Topical Treatments for Diabetic Retinopathy, DME Hold Promise

Findings from a systematic review highlight the potential of topical treatments for patients with diabetic retinopathies. However, while certain studies demonstrated favorable results for eye drops, others were still more heterogenous in their findings.

Currently, there is a dearth of evidence to corroborate the efficacy of topical eye drops; however, recent studies in animal models have shown there to be an effect via various pathogenic pathways.

A team led by Mikkel Thagaard, MD, Department of Ophthalmology, Odense University Hospital, conducted a review of 19 studies, all of which evaluated patients with diabetic retinopathy and/or diabetic macular edema. The goal of their analysis was to ascertain whether topical treatments could have an effect on disease change or progression.

Systematic Review: Summary Findings

Thagaard and colleagues utilized PubMed, Embase, and Scopus to search for relevant and appropriate studies. All eligible and evaluated studies were a mix of randomized clinical trials and non-randomized trials and were heterogenous in target population, interventions, and outcome measure.

Of those included in the meta-analysis, 13 investigated topical eye drop use in DME populations. Further, 3 of those studies were randomized clinical trials, which generally showed favorable outcomes associated with treatment.

For example, Ohira et al (2015)—which compared 1.5% dexamethasone y-cyclodextrin nanoparticles (DexNP) with triamcinolone acetonide injection in patients with central DM— reported that topical treatment was associated with an increase in best-corrected visual acuity (BVCA) and decrease in macular thickness.

Gupta et al (2014) showed that BVCA increased in patients who received 0.2% brimonidine and placebo. Foveal avascular zone (FAZ) decreased in area and diameter for treated patients.

However, results from Friedman et al (2015) indicated no change in BVCA and retinal volume between noncentral DME patients in both 0.1% nepafenac and placebo groups.

The remaining (non-randomized) clinical trials were variable in efficacy outcomes, some showing improvements in BCVA and others showing no change associated with various types of topical treatments.

Similarly, retinal thickness, volume, and foveal thickness (or other retinal outcomes in question) improved for retinopathy populations, while one study (Campochiaro et al) reported no change on OCT.

A total of 6 studies were evaluated that looked at efficacy of eye drops in patients with diabetic retinopathy. Of these studies, 4 were randomized clinical trials.

Mondal et al (2004) assessed 0.1% brimonidine (versus placebo) in patients with very mild non-proliferative diabetic retinopathy. As such, the investigators reported that BCVA improved in 60% of patients; progression of disease was not observed.

Simó et al (2019) showed that 0.2% brimonidine and 0.1% somatostatin in those with no, minimal, or mild non-proliferative diabetic retinopathy had no effect on BCVA but was associated with no worsening mfERG IT in patients with preexisting neurodegeneration.

Grauslund et al (2019) compared 0.2% brimonidine with 0.1% somatostatin and placebo in no - mild non-proliferative diabetic retinopathy. They did not report on visual outcomes but indicated the topical treatment was linked to an increase in central retinal arteriolar equivalent (CRAE) and central retinal venula equivalent (CRVE) in mild diabetic retinopathy.

And finally, Parravano et al (2020)—which enrolled patients with mild non-proliferative diabetic retinopathy with impaired retinal sensitivity—demonstrated an association between 0.05% cyanocobalamin treatment and no worsening of retinal sensitivity and deep vessel densitiy.

Patients with mild non-proliferative diabetic retinopathy in the non-randomized clinical trials experienced no improvement in BCVA with F2-alphablocker and NSAID as well as with carbonic anhydrase inhibitor. F2-alphablocker treatment led to reductions in arteriolar calibre.

Thagaard and colleagues indicated that while overall observations from these studies showed promise for topical eye drops in mild diabetic retinopathy and DME, more research—particularly randomized clinical trials and with longer follow-up periods—are warranted.

“Hopefully, the future will reveal further clinical trials and advances in eye drop treatment not only in diabetic retinopathy but also in other ocular diseases affecting the retina and posterior segment such as age-related macular degeneration, retinitis pigmentosa, and glaucoma,” they wrote.

The study, "Topical treatment of diabetic retinopathy: a systematic review," was published online in Acta Ophthalmologica.