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Intravitreal dexamethasone implant versus anti-vascular endothelial growth factor therapy combined with cataract surgery in patients with diabetic macular oedema: a systematic review with meta-analysis

Eye volume 36, pages 2239–2246 (2022)Cite this article

Subjects

Abstract

Objective

To compare outcomes of cataract surgery combined with either anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy or dexamethasone implant (DEX) in patients with diabetic macular oedema (DMO).

Methods

Pubmed and Embase databases were searched for studies reporting outcomes of diabetic cataract surgery combined with either anti-VEGF or DEX, with a follow-up ≥3 months. The primary outcome was the mean change in central macular thickness (CMT). Mean change in best corrected visual acuity (BCVA) was considered as a secondary outcome. The mean difference between baseline and post-treatment values (MD) with 95%-Confidence Interval (95%CI) was calculated and meta-analyses were performed.

Results

Nine-teen studies were included, 8 in the DEX group and 11 in the anti-VEGF group. A significant reduction of macular thickness was shown in the DEX group at 3 months (MD = −98.35 µm; 95% CI, −147.15/−49.54), while mean CMT change was non-significant in the anti-VEGF group (MD = −21.61 µm; 95% CI, −59.46/16.24; test of group differences, P < 0.001). At 3 months, no difference in visual gain was found between the two groups (P = 0.13).

Conclusions

In DMO patients, cataract surgery combined with DEX seems to provide better anatomical outcomes compared with cataract surgery combined with anti-VEGF therapy. However, our evidence was limited by significant heterogeneity. Randomised trials comparing these two different combined approaches are warranted.

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Fig. 1: One-month central macular thickness (CMT) change.
Fig. 2: Three-month central macular thickness (CMT) change.
Fig. 3: One-month best corrected visual acuity (BCVA) change.
Fig. 4: Three-month best corrected visual acuity (BCVA) change.

References

  1. Wang W, Yan W, Fotis K, Prasad NM, Lansingh VC, Taylor HR, et al. Cataract surgical rate and socioeconomics: a global study. Investig Ophthalmol Vis Sci. 2016;57:5872–81.

    Article  Google Scholar 

  2. Panozzo G, Staurenghi G, Dalla Mura G, Giannarelli D, Alessio G, Alongi S, et al. Prevalence of diabetes and diabetic macular edema in patients undergoing senile cataract surgery in Italy: the DIabetes and CATaract study. Eur J Ophthalmol. 2020;30:315–20.

    Article  PubMed  Google Scholar 

  3. Patel JI, Hykin PG, Cree IA. Diabetic cataract removal: postoperative progression of maculopathy-growth factor and clinical analysis. Br J Ophthalmol. 2006;90:697–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brito PN, Rosas VM, Coentrão LM, Carneiro ÂV, Rocha-Sousa A, Brandão E, et al. Evaluation of visual acuity, macular status, and subfoveal choroidal thickness changes after cataract surgery in eyes with diabetic retinopathy. Retina. 2015;35:294–302.

    Article  PubMed  Google Scholar 

  5. Denniston AK, Chakravarthy U, Zhu H, Lee AY, Crabb DP, Tufail A, et al. The UK Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group, Report 2: Real-world data for the impact of cataract surgery on diabetic macular oedema. Br J Ophthalmol. 2017;101:1673–8.

    Article  PubMed  Google Scholar 

  6. Boscia F, Giancipoli E, Ricci GDA, Pinna A. Management of macular oedema in diabetic patients undergoing cataract surgery. Curr Opin Ophthalmol. 2017;28:23–8.

    Article  PubMed  Google Scholar 

  7. Romero-Aroca P, Fernández-Ballart J, Almena-Garcia M, Méndez-Marín I, Salvat-Serra M, Buil-Calvo JA. Nonproliferative diabetic retinopathy and macular edema progression after phacoemulsification: prospective study. J Cataract Refract Surg. 2006;32:1438–44.

    Article  PubMed  Google Scholar 

  8. Furino C, Boscia F, Niro A, D’Addario M, Grassi MO, Saglimbene V, et al. Diabetic macular edema and cataract surgery: phacoemulsification combined with dexamethasone intravitreal implant compared with standard phacoemulsification. Retina. 2021;41:1102–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fallico M, Avitabile T, Castellino N, Longo A, Russo A, Bonfiglio V, et al. Intravitreal dexamethasone implant one month before versus concomitant with cataract surgery in patients with diabetic macular oedema: the dexcat study. Acta Ophthalmol. 2021;99:e74–80.

