Right versus left eye asymmetry of microvasculature in diabetes revealed by optical coherence tomography angiography.

In this study, we explored inter-ocular asymmetry (between the two eyes of the same patient) using optical coherence tomography angiography (OCTA) in patients with diabetes mellitus (DM) at different retinopathy stages. A total of 258 patients were divided into four groups: no DM, DM without diabetic retinopathy (DR), non-proliferative DR (NPDR), and proliferative DR (PDR). Superficial and deep vessel density (SVD, DVD), superficial and deep perfusion density (SPD, DPD), foveal avascular zone (FAZ) area, perimeter and circularity were calculated, and asymmetry index (AI) was used to evaluate the asymmetry of two eyes of the same subject. AIs of SPD, SVD, FAZ area and FAZ perimeter in the PDR group were larger than all other 3 groups (all p < 0.05). The AIs of DPD, DVD, FAZ area and FAZ perimeter in males were larger than in females (p = 0.015, p = 0.023, p = 0.006 and p = 0.017). Hemoglobin A1c (HbA1c) was positively correlated with AI of FAZ perimeter (p = 0.02) and circularity (p = 0.022). In conclusion, PDR patients' eyes were significantly asymmetric in both vascular density and FAZ metrics. Male sex and HbA1c are risk factors that influenced symmetry. This study highlights that right-left asymmetry should be taken into account in DR-related studies, particularly those analyzing microvascular changes with OCTA.

Racial and ethnic differences in foveal avascular zone in diabetic and nondiabetic eyes revealed by optical coherence tomography angiography.

PURPOSE: The purpose of this study was to examine whether racial and ethnic differences in retinal microvasculature are detectable with quantitative measures derived from optical coherence tomography angiography (OCTA). METHODS: OCTA scans and fundus photography were obtained in 447 eyes from 271 patients with and without diabetes between April and October 2018. Fundus photos were graded by the hospital reading center for diabetic retinopathy (DR) severity. Eight OCTA parameters relating to the foveal avascular zone (FAZ), superficial vascular perfusion, and deep vascular perfusion were analyzed for significant differences between race and ethnicity groups, self-reported by patients and organized according to National Center for Health Statistics groupings. Multiple regression was then used to adjust estimates for possible confounding by age, gender, hypertension, and last hemoglobin A1c level. RESULTS: Significant differences in FAZ area were found between white and non-white patients. After adjustment, the differences between white and all non-white groups were statistically significant (p<0.05) among patients with mild to moderate DR. In those without diabetes, the Hispanic and Asian groups had significantly larger FAZ areas (p<0.005) than NH white patients. In those with mild to moderate non-proliferative diabetic retinopathy (NPDR), NH Black, Hispanic, and Asian patients also had significantly larger FAZ areas than NH white patients (p<0.005). CONCLUSION: Significant differences in FAZ area exist among different racial and ethnic groups. These results highlight the importance of considering and further studying race and ethnicity in OCTA analyses of the retinal microvasculature.

Comparative Analysis of Multiplex Platforms for Detecting Vitreous Biomarkers in Diabetic Retinopathy.

Purpose: To evaluate the feasibility of using the Proximity Extension Assay (PEA) platform to detect biomarkers in vitreous and to compare the findings with results obtained with an electrochemiluminescent (ECL) sandwich immunoassay. Methods: Vitreous samples from patients with proliferative diabetic retinopathy (PDR) and non-diabetic controls were tested using two different proteomics platforms. Forty-one assays were completed with the ECL platform and 459 with the PEA platform. Spearman's rank correlation coefficient (rs ) was used to determine the direction and strength of the relationship between protein levels detected by both platforms. Results: Three hundred sixty-six PEA assays detected the tested protein in at least 25% of samples, and the difference in protein abundance between PDR and controls was statistically significant for 262 assays. Seventeen ECL assays yielded a detection rate ≥ 25%, and the difference in protein concentration between PDR and controls was statistically significant for 13 proteins. There was a subset of proteins that were detected by both platforms, and for those the Spearman's correlation coefficient was higher than 0.8. Conclusions: PEA is suitable for the analysis of vitreous samples, showing a strong correlation with the ECL platform. The detection rate of PEA panels was higher than the panels tested with ECL. The levels of several proinflammatory and angiogenic cytokines were significantly higher in PDR vitreous compared to controls. Translational Relevance: This study provides new information on the yields of small-volume assays that can detect proteins of interest in ocular specimens, and it identifies patterns of cytokine dysregulation in PDR.

