Dear Editor,We read the article titled “Intravitreal anti-vascular endothelial growth factor with and without topical non-steroidal anti-inflammatory in centre-involving diabetic macular edema (DME)” by Mohan et al.[1] published in the Indian Journal of Ophthalmology, with great interest. We congratulate all the authors for their publication. However, there were various shortcomings that we had come across that merit discussion and need to be borne in mind while applying the results of this current study in our day-to-day retina practice.Combination therapy using a topical Non-steroidal anti-inflammatory drugs (NSAID) and an intravitreal anti- Vascular endothelial growth factor (VEGF) agent is known to reduce the treatment burden in DME. Topical NSAIDs, in fact, provide a viable alternative to intravitreal injections for those patients who are either unable to afford or are not medically fit for intravitreal injections in the treatment of DME.[23]The authors of the current study concluded that combination therapy of topical NSAID with intravitreal anti-VEGF had no added beneficial effects in terms of visual outcomes, reduction in central subfield thickness (CST) on Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA), or reduction in the mean number of injections. The study was a retrospective observational in design. A prospective, randomized control trial would have been an ideal study design to support such conclusions. Sample sizes in group 1 and group 2 were 100 and 50, respectively. The authors have not mentioned how the sample size was calculated. The disproportionate sample size can alter the study outcomes and adversely affect the merit of the study.Although treatment-naïve DME was mentioned in the methodology section as inclusion criteria, the results showing more than 60% of patients in both groups had received at least one intravitreal injection at baseline.The study groups were not matched at baseline in terms of duration of diabetes and severity of diabetic retinopathy as correctly mentioned by the authors. Subgroup analysis using these parameters had been done by the authors to address the confounding variables. However, we would like to mention that there may have been other systemic confounders such as hypertension and diabetic nephropathy that have not been discussed in the study.In the study, the authors have used both intravitreal ranibizumab and Razumab. Although studies have shown equal efficacy of the biosimilar Razumab with ranibizumab, it would be interesting to know the number of injections of each anti-VEGF agent in either group. A subgroup analysis would provide a better understanding of the outcomes. In a developing country such as India where affordability of intravitreal anti-VEGFs is a major obstacle, NSAIDs provide an alternative and viable option to reduce the cost burden. Therefore, it is not prudent to undermine the importance of NSAIDs in DME management based on the current evidence provided in this study.