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Clinical and imaging biomarkers of response to intravitreal dexamethasone implant in eyes with non-infectious uveitic macular oedema

Eye volume 38, pages 910–916 (2024)Cite this article

Subjects

Abstract

Objective

To investigate clinical and spectral-domain optical coherence tomography (SD-OCT) biomarkers correlating with pre-injection visual acuity (VA), post-injection VA, and the likelihood of macular oedema (MO) regression following dexamethasone (DEX) implant injection in non-infectious uveitic (NIU) patients.

Methods

Patient data from Uveitis Services in Milan, Paris, and Berlin were analysed. Eligible participants were NIU patients aged >18 years with MO as the primary indication for DEX treatment. SD-OCT scans and clinical data were collected at the time of DEX injection (pre-injection visit) and after 3 months (post-injection visit). Multivariable regression models, adjusted for pre-injection VA and lens status, were employed to explore associations. MO regression was defined as the absence of intraretinal/subretinal fluid at the post-injection visit.

Results

Our analysis comprised data from 173 DEX treatments, encompassing 103 eyes from 80 patients, with 38 eyes (37%) receiving repeated DEX injections. The absence of the ellipsoid zone (EZ) layer and disorganisation of the inner retinal layers (DRIL) were associated with worse pre- (+0.19 LogMAR, 95% CI 0.01–0.38, p = 0.06, and +0.10 LogMAR, 95% CI 0.02–0.21, p = 0.01) and post-injection VA (+0.33 LogMAR, 95% CI 0.08–0.57, p = 0.01, and +0.17 LogMAR, 95% CI 0.01–0.32, p = 0.04). EZ disruption and DRIL increased significantly (p = 0.01 and p = 0.04), and the chance of gaining ≥5 letters declined in eyes undergoing repeated DEX (p = 0.002). The rate of MO regression after each DEX was 67%. Prolonged MO duration (OR = 0.75/each year, p = 0.02) was associated with reduced likelihood of MO regression. Subretinal fluid was associated with higher rate of MO regression (OR = 6.09, p = 0.01).

Conclusion

Integrity of the inner and outer retina is associated with better visual response to DEX. Long-standing or recurrent MO is associated with less chance of both visual and anatomic response. Timely treatment is necessary to maximise the outcomes of MO in NIU patients.

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Fig. 1: Qualitative assessment of spectral-domain optical coherence tomography (SD-OCT).
Fig. 2: Correlation between pre- and post-injection visual acuity (VA).

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References

  1. Tomkins-Netzer O, Talat L, Bar A, Lula A, Taylor SR, Joshi L, et al. Long-term clinical outcome and causes of vision loss in patients with uveitis. Ophthalmology. 2014;121:2387–92.

    Article  PubMed  Google Scholar 

  2. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996;80:332–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492–513.

    Article  CAS  PubMed  Google Scholar 

  4. Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011;129:545–53.

    Article  PubMed  Google Scholar 

  5. Zarranz-Ventura J, Carreno E, Johnston RL, Mohammed Q, Ross AH, Barker C, et al. Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: indications, outcomes, and reinjection frequency. Am J Ophthalmol. 2014;158:1136–45.e5.

    Article  CAS  PubMed  Google Scholar 

  6. Khurana RN, Porco TC. Efficacy and safety of dexamethasone intravitreal implant for persistent uveitic cystoid macular edema. Retina. 2015;35:1640–6.

    Article  CAS  PubMed  Google Scholar 

  7. Tomkins-Netzer O, Taylor SR, Bar A, Lula A, Yaganti S, Talat L, et al. Treatment with repeat dexamethasone implants results in long-term disease control in eyes with noninfectious uveitis. Ophthalmology. 2014;121:1649–54.

    Article  PubMed  Google Scholar 

  8. Tsang AC, Virgili G, Abtahi M, Gottlieb CC. Intravitreal dexamethasone implant for the treatment of macular edema in chronic non-infectious uveitis. Ocul Immunol Inflamm. 2017;25:685–92.

    Article  PubMed  Google Scholar 

  9. Kang EY, Garg SJ, Chen HF, Wu WC, Chen LY, Chou HD, et al. Intravitreal dexamethasone implants for refractory macular edema in eyes with noninfectious uveitis. J Clin Med. 2021;10:3762.

  10. Pohlmann D, Vom Brocke GA, Winterhalter S, Steurer T, Thees S, Pleyer U. Dexamethasone inserts in noninfectious uveitis: a single-center experience. Ophthalmology. 2018;125:1088–99.

