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Open Access 12-09-2023 | Edema | Original Paper

Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study

Authors: José María Ruiz-Moreno, Alfredo Adán, María Lafuente, Mónica Asencio Durán, Luís Arias Barquet, Alfredo García Layana, Javier Araiz Iribarren

Published in: International Ophthalmology | Issue 12/2023

Abstract

Objective

To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies.

Methods

This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values.

Results

Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm³ at baseline to 9.6 ± 2.9 mm³ (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery.

Conclusions

In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events.

Trial registration number

EudraCT identifier: 2016-001680-37.

Available only for authorised users

Im JHB, Jin YP, Chow R, Yan P (2022) Prevalence of diabetic macular edema based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Surv Ophthalmol 67(4):1244–1251. https://doi.org/10.1016/j.survophthal.2022.01.009CrossRefPubMed

Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS et al (2017) Guidelines for the management of diabetic macular edema by the European society of retina specialists (EURETINA). Ophthalmologica 237(4):185–222. https://doi.org/10.1159/000458539CrossRefPubMed

Ruiz-Medrano J, Rodríguez-Leor R, Almazán E, Lugo F, Casado-Lopez E, Arias L, Ruiz-Moreno JM (2021) Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: early versus late switch. Eur J Ophthalmol 31(3):1135–1145. https://doi.org/10.1177/1120672120929960CrossRefPubMed

Alessio G, Boscia F, Caporossi A, Panozzo G, Reibaldi M, Staurenghi G, Varano M, Bandello F (2021) Dexamethasone implants in patients with diabetic macular edema undergoing cataract surgery: Italian expert panel consensus statements. Eur J Ophthalmol 31(3):1122–1127. https://doi.org/10.1177/1120672120939500CrossRefPubMed

Campochiaro PA, Nguyen QD, Hafiz G, Bloom S, Brown DM, Busquets M, Ciulla T, Feiner L, Sabates N, Billman K, Kapik B, Green K, Kane FE, FAMOUS Study Group (2013) Aqueous levels of fluocinolone acetonide after administration of fluocinolone acetonide inserts or fluocinolone acetonide implants. Ophthalmology 120(3):583–587. https://doi.org/10.1016/j.ophtha.2012.09.014CrossRefPubMed

Chakravarthy U, Taylor SR, Koch FHJ, Castro de Sousa JP, Bailey C (2019) Changes in intraocular pressure after intravitreal fluocinolone acetonide (ILUVIEN): real-world experience in three European countries. Br J Ophthalmol 103(8):1072–1077. https://doi.org/10.1136/bjophthalmol-2018-312284CrossRefPubMed

Bodaghi B, Nguyen QD, Jaffe G, Khoramnia R, Pavesio C (2020) Preventing relapse in non-infectious uveitis affecting the posterior segment of the eye – evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant (ILUVIEN^®). J Ophthalmic Inflamm Infect 10(1):32. https://doi.org/10.1186/s12348-020-00225-zCrossRefPubMedPubMedCentral

Hikal M, Celik N, Auffarth GU, Kessler LJ, Mayer CS, Khoramnia R (2021) Intravitreal 0.19 mg fluocinolone acetonide implant in non-infectious uveitis. J Clin Med 10(17):3966. https://doi.org/10.3390/jcm10173966CrossRefPubMedPubMedCentral

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(4):626–635. https://doi.org/10.1016/j.ophtha.2010.12.028CrossRefPubMed

10.

Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, Garretson B, Gupta A, Hariprasad SM, Bailey C, Reichel E, Soubrane G, Kapik B, Billman K, Kane FE, Green K, FAME Study Group (2012) Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 119(10):2125–2132. https://doi.org/10.1016/j.ophtha.2012.04.030CrossRefPubMed

11.

Augustin AJ, Bopp S, Fechner M, Holz F, Sandner D, Winkgen AM, Khoramnia R, Neuhann T, Warscher M, Spitzer M, Sekundo W, Seitz B, Duncker T, Ksinsik C, Höh H, Gentsch D (2020) Three-year results from the Retro-IDEAL study: real-world data from diabetic macular edema (DME) patients treated with ILUVIEN^® (0.19 mg fluocinolone acetonide implant). Eur J Ophthalmol 30(2):382–391. https://doi.org/10.1177/1120672119834474CrossRefPubMed

12.

Mushtaq B, Bhatnagar A, Palmer H (2021) Real-world outcomes in diabetic macular edema for the 0.2 µg/Day fluocinolone acetonide implant: case series from the midlands. UK Clin Ophthalmol 15:2935–2943. https://doi.org/10.2147/OPTH.S283561CrossRefPubMed

13.

