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Objective: Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder that affects the frontal and temporal lobes of the brain, leading to cognitive decline and personality changes. The objective of this cross-sectional study was to characterize angioarchitectural changes in the retina and choroid of individuals with FTD compared to cognitively normal controls using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: Cross-sectional comparison of patients with FTD and controls with normal cognition. All participants underwent Mini-Mental State Examination (MMSE) at the time of imaging. Outcome measures included OCT parameters: retinal nerve fiber layer (RNFL) thickness, ganglion cell layer-inner plexiform layer (GC-IPL) thickness, central subfield thickness (CST), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI); and OCTA superficial capillary plexus parameters: foveal avascular zone (FAZ) area, 3x3mm and 6x6mm macular perfusion density (PD) and vessel density (VD), 4.5x4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equation analysis was used to account for the inclusion of 2 eyes from the same participant. Results: 29 eyes of 19 patients with FTD and 85 eyes of 48 controls were analyzed. In FTD, 3x3mm macular PD (p = 0.02) and VD (p = 0.02) and CFI (p = 0.01) were reduced compared to controls. There was no difference in average 4.5x4.5mm CPD, RNFL thickness, GC-IPL thickness, CST, SFCT, CVI, FAZ, or 6x6mm VD or PD between FTD and controls (all p > 0.05); however, there was a trend toward lower macular 6x6mm PD and VD in patients with FTD. Conclusion: Decline of peripapillary and macular OCT and OCTA parameters merit further investigation as potential biomarkers for FTD detection. Noninvasive retinal and choroidal imaging may hold promise for earlier detection, and future longitudinal studies will clarify their role in monitoring of FTD. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the differential gene expression of BMPs in chick retinal pigment epithelium (RPE) during recovery from short term exposure to optical defocus and form-deprivation (FD) treatments. Methods: 14-day old White-Leghorn chicks wore either monocular +10 or -10 D lenses, or diffusers for 2 or 48 h, after which eyes were allowed unobstructed vision for up to 96 h. Over this recovery period, refractive errors and choroidal thickness (ChT) were tracked using retinoscopy and high-frequency A-scan ultrasonography. Real-time PCR was used to examine the expression of BMP2, 4, and 7 genes in RPE samples collected 0, 15 min, 2, 24, 48, and 96 h after the termination of treatments. Expression levels in treated eyes and their contralateral control eyes were compared. Results: After the termination of the lens and diffuser treatments, eyes gradually recovered from induced shifts in refractive error. With all three treatments, ChT changes reached statistical significance after 48 h of treatment, be it thinning with the -10 D lens and diffuser treatments (-0.06 ± 0.03mm, p < 0.05; -0.11 ± 0.04 mm, p < 0.05, resp.), or thickening with the +10 D lens (0.31 ± 0.04 mm, p < 0.001). BMP2 gene expression was rapidly upregulated in eyes wearing the +10 D lens, being statistical significance after 2 h, as well as 48 h of treatment. With the 2 h treatment, the latter gene expression pattern persisted for 15 min into the recovery period, before decreasing to the same level as that of contralateral control eyes, with a short-lived rebound, i.e., upregulation, 24 h into the recovery period. With the longer, 48 h treatment, BMP2 gene expression decreased more gradually, from 739 ± 121% at the end of the treatment period, to 72 ± 14% after 48 h of recovery. Two and 48 h of both -10 D and FD treatments resulted in BMP2 gene expression downregulation, with the time taken for gene expression levels to fully recover varying with the duration of initial treatments. In both cases, BMP2 gene expression downregulation persisted for 15 min into the recovery period, but reversed to upregulation by 2 h. Similar gene expression patterns were also observed for BMP4, although the changes were smaller. Conclusions: The observed changes in BMP gene expression in chick RPE imply dynamic, albeit complex regulation, with the duration of exposure and recovery being critical variables for all three types of visual manipulations. This study provides further evidence for a role of the RPE as an important signal relay linking the retina to the choroid and sclera in eye growth regulation. [ABSTRACT FROM AUTHOR]

