CurrentUnitedHealthcarePolicy IEXD0042.18

Ophthalmologic Vascular Endothelial Growth Factor (VEGF) Inhibitors

Medical necessity and coverage criteria for intravitreal VEGF and dual VEGF/Ang-2 inhibitors for ophthalmologic conditions; affects providers requesting coverage from UnitedHealthcare for these intravitreal agents.

Policy Summary

PayerUnitedHealthcare

PolicyOphthalmologic Vascular Endothelial Growth Factor (VEGF) Inhibitors

Policy CodePolicy IEXD0042.18

Change TypeNo material change

Effective DateApr 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document a mapped ICD-10 diagnosis and that intravitreal administrations do not exceed 12 doses per year per eye.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12maximum intravitreal administrations per year per eye

10 agentsnamed VEGF or dual VEGF/Ang-2 inhibitors referenced

~13distinct HCPCS J/Q drug codes listed

Part 1document part count (this extract)

J0177–J9035HCPCS/J-codes listed in this part

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Coverage criteria for intravitreal VEGF and dual VEGF/Ang-2 inhibitors

General Requirements

Covered when ALL of the following are met

General Requirements - Initial Therapy: For initial therapy: the member has a documented qualifying ophthalmic diagnosis and the proposed treatment is intravitreal administration of a listed VEGF or dual VEGF/Ang-2 inhibitor; and intravitreal administration will not exceed 12 doses per year per eye.<=12 doses/year/eye

From General Requirements (chunk 5)

General Requirements - Continuation Therapy: For continuation of therapy: documentation demonstrates a positive clinical response to prior anti‑VEGF therapy (clinical improvement or stabilization appropriate to the indication); and intravitreal administration will not exceed 12 doses per year per eye.<=12 doses/year/eye

From General Requirements (chunk 5)

Agent-specific Indications

The following agents are listed as proven and medically necessary for specified indications

Cimerli (ranibizumab-eqrn): Cimerli is medically necessary for myopic choroidal neovascularization (mCNV), diabetic macular edema (DME), diabetic retinopathy (DR), macular edema following retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD).

chunk 10

Pavblu (aflibercept-ayyh): Pavblu is medically necessary for diabetic macular edema (DME), diabetic retinopathy (DR), macular edema following retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD).

chunk 14

Vabysmo (faricimab-svoa): Vabysmo is medically necessary for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO).

chunk 15

Diagnosis mapping coverage criterion (fragment)

Covered when the billed HCPCS/J/Q code is supported by one of the listed ICD-10 diabetes with retinopathy/macular edema diagnosis codes

Diagnosis-to-code match: The claim's ICD‑10 diagnosis must be one of the specific E08/E09/E10/E11/E13 cluster codes listed in the applicable table rows for the HCPCS/J/Q code billed; when laterality is specified in the ICD‑10 code, the laterality must match the treated eye on the claim.

Mapping lines in document indicate which diagnosis codes apply to which HCPCS/Q/J codes (chunks 108–127).

Diagnosis-to-HCPCS mapping requirement

Coverage depends on matching the diagnosis code to the HCPCS/J-code administered as listed below

Mapping requirement: The billed HCPCS/J-code must be one that the document indicates 'Applies to' for the member's ICD‑10 diagnosis code (see table rows marked 'X').

See the ICD‑10 → HCPCS applicability markings in the policy tables (chunks 180, 196).

Neovascular AMD — Indications & Evidence

Covered when medication is indicated for neovascular (exudative) AMD

FDA/indicated agents for nAMD: Aflibercept, aflibercept-ayyh, brolucizumab, pegaptanib, ranibizumab, ranibizumab-eqrn, ranibizumab-nuna and faricimab are indicated for treatment of neovascular age-related macular degeneration.