Discordant vascular parameter measurements in diabetic and non-diabetic eyes detected by different optical coherence tomography angiography devices.

PURPOSE: To compare quantitative changes in macular parameters in diabetic patients detected by two optical coherence tomography angiography (OCTA) instruments. METHODS: 80 phakic eyes were classified as no diabetes, diabetes without diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), and severe NPDR or proliferative DR (PDR). OCTA was performed using devices from two manufacturers (Zeiss and Heidelberg). Superficial and deeper vascular skeleton density (SVSD, DVSD), superficial and deeper vessel area density (SVAD, DVAD), choriocapillaris flow voids (CCFV), and choroidal flow voids (CFV) were calculated. Inter-device comparisons were performed using the size comparison index (SCI) and the discrepancy index (DI). RESULTS: The two devices were inconsistent in SVSD, DVSD, DVAD, CCFV and CFV parameters (all P < 0.05). In addition, the SCI was positive for DVAD (all P < 0.001) and negative for SVSD, DVSD, CCFV and CFV in all groups (all P <0.001), except for DVSD in severe NPDR or PDR. The discrepancy index was not significantly different among groups for SVD, SPD, DVD, DPD and CFV (all P> 0.05). The mean DI of CCFV was statistically different between the four groups (P < 0.001). CONCLUSIONS: The two instruments were largely inconsistent in the measurement of macular parameters relevant to DR. The choice of imaging device can impact OCTA analytics and should be taken into account when drawing conclusions about DR-related changes.

Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy.

Purpose: To investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1ß [MIP-1ß], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection. Results: The following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-α, MCP-1, MIP-1ß, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-α, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01). Conclusions: In this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.

OCT Angiography Assessment of Retinal Microvascular Changes in Diabetic Eyes in an Urban Safety-Net Hospital.

PURPOSE: To determine whether quantitative OCT angiography (OCTA) parameters can be used to distinguish among eyes at various stages of diabetic retinopathy (DR) in an urban safety-net hospital population. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Three hundred twenty-nine eyes from 329 patients were included in this study: 90 nondiabetic patients, 170 diabetic patients without DR, 57 diabetic patients with mild to moderate nonproliferative DR (NPDR), and 12 diabetic patients with severe NPDR to proliferative DR. METHODS: Patients underwent OCTA imaging and ultra-widefield fundus photography at Zuckerberg San Francisco General Hospital and Trauma Center between April and October 2018. For participants with diabetes, imaging was classified according to DR severity by a telemedicine reading center. Eight OCTA parameters were analyzed. Perfusion density and vessel length density (VD) were examined from both the superficial capillary plexus (SCP) and deep capillary plexus. The other 4 parameters were examined only from the SCP. Total extrafoveal avascular area (tEAA) was based on the area of absent capillary vessels. Foveal avascular zone (FAZ)-related metrics consisted of FAZ area, FAZ circularity index, and FAZ acircularity index. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC) for OCTA parameters to distinguish among groups according to DR severity. RESULTS: All OCTA parameters demonstrated a significant relationship with DR severity (P < 0.05). No significant difference was found when comparing nondiabetic participants versus diabetic participants without retinopathy. The FAZ area was the only metric that demonstrated a significant difference between genders: mean of 0.29±0.12 mm2 in men and 0.34±0.13 mm2 in women (P < 0.001). Receiver operating characteristic curve analyses showed that tEAA had the highest AUC when comparing various stages of the disease. CONCLUSIONS: In this urban, public hospital population, quantification of retinal vascular findings with OCTA imaging was a useful means of distinguishing patients according to DR severity. Because these results were similar to those of other tertiary referral centers, it would be reasonable to perform further DR-related OCTA studies in this population and expect generalizable results.