Objective: To investigate choroidal features of idiopathic macular hole (IMH) and determine their relationship with surgical outcomes. Materials and methods: Patients above stage II unilateral IMH who received pars plana vitrectomy (PPV) with the internal limiting membrane (ILM) peeling were enrolled for the retrospective observational study. Preoperative choriocapillaris perfusion (CCP), central choroidal thickness (CCT), base/minimum diameters (BD/MD) and height (HH) of MH were analyzed by optical coherence tomography angiography (OCTA). At 1, 3 and 6 months after PPV, CCT, central foveal thickness (CFT) and maximum parafoveal thickness (MPT) of closed MH were measured. Best-corrected visual acuity (BCVA) was assessed at every visit. The correlations between preoperative characteristics and surgical outcomes were assessed. Results: Twenty-seven patients were evaluated. All eyes (100%) showed successful MH closure after the primary surgery. Until postoperative 6 months, BCVA continued to improve significantly (p < 0.001), while CFT and CCT progressively thinned (p < 0.001, p < 0.001). On correlation tests, final postoperative BCVA was associated with preoperative BCVA (R = 0.506, p = 0.007) and CCP (R = -0.475, p = 0.012), while final CFT was related with preoperative CCT (R = 0.392, p = 0.043). Multiple regression analysis revealed that preoperative CCP was significantly related with final postoperative BCVA (β = -0.403, p = 0.049). Conclusion: Preoperative CCP and CCT were respectively associated with functional and anatomical prognosis of IMH after PPV. [ABSTRACT FROM AUTHOR]

The world-wide prevalence of myopia (nearsightedness) is increasing, but its pathogenesis is incompletely understood. Among many putative mechanisms, laboratory and clinical findings have implicated circadian biology in the etiology of myopia. Consistent with a circadian hypothesis, we recently reported a marked variability in diurnal patterns of gene expression in two crucial tissues controlling post-natal refractive development ‐ the retina and choroid–at the onset of form-deprivation myopia in chick, a widely studied and validated model. To extend these observations, we assayed gene expression by RNA-Seq in retina and choroid during the progression of established unilateral form-deprivation myopia of chick. We assayed gene expression every 4 hours during a single day from myopic and contralateral control eyes. Retinal and choroidal gene expression in myopic vs. control eyes during myopia progression differed strikingly at discrete times during the day. Very few differentially expressed genes occurred at more than one time in either tissue during progressing myopia. Similarly, Gene Set Enrichment Analysis pathways varied markedly by time during the day. Some of the differentially expressed genes in progressing myopia coincided with candidate genes for human myopia, but only partially corresponded with genes previously identified at myopia onset. Considering other laboratory findings and human genetics and epidemiology, these results further link circadian biology to the pathogenesis of myopia; but they also point to important mechanistic differences between the onset of myopia and the progression of established myopia. Future laboratory and clinical investigations should systematically incorporate circadian mechanisms in studying the etiology of myopia and in seeking more effective treatments to normalize eye growth in children. [ABSTRACT FROM AUTHOR]

