Extracellular fluid excess linked to reduced choroidal vascularity index in patients with chronic kidney disease.

Extracellular fluid (ECF) excess is common in patients with chronic kidney disease (CKD). This study (involving 284 patients with CKD) explored the association between choroidal vascularity index (CVI) and ECF excess. We categorised patients into three groups based on extracellular water/total body water: normal, mildly overhydrated, and severely overhydrated. The more severe ECF status was associated with a lower CVI after adjustment (B = - 0.902, p = 0.001). In non-diabetic patients, both vascular luminal (LA, p < 0.001) and stromal areas (SA, p = 0.003) were significantly reduced in patients with severe ECF excess compared to others, whereas diabetic patients showed no significant differences in LA (p = 0.96) and SA (p = 0.86) based on ECF excess status. These findings suggest that ECF status may influence CVI in patients with CKD, underscoring the need for further research to clarify its direct impact on choroidal changes.

Swept-source optical coherence tomography and swept-source optical coherence tomography angiography findings in circumscribed choroidal hemangioma before and after transpupillary thermotherapy.

PURPOSE: To investigate the swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA) findings in circumscribed choroidal hemangioma (CCH) before and after treatment with transpupillary thermotherapy (TTT). METHODS: The clinical records of 21 eyes having CCH imaged with SS-OCT/SS-OCTA between September 2018 and December 2022 were evaluated. RESULTS: SS-OCT examination in CCH showed dome-shaped appearance (100%), choroidal shadowing (100%), expansion of choroidal structures (100%), subretinal fluid (66.7%), intraretinal edema/schisis (33.3%), retinal pigment epithelium (RPE) atrophy (19.0%), hyperreflective dots (19.0%), and epiretinal membrane (4.8%). Internal arborizing tumor vessels showing hyperreflectivity were observed in the choriocapillaris slab on SS-OCTA in all eyes. In the deep capillary plexus (DCP), flow void changes were seen in 7 eyes with intraretinal schisis/cystoid macular edema. Four CCHs > 2 mm in thickness showed outer retinal involvement due to unmasking of flow in intratumoral vessels related to RPE atrophy. Following TTT/indocyanine green-enhanced TTT (ICG-TTT) of CCH, SS-OCT findings included total/partial resolution of subretinal fluid (57.1%), complete/partial regression of the tumor (52.4%), and RPE atrophy (33.3%). After treatment; loss of choriocapillaris, decrease in tumor vascularity together with increase in the fibrous component and flow void areas were detected on SS-OCTA. CONCLUSIONS: SS-OCT/SS-OCTA are useful non-invasive tools for imaging the structural/vascular changes in CCHs managed with TTT or ICG-TTT. On SS-OCTA, hyporeflective spaces localizing to edema/schisis in the DCP and arborizing tumor vessels within a hyporeflective stromal background in the choriocapillaris slab were observed. After TTT/ICG-TTT, a decrease in tumor vessels and an increase in the fibrous component and flow-void areas inside the CCH were detected on SS-OCTA.

Assessment of retinal and choroidal microvasculature in night shift medical workers by OCT angiography.

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.

Choroidalyzer: An Open-Source, End-to-End Pipeline for Choroidal Analysis in Optical Coherence Tomography.

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.

Observation of structural and vascular features of retina and choroid in myopia using ultra-widefield SS-OCTA.

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.

