Treatment of the patient with nonproliferative diabetic retinopathy (NPDR) is complicated. While anti-VEGF therapy has proven successful at reducing the risk of progression and in yielding regression in eyes with DR without center-involving diabetic macular edema (DME), the data to date show no benefit for visual outcomes.1 Moreover, starting a patient on treatment then obligates that individual to routine monitoring, follow-up, and continued intravitreal injections. For these reasons, most eyes with NPDR are currently followed without active therapy, and treatment is initiated upon signs of progression—admittedly an imperfect solution given the risk of losing a patient to follow-up.
But there is certainly good news for patients with NPDR. The innovation pipeline in DR is robust, to say the least, offering several candidate molecules acting on unique targets and featuring novel mechanisms of action and delivery. Altogether, and with the usual caveats about clinical development, clinicians can be optimistic that we are closing in on addressing a significant unmet need in DR.
Figure. Shown left to right, Jeffrey S. Heier, MD; David S. Boyer, MD; Caroline R. Baumal, MD; and Peter K. Kaiser, MD, discuss the treatment of NPDR at a roundtable at ARVO 2022 in Denver.
I recently moderated a discussion panel on the current state of treatment in DR, where we focused on identifying current treatment gaps and looked down the developmental pipeline at some options that may soon be available for clinical use (Figure). There is one proposed molecule that seems to offer significant promise: OTT166 (OcuTerra) is an integrin inhibitor designed for topical delivery; after instillation onto the conjunctival surface, the small molecule travels to the retina transclerally and crosses the choroid, where it then affects multiple signaling pathways involved in DR pathophysiology including Tie-2, VEGF, PDGF, βFGF, and TGF-βR. If OTT166 is able to complete development and successfully navigate regulatory review, such a treatment molecule would have tremendous impact as an easily used, patient-friendly option suitable for use in earlier stage disease. Having a topical therapy like this would, quite literally, propel a paradigm shift in treatment of DR: it would allow clinicians to take a proactive approach instead of waiting for the disease to progress before intervening.
—Peter K. Kaiser, MD
1. Brown DM, Wykoff CC, Boyer D, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: results from the PANORAMA Randomized Clinical Trial. JAMA Ophthalmol. 2021;139(9):946-955.