The estimation of central choroidal thickness from colour fundus images can improve disease detection. We developed a deep learning method to estimate central choroidal thickness from colour fundus images at a single institution, using independent datasets from other institutions for validation. A total of 2,548 images from patients who underwent same-day optical coherence tomography examination and colour fundus imaging at the outpatient clinic of Jichi Medical University Hospital were retrospectively analysed. For validation, 393 images from three institutions were used. Patients with signs of subretinal haemorrhage, central serous detachment, retinal pigment epithelial detachment, and/or macular oedema were excluded. All other fundus photographs with a visible pigment epithelium were included. The main outcome measure was the standard deviation of 10-fold cross-validation. Validation was performed using the original algorithm and the algorithm after learning based on images from all institutions. The standard deviation of 10-fold cross-validation was 73 μm. The standard deviation for other institutions was reduced by re-learning. We describe the first application and validation of a deep learning approach for the estimation of central choroidal thickness from fundus images. This algorithm is expected to help graders judge choroidal thickening and thinning. [ABSTRACT FROM AUTHOR]

Objective: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). Methods: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. Results: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. Conclusions: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD. [ABSTRACT FROM AUTHOR]

Stress is a risk factor for central serous chorioretinopathy (CSC), but a suitable biomarker of this stress has not been identified. We aimed to evaluate alpha-klotho (αKl) as a potential biomarker of CSC. The circulating concentrations of αKl in patients diagnosed with acute or chronic CSC and treated at Hyogo College of Medicine between December 2019 and July 2021 were retrospectively compared with those of healthy individuals. We also compared the αKl concentrations of patients with acute or chronic CSC. Furthermore, we evaluated the relationships of age, sex, smoking status, and subfoveal choroidal thickness (SFCT) with αKl concentration. Patients in whom subretinal fluid reaccumulated in the same eye after its resolution were defined as having recurrent CSC. We studied 56 patients (46 men and 10 women) and 27 healthy controls (19 men and 8 women); and 38 and 18 eyes with acute and chronic CSC, respectively. The mean circulating concentration of αKl was higher in patients with CSC than in controls (827±232 and 724±183 pg/mL, respectively; p = 0.035). The mean SFCT was greater in patients with CSC than in controls (416±91.0 and 278±96.3 μm, respectively; p<0.0001). The mean αKl concentration was significantly higher in the patients with acute CSC than in those with chronic CSC (898±221 and 740±224 pg/mL, respectively; p = 0.038). Recurrence of CSC occurred in 10 of 56 (17.9%) eyes, of which five eyes were in the acute CSC group and five were in the chronic CSC group. Patients who experienced recurrence had significantly higher αKI concentrations than those who did not (p = 0.0219). There were no significant relationships of αKl concentration with age, sex, smoking history, or SFCT. In summary, the circulating αKI concentrations of patients with CSC are high, which suggests that αKI may be an indicator of stress in such patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate variation in reflectivity of choroidal layers in normal eyes. Methods: From the swept-source optical coherence tomography database, we retrospectively included eyes with a normal fundus. Choroidal reflectivity was measured on the horizontal and vertical B-scan optical coherence tomography images. The optical barrier of the choroid was defined as the first hill in the middle of the reflectance graph from the retinal pigment epithelium-Bruch's membrane complex to the chorioscleral junction. Results: The optical barrier of the choroid was identified in 91 eyes of 91 individuals. The amplitude of peak reflectivity of the optical barrier of the choroid at macular center (142.85 ± 15.04) was greater than those in superior (136.12 ± 14.08) or inferior macula (135.30 ± 16.13) (P = 0.028, P = 0.008, respectively). Latency between the peak of the retinal pigment epithelium-Bruch's membrane complex and the optical barrier of the choroid at macular center (48.11 ± 13.78 μm) was shorter than those in nasal macula (55.58 ± 19.21 μm) (P = 0.021). The amplitude of the peak reflectivity of the optical barrier of the choroid in the center negatively correlated with the latency between the retinal pigment epithelium-Bruch's membrane complex and the optical barrier of the choroid (P < 0.001). Conclusion: An optical barrier exists in the inner choroid of the normal eye. Its depth depends on the location within the macula. Further studies are mandatory to evaluate variations in the barrier in the eyes with chorioretinal disease. [ABSTRACT FROM AUTHOR]