Diagnostic value of visual evoked potentials for clinical diagnosis of multiple sclerosis.

PURPOSE: Prolonged latency of visual evoked potentials (VEP) has been used to identify clinically silent lesions in multiple sclerosis (MS) suspects. The objective of this study was to determine the reliability of VEP to predict the development of MS in MS suspects. METHODS: Retrospective hospital records of MS suspects were evaluated. VEP was analyzed together with subsequent diagnostic confirmation of MS by McDonald diagnostic criteria for MS-2005. RESULTS: MS developed in 12 of 35 patients (34 %) and 23 (66 %) failed to exhibit diagnostic characteristics. P100 latencies and interocular latency differences were longer in clinically definite multiple sclerosis (CDMS) than non-CDMS patients (p = 0.002, 0.001, respectively). All patients in the subsequent MS group had P100 latencies longer than102 ms, a mean of our MS-free subjects thus providing 100 % of sensitivity. No patient developed MS with a P100 latency <102 ms. Brain MRI lesions associated significantly with developing CDMS (p = 0.001). Predictability of developing CDMS was highest when criteria for P100 latency, interocular latency difference, and brain MRI lesions were combined. CONCLUSION: MS suspects with a P100 latency longer than mean of MS-free subjects are more likely to develop MS than those with lower values. VEP latency combined with MRI could improve the accuracy of MS prediction.

Enhanced depth imaging spectral-domain optical coherence tomography of the choroid in Thai population.

OBJECTIVE: To examine subfoveal choroidal thickness (SFCT) in Thai population using enhanced depth imaging spectral- domain optical coherence tomography (EDI-OCT) and to study its correlation with foveal retinal pigment epithelium thickness (FRPE), central neurosensory retinal thickness (CNRT), age, and refraction. MATERIAL AND METHOD: Four hundred eighty eyes from 240 subjects without glaucoma, retinal, or choroidal diseases underwent scanning of the retina and choroid using EDI-OCT SFCT FRPE, and CNRT measurements were based on the 1:1 micron images and wereperformed by two independent observers. The reliability ofmeasurements between the observers was evaluated by intraclass correlation coefficient (ICC). The correlations of SFCT with FRPE, CNRT, age, and refractive error were analyzed RESULTS: The mean age of the subjects was 36.22 years (range 20-81years). The means (95% reference intervals) of SFCT, CNRT andFRPE were 294.02 µm (137.14-450.90 µm), 174.22 µm (141.82-206.62 µm), and 41.94 µm (34.65-49.23 µm), respectively. SFCT and CNRThad excellent reliability between the two observers [ICC = 0.947 (95% CI, 0.918-0.963) and 0.929 (95% CI, 0.906-0.945), respectively], while FRPE showed good reliability [ICC = 0. 729 (95% CI, 0.637-0.793)]. SFCT had a low positive correlation with FRPE (r = 0.179, p<0. 0001) but not with CNRT (p = 0.317). SFCT showed a positive correlation with refraction (r = 0.338, p<0.0001) and a negative correlation with age (r = -0.166, p<0.0001). Regression analysis suggested that the SFCT decreased by 12.23 pm per one decade oflife and by 11.42 pm per one diopter of myopia. CONCLUSION: Normal values of SFCT in Thai population were obtained SFCT significantly decreased with older age and higher myopia. SFCT was associated with FRPE, reflecting the same vascular supply of the choroid and retinal pigment epithelium. When measured with our technique based on the 1:1 micron images, the reliability ofSFCT measurement was very high despite highly morphologic inter-individual variations.