In 2023, 5 Medicare Administrative Contractors (MACs) proposed local coverage determination (LCD) policies for microinvasive glaucoma surgery (MIGS), but subsequently withdrew them at the beginning of 2024. On May 30, CGS, NGS, Noridian, Palmetto, and WPS each published a new proposed LCD with associated article. Subsequently, public hearings occurred in June to gather a response from interested parties. 

On behalf of the American Academy of Ophthalmology (AAO), American Glaucoma Society (AGS), American Society of Cataract and Refractive Surgery (ASCRS), and the Outpatient Ophthalmic Surgery Society (OOSS), several ophthalmologists submitted thoughtful recommendations for revision of the proposed LCDs. In particular, they commented on the meaning of the term refractory glaucoma. How this term is defined has significant ramifications for patient selection for the Xen gel stent (AbbVie) and, indirectly, for the iStent infinite (Glaukos). Other products in development may also be affected by these LCDs. 

Within the proposed LCD, a straightforward and easily understandable definition is, “glaucoma that is difficult to treat and poorly controlled on maximally tolerated medical therapy or failed surgical therapy regardless of stage of disease.” It comes from the AGS position paper on MIGS.¹ Elsewhere in the proposed LCD, refractory glaucoma is defined as, “prior failure of a filtering/cilioablative procedure or uncontrolled intraocular pressure (IOP) defined as progressive damage or mean diurnal medicated IOP ≥20 mmHg on maximally tolerated medical therapy (ie, ≥4 classes of topical IOP-lowering medications, or fewer in the case of tolerability or efficacy issues).” This longer and more rigorous definition is based on the pivotal trial criteria for the Xen gel stent.

Xen was developed by AqueSys in Europe, where it received CE mark, and was subsequently acquired by Allergan (now AbbVie) in 2015.² Thereafter, Allergan shepherded the product through the US Food and Drug Administration’s 510(k) clearance process that relied on the American National Standards Institute (ANSI) Z80.27 definition of “refractory glaucoma,”³ which is medically uncontrolled glaucoma with one of the following:

• prior failed incisional intraocular surgery (eg, failed trabeculectomy or tube shunt);
• prior failed cilioablative procedure (eg, cyclodestruction);
• neovascular glaucoma; or 
• high risk for surgical failure of a trabeculectomy due to conjunctival scarring, uveitis, or other secondary factors.

Subsequently, “Xen45 was granted FDA clearance for the management of refractory glaucoma, including cases where previous surgical treatment has failed, cases of primary open-angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy.”⁴

Similarly, Glaukos followed the FDA 510(k) clearance process for iStent infinite and relied on the same pivotal trial design as Xen. The FDA approved directions for use of iStent infinite state, “The iStent infinite Trabecular Micro-Bypass System Model iS3 is an implantable device intended to reduce the intraocular pressure (IOP) of the eye. It is indicated for use in adult patients with primary open-angle glaucoma in whom previous medical and surgical treatment has failed.”⁵ Here, “surgical treatment” means “conventional incisional or cilioablative procedures (eg, trabeculectomy, tube implantation, cryotherapy, and cyclodiode therapy.”⁵ It does not mean cataract surgery or selective laser trabeculoplasty, even though both reduce IOP.

In May 2021, the AGS, AAO, and ASCRS wrote to the ANSI Z-80 Committee and the FDA, requesting an update to the definition of refractory glaucoma as follows:

Glaucoma is a progressive optic neuropathy that is characterized by sectoral or generalized morphologic loss of neural tissue at the optic nerve head as well as within the retinal cell layers. Such loss of neural tissue eventually causes loss of sensitivity in the visual field. Glaucoma progression can be reduced by lowering the intraocular pressure, which is the only known modifiable risk factor for glaucoma. Due to multiple factors, the effectiveness of glaucoma control by the addition of sequential medications is reduced as the number of medications is increased. Given these factors, glaucoma is “refractory” when the intraocular pressure remains above target values selected to slow or halt the disease, despite the use of multiple classes of medications, or fewer medications when tolerability or effectiveness limits the use of other drug classes.⁶

During the MACs’ public hearings, it was suggested that the proposed LCD incorporate this updated version. At this time, the ANSI website still contains the earlier 2019 version of ANSI Z80.27. 