PurposeMitochondrial (mt) DNA damage is associated with age-related macular degeneration (AMD) and other human aging diseases. This study was designed to quantify and characterize mtDNA low-frequency heteroplasmy single nucleotide polymorphisms (SNPs) of three different tissues isolated from AMD subjects using Next Generation Sequencing (NGS) technology.MethodsDNA was extracted from neural retina, [RPE+choroid] and blood from three deceased age-related macular degeneration (AMD) subjects. Entire mitochondrial genomes were analyzed for low-frequency heteroplasmy SNPs using NGS technology that independently sequenced both mtDNA strands. This deep sequencing method (average sequencing depth of 30,000; range 1,000-100,000) can accurately differentiate low-frequency heteroplasmy SNPs from DNA modification artifacts. Twenty-three 'hot-spot' heteroplasmy mtDNA SNPs were analyzed in 222 additional blood samples.ResultsGermline homoplasmy SNPs that defined mtDNA haplogroups were consistent in the three tissues of each subject. Analyses of SNPs with T, m.1284T>C, m.1556C>T, m.7256C>T) were found in additional samples (n = 222). Five heteroplasmy SNPs (m.4104A>G, m.5320C>T, m.5471G>A, m.5474A>G, m.5498A>G) declined with age. Two heteroplasmy SNPs (m.13095T>C, m.13105A>G) increased in AMD compared to Normal samples. In the heteroplasmy SNPs, very few transversion mutations (purine to pyrimidine or vice versa, associated with oxidative damage) were found and the majority were transition changes (purine to purine or pyrimidine to pyrimidine, associated with replication errors).ConclusionWithin an individual, the blood, retina and [RPE+choroid] contained identical homoplasmy SNPs representing inherited germline mtDNA haplogroup. NGS methodology showed significantly more mtDNA heteroplasmy SNPs in blood compared to retina and [RPE+choroid], suggesting the latter tissues have substantial protection. Significantly higher heteroplasmy levels of m.13095T>C and m.13105A>G may represent potential AMD biomarkers. Finally, high levels of transition mutations suggest that accumulation of heteroplasmic SNPs may occur through replication errors rather than oxidative damage.

Purpose: To evaluate the choroidal vascularity index (CVI) in different types of central serous chorioretinopathy (CSC), healthy control eyes, and fellow eyes. Methods: Relevant studies published up to January 2023 were identified by searching multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). Studies investigating the difference in CVI between CSC and control eyes were included. Data from these studies were analyzed using Stata (version 17) software. Weighted mean difference (WMD) and 95% confidence interval (95%CI) were calculated for the CVI in CSC eyes, control eyes, and fellow eyes. Results: The meta-analysis included 15 studies, with 213 acute CSC eyes, 153 chronic CSC eyes, 92 uncategorized CSC eyes, 40 resolved CSC eyes, 409 eyes of normal healthy controls, and 318 fellow eyes. The result revealed that CVI was higher in acute CSC eyes (WMD = 5.40, 95%CI = 2.36–8.44, P = 0.001) compared to control eyes. Also, CVI in chronic CSC eyes was higher than in control eyes (WMD = 1.26, 95%CI = 0.03–2.49, p = 0.046). The fellow eyes of acute CSC had a higher CVI when compared to control eyes (WMD = 2.53, 95%CI = 0.78–4.28, p = 0.005). There was no significant difference in CVI between acute and chronic CSC eyes (WMD = 0.75, 95%CI = -0.31–1.82, P = 0.167). In the sub-analysis based on the area selected for CVI calculation, the WMDs in the whole image subgroups were lower than the main analysis for the comparisons of fellow eyes of acute CSC and control eyes, acute CSC eyes and control eyes, and acute CSC eyes and fellow eyes. In the macular area subgroups, the WMDs were higher than in the whole image subgroups, suggesting a potential regional variation of CVI in CSC eyes. Conclusions: The results demonstrated that CVI is increased in CSC eyes and fellow eyes of acute CSC. There is no significant difference in CVI between acute and chronic CSC eyes. The area selected for CVI calculation can influence the outcome, which requires further clinical research to clarify. [ABSTRACT FROM AUTHOR]

