YUTIQ, Fluocinolone Acetonide (Ophth) OZURDEX, Dexamethasone (Ophth) RETISERT, Fluocinolone Acetonide (Ophth) ILUVIEN, Fluocinolone Acetonide (Ophth) Form

The following are corticosteroids for ophthalmic injection requiring prior authorization: dexamethasone intravitreal implant (Ozurdex®), dexamethasone ophthalmic insert (Dextenza®), fluocinolone acetonide intravitreal implant (Iluvien®, Retisert®, Yutiq™), and triamcinolone acetonide suprachoroidal injection (Xipere™). FDA Approved Indication(s) Dextenza is indicated for the treatment of: • Ocular inflammation and pain following ophthalmic surgery • Ocular itching associated with allergic conjunctivitis Iluvien is indicated for the treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. Ozurdex is indicated for the treatment of: • Macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) • Non-infectious uveitis affecting the posterior segment of the eye • Diabetic macular edema (DME) Retisert and Yutiq are indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. Xipere is indicated for the treatment of macular edema associated with uveitis. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that corticosteroids for ophthalmic injection are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Ocular Inflammation and Pain Following Ophthalmic Surgery (must meet all):

1. Diagnosis of ocular inflammation and pain following ophthalmic surgery; Page 1 of 12

   CLINICAL POLICY Corticosteroids for Ophthalmic Injection

2. Request is for Dextenza;
   3. Prescribed by or in consultation with an ophthalmologist;
   4. Age ≥ 18 years;
   5. Member has received or is scheduled to receive ophthalmic surgery within 30 days of this request;
3. Failure of a topical corticosteroid (see Appendix B), unless contraindicated, clinically significant adverse effects are experienced, or member is unable to manage regular eye drop use (e.g., due to age or comorbidities including visual impairment);
4. Dose does not exceed 0.4 mg (1 insert) per eye every 30 days. Approval duration: 1 month (one insert per eye)
   B. Ocular Itching Associated with Allergic Conjunctivitis (must meet all):
   
   1. Diagnosis of ocular itching associated with allergic conjunctivitis;
   2. Request is for Dextenza;
   3. Prescribed by or in consultation with an ophthalmologist;
   4. Age ≥ 18 years;
   5. Failure of both of the following (a and b), unless contraindicated or clinically significant adverse effects are experienced (see Appendix B): a. Topical mast cell stabilizer and topical antihistamine (as a single dual-acting product or as two products used in combination); b. Topical corticosteroid;
5. Dose does not exceed 0.4 mg (1 insert) per eye every 30 days. Approval duration: 1 month (one insert per eye) C. Macular Edema following BRVO or CRVO (must meet all):
   
   1. Diagnosis of macular edema following BRVO or CRVO;
   2. Request is for Ozurdex;
   3. Prescribed by or in consultation with an ophthalmologist;
   4. Age ≥ 18 years;
   5. Failure of both of the following (a and b), unless contraindicated or clinically significant adverse effects are experienced (see Appendix B): a. Intravitreal corticosteroid injections, if available; b. Intravitreal anti-vascular endothelial growth factor (VEGF) agents;
6. Dose does not exceed 1 implant per eye. Approval duration: 3 months (one implant per eye)
   D. Non-Infectious Uveitis (must meet all):
7. Diagnosis of non-infectious uveitis affecting the posterior segment of the eye;
   2. Request is for Ozurdex, Retisert, or Yutiq;
   3. Prescribed by or in consultation with an ophthalmologist;
   4. Member meets one of the following (a or b): a. For Ozurdex, Yutiq: Age ≥ 18 years;
      b. For Retisert: Age ≥ 12 years;

8. Failure of intravitreal corticosteroid injections, if available, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B); Page 2 of 12

   CLINICAL POLICY Corticosteroids for Ophthalmic Injection

9. Failure of one of the following (a or b), unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B): a. Systemic corticosteroid; b. Non-biologic immunosuppressive therapy;
10. Dose does not exceed 1 implant per eye. Approval duration: 3 months (one implant per eye)
    E. Diabetic Macular Edema (must meet all):
11. Diagnosis of DME;
    2. Request is for Ozurdex or Iluvien;
    3. Prescribed by or in consultation with an ophthalmologist;
    4. Age ≥ 18 years;
    5. Failure of both of the following (a and b), unless contraindicated or clinically significant adverse effects are experienced (see Appendix B): a. Intravitreal corticosteroid injections, if available; b. Intravitreal anti-VEGF agents;
    6. Dose does not exceed 1 implant per eye. Approval duration: 3 months (one implant per eye)
       F. Macular Edema with Uveitis (must meet all):
12. Diagnosis of macular edema associated with non-infectious uveitis;
    2. Request is for Xipere;
    3. Prescribed by or in consultation with an ophthalmologist;
    4. Age ≥ 18 years;
    5. Inadequate response to Triesence® intravitreal injection, if available, unless contraindicated or clinically significant adverse effects are experienced;
13. Dose does not exceed 4 mg (1 vial) per eye every 12 weeks. Approval duration: 6 months (two injections per eye)
    G. Other diagnoses/indications (must meet 1 or 2):
14. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

15. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line Page 3 of 12

    CLINICAL POLICY Corticosteroids for Ophthalmic Injection of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. All Indications in Section I (must meet all):

16. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy;
    3. If request is for Dextenza, one of the following (a or b): a. Both of the following (i and ii): i. Request is for an ophthalmic surgery unrelated to the previous request; ii. Member has received or is scheduled to receive the new surgery within 30 days of this request; b. Member continues to experience ocular inflammation and pain/itching related to their ophthalmic surgery/allergic conjunctivitis as evidenced by findings on magnified examination;
17. Member meets one of the following (a, b, c, d, e, or f): a. At least 1 month has passed since last treatment with Dextenza; b. At least 3 months have passed since last treatment with Ozurdex; c. At least 12 months have passed since last treatment with Iluvien; d. At least 30 months have passed since last treatment with Retisert; e. At least 36 months have passed since last treatment with Yutiq; f. At least 12 weeks have passed since last treatment with Xipere;
18. Dose does not exceed (a, b, or c): a. Dextenza: 0.4 mg (1 insert) per eye; b. Ozurdex, Iluvien, Retisert, Yutiq: 1 implant per eye; c. Xipere: 4 mg (1 vial) per eye. Approval duration:
    Ozurdex, Iluvien, Retisert, Yutiq, Xipere – 3 months (one implant or injection per eye)
    Dextenza – 1 month (one insert per eye) B. Other diagnoses/indications (must meet 1 or 2):

19. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: Page 4 of 12

    CLINICAL POLICY Corticosteroids for Ophthalmic Injection CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

20. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BRVO: branch retinal vein occlusion CRVO: central retinal vein occlusion
    DME: diabetic macular edema FDA: Food and Drug Administration VEGF: vascular endothelial growth factor
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen anti-VEGF agents (e.g., bevacizumab, Lucentis®, Eylea®) systemic corticosteroids (e.g., prednisone) azathioprine (Azasan®, Imuran®)
    chlorambucil (Leukeran®) cyclophosphamide (Cytoxan®) cyclosporine (Sandimmune®, Neoral®) methotrexate (Rheumatrex®) mycophenolate mofetil (Cellcept®) Macular Edema Refer to prescribing information Uveitis prednisone 5 – 60 mg/day PO in 1 – 4 divided doses Uveitis 1.5 – 2 mg/kg/day PO Uveitis 0.2 mg/kg PO QD, then taper to 0.1 mg/kg PO QD or less Uveitis 1 – 2 mg/kg/day PO Uveitis 2.5 – 5 mg/kg/day PO in divided doses Uveitis 7.5 – 20 mg/week PO Uveitis 500 – 1,000 mg PO BID Page 5 of 12 Dose Limit/ Maximum Dose Refer to prescribing information Varies 2.5 mg/kg/day 0.2 mg/kg/day N/A 5 mg/kg/day 30 mg/week 3 g/day

    CLINICAL POLICY Corticosteroids for Ophthalmic Injection Drug Name Dosing Regimen tacrolimus (Prograf®) intravitreal corticosteroids: Triesence (triamcinolone) artificial tears topical dual-acting mast cell stabilizer/antihistamine (e.g., azelastine, bepotastine, epinastine, ketotifen, olopatadine) topical mast cell stabilizer (e.g., cromolyn, lodoxamide, nedocromil) topical antihistamine (e.g., alcaftadine, emedastine) topical corticosteroids (e.g., loteprednol, dexamethasone) Uveitis 0.1 – 0.15 mg/kg/day PO in 2 divided doses given for 12 weeks DME, Macular Edema, Uveitis
    4 mg injected intravitreally per affected eye Allergic Conjunctivitis 1 to 2 drops in affected eye(s) BID or QID Allergic Conjunctivitis 1 to 2 drops in affected eye(s) per day Allergic Conjunctivitis 2 to 6 drops in affected eye(s) per day Allergic Conjunctivitis 1 to 4 drops in affected eye(s) per day Allergic Conjunctivitis
    Loteprednol: 1 to 2 drops in affected eye(s) QID Ocular Pain and Inflammation
    Dexamethasone: 1 to 2 drops in affected eye(s) up to every hour for severe disease Dose Limit/ Maximum Dose N/A 4 mg/eye Various Various Various Various Various Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications / Boxed Warnings • Contraindication(s):
    o Dextenza: active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye, and dacryocystitis o Iluvien, Ozurdex, Retisert, Yutiq: patients with active or suspected viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in active bacterial, mycobacterial or fungal infections of the eye. o Xipere: ocular or periocular infections. o Iluvien, Ozurdex: patients with glaucoma with cup to disc rations of greater than 0.8 o Ozurdex: patients with posterior lens capsules that is torn or ruptured because of the risk of migration into the anterior chamber. Page 6 of 12

