iStent insertion orientation and impact on trabecular meshwork motion resolved by optical coherence tomography imaging.

Significance: The iStent is a popular device designed for glaucoma treatment, functioning by creating an artificial fluid pathway in the trabecular meshwork (TM) to drain aqueous humor. The assessment of iStent implantation surgery is clinically important. However, current tools offer limited information. Aim: We aim to develop innovative assessment strategies for iStent implantation using optical coherence tomography (OCT) to evaluate the position and orientation of the iStent and its biomechanical impact on outflow system dynamics. Approach: We examined four iStents in the two eyes of a glaucoma patient. Three-dimensional (3D) OCT structural imaging was conducted for each iStent, and a semi-automated algorithm was developed for iStent segmentation and visualization, allowing precise measurement of position and orientation. In addition, phase-sensitive OCT (PhS-OCT) imaging was introduced to measure the biomechanical impact of the iStent on the outflow system quantified by cumulative displacement (CDisp) of pulse-dependent trabecular TM motion. Results: The 3D structural image processed by our algorithm definitively resolved the position and orientation of the iStent in the anterior segment, revealing substantial variations in relevant parameters. PhS-OCT imaging demonstrated significantly higher CDisp in the regions between two iStents compared to locations distant from the iStents in both OD ( p = 0.0075 ) and OS ( p = 0.0437 ). Conclusions: Our proposed structural imaging technique improved the characterization of the iStent's placement. The imaging results revealed inherent challenges in achieving precise control of iStent insertion. Furthermore, PhS-OCT imaging unveiled potential biomechanical alterations induced by the iStent. This unique methodology shows potential as a valuable clinical tool for evaluating iStent implantation.

Calcified Drusen Prevent the Detection of Underlying Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: In age-related macular degeneration (AMD), choriocapillaris flow deficits (CCFDs) under soft drusen can be measured using established compensation strategies. This study investigated whether CCFDs can be quantified under calcified drusen (CaD). Methods: CCFDs were measured in normal eyes (n = 30) and AMD eyes with soft drusen (n = 30) or CaD (n = 30). CCFD density masks were generated to highlight regions with higher CCFDs. Masks were also generated for soft drusen and CaD based on both structural en face OCT images and corresponding B-scans. Dice similarity coefficients were calculated between the CCFD density masks and both the soft drusen and CaD masks. A phantom experiment was conducted to simulate the impact of light scattering that arises from CaD. Results: Area measurements of CCFDs were highly correlated with those of CaD but not soft drusen, suggesting an association between CaD and underlying CCFDs. However, unlike soft drusen, the detected optical coherence tomography (OCT) signals underlying CaD did not arise from the defined CC layer but were artifacts caused by the multiple scattering property of CaD. Phantom experiments showed that the presence of highly scattering material similar to the contents of CaD caused an artifactual scattering tail that falsely generated a signal in the CC structural layer but the underlying flow could not be detected. Similarly, CaD also caused an artifactual scattering tail and prevented the penetration of light into the choroid, resulting in en face hypotransmission defects and an inability to detect blood flow within the choriocapillaris. Upon resolution of the CaD, the CC perfusion became detectable. Conclusions: The high scattering property of CaD leads to a scattering tail under these drusen that gives the illusion of a quantifiable optical coherence tomography angiography signal, but this signal does not contain the angiographic information required to assess CCFDs. For this reason, CCFDs cannot be reliably measured under CaD, and CaD must be identified and excluded from macular CCFD measurements.

A Clinician's Guide to Sharing Data for AI in Ophthalmology.

Data is the cornerstone of using AI models, because their performance directly depends on the diversity, quantity, and quality of the data used for training. Using AI presents unique potential, particularly in medical applications that involve rich data such as ophthalmology, encompassing a variety of imaging methods, medical records, and eye-tracking data. However, sharing medical data comes with challenges because of regulatory issues and privacy concerns. This review explores traditional and nontraditional data sharing methods in medicine, focusing on previous works in ophthalmology. Traditional methods involve direct data transfer, whereas newer approaches prioritize security and privacy by sharing derived datasets, creating secure research environments, or using model-to-data strategies. We examine each method's mechanisms, variations, recent applications in ophthalmology, and their respective advantages and disadvantages. By empowering medical researchers with insights into data sharing methods and considerations, this review aims to assist informed decision-making while upholding ethical standards and patient privacy in medical AI development.

