Update on Medications and Surgical Techniques for Glaucoma Management

Educational Objectives

The goal of this program is to improve the diagnosis and management of glaucoma. After hearing and assimilating this program, the clinician will be better able to:

1. Integrate novel drug therapies and microinvasive glaucoma surgery into clinical practice.
2. Select appropriate treatments for patients with primary angle-closure disease.

Summary

Latanoprostene bunod (LBN; Vyzulta): consists of latanoprost (increases uveoscleral outflow) and a nitric oxide-donating component (relaxes the trabecular meshwork [TM]), allowing for a dual mechanism of action; reduced intraocular pressure (IOP) by 30% to 33% from mean baseline IOP of ≥27 mm Hg in phase 3 trials; VOYAGER study — compared with latanoprost, LBN provided an additional 1 mm Hg reduction; side effects of both drugs are similar; pH of LBN is slightly lower vs latanoprost (ie, more stinging)

Netarsudil (Rhopressa): ρ-kinase inhibitor with multiple mechanisms of action, eg, relaxes the TM, reduces episcleral venous pressure, and reduces aqueous production; in phase 3 trials, netarsudil yielded IOP reduction of 15% to 22%; in the ROCKET-4 study, netarsudil was effective across various IOP ranges; conjunctival hyperemia is the most common side effect (≈50% of patients); pain at instillation site and pinpoint subconjunctival hemorrhages are other common side effects; corneal verticillata occurs in 25% of patients, does not impair vision, and often resolves after discontinuing the drug

Latanoprost (Xelpros, Xelatan): latanoprost preserved with potassium sorbate; in phase 3 studies, efficacy was slightly lower (22%-25%) with Xelpros vs Xalatan; eye pain was reported in 67% of patients on Xelpros and 47% of patients on Xalatan; Xelpros does not require refrigeration

Netarsudil/latanoprost (Rocklatan): IOP reduction is 31% to 37% from a mean baseline of 22 to 25 mm Hg; compared with latanoprost, netarsudil/latanoprost yields an additional reduction of 1.3 to 2.5 mm Hg and a higher proportion of patients achieve IOP <15 mm Hg; conjunctival hyperemia is the most common side effect

Applications of new glaucoma drugs: all drugs are dosed once daily (improves compliance) and may be used as first-line or adjunct therapy; LBN — efficacious and well-tolerated as first-line therapy, particularly in younger patients; when added to existing drug regimen, LBN reduces IOP by 13% to 30%; when substituted for prostaglandin analog, LBN reduces IOP by 9%; netarsudil — useful as an adjunct therapy and is effective during day and night; can achieve lower IOP via multiple mechanisms of action; efficacious regardless of the number of medications a patient is using; some patients achieve single-digit IOPs with netarsudil; similar to brimonidine, netarsudil can cause follicular conjunctivitis and eyelid dermatitis; reticular corneal edema is a rare side effect that resolves upon discontinuation; cost — Xelpros is not covered by insurance and uses a direct pay model; availability formularies is improving, with fewer prior authorization requests and denials

Primary angle-closure disease (PACD): consists of 3 categories; PAC suspect (PACS) — includes >180° of iridotrabecular contact (ITC) and no visible posterior TM on gonioscopy; has normal IOP, normal optic nerve, and no peripheral anterior synechiae (PAS); PAC — has >180° of ITC with elevated IOP or PAS; PAC glaucoma (PACG) — occurs when optic nerve damage is present; diagnosis — gonioscopy is the gold standard for diagnosing PACD; swept-source optical coherence tomography (SS-OCT) produces repeatable 360° scans of anterior chamber structures; ultrasound biomicroscopy is useful for visualizing plateau iris or lesions behind the iris; speaker’s study found that SS-OCT is useful in differentiating control eyes from those with PACD; SS-OCT has 90% sensitivity and 85% specificity with a cutoff anterior chamber depth (ACD) of 2.2 mm; ACD <2.2 mm indicates high likelihood of PACD; it is more difficult to separate patients with PACS from those with PAC and PACG