    Article  PubMed  Google Scholar 

  11. Marchese A, Cicinelli MV, Amato A, Bandello F, Gupta V, Miserocchi E, et al. The next steps in ocular imaging in uveitis. Ocul Immunol Inflamm. 2023;31:1–8.

  12. Ciulla TA, Kapik B, Grewal DS, Ip MS. Visual acuity in retinal vein occlusion, diabetic, and uveitic macular edema: central subfield thickness and ellipsoid zone analysis. Ophthalmol Retin. 2021;5:633–47.

    Article  Google Scholar 

  13. Zur D, Iglicki M, Busch C, Invernizzi A, Mariussi M, Loewenstein A, et al. OCT biomarkers as functional outcome predictors in diabetic macular edema treated with dexamethasone implant. Ophthalmology. 2018;125:267–75.

    Article  PubMed  Google Scholar 

  14. Cicinelli MV, Chatziralli I, Touhami S, Smaoui A, Tombolini B, Nassisi M, et al. Epiretinal membrane peeling in eyes with retinal vein occlusion: visual and morphologic outcomes. Ophthalmol Ther. 2022;11:661–75.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rübsam A, Wernecke L, Rau S, Pohlmann D, Müller B, Zeitz O, et al. Behavior of SD-OCT detectable hyperreflective foci in diabetic macular edema patients after therapy with anti-VEGF agents and dexamethasone implants. J Diabetes Res. 2021;2021:8820216.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhang Z, Yuan KH. Practical Statistical power analysis using webpower and R. Granger: ISDSA Press; 2018.

  17. Grewal DS, O’Sullivan ML, Kron M, Jaffe GJ. Association of disorganization of retinal inner layers with visual acuity in eyes with uveitic cystoid macular edema. Am J Ophthalmol. 2017;177:116–25.

    Article  PubMed  Google Scholar 

  18. Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Methodol. 1996;58:267–88.

    Google Scholar 

  19. Khurana RN, Bansal AS, Chang LK, Palmer JD, Wu C, Wieland MR. Prospective evaluation of a sustained-release dexamethasone intravitreal implant for cystoid macular edema in quiescent uveitis. Retina. 2017;37:1692–9.

    Article  CAS  PubMed  Google Scholar 

  20. Cao JH, Mulvahill M, Zhang L, Joondeph BC, Dacey MS. Dexamethasone intravitreal implant in the treatment of persistent uveitic macular edema in the absence of active inflammation. Ophthalmology. 2014;121:1871–6.

    Article  PubMed  Google Scholar 

  21. Matas J, Llorenç V, Fonollosa A, Esquinas C, Diaz-Valle D, Berasategui B, et al. Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis. PLoS ONE. 2019;14:e0210799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Habot-Wilner Z, Sorkin N, Goldenberg D, Loewenstein A, Goldstein M. Long-term outcome of an intravitreal dexamethasone implant for the treatment of noninfectious uveitic macular edema. Ophthalmologica. 2014;232:77–82.

    Article  CAS  PubMed  Google Scholar 

  23. Miserocchi E, Modorati G, Pastore MR, Bandello F. Dexamethasone intravitreal implant: an effective adjunctive treatment for recalcitrant noninfectious uveitis. Ophthalmologica. 2012;228:229–33.

    Article  CAS  PubMed  Google Scholar 

  24. 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  PubMed  Google Scholar 

  25. Sun JK, Lin MM, Lammer J, Prager S, Sarangi R, Silva PS, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132:1309–16.

    Article  PubMed  Google Scholar 

  26. Cavalleri M, Cicinelli MV, Parravano M, Varano M, De Geronimo D, Sacconi R, et al. Prognostic role of optical coherence tomography after switch to dexamethasone in diabetic macular edema. Acta Diabetol. 2020;57:163–71.

    Article  CAS  PubMed  Google Scholar 

  27. Berry D, Thomas AS, Fekrat S, Grewal DS. Association of disorganization of retinal inner layers with ischemic index and visual acuity in central retinal vein occlusion. Ophthalmol Retin. 2018;2:1125–32.

    Article  Google Scholar 

  28. Zur D, Iglicki M, Feldinger L, Schwartz S, Goldstein M, Loewenstein A, et al. Disorganization of retinal inner layers as a biomarker for idiopathic epiretinal membrane after macular surgery—the DREAM Study. Am J Ophthalmol. 2018;196:129–35.

