Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of a variety of ocular vascular conditions. The macula, with the fovea at its center, has the highest photoreceptor concentration and is where visual detail is discerned. The anti-VEGF agent’s brolucizumab-dbll (Beovu®), ranibizumab (Lucentis^TM), ranibizumab injection ocular implant (Susvimo^TM), bevacizumab (Avastin®), aflibercept (Eylea^TM and Eylea HD®) and faricimab-svoa (Vabysmo^TM) are used to treat certain ocular disorders and are given by intravitreal injection.

Aflibercept-ayyh (Pavblu™), aflibercept-abzv (Enzeevu™), aflibercept-boav (Eydenzelt®), aflibercept-jbvf (Yesafili™) aflibercept-mrbb (Ahzantive™), aflibercept-yszy (Opuviz) are biosimilars of aflibercept (Eylea).

Ranibizumab-eqrn (Cimerli^TM), ranibizumab-leyk (Nufymco™) and ranibizumab-nuna (Byooviz^TM) are biosimilars of ranibizumab (Lucentis).

Geographic atrophy (GA) is a late stage of dry age-related macular degeneration (AMD). Pegcetacoplan (Syfovre^TM) and avacincaptad pegol (Izervay^TM) are intravitreal injections for the treatment of GA that works by slowing progression of GA lesions that can permanently damage the macula. 

Preferred Products

Bevacizumab (Avastin), bevacizumab-awwb (Mvasi), or bevacizumab-bvzr (Zirabev) are the preferred products required for members initiating new therapy for neovascular (wet) age-related macular degeneration (AMD). 

Non-Preferred Products

In order for a request for a non-preferred product [brolucizumab-dbll (Beovu), ranibizumab (Lucentis), ranibizumab-eqrn (Cimerli), ranibizumab-leyk (Nufymco), ranibizumab-nuna (Byooviz), ranibizumab injection ocular implant (Susvimo), aflibercept (Eylea and Eylea HD), aflibercept-ayyh (Pavblu), aflibercept-abzv (Enzeevu), aflibercept-boav (Eydenzelt), aflibercept-jbvf (Yesafili) aflibercept-mrbb (Ahzantive), aflibercept-yszy (Opuviz) or faricimab-svoa (Vabysmo)] to be approved the individual must have had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to one (1) of the preferred products or the preferred products are contraindicated.

Adequate therapeutic trial is defined as three (3) months following the injection series at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

New therapy is defined as no previous utilization within the last 365 calendar days.

Aflibercept (Eylea) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Diabetic macular edema (DME); or
• Diabetic retinopathy in patients with or without DME; or
• Macular edema following retinal vein occlusion (RVO); or
• Retinopathy of prematurity; or
• Neovascular (wet) age-related macular degeneration (AMD) when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of aflibercept (Eylea) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of aflibercept (Eylea) not meeting the criteria as indicated in this policy is considered not medically necessary.

Aflibercept (Eylea HD) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Diabetic Macular Edema (DME); or
• Diabetic Retinopathy (DR); or
• Macular edema following retinal vein occulsion (RVO); or
• Neovascular (wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of aflibercept (Eylea) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of aflibercept (Eylea HD) not meeting the criteria as indicated in this policy is considered not medically necessary.

Aflibercept-ayyh (Pavblu) aflibercept-abzv (Enzeevu), aflibercept-boav (Eydenzelt), aflibercept-jbvf (Yesafili) aflibercept-mrbb (Ahzantive) or aflibercept-yszy (Opuviz) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Macular Edema Following Retinal Vein Occlusion (RVO); or
• Diabetic Macular Edema (DME); or
• Diabetic Retinopathy (DR); or
• Neovascular (wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of aflibercept-ayyh (Pavblu) aflibercept-abzv (Enzeevu), aflibercept-boav (Eydenzelt), aflibercept-jbvf (Yesafili) aflibercept-mrbb (Ahzantive) or aflibercept-yszy (Opuviz) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of aflibercept-ayyh (Pavblu) aflibercept-abzv (Enzeevu), aflibercept-boav (Eydenzelt), aflibercept-jbvf (Yesafili) aflibercept-mrbb (Ahzantive) or aflibercept-yszy (Opuviz) not meeting the criteria as indicated in this policy is considered not medically necessary.

