Is Eylea (aflibercept) medically indicated for a patient with Proliferative Diabetic Retinopathy (PDR) without macular edema?

Is Eylea (Aflibercept) Medically Indicated for This Patient?

Yes, Eylea (aflibercept) is medically indicated for this patient with proliferative diabetic retinopathy (PDR) without macular edema, particularly given his documented clinical response to anti-VEGF therapy and the recurrent vitreous hemorrhage requiring recent vitrectomy.

Rationale Based on Guidelines and Evidence

FDA-Approved Indication for PDR Without Macular Edema

• Aflibercept is FDA-approved for the treatment of diabetic retinopathy, which includes PDR, regardless of macular edema status 1.
• The American Diabetes Association 2024 guidelines explicitly state that intravitreal anti-VEGF injections are a reasonable alternative to panretinal photocoagulation for individuals with PDR and reduce the risk of vision loss 1.
• The International Council of Ophthalmology confirms that anti-VEGF injections (including aflibercept) are safe and effective for PDR treatment through at least 2 years 1.

Clinical Evidence Supporting Use in PDR Without DME

• The American Academy of Ophthalmology's Diabetic Retinopathy Preferred Practice Pattern (2020) specifically notes that aflibercept is similar to PRP for treatment of PDR and may have superior visual acuity outcomes in eyes without center-involving DME at 1 year 1.
• The CLARITY trial demonstrated that aflibercept was non-inferior and superior to PRP in treatment-naive PDR patients, with improved best-corrected visual acuity outcomes at 52 weeks 2.
• DRCR.net Protocol S showed that ranibizumab (and by extension, other anti-VEGF agents) resulted in better average visual acuity, less visual field loss, and fewer vitrectomies compared to PRP 1.

Patient-Specific Factors Supporting Approval

This patient demonstrates clear clinical response to anti-VEGF therapy:

• Visual acuity improved from count fingers at 6 feet (10/8/2025) to 20/30 (10/20/2025) following recent vitrectomy [@case details].
• Patient reports subjective improvement, stating vision clears within 2.5 weeks after injections versus 2.5 months without injections [@case details].
• The vitreous hemorrhage has resolved, indicating treatment efficacy [@case details].

The patient has high-risk PDR features:

• History of recurrent vitreous hemorrhage requiring multiple interventions [@case details].
• Required vitrectomy in both eyes (left eye April 2023 and October 2025) [@case details].
• Has already undergone panretinal photocoagulation bilaterally, indicating advanced disease [@case details].

Addressing the Off-Label Dosing Concern

The proposed every 4-6 week dosing interval is clinically appropriate despite being off-label:

• The FDA-approved dosing for diabetic retinopathy is 2 mg every 4 weeks for the first 5 injections, then every 8 weeks [@Lexicomp].
• However, the American Academy of Ophthalmology acknowledges that some patients may require every-4-week dosing after the first 20 weeks of therapy [@5@, 1].
• Patient compliance is a critical consideration when choosing anti-VEGF over PRP - guidelines emphasize that anti-VEGF requires more frequent visits and treatments [@7@, 1].
• Given this patient's documented response pattern (vision clearing in 2.5 weeks with injections), individualized dosing intervals between 4-6 weeks represent appropriate clinical judgment for maintenance therapy.

Addressing the Macular Edema Discrepancy

The absence of documented macular edema does NOT preclude aflibercept use:

• The FDA approval for aflibercept includes "diabetic retinopathy" as a standalone indication, separate from diabetic macular edema 1.
• Guidelines explicitly support anti-VEGF use in PDR without requiring concurrent macular edema 1.
• The clinical documentation states "PDR without macular edema" consistently, which is an appropriate indication for treatment [@case details].

Important Clinical Considerations

Advantages of Anti-VEGF Over Additional PRP

• This patient has already received bilateral PRP, making additional laser less desirable [@case details].
• Anti-VEGF therapy results in less peripheral visual field loss compared to PRP [@1@, @5@].
• Lower risk of developing new diabetic macular edema with anti-VEGF versus PRP [1, @10@].
• Fewer vitrectomy surgeries required with anti-VEGF treatment 1.

Potential Concerns and Mitigation

Treatment burden and compliance:

• Anti-VEGF requires more frequent visits than PRP (a key consideration per guidelines) [1, @9@].
• However, this patient has demonstrated good compliance with multiple prior treatments and follow-up visits [@case details].
• Studies show 22% of PDR patients on anti-VEGF are lost to follow-up over 4 years, emphasizing the need for reliable follow-up 1.

Resistance of neovascularization:

• Neovascularization of the disc (NVD) is more resistant to treatment than neovascularization elsewhere (NVE) 3.
• If NVD is present, closer monitoring may be required as regression rates are lower (53.5% vs 87.3% for NVE) 3.

Continuation Criteria Met

The patient meets continuation criteria per the CPB policy:

• Demonstrated positive clinical response with improvement in visual acuity from count fingers to 20/30 [@case details].
• Subjective improvement in vision quality and duration of effect [@case details].
• Resolution of vitreous hemorrhage [@case details].

Recommendation

Approve Eylea (aflibercept) 2 mg intravitreal injection for the left eye with dosing intervals of 4-6 weeks as clinically indicated. The patient has FDA-approved indication (PDR), meets continuation criteria with documented clinical response, and has high-risk features warranting ongoing anti-VEGF therapy. The absence of macular edema does not contraindicate use, as aflibercept is approved for diabetic retinopathy independent of edema status. Close monitoring for treatment response and compliance is essential given the treatment burden associated with anti-VEGF therapy [@1@, @4@, @7