    Article  PubMed  Google Scholar 

  10. Agarwal A, Gupta V, Ram J, Gupta A. Dexamethasone intravitreal implant during phacoemulsification. Ophthalmology. 2013;120:211, 211.e1-5.

  11. Feng Y, Zhu S, Skiadaresi E, McAlinden C, Tu R, Gao R, et al. Phacoemulsification cataract surgery with prophylactic intravitreal bevacizumab for patients with coexisting diabetic retinopathy: a meta-Analysis. Retina. 2019;39:1720–31.

    Article  CAS  PubMed  Google Scholar 

  12. Cheema RA, Al-Mubarak MM, Amin YM, Cheema MA. Role of combined cataract surgery and intravitreal bevacizumab injection in preventing progression of diabetic retinopathy. Prospective randomized study. J Cataract Refract Surg. 2009;35:18–25.

    Article  PubMed  Google Scholar 

  13. Chae JB, Joe SG, Yang SJ, Lee JY, Sung KR, Kim JY, et al. Effect of combined cataract surgery and ranibizumab injection in postoperative macular edema in nonproliferative diabetic retinopathy. Retina. 2014;34:149–56.

    Article  PubMed  Google Scholar 

  14. Corbelli E, Fasce F, Iuliano L, Sacconi R, Lattanzio R, Bandello F, et al. Cataract surgery with combined versus deferred intravitreal dexamethasone implant for diabetic macular edema: long-term outcomes from a real-world setting. Acta Diabetol. 2020;57:1193–201. https://doi.org/10.1007/s00592-020-01509-5.

    Article  CAS  PubMed  Google Scholar 

  15. Barone A, Russo V, Maggiore G, Loiodice MS, Stella A, Bux AV, et al. Dexamethasone intravitreal implant in patients with cataract and naïve diabetic macular edema. Eur. J. Ophthalmol. 2021:11206721211004395.

  16. Minnella AM, Maceroni M, Picardi SM, Placidi G, De Siena E, Rizzo S, et al. Combined intravitreal dexamethasone implant and cataract surgery in patients with diabetic retinopathy: effect on retinal morphology and function. Adv Ther. 2020;37:4675–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. editors. Cochrane Handbook for Systematic Reviews of Interventions. 2nd Edition. Chichester (UK): John Wiley & Sons; 2019.

  19. Fallico M, Reibaldi M, Avitabile T, Longo A, Bonfiglio V, Chronopoulos A, et al. Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma. Graefe’s Arch Clin Exp Ophthalmol. 2019;257:1547–54.

    Article  CAS  Google Scholar 

  20. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (Minors): development and validation of a new instrument. ANZ J Surg. 2003;73:712–6.

    Article  PubMed  Google Scholar 

  21. Fallico M, Chronopoulos A, Schutz JS, Reibaldi M. Treatment of radiation maculopathy and radiation-induced macular edema: a systematic review. Surv. Ophthalmol. 2021;66:441–60.

    Google Scholar 

  22. Nyaga VN, Arbyn M, Aerts M. Metaprop: a stata command to perform meta-analysis of binomial data. Arch. Public Heal. 2014;72:39.

    Article  Google Scholar 

  23. Furino C, Boscia F, Niro A, Giancipoli E, Grassi MO, D’Amico Ricci G, et al. Combined phacoemulsification and intravitreal dexamethasone implant (Ozurdex®) in diabetic patients with coexisting cataract and diabetic macular edema. J. Ophthalmol. 2017; 2017. https://pubmed.ncbi.nlm.nih.gov/28884024/.

  24. Panozzo GA, Gusson E, Panozzo G, Dalla Mura G. Dexamethasone intravitreal implant at the time of cataract surgery in eyes with diabetic macular edema. Eur J Ophthalmol. 2017;27:433–7.

    Article  PubMed  Google Scholar 

  25. Akinci A, Batman C, Ozkilic E, Altinsoy A. Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract. Retina. 2009;29:1432–5.

    Article  PubMed  Google Scholar 

  26. Gallego-Pinazo R, Dolz-Marco R, Berrocal M, Wu L, Maia M, Serrano M, et al. Outcomes of cataract surgery in diabetic patients: results of the pan american collaborative retina study group. Arq Bras Oftalmol. 2014;77:355–9. https://pubmed.ncbi.nlm.nih.gov/25627180/.

    Article  PubMed  Google Scholar 

  27. Lanzagorta-Aresti A, Palacios-Pozo E, Menezo Rozalen JL, Navea-Tejerina A. Prevention of vision loss after cataract surgery in diabetic macular edema with intravitreal bevacizumab: a pilot study. Retina. 2009;29:530–5. https://pubmed.ncbi.nlm.nih.gov/19357559/.

