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In an era when pharmacological therapy has become the mainstay for treatment of diabetic macular edema (DME), pars plana vitrectomy (PPV) deserves consideration as a reasonable alternative for early DME in appropriate patients, according to Maurice B. Landers III, MD.
“Anti-VEGF therapy has become the current standard of care for treatment of DME in the United States,” said Dr. Landers, professor of ophthalmology, University of North Carolina Medical School, Chapel Hill. “But it is extremely expensive and outcomes with its use in the real world are nowhere near as good as the results obtained in clinical trials.”
Dr. Landers pointed out that modern PPV is safe, effective for reducing DME, less expensive, and the only affordable option for treating DME in most countries of the world.”
An analysis conducted by the DRCR.net demonstrates that anti-VEGF therapy for DME with either of the two drugs that have an indication for this use (ranibizumab [Lucentis, Genentech]; aflibercept [Eylea, Regeneron]) is not a cost-effective treatment using a liberal standard of $100,000 per quality-adjusted life-year.
Bevacizumab (Avastin, Genentech) is a less expensive alternative. Its use, however, is accompanied by issues relating to the need for compounding and potential for counterfeiting. It also may be prohibited by regulatory agencies in some countries, Dr. Landers added.
Furthermore, the DRCR.net cost-effectiveness calculations are based on results of its comparative effectiveness in clinical trials. However, research using Medicare data shows that in the real-world, patients are receiving anti-VEGF injections less frequently and achieving less improvement than has been reported in clinical trials.
“In clinical trials, there is a lot more effort devoted to ensure patients attend follow-up visits,” said Dr. Landers. “Compliance in the real world is simply not as good.”
Dr. Landers said there is considerable evidence that PPV reduces macular edema in patients with DME. In the DRCR.net Vitrectomy for DME study, central subfield thickness (CST) decreased in more than 90% of patients and was reduced 33% overall, from 412 µm to 278 µm.
Figure 1: The top graph shows the results of the meta-analysis of 1,800+ cases of vitrectomy for DME in the literature, showing the resulting decreased macular thickness after vitrectomy. The bottom graph outlines the duration of follow-up in these studies, showing the long term, beneficial effect of vitrectomy on macular thickness, up to 30 months in some cases (Images courtesy of Maurice Landers III, MD)
Furthermore, in a 2013 publication that reviewed data from more than 1,800 patients with DME, Dr. Landers and colleagues found the vast majority of patients achieved a durable decrease in macular thickness, showing persistence through follow-up periods that extended up to 30 months.
Doubt that PPV has benefit for treating DME may exist because in the DRCR.net Vitrectomy for DME study, it was not associated with improvement in visual acuity. Dr. Landers suggested, however, that selection bias may explain that study’s outcome.
“We know from other studies that vision of patients with DME never improves without an associated decrease in CST,” Dr. Landers said. “The DRCR.net study, however, recruited patients who had failed all other treatments and they likely had irreversible retinal damage that limited their potential for vision improvement even after successful reduction of their macular edema.”
He suggested that with the availability of spectral-domain optical coherence tomography (SD-OCT), which enables preoperative determination of the integrity of the outer retina, patients with potential to gain visual acuity can be selected for PPV.
Figure 2. These images show the different visual results obtained after thinning the retina with vitrectomy. The top (before and after) images of the retina show good visual result if patients start with intact outer retina (by SD-OCT). The bottom (before and after) images of retina show poor visual results (20/200 only improved to 20/160, in spite of good anatomical result) if patients start with damaged outer retina by SD-OCT (Images courtesy of Maurice Landers III, MD)
“We now have evidence that the integrity of the outer retinal layers correlates with visual acuity in patients with DME,” Dr. Landers explained. “There is a correlation between the previtrectomy integrity of the external limiting membrane and ellipsoid zone and the potential for functional improvement with improvement in DME.”
Dr. Landers noted that the techniques and instrumentation for PPV have advanced significantly since the procedure was first introduced almost 50 years ago. It has an acceptable risk profile compared with anti-VEGF therapy, considering rates of major complications.
“There is an about 1% incidence of sight-threatening retinal detachment with PPV and an about 1% cumulative three-year incidence of endophthalmitis with intravitreal injections,” Dr. Landers said.
Maurice Landers III, MD
Dr. Landers has no relevant financial interests to disclose.