Ophthalmologic Policy. Vascular Endothelial Growth Factor (VEGF) Inhibitors

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Ophthalmologic Policy UnitedHealthcare Commercial Drug Policy Vascular Endothelial Growth Factor (VEGF) Inhibitors Policy Number: 2016D0042H Effective Date: October 1, 2016 Table of Contents Page INSTRUCTIONS FOR USE... 1 BENEFIT CONSIDERATIONS... 1 COVERAGE RATIONALE... 2 U.S. FOOD AND DRUG ADMINISTRATION... 3 BACKGROUND... 3 APPLICABLE CODES... 3 CLINICAL EVIDENCE... 14 CENTERS FOR MEDICARE AND MEDICAID SERVICES... 23 REFERENCES... 23 POLICY HISTORY/REVISION INFORMATION... 25 Related Commercial Policies Macular Degeneration Treatment Procedures Maximum Dosage Policy Oncology Medication Clinical Coverage Policy Related Coverage Determination Guidelines None INSTRUCTIONS FOR USE This Drug Policy provides assistance in interpreting UnitedHealthcare benefit plans. When deciding coverage, the member specific benefit plan document must be referenced. The terms of the member specific benefit plan document [e.g., Certificate of Coverage (COC), Schedule of Benefits (SOB), and/or Summary Plan Description (SPD)] may differ greatly from the standard benefit plan upon which this Drug Policy is based. In the event of a conflict, the member specific benefit plan document supersedes this Drug Policy. All reviewers must first identify member eligibility, any federal or state regulatory requirements, and the member specific benefit plan coverage prior to use of this Drug Policy. Other Policies and Coverage Determination Guidelines may apply. UnitedHealthcare reserves the right, in its sole discretion, to modify its Policies and Guidelines as necessary. This Drug Policy is provided for informational purposes. It does not constitute medical advice. UnitedHealthcare may also use tools developed by third parties, such as the MCG Care Guidelines, to assist us in administering health benefits. The MCG Care Guidelines are intended to be used in connection with the independent professional medical judgment of a qualified health care provider and do not constitute the practice of medicine or medical advice. BENEFIT CONSIDERATIONS Before using this policy, please check the member specific benefit plan document and any federal or state mandates, if applicable. Some Certificates of Coverage allow for coverage of experimental/investigational/unproven treatments for lifethreatening illnesses when certain conditions are met. The enrollee-specific benefit document must be consulted to make coverage decisions for this service. Some states mandate benefit coverage for off-label use of medications for some diagnoses or under some circumstances when certain conditions are met. Where such mandates apply, they supersede language in the benefit document or in the medical or drug policy. Benefit coverage for an otherwise unproven service for the treatment of serious rare diseases may occur when certain conditions are met. See the Policy and Procedure addressing the treatment of serious rare diseases. Essential Health Benefits for Individual and Small Group For plan years beginning on or after January 1, 2014, the Affordable Care Act of 2010 (ACA) requires fully insured non-grandfathered individual and small group plans (inside and outside of Exchanges) to provide coverage for ten categories of Essential Health Benefits ( EHBs ). Large group plans (both self-funded and fully insured), and small group ASO plans, are not subject to the requirement to offer coverage for EHBs. However, if such plans choose to provide coverage for benefits which are deemed EHBs, the ACA requires all dollar limits on those benefits to be removed on all Grandfathered and Non-Grandfathered plans. The determination of which benefits constitute EHBs is made on a state by state basis. As such, when using this policy, it is important to refer to the member specific benefit plan document to determine benefit coverage. Ophthalmologic (VEGF Inhibitors) Page 1 of 26