Bevacizumab (Avastin) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Choroidal neovascularization secondary to ANY ONE of the following:
  • Angioid streaks; or
  • Central serous chorioretinopathy; or
  • Choroidal rupture or trauma; or
  • Pathologic myopia; or
  • Presumed ocular histoplasmosis syndrome; or
• DME; or
• Idiopathic choroidal neovascularization; or
• Macular edema following RVO; or
• Neovascular (wet) AMD; or
• Neovascular glaucoma; or
• Non-proliferative diabetic retinopathy with macular edema; or
• Proliferative diabetic retinopathy; or
• Retinopathy of prematurity; or
• Rubeosis (neovascularization of the iris); or
• Traction retinal detachment as an adjunct to surgery.

The use of bevacizumab (Avastin) not meeting the criteria as indicated in this policy is considered not medically necessary.

Brolucizumab-dbll (Beovu) may be considered medically necessary for the treatment of individuals with:

• Diabetic Macular Edema (DME); or
• Neovascular (wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months

Reauthorization Criteria

• Continuation of brolucizumab-dbll (Beovu) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of brolucizumab-dbll (Beovu) not meeting the criteria as indicated in this policy is considered not medically necessary.

Ranibizumab (Lucentis), ranibizumab-leyk (Nufymco) or ranibizumab-eqrn (Cimerli) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Diabetic macular edema (DME); or
• Diabetic retinopathy in patients with or without DME; or
• Macular edema following RVO; or
• Myopic Choroidal Neovascularization (mCNV); or
• Neovascular (wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of ranibizumab (Lucentis), ranibizumab-leyk (Nufymco) or ranibizumab-eqrn (Cimerli) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of ranibizumab (Lucentis), ranibizumab-leyk (Nufymco) or ranibizumab-eqrn (Cimerli) not meeting the criteria as indicated in this policy is considered not medically necessary.

Ranibizumab-nuna (Byooviz) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Macular Edema Following Retinal Vein Occlusion (RVO); or
• Myopic Choroidal Neovascularization; or 
• Neovascular (Wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of ranibizumab-nuna (Byooviz) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of ranibizumab-nuna (Byooviz) not meeting the criteria as indicated in this policy is considered not medically necessary.

Ranibizumab (Susvimo) intravitreal injection via ocular implant may be considered medically necessary for the treatment of individuals with:

• Neovascular (wet) AMD who have previously responded to at least two (2) intravitreal injections of a VEGF inhibitor medication within the past six (6) months; and
• Treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; and
• Diabetic Macular Edema (DME) or Diabetic Retinopathy (DR) who have previously responded to at least two (2) intravitreal injections of a WEGF inhibitor medication within the past six (6) months; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of ranibizumab (Susvimo) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of ranibizumab (Susvimo) not meeting the criteria as indicated in this policy is considered not medically necessary.

Faricimab-svoa (Vabysmo) may be considered medically necessary for the treatment of individuals with ANY ONE of the following conditions:

• Neovascular (Wet) AMD when treatment with bevacizumab (Avastin) or a bevacizumab biosimilar (Mvasi or Zirabev) has been ineffective, not tolerated, or is contraindicated; or
• Diabetic Macular Edema (DME); or
• Macular edema following RVO; and
• Initial authorization will be for a 12 month period

Reauthorization Criteria

• Continuation of faricimab-svoa (Vabysmo) may be considered medically necessary when there is positive clinical response (e.g. improvement in visual acuity); and
• Reauthorization will be for a period of 12 months.

The use of faricimab-svoa (Vabysmo) not meeting the criteria as indicated in this policy is considered not medically necessary.

