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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 4INTERVENTIONAL

High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy

High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy (NCT06662994) is a Phase 4 interventional studying Diabetic Macular Edema (DME), sponsored by Retina Consultants of Orange County. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 15 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - 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: 1. Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus 2. DME with central involvement in the study eye with CRT ≥320 μm on Spectralis. 3. 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 4. Willing and able to comply with clinic visits and study-related procedures 5. Provide willing to sign a consent form signed by study patient or legally acceptable representative 6. Have a previous history of vitrectomy surgery. Who Should NOT Join This Trial: - A patient who meets any of the following criteria at either the screening or randomization visits will be excluded from the study: 1. Evidence of macular edema due to any cause other than diabetes mellitus in either eye 2. Prior intravitreal investigational agents in the study eye (gene therapy, etc.) at any time 3. IOP ≥28 mmHg in the study eye 4. History of glaucoma filtration surgery in the past 5. Evidence of infectious blepharitis, keratitis, scleritis , or conjunctivitis in either eye within 4 weeks (28 days) of the screening visit. 6. Any intraocular inflammation/infection in either eye within 6 weeks (42 days) of the screening visit. 7. History of idiopathic or autoimmune uveitis in the study eye 8. Vitreomacular traction or epiretinal membrane in the study eye evident on biomicroscopy or OCT that is thought to affect central vision 9. Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye 10. History of corneal transplant or corneal dystrophy in study eye ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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: 1. Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus 2. DME with central involvement in the study eye with CRT ≥320 μm on Spectralis. 3. 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 4. Willing and able to comply with clinic visits and study-related procedures 5. Provide informed consent signed by study patient or legally acceptable representative 6. 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: 1. Evidence of macular edema due to any cause other than diabetes mellitus in either eye 2. Prior intravitreal investigational agents in the study eye (gene therapy, etc.) at any time 3. IOP ≥28 mmHg in the study eye 4. History of glaucoma filtration surgery in the past 5. Evidence of infectious blepharitis, keratitis, scleritis , or conjunctivitis in either eye within 4 weeks (28 days) of the screening visit. 6. Any intraocular inflammation/infection in either eye within 6 weeks (42 days) of the screening visit. 7. History of idiopathic or autoimmune uveitis in the study eye 8. Vitreomacular traction or epiretinal membrane in the study eye evident on biomicroscopy or OCT that is thought to affect central vision 9. Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye 10. History of corneal transplant or corneal dystrophy in study eye 11. 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. 12. 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 13. 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 14. 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 15. Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) \> 14% 16. History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) of screening visit 17. Known sensitivity to any of the compounds of the study formulation 18. Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device 19. Pregnant or breastfeeding women 20. 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.

Treatments Being Tested

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.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Retina Consultants of Orange County
Fullerton, California, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06662994), the sponsor (Retina Consultants of Orange County), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06662994 clinical trial studying?

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 … The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06662994?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06662994?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06662994. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06662994. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.