What Is Step Therapy for Anti-VEGF Drugs?
Step therapy is a payer coverage policy that requires a patient to try and fail on a lower-cost drug before the insurer will cover a more expensive alternative. As of 2026, a growing number of commercial payers and Medicare Advantage plans are implementing step therapy protocols for anti-VEGF intravitreal injections, requiring ophthalmology practices to administer a biosimilar such as ranibizumab-nuna (Byooviz) or bevacizumab before the insurer will approve branded aflibercept (Eylea) or branded ranibizumab (Lucentis). For retina practices, this creates a prior authorization and documentation burden on every injection, changes the drug acquisition and billing workflow, and introduces clinical disputes when the treating physician believes the branded drug is the better choice for a specific patient.
What changed: Multiple commercial payers and Medicare Advantage plans added anti-VEGF step therapy requirements in 2025 and 2026, requiring biosimilar-first or bevacizumab-first protocols before covering branded products.
What it costs the practice: Each step therapy denial requires a prior authorization, a clinical justification letter, and often a peer-to-peer review. Practices report 20 to 45 minutes of staff time per exception request, plus treatment delays of 5 to 14 days.
How to respond: Document every clinical rationale for the preferred drug, file step therapy exceptions using the payer’s specific process, and track which payers enforce step therapy so the billing team can anticipate the requirement before the injection is scheduled.
Step Therapy Expansion in 2026
The anti-VEGF biosimilar market has grown rapidly since the FDA approved the first ranibizumab biosimilar (Byooviz/ranibizumab-nuna) in 2022 and the first bevacizumab biosimilar for ophthalmic use (Lytenava/bevacizumab-bvzr, Outlook Therapeutics) received approval. With lower-cost alternatives now available, payers are using step therapy to steer utilization toward the cheaper products.
As of October 2026, step therapy requirements for anti-VEGF intravitreal injections have appeared in formulary updates from several major commercial payers and Medicare Advantage plans. The typical policy requires the patient to try bevacizumab (compounded or branded) or a ranibizumab biosimilar for a defined period (usually 3 to 6 months) before the insurer will cover branded aflibercept (Eylea), branded ranibizumab (Lucentis), or faricimab (Vabysmo). Some plans go further and require failure on two lower-tier drugs before approving a branded product.
The American Academy of Ophthalmology and the American Society of Retina Specialists have both raised concerns about step therapy in retina care, arguing that anti-VEGF treatment decisions should be made by the treating physician based on the patient’s clinical response, not by a formulary algorithm. Despite these objections, the trend is accelerating as payers seek to reduce per-injection costs in one of the highest-spend drug categories in ophthalmology.
Which Anti-VEGF Drugs Are Affected by Step Therapy?
| Drug | Brand/Biosimilar | Step Therapy Position | Approx. ASP per Injection |
|---|---|---|---|
| Bevacizumab (compounded) | Generic (off-label) | Step 1 (most plans) | $50 to $70 |
| Ranibizumab-nuna (Byooviz) | Biosimilar | Step 1 or 2 | ~$1,100 |
| Bevacizumab-bvzr (Lytenava) | Biosimilar (ophthalmic) | Step 1 or 2 | ~$800 to $1,000 |
| Ranibizumab (Lucentis) | Branded | Step 2 or 3 | ~$1,800 |
| Aflibercept (Eylea) | Branded | Step 2 or 3 | ~$1,850 |
| Faricimab (Vabysmo) | Branded | Step 3 (some plans) | ~$2,200 |
| Aflibercept 8mg (Eylea HD) | Branded | Step 3 (some plans) | ~$2,400 |
In our experience matching ophthalmology providers with billing partners, the step therapy landscape varies dramatically by payer. UnitedHealthcare, Aetna, and several Blue Cross Blue Shield plans have implemented formal step therapy protocols. Medicare Part B does not use step therapy for physician-administered drugs, but Medicare Advantage plans can and do apply it through their own formulary management. The billing team must check step therapy requirements for every patient and every payer before the injection is scheduled. For practices that also bill OCT imaging alongside intravitreal injections, the step therapy status of the drug affects the entire visit workflow.
What Does Step Therapy Cost an Ophthalmology Practice?
Step therapy affects the practice in three ways: treatment delays, staff time on prior authorizations, and drug acquisition economics.
- Treatment delays. When a step therapy denial blocks the preferred drug, the patient either waits for the exception to process (5 to 14 days) or starts on the step-one drug. For retina conditions like wet AMD and diabetic macular edema, treatment delays can result in irreversible vision loss. The clinical urgency creates pressure to start the step-one drug even when the physician believes the branded product is more appropriate.
- Staff time. Each step therapy exception request requires the billing team to document the clinical rationale, submit the prior authorization, and often participate in a peer-to-peer review with the payer’s medical director. Practices report 20 to 45 minutes of staff time per exception. A retina practice handling 50 step therapy exceptions per month is spending 17 to 38 hours on step therapy administration alone.
- Drug acquisition economics. Buy-and-bill practices purchase the drug and are reimbursed at ASP plus a percentage. When a step therapy policy forces the practice to use a lower-ASP drug, the dollar margin per injection decreases even though the clinical work is the same. A practice switching 100 monthly injections from Eylea (~$1,850 ASP) to bevacizumab (~$60 ASP) loses the buy-and-bill margin on the branded product, which can represent tens of thousands of dollars in monthly revenue.