Quantitative Microvascular Change Analysis Using a Semi-Automated Software in Macula-off Rhegmatogenous Retinal Detachment Assessed by Swept-Source Optical Coherence Tomography Angiography.

Objective: To analyze the performance of custom semi-automated software for quantitative analysis of retinal capillaries in eyes with macula-off rhegmatogenous retinal detachment (RRD) and the role of these microvascular measures as potential biomarkers of postoperative visual outcomes. Methods: A prospective, observational, and single-center study was conducted on consecutive patients who underwent 25G pars-plana vitrectomy for primary uncomplicated macula-off RRD. Optical coherence tomography angiography (OCTA) was performed in the fellow and RRD eyes before surgery and in months 1, 3, and 6 after surgery. The preoperative values of the fellow eyes were used as surrogates of macula-off ones. The primary endpoints were the mean vessel diameter index (VDI); vessel area density (VAD); and vessel skeleton density (VSD) at month 6. Results: Forty-four eyes (44 patients) were included in the study. Considering the fellow eyes as a surrogate of preoperative values of macula-off eyes, VDI in superficial (SCP) and deep (DCP) capillary plexuses was significantly reduced at month 6 (p = 0.0087 and p = 0.0402, respectively); whereas VSD in SCP increased significantly from preoperative values (p = 0.0278). OCTA built-in software parameters were significantly reduced from month 1 to month 6 in both SCP and DCP (p values ranged between 0.0235 and <0.0001). At month 6, 25 (56.8%) eyes achieved a best-corrected visual acuity BCVA ≥ 0.3 (LogMAR). The greater the preoperative BCVA, the greater the probability of achieving good visual outcomes (Odds ratio: 11.06; p = 0.0037). However, none of the OCTA parameters were associated with the probability of achieving a BCVA improvement ≥ 0.3. Conclusions: Quantitative evaluation of capillary density and morphology through OCTA and semi-automated software represents a valuable tool for clinical assessment and managing the disease comprehensively.

Influence of Carotid Endarterectomy on Choroidal Perfusion: The INFLATE Study.

PURPOSE: Patients with clinically significant carotid artery stenosis (CAS) undergoing carotid artery endarterectomy (CEA) were imaged with swept-source OCT angiography (SS-OCTA) imaging protocol to determine if there were changes in choroidal blood flow after surgery. DESIGN: Prospective observational study. PARTICIPANTS: Patients with clinically significant CAS undergoing unilateral CEA. METHODS: All participants underwent SS-OCTA imaging using a 6 × 6-mm scan pattern on both eyes before CEA and within 1 week after CEA. Previously validated automated algorithms were used to measure the mean choroidal thickness (MCT) and choroidal vascular index (CVI) within 2.5-mm and 5-mm circles centered on the fovea. Multivariable regression analysis was conducted to evaluate the impact of various baseline factors including age, mean arterial blood pressure, and degree of stenosis, on both baseline of MCT and CVI, and the changes in MCT and CVI. MAIN OUTCOME MEASURES: Changes in MCT and CVI. RESULTS: One hundred sixteen eyes from 60 patients with a mean age of 71.57 ± 7.37 years were involved in the study. At baseline, MCT in both the 2.5-mm and 5-mm circles was significantly thinner on the surgical side compared with the nonsurgical side (P = 0.03), while no significant differences were seen in the CVI at baseline between the 2 sides (2.5-mm circle: P = 0.24; 5-mm circle: P = 0.09). Within 1 week after CEA, there were significant increases in the MCT on the surgical side, as compared with the nonsurgical side, in both the 2.5-mm (P < 0.001) and the 5-mm (P < 0.001) circles. No significant change in mean CVI was noted before and after CEA on the surgical side versus the nonsurgical side (2.5-mm circle: P = 0.30; 5-mm circle: P = 0.97). Multivariable regression analysis revealed that baseline MCT before CEA significantly decreased with age on both the surgical (P < 0.001) and nonsurgical sides (P = 0.003) while the changes in MCT and CVI after CEA were not associated with age, mean arterial blood pressure, or degree of stenosis. CONCLUSION: A rapid and significant increase in MCT was observed on the ipsilateral side of CEA, suggesting an improvement in choroidal perfusion within 1 week after surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Impact of Carotid Endarterectomy on Choriocapillaris Perfusion.

