Patients with diabetic macular edema (DME) sometimes must undergo vitrectomy surgery (PPV) for diabetic and non-diabetic related issues. Patients may have improved DME with anti-VEGF therapy and ranibizumab has been found to reduce central macular thickness (CMT) with anti-VEGF therapy following vitrectomy. Those patients still require intravitreal injections but the pharmacokinetics of a vitrectomized eye are different than those eyes that have not undergone vitrectomy. The clearance of protein molecules is quicker in vitrectomized eyes so these patients may be more refractory to standard of care anti-VEGF therapy. In rabbit models, the half-life of both bevacizumab and ranibizumab were reduced by a factor 1.8 and 1.3, respectively, after pars plana vitrectomy. In a study examining intravitreal triamcinolone acetonide in human eyes, the half-life was found to be 18.6 days in non-vitrectomized eyes and 3.2 days in vitrectomized eyes, but there was considerable intrasubject variation. Patients with various disease states, including neovascular age-related macular degeneration (nAMD) have been managed with monthly anti-VEGF therapy successfully after vitrectomy surgery. Another study performed by the DRCR net showed that patients with DME treated with anti-VEGF are not affected in the long term if they had had a previous vitrectomy. High dose aflibercept may improve anatomic and visual outcomes in this patient population. Also, high dose aflibercept may allow for longer treatment intervals in these vitrectomized eyes.
Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus
DME with central involvement in the study eye with CRT ≥320 μm on Spectralis.
BCVA early treatment diabetic retinopathy study (ETDRS) letter score of 84 to 20 (approximate Snellen equivalent of 20/25 to 20/400) in the study eye with decreased vision determined to be primarily the result of DME
Willing and able to comply with clinic visits and study-related procedures
Evidence of macular edema due to any cause other than diabetes mellitus in either eye
Prior intravitreal investigational agents in the study eye (gene therapy, etc.) at any time
IOP ≥28 mmHg in the study eye
History of glaucoma filtration surgery in the past
Single group
Aflibercept 8 mg (VEGF Trap-Eye, BAY86-5321)
DrugIdentify patients that have had a previous vitrectomy and have DME that requires anti-VEGF therapy. Then using a treat-extend-stop protocol6,7 that I previously published, treat patients with DME using high dose aflibercept, until the fluid has resolved and then extend the time interval in between treatments for those patients, while maintaining a fluid-free macula.
Visual acuity changes
Visual Acuity will be measured at each visit.
Central Macular Thickness
With SD-OCT measure central macular thickness at each visit and compare this over time
Time Interval
Measure time interval between treatments with aflibercept 8 mg.
Click on the lead sponsor to view all of their trials.
Retina Consultants of Orange County
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