Pegcetacoplan injection (Syfovre) may be considered medically necessary for the treatment of individuals with the following condition:

• Geographic atrophy (GA) secondary to nonexudative (dry) AMD; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of pegcetacoplan injection (Syfovre) may be considered medically necessary when there is positive clinical response (e.g. reduction in rate of GA lesion growth documented by difference in mm²); and
• Reauthorization will be for a period of 12 months.

The use of pegcetacoplan injection (Syfovre) not meeting the criteria as indicated in this policy is considered not medically necessary.

Avacincaptad pegol intravitreal solution (Izervay) may be considered medically necessary for the treatment of individuals with the following condition:

• Geographic atrophy (GA) secondary to nonexudative (dry) AMD; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of avacincaptad pegol intravitreal solution (Izervay) may be considered medically necessary when there is positive clinical response (e.g. reduction in rate of GA lesion growth documented by difference in mm²); and
• Reauthorization will be for a period of 12 months.

The use of avacincaptad pegol (Izervay) not meeting the criteria as indicated in this policy is considered not medically necessary.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

NOTE: If an individual has already had a trial of Bevacizumab (Avastin) or a biosimilar, they are not required to “step back” and try Bevacizumab (Avastin) or a biosimilar again when switching between VEGF inhibitors.

NOTE: A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences in safety, purity and effectiveness from the reference product. 

References

1.     Eylea® (aflibercept) injection, for intravitreal use [package insert]. Regeneron Pharmaceuticals, Inc. Tarrytown, NY. Revised 10/2024.

2.     Lucentis® (ranibizumab injection) injection, for intravitreal use [package insert]. Genentech, Inc., South San Francisco, CA. Revised 02/2024.

3.     Avastin (bevacizumab) injection, for intravitreal use [package insert]. Genentech, Inc., South San Francisco, CA. Revised 09/2022.

4.     Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. aflibercept.

5.     Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. ranibizumab injection.

6.     Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc.bevacizumab.

7.     Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. Brolucizumab-dbll.

8.     Beovu® (brolucizumab-dbll) injection, for intravitreal use [package insert]. Novartis Pharmaceuticals Corp., East Hanover, NJ. Revised 07/2024.

9.     Micromedex DrugDex Compendium®. 2025. Bevacizumab.

10.  Dugel P, Koh A, Ogura Y, et al. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular Degeneration.Ophthalmology. 2020;127:72-84.

11.  Cheung C, Arnold J, Holz F, et al. Myopic choroidal neovascularization: review, guidance, and consensus statement on management. Opthalmology. 2017;124:16901711.

12.  Micromedex DrugDex Compendium®. 2025. Brolucizumab.

13.  Micromedex DrugDex Compendium®. 2025. Ranibizumab.

14.  Micromedex DrugDex Compendium®. 2025. Aflibercept.

15.  Micromedex DrugDex Compendium®. 2025. Faricimab-svoa.

16.  Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. Faricimab

17.  Susvimo^TM (ranibizumab injection) intravitreal injection via ocular implant [package insert]. Genentech Inc., South San Francisco, CA. Revised 05/2025.

18.  Byooviz® (ranibizumab-nuna) injection, for intravitreal use [package insert] Biogen Inc., Cambridge, MA. Revised 10/2023.

19. Vabysmo^TM (faricimab-svoa) injection, for intravitreal use [package insert]. Genentech Inc., South San Francisco, CA. Revised 07/2024.

20.   Aflibercept In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated February 1, 2022.

21.  Brolucizumab In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated July 20, 2020.

22.  Faricimab In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated April 10, 2024.

23.  Ranibizumab.ln: AHFS Drug Information Online Electronic Medical Library.Bethesda, MD: American Society of Health-System Pharmacists. Updated February 1, 2022.

24.  Khanani AM, Patel SS, Ferrone PJ, et al. Efficacy of every four monthly and quarterly dosing of faricimab vs ranibizumab in neovascular age-related macular degeneration: The STAIRWAY phase 2 randomized clinical trial. JAMA Ophthalmol. 2020;138(9):964-972.

25.  Sahni J, Patel SS, Dugel PU, et al. Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-a with faricimab in diabetic macular edema: BOULEVARD Phase 2 randomized trial. Ophthalmology. 2019;126(8):1155-1170.

