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Current Therapeutic Options and Treatments in Development for the Management of Primary Open-Angle Glaucoma
Jeffrey M. Liebmann, MD, FACS, and Jeannie K. Lee, PharmD, FASHP

Current Therapeutic Options and Treatments in Development for the Management of Primary Open-Angle Glaucoma

Jeffrey M. Liebmann, MD, FACS, and Jeannie K. Lee, PharmD, FASHP
Primary open angle glaucoma (POAG) is the most common type of glaucoma, and is responsible for approximately 90% of glaucoma cases in North America. POAG is characterized by an asymptomatic onset, where patients do not present with symptoms until significant visual loss occurs in late stages of the disease. Importantly, while glaucoma is associated with several risk factors that contribute to damage and disease progression, intraocular pressure (IOP) is the only proven modifiable risk factor at this time. Treatments for POAG include use of pharmacologic and surgical interventions. As of this writing, available pharmacologic options reduce IOP through reduction of aqueous humor production or by facilitating aqueous humor drainage through the uveoscleral outflow pathway (the unconventional pathway). Although cholinergic agonists (eg, pilocarpine) indirectly targets aqueous humor draining through the trabecular meshwork/Schlemm’s canal (the conventional outflow pathway), cholinergic agonists are not frequently used, and as of this writing, no agents are currently available that target both the conventional and unconventional outflow pathways. Therapies in late-stage development include trabodenoson, netardsudil, and latanoprostene bunod.

Am J Manag Care. 2017;23:-S0

Glaucoma: Definition and Associated Risk Factors

Glaucoma comprises a heterogeneous group of chronic, progressive, optic neuropathies characterized by loss of retinal ganglion cells and their axons. Glaucoma results in visual impairment and is the second leading cause of irreversible blindness worldwide.1,2 Primary open-angle glaucoma (POAG) is the most common type of glaucoma, and is estimated to account for approximately 90% of cases of glaucoma in North America.3,4 Because symptoms of POAG do not manifest until the disease process is already in advanced stages, and because the progression of disease occurs gradually over the course of many years, POAG is sometimes referred to as the “silent thief of sight.”5

Current management guidelines from the American Academy of Ophthalmology Preferred Practice Pattern cite several important risk factors for POAG, including advanced age, African American and Latino/Hispanic ethnicity, elevated intraocular pressure (IOP), family history of glaucoma, low ocular perfusion pressure (OPP), type 2 diabetes, myopia, and having a thinner central cornea.2
OPP is defined as the difference between arterial blood pressure and the IOP. Although further investigation is needed, it is thought that low OPP alters blood flow at the optic nerve head, contributing to glaucomatous damage to the optic nerve.2 Importantly, while glaucoma is associated with several risk factors that contribute to damage and disease progression, IOP is the only proven modifiable risk factor at this time.3

Burden of Glaucoma

Disease Burden
Globally, glaucoma affects 3.5% of adults 40 to 80 years of age (POAG 3.1% plus angle closure glaucoma [ACG] 0.5%).4 With the average age increasing worldwide, the incidence of glaucoma in this population of adults is projected to increase by 74% from 2013 to 2040.4 With this increase in prevalence of glaucoma, the consequences of glaucoma in terms of vision loss are also expected to grow. Worldwide, the number of people experiencing bilateral blindness from primary glaucoma is expected to reach 11.1 million by 2020.6

The increasing burden of glaucoma has important implications for the United States health care system. The CDC estimates that in 2015, 2.2 million Americans 40 years and older (about 2% of the population) had glaucoma.7 Another estimate suggests that by 2050, the number of people in the United States with POAG aged 40 years and older is expected to increase to 7.32 million individuals, a nearly 3-fold increase from the incidence of POAG from 2011.8

The prevalence of POAG is highest among individuals of Latino/Hispanic and African heritage.8 In a 2016 meta-analysis by Kapetanakis et al, researchers estimated the prevalence of POAG among those aged 65 years to be 6.4% and 4.0% in patients of African descent and Latino patients, respectively, versus a prevalence of 2.0% among those of European descent.9 Moreover, in an adjusted analysis, the risk of developing POAG increases by a factor of 2.3 with each advancing decade among Hispanic patients versus a factor of 1.6 among patients of African descent, and a factor of 2.0 among those of European descent.9 The Hispanic/Latino population is estimated to contribute to the greatest number of individuals with POAG in the United States over the next 4 decades.8
POAG is characterized by an asymptomatic onset, where patients do not present with symptoms until significant visual loss occurs in late stages of the disease. As patients do not have symptoms until visual damage has already occurred, many cases remain undiagnosed and untreated.2 The National Health and Nutrition Examination Survey published in 2014 found approximately 2.4 million individuals in the United States (2.9% of the US population) had undiagnosed and untreated glaucoma, suggesting that 78% of glaucoma was untreated and undiagnosed.10 The rate of undiagnosed and untreated glaucoma is estimated to be 85% for blacks, 81% for Hispanics, and 73% for non-Hispanic whites.10

Economic Burden
As a chronic and progressive disease, glaucoma poses a substantial burden to the healthcare system. Management of glaucoma has direct medical costs (eg, visits to providers, tests, medications, and surgery), direct nonmedical costs (eg, home healthcare, and transportation), and indirect costs (eg, loss of productivity for both patient and caregiver).2

According to a Prevent Blindness study, the $6 billion spent annually in 2014 on the direct costs of glaucoma care is expected to reach $12 billion by 2032, and exceed $17 billion by 2050.11,12
Medicare beneficiaries with glaucoma had higher mean annual total healthcare costs compared with those without glaucoma, and more severe cases of glaucoma in Medicare beneficiaries are associated with higher direct annual costs. One study found that the mean annual total cost of healthcare per patient was $16,760 among Medicare beneficiaries aged 65 years and older with glaucoma versus $13,094 for Medicare beneficiaries without glaucoma. The cost increased by severity of disease. Those with visual disability had costs of $18,073, while those without visual disability had costs of $15,829. In this population, the primary drivers of cost were physician services, inpatient care, and prescription medications.13



 
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