Statement of indicated agents (chunk 211)

Evidence of benefit vs control: Randomized trials (systematic review, pooled n ≈ 5,496) demonstrate anti‑VEGF agents improve or preserve vision compared with no anti‑VEGF treatment.1 year endpoints

Systematic review summary (chunks 211–212)

Head-to-head noninferiority data: Head‑to‑head randomized trials (e.g., CATT, HAWK/HARRIER) showed bevacizumab noninferior to ranibizumab when dosed similarly and brolucizumab noninferior to aflibercept for BCVA at 48 weeks with many brolucizumab eyes maintained on q12w dosing.48 weeks

Efficacy evidence by indication

Evidence summaries supporting use of specific anti-VEGF agents for indicated retinal diseases

nAMD - brolucizumab: HAWK and HARRIER (n=1817) demonstrated brolucizumab noninferior to aflibercept for BCVA at 48 weeks; >50% of brolucizumab 6 mg eyes maintained q12w dosing with favorable anatomic outcomes.48 weeks

chunks 216–217

nAMD - faricimab: TENAYA and LUCERNE (n=1329) showed faricimab noninferior to aflibercept for mean BCVA change at primary endpoint with many patients assigned to Q16W/Q12W/Q8W regimens by week 48.week 48

chunk 218

DME - faricimab and aflibercept: YOSEMITE and RHINE (n=1891) found faricimab regimens noninferior to aflibercept for mean BCVA change at year‑1 with a subset achieving extended dosing intervals.

Clinical evidence summary by indication

Summary of coverage-relevant clinical evidence for common ophthalmologic indications

Macular edema from BRVO/CRVO: FDA‑indicated agents (aflibercept, faricimab, ranibizumab and biosimilars) demonstrate efficacy for macular edema following RVO with BCVA improvements at 24 weeks; prospective bevacizumab studies report substantial VA and CRT gains with repeated injections (e.g., Zhang et al., BALATON/COMINO, VIBRANT).BCVA gains and CRT reductions reported in cited trials

chunks 235–238

Proliferative diabetic retinopathy: Aflibercept and ranibizumab are indicated for diabetic retinopathy; intravitreal bevacizumab has RCT evidence supporting adjunctive preoperative use to reduce early post‑vitrectomy hemorrhage and improve surgical outcomes.Study‑specific outcomes

chunks 239–242

Choroidal neovascularization (myopia, PXE, OHS): Ranibizumab (and biosimilars) are indicated for myopic CNV; bevacizumab and ranibizumab series for PXE and POHS show improvements in BCVA and CRT with variable numbers of injections over long‑term follow‑up.

Indication-specific coverage criteria

Coverage supported by clinical evidence when treatment is for listed ophthalmic indications with appropriate monitoring and follow-up:

CNV secondary to pathologic myopia: Intravitreal ranibizumab demonstrated improvement or stabilization of BCVA in prospective series with median follow‑up ≈13 months and a low mean number of injections (≈2.8).

chunk 252

CNV secondary to angioid streaks / PXE: Intravitreal bevacizumab or ranibizumab case series and long‑term follow‑up report visual and anatomic improvements with repeated injections commonly required (mean injections up to ~6.5 over 28 months).

chunks 253–256

CNV secondary to ocular histoplasmosis syndrome (POHS): Intravitreal bevacizumab monotherapy or combined with PDT produced significant visual stabilization/improvement with an average ~4.24 injections per year in reported series.~4.24 injections/year

chunk 257

Compounded bevacizumab (Avastin) used for intravitreal administration must be prepared by compounding pharmacies that comply with USP Chapter 797. Documented operational safeguards are recommended: use of accredited compounding sources, recording lot numbers in the patient record and a local log, and documentation of pharmacy credentials and informed consent when off-label use is involved. For U.S. Veterans, the Veterans Health Administration requires dispensing and preparation through VA pharmacies with strict labeling, storage, and a requirement that only one dose be prepared from each vial (separate vials/syringes if both eyes are treated).

The lists of HCPCS and Q-codes in this policy are provided for reference only. Inclusion of a code does not imply the service is covered or guarantee reimbursement; benefit coverage is determined by the member’s benefit plan and applicable laws and other policy rules.

Diagnoses that are not present in the ICD-10 → HCPCS mapping tables shown in this excerpt may not be supported for billing the listed intravitreal VEGF/Q/J codes. Providers should confirm that the member’s billed ICD-10 diagnosis appears in the applicable mapping before submitting claims.