Purpose: The impact of carotid endarterectomy (CEA) on choriocapillaris (CC) perfusion was investigated using swept-source optical coherence tomography angiography (SS-OCTA) imaging before and after surgery in patients with clinically significant carotid artery stenosis (CAS). Methods: In this prospective observational study, patients with clinically significant CAS undergoing unilateral CEA had SS-OCTA imaging performed in both eyes before and within 1 week after surgery. The percent CC flow deficits (CC FD%) and CC thickness were assessed using previously validated algorithms. Multivariable regression analysis was conducted to evaluate the impact of variables on the change in CC measurements. Results: A total of 112 eyes from 56 patients with an average age of 72.6 ± 6.9 years were enrolled. At baseline, significantly higher CC FD% and thinner CC thickness were observed on the surgical side (eyes ipsilateral to the side of CEA) versus the nonsurgical side (eyes contralateral to the side of CEA) (P = 0.001 and P = 0.03, respectively). Following CEA, a significant reduction in CC FD% and a significant increase in CC thickness were detected on the surgical as compared with the nonsurgical side (P = 0.008 and P = 0.01, respectively). Smoking status positively affected CC FD% change (coefficient of variation [CV] = 0.84, P = 0.01) on the surgical side and negatively affected CC thickness change on both the surgical side (CV = -0.382, P = 0.009) and the nonsurgical side (CV = -0.321, P = 0.04). The degree of stenosis demonstrated a positive influence on CC FD% change (CV = 0.040, P = 0.02) on the surgical side. Conclusions: Unilateral CEA on the side of clinically significant CAS increases carotid blood flow, which further results in improved CC perfusion.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (AµT) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from ∼100 µm in the periphery to ∼150 µm in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (A$\mu$T) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from $\sim 100\mu m$ in the periphery to $\sim 150\mu m$ in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Evaluation of Insulin Pump Infusion Sites in Type 1 Diabetes: The DERMIS Study.

OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) for type 1 diabetes is increasing in use. Pump site failures are common, but little is known about skin changes from pump use. Using noninvasive optical coherence tomography (OCT), OCT angiography (OCTA), and skin biopsies, we evaluated skin changes from chronic insulin infusion. RESEARCH DESIGN AND METHODS: In this cross-sectional study, OCT operating at a 1,310-nm central wavelength with a bandwidth of 100 nm was performed immediately before skin punch biopsies were collected at three sites: the current site, with the infusion set removed at time of OCT and biopsy; the recovery site, with the infusion set removed 3 days before biopsy; and the control site, which was never used for any insulin infusion or injection. RESULTS: OCT and OCTA identified characteristics of increased inflammation and vessel density at pump sites compared with control sites. Histologic analysis of pump sites showed differences in skin architecture, including fibrosis, inflammation (including increased tissue eosinophils), and fat necrosis. Immunohistochemical staining showed differences between infusion and control sites regarding staining of ILGF-I and transforming growth factor-ß3. CONCLUSIONS: These findings support allergic sensitization as a potentially common reaction at CSII sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing. The inflammatory response caused by these common allergic responses may result in tissue changes responsible for the infusion site failures seen frequently in clinical practice.

The Impact of Cataracts on the Measurement of Macular Choriocapillaris Flow Deficits Using Swept-Source OCT Angiography.

Purpose: The impact of cataracts on the measurement of macular choriocapillaris flow deficits (CC FDs) was assessed by comparing the quantitative results before and after cataract surgery using an image quality algorithm developed for swept-source optical coherence tomography angiography (SS-OCTA) scans and a validated strategy for quantifying the CC FDs. Methods: SS-OCTA image quality scores and CC FDs measurements within the fovea-centered 1-mm, 3-mm, and 5-mm diameter circles were compared before and after cataract surgery. CC FDs changes in a modified Early Treatment Diabetic Retinopathy Study (ETDRS) grid were further investigated. Results: Twenty-four eyes were studied. Overall image quality in all three circles was observed to improve significantly following the removal of cataracts (all P < 0.05). Although there was good repeatability in the measurements of CC FDs at both visits (intraclass correlation coefficients were over 0.95), significant decreases in CC FD measurements were observed after surgery within the 1-mm circle (P < 0.001) and the 3-mm circle (P = 0.011), but no changes were observed within the 5-mm circle (P = 0.509) or any of the quadrant sectors of the modified ETDRS grid (all P > 0.05). Conclusions: The presence of cataracts resulted in worse image quality and increased CC FD measurements within the fovea-centered 1-mm and 3-mm circles, with the 1-mm circle being impacted the most. Translational Relevance: The impaired detection of CC perfusion deficits within the central macula of cataract eyes needs to be appreciated when imaging the CC in phakic eyes, especially in clinical trials.