Purpose: To compare the two-year outcome of half-time photodynamic therapy (htPDT) in chronic central serous chorioretinopathy (cCSC) with and without choroidal neovascularization (CNV). Methods: In this retrospective study, we included 88 eyes of 88 patients with cCSC who underwent htPDT and were followed up for more than 24 months. Patients were divided into two groups with (21 eyes) or without (67 eyes) CNV before htPDT treatment. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and the presence of subretinal fluid (SRF) were evaluated at baseline and at 1, 3, 6, 12, and 24 months after PDT. Results: A significant intergroup difference was noted in terms of age (P = 0.038). Significant improvements in the BCVA and SCT were found at all time points in eyes without CNV but only at 24 months in eyes with CNV. CRT was significantly reduced in both groups at all time points. No significant intergroup differences were noted in terms of BCVA, SCT and CRT at all time points. There were significant differences in the rate of recurrent and persistent SRF between groups (22.4% (without CNV) vs. 52.4% (with CNV), P = 0.013, and 26.9% (without CNV) vs. 57.1% (with CNV), P = 0.017, respectively). The presence of CNV was significantly associated with the recurrence and persistence of SRF after initial PDT (P = 0.007 and 0.028, respectively). Logistic regression analyses showed that the baseline BCVA, and not the presence of CNV, was significantly associated with BCVA at 24 months after initial PDT (P < 0.01). Conclusions: A htPDT for cCSC was less effective in eyes with CNV than in those without CNV regarding the recurrence and persistence of SRF. Additional treatment might be required in eyes with CNV during 24-month follow-up periods. [ABSTRACT FROM AUTHOR]

Purpose: Optical coherence tomography angiography (OCT-A) can visualize retinal capillary microcirculation non-invasively. In order to investigate potential factors influencing OCT-A diagnostics, the aim of the present study was to determine circadian changes in macular vessel density (VD) in healthy adults during office hours, considering axial length (AL) and subfoveal choroidal thickness (CT). Methods: In the prospective study 30 eyes of 30 healthy subjects (mean age 28.7 ± 11.8, range 19–60 years) were recruited who underwent repeated measurements of AL, subfoveal CT and three-layer macula VD (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) on a single day at three predetermined timepoints (9 AM, 3 PM, and 9 PM). For better intra- and interindividual scan comparability, the new Anatomic Positioning System function (APS, part of Glaucoma Module Premium Edition [GMPE], Heidelberg Engineering, Germany) allowing analysis of identical retinal areas, was used for quantitative OCT-A analysis. Results: Overall mean macula VD was unchanged during office hours in SVP, ICP and DCP, respectively (p>0.05). In addition, AL and CT showed no statistically significant changes over time (p>0.05). Rather, a large interindividual variance of VD with different peak time was observed. Contrary to the overall data, sectorial VD changed in dependency of office hours in all layers with an increase of VD in SVP between 9 AM and 9 PM (p = 0.003), in ICP between 3 PM and 9 PM (p = 0.000), in DCP between 9 AM and 9 PM (p = 0.048), and 3 PM and 9 PM (p = 0.000), respectively. Conclusion: Overall mean macula VD, subfoveal CT and AL tended not to show statistically significant changes over time in this cohort, whereas a regional analysis of VD did. Therefore, a circadian influence on capillary microcirculation should be kept in mind. Moreover, the results highlight the importance of a more detailed analysis of VD in different sectors and different vascular layers. In addition, the pattern of diurnal variation could vary inter-individually, thus a patient-specific fluctuation pattern would need to be considered when evaluating these parameters in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effect of photodynamic therapy (PDT) on the choroid of medial area from optic disc and factors correlated with treatment outcomes, we evaluated