    Article  PubMed  Google Scholar 

  29. Ciulla TA, Kapik B, Barakat MR, Khurana RN, Nguyen QD, Grewal DS, et al. Optical coherence tomography anatomic and temporal biomarkers in uveitic macular edema. Am J Ophthalmol. 2022;237:310–24.

    Article  CAS  PubMed  Google Scholar 

  30. Bodaghi B, Brézin AP, Weber M, Delcourt C, Kodjikian L, Provost A, et al. Real-life efficacy, safety, and use of dexamethasone intravitreal implant in posterior segment inflammation due to non-infectious uveitis (LOUVRE 2 Study). Ophthalmol Ther. 2022;11:1775–92.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Jonas JB, Spandau UH, Kamppeter BA, Vossmerbaeumer U, Harder B, Sauder G. Repeated intravitreal high-dosage injections of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology. 2006;113:800–4.

    Article  PubMed  Google Scholar 

  32. Nicholson BP, Zhou M, Rostamizadeh M, Mehta P, Agrón E, Wong W, et al. Epidemiology of epiretinal membrane in a large cohort of patients with uveitis. Ophthalmology. 2014;121:2393–8.

    Article  PubMed  Google Scholar 

  33. Rao P, Todorich B, Yonekawa Y, Wang J, Sobrin L, Faia LJ. Surgical outcomes of epiretinal membranes in patients with a history of well-controlled preoperative uveitis. Ophthalmol Retin. 2018;2:192–6.

    Article  Google Scholar 

  34. Munk MR, Bolz M, Huf W, Sulzbacher F, Roberts P, Simader C, et al. Morphologic and functional evaluations during development, resolution, and relapse of uveitis-associated cystoid macular edema. Retina. 2013;33:1673–83.

    Article  PubMed  Google Scholar 

  35. Berasategui B, Fonollosa A, Artaraz J, Ruiz-Arruza I, Ríos J, Matas J, et al. Behavior of hyperreflective foci in non-infectious uveitic macular edema, a 12-month follow-up prospective study. BMC Ophthalmol. 2018;18:179.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lehpamer B, Moshier E, Goldberg N, Ackert J, Godbold J, Jabs DA. Subretinal fluid in uveitic macular edema: effect on vision and response to therapy. Am J Ophthalmol. 2013;155:143–9.

    Article  PubMed  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Financial disclosures: CG, PS, EM: no financial disclosures. MVC, ST, DP, AG, AR previously received travel grants from Allergan as International Retinal Panel members. FB consultant for: Allergan Inc (Irvine, California, USA), Bayer Schering-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. AL consultant for: Allergan, Bayer health care, Beyeonics, ForSight Labs, Notal Vision, Novartis, Roche, WebMD, Syneos, Xbrane, Nanoretina, Ocuterra, Ripple Therapeutics, Annexon, MJHEvents, Iveric Bio, Biogen, Johnson & Johnson, Ophtimedrx, Ocuphire Pharma, Iqvia.

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Authors and Affiliations

  1. School of Medicine, Vita-Salute San Raffaele University, Milan, Italy

    Maria Vittoria Cicinelli, Claudia Gerosolima, Pierluigi Scandale, Francesco Bandello & Elisabetta Miserocchi

  2. Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Maria Vittoria Cicinelli, Claudia Gerosolima, Pierluigi Scandale, Francesco Bandello & Elisabetta Miserocchi

  3. Department of Ophthalmology, Reference Center in Rare Diseases, DHU Sight Restore, Hôpital Pitié Salpêtrière, Sorbonne Université, Paris, France

    Sarah Touhami

  4. Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Dominika Pohlmann

  5. Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 13353, Berlin, Germany

    Dominika Pohlmann

  6. INSERM, Bordeaux Population Health Research Center, UMR1219, Université de Bordeaux, Bordeaux, France

    Audrey Giocanti

  7. Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Amir Rosenblatt & Anat Loewenstein

  8. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Amir Rosenblatt & Anat Loewenstein

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On behalf of the International Retina Panel

  • Maria Vittoria Cicinelli
  • , Sarah Touhami
  • , Dominika Pohlmann
  • , Audrey Giocanti
  • , Amir Rosenblatt
  •  & Anat Loewenstein

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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, and revising it critically for intellectual content. Each coauthor has seen and agrees with how his or her name is listed.

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Cicinelli, M.V., Gerosolima, C., Scandale, P. et al. Clinical and imaging biomarkers of response to intravitreal dexamethasone implant in eyes with non-infectious uveitic macular oedema. Eye 38, 910–916 (2024). https://doi.org/10.1038/s41433-023-02802-7

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