Refractory Diabetic Macular Edema

Diabetic macular edema (DME) is arguably one of the most important challenges in ophthalmology. Macular edema refractory to laser photocoagulation remains the most prevalent cause of untreatable vision loss in diabetes and is responsible for visual disability in millions of people worldwide. The lack of an effective therapeutic solution accounts for the range of interventions proposed. These include intraocular delivery of corticosteroids and anti-VEGF antibodies, and the surgical alternative of vitrectomy with or without removal of the internal limiting membrane (ILM). In this issue of Journal of Ophthalmic & Vision Research, Dehghan and co-authors 1 present the results of a prospective interventional case series of triamcinolone-assisted vitrectomy with ILM peeling for refractory diffuse non-tractional DME. They found no significant effect on visual acuity despite a reduction in mean macular thickness. The publication of studies such as this helps redress the biases that tend to promote the reporting and publication of positive findings. This study also illustrates the challenges associated with designing an experiment that will allow clear conclusions to be drawn about the value of combination treatments in such a complex condition. A number of series have suggested that vitrectomy alone can improve macular function in DME. The rationale for this approach involves relief of mechanical tangential or antero-posterior tractional forces associated with a taut thickened posterior hyaloid at the macula. There is consensus that DME associated with such traction, evident on biomicroscopy or optical coherence tomography (OCT), can benefit from vitrectomy with removal of the attached posterior hyaloid membrane. Removal of the ILM, which can itself be thickened in diabetic eyes, has been proposed as an additional procedure to ensure complete removal of cortical vitreous, and to reduce the likelihood of subsequent epiretinal membrane formation by inhibiting migration and reproliferation of astrocytes. Whether vitrectomy can improve vision in eyes with DME but no evidence of vitreomacular traction, however, has not been established. The rationale for vitrectomy in this context is certainly less obvious but possible benefits include improved retinal oxygenation by promotion of intraocular fluid currents, and relief of any subclinical tractional forces. Removal of the ILM in non-tractional refractory DME might favorably alter hydrostatic forces across the inner retina and/or stimulate beneficial, if short-lived, inflammatory responses. Few studies have been able to determine with confidence the efficacy and adverse effects of these interventions and we have to rely on non-randomized and poorly controlled case series that are frequently …