The treatment of diabetic retinopathy and diabetic macular edema has been turned on its head during my career in ophthalmology. When I was in training, the only treatment available was the use of tissue-destructive laser photocoagulation. While studies then and now confirm that over a lifetime laser retinal photocoagulation procedures are far better than no treatment, we are all well aware of the meaningful loss of vision that laser treatment itself causes in many patients.
As noted in the comprehensive and very well-written cover story in this issue, laser treatment has now been relegated to third-line therapy and is usually utilized for only a select group of patients with DME that is noncentral in location. We are now in the injection era of retinal therapy, including the treatment of DME.
The core take-home messages to me include that DME is best treated at the earliest possible date. This requires the comprehensive ophthalmologist to be aggressive in early diagnosis. It is becoming apparent this likely requires OCT, which can pick up subtle macular edema that a typical eye examination might miss. Much like exudative or wet age-related macular degeneration, DME often requires three to four injections at a once-a-month interval to achieve a response. DRCR.net Protocol T outcomes suggested that any anti-VEGF, including Avastin (bevacizumab, Genentech), is effective for milder DME, so catching DME early can allow patients the opportunity to undergo a much less expensive therapy. For the patient with more severe DME, the more expensive branded drugs, especially Eylea (aflibercept, Regeneron), appear superior.
For most patients, treatment of wet AMD is a life sentence, at least until the patient develops geographic atrophy of the macula. In DME, it is possible over time to achieve a cure with the chance that lifelong injections will not be required. This possible outcome can be shared with patients and might increase their compliance during the active treatment period. All patients with diabetes should be reminded that lifestyle matters. Good diabetic control, such as stopping smoking, controlling weight, having a healthy diet and exercising, are important adjuncts to their medical therapy.
Steroids, either by injection or with extended-release implantables such as Ozurdex (dexamethasone intravitreal implant, Allergan) and Iluvien (fluocinolone acetonide intravitreal implant 0.19 mg, Alimera Sciences), are the second line of therapy. When to add steroids to anti-VEGF therapy or transition from anti-VEGF to steroid therapy is an art; different clinicians have different practice patterns, and these patterns continue to evolve. Some retina specialists have found that in poorly responsive patients, switching the anti-VEGF can be helpful. This concept is familiar to comprehensive ophthalmologists as we sometimes find that the glaucoma patient unresponsive to generic latanoprost responds to branded Travatan Z (travoprost ophthalmic solution 0.004%, Novartis), Lumigan (bimatoprost ophthalmic solution 0.01%, Allergan) or Vyzulta (latanoprostene bunod ophthalmic solution 0.024%, Bausch + Lomb). The double-edged sword of steroids is especially seen in patients treated with Iluvien implants, in which steroid-induced glaucoma is a common occurrence. The patient on chronic intense steroid therapy needs careful follow-up and treatment for the highly likely elevated IOP. Some patients even require glaucoma surgery.
Much research capital, human and financial, is being spent to reduce the patient and physician burden of monthly injections. I believe we can anticipate having more extended-release therapies available in the future, and these are especially needed in the anti-VEGF category. In addition, it is hard to imagine, considering the epidemic of diabetes we are facing in the world, that retina specialists can be expected to meet the demand for monthly DME examinations and injections along with all of their other duties. A better care model will have to evolve. This care model will require the active participation of comprehensive ophthalmologists, certified nurse practitioners or physicians assistants, maybe specially trained registered nurses, and on the diagnostic side our optometric colleagues and the patients themselves with home monitoring. In the case of diabetes, diabetic retinopathy and diabetic macular edema, we need meaningful innovation in our treatments but also in our care delivery models.
Disclosure: Lindstrom reports no relevant financial disclosures.