Not every ICD-10 diagnosis listed in the tables maps to every HCPCS/J-code; some table cells are blank, indicating that a particular diagnosis-to-HCPCS combination is not applicable. Ensure the submitted ICD-10 diagnosis is one of the codes marked as 'Applies to' for the HCPCS/J/Q code billed.

This document fragment does not show mappings for every possible diagnosis. Absence of a diagnosis code in this excerpt means that the code is not shown as mapped here; absence in this portion alone should prompt verification in the full policy or payer resources rather than being interpreted as an absolute coverage decision.

Multiple entries for H21.1Xx (other vascular disorders of the iris and ciliary body) in the mapping table are marked as applying only to J9035 (bevacizumab) and show no applicability marks for other J/Q codes in this excerpt, indicating limited product applicability for these diagnoses in the table shown.

Diagnoses that do not appear in this section of the policy are not shown as applicable in this excerpt. Absence from this excerpt implies no mapping within these pages and should trigger review of the complete mapping tables or payer guidance for the full applicability determination.

No explicit exclusions are listed in this document segment. Coverage decisions in the excerpt rely on mapped diagnosis-to-HCPCS relationships and general requirements rather than standalone exclusion statements in these pages.

Percentages reported in clinical trials for patients maintained on extended dosing intervals (for example, Q12W or Q16W) reflect the trial populations and protocols; these proportions are not necessarily generalizable to broader clinical practice because trial inclusion/exclusion criteria and monitoring schedules differ from routine care.

Within the chunks cited there are no explicit policy exclusions described for the listed agents or indications. The tables and evidence summaries provide mappings and supporting data but do not add discrete exclusion language in these excerpts.

Current evidence does not support routine, unconditional use of intravitreal anti‑VEGF agents as standard first‑line therapy for all preterm infants with type 1 ROP. Systematic and technical assessments note limited quality of evidence, uncertainty about long‑term systemic effects, and zone‑specific differences in recurrence and retreatment risk; therefore use in ROP requires careful case selection and documented clinical rationale.

Reiterating the coding guidance: listing a HCPCS or Q-code in the policy is for reference only and does not itself establish coverage. Providers must confirm coverage and reimbursement rules with the member’s benefit plan and follow claim submission requirements.

There are no explicit 'not medically necessary' statements in this fragment. Medical necessity determinations in the excerpt are governed by the General Requirements and the diagnosis-to-HCPCS mapping presented elsewhere in the policy.

This excerpt does not contain explicit 'not medically necessary' language. The policy segment focuses on applicable diagnosis-to-HCPCS mappings and evidence summaries rather than listing services that are explicitly non‑covered in these pages.

No explicit not‑medically‑necessary statements appear in the trials and evidence summary excerpts. The clinical trial data are presented to support indicated uses and to inform coverage with criteria rather than to enumerate non‑covered services in this segment.

The provided text in these chunks does not specify any services as not medically necessary; instead it summarizes trial results and applicable indications for specific agents.

The technical assessment and evidence discussion emphasize that routine, unconditional intravitreal anti‑VEGF therapy for type 1 ROP is not supported without consideration of zone, follow‑up needs, and the current limited long‑term safety data; this functions as a caution rather than a simple blanket exclusion.

Relevant HCPCS/J/Q and ICD-10 codes

Applicable HCPCS / J / Q CodesHCPCS

J0177	Injection, aflibercept hd, 1 mg (Eylea HD)
J0178	Injection, aflibercept, 1 mg (Eylea)
J0179	Injection, brolucizumab-dbll, 1 mg (Beovu)
J2777	Injection, faricimab-svoa, 0.1 mg (Vabysmo)
J2778	Injection, ranibizumab, 0.1 mg (Lucentis)
J9035	Injection, bevacizumab, 10 mg (Avastin)
Q5147	Injection, aflibercept-ayyh (Pavblu), biosimilar, 1 mg
Q5124	Injection, ranibizumab-nuna (Byooviz), biosimilar, 0.1 mg
Q5128	Injection, ranibizumab-eqrn (Cimerli), biosimilar, 0.1 mg

