Spectral Domain Optical Coherence Tomography-Based Imaging Biomarkers and Hyperspectral Imaging




© Springer India 2017
Carsten H. Meyer, Sandeep Saxena and SriniVas R Sadda (eds.)Spectral Domain Optical Coherence Tomography in Macular Diseases10.1007/978-81-322-3610-8_7


7. Spectral Domain Optical Coherence Tomography-Based Imaging Biomarkers and Hyperspectral Imaging



Surabhi Ruia1 and Sandeep Saxena 


(1)
Department of Ophthalmology, King George’s Medical University, Lucknow, UP, India

 



 

Sandeep Saxena





7.1 Introduction


“Biomarker”, a merged word of “biological marker”, refers to a broad subcategory of medical signs that objectively indicate the state of health and well-being of an individual. These can be anatomical, biochemical, molecular parameters or imaging features. They are measurable by laboratory assay, physical examination or medical imaging. In clinical practice, they are useful in the refinement of diagnosis, measuring disease progression or predicting and monitoring effects of therapeutic interventions. Their source can be tissue or body fluid such as plasma, urine, synovial fluid or tissue biopsy (Strimbu and Tavel 2010). Imaging biomarkers target the diseased organ or tissue and are hence specific indicators. The biochemical biomarkers, in contrast, tend to integrate information from the entire body. Biomarkers hold great promise for customization of treatment for the individual as information gained from diagnostic or progression markers would result in a highly efficient intervention in the disease process. With the introduction of imaging biomarkers, improved imaging technologies are being used for detection of molecules, biochemical processes in the retina. These will facilitate in early detection, assessment and monitoring of retinal pathologies. Hyperspectral imaging, a novel technology, collects information from across the electromagnetic spectrum for every pixel in an image. Spectral imaging techniques facilitate higher signal-to-noise ratio and lower light intensity at the retina in comparison with Fourier transform approach.


7.2 Biomarkers as Surrogate End points


Biomarkers are often used as surrogate end points in clinical trials. They act as surrogates or substitutes for clinically meaningful end points. Clinical end points are variables that represent a study subject’s health and well-being from the subject’s perspective. These end points have the potential to definitively demonstrate whether interventions in a trial are effective or ineffective, as well as safe or unsafe. For example “survival” is considered the gold-standard clinical end point for most HIV trials. To be considered a surrogate end point, there must be solid scientific evidence (epidemiological, therapeutic and/or pathophysiological) that a biomarker consistently and accurately predicts a clinical outcome (Strimbu and Tavel 2010). This requires the determination of relevance and validity. Relevance refers to a biomarker’s ability to appropriately provide clinically relevant information to the public, the healthcare providers, or the health policy officials. Validity refers to the need to characterize a biomarker’s effectiveness or utility as a surrogate end point. The biomarker proposed as a surrogate should be capable of being measured objectively, accurately, precisely and reproducibly. Biomarkers are also important in the development of new drug therapies through identification of drug targets. They also serve as “progression” markers to delineate the development and course of a disease. The changes in these progression markers can be used to understand the effect of therapy in altering the disease process.


7.3 Biomarkers of Imaging in Ocular Diseases


Spectral domain optical coherence tomography (SD-OCT) with its high-resolution in vivo imaging has proven to be useful in identifying various imaging biomarkers in a range of ocular diseases. These include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and epiretinal membrane. SD-OCT-based imaging parameters have also been documented as prognostic biomarkers in neurological diseases like spinocerebellar ataxia, Huntington’s disease, Parkinson’s disease and systemic lupus nephritis.


7.3.1 Age-Related Macular Degeneration


Age-related macular degeneration (AMD) is a progressive degenerative disorder leading to gradual deterioration of central vision. One of the early clinical features in AMD is the appearance of drusen. It has been shown histologically that photoreceptors overlying and distal to drusen undergo degeneration. Ability to use imaging biomarkers for detection of cases which are likely to progress rapidly will benefit from early preventative interventions. SD-OCT and adaptive optics have been used to monitor drusen over time, for their progression in terms of size and their direct effect on the overlying photoreceptor layers (Godara et al. 2010). With the use of microperimetry, functional data of photoreceptors can be obtained to correlate with the high-resolution structural imaging information. These qualitative imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression and monitoring treatment response.

SD-OCT has also been used for imaging morphology, reflectivity properties of drusen, quantifying their number and monitoring the longitudinal evolution in these characteristics. Area, volume, height and reflectivity of drusen are informative features useful for estimating the likelihood of progression to exudative AMD from an early or intermediate stage (Folgar et al. 2016).

High-density SD-OCT macular volumes have been documented to have a potential role in the prediction of disease progression risk in cases of intermediate AMD (de Sisternes et al. 2014). The novel measures of retinal pigment epithelium-drusen complex (RPEDC) are obtained by high-density SD-OCT. The RPEDC abnormal thickening (OCT drusen) and RPEDC abnormal thinning volumes are generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. OCT drusen volume changes predict progression to advanced AMD with choroidal neovascularization. The alteration in RPEDC thinning volume predicts progression to geographic atrophy. These quantitative SD-OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials.


7.3.2 Diabetic Retinopathy


A new parameter, “parallelism”, has been projected to evaluate retinal layer integrity using SD-OCT. OCT images are skeletonized, and the orientation of segmented lines in the image is termed “parallelism”. The orientation of photoreceptor layer status at the fovea has been categorized, including continuity of the external limiting membrane (ELM) band, inner segment ellipsoid zone and the presence of hyperreflective foci in the outer retinal layers. Parallelism was observed to be significantly lower in eyes with diabetic macular edema (DME) in comparison with normal eyes. A positive correlation with visual acuity was also documented. Eyes with an intact inner segment ellipsoid zone or ELM band had significantly better visual acuity and higher parallelism, than eyes with a discontinuous or absent inner segment ellipsoid zone or ELM band. Significantly higher parallelism and better visual acuity were observed in the group without hyperreflective foci in the outer retinal layers. This novel image parameter, “parallelism”, serves as a potential biomarker to prognosticate visual outcome in DME (Uji et al. 2014a).

Three different phenotypes have been recently characterized in diabetic retinopathy to stratify risk of progression to vision-threatening complications. Microaneurysm turnover has been validated as a prognostic biomarker of the development of DME (Cunha-Vaz et al. 2014). SD-OCT for identification of subclinical macular oedema and multifocal electroretinogram for providing functional data appear to be good candidates for organ-specific biomarkers for diabetic retinopathy. Disorganization of the foveal retinal inner layers and photoreceptor ELM disruption have also been documented as robust SD-OCT-based imaging biomarkers for predicting visual outcome in eyes with center involving DME (Sun et al. 2014).

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Jul 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Spectral Domain Optical Coherence Tomography-Based Imaging Biomarkers and Hyperspectral Imaging

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