    Article  PubMed  Google Scholar 

  28. Kandasamy R, Constantinou M, Rogers SL, Sandhu SS, Wickremasinghe S, Al-Qureshi S, et al. Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results. Br J Ophthalmol. 2019;103:1753–8. https://pubmed.ncbi.nlm.nih.gov/30819688/.

    PubMed  Google Scholar 

  29. Salehi A, Beni AN, Razmjoo H, Beni ZN. Phacoemulcification with intravitreal bevacizumab injection in patients with cataract and coexisting diabetic retinopathy: prospective randomized study. J Ocul Pharmacol Ther. 2012;28:212–8.

    Article  CAS  PubMed  Google Scholar 

  30. Takamura Y, Kubo E, Akagi Y. Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema after cataract surgery. Ophthalmology. 2009;116:1151–7. https://doi.org/10.1016/j.ophtha.2009.01.014.

    Article  PubMed  Google Scholar 

  31. Wahab S, Ahmed J. Management of cataract with macular oedema due to diabetes mellitus type-II and hypertension with grid laser prior to surgery and intra-vitreal bevacizumab (Avastin) peroperatively. J Pak Med Assoc. 2010;60:836–9.

    PubMed  Google Scholar 

  32. Chen CH, Liu YC, Wu PC. The combination of intravitreal bevacizumab and phacoemulsification surgery in patients with cataract and coexisting diabetic macular edema. J Ocul Pharmacol Ther. 2009;25:83–9.

    Article  CAS  PubMed  Google Scholar 

  33. Yumuşak E, Örnek K. Comparison of perioperative ranibizumab injections for diabetic macular edema in patients undergoing cataract surgery. J. Ophthalmol. 2016; 2016:7945619.

  34. Rauen PI, Ribeiro JAS, Almeida FPP, Scott IU, Messias A, Jorge R. Intravitreal injection of ranibizumab during cataract surgery in patients with diabetic macular edema. Retina. 2012;32:1799–803.

    Article  CAS  PubMed  Google Scholar 

  35. Kim SJ, Equi R, Bressler NM. Analysis of macular edema after cataract surgery in patients with diabetes using optical coherence tomography. Ophthalmology. 2007;114:881–9. https://pubmed.ncbi.nlm.nih.gov/17275910/.

    Article  PubMed  Google Scholar 

  36. Chu CJ, Johnston RL, Buscombe C, Sallam AB, Mohamed Q, Yang YC. Risk factors and incidence of macular edema after cataract surgery: a database study of 81984 eyes. Ophthalmology. 2016;123:316–23.

    Article  PubMed  Google Scholar 

  37. Fard MA, Abyane AY, Malihi M. Prophylactic intravitreal bevacizumab for diabetic macular edema (thickening) after cataract surgery: prospective randomized study. Eur. J. Ophthalmol. 2011;21:276–81. https://doi.org/10.5301/EJO.2010.1405.

  38. Funatsu H, Yamashita H, Noma H, Shimizu E, Mimura T, Hori S. Prediction of macular edema exacerbation after phacoemulsification in patients with nonproliferative diabetic retinopathy. J Cataract Refract Surg. 2002;28:1355–63. https://pubmed.ncbi.nlm.nih.gov/12160804/.

    Article  PubMed  Google Scholar 

  39. Bonfiglio V, Reibaldi M, Fallico M, Russo A, Pizzo A, Fichera S, et al. Widening use of dexamethasone implant for the treatment of macular edema. Drug Des Devel Ther. 2017;11:2359–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bonfiglio V, Reibaldi M, Macchi I, Fallico M, Pizzo C, Patane C, et al. Preoperative, intraoperative and postoperative corticosteroid use as an adjunctive treatment for rhegmatogenous retinal detachment. J Clin Med. 2020;9:1556.

    Article  CAS  PubMed Central  Google Scholar 

  41. Bonfiglio V, Fallico MR, Russo A, De Grande V, Longo A, Uva MG, et al. Intravitreal dexamethasone implant for cystoid macular edema and inflammation after scleral buckling. Eur J Ophthalmol. 2015;25:e98–e100.

    Article  PubMed  Google Scholar 

  42. Fallico M, Maugeri A, Romano GL, Bucolo C, Longo A, Bonfiglio V, et al. Epiretinal membrane vitrectomy with and without intraoperative intravitreal dexamethasone implant: a systematic review with meta-analysis. Front. Pharmacol. 2021;12. https://pubmed.ncbi.nlm.nih.gov/33935724/.