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

Identification of the joint line in revision total knee arthroplasty using a multiple linear regression model: a cadaveric study.

INTRODUCTION: The results of revision total knee arthroplasty (rTKA) may be compromised by excessive joint line (JL) elevation. It is critical but challenging in reestablishing the JL in rTKA. Previous studies have confirmed that, biomechanically and clinically, JL elevation should not exceed 4 mm. Image-based studies described several approaches to locate the JL intraoperatively, however magnification errors could occur. In this cadaveric study, we aim to define an accurate and reliable method to determine the JL. MATERIALS AND METHODS: Thirteen male and eleven female cadavers were used, with an average age of death being 48.3 years. The transepicondylar width (TEW), the distance from the medial (MEJL) and lateral (LEJL) epicondyle, adductor tubercle (ATJL), fibular head (FHJL) and tibial tubercle (TTJL) to the JL were measured in 48 knees. Intra- and interobserver reliability and validity were tested prior to any additional analysis. Pearson correlation and linear regression analysis were used to examine the correlations between landmark-JL distances (LEJL, MEJL, ATJL, FHJL and TTJL) and the TEW, and to further derive models for intraoperative JL determination. The accuracy of different models, quantified by errors between estimated and measured landmark-JL distances, was compared using the Friedman and post hoc Dunn tests. RESULTS: The intra- and inter-observer measurements for TEW, MEJL, LEJL, ATJL, TTJL and FHJL did not differ significantly (p > 0.05). Between genders, significant differences were found on TEW, MEJL, LEJL, ATJL, FHJL and TTJL (p < 0.05). There was no association between TEW and either FHJL or TTJL (p > 0.05), while ATJL, MEJL, and LEJL were found to be correlated with TEW (p < 0.05). Six models were derived: (1) MEJL = 0.37*TEW (r = 0.384), (2) LEJL = 0.28*TEW (r = 0.380), (3) ATJL = 0.47*TEW (r = 0.608), (4) MEJL = 0.413*TEW - 4.197 (R2 = 0.473), (5) LEJL = 0.236*TEW + 3.373 (R2 = 0.326), (6) ATJL = 0.455*TEW + 1.440 (R2 = 0.556). Errors were defined as deviations between estimated and actual landmark-JL distances. The mean absolute value of the errors, created by Model 1-6 was 3.18 ± 2.25, 2.53 ± 2.15, 2.64 ± 2.2, 1.85 ± 1.61, 1.60 ± 1.59 and 1.71 ± 1.5, respectively. The error could be limited to 4 mm in 72.9%, 83.3%, 72.9%, 87.5%, 87.5%, and 93.8% of the cases by referencing Model 1-6, respectively. CONCLUSION: Compared to previous image-based measurements, the current cadaveric study most closely resembles a realistic view of intraoperative settings and could circumvents magnification errors. We recommend using Model 6, the JL can be best estimated by referencing the AT and the ATJL can be calculated as ATJL (mm) = 0.455*TEW (mm) + 1.440 (mm).

Ocular and systemic determinants of perifoveal and macular vessel parameters in healthy African Americans.

PURPOSE: To determine the relationship of various systemic and ocular characteristics with perifoveal and macular vessel density in healthy African American eyes. DESIGN: A population-based cross-sectional study of prospectively recruited African Americans ≥40 years of age. Participants underwent 3×3 mm and 6×6 mm macula scans using spectral-domain optical coherence tomography angiography (OCTA), clinical examinations and clinical questionnaires. Participants with glaucoma, severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular oedema were excluded. Custom MATLAB based software quantified vessel area density (VAD) and vessel skeleton density (VSD) in the superficial retinal layer of the macula. Multivariable regression analysis, controlling for inter-eye correlation, was performed to determine systemic and ocular determinants of macular vessel metrics using stepwise selection. Candidate variables included: age, gender, body mass index, history of smoking, history of diabetes, diabetes duration, history of stroke or brain haemorrhage, systolic blood pressure, diastolic blood pressure (DBP), pulse pressure, mean arterial pressure, central subfield thickness (CSFT), visual field mean deviation, intraocular pressure, axial length (AL), mean ocular perfusion pressure and signal strength (SS). RESULTS: A total of 2221 OCTA imaged eyes from 1472 participants were included in this study. Reduced perifoveal and macular VAD and VSD were independently associated with longer AL, reduced SS, reduced CSFT and older age. Male gender and lower DBP were also associated with reduced perifoveal and macular VSD. CONCLUSIONS: When interpreting OCTA images in a clinical setting, it is important to consider the effects ocular and systemic characteristics may have on the macular microcirculation.

