Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging

• Published in: Investigative ophthalmology & visual science 2017-05, Vol.58 (6), p.BIO131-BIO140
• Main Authors: Denniston, Alastair K, Keane, Pearse A, Srivastava, Sunil K
• Format: Article
• Language: English
• Subjects: Biomarkers; Diagnostic Techniques, Ophthalmological; Humans; Macular Edema - diagnosis; Reproducibility of Results; Tomography, Optical Coherence - methods; Uveitis - diagnosis; Uveitis - diagnostic imaging
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.17-21788

Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.