  43. Parisi G, Fallico M, Avitabile T, Longo A, Ortisi E, Russo A, et al. Intravitreal dexamethasone implant for postoperative macular oedema secondary to vitrectomy for epiretinal membrane and retinal detachment: a systematic review and meta-analysis. J. Ophthalmol. 2021. https://pubmed.ncbi.nlm.nih.gov/33953965/.

  44. Malcles A, Dot C, Voirin N, Agard E, Vie AL, Bellocq D, et al. Real-life study in diabetic macular edema treated with dexamethasone implant: the reldex study. Retina. 2017;37:753–60.

    Article  CAS  PubMed  Google Scholar 

  45. Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world outcomes of anti–vascular endothelial growth factor therapy in diabetic macular edema in the United States. Ophthalmol Retin. 2018;2:1179–87.

    Article  Google Scholar 

  46. Reibaldi M, Avitabile T, Bandello F, Longo A, Bonfiglio V, Russo A, et al. The effectiveness of 0.6% povidone iodine eye drops in reducing the conjunctival bacterial load and needle contamination in patients undergoing anti-VEGF intravitreal injection: a prospective, randomized study. J Clin Med. 2019;8:1031.

    Article  CAS  PubMed Central  Google Scholar 

  47. Reibaldi M, Fallico M, Avitabile T, Bonfiglio V, Russo A, Castellino N, et al. Risk of death associated with intravitreal anti-vascular endothelial growth factor therapy: a systematic review and meta-analysis. JAMA Ophthalmol. 2020;138:50–7.

    Article  PubMed  Google Scholar 

  48. Rezkallah A, Mathis T, Abukhashabah A, Voirin N, Malclès A, Agard É, et al. Long-term incidence and risk factors of ocular hypertension following Dexamethasone-implant injections. The SAFODEX-2 study. Retina. 2021;41:1438–45.

    Article  CAS  PubMed  Google Scholar 

  49. Fallico M, Maugeri A, Lotery A, Longo A, Bonfiglio V, Russo A, et al. Intravitreal anti-vascular endothelial growth factors, panretinal photocoagulation and combined treatment for proliferative diabetic retinopathy: a systematic review and network meta-analysis. Acta Ophthalmol. 2021;99:e795–805.

    Article  PubMed  Google Scholar 

  50. Fallico M, Maugeri A, Lotery A, Longo A, Bonfiglio V, Russo A, et al. Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience. Sci Rep. 2021;11. https://pubmed.ncbi.nlm.nih.gov/33637841/.

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Acknowledgements

We are thankful to Giorgio Pulvirenti for his contribution in data collection.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of Catania, 95123, Catania, Italy

    Matteo Fallico, Andrea Russo, Antonio Longo & Teresio Avitabile

  2. Faculty of Medicine, University of Southampton, Southampton, UK

    Andrew Lotery

  3. Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123, Catania, Italy

    Andrea Maugeri, Giuliana Favara, Martina Barchitta & Antonella Agodi

  4. Department of Experimental Biomedicine and Clinical Neuroscience, Ophthalmology Section, University of Palermo, 90127, Palermo, Italy

    Vincenza Bonfiglio

  5. Department of Surgical Sciences, Eye Clinic Section, University of Turin, 10122, Turin, Italy

    Paola Marolo, Guglielmo Parisi & Michele Reibaldi

  6. Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy

    Enrico Borrelli

  7. Department of Public Health, University of Naples Federico II, 80131, Naples, Italy

    Gilda Cennamo

  8. Department of Ophthalmology, University of Bari, 70124, Bari, Italy

    Claudio Furino

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  1. Matteo Fallico
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Contributions

Conceptualization, MR, MF, AA, ALotery; methodology, AM, EB, MB, GF, ALongo; investigation, MF, PM, ALongo, TA; data curation: MF, PM, AM, GF, MB, GP, AR, VB; writing—original draft preparation, VB, AR, CF, GC, EB; writing—review and editing, all authors; supervision, TA, ALotery, MR, AA. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Matteo Fallico.

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AL has consulted for Novartis Pharmaceuticals, Allergan, Janssen and Gyroscope Therapeutics. Other authors declare no competing interests.

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Fallico, M., Lotery, A., Maugeri, A. et al. Intravitreal dexamethasone implant versus anti-vascular endothelial growth factor therapy combined with cataract surgery in patients with diabetic macular oedema: a systematic review with meta-analysis. Eye 36, 2239–2246 (2022). https://doi.org/10.1038/s41433-021-01847-w

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