Xuedan Sustained Release Pellets Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats by Targeting Gut Microbiota and MAPK Signaling Pathways.

Cucurbitacins have a variety of bioactivities, such as anticancer, anti-inflammatory, antidepressant-like, and antiviral effects, but their pharmacological effect in ulcerative colitis (UC) has not been reported until now. Thus, this study aims to investigate the preventive effects of Xuedan sustained release pellets (XSPs) on UC rats and the underlying mechanisms. XSPs were prepared by extracting cucurbitacins from Hemsleya. Experimental UC rats were induced by the intake of 4% dextran sulfate sodium (DSS) for a week and treated with different doses of XSP (0.95, 1.90, and 3.8 mg/kg). The body weight, colon length, disease activity index (DAI), and histological changes of colonic tissue were measured. In addition, the expressions of pro-inflammatory cytokines were detected by using the enzyme-linked immunosorbent assay. Pathways involved in the intestinal inflammation were targeted by RNA-sequencing. Moreover, the changes of gut microbial diversity and composition were analyzed by the 16SrNA analysis and the contents of short-chain fatty acids (SCFAs) were detected by GC-MS. The results revealed that XSP intervention greatly restored the weight loss and colonic shortening (p < 0.05) and reduced the raised DAI scores, myeloperoxidase, and nitric oxide activities in UC in rats (p < 0.05). XSP administration also downregulated the protein levels of pro-inflammatory factors IL-1ß, IL-6, and TNF-α. Notably, it was found that XSP considerably suppressed the activation of the MAPK signaling pathway. In addition, XSP treatment improved the balance of gut microbiota that was disturbed by DSS. The beneficial bacteria Lachnospiraceae_NK4A136 group and Lactobacillus at the genus level significantly increased in the XSP group, which had decreased with the use of DSS (p < 0.05). Pathogenic bacteria including Escherichia-Shigella and Bacteroides in UC in rats were reduced by XSP intervention. Furthermore, XSP significantly elevated the production of SCFAs in UC in rats (p < 0.05). These alterations in inflammatory status were accompanied with changes in gut microbiota diversity and SCFA production. In conclusion, XSP exhibited protective effects against DSS-induced UC in rats. XSP treatment decreased inflammation via modulation of gut microbiota composition and SCFA production.

Valve-Like Outflow System Behavior With Motion Slowing in Glaucoma Eyes: Findings Using a Minimally Invasive Glaucoma Surgery-MIGS-Like Platform and Optical Coherence Tomography Imaging.

Purpose: This study aimed to investigate anatomic relationships and biomechanics of pressure-dependent trabecular meshwork and distal valve-like structure deformation in normal and glaucoma eyes using high-resolution optical coherence tomography (HR-OCT). Methods: We controlled Schlemm's canal (SC) pressure during imaging with HR-OCT in segments of three normal (NL) and five glaucomatous (GL) ex vivo eyes. The dissected limbal wedges were studied from 15 locations (5 NL and 10 GL). A minimally invasive glaucoma surgery (MIGS)-like cannula was inserted into the SC lumen, whereas the other end was attached to a switch between two reservoirs, one at 0, the other at 30 mm Hg. A steady-state pressure of 30 mm Hg was maintained to dilate SC and collector channels (CC) during 3D volume imaging. The resulting 3D lumen surface relationships were correlated with internal structural features using an image mask that excluded tissues surrounding SC and CC. While imaging with HR-OCT, real-time motion responses in SC and CC areas were captured by switching pressure from 0 to 30 or 30 to 0 mm Hg. NL vs. GL motion differences were compared. Results: Lumen surface and internal relationships were successfully imaged. We identified SC inlet and outlet valve-like structures. In NL and GL, the mean SC areas measured at the steady-state of 0 and 30 mm Hg were each significantly different (p < 0.0001). Synchronous changes in SC and CC lumen areas occurred in <200 ms. Measured SC area differences at the steady-state 0 and 30 mmHg, respectively, were larger in NL than GL eyes (p < 0.0001). The SC motion curves rose significantly more slowly in GL than NL (p < 0.001). Pressure waves traveled from the cannula end along the SC lumen to CC and deep intrascleral channels. Conclusion: HR-OCT provided simultaneous measurements of outflow pathway lumen surfaces, internal structures, and biomechanics of real-time pressure-dependent dimension changes. We identified SC inlet and outlet valve-like structures. GL tissues underwent less motion and responded more slowly than NL, consistent with increased tissue stiffness. A MIGS-like shunt to SC permitted pulse waves to travel distally along SC lumen and into CC.

