Glaucoma

Glaucoma is a chronic condition characterized by the damage to the optic nerve, which if left untreated, can lead to vision loss and ultimately, blindness. Often, but not always, this damage is associated with elevated intraocular pressure (IOP). There are several types of glaucoma, the most common being primary open-angle glaucoma.

Angle-closure glaucoma and congenital glaucoma are typically managed by surgical intervention, while primary open-angle glaucoma is primarily managed pharmacologically. The overarching goal of treatment is to reduce IOP, which is currently the only modifiable risk factor for glaucoma.

IOP reduction can be achieved by decreasing the production of aqueous humor or by increasing the outflow of this fluid from the anterior chamber of the eye.

The American Academy of Ophthalmology recommends considering medication efficacy, side effects, and dosing frequency when selecting a pharmacological treatment, as these factors can significantly influence patient adherence to therapy.

Brimonidine and timolol, which are combined in an ophthalmic solution (Combigan), can reduce IOP in patients with open-angle glaucoma or ocular hypertension. This medication may be indicated when patients require adjunctive or replacement therapy due to inadequate IOP control.

Brimonidine is a selective alpha-agonist and timolol is a beta-blocker, with the hypotensive effect of brimonidine being additive to timolol.

The brimonidine tartrate/timolol maleate ophthalmic solution 0.2%/0.5% (Combigan) is FDA-approved for the treatment of glaucoma or ocular hypertension for topical ophthalmic use.

Definitions

Ocular hypertension refers to a condition where the pressure inside the eye, known as intraocular pressure (IOP), is consistently higher than normal ranges. It's important to note that ocular hypertension does not necessarily imply damage to the optic nerve, but it is a risk factor for developing glaucoma.

Open-angle glaucoma is a form of glaucoma characterized by an anatomically normal angle between the iris and cornea, but a dysfunction in the eye's natural drainage system. This dysfunction leads to the build-up of fluid, increased IOP, and over time, can cause progressive damage to the optic nerve. This condition, also known as primary or chronic glaucoma, typically develops slowly and painlessly and can lead to a gradual loss of vision if not effectively managed.

Medical Necessity Criteria for Initial Authorization

The Plan considers brimonidine/timolol (Combigan) medically necessary when ALL of the following criteria are met:

1. The member is 2 years of age or older; AND
2. The member has a documented diagnosis of open-angle glaucoma or ocular hypertension; AND
3. The member is unable to use, or has tried and failed the individual components (brimonidine and timolol) as separate products taken concomitantly; AND
4. The member is unable to use, or has tried and failed TWO of the following:
   • Apraclonidine Hcl (Iopidine); and/or
   • Betaxolol Hcl; and/or
   • Brinzolamide; and/or
   • Brinzolamide/Brimonidine (Simbrinza); and/or
   • Carteolol Hcl; and/or
   • Dorzolamide Hcl; and/or
   • Dorzolamide Hcl/Timolol maleate (Cosopt); and/or
   • Levobunolol Hcl; and/or
   • Metipranolol;
   AND
5. Chart documentation is provided for review to validate the above-listed requirements.

If the above prior authorization criteria are met, brimonidine/timolol (Combigan) will be approved for 12 months.

Medical Necessity Criteria for Reauthorization

Reauthorization for 12 months will be granted if ALL of the following are met:

1. the member still meets the applicable initial criteria; AND
2. recent chart documentation (within the last 12 months) shows the member has experienced a therapeutic response to the requested medication as evidenced by ONE of the following:
   • clinical improvement in symptoms since starting the requested medication; or
   • disease stability since starting the requested medication; AND
3. the member maintains adherence to the prescribed dosing regimen as evidenced by pharmacy claims record.

Experimental or Investigational / Not Medically Necessary:

brimonidine/timolol (Combigan) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. Alcon. Simbrinza® (brinzolamide and brimonidine tartrate) ophthalmic suspension prescribing information. Fort Worth, TX; 2015 Nov.
2. Allergan. Combigan® (brimonidine tartrate and timolol maleate) ophthalmic solution prescribing information. Irvine, CA; 2019 Jun.
3. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern® Guidelines.Primary Angle Closure. San Francisco, CA: American Academy of Ophthalmology; 2015. Available at: https://www.aao.org/preferred-practicepattern/primary-angle-closure-ppp-2015.
4. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern® Guidelines. Primary Open-Angle Glaucoma.

5. Bausch & Lomb Pharmaceuticals, Inc. Brimonidine tartrate ophthalmic solution 0.2% prescribing information. Bridgewater, NJ; 2018 Nov.
6. Bausch & Lomb. Lumify® (brimonidine tartrate) ophthalmic solution drug facts. Bridgewater, NJ; Undated.
7. Boyd K. What is Glaucoma? American Academy of Ophthalmology. Last Updated Sept 2021. Accessed Sept 2021. Available at: https://www.aao.org/eye-health/diseases/what-is-glaucoma.
8. Boyd K. What is Ocular Hypertension? American Academy of Ophthalmology. Last Updated Mar 2021. Accessed Sept 2021. Available at: https://www.aao.org/eye-health/diseases/what-is-ocular-hypertension.
9. Clinical Pharmacology [database on the Internet]. Tampa (FL): Elsevier Inc.: 2022. Available from: www.clinicalpharmacology.com. Updated periodically. Accessed: May, 2022.
10. DailyMed. Package Inserts. U.S. National Library of Medicine, a National Institutes of Health (NIH) website. Accessed May, 2022. https://dailymed.nlm.nih.gov/dailymed/index.cfm.
11. Gedde SJ, Vinod K, Wright MW, et al. Primary open-angle glaucoma Preferred Practice Pattern guidelines. The American Academy of Ophthalmology. 2020. Available at: http://www.aao.org/guidelinesbrowse.
12. Glaucoma Research Foundation. Open-Angle Glaucoma. Last updated Dec 2019. Accessed Sept 2021. Available at: https://www.glaucoma.org/glaucoma/symptoms-of-primary-open-angle-glaucoma.php
13. Gupta D, Chen PP. Glaucoma. Am Fam Physician. 2016; 93:668-74.
14. Kerr N. Combination Brimonidine and Timolol. Ophthalmology. 2010 January; 117(1): 193.

    Indicates that peripheral skin necrosis is a potential complication of Combigan

15. Lexicomp Online Database [database on the Internet]. Hudson (OH): Lexicomp Inc.: 2022. Available from: http://online.lexi.com. Updated periodically. Accessed: May, 2022.
16. Liebmann JM, Lee JK. Current therapeutic options and treatments in development for the management of primary open-angle glaucoma. Am J Manag Care. 2017; 23(15 Suppl):S279-S292.
17. Micromedex Solutions [database on the Internet]. Greenwood Village, CO: Truven Health Analytics: 2022. Available from: http://micromedex.com/. Updated periodically. Accessed: May, 2022.
18. Prum BE Jr, Rosenberg LF, Gedde SJ et al. Primary open-angle glaucoma preferred practice pattern® guideline [published corrigendum appears in Ophthalmology. 2018; 125: 949]. San Francisco, CA: American Academy of Ophthalmology; 2015. From the American Academy of Ophthalmology website.
19. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311:1901-11.

Clinical Guideline Revision / History Information

Original Date: 10/14/2021
Reviewed/Revised: 12/01/2021, 06/23/2022, 06/29/2023