Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients.

Data on how retinal structural and vascular parameters jointly influence the diagnostic performance of detection of multiple sclerosis (MS) patients without optic neuritis (MSNON) are lacking. To investigate the diagnostic performance of structural and vascular changes to detect MSNON from controls, we performed a cross-sectional study of 76 eyes from 51 MS participants and 117 eyes from 71 healthy controls. Retinal macular ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the Cirrus AngioPlex. The best structural parameter for detecting MS was compensated RNFL from the optic nerve head (AUC = 0.85), followed by GCC from the macula (AUC = 0.79), while the best vascular parameter was the SCP (AUC = 0.66). Combining structural and vascular parameters improved the diagnostic performance for MS detection (AUC = 0.90; p<0.001). Including both structure and vasculature in the joint model considerably improved the discrimination between MSNON and normal controls compared to each parameter separately (p = 0.027). Combining optical coherence tomography (OCT)-derived structural metrics and vascular measurements from optical coherence tomography angiography (OCTA) improved the detection of MSNON. Further studies may be warranted to evaluate the clinical utility of OCT and OCTA parameters in the prediction of disease progression.

Investigating the macular choriocapillaris in early primary open-angle glaucoma using swept-source optical coherence tomography angiography.

Introduction: There has been a growing interest in the role of vascular factors in glaucoma. Studies have looked at the characteristics of macular choriocapillaris in patients with glaucoma but with conflicting results. Our study aims to use swept-source optical coherence tomography angiography (SS-OCTA) to evaluate macular choriocapillaris metrics in normal participants and compare them with patients with early primary open-angle glaucoma (POAG) (mean deviation better than -6dB). Methods: In this prospective, observational, cross-sectional study, 104 normal controls (157 eyes) and 100 patients with POAG (144 eyes) underwent 3 mm × 3mm imaging of the macula using the Plex Elite 9000 (Zeiss Meditec, Dublin, CA, USA). Choriocapillaris OCTA images were extracted from the device's built-in review software and were subsequently evaluated for the density and size of choriocapillaris flow deficits. Results: After adjusting for confounding factors, the density of flow deficits was independently higher in those aged 53 years and above (P ≤ 0.024) whereas the average flow deficit size was significantly larger in those aged 69 years and above (95% CI = 12.39 to 72.91; P = 0.006) in both normal and POAG patients. There were no significant differences in the density of flow deficits (P = 0.453) and average flow deficit size (P = 0.637) between normal and POAG participants. Conclusion: Our study found that macular choriocapillaris microvasculature on SS-OCTA is unaltered by subjects with POAG. This suggests that OCTA macular choriocapillaris may not be potentially helpful in differentiating early glaucoma from healthy eyes.

Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis.

Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing-remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case-control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, and flow deficit in the CC. MS group had on average higher intraocular pressure (IOP) than controls (P < 0.001). After adjusting for confounders, MS participants showed significantly increased PD in SCP (P = 0.003) and decreased PD in DCP (P < 0.001) as compared to controls. A significant difference was still noted when large vessels (LV) in the SCP were removed from the PD calculation (P = 0.004). Deep FAZ was significantly larger (P = 0.005) and less circular (P < 0.001) in the eyes of MS participants compared to the control ones. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS group and control group (P > 0.186). Our study indicates that there are microvascular changes in the macular parafoveal retina of RRMS patients without ON, showing increased PD in SCP and decreased PD in DCP. Further studies with a larger cohort of MS patients and MRI correlations are necessary to validate retinal microvascular changes as imaging biomarkers for diagnosis and screening of MS.

A multi-regression approach to improve optical coherence tomography diagnostic accuracy in multiple sclerosis patients without previous optic neuritis.

BACKGROUND: Optical coherence tomography (OCT) is a retinal imaging system that may improve the diagnosis of multiple sclerosis (MS) persons, but the evidence is currently equivocal. To assess whether compensating the peripapillary retinal nerve fiber layer (pRNFL) thickness for ocular anatomical features as well as the combination with macular layers can improve the capability of OCT in differentiating non-optic neuritis eyes of relapsing-remitting MS patients from healthy controls. METHODS: 74 MS participants (n = 129 eyes) and 84 age- and sex-matched healthy controls (n = 149 eyes) were enrolled. Macular ganglion cell complex (mGCC) thickness was extracted and pRNFL measurement was compensated for ocular anatomical factors. Thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between groups. RESULTS: Participants with MS showed significantly thinner mGCC, measured and compensated pRNFL (p ≤ 0.026). Compensated pRNFL achieved better performance than measured pRNFL for MS differentiation (AUC, 0.75 vs 0.80; p = 0.020). Combining macular and compensated pRNFL parameters provided the best discrimination of MS (AUC = 0.85 vs 0.75; p < 0.001), translating to an average improvement in sensitivity of 24 percent for differentiation of MS individuals. CONCLUSION: The capability of OCT in MS differentiation is made more robust by accounting OCT scans for individual anatomical differences and incorporating information from both optic disc and macular regions, representing markers of axonal damage and neuronal injury, respectively.