Mitigating the effects of choroidal hyper- and hypo-transmission defects on choroidal vascularity index assessments using optical coherence tomography.

Background: Changes in choroidal vascularity index (CVI) are associated with multiple choroid-related ocular diseases. CVI is calculated as the area/volume ratio of vessels in the choroid, which could be affected by alterations in regional signal intensities due to hypo-transmission defects (hypoTDs) caused by drusen and retinal pigment epithelium (RPE) detachments, and hyper-transmission defects (hyperTDs) caused by the absence of RPE. To develop a simulation model to verify the CVI assessments in eyes with hyper/hypoTDs and demonstrate that accurate CVIs can be achieved after attenuation correction on swept-source optical coherence tomography (SS-OCT). Methods: A simulation model was developed on 6×6 mm macular scans from normal subjects. Signal intensity in a cylindrical region below RPE was altered to mimic hyper/hypoTDs. CVIs were compared inside and outside the simulated regions before and after attenuation correction. CVI assessments of OCT scans from patients with hyperTDs due to geographic atrophy (GA) and from patients with hypoTDs due to drusen that subsequently resolved with the disappearance of the hypoTDs were compared with and without attenuation correction. Results: Ten normal eyes were recruited to generate the hyper/hypoTD simulation model. In eyes with hypoTDs, CVIs were overestimated, and in eyes with hyperTDs, the CVIs were underestimated (P<0.001). After attenuation correction, the uneven distribution of signal intensity was eliminated and the resulting CVI showed no significant difference compared with the 'ground truth', which is measured from the original scans. Attenuation correction successfully eliminated the influence of hyperTDs caused by GA on CVI measurements (n=38). Quantitatively, no significant difference was found in the CVIs of eyes before and after drusen collapse with attenuation correction (n=8). Conclusions: The simulation model could reveal the impact of hypo/hyperTDs on CVI quantification in eyes with choroid-involved ocular diseases. The importance of attenuation correction to ensure accuracy in choroidal vessel segmentation was demonstrated by analyzing eyes with GA or drusen.

Interocular asymmetry of choroidal thickness and vascularity index measurements in normal eyes assessed by swept-source optical coherence tomography.

BACKGROUND: To investigate the symmetry of interocular choroidal thickness and vascularity index measurements in normal eyes using swept-source optical coherence tomography (SS-OCT). Cross-sectional and observational study. This study included 244 eyes of 122 normal adults with ages uniformly distributed from 19 to 89 years. METHODS: SS-OCT imaging was performed using a scanning pattern of 12×12 mm. Mean choroidal thickness (MCT) and choroidal vascularity index (CVI) measurements in the entire scanning region were obtained using a validated and published automatic method. The correlation and differences (including signed and absolute differences) between bilateral MCT and CVI measurements were analyzed at the following 6 regions: 3 concentric circles centered on the fovea with diameters of 2.5, 5, and 11 mm; the inner rim from 2.5 to 5 mm circle; the outer rim from 5 to 11 mm circle; and the entire 12×12-mm scan region, respectively. Comparison of interocular MCT and CVI measurements. RESULTS: MCT measurements in right and left eyes were strongly correlated in all regions [all intraclass correlation (ICC) >0.73], but MCT measurements in right eyes were significantly thicker than in left eyes. CVI measurements in right and left eyes were moderately correlated in all regions (all ICC >0.46), but CVI measurements in right eyes were significantly smaller than that in left eyes in the macular subregions (2.5 mm circle, 5 mm circle, and the inner rim). Neither signed nor absolute interocular differences in MCT were correlated with corresponding CVI interocular differences. CONCLUSIONS: Choroidal differences exist between normal fellow eyes in adults in the absence of obvious pathology. This study is useful in assisting clinicians and researchers in distinguishing asymmetric changes that are to be expected in normal eyes versus changes that could be associated with diseases.

