Comparative assessment of intravitreal steroid implant with combination therapy for diabetic macular edema
Year: 2024
Type: article
Abstract: Dear Editor, A prospective single-masked, double-arm randomized pilot study was performed to determine if adding an anti-VEGF agent to standalone steroid implants provided any additional anatomical advantage in managing DME. Forty-nine eyes of adult patients with DME-related visual loss and central macular thickness (CMT) ≥300 µm were randomized to receive either dexamethasone implant (group 1 – steroids) alone or in combination with bevacizumab (group 2 – combination). Injections were given at baseline, followed by a PRN schedule with a minimum interval of 4 months. Mean CMT (µm) at baseline was 462.56 ± 119.71 in the steroid group and 389.71 ± 102.14 in the combination group (P = 0.027, significantly higher in group 1). On day 180, the mean CMT (µm) decreased to 272.36 ± 77.5 in group 1 and 277.83 ± 85.03 in group 2 (P = 0.815, not significant; the difference between the two groups disappeared; Table 1). The rate of resolution of edema was similar in both groups [Fig. 1].Figure 1: Graphical representation of central macular thickness at every visit. This graph shows the variation in macular thickness at each visit for both study groups. The x-axis shows time elapsed from the first injection, and the y-axis shows the central macular thickness (in microns)Table 1: Changes in central macular thickness during the study periodThe mean reduction in CMT from baseline did not show any statistically significant difference in the initial visits. This indicates that the addition of an anti-VEGF agent in group 2 did not hasten the resolution of edema. The absolute reduction in CMT at the end of the study period was more in group 1, which was statistically significant. However, this can also be ascribed to the fact that group 1 had a higher CMT in the beginning. Six patients in group 1 and five in group 2 developed a rise in intraocular pressure controlled with only topical therapy. Most trials in the literature have compared combination therapy with standalone anti-VEGF therapy and have worked on the inherent assumption of superiority of anti-VEGF agents. Only a few trials in the literature have performed a direct comparison of dexamethasone (DEX) implants with anti-VEGF agents. A Cochrane Review[1] published in 2020 could identify merely two suitable trials that had undertaken a head-to-head comparison of DEX implants and anti-VEGF agents for DME and concluded that dexamethasone was more effective than anti-VEGFs at lowering retinal thickness. Both these trials, the BEVORDEX study[2] and the trial by Callanan et al.,[3] independently concluded that DEX implant is non-inferior to anti-VEGF. Another important issue that needs to be discussed is the dosing frequency of DEX implants. The FDA label does not provide any recommendations about the timing of reinjection. In our clinical experience, the effectiveness of the implant ranges from 12 to 16 weeks. Gillies et al.[2] rightly state that industry-sponsored studies fail to show the beneficial effects of DEX implants as they assume a therapeutic window of 6 months, which is misleading. Callanan et al.[3] compared ranibizumab with DEX implant in DME and observed a see-saw pattern in retinal thickness. Thickness started increasing 3 months after injection and decreased again after reinjection. This pattern of retinal thickness variation prompted the authors to suggest a reduction in treatment frequency below the 5-monthly interval used in the study. Totan et al.[4] also noted a fall in the efficacy of DEX implants between 3 and 6 months after injection. The addition of an anti-VEGF agent did not give any anatomical benefit or hasten the resolution of DME in our study. To conclude, steroid agents offer similar outcomes as anti-VEGFs with the advantage of less frequent dosing, reduced costs and visits, decreased risk of endophthalmitis, and no systemic adverse effects. The strengths of our study include randomization, participant masking, and standardized treatment protocol. The study could be improved by assessing the effect of cataract and macular ischemia on visual acuity and recruiting a larger number of eyes over a longer study period. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.
Source: Indian Journal of Ophthalmology
Authors: Surbhi Agrawal, Rajesh Ramanjulu, P Mahesh Shanmugam, Ajith Havanje
Institution: Sankara Eye Hospital, Bangalore
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4403850331