    CLINICAL POLICY Corticosteroids for Ophthalmic Injection o Iluvien, Ozurdex, Yutiq, Xipere: hypersensitivity. • Boxed warning(s): none reported Appendix D: General Information • Based on clinical trials with Retisert: o Within 3 years post-implantation, approximately 77% of patients will require intraocular pressure (IOP) lowering medications to control intraocular pressure and 37% of patients will require filtering procedures to control intraocular pressure. o Following implantation of Retisert, nearly all patients will experience an immediate and temporary decrease in visual acuity in the implanted eye which lasts for approximately one to four weeks post-operatively. • o During the 3-year post-implantation period, nearly all phakic eyes are expected to develop cataracts and require cataract surgery. In one study, intravitreal bevacizumab (1.25 mg) and the dexamethasone (DEX) (0.7 mg) implant were compared in a randomized, Phase II trial called the BEVORDEX study. 79 Forty-two eyes received intravitreal bevacizumab every 4 weeks, and 46 eyes received an intravitreal DEX (0.7 mg) implant every 16 weeks, with a when necessary (PRN) regimen for 12 months. The primary outcome of the study was to gain ten or more letters in the best-corrected distance visual acuity (BCVA) at 12 months, which was achieved in 40% of the bevacizumab-treated eyes and 41% of the DEX implant-treated group (P = 0.99). The mean corneal refractive therapy (CRT) decrease was statistically significant between the groups, and the reduction was 122 µm in the bevacizumab group and 187 µm in the DEX implant group (P=0.015). The mean number of injections over 1 year was 8.6 for the bevacizumab group and 2.7 for the DEX implant group. Finally, in the DEX implant-treated eyes, 11% lost ten or more letters of the BCVA, which was due to cataracts in 4 of 5 cases; none lost ten letters in the bevacizumab-treated eyes. • The Chart Review of Ozurdex in Macular Edema (CHROME) study evaluated the real- world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in 120 eyes with macular edema (ME). The mean number of DEX implant injections was 1.7 ± 0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3-4.9 months). • According to Pommier et al., an average of 2.6 injections of Ozurdex were needed to obtain a 58.6% of patients who gained more than 15 letters, and 51.1% of patients showed macular edema resolution. • The POINT trial by Thorne et al. found no significant difference between intravitreal triamcinolone acetonide injection and intravitreal dexamethasone implant in terms of safety and efficacy for the treatment of uveitic macular edema. V. Dosage and Administration
    Drug Name Dexamethasone (Dextenza)
    Indication Ocular inflammation and pain after surgery, ocular itching associated Dosing Regimen Insert into the lower lacrimal punctum and into the canaliculus. A single insert releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion Maximum Dose 1 insert per eye per 30 days Page 7 of 12

    CLINICAL POLICY Corticosteroids for Ophthalmic Injection Drug Name Dexamethasone (Ozurdex) Indication with allergic conjunctivitis
    Macular edema, uveitis Fluocinolone (Iluvien) Diabetic macular edema Fluocinolone (Retisert) Fluocinolone (Yutiq) Triamcinolone (Xipere) Uveitis Uveitis Macular edema associated with uveitis Dosing Regimen Maximum Dose Inject the implant containing 0.7 mg dexamethasone intravitreally Inject the implant containing 0.19 mg fluocinolone intravitreally Inject the implant containing 0.59 mg fluocinolone intravitreally
    Inject the implant containing 0.18 mg fluocinolone intravitreally 4 mg (0.1 mL) administered as a suprachoroidal injection One implant injection per eye every 4 months One implant injection per eye every 12 months One implant injection per eye every 30 months One implant injection per eye every 36 months One injection per eye every 12 weeks VI. Product Availability
    Drug Name Availability Dexamethasone (Dextenza) Ophthalmic intracanalicular insert: 0.4 mg Dexamethasone (Ozurdex) Biodegradable intravitreal implant: 0.7 mg Fluocinolone (Iluvien) Fluocinolone (Retisert) Fluocinolone (Yutiq) Triamcinolone (Xipere) Non-biodegradable intravitreal implant: 0.19 mg
    Non-biodegradable intravitreal implant: 0.59 mg Non-biodegradable intravitreal implant: 0.18 mg Injectable suspension in a single-dose vial: 40 mg/mL VII.