COVERAGE RATIONALE This policy provides information about the use of certain specialty pharmacy medications administered by the intravitreal route for ophthalmologic conditions. This policy refers to the following drug products, all of which are vascular endothelial growth factor (VEGF) inhibitors: Eylea (aflibercept) Avastin (bevacizumab) Macugen (pegaptanib) Lucentis (ranibizumab) Proven A. Eylea is proven and medically necessary for the treatment of: 1. Neovascular age-related macular degeneration (AMD) 2. Diabetic macular edema (DME) 3. Macular edema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) 4. Diabetic retinopathy in patients with diabetic macular edema (DME) B. Avastin is proven and medically necessary for the treatment of: 1. Neovascular age-related macular degeneration (AMD) 2. Diabetic macular edema 3. Macular edema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) 4. Proliferative diabetic retinopathy 5. Neovascular glaucoma 6. Choroidal neovascularization secondary to pathologic myopia, angioid streaks/pseudoxanthoma elasticum, or ocular histoplasmosis syndrome (OHS) C. Macugen is proven and medically necessary for the treatment of: 1. Neovascular age-related macular degeneration (AMD) 2. Diabetic macular edema D. Lucentis is proven and medically necessary for the treatment of: 1. Neovascular age-related macular degeneration (AMD) 2. Diabetic macular edema (DME) 3. Macular edema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) 4. Choroidal neovascularization secondary to pathologic myopia, angioid streaks/pseudoxanthoma elasticum, or ocular histoplasmosis syndrome (OHS) 5. Diabetic retinopathy in patients with diabetic macular edema (DME) Unproven Aflibercept, bevacizumab, pegaptanib, and ranibizumab are unproven and not medically necessary for the treatment of retinopathy of prematurity. Because VEGF is involved in a wide variety of physiologic processes, the ocular and systemic safety of anti-vegf agents is of prime concern in neonates. Additional Information: Bevacizumab is supplied in sterile vials containing a solution of 25 mg/ml. Doses utilized in ophthalmic conditions generally range from 6.2 mcg to 2.5 mg. Therefore, bevacizumab in vials is often divided into single-dose, prefilled syringes for intravitreal use by compounding pharmacies. Compounding pharmacies must comply with United States Pharmacopeia (USP) Chapter 797, which sets standards for the compounding, transportation, and storage of compounded sterile products (CSP). 1 The Pharmacy Compounding Accreditation Board can verify that the pharmacy is adhering to these standards. 2 The American Society of Retinal Specialists (ASRS) is committed to ensuring that retina specialists have access to compounded drugs (such as Avastin) that are prepared with high-quality material following good quality controls and sound engineering design by appropriately trained personnel. Please refer to their information page at https://www.asrs.org/advocacy-practice/access-to-safe-compounded-agents for resources pertaining to access of safe compounded agents. 14 Please refer to the US Food and Drug Administration (FDA) Section of this policy for information related to contamination of compounded bevacizumab. In an effort to guard against contamination during the compounding Ophthalmologic (VEGF Inhibitors) Page 2 of 26

process, the United States Veterans Health Administration (USVHA) requires that only USVHA pharmacies may dispense bevacizumab for intravitreal administration to Veterans Administration beneficiaries. The medication must be dispensed directly to the VA ophthalmologist, who will then be responsible for preparing and administering the bevacizumab dose for each patient. In addition to strict labeling and storage requirements, the ophthalmologist is required to prepare only one dose of medication from each vial; if both eyes are to be treated, a separate vial and syringe must be utilized. 3 U.S. FOOD AND DRUG ADMINISTRATION Avastin (bevacizumab) The statements below are for information only. Oncology indications for bevacizumab are listed in the NCCN Drugs & Biologics Compendium. Bevacizumab, in combination with intravenous 5-fluorouracil based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. 57 Bevacizumab, in combination with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab-containing regimen. 57 Bevacizumab, in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer. 57 Bevacizumab for treatment of glioblastoma, is indicated as a single agent for patients with progressive disease following prior therapy. 57 Bevacizumab, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic cervical cancer. 57 Bevacizumab, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma. 57 Administration of bevacizumab infusions or intravitreal injections for the treatment of ophthalmologic conditions is considered off-label. The FDA issued an alert dated August 30, 2011 that notification had been received from the Florida Department of Health (DOH) regarding a cluster of Streptococcus endophthalmitis infections in three clinics following intravitreal injection of repackaged Avastin. 58 Investigators traced the tainted injections to a single pharmacy that had repackaged the Avastin from sterile injectable 100 mg/4 ml, single-use, preservative-free vials into individual 1 ml single-use syringes. The alert reminded health care professionals that repackaging sterile drugs without proper aseptic technique can compromise product sterility, potentially putting the patient at risk for microbial infections. Health care professionals should ensure that drug products are obtained from appropriate, reliable sources and properly administered. Eylea (aflibercept) Aflibercept is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy in patients with DME. 5 Lucentis (ranibizumab) Ranibizumab is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME); and diabetic retinopathy in patients with DME. 7 Macugen (pegaptanib) Pegaptanib is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD). 6 BACKGROUND Vascular endothelial growth factor (VEGF) is a protein that stimulates the growth, proliferation and survival of vascular endothelial cells. VEGF plays a critical role in the development of new blood vessels (angiogenesis), increases vascular permeability in small blood vessels and prevents apoptosis of vascular endothelial cells in immature blood vessels. VEGF has been implicated in blood retinal barrier breakdown and pathological ocular neovascularization. 4 APPLICABLE CODES The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all inclusive. Listing of a code in this policy does not imply that the service described by the code is a covered or non- Ophthalmologic (VEGF Inhibitors) Page 3 of 26

