. Baseline visual acuity strongly predicts visual acuity gain in patients with diabetic macular edema following anti-vascular endothelial growth factor treatment across trials. Clin Ophthalmol. 2016;10:1103–10.

    CAS  Article  Google Scholar 

  37. Parrish RK II, Campochiaro PA, Pearson PA, Green K, Traverso CE, Group FS. Characterization of intraocular pressure increases and management strategies following treatment with fluocinolone acetonide intravitreal implants in the FAME trials. Ophthalmic Surg Lasers Imaging Retina. 2016;47:426–35.

    Article  Google Scholar 

  38. Zarranz-Ventura J, Sala-Puigdollers A, Velazquez-Villoria D, Figueras-Roca M, Copete S, Distefano L, et al. Long-term probability of intraocular pressure elevation with the intravitreal dexamethasone implant in the real-world. PLoS One. 2019;14:e0209997.

    CAS  Article  Google Scholar 

  39. Nehme A, Lobenhofer EK, Stamer WD, Edelman JL. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. BMC Med Genomics. 2009;2:58.

    Article  Google Scholar 

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The International Retina Collaborative is an independent research branch of the International Retina Panel, which receives travel support from Allergan.

On behalf of the International Retina Collaborative:

Maria Vittoria Cicinelli1,2, Amir Rosenblatt3,4, Marco Nassisi6,7, Anna Tan8,9,10, Rhianon Reynolds11, Sumit Randhir Singh12, Kaivon P. Vaezi13, Audrey Giocanti-Aurégan14, Tamir Weinberg15, Livia Faes16, Roy Schwartz17,18,19, Denis Yurani Anaya Reyes20, Alfonso Savastano21,22, Sara Touhami23, Humberto Ruiz Garcia24, Dominika Pohlmann25, Adam Plant26, Camila V. Ventura27,28, Irini Chatziralli29, Nopasak Phasukkijwatana30, Jorge Ruiz-Medrano31,32, Miner Yuan33, İhsan Yılmaz34, Denise Vogt35, Daniel Shu Wei Ting8,9,10, Mushawiahti Mustapha36, Marcos Mendaro37


MVC, LC, PZ, AR, DG: No financial disclosures. RL: Allergan (Irvine, California, USA), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), SIFI (Aci Sant’Antonio, Italy). AR reports grant/fees from Allergan Inc (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland). AL reports grant/fees from: Allergan Inc (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Notal-Vision, Sensor, Syneos Health, Beyeonics, Roche, Oxurion Oculis, Pres-by, Xbran, WebMD. FB consultant for: Allergan Inc (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Hoffmann-La-Roche (Basel, Switzerland), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA), Boehringer-Ingelheim, Fidia Sooft, Ntc Pharma, SIFI (Aci Sant’Antonio, Italy).

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All the authors contributed to the conception or design of the work, the acquisition, analysis and interpretation of data, drafting the work, revising it critically for important intellectual content.

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Correspondence to Maria Vittoria Cicinelli.

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Members of the International Retina Collaborative are listed below acknowledgements.

The original online version of this article was revised: In some instances, “edema” was changed to “oedema” and “DME” to “DMO” to be consistent throughout the article.

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Cicinelli, M.V., Rosenblatt, A., Grosso, D. et al. The outcome of fluocinolone acetonide intravitreal implant is predicted by the response to dexamethasone implant in diabetic macular oedema. Eye 35, 3232–3242 (2021).

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