Step therapy is adding a prior authorization layer to every anti-VEGF injection in retina practices with commercial and Medicare Advantage patients. If your billing team is spending hours on step therapy exceptions instead of posting payments and following up on denials, a billing partner with ophthalmology-specific payer expertise handles the step therapy workflow. Ophthalmology Bill Co matches your practice with vetted billing companies, free.
How to File a Step Therapy Exception
When the treating physician determines that the step-one drug is not clinically appropriate for a specific patient, the practice files a step therapy exception request. These six steps cover the process for most payers.
1. Identify the payer’s step therapy policy. Check the patient’s formulary before scheduling the injection. Know which drugs are on which tier and what the payer requires before approving the preferred product.
2. Document the clinical rationale. The exception letter must state why the step-one drug is not appropriate for this patient. Valid reasons include prior adverse reaction, contraindication, anatomic or clinical factors that favor the branded product, or documented treatment failure on the step-one drug.
3. Submit the prior authorization with the exception request. Most payers require the exception to be filed as part of the prior authorization process, not as a separate appeal. Include the clinical documentation, relevant imaging (OCT, fluorescein angiography), and the physician’s signed statement.
4. Prepare for peer-to-peer review. Many payers require the prescribing physician to discuss the case with the payer’s medical director before approving an exception. Schedule the peer-to-peer promptly to avoid extending the treatment delay.
5. Track the outcome and the timeline. Document the date submitted, the payer response, and the approval or denial. If denied, the practice can file a formal appeal. Tracking this data across patients and payers reveals which payers approve exceptions routinely and which deny them systematically.
6. Bill the approved drug correctly. Once approved, bill the branded drug with the correct J-code and any required prior authorization number on the claim. A claim without the auth number will deny even if the exception was approved. For practices also managing myopia and refractive diagnosis coding, the documentation discipline is the same: every claim must match what was authorized.
Common Step Therapy Billing Errors
Across the billing companies we vet for ophthalmology practices, four step therapy errors appear most frequently.
- Injecting before checking step therapy status. Administering the branded drug without verifying the payer’s step therapy requirement results in a denial after the drug is already in the patient’s eye. The practice absorbs the drug cost because the patient cannot return the injection.
- Filing a generic prior authorization instead of a step therapy exception. Some payers route step therapy exceptions through a different process than standard prior authorizations. Filing the wrong form delays the approval.
- Weak clinical documentation on the exception. An exception letter that says ‘patient needs Eylea’ without a specific clinical rationale (documented treatment failure, adverse reaction, contraindication) gets denied. The documentation must connect the patient’s clinical picture to the medical necessity of the specific drug.
- Not tracking step therapy outcomes by payer. A practice that does not track which payers approve exceptions and which deny them systematically cannot adjust its workflow. The data tells you which payers to fight and which to accommodate, and it saves staff time on exception requests that will not be approved. Learn more about how Ophthalmology Bill Co connects practices with billing experts who handle payer-specific anti-VEGF billing daily.
Frequently Asked Questions
Step therapy is a payer policy requiring the patient to try a lower-cost anti-VEGF drug (typically bevacizumab or a biosimilar) before the insurer will cover a branded alternative such as Eylea, Lucentis, or Vabysmo. It applies to intravitreal injections for wet AMD, diabetic macular edema, and other retinal conditions.
No. Medicare Part B does not apply step therapy to physician-administered drugs billed under Part B. However, Medicare Advantage plans can and do implement step therapy through their own formulary management. Check the patient’s specific MA plan for step therapy requirements before scheduling the injection.
Most payers process step therapy exceptions within 5 to 14 days. Urgent or expedited exceptions can be processed in 24 to 72 hours if the practice documents that the treatment delay could cause irreversible harm. Peer-to-peer reviews, when required, add additional time to the process.
Yes. If a step therapy exception is denied, the practice can file a formal appeal with additional clinical documentation. Most payers allow at least one level of appeal, and some states have step therapy override laws that require payers to grant exceptions when the prescribing physician documents clinical necessity.
Step therapy forces practices to use lower-ASP drugs, which reduces the dollar margin on buy-and-bill reimbursement. A practice switching from Eylea at approximately $1,850 ASP to compounded bevacizumab at approximately $60 ASP loses the buy-and-bill spread on the branded product, even though the clinical work of the injection is identical.
Several states have enacted step therapy reform laws that require payers to grant exceptions when the prescribing physician documents clinical necessity, prior treatment failure, or contraindication. As of 2026, over 30 states have some form of step therapy legislation. Check your state’s specific requirements, as coverage and exception rules vary.
Next Steps
For OCT billing alongside intravitreal injections, see our CPT 92134 billing guide.
Check each payer’s 2026 formulary for anti-VEGF step therapy requirements before scheduling injections.
Track step therapy exception outcomes by payer so your billing team knows which exceptions to file and which to accommodate.
Ready to stop losing revenue and staff time to step therapy denials? Get matched with a billing partner who handles anti-VEGF payer workflows.
Step therapy is reshaping how retina practices bill for every anti-VEGF injection. The prior authorization burden, the exception documentation, and the buy-and-bill economics all change when the payer dictates which drug to use first. A billing partner with ophthalmology-specific payer expertise handles the step therapy workflow so your team focuses on patient care. Ophthalmology Bill Co matches your practice with vetted billing companies, free. All 50 states, rates starting at 2.95%.
