Beyond intraocular pressure: Optimizing patient-reported outcomes in glaucoma
Introduction
Glaucoma refers to a related, but somewhat heterogenous, group of optic neuropathies that differ in their causes, risk factors, demographics, symptoms, treatment and diagnosis. The progressive degeneration of retinal ganglion cells in glaucoma results in thinning of the neuroretinal rim and optic disc cupping, a defining characteristic of glaucomatous damage associated with visual field (VF) loss and loss of contrast sensitivity (Fig. 1a and b) (Weinreb and Khaw, 2004). From pathophysiological and treatment standpoints, intraocular pressure (IOP) remains the disease's primary modifiable risk factor, since glaucoma progression can slow significantly if IOP is lowered by 20–50% of its baseline value (Sihota et al., 2018; Wormald, 2003).
Glaucoma can be classified into two broad categories, namely primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on the morphology of the anterior chamber angle, located between the peripheral cornea and iris; and containing the Schlemm's canal through which the aqueous humour leaves the eye. As the name implies, the anterior chamber angle is wide open in POAG, and the rise in IOP, if present at all, is a gradual and painless process (Kwon et al., 2009). In contrast, the anterior chamber angle in PACG is either narrowed or completely closed, leading to either asymptomatic chronic PACG, or a rapid increase in IOP with associated notable symptoms, including headaches, eye pain, nausea and blurred vision, termed acute primary angle closure (Nongpiur et al., 2011). Glaucoma can also occur secondary to trauma, medications (e.g. corticosteroids), inflammation (e.g. uveitis), tumours, or other conditions (e.g. pigment dispersion syndrome, exfoliation syndrome).
Glaucoma is the most common cause of irreversible blindness globally, and is set to increase due to a rapidly aging global population (Bourne et al., 2013, 2016, 2018; Stevens et al., 2013; Tham et al., 2014). In 2014, our group synthesized data from 50 population-based studies worldwide to estimate the prevalence of primary glaucoma (open angle and angle-closure) cases (Tham et al., 2014). Using these data, we estimated that approximately 64.3 millions of 2.33 billion individuals (3.5%) aged 40–80 years had glaucoma globally, with POAG cases being approximately six times more common than PACG (3.1% versus 0.5%) (Tham et al., 2014). Those of African ancestry had the highest prevalence of primary glaucoma (6.1%) and POAG (4.2%), whilst PACG prevalence was highest in East Asians (1.1%) (Tham et al., 2014). Importantly, using age and region-adjusted Bayesian models, we projected a 74.0% increase (111.8 million) by the year 2040 (Tham et al., 2014).
Increasing age is a strong predisposing risk factor for glaucoma, with the prevalence of the disease in black and Hispanic populations increasing from approximately 0.5% and 1%, respectively, in individuals between 40 and 49 years of age, to 11–22% in those aged 80 years and older (Leske et al., 1994; Tielsch et al., 1991; Varma et al., 2004; Wormald et al., 1994). Race is another known risk factor: blacks and Hispanics have increased prevalence of POAG, while PACG is proportionately more prevalent in those of Inuit, Chinese, Asian Indian or South-East Asian origin, compared to Caucasians (Arkell et al., 1987; Quigley and Broman, 2006; Tham et al., 2014; Tielsch et al., 1991; Varma et al., 2004; Wormald et al., 1994). A history of glaucoma in a first-degree relative, e.g. parents and siblings, is also associated with a higher risk (Kong et al., 2011; Tielsch et al., 1994; Wolfs et al., 1998). For instance, having a sibling with POAG increases the likelihood of an individual developing glaucoma by almost fourfold (Tielsch et al., 1994). Other established risk factors for POAG include diabetes (Zhao et al., 2015), obstructive sleep apnoea (Liu et al., 2016), and refractive error (Marcus et al., 2011; Shen et al., 2016).
Studies have consistently demonstrated the high economic burden of glaucoma, both in terms of direct (e.g., financial cost of treatment) and indirect costs (e.g., loss of well-being, assessed in disability-adjusted life years [DALYs], and loss of work productivity) (Lazcano-Gomez et al., 2016; Varma et al., 2011). Wittenborn and Rein estimated, using data between 2003 and 2011, that glaucoma costs the US population US$5.8 billion per annum in direct and indirect costs, excluding DALYs (Wittenborn and Rein, 2013). Moreover, the economic impact of the disease increases as severity worsens (Lee et al., 2006), with the majority of costs related to medication at all severity stages (Traverso et al., 2005). In terms of DALYs, the Global Burden of Disease Study showed that glaucoma had an estimated global DALYs of 943,000 in 2010, which is again driven by individuals with late-stage disease (Boyers et al., 2015). Assuming a monetary value of US$50,000 per DALY (Gordois et al., 2012), glaucoma contributed an additional ~ US$4.7 billion to the global disease burden.
Section snippets
IOP and beyond
IOP lowering remains a common clinical outcome for glaucoma, with studies unequivocally measuring and reporting changes in IOP in relation to treatment and its associated adherence. IOP, of course, is carefully evaluated in glaucoma because of its strong relevance to future disease progression (Kass et al., 2002; Leske et al., 2007; The Advanced Glaucoma Intervention Study (AGIS), 2000). Indeed, major clinical trials continue to incorporate VF progression as a primary endpoint (Garway-Heath et
What are patient-reported outcomes?
Patient-reported outcomes are reports associated with health conditions, that come directly from the patient, without external interpretation (Food and Drug Administration, 2009). They encompass a range of measurable outcomes from the patient's perspective, including the effect of a disease or health condition on generic health and functioning; as well as disease-specific symptoms and aspects of QoL, self-management, coping, and self-efficacy (Basch, 2014). Patient-reported outcomes can be
Critical review of PCOMs and PROMs in glaucoma
In the following sections, we critically review the psychometric properties of glaucoma-specific PCOMs (objective measures) and PROMs (subjective measures). We evaluate Classical Test Theory (CTT) metrics, such as validity (i.e. the degree to which a PROM measures what it purports to measure), reliability (i.e. the degree to which the measurement is free from measurement error), responsiveness (i.e. the ability of a PROM to detect change over time in the construct being measured) and
Future developments
Healthcare is transitioning from volume-based care (i.e. reimbursement based on the volume of healthcare doctors provide, also known as ‘fee-for-service’ care) to value-based care which is based more on quality of care and patient outcomes rather than quantity of care. This has resulted in a global initiative to incorporate systematic collection of high-quality patient-reported data in clinical care (Basch, 2017). However, as previously outlined, paper-pencil questionnaires are often lengthy,
Conclusions
People with moderate to severe levels of VF damage from glaucoma and/or those undergoing complicated treatment regimens may experience a substantial negative impact on multiple domains of QoL. However, more detailed studies including clinical, population-based and longitudinal data are still needed to fully elucidate people's understanding of their condition and its perceived impact, especially in the early stages which are generally asymptomatic (Crabb, 2016; McDonald et al., 2019). The
Author statement
Eva Fenwick - 25%
Ryan Man- 20%
Tin Aung – 10%
Pradeep Ramulu – 20%
Ecosse Lamoureux – 25%
Funding
E.L. and T.A. are supported by the Singapore National Medical Research Council's Clinician Scientist (NMRC-CSA-SI #JRNMRR140601) and Singapore Translational Research Investigator Awards (NMRC/STAR/0023/2014), respectively.
Declaration of competing interest
None of the authors have conflicts of interest to disclose.
Acknowledgements
We thank Dr. Preeti Gupta for her contribution in undertaking a comprehensive literature review on specific sections of this review.
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Percentage of work contributed by each author in the production of the manuscript is as follows: Eva Fenwick 25%; Ryan Man 20%; Tin Aung 10%; Pradeep Ramulu 20%; Ecosse Lamoureux 25%.