Applicable ICD-10 Diagnosis Codes (consolidated list)ICD-10

E08.3411	Diabetes mellitus due to underlying condition with severe nonproliferative diabetic retinopathy with macular edema, right eye
E08.3412	... left eye
E08.3413	... bilateral
E08.3419	... unspecified eye
E08.3491	Severe nonproliferative diabetic retinopathy without macular edema, right eye
E08.3492	... left eye
E08.3493	... bilateral
E08.3499	... unspecified eye
E08.3511	Proliferative diabetic retinopathy with macular edema, right eye
E08.3512	... left eye

1–10 of 90

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Prior authorization, documentation, and billing actions

Prior Authorization

Prior authorization required

Prior authorization is required for the intravitreal VEGF and dual VEGF/Ang‑2 inhibitors listed in this policy. When requesting prior authorization or submitting claims, providers must use the specific HCPCS/J/Q codes listed below and document an applicable ICD‑10 diagnosis code that maps to the billed drug code. Inclusion of a code in this policy is for reference only and does not guarantee payment. Requests that exceed 12 intravitreal administrations per year per eye risk denial.

Applicable HCPCS/J/Q codes (reference): J0177, J0178, J0179, J2777, J2778, J9035, Q5147, Q5124, Q5128, J2777
Prior authorization required when billing any of the listed HCPCS/J/Q codes for intravitreal VEGF or VEGF/Ang‑2 inhibitors
Annual dose limit: Intravitreal administrations must not exceed 12 doses per year per eye (initial and continuation therapy)

Billing Rule

Background and clinical evidence

Background: Intravitreal vascular endothelial growth factor (VEGF) inhibitors and dual VEGF/Ang‑2 inhibitors are specialty injectable medications used to treat retinal vascular and neovascular conditions such as neovascular age‑related macular degeneration (nAMD), diabetic macular edema (DME), diabetic retinopathy (DR), macular edema following retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV). Clinical trial data summarized in this policy support efficacy of labeled agents (e.g., aflibercept, ranibizumab, faricimab, brolucizumab) for these indications; off‑label bevacizumab use is common in ophthalmology and is discussed in the evidence and compounding guidance.

inv-05 (evidence overlap): Neovascular AMD — Indications & Evidence

Neovascular AMD — evidence overlap: Randomized trials and systematic reviews demonstrate effectiveness of anti‑VEGF agents for nAMD; head‑to‑head trials (CATT, HAWK/HARRIER, TENAYA/LUCERNE) inform comparative efficacy and potential extended dosing strategies.

Evidence summarized in chunks 211, 216–218

inv-06: Efficacy evidence by indication — Evidence summaries supporting use of specific anti-VEGF agents

Key definitions and terms

Type I ROP — definition and criteria

DefinitionType I Retinopathy of Prematurity (ROP) — 'high-risk prethreshold ROP' defined as any stage ROP with plus disease in zone I; stage 3 ROP without plus disease in zone I; or zone II stage 2 or 3 ROP with plus disease.

Typical trials/populationEligibility in ROP trials included Zone I Stage 1+, 2+, 3 or 3+, Zone II Stage 2+ or 3+, or AP-ROP; used in randomized infant ROP studies (BUTTERFLEYE, FIREFLEYE).

Clinical implicationsHigh-risk lesions (Type I) are indications where anti-VEGF therapy has randomized trial support but require extended follow-up for vascularization and recurrence monitoring.

HCPCS J/Q codes — billing codes used to identify injectable VEGF agents

Representative HCPCS/J/Q codesJ0177, J0178, J0179, J2777, J2778, J9035, Q5147, Q5124, Q5128

Purpose

Policy revision history

2025-04-01policy_effectiveLatest

Policy IEXD0042.18 became effective; updates included changes to coverage rationale, applicable codes (replaced J3490/J3590 with Q5147 for Pavblu), revised HCPCS descriptions, removal of Maximum Allowed Frequencies list, and archiving of prior version IEXD0042.17.

Policy Summary

PayerUnitedHealthcare

PolicyOphthalmologic Vascular Endothelial Growth Factor (VEGF) Inhibitors

Policy CodePolicy IEXD0042.18

Change TypeNo material change

Effective DateApr 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and document a mapped ICD-10 diagnosis and that intravitreal administrations do not exceed 12 doses per year per eye.