covered health service. Benefit coverage for health services is determined by the member specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee claim payment. Other Policies and Coverage Determination Guidelines may apply. HCPCS Code J0178 J2503 J2778 J9035 Description Injection, aflibercept, 1 mg Injection, pegaptanib sodium, 0.3 mg Injection, ranibizumab, 0.1 mg Injection, bevacizumab, 10 mg ICD-10 Diagnosis Code Description B39.4 Histoplasmosis capsulati, unspecified B39.5 Histoplasmosis duboisii B39.9 Histoplasmosis, unspecified E08.311 Diabetes mellitus due to underlying condition with unspecified diabetic retinopathy with macular edema E08.3211 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, right eye E08.3212 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, left eye E08.3213 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, bilateral E08.3219 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye E08.3291 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, right eye E08.3292 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, left eye E08.3293 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, bilateral E08.3299 Diabetes mellitus due to underlying condition with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye E08.3311 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, right eye E08.3312 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, left eye E08.3313 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, bilateral E08.3319 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye E08.3391 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, right eye E08.3392 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, left eye E08.3393 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, bilateral E08.3399 Diabetes mellitus due to underlying condition with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye E08.3411 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, right eye E08.3412 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, left eye E08.3413 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, bilateral E08.3419 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye E08.3491 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, right eye E08.3492 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, left eye Ophthalmologic (VEGF Inhibitors) Page 4 of 26

ICD-10 Diagnosis Code Description E08.3493 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, bilateral E08.3499 Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye E08.3511 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, right eye E08.3512 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, left eye E08.3513 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, bilateral E08.3519 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with macular edema, unspecified eye E08.3521 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye E08.3522 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye E08.3523 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral E08.3529 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye E08.3531 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye E08.3532 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye E08.3533 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral E08.3539 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye E08.3541 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye E08.3542 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye E08.3543 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral E08.3549 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye E08.3551 Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, right eye E08.3552 Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, left eye E08.3553 Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, bilateral E08.3559 Diabetes mellitus due to underlying condition with stable proliferative diabetic retinopathy, unspecified eye E08.3591 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, right eye E08.3592 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, left eye E08.3593 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, bilateral E08.3599 Diabetes mellitus due to underlying condition with proliferative diabetic retinopathy without macular edema, unspecified eye E08.37X1 Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, right eye E08.37X2 Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, left eye Ophthalmologic (VEGF Inhibitors) Page 5 of 26

ICD-10 Diagnosis Code Description E08.37X3 Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, bilateral E08.37X9 Diabetes mellitus due to underlying condition with diabetic macular edema, resolved following treatment, unspecified eye E09.311 Drug or chemical induced diabetes mellitus with unspecified diabetic retinopathy with macular edema E09.3211 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye E09.3212 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye E09.3213 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral E09.3219 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye E09.3291 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye E09.3292 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye E09.3293 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral E09.3299 Drug or chemical induced diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye E09.3311 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye E09.3312 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye E09.3313 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral E09.3319 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye E09.3391 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye E09.3392 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye E09.3393 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral E09.3399 Drug or chemical induced diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye E09.3411 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye E09.3412 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye E09.3413 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral E09.3419 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye E09.3491 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye E09.3492 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye E09.3493 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral E09.3499 Drug or chemical induced diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye E09.3511 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye E09.3512 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye E09.3513 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral Ophthalmologic (VEGF Inhibitors) Page 6 of 26

ICD-10 Diagnosis Code Description E09.3519 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye E09.3521 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye E09.3522 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye E09.3523 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral E09.3529 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye E09.3531 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye E09.3532 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye E09.3533 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral E09.3539 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye E09.3541 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye E09.3542 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye E09.3543 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral E09.3549 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye E09.3551 Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, right eye E09.3552 Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, left eye E09.3553 Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, bilateral E09.3559 Drug or chemical induced diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye E09.3591 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye E09.3592 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye E09.3593 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral E09.3599 Drug or chemical induced diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye E09.37X1 Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, right eye E09.37X2 Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, left eye E09.37X3 Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral E09.37X9 Drug or chemical induced diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye E10.311 Type 1 diabetes mellitus with unspecified diabetic retinopathy with macular edema E10.3211 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye E10.3212 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye E10.3213 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral Ophthalmologic (VEGF Inhibitors) Page 7 of 26

ICD-10 Diagnosis Code Description E10.3219 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye E10.3291 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye E10.3292 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye E10.3293 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral E10.3299 Type 1 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye E10.3311 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye E10.3312 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye E10.3313 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral E10.3319 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye E10.3391 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye E10.3392 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye E10.3393 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral E10.3399 Type 1 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye E10.3411 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye E10.3412 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye E10.3413 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral E10.3419 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye E10.3491 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye E10.3492 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye E10.3493 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral E10.3499 Type 1 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye E10.3511 Type 1 diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye E10.3512 Type 1 diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye E10.3513 Type 1 diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral E10.3519 Type 1 diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye E10.3521 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye E10.3522 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye E10.3523 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral E10.3529 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye E10.3531 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye Ophthalmologic (VEGF Inhibitors) Page 8 of 26

ICD-10 Diagnosis Code Description E10.3532 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye E10.3533 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral E10.3539 Type 1 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye E10.3541 Type 1 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye E10.3542 Type 1 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye E10.3543 Type 1 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral E10.3549 Type 1 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye E10.3551 Type 1 diabetes mellitus with stable proliferative diabetic retinopathy, right eye E10.3552 Type 1 diabetes mellitus with stable proliferative diabetic retinopathy, left eye E10.3553 Type 1 diabetes mellitus with stable proliferative diabetic retinopathy, bilateral E10.3559 Type 1 diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye E10.3591 Type 1 diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye E10.3592 Type 1 diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye E10.3593 Type 1 diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral E10.3599 Type 1 diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye E10.37X1 Type 1 diabetes mellitus with diabetic macular edema, resolved following treatment, right eye E10.37X2 Type 1 diabetes mellitus with diabetic macular edema, resolved following treatment, left eye E10.37X3 Type 1 diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral E10.37X9 Type 1 diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye E11.311 Type 2 diabetes mellitus with unspecified diabetic retinopathy with macular edema E11.3211 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye E11.3212 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye E11.3213 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral E11.3219 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye E11.3291 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye E11.3292 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye E11.3293 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral E11.3299 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye E11.3311 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye E11.3312 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye E11.3313 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral E11.3319 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye Ophthalmologic (VEGF Inhibitors) Page 9 of 26

ICD-10 Diagnosis Code Description E11.3391 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye E11.3392 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye E11.3393 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral E11.3399 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye E11.3411 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye E11.3412 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye E11.3413 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral E11.3419 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye E11.3491 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye E11.3492 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye E11.3493 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral E11.3499 Type 2 diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye E11.3511 Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye E11.3512 Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye E11.3513 Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral E11.3519 Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye E11.3521 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye E11.3522 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye E11.3523 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral E11.3529 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye E11.3531 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye E11.3532 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye E11.3533 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral E11.3539 Type 2 diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye E11.3541 Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye E11.3542 Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye E11.3543 Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral E11.3549 Type 2 diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye E11.3551 Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, right eye E11.3552 Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, left eye E11.3553 Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, bilateral E11.3559 Type 2 diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye Ophthalmologic (VEGF Inhibitors) Page 10 of 26

ICD-10 Diagnosis Code Description E11.3591 Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye E11.3592 Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye E11.3593 Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral E11.3599 Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye E11.37X1 Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, right eye E11.37X2 Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, left eye E11.37X3 Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral E11.37X9 Type 2 diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye E13.311 Other specified diabetes mellitus with unspecified diabetic retinopathy with macular edema E13.3211 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, right eye E13.3212 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, left eye E13.3213 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, bilateral E13.3219 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy with macular edema, unspecified eye E13.3291 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, right eye E13.3292 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, left eye E13.3293 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, bilateral E13.3299 Other specified diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema, unspecified eye E13.3311 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye E13.3312 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, left eye E13.3313 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, bilateral E13.3319 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, unspecified eye E13.3391 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, right eye E13.3392 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, left eye E13.3393 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, bilateral E13.3399 Other specified diabetes mellitus with moderate nonproliferative diabetic retinopathy without macular edema, unspecified eye E13.3411 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, right eye E13.3412 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, left eye E13.3413 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, bilateral E13.3419 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy with macular edema, unspecified eye E13.3491 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, right eye Ophthalmologic (VEGF Inhibitors) Page 11 of 26

ICD-10 Diagnosis Code Description E13.3492 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, left eye E13.3493 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, bilateral E13.3499 Other specified diabetes mellitus with severe nonproliferative diabetic retinopathy without macular edema, unspecified eye E13.3511 Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye E13.3512 Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, left eye E13.3513 Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, bilateral E13.3519 Other specified diabetes mellitus with proliferative diabetic retinopathy with macular edema, unspecified eye E13.3521 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, right eye E13.3522 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, left eye E13.3523 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, bilateral E13.3529 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment involving the macula, unspecified eye E13.3531 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, right eye E13.3532 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, left eye E13.3533 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, bilateral E13.3539 Other specified diabetes mellitus with proliferative diabetic retinopathy with traction retinal detachment not involving the macula, unspecified eye E13.3541 Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, right eye E13.3542 Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, left eye E13.3543 Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, bilateral E13.3549 Other specified diabetes mellitus with proliferative diabetic retinopathy with combined traction retinal detachment and rhegmatogenous retinal detachment, unspecified eye E13.3551 Other specified diabetes mellitus with stable proliferative diabetic retinopathy, right eye E13.3552 Other specified diabetes mellitus with stable proliferative diabetic retinopathy, left eye E13.3553 Other specified diabetes mellitus with stable proliferative diabetic retinopathy, bilateral E13.3559 Other specified diabetes mellitus with stable proliferative diabetic retinopathy, unspecified eye E13.3591 Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, right eye E13.3592 Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, left eye E13.3593 Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, bilateral E13.3599 Other specified diabetes mellitus with proliferative diabetic retinopathy without macular edema, unspecified eye E13.37X1 Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, right eye E13.37X2 Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, left eye E13.37X3 Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, bilateral Ophthalmologic (VEGF Inhibitors) Page 12 of 26