LONGITUDINAL ANALYSIS OF DIABETIC CHOROIDOPATHY IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION USING WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Widefield swept-source optical coherence tomography (OCT) imaging was used to characterize choroidal thickness and vascularity at baseline in proliferative diabetic retinopathy (PDR) and longitudinally after panretinal photocoagulation (PRP). METHODS: Patients with treatment-naive PDR were imaged at baseline and at 1 week, 1 month, and 3 months after PRP. Previously validated algorithms were used to calculate the mean choroidal thickness (MCT) and choroidal vascularity index (CVI) in 5 regions of 12 mm × 12 mm scans. RESULTS: Fourteen PDR eyes were included. Baseline MCT in PDR eyes did not differ significantly from normal eyes, but CVI measurements in PDR eyes were lower in all regions (P < 0.001-0.008). After PRP, MCT measurements in PDR eyes were significantly lower at 1 month and 3 months in all regions (P < 0.001-0.005) except the fovea (P = 0.074). However, CVI measurements did not change over time in any region after PRP. CONCLUSION: The choroid in PDR eyes has a smaller CVI than that in normal eyes. After PRP, the choroidal thickness decreases outside the fovea, but the CVI remains constant, which suggests that a relative decrease in choroidal vascularity persists. These widefield swept-source OCT results are consistent with choroidal alterations found in histopathological reports of diabetic choroidopathy.

LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

In the course of our studies aiming to discover vascular bed-specific endothelial cell (EC) mitogens, we identified leukemia inhibitory factor (LIF) as a mitogen for bovine choroidal EC (BCE), although LIF has been mainly characterized as an EC growth inhibitor and an anti-angiogenic molecule. LIF stimulated growth of BCE while it inhibited, as previously reported, bovine aortic EC (BAE) growth. The JAK-STAT3 pathway mediated LIF actions in both BCE and BAE cells, but a caspase-independent proapoptotic signal mediated by cathepsins was triggered in BAE but not in BCE. LIF administration directly promoted activation of STAT3 and increased blood vessel density in mouse eyes. LIF also had protective effects on the choriocapillaris in a model of oxidative retinal injury. Analysis of available single-cell transcriptomic datasets shows strong expression of the specific LIF receptor in mouse and human choroidal EC. Our data suggest that LIF administration may be an innovative approach to prevent atrophy associated with AMD, through protection of the choriocapillaris.

Choroidal Changes in Eyes With Polypoidal Choroidal Vasculopathy After Anti-VEGF Therapy Imaged With Swept-Source OCT Angiography.

Purpose: Swept-source optical coherence tomography angiography was used to investigate choroidal changes and their association with pigment epithelial detachments (PEDs) in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors. Methods: Patients with treatment-naïve PCV were included and underwent anti-VEGF therapy. Mean choroidal thickness (MCT), choroidal vascularity index (CVI), and PED volume measurements were obtained before and after treatment. Results: Thirty-four treatment-naïve PCV eyes from 33 patients were included. The PED volume decreased after treatment (P < 0.05). The MCT decreased from 223.0 ± 79.6 µm at baseline to 210.9 ± 76.2 µm after treatment (P < 0.001). The CVI at baseline was 0.599 ± 0.024, and the CVI after treatment was 0.602 ± 0.023 (P = 0.16). There was a correlation between the decreased PED volumes and the decreased MCT measurements (r = 0.47; P = 0.006). Also, there was a correlation between the decreased PED volumes and the increased CVI measurements (r = -0.63; P < 0.001). Conclusions: In treatment-naïve eyes with PCV, the decreases in PED volumes were correlated with the decrease in MCT and the increase in CVI measurements. We propose that, at baseline, the PCV lesions serve as high-volume arteriovenous shunts between choroidal arterial and venous circulation, causing transudation into the choroidal stroma. We propose that, after treatment, the blood flow through the vascular shunt is reduced, the excess stromal transudation is resorbed, and the exudation from the neovascular lesion is reduced, resulting in thinning of the choroid, resolution of the PEDs, and an increase in the CVI due to the resorption of excess choroidal transudation.