SourceLink

On This Page

CATT and HAWK/HARRIER trial summaries (chunks 213–217)

RVO-related macular edema: BALATON/COMINO (faricimab) and VIBRANT (aflibercept) and other trials demonstrate efficacy of indicated agents for macular edema following RVO; off‑label bevacizumab trials also show meaningful VA and CRT improvements.24 weeks to 18 months follow‑up depending on study

chunks 235–237

median injections 2–8 over 12–28 months in cited series

chunks 247,252–257

Retinopathy of prematurity (ROP)

Bevacizumab vs laser (ROP): Randomized trials (e.g., Mintz‑Hittner et al.) showed reduced recurrence for zone I ROP with intravitreal bevacizumab versus laser and less very high myopia at follow‑up.0.625 mg/0.025 mL dose noted in trials
chunks 259–260
Aflibercept ROP trials: Randomized aflibercept trials (BUTTERFLEYE, FIREFLEYE) did not show superiority or inferiority versus laser for absence of active ROP/unfavorable structural outcomes through study follow‑up.study‑specific endpoints
chunk 261

HCPCS/J/Q codes referenced for prior authorization

Providers must reference and use the HCPCS/J/Q codes in the policy when submitting prior authorization requests and claims. The following HCPCS/J/Q codes are mapped to retina-related indications and are applicable to the diagnosis-to-code tables in this policy: J0177 (aflibercept HD), J0178 (aflibercept), J0179 (brolucizumab-dbll), J2777 (faricimab-svoa), J2778 (ranibizumab), J9035 (bevacizumab), Q5147 (aflibercept-ayyh Pavblu), Q5124 (ranibizumab-nuna Byooviz), Q5128 (ranibizumab-eqrn Cimerli). Use the specific code that corresponds to the drug administered.

List of referenced HCPCS/J/Q codes: J0177, J0178, J0179, J2777, J2778, J9035, Q5147, Q5124, Q5128

Documentation Required

Mapped HCPCS/J/Q codes require corresponding ICD‑10 diagnosis

Mapped HCPCS/J/Q codes require a corresponding ICD‑10 diagnosis code that appears in the Diagnosis-to-HCPCS mapping table. The claim and prior authorization must include one of the ICD‑10 codes listed as “Applies to” the requested HCPCS/J/Q code. A mismatch between the billed HCPCS/J/Q code and the ICD‑10 diagnosis code on the request or claim may result in denial or delay.

Ensure the ICD‑10 diagnosis code is one of the codes listed in the policy mapping for the billed HCPCS/J/Q code
Claims may be denied if the submitted ICD‑10 diagnosis is not among the listed codes that map to the billed HCPCS/J/Q code

Documentation Required

Use listed HCPCS/J/Q codes with the mapped ICD‑10 on requests/claims

When requesting prior authorization or submitting a claim, include the HCPCS/J/Q code for the intravitreal product AND the mapped ICD‑10 diagnosis code from the policy. Indicate laterality (right/left eye) in the diagnosis when applicable. Document the clinical indication and relevant trial-supported measures (for example, OCT-measured central retinal thickness and baseline/follow‑up best-corrected visual acuity) to support medical necessity.

Include HCPCS/J/Q code and the mapped ICD‑10 diagnosis code on the prior authorization and claim
Specify laterality (treated eye) in the ICD‑10 diagnosis when applicable
Provide clinical documentation: diagnosis, baseline and follow-up BCVA, OCT-measured CRT and other indication‑specific data

Billing Rule

Diagnosis-to-HCPCS mapping for prior authorization and claims

Diagnosis-to-HCPCS mapping in this policy links specific retina-related ICD‑10 codes (diabetic retinopathy/DME, RVO-related macular edema, neovascular AMD, ROP, CNV secondary to OHS, etc.) to the HCPCS/J/Q codes above. Providers must verify the diagnosis code on the claim matches one of the codes shown as “Applies to” the requested drug code.

Examples of mapped indications supported by the policy: diabetic macular edema, macular edema secondary to BRVO/CRVO, neovascular AMD, retinopathy of prematurity, choroidal neovascularization secondary to ocular histoplasmosis syndrome (POHS)
Verify the diagnosis code on the claim is among the policy’s listed ICD‑10 codes that map to the HCPCS/J/Q code being billed

Documentation Required

Indication-specific, evidence-backed documentation required

Provide evidence-backed documentation for indication‑specific requests. For RVO and macular edema, supporting documentation should include OCT-measured central retinal thickness, BCVA at baseline and follow‑up visits, response to prior injections, and retreatment rationale per study protocols cited. For ROP and other pediatric indications, document disease zone/stage and relevant trial endpoints.

For RVO/macular edema: OCT CRT values, BCVA measurements, dates and number of prior injections, treatment response criteria used for retreatment
For ROP: IC‑ROP classification, zone/stage, trial-defined outcomes and follow‑up plan

Note

Document clinical rationale and trial‑supported evidence when selecting agent

Comparative trial data (for example, CATT for AMD and trials in DME and RVO) are summarized in the policy and can support use of different agents. Document the clinical rationale when selecting an agent, including comparative efficacy, number of injections required, safety concerns, and cost considerations (e.g., use of compounded bevacizumab). For off‑label use (bevacizumab), include informed consent and compounding pharmacy credentialing and lot information.

CATT and other randomized trials: evidence on visual acuity outcomes and injection frequency differences
Compounded bevacizumab (Avastin): document compounding pharmacy credentials, lot numbers, USP <797> compliance and informed consent regarding off‑label use

Step Therapy

Therapy sequencing and step‑therapy notes

Prior authorization decisions and claims are contingent on both the clinical criteria in the General Requirements and the Diagnosis‑Specific Requirements. There is no prescriptive step‑therapy sequence listed in this excerpt; coverage is determined by meeting those requirements and mapped diagnosis‑to‑HCPCS rules. If clinical rationale supports a different sequencing (e.g., for POHS), document relevant trial or literature support.

No explicit step therapy sequence specified — coverage contingent on meeting General and Diagnosis‑Specific Requirements
For CNV secondary to POHS, document clinical rationale and evidence when selecting monotherapy versus combination therapy

Denial Risk

Coding and denial risk — include mapped diagnosis and laterality

Billing and documentation cautions: a listed HCPCS/J/Q code in this policy does not guarantee coverage. Claims may be denied if the diagnosis-to-HCPCS mapping is absent or does not match. Always include the mapped ICD‑10 diagnosis code (with laterality when applicable) that corresponds to the billed HCPCS/J/Q code on prior authorization requests and claims to reduce denial risk.

Listing of a code is reference only and does not imply coverage
Mismatch between billed HCPCS/J/Q code and ICD‑10 diagnosis listed in the policy may trigger denial or require mapping

Documentation Required

Documentation required for initial and continuation therapy

Required documentation for initial and continuation therapy: initial requests must include the diagnosis and confirmation that intravitreal administrations will not exceed 12 doses per year per eye. Continuation requests must include documentation of prior clinical response (for example, improved or stabilized BCVA and OCT findings) and ongoing plan demonstrating adherence to dosing limits and monitoring.

Initial therapy: documented diagnosis and statement that planned intravitreal administrations ≤ 12 doses/year/eye
Continuation therapy: documentation of positive clinical response to prior anti‑VEGF therapy, interval BCVA and OCT data, treatment plan and monitoring schedule

Documentation Required

Compounded bevacizumab sourcing and informed consent

Compounded bevacizumab (Avastin) — when used for ophthalmic intravitreal injection, document compounding pharmacy credentialing, vial lot numbers, beyond‑use dating, and that the pharmacy follows appropriate aseptic compounding standards (for example, USP <797>) as recommended by OMIC. Include informed consent discussion noting bevacizumab’s off‑label status when used for AMD.

