Combined intravitreal ranibizumab and posterior subtenon triamcinolone acetonide injections for patients with diabetic macular edema refractory to intravitreal ranibizumab monotherapy

Abstract

PURPOSE: The purpose of this study is to compare the efficacy of intravitreal ranibizumab (IVR) alone and concurrent IVR with posterior subtenon triamcinolone acetonide (PSTA) injection for patients with diabetic macular edema (DME) refractory to IVR monotherapy. MATERIALS AND METHODS: We enrolled 43 eyes of 43 patients with DME who received at least three times of IVR, which resulted in poor anatomical responses, with central foveal thickness (CFT) reduction <10% and postinjection CFT >300 μm. All the eyes received initial 3 monthly then pro re nata (PRN) IVR 0.5-mg injections. Twenty eyes continued PRN injections and 23 eyes received combined IVR 0.5 mg and PSTA 40 mg with at least 1-year follow-up. Best-corrected visual acuity (BCVA) and CFT were recorded from 1-month to 1-year follow-up. RESULTS: Following switch to combined therapy, the mean BCVA significantly improved from 0.61 ± 0.32 logarithm of the minimum angle of resolution (logMAR) to 0.45±0.39 logMAR at 6 month ( P = 0.003), 0.43±0.35 logMAR at 9 months ( P < 0.001), and 0.48±0.45 logMAR at 1 year ( P = 0.03). In eyes with IVR alone, no significant VA improvement was noted throughout the year. Significantly better BCVA was noted in the combined group at 6-month, 9-month, and 1-year follow-up compared to IVR-alone group. The timing of combined therapy showed a significant association with 1-year BCVA ( t = 3.25, P = 0.018). CONCLUSION: Concurrent IVR and PSTA resulted in significantly better visual outcomes in 1-year follow-up for those refractory to preceding ranibizumab monotherapy for DME. Early addition of PSTA predicted a better visual outcome.

Anti‐VEGF and steroid combination therapy relative to anti‐VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta‐analysis of safety

“…This systematic review and meta‐analysis investigated the efficacy and safety of combined intravitreal anti‐VEGF and steroid treatment for refractory DME. The majority of studies in our review found that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared with anti‐VEGF monotherapy (Ahmadieh et al, 2008; Chiu et al, 2021; Eriş et al, 2019; Limon, 2021; Maturi et al, 2015, 2018; Yolcu & Sobaci, 2015). Two studies (one RCT and one non‐randomized prospective) found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared with anti‐VEGF monotherapy (Ahmadieh et al, 2008; Limon, 2021).…”

“…Chiu et al conducted a retrospective study of 43 Taiwanese adults with persistent DME and poor anatomical response after at least three doses of IVR (Chiu et al, 2021). 20 eyes continued PRN injections of IVR and 23 eyes received combined IVR and PSTA with at least 1‐year follow‐up.…”

“…For RCTs of patients refractory to anti‐VEGF treatment, treatment resistance was defined as CMT over 350 μm, less than three lines of visual gain at least after six anti‐VEGF injections, (Eriş et al, 2019) incomplete response to multiple anti‐VEGF injections and CST of 250 μm (Maturi et al, 2015) and persistent DME after the 12‐week run in phase where CST greater than the threshold (≥290 μm in women, ≥305 μm in men) values were maintained despite each eye receiving three additional anti‐VEGF injections (Maturi et al, 2018). The observational studies defined anti‐VEGF resistance as receiving at least three IVR injections, that resulted in poor anatomical responses, with central foveal thickness (CFT) reduction <10% and post‐injection CFT >300 μm (Chiu et al, 2021), or (CMT) >300 μm on spectral‐domain OCT and ETDRS BCVA letters score >20 after at least six monthly interval injections of bevacizumab, ranibizumab or aflibercept (Limon, 2021). One observational study included patients resistant to both anti‐VEGF and steroid, specifically refractory to two normal and higher dose mono‐injections of previous successive intravitreal bevacizumab (IVB) and triamcinolone (IVTA) injections (Yolcu & Sobaci, 2015).…”

“…Seven studies (four RCTs and three observational studies) reporting on 452 eyes were included in our systematic review from a total of 2674 studies in title and abstract screening followed by 183 studies in full-text review (Figure 1) (Ahmadieh et al, 2008;Chiu et al, 2021;Eriş et al, 2019;Limon, 2021;Maturi et al, 2015Maturi et al, , 2018Yolcu & Sobaci, 2015). All included studies investigated effects of anti-VEGF/steroid combination therapy for DME patients refractory to either anti-VEGF injections (Chiu et al, 2021;Eriş et al, 2019;Limon, 2021;Maturi et al, 2015Maturi et al, , 2018Yolcu & Sobaci, 2015) or laser photocoagulation (Ahmadieh et al, 2008). Baseline information and patient characteristics are summarized in Table 1.…”

“…Five studies reported total number of injections (Chiu et al, 2021;Eriş et al, 2019;Limon, 2021;Maturi et al, 2015Maturi et al, , 2018, and four of those studies (two observational (Chiu et al, 2021;Limon, 2021) and one RCT (Eriş et al, 2019;Maturi et al, 2018)) reported values in mean and standard deviation which allowed us to conduct a meta-analysis. The total number of injections between intravitreal anti-VEGF agents and combined anti-VEGF and steroid agents were similar across studies (p = 0.86, Figure 3a) (total number of patients = 293, mean follow-up = 6.38 ± 3.77 months).…”