Diurnal Variation in Choroidal Parameters Among Healthy Subjects Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to evaluate the diurnal variation in choroidal parameters in a wide field area among healthy subjects and to identify correlations between choroidal luminal area and stromal area and various systemic factors. Methods: In this cross-sectional study, 42 eyes from 21 healthy participants (mean age = 32.4 ± 8.8 years) were examined using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA, 24 mm × 20 mm). Measurements of choroidal parameters, including choroidal volume (CV), choroidal thickness (CT), choroidal vessel volume (CVV), and choroidal stromal volume (CSV), were taken at 8:00, 12:00, 18:00, and 22:00. Systemic factors, such as blood pressure and heart rate, were concurrently monitored. Results: Our study observed significant diurnal variations in the mean total CV, CT, CVV, and CSV, with minimum measurements around 12:00 (P < 0.001) and peak values at 22:00 (P < 0.001). Furthermore, changes in CV in specific regions were more closely associated with fluctuations in CVV than CSV in the same regions. No significant diurnal variations were found in systolic (P = 0.137) or diastolic blood pressure (P = 0.236), whereas significant variations were observed in the heart rate (P = 0.001). Conclusions: Our study reveals diurnal variations in choroidal parameters and their associations, emphasizing that changes in choroidal volume relate more to the luminal than the stromal area in vessel-rich regions. This enhances our understanding of choroidal-related ocular diseases. Translational Relevance: Regions with higher choroidal vasculature observed greater choroidal volume changes.

Correlation between vessel density and thickness in the retina and choroid of severe non-proliferative diabetic retinopathy patients.

Objectives: To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). Methods: We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. Results: The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Conclusions: Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.

Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

Choroidal Layer Analysis in OCT images via Ambiguous Boundary-aware Attention.

Optical Coherence Tomography (OCT) is a commonly used retina imaging technique, and it is capable of revealing the morphology of the choroid. However, the segmentation and quantitative analysis of the sublayers and vessels in choroid are rarely explored, primarily due to the indistinct boundaries of choroidal sublayers, and imbalanced distribution of vessels observed in OCT imagery. In this paper, we propose a novel two-stage architecture called Choroidal Layer Analysis network (CLA), that may be considered the first attempt in this research community for joint segmentation of choroidal sublayers and choroidal vessels in OCT images. CLA employs the encoder-decoder network with the residual U-shape module as the backbone. In order to empower the ability of the segmentation model to identify the inconspicuous boundaries of choroidal sublayers, we introduce an Ambiguous Boundary Attention block (ABA) into the bottleneck of the encoder-decoder network in the first stage. For more accurate segmentation of large choroidal vessels with ambiguous contours and imbalanced spatial distribution, the second stage introduces an active contour-based loss to refine the contours of choroidal vessels simultaneously with precise identification of each vessel via contextual modeling. To train, test and validate the proposed model, we conducted a choroidal segmentation dataset containing 800 OCT images, with their sublayers and large choroidal vessels manually annotated. Experimental results demonstrate the superiority of the proposed approach compared with other state-of-the-art segmentation networks in large margins. It is worth noting that we also reconstructed the large choroidal vessels in three-dimensional (3D) based on the segmentation results, and multiple 3D morphological parameters were calculated. The statistical analysis of these parameters demonstrates significant differences between the healthy control and high myopia group, and this further confirms the proposed work may facilitate subsequent disease understanding and clinical decision-making.

Quantitative assessment of choroidal parameters and retinal thickness in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography: a cross-sectional study.

OBJECTIVE: In this study, we used ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA) to assess changes in retinal thickness (RT) and choroidal parameters in individuals who had received a diagnosis of central serous chorioretinopathy (CSC). METHODS: The study encompassed the evaluation of 59 eyes from 47 patients with a diagnosis of CSC, alongside 33 fellow eyes and 31 eyes from healthy individuals (controls). The parameters assessed included RT, choroidal thickness (CT), choriocapillaris density, vascular density of the large choroidal vessel layer, three-dimensional choroidal vascularity index (3D-CVI), choroidal vessel volume per unit area (mCVV/a), and choroidal stroma volume per unit area (mCSV/a). RESULTS: Metrics including mCVV/a, mCSV/a, 3D-CVI, CT, and RT exhibited significantly elevated values in the eyes affected by CSC compared to those of the control group across nine subfields. Moreover, a substantial number of the subfields in both CSC-affected and fellow eyes exhibited increased values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT when compared with the control group. Additionally, acute and chronic CSC subfields demonstrated significantly elevated values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT in comparison to healthy control eyes. Notably, specific subfields associated with complex and atypical forms of CSC revealed higher metrics compared to those of the control group. CONCLUSION: In conclusion, the UWF SS-OCTA proved to be a valuable tool for exploring the anatomical etiology and clinical classification and diagnosis of CSC.

Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study.

BACKGROUND: Although choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis. METHODS: This retrospective case-control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated. RESULTS: Compared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness. CONCLUSION: Total and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

Association between the arm-to-choroidal circulation time and clinical profile in patients with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the association between the arm-to-choroidal circulation time (ACT) on indocyanine green angiography (IA) and clinical profile in patients with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Single-center retrospective study. METHODS: We included 38 eyes of 38 patients with PCV diagnosed using multimodal imaging and did not undergo previous treatment. All patients were treated with monthly aflibercept injections for 3 months and treat-and-extend regimens for the subsequent 12 months. Posterior vortex vein ACT was assessed on the first visit using Heidelberg IA. The patients were divided into two groups: ACT ≥20 s (L group; eight eyes) and ACT <20 s (S group; 30 eyes). The clinical profiles before and after treatment were analyzed to assess associations with ACT. RESULTS: The mean ACT was 16.39±3.3 s (L group: 21.25±1.49 s, women:men=2:6, mean age: 77.3±6.5 years; S group: 15.10±2.17 s, women:men=7:23, mean age: 75.5±6.9 years). No significant difference was observed in the mean subfoveal choroidal thickness between the L and the S groups (176±75 µm vs. 230±79 µm, P=0.10). However, there were significant differences between the L and S groups in retinal fluid accumulation and hemorrhage recurrence (eight/eight eyes, 100% vs. 13/30 eyes, 43%, P<0.001), mean aflibercept injections (8.8±1.6 vs. 7.0±1.6, P<0.01) during the 12-month period, and the number of polypoidal lesions (1.8±0.7 vs. 1.3±0.5, P<0.05). CONCLUSION: Patients with PCV and ACT >20 s are more likely to experience exudative change recurrence in the retina during treatment because they have more polypoidal lesions.

Quantitative assessment of retinochoroidal microvasculature in patients with carotid artery stenosis using OCT angiography.

PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.

Choroidal macrovascular and capillary alterations in eyes with idiopathic epiretinal membranes.

PURPOSE: To evaluate the choroidal vascular alterations and effect of surgical treatment in the setting of idiopathic epiretinal membranes. METHODS: The structure of the choroid was studied in 33 patients with unilateral idiopathic epiretinal membrane using optical coherence tomography with enhanced depth imaging and optical coherence tomography angiography. Eyes with epiretinal membrane underwent 25-gauge vitrectomy with epiretinal membrane and internal limiting membrane peeling. The choroidal vascularity index, Haller layer/choroidal thickness ratio, and choriocapillaris flow density were used to evaluate changes in choroidal structure after surgery and compare with the healthy fellow eyes. RESULTS: The choroidal vascularity index and Haller layer/choroidal thickness ratio of the eyes with epiretinal membrane were higher than those of the fellow eyes at baseline (p=0.009 and p=0.04, respectively) and decreased postoperatively compared with preoperative values (p=0.009 and p=0.001, respectively). The choriocapillaris flow of eyes with epiretinal membrane was lower than that of the fellow eyes at baseline (p=0.001) and increased after surgery compared with the preoperative value (p=0.04). The choroidal vascularity index, Haller layer/choroidal thickness ratio, and choriocapillaris flow values of the healthy fellow eyes were comparable at baseline and final visit. In eyes with epiretinal membrane, the final choroidal vascularity index correlated with the final choriocapillaris flow (r=-0.749, p=0.008) in the multivariate analysis. CONCLUSION: Idiopathic epiretinal membrane appears to affect the choroidal structure with increased choroidal vascularity index and Haller layer/ choroidal thickness ratio and decreased choriocapillaris flow. These macrovascular (choroidal vascularity index and Haller layer/choroidal thickness) and microvascular (choriocapillaris flow) alterations appear to be relieved by surgical treatment of the epiretinal membranes.

