NCT06662994 · Retina Consultants of Orange County
High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Aflibercept 8 mg (VEGF Trap-Eye, BAY86-5321)
Identify 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.
Primary outcome measures
Visual acuity changes
Time frame: 12 months
Visual Acuity will be measured at each visit.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- A patient must meet the following criteria at both the screening and randomization visits (except where indicated) to be eligible for inclusion in the study:
- 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
- Provide informed consent signed by study patient or legally acceptable representative
- Have a previous history of vitrectomy surgery.
Exclusion criteria
- A patient who meets any of the following criteria at either the screening or randomization visits will be excluded from the study:
- 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
- Evidence of infectious blepharitis, keratitis, scleritis , or conjunctivitis in either eye within 4 weeks (28 days) of the screening visit.
- Any intraocular inflammation/infection in either eye within 6 weeks (42 days) of the screening visit.
- History of idiopathic or autoimmune uveitis in the study eye
- Vitreomacular traction or epiretinal membrane in the study eye evident on biomicroscopy or OCT that is thought to affect central vision
- Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
- History of corneal transplant or corneal dystrophy in study eye
- Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of IVT injections, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
- Structural damage to the center of the macula in the study eye that is likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia, or organized hard exudates
- Inability to obtain photographs, FA, or SD-OCT in the study eye, eg, due to media opacity, allergy to fluorescein dye, or lack of venous access
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of high dose aflibercept or that might affect interpretation of the results of the study or render the patient at high risk for treatment complications
- Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) \> 14%
- History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) of screening visit
- Known sensitivity to any of the compounds of the study formulation
- Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device
- Pregnant or breastfeeding women
- Men or women of childbearing potential (WOCBP)\
- who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment and during the study.
Where
- Fullerton, California
Collaborators
Regeneron Pharmaceuticals
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 10, 2025 · Source of record for eligibility and locations