Management of PACD: for cataracts, cataract surgery (CS) is performed (alone or with goniosynechialysis [GSL]); recent trials show no difference in outcomes between CS alone vs CS with GSL; ZAP study — followed 900 patients with PACS without cataracts; primary outcome was elevated IOP, PAS formation, or acute angle closure; found a very low incidence at 5 yr; concluded that prophylactic laser iridotomy is not recommended in all patients with PACS (instead, may be observed); excluded patients with a positive provocation test; consider iridotomy or early CS if the fellow eye has acute angle closure, the patient has difficulty adhering to follow-up visits, or provocation test is positive; EAGLE study — followed 400 patients with PAC or PACG; inclusion criteria consisted of PAC with IOP >30 mm Hg or PACG; clear-lens extraction showed greater efficacy and was more cost-effective than laser iridotomy

Microinvasive glaucoma surgery (MIGS) devices: Glaukos recently introduced iStent Inject W, which has a wider flange, allowing for more predictable implantation; Hydrus Microstent has a dual mechanism of action, ie, aqueous bypass through TM and scaffolding of Schlemm canal; HORIZON study — evaluated Microstent plus CS vs CS alone in patients with mild to moderate glaucoma; at 4 yr, the combined procedure group had a greater proportion of patients that remained free of medication; patients with the Microstent had a 3-fold reduction in risk for future incisional glaucoma surgery; concerns — CyPass was recalled because of long-term endothelial cell loss; iStent and Hydrus have demonstrated comparable endothelial cell loss vs CS alone; Microstent reduces the rate of postoperative IOP spikes from 15% to 1.4%

OMNI Surgical System: performs viscocanaloplasty and trabeculotomy; study — divided patients with mild to moderate open-angle glaucoma into groups with IOP >18 or <18 mm Hg; at 1 yr, greater reduction occurred in baseline IOP >18 mm Hg; both groups showed significant reduction in medication use; clinically significant hyphema occurred in <5% of patients; rate of IOP spike >10 mm Hg was 6%; no difference in IOP reduction between 180° and 360° treatment

XEN Gel Stent: placed transclerally to create a filtering bleb; ab externo open conjunctiva technique improves placement of device and reduces risk for device failure, fibrosis, and device erosion; open conjunctiva technique has the highest rate of success and lowest rate of failure compared with other techniques

Preserflo MicroShunt: compared with trabeculectomy, this device showed an average IOP reduction to 14 mm Hg on 0.6 medications at 1 yr; has a significantly lower rate of hypotony and bleb leak compared with trabeculectomy; loss of endothelial cell is similar between both procedures; efficacious in patients who had failed incisional glaucoma surgeries; can be implanted inferiorly, which is ideal for patients who have scarring in the superior conjunctiva

Readings

Ahmed IIK, Rhee DJ, Jones J, et al. Three-year findings of the HORIZON Trial: a Schlemm canal microstent for pressure reduction in primary open-angle glaucoma and cataract. Ophthalmology. 2021 Jun;128(6):857-865; Dasso L, Al-Khaled T, Sonty S, et al. Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date. Clin Ophthalmol. 2018;12:1939-1944; He M, Jiang Y, Huang S, et al. Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. Lancet. 2019 Apr;393(10181):1609-1618; Hughes T, Traynor M. Clinical results of ab interno canaloplasty in patients with open-angle glaucoma. Clin Ophthalmol. 2020;14:3641-3650; Ma P, Wu Y, Oatts J, et al. Evaluation of the diagnostic performance of swept-source anterior segment optical coherence tomography in primary angle closure disease [published online ahead of print, 2021 Jul 17]. Am J Ophthalmol. 2021 Jul;S0002-9394(21)00362-7; Mehran NA, Sinha S, Razeghinejad R. New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost. Eye (Lond). 2020 Jan;34(1):72-88; Panarelli JF, Yan DB, Francis B, et al. XEN gel stent open conjunctiva technique: a practical approach paper. Adv Ther. 2020 May;37(5):2538-2549.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Han, Dr. Hsia, and Dr. Radhakrishnan spoke at the University of California, San Francisco School of Medicine Virtual Ophthalmology Update 2020, sponsored by the University of California, San Francisco, School of Medicine, and held December 5, 2020. For information about upcoming CME conferences from this presenter, please visit meded.ucsf.edu/cme/upcoming-ce-courses. Audio Digest thanks the speakers and meeting presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP592202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.