The relationship between Choroidal Vascular Index and non-invasive ultrasonographic atherosclerosis predictors.

BACKGROUND: This study explores the intricate connections between choroidal vascular index (CVI) and non-invasive ultrasonographic atherosclerosis predictors, shedding light on the potential links between ocular vascular dynamics and systemic cardiovascular health. METHODS: We conducted a cross-sectional analysis of 81 participants, assessing CVI, intima-media thickness (IMT), extra-media thickness (EMT), and the PATIMA index. The presence of coronary artery disease (CAD) was also evaluated. Statistical methods included descriptive statistics, t-tests for group comparisons, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: Our findings revealed that patients with CAD had lower CVI values compared to those without CAD, underscoring a potential association between CVI and CAD. Significant negative correlations were observed between CVI and IMT, EMT, PATIMA, and CAD. ROC curve analysis identified optimal CVI cutoff values for hypertension and CAD detection, showcasing its potential as a diagnostic marker. DISCUSSION: Our results align with existing literature on ocular vascular changes, supporting the notion that CVI may be a promising indicator of systemic vascular conditions. The study contributes to the broader understanding of the relationships between ocular and cardiovascular health, providing a foundation for future research and clinical applications. CONCLUSION: The study suggests that CVI holds clinical relevance as a non-invasive marker for identifying systemic conditions, offering insights into the fields of neurology, physical therapy, and rehabilitation. Addressing its limitations, this research encourages further investigation into the multifaceted connections between CVI and atherosclerosis predictors.

Visual Outcome and Fluid Changes Between Eyes With Polypoidal Choroidal Vasculopathy Receiving Biosimilar CKD-701 or Reference Ranibizumab Therapy: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial.

PURPOSE: To compare the visual outcome and fluid features of a proposed biosimilar, CKD-701, versus the reference ranibizumab in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: This was a post hoc analysis of a phase 3 randomized clinical trial assessing the efficacy and safety of CKD-701 and ranibizumab. A total of 73 PCV eyes were assigned randomly to either CKD-701 (36 eyes) or ranibizumab (37 eyes). The mean changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) volume, and fluid features were compared. RESULTS: After three loading injections, the mean change in BCVA (letters) was +7.50 in the CKD-701 group and +6.32 in the ranibizumab group (p = .447). The changes in CRT and PED volume of the CKD-701 group (-107.25 ± 102.66 µm and -0.22 ± 0.46 mm3) were similar to those of the ranibizumab group (-96.78 ± 105.00 µm and -0.23 ± 0.54 mm3) (p = .668 and p = .943, respectively). Proportions of eyes with subretinal, intraretinal and sub-retinal pigment epithelium (RPE) fluids after three loading injections were not different between CKD-701 group (33.3%, 13.9% and 42.9%) and ranibizumab group (51.4%, 16.2% and 40.0%) (p = .071, p = 1.000 and p = .808). The visual and anatomical changes were similar between two groups at month 6 and 12 (all, p > .05). CONCLUSION: Biosimilar CKD-701 monotherapy resulted in comparable visual and anatomical changes to those achieved with reference ranibizumab in PCV eyes.

The structure and function of the human choroid.

In this manuscript, the structure of the human choroid is reviewed with emphasis of the macro- and microscopic anatomy including Bruch's membrane, choriocapillaris, Sattler's and Haller's layer, and the suprachoroid. We here discuss the development of the choroid, as well as the question of choroidal lymphatics, and further the neuronal control of this tissue, as well as the pathologic angiogenesis. Wherever possible, functional aspects of the various structures are included and reviewed.

The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina.

Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non-random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion-limited regions represent areas of reduced exchange with the outer retina. The width of diffusion-limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina. KEY POINTS: The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina. The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body. Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina. Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.

Qualitative and quantitative comparisons of type 1 macular neovascularizations between pachychoroid neovasculopathy and neovascular age-related macular degeneration using optical coherence tomography angiography.