Although a new Medicare LCD and article might be finalized sometime in the third quarter of 2024, physicians can improve their chart documentation immediately to better support an assessment of refractory glaucoma, particularly if recommending a Xen gel stent or iStent infinite. Key points include:

• Target IOP^7,8,9
• Poorly controlled IOP on current therapy
• Maximally tolerated medical therapy
• Identify the classes of current antiglaucoma medications and those contraindicated
• Progression of glaucoma based on visual field and OCT of the optic nerve 
• History (if any) of conventional incisional or cilioablative procedures 
• Type of glaucoma, especially those that do not respond to trabeculectomy¹⁰
• High risk for surgical failure of trabeculectomy¹¹

Each of these points is a relevant consideration, although the weighting will vary for individual patients.  GP

Kevin J. Corcoran, COE, CPC, CPMA, FNAO is a principal of Corcoran & Corcoran in Las Vegas, Nevada.

References

1. Fellman RL, Mattox C, Singh K, et al. American Glaucoma Society position paper: microinvasive glaucoma surgery. Ophthalmol Glaucoma. 2020;3(1):1-6. doi:10.1016/j.ogla.2019.12.003

2. Allergan to acquire glaucoma treatment company AqueSys to add minimally invasive implantable shunt to eye care offering. Press release. September 15, 2015. Accessed July 16, 2024. https://www.prnewswire.com/news-releases/allergan-to-acquire-glaucoma-treatment-company-aquesys-to-add-minimally-invasive-implantable-shunt-to-eye-care-offering-300137935.html

3. American National Standards Institute. Accessed July 16, 2024. https://www.ansi.org

4. Centers for Medicare & Medicaid Services. Micro-invasive glaucoma surgery (MIGS) proposed LCD. May 30, 2024. Accessed July 16, 2024. https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39826 

5. Sarkisian SR Jr, Grover DS, Gallardo MJ, et al. Effectiveness and safety of iStent infinite trabecular micro-bypass for uncontrolled glaucoma. J Glaucoma. 2023;32(1):9-18. doi:10.1097/IJG.0000000000002141

6. American Glaucoma Society, American Society of Cataract and Refractive Surgeons, and American Glaucoma Society. Re: Redefining refractive glaucoma. May 7, 2021. Accessed July 25, 2024. https://higherlogicdownload.s3.amazonaws.com/AMERICANGLAUCOMASOCIETY/9f15f56c-64ed-4e90-ab3e-9bc3fb0c245e/UploadedImages/AGS_ASCRS_AAO_Refractory_Glaucoma_Letter_5721.pdf

7. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429-440. doi:10.1016/s0002-9394(00)00538-9

8. Fechtner RD. Target IOP for advanced glaucoma. Glaucoma Today. January/February 2004. Accessed July 16, 2024. https://glaucomatoday.com/articles/2004-jan-feb/0104new_name_052.html

9. Griffin JS. Trabeculectomy-induced hypotony: when and how to intervene. EyeNet Magazine. September 25, 2018. Accessed July 16, 2024. https://www.aao.org/eyenet/article/trabeculectomy-induced-hypotony

10. Abdelrahman AM. Refractory glaucomas: types and management. JORS. 2017;1(1):1-14. doi:10.21608/JORS.2017.3597 

11. Kitazawa Y, Yamamoto T, Sawada A, Hagiwara Y. Surgery for refractory glaucoma. ANZ J Ophthalmol. 1996;24(4):327-332. doi:https://doi.org/10.1111/j.1442-9071.1996.tb01603.x