Khoramnia R, Peto T, Koch F, Taylor SR, Castro de Sousa JP, Hill L, Bailey C, Chakravarthy U, ILUVIEN Registry Safety Study (IRISS) Investigators Group (2022) Safety and effectiveness of the fluocinolone acetonide intravitreal implant (ILUVIEN): 3-year results from the European IRISS registry study. Br J Ophthalmol. https://doi.org/10.1136/bjo-2022-32141CrossRefPubMed

14.

Singer MA, Sheth V, Mansour SE, Coughlin B, Gonzalez VH (2022) Three-year safety and efficacy of the 0.19-mg fluocinolone acetonide intravitreal implant for diabetic macular edema: the PALADIN study. Ophthalmology 129(6):605–613. https://doi.org/10.1016/j.ophtha.2022.01.015CrossRefPubMed

15.

Gallén LS, Del Rio NR, Vilaplana-Mora JM, Alarcón-Correcher F, Natividad SA, Ibor FG, Duch-Samper AM (2022) Fluocinolone acetonide intravitreal implant for the treatment of macular edema: long-term outcomes from a single tertiary hospital. Acta Ophthalmol. https://doi.org/10.1111/j.1755-3768.2022.0756CrossRef

16.

Miguel-Escuder L, Olate-Pérez Á, Sala-Puigdoners A, Moll-Udina A, Figueras-Roca M, Navarro-Angulo MJ, Adán A, Pelegrín L (2023) Intravitreal fluocinolone acetonide implant for the treatment of persistent post-surgical cystoid macular edema in vitrectomized eyes. Eur J Ophthalmol 33(1):NP23–NP27. https://doi.org/10.1177/11206721211046718CrossRefPubMed

17.

World Medical Association. World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects. 64th WMA General Assembly, Fortaleza, Brazil, October 2013. Available in: https://www.wma.net/wp-content/uploads/2016/11/DoH-Oct2013-JAMA.pdf Last Accessed from 12 Jul 2023

18.

Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg for intravitreal injection. Summary of Product Characteristic. Available in https://webcache.googleusercontent.com/search?q=cache:gu3-KoUuX6gJ:https://www.alimerasciences.com/wp-content/uploads/2016/02/Prescribing-Information.pdf+&cd=1&hl=es&ct=clnk&gl=es Last Accessed from 12 Jul 2023

19.

Gonzalez VH, Campbell J, Holekamp NM, Kiss S, Loewenstein A, Augustin AJ, Ma J, Ho AC, Patel V, Whitcup SM, Dugel PU (2016) Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol 172:72–79. https://doi.org/10.1016/j.ajo.2016.09.012CrossRefPubMed

20.

Ciulla TA, Pollack JS, Williams DF (2021) Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. Br J Ophthalmol 105(2):216–221. https://doi.org/10.1136/bjophthalmol-2020-315933CrossRefPubMed

21.

Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122(7):1375–1394. https://doi.org/10.1016/j.ophtha.2015.03.024CrossRefPubMed

22.

Fusi-Rubiano W, Blow RR, Lane M, Morjaria R, Denniston AK (2018) Iluvien™ (Fluocinolone Acetonide 0.19 mg Intravitreal Implant) in the treatment of diabetic macular edema: a review. Ophthalmol Ther 7(2):293–305. https://doi.org/10.1007/s40123-018-0145-7CrossRefPubMedPubMedCentral

23.

Iovino C, Mastropasqua R, Lupidi M, Bacherini D, Pellegrini M, Bernabei F, Borrelli E, Sacconi R, Carnevali A, D’Aloisio R, Cerquaglia A, Finocchio L, Govetto A, Erba S, Triolo G, Di Zazzo A, Forlini M, Vagge A, Giannaccare G (2020) Intravitreal dexamethasone implant as a sustained release drug delivery device for the treatment of ocular diseases: a comprehensive review of the literature. Pharmaceutics 12(8):703. https://doi.org/10.3390/pharmaceutics12080703CrossRefPubMedPubMedCentral

24.

Wu Z, McGoogan JM (2020) Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the chinese center for disease control and prevention. JAMA 323(13):1239–1242. https://doi.org/10.1001/jama.2020.2648CrossRefPubMed

25.

Mansour SE, Kiernan DF, Roth DB, Eichenbaum D, Holekamp NM, Kaba S, Werts E (2021) Two-year interim safety results of the 0.2 µg/day fluocinolone acetonide intravitreal implant for the treatment of diabetic macular oedema: the observational PALADIN study. Br J Ophthalmol 105(3):414–419. https://doi.org/10.1136/bjophthalmol-2020-315984CrossRefPubMed

26.