Record compounding pharmacy name, accreditation/licensure, method of compounding, vial lot number and beyond‑use date
Document informed consent discussion that includes off‑label status and risks/benefits

Efficacy evidence by indication — summary:

Key randomized trials by indication: HAWK/HARRIER (brolucizumab vs aflibercept for nAMD), TENAYA/LUCERNE (faricimab vs aflibercept for nAMD), YOSEMITE/RHINE (faricimab vs aflibercept for DME), BALATON/COMINO and VIBRANT for RVO macular edema; off‑label bevacizumab studies provide additional efficacy data.

study‑specific endpoints/timepoints

chunks 216,218,225,235

inv-07: Clinical evidence summary by indication — Summary of coverage-relevant clinical evidence

Clinical evidence summary — RVO and other indications: Prospective and randomized studies demonstrate clinically meaningful VA and CRT improvements with indicated agents in RVO and with bevacizumab in several trials/series; trial endpoints commonly include ETDRS letter gains and CRT reductions measured by OCT.≥15 ETDRS letters is a common primary endpoint in RVO trials

chunks 235–237, 238

Procedure/product codes used to identify intravitreal VEGF and related biosimilar injectable agents for claims and prior authorization.

NoteListing of codes is for reference and does not guarantee coverage or payment; benefit plan rules apply.

E09.x codes — diabetes due to underlying condition (drug/chemical-induced) with retinopathy

Code familyE09.x — Drug- or chemical-induced diabetes mellitus with specified diabetic retinopathy and macular edema subtypes (e.g., E09.3313, E09.3591).

Use in mappingE09.* codes are included in the ICD-10 → HCPCS applicability table and are mapped to listed intravitreal HCPCS/J/Q product codes where marked 'X'.

Laterality variantsE09 codes include laterality designations (right, left, bilateral, unspecified) which must match the billed eye when applicable.

Laterality — ICD-10 codes specify laterality and must match billed site

RequirementICD-10 diagnosis codes in the policy include laterality (right, left, bilateral, unspecified) and the selected diagnosis code must correspond to the treated eye on the claim.

Claiming noteProviders should document and submit the specific ICD-10 code corresponding to the eye treated (e.g., E11.3311 = right eye) to match HCPCS billed.

Mapping consequenceA mismatch between laterality in the ICD-10 code and the billed site/HCPCS may result in denial or mapping errors.

Example ICD-10 codes E11.3311 / E11.3511 — examples of Type 2 diabetes with retinopathy for a particular eye

Example codesE11.3311 — Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema, right eye; E11.3511 — Type 2 diabetes mellitus with proliferative diabetic retinopathy with macular edema, right eye.

ContextThese codes are shown in the policy mapping rows as applying to multiple HCPCS/J/Q product codes when marked 'X'.

Claiming tipUse the exact laterality-specific ICD-10 (e.g., E11.3311/E11.3511) on the claim to correspond to the HCPCS code billed per the mapping table.

E13.37X1–E13.37X9 — Diabetic macular edema resolved following treatment

Code rangeE13.37X1–E13.37X9 — 'diabetic macular edema, resolved following treatment' cluster for other specified diabetes mellitus with laterality variants.

Purpose in policyUsed to indicate prior treated DME status in the ICD-10 → HCPCS applicability table; these lines are mapped to multiple HCPCS/J/Q codes where marked.

Claiming implicationPresence of a resolved-DME code documents prior treated macular edema and should be paired with the billed HCPCS when applicable.

Exudative AMD — AMD with CNV and related subtypes mapped to VEGF therapy codes

DefinitionExudative (neovascular) AMD — AMD with choroidal neovascularization and related subtypes (active CNV, inactive CNV, scar) represented by H35.321x–H35.323x codes.

MappingH35.321x–H35.323x diagnosis codes are mapped to applicable HCPCS/J/Q VEGF inhibitor product codes in the policy table (marked 'X').

EvidenceMultiple randomized trials support use of aflibercept, brolucizumab, ranibizumab (and biosimilars) and faricimab for neovascular AMD.

Retinopathy of prematurity (ROP) — ROP stages and codes mapped to HCPCS/J-codes

ScopeRetinopathy of prematurity (ROP) includes stages 0–5 and retrolental fibroplasia represented by H35.10x–H35.17x and specific stage codes (H35.111–H35.163).

Policy mappingROP diagnosis codes in the H35.10x–H35.17x ranges are mapped to selected HCPCS/J-codes (applicability indicated per table entries).

Clinical noteAnti-VEGF agents (bevacizumab, ranibizumab, aflibercept) have randomized trial support for posterior/zone I or posterior zone II stage 3+ ROP but require extended follow-up due to recurrence and vascularization concerns.

