Surabhi Ruia

The potential of spectral domain optical coherence tomography imaging based retinal biomarkers

BackgroundBiomarker”, 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. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases.Main bodySpectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints.ConclusionOCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.

Nitric oxide in the pathophysiology of retinopathy: evidences from preclinical and clinical researches

Retinopathy is the leading cause of blindness and visual disability in working‐aged people. The pathogenesis of retinopathy is an actual and still open query. Alterations contributing to oxidative and nitrosative stress, including elevated nitric oxide and superoxide production, changes in the expression of different isoforms of nitric oxide synthase or endogenous antioxidant system, have been implicated in the mechanisms how this ocular disease develops. In addition, it was documented that renin–angiotensin system has been implicated in the progression of retinopathy. Based on comprehensive preclinical and clinical researches in this area, the role of above‐mentioned factors in the pathogenesis of diabetic retinopathy, hypertensive retinopathy and ischaemic proliferative retinopathy is reviewed in this study. Moreover, the genetic susceptibility factors involved in the development of the retinopathy and possible strategies that utilize antioxidants as additive therapy are also highlighted here.

INCREASED SERUM LEVELS OF UREA AND CREATININE ARE SURROGATE MARKERS FOR DISRUPTION OF RETINAL PHOTORECEPTOR EXTERNAL LIMITING MEMBRANE AND INNER SEGMENT ELLIPSOID ZONE IN TYPE 2 DIABETES MELLITUS

Purpose: To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time. Methods: One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically. Results: Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (&ggr; = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001). Conclusion: Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.

Retinal Photoreceptor Ellipsoid Zone Integrity in Diabetic Macular Edema

Spectral domain optical coherence tomography (SD-OCT) and further advances in OCT technology have enabled higher resolution retinal imaging. With the delineation of the four hyperreflective bands in the outer retina, retinal microstructural changes have been documented in diabetic retinopathy. The integrity of photoreceptor external limiting membrane and inner segment ellipsoid zone, in particular, has been correlated with disease severity and visual acuity. Various OCT-based grading systems with regard to disruption of photoreceptor external limiting membrane and inner segment ellipsoid zone have been proposed. The pretreatment status of photoreceptor layer is also useful in predicting the post-treatment recovery of inner segment ellipsoid zone and visual acuity.

Three-Dimensional Spectral Domain Optical Coherence Tomography

Optical coherence tomography (OCT) is an ever evolving technology that has revolutionized ophthalmic imaging. With the advent of spectral domain technology, an unparalleled micrometer axial resolution of 5–10 μm is achieved. With more data acquisition per scanning session, volumetric analysis and three-dimensional imaging are realized (Puliafito et al. 1995; Regatieri et al. 2012; Yannuzzi et al. 2004). Three-dimensional OCT generates OCT fundus images that enable precise registration of OCT images with the image of fundus on standard ophthalmoscopic examination techniques. This allows effortless localization of images for monitoring disease progression and response to therapy. Preservation of retinal topography enables visualization of subtle changes associated with the disease. With rapid evolution in technology, clinical usage of OCT has extended to diseases with more complex morphological features. Improved cellular level resolution has extended the application of spectral domain OCT to retinal degenerations and dystrophies. Three-dimensional imaging, with its increased potential in elucidating retinal morphology, provides a global perspective to various retinal diseases.

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

Biomarkers, are biochemical or imaging parameters, that objectively indicate the state of health of an individual. These are measurable by laboratory assay or medical imaging and are useful in prognosticating the disease and monitoring the effects of therapeutic interventions. Spectral domain optical coherence tomography has proved useful in identifying various imaging biomarkers in a range of ocular diseases. Hyperspectral imaging, a novel technology, collects information from across the electromagnetic spectrum for every pixel in an image. Hyperspectral imaging of the retina identifies materials or detects biochemical and metabolic processes within the retina. It provides a feasible method for measurement and analysis of vascular oxygen content in healthy and diseased retina.

Increased levels of Nε- Carboxy methyl lysine (Nε-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study

PURPOSE To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT). METHOD Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done. RESULTS Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant. CONCLUSION Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy.

In vivo early retinal structural alterations following laser photocoagulation using three-dimensional spectral domain optical coherence tomography

To study the retinal structural alterations and surface topography of retinal pigment epithelium (RPE) immediately following laser photocoagulation up to day 7. Cross-sectional retinal imaging and RPE segmentation maps on spectral domain optical coherence tomography were obtained immediately at hour 1, day 1, day 4 and day 7 following 532 nm neodymium:YAG laser photocoagulation in a 56-year-old male patient for branch retinal vein occlusion. Immediately postlaser, loss of reflectivity of all the retinal layers was observed. At hour 1, hyper-reflectivity of outer retinal layers was observed with increase in hyporeflective spaces by day 1. Immediately postlaser, pitting of the RPE was observed on surface topography which regressed at day 1. On day 4, smooth RPE surface topography was observed with the occurrence of small elevated areas on day 7. The present report provides an insight into the in vivo changes in the retinal structure and RPE surface topography after laser photocoagulation.