26.  Woo SJ, Veith M, Hamouz J, et al. Efficacy and safety of a proposed ranibizumab biosimilar product vs a reference ranibizumab product for patients with neovascular age-related macular degeneration: A randomized clinical trial. JAMA Ophthalmol. 2021;139(1):68-76.

27.  Holekamp NM, Campochiaro PA, Chang MA, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2022;129(3):295-307.

28.  Cimerli^TM (ranibizumab-eqrn) injection, for intravitreal use [package insert]. Coherus BioSciences, Inc. Redwood City, CA. Revised 05/2024.

29.  Syfovre ^TM (pegcetacoplan injection), for intravitreal use [package insert]. Apellis Pharmaceuticals, Inc. Waltham, MA. Revised 07/2025.

30.  Micromedex DrugDex Compendium®. 2025. Pegcetacoplan

31.  Clinical Pharmacology^TM Compendium.2025. Tampa FL: Gold Standard, Inc. Pegcetaclopan.

32.  Pegcetaclopan.ln: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. June 10, 2024.

33.  Izervay^TM (avacincaptad pegol intravitreal solution) [package insert]. Iveric bio, Inc. Parsippany, NJ. Revised 03/2025.

34.  Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: A randomized pivotal phase 2/3 trial. Ophthalmology. 2021;128:576–86

35.  ClinicalTrials.gov. A Phase 3 Multicenter, Randomized, Double Masked, Sham- Controlled Clinical Trial to Assess the Safety and Efficacy of Intravitreal Administration of Zimura (Complement C5 Inhibitor) in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration. ClinicalTrials.gov Identifier: NCT04435366. Available at: https://clinicaltrials.gov/ct2/show/NCT04435366(accessed 10September2023).

36.  ClinicalTrials.gov. A Phase 2/3 Randomized, Double-Masked, Controlled Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura^TM (Anti-C5 Aptamer) in Subjects With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration. ClinicalTrials.gov Identifier: NCT02686658. Available at: https://clinicaltrials.gov/ct2/show/NCT02686658(accessed 10September 2023).

37.  Micromedex DrugDex Compendium®. 2025. Avacincaptad Pegol.

38.  Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. Avacincaptad Pegol.

39.  Eylea® HD (aflibercept) injection, for intravitreal use [package insert]. Regeneron Pharmaceuticals, Inc. Tarrytown, NY. Revised 11/2025.

40.  Scott IU, Campochiaro PA, Newman NJ, Biousse V. Retinal vascular occlusions. Lancet. 2020;396:1927– 1940.

41.  Hattenbach LO, Abreu F, Arrisi P, et al. BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale. Ophthalmol Sci. 2023;3(3):100302.

42.  Pavblu™ (aflibercept-ayyh) injection, for intravitreal use [package insert]. Amgen Inc., Thousand Oaks, CA. Revised 08/2024.

43.  Clinical Pharmacology^TM Compendium. 2025. Tampa FL: Gold Standard, Inc. Aflibercept.

44.  Micromedex DrugDex Compendium®. 2025. Aflibercept-ayyh.

45.  Enzeevu™ (aflibercept-abzv) injection, for intravitreal use [package insert]. Sandoz Inc., Princeton, NJ. Revised 02/2025.

46.  Yesafili™ (aflibercept-jbvf) injection, for intravitreal use [package insert]. Biocon Biologics Inc., Cambridge, MA. Revised 05/2024.

47.  Ahzantive™ (aflibercept-mrbb) injection, for intravitreal use [package insert]. Formycon AG, Thousand Martinsried, Germany. Revised 06/2024.

48.  Opduviz™ (aflibercept-yszy) injection, for intravitreal use [package insert]. Samsung Bioepis Co., Yeonsu-gu, Incheon, Korea. Revised 06/2025.

49.  Eydenzelt® (aflibercept-boav) injection, for intravitreal use [package insert]. Celltrion, Inc., Yeonsu-gu, Incheon, Korea. Revised 10/2025.