choroidal changes using ultra-widefield optical coherence tomography (UWF-OCT) after PDT for central serous chorioretinopathy (CSC). Methods: In this retrospective case-series, we included CSC patients who received a standard-dose of full-fluence PDT. UWF-OCT were examined at baseline and 3 months after treatment. We measured choroidal thickness (CT), classified into central, middle, and peripheral sectors. We examined CT changes after PDT by sectors and treatment outcome. Results: Twenty-two eyes of 21 patients (20 males; mean age 58.7 ± 12.3 years) were included. CT reduction after PDT was significant in all sectors, including peripheral areas: supratemporal, 330.5 ± 90.6 μm vs. 237.0 ± 53.2 μm; infratemporal, 240.0 ± 89.4 μm vs. 209.9 ± 55.1 μm; supranasal, 237.7 ± 59.8 vs 209.3 ± 69.3 μm; infranasal, 172.6 ± 47.2 μm vs. 155.1 ± 38.2 μm (P < 0.001, for all). In patients with retinal fluid resolution, despite no apparent difference in baseline CT, there was more significant reduction after PDT in supratemporal and supranasal peripheral sectors, compared with patients without resolution: supratemporal, 41.9 ± 30.3 μm vs. −1.6 ± 22.7 μm; supranasal, 24.7 ± 15.3 μm vs. 8.5 ± 3.6 μm (P < 0.019, for both). Conclusions: Whole CT decreased after PDT, including in medial areas from optic disc. This may be associated with the treatment response of PDT for CSC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the choriocapillaris (CC) flow changes in branched retinal vascular obstruction (BRVO) on optical coherence tomography angiography (OCTA). Methods: Retrospective analysis of 29 patients with unilateral BRVO (58 eyes, including unaffected fellow eyes for controls). 4.5 x 4.5 mm macular scans were divided into 4 quadrants. Serial analyses were conducted on CC flow voids of the opposite quadrant to the active occluded area in BRVO eyes. Each of the quadrants were also compared to the occluded quadrant of resolved eyes and the contralateral quadrant of fellow eyes by matched data analysis. A regression analysis was performed on the several parameters (Choroidal thickness; CT, Choroidal vascularity index; CVI, Central macular thickness; CMT, The number of intravitreal injections) and CC flow voids. Results: The CC flow void increased sequentially: The uninvolved quadrant of acute BRVO-affected eyes, that of resolved eyes after 3-month/1-year, the contralateral quadrant of fellow eye, the involved (occluded) quadrant of resolved eyes. There were significant correlations between initial CMT, the number of injections and the CC flow void of uninvolved quadrants (P = 0.025, 0.031, respectively), and between the involved (occluded) quadrants and fellow CT (P = 0.029). Conclusion: CC flow void of uninvolved macular areas decreased significantly in eyes with acute BRVO, suggesting that CC changes were limited to the blocked area and a compensatory mechanism would work in surrounding areas. [ABSTRACT FROM AUTHOR]

This study aimed to provide volumetric choroidal readings regarding sex, origin, and eye side from healthy cynomolgus monkey eyes as a reference database using optical coherence tomography (OCT) imaging. A machine learning (ML) algorithm was used to extract the choroid from the volumetric OCT data. Classical computer vision methods were then applied to automatically identify the deepest location in the foveolar depression. The choroidal thickness was determined from this reference point. A total of 374 eyes of 203 cynomolgus macaques from Asian and Mauritius origin were included in the analysis. The overall subfoveolar mean choroidal volume in zone 1, in the region of the central bouquet, was 0.156 mm3 (range, 0.131–0.193 mm3). For the central choroid volume, the coefficient of variation (CV) was found of 6.3%, indicating relatively little variation. Our results show, based on analyses of variance, that monkey origin (Asian or Mauritius) does not influence choroid volumes. Sex had a significant influence on choroidal volumes in the superior-inferior axis (p ≤ 0.01), but not in the fovea centralis. A homogeneous foveolar choroidal architecture was also observed. [ABSTRACT FROM AUTHOR]

