Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may offer modest visual benefits as adjunctive therapy for diabetic macular edema (DME), according to a new systematic review and meta-analysis published in BMC Ophthalmology — although the anatomical effects appear less convincing.
The analysis, led by researchers in Kuwait, reviewed six studies involving 446 patients and 892 eyes to assess whether topical NSAIDs could improve outcomes in DME either alone or alongside intravitreal anti-VEGF therapy.
While anti-VEGF injections remain the standard first-line treatment for DME, the authors note that inflammation also plays a major role in disease pathogenesis, creating interest in adjunctive anti-inflammatory approaches.
The review included randomized controlled trials, observational studies, and pilot investigations published up until December 2023. Interventions included bromfenac, ketorolac, and nepafenac administered either as monotherapy or combined with intravitreal ranibizumab or bevacizumab.
The primary endpoint was best-corrected visual acuity (BCVA). Pooled analysis from three studies demonstrated a statistically significant improvement favoring topical NSAID therapy, with a mean difference of 1.82 ETDRS letters compared with controls.
However, the clinical relevance of that gain remains uncertain.
“The effect is below the standard change deemed clinically meaningful,” the authors acknowledged, cautioning against overinterpreting the functional benefits of topical NSAIDs despite this statistical significance.
Anatomical outcomes proved even more ambiguous. Meta-analysis of four studies showed a trend toward greater central macular thickness (CMT) reduction in NSAID-treated eyes, but the difference did not reach statistical significance. The pooled mean difference was 51.84 µm, accompanied by very high heterogeneity across studies.
Similarly, no meaningful benefit was observed for macular volume reduction. Analysis of three studies showed no statistically significant difference between treatment groups, again with substantial variability between datasets.
Still, the review reinforces growing interest in inflammatory mechanisms underlying DME. NSAIDs inhibit cyclooxygenase enzymes and reduce prostaglandin production, potentially decreasing vascular permeability and retinal inflammation. The study authors also note evidence suggesting NSAIDs may suppress VEGF expression itself, theoretically offering dual anti-inflammatory and antiangiogenic activity.
The authors conclude that while topical NSAIDs may provide modest adjunctive benefit in DME management, the current evidence remains insufficient to establish a clear anatomical advantage or define their long-term role in treatment algorithms. In conclusion, they note that “further exploration, larger-scale studies, and individualized treatment approaches are warranted to establish their long-term efficacy and safety profiles.”