Mathis T, Papegaey M, Ricard C, Rezkallah A, Matonti F, Sudhalkar A, Vartin C, Dot C, Kodjikian L (2022) Efficacy and safety of intravitreal fluocinolone acetonide implant for chronic diabetic macular edema previously treated in real-life practice: the REALFAc study. Pharmaceutics 14(4):723. https://doi.org/10.3390/pharmaceutics14040723CrossRefPubMedPubMedCentral

27.

Alfaqawi F, Lip PL, Elsherbiny S, Chavan R, Mitra A, Mushtaq B (2017) 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 (Lond) 31(4):650–656. https://doi.org/10.1038/eye.2016.301CrossRefPubMed

28.

Bailey C, Chakravarthy U, Lotery A, Menon G, Talks J, Medisoft Audit Group (2017) Real-world experience with 0.2 μg/day fluocinolone acetonide intravitreal implant (ILUVIEN) in the United Kingdom. Eye (Lond) 31(12):1707–1715. https://doi.org/10.1038/eye.2017.125CrossRefPubMed

29.

Fusi-Rubiano W, Mukherjee C, Lane M, Tsaloumas MD, Glover N, Kidess A, Denniston AK, Palmer HE, Manna A, Morjaria R (2018) Treating diabetic macular oedema (DMO): real world UK clinical outcomes for the 0.19mg Fluocinolone Acetonide intravitreal implant (Iluvien™) at 2 years. BMC Ophthalmol 18(1):62. https://doi.org/10.1186/s12886-018-0726-1CrossRefPubMedPubMedCentral

30.

Eaton A, Koh SS, Jimenez J, Riemann CD (2019) The USER study: a chart review of patients receiving a 0.2 µg/day fluocinolone acetonide implant for diabetic macular edema. Ophthalmol Ther 8(1):51–62. https://doi.org/10.1007/s40123-018-0155-5CrossRefPubMed

31.

Young JF, Walkden A, Stone A, Mahmood S (2019) Clinical effectiveness of intravitreal fluocinolone acetonide (FAc) (ILUVIEN™) in patients with diabetic macular oedema (DMO) refractory to prior therapy: the manchester experience. Ophthalmol Ther 8(3):477–484. https://doi.org/10.1007/s40123-019-0197-3CrossRefPubMedPubMedCentral

32.

Panos GD, Arruti N, Patra S (2021) The long-term efficacy and safety of fluocinolone acetonide intravitreal implant 190 μg (ILUVIEN<sup>®</sup>) in diabetic macular oedema in a multi-ethnic inner-city population. Eur J Ophthalmol 31(2):620–629. https://doi.org/10.1177/1120672119898414CrossRefPubMed

33.

Bailey C, Chakravarthy U, Lotery A, Menon G, Talks J, Medisoft Audit Group (2022) Extended real-world experience with the ILUVIEN^® (fluocinolone acetonide) implant in the United Kingdom: 3-year results from the Medisoft^® audit study. Eye (Lond) 36(5):1012–1018. https://doi.org/10.1038/s41433-021-01542-CrossRefPubMed

34.

Elbarky AM (2021) Effectiveness and tolerability of the fluocinolone acetonide implant in patients with diabetic macular edema in UAE: 12-Month results. Eur J Ophthalmol 31(6):3196–3202. https://doi.org/10.1177/1120672120982948CrossRefPubMed

35.

Kodjikian L, Baillif S, Creuzot-Garcher C, Delyfer MN, Matonti F, Weber M, Mathis T (2021) Real-world efficacy and safety of fluocinolone acetonide implant for diabetic macular edema: a systematic review. Pharmaceutics 13(1):72. https://doi.org/10.3390/pharmaceutics13010072CrossRefPubMedPubMedCentral

36.

Fallico M, Maugeri A, Lotery A, Longo A, Bonfiglio V, Russo A, Avitabile T, Furino C, Cennamo G, Barchitta M, Agodi A, Marolo P, Ventre L, Caselgrandi P, Reibaldi M (2021) Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience. Sci Rep 11(1):4800. https://doi.org/10.1038/s41598-021-84362-yCrossRefPubMedPubMedCentral

Title: Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study
Authors: José María Ruiz-Moreno
Alfredo Adán
María Lafuente
Mónica Asencio Durán
Luís Arias Barquet
Alfredo García Layana
Javier Araiz Iribarren
Publication date: 12-09-2023
Publisher: Springer Netherlands
Keywords: Edema
Cataract
Published in: International Ophthalmology / Issue 12/2023
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-023-02864-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study

Abstract

Objective

Methods

Results

Conclusions

Trial registration number

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Trial registration number

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