ICD-10 Diagnosis Code Description E13.37X9 Other specified diabetes mellitus with diabetic macular edema, resolved following treatment, unspecified eye H32 Chorioretinal disorders in diseases classified elsewhere H34.8110 Central retinal vein occlusion, right eye, with macular edema H34.8111 Central retinal vein occlusion, right eye, with retinal neovascularization H34.8112 Central retinal vein occlusion, right eye, stable H34.8120 Central retinal vein occlusion, left eye, with macular edema H34.8121 Central retinal vein occlusion, left eye, with retinal neovascularization H34.8122 Central retinal vein occlusion, left eye, stable H34.8130 Central retinal vein occlusion, bilateral, with macular edema H34.8131 Central retinal vein occlusion, bilateral, with retinal neovascularization H34.8132 Central retinal vein occlusion, bilateral, stable H34.8190 Central retinal vein occlusion, unspecified eye, with macular edema H34.8191 Central retinal vein occlusion, unspecified eye, with retinal neovascularization H34.8192 Central retinal vein occlusion, unspecified eye, stable H34.821 Venous engorgement, right eye H34.822 Venous engorgement, left eye H34.823 Venous engorgement, bilateral H34.829 Venous engorgement, unspecified eye H34.8310 Tributary (branch) retinal vein occlusion, right eye, with macular edema H34.8311 Tributary (branch) retinal vein occlusion, right eye, with retinal neovascularization H34.8312 Tributary (branch) retinal vein occlusion, right eye, stable H34.8320 Tributary (branch) retinal vein occlusion, left eye, with macular edema H34.8321 Tributary (branch) retinal vein occlusion, left eye, with retinal neovascularization H34.8322 Tributary (branch) retinal vein occlusion, left eye, stable H34.8330 Tributary (branch) retinal vein occlusion, bilateral, with macular edema H34.8331 Tributary (branch) retinal vein occlusion, bilateral, with retinal neovascularization H34.8332 Tributary (branch) retinal vein occlusion, bilateral, stable H34.8390 Tributary (branch) retinal vein occlusion, unspecified eye, with macular edema H34.8391 Tributary (branch) retinal vein occlusion, unspecified eye, with retinal neovascularization H34.8392 Tributary (branch) retinal vein occlusion, unspecified eye, stable H35.051 Retinal neovascularization, unspecified, right eye H35.052 Retinal neovascularization, unspecified, left eye H35.053 Retinal neovascularization, unspecified, bilateral H35.059 Retinal neovascularization, unspecified, unspecified eye H35.3210 Exudative age-related macular degeneration, right eye, stage unspecified H35.3211 Exudative age-related macular degeneration, right eye, with active choroidal neovascularization H35.3212 Exudative age-related macular degeneration, right eye, with inactive choroidal neovascularization H35.3213 Exudative age-related macular degeneration, right eye, with inactive scar H35.3220 Exudative age-related macular degeneration, left eye, stage unspecified H35.3221 Exudative age-related macular degeneration, left eye, with active choroidal neovascularization H35.3222 Exudative age-related macular degeneration, left eye, with inactive choroidal neovascularization H35.3223 Exudative age-related macular degeneration, left eye, with inactive scar H35.3230 Exudative age-related macular degeneration, bilateral, stage unspecified H35.3231 Exudative age-related macular degeneration, bilateral, with active choroidal neovascularization H35.3232 Exudative age-related macular degeneration, bilateral, with inactive choroidal neovascularization H35.3233 Exudative age-related macular degeneration, bilateral, with inactive scar H35.3290 Exudative age-related macular degeneration, unspecified eye, stage unspecified H35.3291 Exudative age-related macular degeneration, unspecified eye, with active choroidal neovascularization H35.3292 Exudative age-related macular degeneration, unspecified eye, with inactive choroidal neovascularization H35.3293 Exudative age-related macular degeneration, unspecified eye, with inactive scar Ophthalmologic (VEGF Inhibitors) Page 13 of 26