Relationship of Quantitative Retinal Capillary Network and Myocardial Remodeling in Systemic Hypertension.

Background This study examined the associations between quantitative optical coherence tomography angiography (OCTA) parameters and myocardial abnormalities as documented on cardiovascular magnetic resonance imaging in patients with systemic hypertension. Methods and Results We conducted a cross-sectional study of 118 adults with hypertension (197 eyes). Patients underwent cardiovascular magnetic resonance imaging and OCTA (PLEX Elite 9000, Carl Zeiss Meditec). Associations between OCTA parameters (superficial and deep retinal capillary density) and adverse cardiac remodeling (left ventricular mass, remodeling index, interstitial fibrosis, global longitudinal strain, and presence of left ventricular hypertrophy) were studied using multivariable linear regression analysis with generalized estimating equations. Of the 118 patients with hypertension enrolled (65% men; median [interquartile range] age, 59 [13] years), 29% had left ventricular hypertrophy. After adjusting for age, sex, systolic blood pressure, diabetes, and signal strength of OCTA scans, patients with lower superficial capillary density had significantly higher left ventricular mass (ß=-0.150; 95% CI, -0.290 to -0.010), higher interstitial volume (ß=-0.270; 95% CI, -0.535 to -0.0015), and worse global longitudinal strain (ß=-0.109; 95% CI, -0.187 to -0.032). Lower superficial capillary density was found in patients with hypertension with replacement fibrosis versus no replacement fibrosis (16.53±0.64 mm-1 versus 16.96±0.64 mm-1; P=0.003). Conclusions We showed significant correlations between retinal capillary density and adverse cardiac remodeling markers in patients with hypertension, supporting the notion that the OCTA could provide a non-invasive index of microcirculation alteration for vascular risk stratification in people with hypertension.

MACULAR SENSITIVITY AND CAPILLARY PERFUSION IN HIGHLY MYOPIC EYES WITH MYOPIC MACULAR DEGENERATION.

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

Effect of hyperoxia and hypoxia on retinal vascular parameters assessed with optical coherence tomography angiography.

PURPOSE: To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT-A) and retinal vessel analyzer. METHODS: Twenty-four healthy volunteers participated in this randomized, double-masked, cross-over study. For each subject, two study days were scheduled: on one study day, hyperoxia was induced by breathing 100% oxygen whereas on the other study day, hypoxia was induced by breathing a mixture of 88% nitrogen and 12% oxygen. Perfusion density was calculated in the superficial vascular plexus (SVP) and the deep capillary plexus (DCP), using OCT-A before (normal breathing) and during breathing of the gas mixtures. Retinal vessel calibres in major retinal vessels were measured using a dynamic vessel analyzer. RESULTS: During 100% oxygen breathing, a significant decrease in DCP perfusion density from 41.7 ± 2.4 a.u to 35.6 ± 3.1 a.u. (p < 0.001) was observed, which was accompanied by a significant decrease in vessel diameters in major retinal arteries and veins (p < 0.001 each). No significant change in perfusion density in the SVP occurred (p = 0.33). In contrast, during hypoxia, perfusion density in the SVP significantly increased from 34.4 ± 3.0 a.u. to 37.1 ± 2.2 a.u. (p < 0.001), while it remained stable in the DCP (p = 0.25). A significant increase in retinal vessel diameters was found (p < 0.01). Systemic oxygen saturation correlated negatively with perfusion density in the SVP and the DCP and retinal vessel diameters (p < 0.005 each). CONCLUSION: Our results show that systemic hyperoxia induces a significant decrease in vessel density in the DCP, while hypoxia leads to increased vessel density limited to the SVP. These results indicate that the retinal circulation shows the ability to adapt its blood flow to metabolic changes with high local resolution dependent on the capillary plexus.

Ultrawide field, distortion-corrected ocular shape estimation with MHz optical coherence tomography (OCT).

Ocular deformation may be associated with biomechanical alterations in the structures of the eye, especially the cornea and sclera in conditions such as keratoconus, congenital glaucoma, and pathological myopia. Here, we propose a method to estimate ocular shape using an ultra-wide field MHz swept-source optical coherence tomography (SS-OCT) with a Fourier Domain Mode-Locked (FDML) laser and distortion correction of the images. The ocular biometrics for distortion correction was collected by an IOLMaster 700, and localized Gaussian curvature was proposed to quantify the ocular curvature covering a field-of-view up to 65°×62°. We achieved repeatable curvature shape measurements (intraclass coefficient = 0.88 ± 0.06) and demonstrated its applicability in a pilot study with individuals (N = 11) with various degrees of myopia.

Developing a normative database for retinal perfusion using optical coherence tomography angiography.

Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual's data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12×12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and >69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12×12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma.