Precision Medicine to Prevent Glaucoma-Related Blindness

Sayoko E. Moroi; David M. Reed; David S. Sanders; Ahmed Almazroa; Lawrence Kagemann; Neil Shah; Nakul Shekhawat; Julia E. Richards

Disclosures

Curr Opin Ophthalmol. 2019;30(3):187-198. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: Approximately 10% of patients become blind despite using evidence-based guidelines developed from clinical trials and epidemiology studies. Our purpose is to review opportunities to decrease glaucoma-related blindness using the emerging principles of precision medicine.

Recent findings: The current review focuses on three topics: first, candidate biomarkers for angle-based surgeries, second, head-mounted display (HMD) technology for vision and testing, and third, glaucoma risk alleles discovered by genome-wide association studies. First, in angle-based surgeries, tracers injected into the anterior chamber or Schlemm's canal have allowed visualization of aqueous veins. We describe an innovative use of optical coherence tomography angiography to visualize aqueous veins in a case with 6-year successful outcome following catheter-based trabeculotomy. Second, HMD technology can augment perceived vision and can be used for perimetry testing. Third, developing genetic risk scores that characterize patients who are at highest risk for blindness is a priority. Such biomarker risk scores will integrate genome-wide association study-based risk alleles for glaucoma along with well known demographic and clinical risk factors.

Summary: As we gain more knowledge, precision medicine will enable clinicians to decrease glaucoma-related blindness by providing more timely interventions to those patients who are at highest risk for progression to blindness.

Introduction

Glaucoma remains a major cause of blindness with estimates of 13.5–42% of patients blind unilaterally and 4–16% blind bilaterally.[1,2,3–8] The 39th Shaffer Lecture focused on applying precision medicine for individualized care to patients with the goals of enhancing vision and preventing glaucoma-related blindness.[9] The intent of health service systems is to address reasons for glaucoma-related blindness that include poor access to care,[10] failure to adhere to medications and follow-up care,[11] and lack of application of best practices.[12–15] In spite of access and adherence to care, the current event-based approach based on progressive visual field loss[16,17] reveals a major gap in the ability to identify patients at risk for blindness.

Glaucoma-related blindness is an unfortunate consequence of progression with a clear phenotype of large cup-to-disc ratio with profound retinal nerve fiber layer thinning. Quigley highlighted future glaucoma care needs to prevent glaucoma-related blindness and vision impairment.[18] First, there is a need to improve the definition of glaucoma to enhance ability for comparing research studies. Second, there is a need to advance evidence-based diagnostic and therapeutic approaches, that will involve biomarkers. Third, there is a need to address the current office-based intraocular pressure (IOP) data collection as this approach because of inadequate sampling of IOPs to assess variance. Fourth, there is a need to adopt systems to improve medication adherence and follow-up care, and shift to sustained drug delivery. Fifth, there is a need to develop and validate new technology for more patient-friendly visual field testing.

According to the NIH Precision Medicine Initiative, precision medicine is described as 'an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person' (https://ghr.nlm.nih.gov/primer/precisionmedicine/definitionaccessed 8 December 2018). We categorize three principles of precision medicine relevant to glaucoma care: first, phenotyping with evolving glaucoma disease definitions using newest technology for earlier diagnosis and detecting disease progression;[18] second, discovery, validation, and understanding of biomarkers for glaucoma, risk factors, disease progression, drug response and surgical outcome; and third, revamping epidemiology studies and clinical trials to discover and validate environmental risk factors and lifestyle behaviors that affect disease onset and progression.

An integral concept for precision medicine is the role of biomarkers to assess the disease phenotypes, disease stage, risk factors, and response to treatments. The US Food and Drug Administration has defined a biomarker 'as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.' (https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/
DrugDevelopmentToolsQualificationProgram/ucm533161.pdfaccessed
8 December 2018). The types of biomarkers include molecular, histologic, radiographic or other imaging, and physiologic. At this time, the role of biomarkers for glaucoma care is limited to the physiologic parameter of IOP and functional testing using visual fields.[19] At present, there is insufficient evidence for structural endpoints of optical coherence tomography (OCT) as a predictor for diagnosis or progression. This review focuses on three topics that represent principles of precision medicine.

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