Neovascular AMD — definition used in trials and mapping

Definition used in trialsNeovascular (exudative) AMD: presence of active choroidal neovascularization treated with intravitreal anti-VEGF agents; trials typically enroll treatment-naïve patients with active CNV.

Trial mappingRandomized trials (e.g., HAWK/HARRIER, TENAYA/LUCERNE) used intravitreal VEGF agents and informed product approvals and labeling for nAMD.

Regulatory notePolicy lists indicated agents for nAMD (aflibercept, ranibizumab, brolucizumab, faricimab, biosimilars) and maps H35.* codes to HCPCS products.

Q8W / Q12W / Q16W — dosing interval abbreviations used in trials

AbbreviationQ8W / Q12W / Q16W — dosing interval abbreviations meaning every 8 weeks, every 12 weeks, every 16 weeks as used in trial regimens.

Trial usageHAWK/HARRIER and TENAYA/LUCERNE used fixed or variable Q8W/Q12W/Q16W regimens to evaluate extended-interval dosing strategies with faricimab and brolucizumab.

Documentation tipWhen documenting dosing history for prior authorization, indicate interval (e.g., Q8W) consistent with trial/regimen terminology.

BCVA — best-corrected visual acuity endpoint definition

EndpointBCVA (Best-Corrected Visual Acuity) — primary efficacy endpoint in many trials measured by ETDRS letters to quantify change from baseline.

Use in documentationPrior authorization and continuation requests should include baseline and follow-up BCVA (ETDRS or equivalent) to demonstrate clinical response.

Trial contextNoninferiority and superiority analyses in major trials used mean BCVA change averaged across specified week visits (e.g., weeks 40–48).

Macular edema secondary to RVO — definition and monitoring (OCT CRT)

DefinitionMacular edema secondary to retinal vein occlusion (RVO) — central or branch RVO causing macular thickening and visual impairment monitored by OCT-measured central retinal thickness (CRT) and BCVA.

Monitoring metricOCT-measured CRT (central subfield thickness) is used in trials to guide retreatment and assess anatomic response; trials report CRT reductions in μm.

Trial endpointsClinically meaningful VA gains (e.g., ≥15 ETDRS letters) and CRT reduction are primary outcomes in RVO/BRVO/CRVO studies used to support coverage rationale.

Proliferative diabetic retinopathy (PDR) — definition and clinical context

DefinitionProliferative diabetic retinopathy (PDR) — advanced diabetic retinopathy characterized by retinal neovascularization with risk of vitreous hemorrhage or tractional retinal detachment; treatments include laser, vitrectomy, and adjunctive intravitreal anti-VEGF.

Clinical contextIntravitreal anti-VEGF agents are used as adjuncts preoperatively and as monotherapy in certain PDR contexts; trials demonstrate reduced early postvitrectomy hemorrhage and improved surgical metrics.

DocumentationWhen billing HCPCS for PDR indications, include the mapped ICD-10 PDR code and clinical rationale (e.g., preoperative IVB to reduce hemorrhage).

Type 1 ROP — formal definition repeated for clarity

Restated definitionType I ROP: zone I any stage with plus disease; zone I stage 3 with or without plus disease; or zone II stage 2 or 3 with plus disease — high-risk prethreshold disease used for trial eligibility and treatment decisions.

ImplicationType I designation identifies infants most likely to benefit from intervention and is used in randomized ROP treatment trials and policy mapping.

Follow-up requirementAnti-VEGF therapy for Type I ROP necessitates prolonged vascularization monitoring due to risk of delayed or recurrent disease.

Compounded bevacizumab — definition and USP compliance guidance

DefinitionCompounded bevacizumab — bevacizumab repackaged by compounding pharmacies for intravitreal use (Avastin), requiring USP <797>-compliant aseptic standards and accredited compounding sources.

Documentation requirementsRecord lot numbers in the patient's record and in a log; document compounding pharmacy accreditation, USP <797> compliance, and informed consent addressing off-label use.

Risk mitigationOM I C/AAO guidance recommends credentialing compounding pharmacies, verifying sterility and beyond-use dating, and using proper aseptic technique to reduce infection risk.