Marianeli Rodriguez, MD
Vitreoretinal Surgery Fellow
Mass Eye & Ear, Harvard Medical School
Dr. Geeta Lalwani first discussed the 2-year pooled outcomes from various randomized trials of anti-VEGF treatment for diabetic retinopathy and DME. Across trials, anti-VEGF treatments improved diabetic retinopathy. However, based on her findings, it is still unclear what the treatment paradigm should be if treating diabetic retinopathy with anti-VEGF alone.
Dr. Raj Maturi then discussed DRCR.net Protocol U for persistent DME after 3 anti-VEGF treatments, comparing the dexamethasone implant/ranibizumab combination vs. ranibizumab alone. The primary outcome of the study was BCVA at 24 weeks, and secondary outcome was OCT thickness. Mean BCVA was not different between the two groups but the distribution of BCVA in the combination treatment was wider. OCT CST showed a greater reduction in retinal thickness in the combination group.
Dr. Nikolas London discussed the SOLAR study, which prospectively compared intraocular inflammation and eye pain within the first 7 days after aflibercept vs. ranibizumab in patients with DME. This trial excluded patients with endophthalmitis, uveitis or uncontrolled symptomatic dry eye. Baseline characteristics were balanced. AC inflammation at 1 day was slightly higher in the patients receiving ranibizumab which was not statistically significant. Absence of pain at post-injection day 1 and 7 was comparable between the 2 groups.
Then, Dr. Peter Kaiser from Cole Eye Institute presented data from the Phase 2b DEL MAR study, comparing risuteganib and bevacizumab. Risuteganib targets multiple integrins isoforms, which are thought to be key mediators of oxidative cells stress. In the retina, oxidative stress leads to increase vascular permeability, angiogenesis, inflammation, and apoptosis/neurodegeneration. Risuteganib works upstream of VEGF and the hypothesis is that it can more broadly address the various components of the oxidative pathway. It is known that although 50% of patients with DME respond well to anti-VEGF treatment, there is another 50% of patients that do not. In this trial the primary endpoint was BCVA and the secondary endpoint was CRT in OCT. It was shown that adding a single bevacizumab pre-retreatment, improved the BCVA achieved with risuteganib. Phase 3 of this trial will start in Q1 of 2019, so stay tuned
Next, Dr. Jeff Heier discussed the Phase 2 RUBY trial, which examined combination therapy with intravitreal nesvacumab + aflibercept (co-formulation) vs. aflibercept alone in DME. Nesvacumab is an Ang2 inhibitor. Randomization was to 3 arms: low dose combination, high dose (HD) combination, and aflibercept alone. Superiority was not achieved for vision or CFT. Although there was no statistical difference in mean BCVA or CFT in OCT, a proportion of patients with resolution of fluid at the foveal center as well as the 2-point diabetic retinopathy scale was significantly improved in patients in the HD combo arm.
Next Dr. Rishi Singh discussed the BOULEVARD Trial, looking at anti-VEGF/anti-angiopoietin 2 bispecific antibody RG7716 in DME vs. ranibizumab at 26 weeks from the Phase 2 study. The primary outcome was BCVA, and the secondary outcome was CFT. Both anti-VEGF treatment- naïve patients and those patients previously treated with anti-VEGF showed improvement in BCVA with high dose 6.0mg RG7716 compared to ranibizumab. Importantly, the 2-step DRSS (diabetic retinopathy score) was better in those patients receiving RG7716.
Dr. Sam Mansour then discussed the reduction in frequency of DME therapies post fluocinolone acetonide (FAc) implant, looking at the data from the USER and PALADIN studies. This implant is used in patients with persistent DME despite anti-VEGF treatment which is present in 35-65% of patients. The main conclusion from this study was that treatment burden decreased in the 2 studies when compared to pre-implantation of the fluocinolone acetonide implant. The majority of patients with persistent/recurrent DME had stable or improved anatomical and functional outcomes when treated with the FAc implant .
Dr. Justis Ehlers presented his research on the Permeate Study: Advanced image analysis and machine learning assessment of the impact of aflibercept on anatomic features and flow dynamics. There were 30 patients enrolled in this study. Advanced imaging analysis demonstrated that EZ/RPE volume and integrity improved, as well as IRF/SRF in those patients receiving aflibercept. Similarly, panretinal leakage index dramatically improved. Advanced radiomics analysis with baseline vascular tortuosity assessment was able to distinguish those eyes that tolerated a longer dosing interval for macular edema.
Dr. Bobeck Modjtahedi discussed a model to predict the 3-yr risk of needing treatment for DME in diabetic patients. Analysis of over 170,000 charts and looking at 20 different factors, Age, sex, race, duration of DME, A1C, insulin use, CKD stage, retinopathy status came up to be the most reliable predictors of the likelihood of developing DME. The goal is to create a scale to stratify those patients that may need more intensive monitoring of DME and more aggressive systemic treatment. This tool may be considerably useful not only for retinal specialist, but also for primary care physicians taking care of these patients. During the discussion, it was suggested to create an online calculator or app that could help physicians arrive at the relative risk using data available from electronic medical records.
Dr. John Pitcher discussed the outcomes of intravitreal anti-VEGF therapy for DME in routine clinical practice. He analyzed the visual and anatomical outcomes of patients who were treated less frequently vs. those with more intensive treatment for DME. Consistent with results of clinical trials, in routine clinical practice, maintenance of visual gain was associated with more frequent injections
Finally, Dr. Nancy Holekamp discussed the treatment burden with anti-VEGF after the implantation of the FAc implant. It is establish that treatment burden is a barrier to patient adherence to monthly ophthalmology appointments, treatment and treatment efficacy. To look at treatment burden, results from USER and PALADIN were analyzed, comparing pre- and post- FAc treatment frequency. There was a significant reduction in the treatment burden (number of anti-VEGF injections) after implantation of the FAc implant.