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Investigators research safety, efficacy of endolaserless vitrectomy.
This article was reviewed by Dennis M. Marcus, MD
Patients achieved substantial visual gains following vitrectomy without endolaser combined with aflibercept (Eylea, Regeneron Pharmaceuticals) to treat vitreous hemorrhages (VHs) associated with proliferative diabetic retinopathy (PDR), according to the results of the LASERLESS trial (NCT02976012).
Anti-vascular endothelial growth factor (VEGF) therapy is an effective treatment for PDR in less complicated eyes that do not require vitrectomy.
Related: Probe of IRIS Registry shows anti-VEGF injections leading treatment for PDR
The 5-year results of the Protocol S study with ranibizumab (Lucentis, Genentech; NCT01489189) compared with panretinal photocoagulation (PRP) for PDR not requiring pars plana vitrectomy showed that vitrectomy with endolaser resulted in large losses of visual fields and significantly decreased visual field point scores.
In addition, the CLARITY study (ISRCTN32207582) showed that aflibercept was noninferior to PRP for PDR and achieved better visual acuity (VA) levels and less visual field loss.1,2
“Thus, anti-VEGF therapy is a viable alternative to endolaser for PDR-related vitreous hemorrhages,” according to Dennis M. Marcus, MD, who is in private practice in Augusta, Georgia.
Related: Saving memories: Do anti-VEGF agents contribute to cognitive loss?
The LASERLESS trial
Marcus presented the 2-year results of LASERLESS, a phase 1/2 prospective, randomly assignedinterventional study of the safety and efficacy of endolaserless vitrectomy in which preoperative, intraoperative, and postoperative intravitreal injections of aflibercept were administered in eyes with VHs associated with PDR in patients who had not undergone retinopexy.
In addition to the 2-year results, the investigators wanted to determine the complications with and adherence to intravitreal aflibercept injection monotherapy for PDR-related VH.
The eligible patients were randomly assigned postoperatively to mandatory aflibercept injections either every 8 weeks or every 16 weeks with as-needed injections because of progressive PDR or diabetic macular edema.
The primary outcome was safety issues that included large losses of vision or proliferative consequences of PDR. The secondary outcomes included VA, anatomic, functional, and treatment outcomes, Marcus said.
Related: Identifying biomarkers to predict diabetic retinopathy progression
Of the 40 eyes enrolled, 14 were randomly assigned to the every-8-week group and 17 to the every-16-week group, and 9 were not randomly assigned. The average baseline VA was 20/200, with a wide range of baseline VA levels.
Throughout the first 2 years of this 3-year study, the average number of aflibercept injections per patient in the every-8-week and every-16-week groups were, respectively, 14.3 and 8.8.
“On average, VA improved in 31 randomized eyes from the baseline level of 20/200 to 20/40. At the 2-year time point, there were trends for greater visual improvement in the q8 [every-8]-week group that gained a mean of 33 letters compared with in the q16-week group that gained a mean of 22 letters,” Marcus said.
More proliferative consequences such as recurrent VH were seen in the every-16-week group.
One patient in that group developed neovascular glaucoma but had a good outcome; no patients in either group had progression of tractional retinal detachments.
Related: Determining risk of ocular damage from chronic intravitreal injections
Repeated vitrectomies were not needed in either group in eyes with recurrent VHs after additional aflibercept injections were administered.
A rhegmatogenous retinal detachment developed in 1 eye in each group that was repaired with vitrectomy and endolaser application, Marcus noted.
Despite the good results, the patient adherence rates at the 2-year time point were suboptimal, he commented.
Overall, 25 eyes completed the final visit at 104 weeks. Through 104 weeks, 12 of 14 (86%) eyes and 13 of 17 (76%) eyes completed the 2-year evaluation in the every-8-week and every-16-week groups, respectively.
Caveats regarding the study are that only the 2-year results have been reported, a moderate number of eyes were included, cost is an issue, and adherence is the main concern, he pointed out.
“Avoiding PRP or endolaser for PDR has great potential to reduce visual field reduction,” Marcus said. “Retina surgeons can highly impact visual field preservation by avoiding peripheral ablation.”
Related: Retinal pathologies challenging to image with current technologies
The primary takeaways of the study are that the eyes treated with aflibercept every 8 weeks gained more letters with fewer proliferative complications.
Marcus concluded that aflibercept may be a better alternative to endolaser. With adherence a concern, clinicians have not used the approach outside of this clinical trial.
“Persistent and frequent anti-VEGF treatment is needed to optimize outcomes and prevent proliferative complications,” he said. “Data provide an important framework for future longer-acting anti-VEGF platforms such as gene therapy or a port delivery system implant. Three-year follow-up will further determine the safety, durability, VA efficacy, optimal dosing, and visual field outcomes with this approach.”
Read more by Lynda Charters
Dennis M. Marcus, MD
Dr Marcus has received research funds from Regeneron Pharmaceuticals.
1. Sivaprasad S, Prevost AT, Vasconcelos JC, et al; CLARIT Study Group. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet. 2017; 389(10085):2193-2203. doi:10.1016/S0140-6736(17)31193-5
Gross JG, Glassman AR, Liu D, et al; Diabetic Retinopathy Clinical Research Network. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136(10):1138-1148. doi: 10.1001/jamaophthalmol.2018.3255