Biomarkers of Diabetic Retinopathy.

Diabetic retinopathy (DR), a leading cause of acquired vision loss, is a microvascular complication of diabetes. While traditional risk factors for diabetic retinopathy including longer duration of diabetes, poor blood glucose control, and dyslipidemia are helpful in stratifying patient's risk for developing retinopathy, many patients without these traditional risk factors develop DR; furthermore, there are persons with long diabetes duration who do not develop DR. Thus, identifying biomarkers to predict DR or to determine therapeutic response is important. A biomarker can be defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Incorporation of biomarkers into risk stratification of persons with diabetes would likely aid in early diagnosis and guide treatment methods for those with DR or with worsening DR. Systemic biomarkers of DR include serum measures including genomic, proteomic, and metabolomics biomarkers. Ocular biomarkers including tears and vitreous and retinal vascular structural changes have also been studied extensively to prognosticate the risk of DR development. The current studies on biomarkers are limited by the need for larger sample sizes, cross-validation in different populations and ethnic groups, and time-efficient and cost-effective analytical techniques. Future research is important to explore novel DR biomarkers that are non-invasive, rapid, economical, and accurate to help reduce the incidence and progression of DR in people with diabetes.

CHOROIDAL VASCULARITY INDEX IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate choroidal vascularity index (CVI) in eyes with central serous chorioretinopathy (CSC) using an image binarization tool on enhanced depth imaging using spectral domain optical coherence tomography scans. METHODS: In this retrospective cohort study, enhanced depth imaging optical coherence tomography scans of both eyes of patients with CSC were taken at baseline; they were segmented and compared with enhanced depth imaging optical coherence tomography scans of fellow eyes without CSC as well as age-matched healthy subjects. Subfoveal choroidal area (1,500 µm) was segmented into luminal area and stromal area using image binarization. Choroidal vascularity index was defined as the proportion of luminal area to the total circumscribed subfoveal choroidal area. RESULTS: Eyes with acute CSC (32 eyes) had significantly higher CVI compared with their fellow eyes (27 eyes) (P < 0.0001), 19 eyes with resolved CSC (P < 0.0001) and with 30 eyes of age-matched healthy eyes (P < 0.0001). Fellow eyes of subjects with acute CSC also had significantly higher CVI compared with eyes with resolved CSC (P < 0.0001) and age-matched healthy eyes (P < 0.0001). CONCLUSION: Increased CVI suggests increased vascular component compared with the stromal component in acute CSC. Increased CVI was noted in fellow eye of the subjects with acute CSC in comparison with age-matched healthy subjects. The CVI could be a useful index for early diagnosis of CSC and to assess the treatment response after laser photocoagulation or photodynamic therapy.

A longitudinal study of choroidal changes following cataract surgery in patients with diabetes.

OBJECTIVE: To study the structural changes in the choroid of diabetic patients following cataract surgery, using choroidal vascularity index and choroidal thickness. METHODS: A prospective case-control study was conducted in 18 diabetic and 18 non-diabetic patients undergoing cataract surgery (phacoemulsification) in one eye. Enhanced depth imaging optical coherence tomography images were obtained before and after surgery. Niblack's image binarization of images was performed to derive the choroidal vascularity index. Independent sample T-test compared the differences of choroidal vascularity index and choroidal thickness between diabetic and non-diabetic patients. RESULTS: The baseline choroidal vascularity index was significantly lower in diabetic patients for both operated (mean difference vs non-diabetic: 0.0184, 95% CI: 0.004-0.0324, p = 0.012) and non-operated (mean difference vs non-diabetic: 0.0145, 95% CI: 0.003-0.0256, p = 0.012) eyes. Choroidal thickness increased following cataract surgery (diabetes: mean difference = 12.4, 95% CI: 0.70-24.0, adjusted p = 0.036; non-diabetic: mean difference = 21.0, 95% CI: 4.39-37.6, adjusted p = 0.011). CONCLUSION: Diabetic patients have reduced choroidal vascularity index than non-diabetic patients, suggestive of possible reduction in choroidal vascularity in diabetes. Choroidal thickness increased following cataract surgery in both diabetic and non-diabetic patients.

State of science: Choroidal thickness and systemic health.

The choroid is a highly vascular structure; therefore, a wide range of systemic conditions can affect it. Conversely, choroid health may also give us insight into systemic health. With the emergence of optical coherence tomography, there has been a surge in the research on choroidal thickness and factors affecting it. Studies regarding the effect of systemic health on the choroid have largely been in the form of cross-sectional, prospective, and case studies. We offer a summary of recent findings on the topic.

Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study.

The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

Choroidal vascularity index - a novel optical coherence tomography parameter for disease monitoring in diabetes mellitus?

PURPOSE: To propose the use of choroidal vascularity index (CVI) as a novel tool to assess vascular status of the choroid using image binarization of enhanced depth imaging (EDI) optical coherence tomography (OCT) scans in diabetes mellitus (DM). METHODS: A prospective cross-sectional study was performed at a tertiary referral eye care centre in Singapore. Age and gender matched EDI-OCT scans of 38 eyes of 19 patients with DM were compared with eyes of healthy controls (n = 19). The choroidal images were binarized into luminal areas (LA) and stromal areas (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to total circumscribed subfoveal choroid area (TCA). Mean choroidal thickness, mean retinal thickness and mean CVI between patients and controls were compared using student's t-test. RESULTS: There were no significant differences in TCA (p = 0.78), LA (p = 0.90), SA (p = 0.33), average choroidal (p = 0.40) or retinal thickness (p = 0.70) between patients with DM and controls. However, there was a significantly lower CVI in patients with DM as compared to controls (65.10 ± 0.20 versus 67.20 ± 0.16, p < 0.0001). CONCLUSION: Eyes of patients with DM showed decreased CVI with no corresponding change in choroidal thickness. Image binarization may be potentially useful as a tool to assess choroidal structures and vasculature.

Choroidal Vascularity Index (CVI)--A Novel Optical Coherence Tomography Parameter for Monitoring Patients with Panuveitis?

PURPOSE: To compute choroidal vascularity index (CVI) using an image binarization tool on enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans as a non-invasive optical tool to monitor progression in panuveitis and to investigate the utility of volumetric data from EDI-OCT scans using custom image analysis software. MATERIALS AND METHODS: In this retrospective cohort study, segmented EDI-OCT scans of both eyes in 19 patients with panuveitis were taken at baseline and at 3-month follow-up and were compared with EDI-OCT scans of normal eyes. Subfoveal choroidal area was segmented into luminal (LA) and stromal interstitial area (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to the total circumscribed subfoveal choroidal area (TCA). RESULTS: The mean choroidal thickness was 265.5±100.1µm at baseline and 278.4±102.6µm at 3 months follow up (p = 0.06). There was no statistically significant difference in TCA between study and control eyes (p = 0.08). CVI in the control group was 66.9±1.5% at baseline and 66.4±1.5% at follow up. CVI was 74.1±4.7% at baseline and 69.4±4.8% at 3 months follow up for uveitic eyes (p<0.001). The % change in CVI was 6.2 ±3.8 (4.3 to 8.0) for uveitic eyes, which was significantly higher from % change in CVI for control eyes (0.7±1.1, 0.2 to 1.3, p<0.001). CONCLUSION: The study reports composite OCT-derived parameters and CVI as a possible novel tool in monitoring progression in panuveitis. CVI may be further validated in larger studies as a novel optical tool to quantify choroidal vascular status.