OBJECTIVES: To compare qualitative and quantitative features of type 1 macular neovascularizations (MNV) in pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD). METHODS: Forty-three treatment-naive eyes of 41 PNV patients and 40 treatment-naive eyes of 38 patients with nAMD were included. The patients were classified as PNV or nAMD according to the presence of pachychoroid features and soft/reticular drusen. Presence of central trunk and maturity of the MNV were evaluated on optical coherence tomography angiography (OCTA) images. MNV area, vessel density (VD), total vessel length (VL), number of intersection points (IPs), fractal dimension (FD), and lacunarity (LAC) were calculated using ImageJ software and FracLac plugin. RESULTS: The mean age was 56.8 ± 8.7 years in PNV and 70.4 ± 8.8 years in neovascular AMD groups (p < 0.001). Compared to nAMD, the presence of central trunk was less frequent in PNV (48.8% vs 77.5%, p = 0.007). Immature MNV pattern was observed more frequently in PNV eyes than nAMD (41.9% vs 20.0%, p = 0.009). PNV cases had significantly lower median MNV area [0.913(1.115) vs 2.542(3.273) mm²], total VL [14.84 (20.46) vs 36.34 (44.68) mm], number of IPs [104(140) vs 335(417.3)], and FD [1.56(0.10) vs 1.59(0.11)] comparing to nAMD cases (p < 0.001, p = 0.001, p < 0.001, p = 0.043 respectively). However, the mean VD (42.4 ± 6.8 vs 42.9 ± 9.0%) and the median LAC values [0.42 (0.09) vs 0.42 (0.09)] did not differ significantly between groups (p = 0.776, p = 0.526, respectively). CONCLUSION: Morphological and quantitative differences exist in type 1 neovascular lesions. Type 1 MNVs in the PNV group are characterized by a smaller and less complex structure.

Vascular changes of the choroid and their correlations with visual acuity in diabetic retinopathy.

Objective: To investigate changes in the choroidal vasculature and their correlations with visual acuity in diabetic retinopathy (DR). Methods: The cohort was composed of 225 eyes from 225 subjects, including 60 eyes from 60 subjects with healthy control, 55 eyes from 55 subjects without DR, 46 eyes from 46 subjects with nonproliferative diabetic retinopathy (NPDR), 21 eyes from 21 subjects with proliferative diabetic retinopathy (PDR), and 43 eyes from 43 subjects with clinically significant macular edema (CSME). Swept-source optical coherence tomography (SS-OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of region centered on the macular fovea were analyzed. Initially, a custom deep learning algorithm based on a modified residual U-Net architecture was utilized for choroidal boundary segmentation. Subsequently, the SS-OCT image was binarized and the Niblack-based automatic local threshold algorithm was employed to calibrate subfoveal choroidal thickness (SFCT), luminal area (LA), and stromal area (SA) by determining the distance between the two boundaries. Finally, the ratio of LA and total choroidal area (SA + LA) was defined as the choroidal vascularity index (CVI). The choroidal parameters in five groups were compared, and correlations of the choroidal parameters with age, gender, duration of diabetes mellitus (DM), glycated hemoglobin (HbA1c), fasting blood sugar, SFCT and best-corrected visual acuity (BCVA) were analyzed. Results: The CVI, SFCT, LA, and SA values of patients with DR were found to be significantly lower compared to both healthy patients and patients without DR (P < 0.05). The SFCT was significantly higher in NPDR group compared to the No DR group (P < 0.001). Additionally, the SFCT was lower in the PDR group compared to the NPDR group (P = 0.014). Furthermore, there was a gradual decrease in CVI with progression of diabetic retinopathy, reaching its lowest value in the PDR group. However, the CVI of the CSME group exhibited a marginally closer proximity to that of the NPDR group. The multivariate regression analysis revealed a positive correlation between CVI and the duration of DM as well as LA (P < 0.05). The results of both univariate and multivariate regression analyses demonstrated a significant positive correlation between CVI and BCVA (P = 0.003). Conclusion: Choroidal vascular alterations, especially decreased CVI, occurred in patients with DR. The CVI decreased with duration of DM and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of DR.