Retinal vein occlusion (RVO) is a major retinal disease caused by venous thrombosis. Although several studies have proposed an association between venous thrombosis and von Willebrand factor (VWF), the association between RVO and VWF remains unclear. We aimed to investigate the association between RVO and VWF and the alteration of VWF levels under anti-vascular endothelial growth factor (VEGF) treatment. We enrolled 55 patients with RVO involved cystoid macular edema. They received intravitreal injection of anti-VEGF drugs, either ranibizumab or aflibercept. We examined the clinical data and measured plasma VWF antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity to identify variabilities during treatment. At baseline, there was no significant difference between the RVO group and age-matched controls in both VWF antigen and ADAMTS13 activity levels, but ADAMTS13 activity was significantly lower in central RVO than in branch RVO (P = 0.015). In branch RVO, VWF antigen was negatively correlated with central choroidal thickness (r = −0.51, P < 0.001). In branch RVO after anti-VEGF treatment, VWF antigen levels decreased significantly from 134% at baseline to 109% at 1 day (P = 0.002) and 107% at 1 month (P = 0.030) after treatment. In contrast, ADAMTS13 activity showed no significant difference during this period. In branch RVO at 1 month after treatment, VWF antigen was negatively correlated with central choroidal thickness (r = −0.47, P = 0.001). Our findings suggest an association between VWF and central choroidal thickness in patients with branch RVO, thus the measurement of VWF may be useful for evaluating disease activity and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the choriocapillaris changes associated with pachychoroid pigment epitheliopathy (PPE) in comparison with healthy eyes. Methods: Nine 3 × 3 mm macular optical coherence tomography angiography images were acquired in patients with PPE and age-matched healthy participants. Multiple en face image averaging of the choriocapillaris was binarized for quantitative image analysis of the flow voids. In PPE eyes, we evaluated the presence of pachyvessels and the association between the location of the choriocapillaris flow deficit and pachyvessels. Results: Thirty-two eyes with PPE and 30 eyes of healthy participants were included. In PPE eyes, the mean total area (1.16 ± 0.18 vs. 0.91 ± 0.16, p < 0.001) and average size of the flow voids (790 ± 144 vs. 520 ± 138; p < 0.001) were significantly larger than those in control eyes. Composite images of the choriocapillaris and choroid showed choriocapillaris flow deficits just above and outside the pachyvessels. The mean proportion of the flow void area overlying the pachyvessels against the whole flow void area of the choriocapillaris was 21.3% ± 10.2% (9.38%-44.42%) in PPE eyes. Conclusions: In PPE eyes, the blood flow area of the choriocapillaris decreased diffusely within the macular area compared to control eyes, and the choriocapillaris flow deficit was not necessarily related to pachyvessel location. [ABSTRACT FROM AUTHOR]

Purpose: To create vortex vein congestion in the monkey eye as a possible pachychoroid model. Methods: We ligated superotemporal and inferotemporal vortex veins at the surface of the sclera in monkey eyes. Optical coherence tomography (OCT) and indocyanine green angiography (ICGA) were performed before and 2, 7, and 28 days after the vortex vein ligations to investigate changes in vortex vein morphology and alterations in choroidal blood flow. Results: Before the vortex vein ligations, en face OCT and ICGA images showed well organized vortex veins as well as horizontal and vertical watershed zones. Two days after the vortex vein ligations, dilatation of the superotemporal and inferotemporal vortex veins as well as intervortex venous anastomoses were seen on en face OCT and ICGA images. B-mode OCT images showed choroidal thickening associated with dilatation of the outer choroidal vessels. Moreover, video ICGA revealed choriocapillaris filling delay and pulsatile flow in the dilated vortex veins. At 7 and 28 days after we ligated the vortex veins, these findings were reduced, except for the intervortex venous anastomoses. Conclusions: We created a monkey model of vortex vein congestion by ligating two vortex veins. This animal model demonstrated pachychoroid-related findings, indicating that vortex vein congestion is involved in the pathogenesis of pachychoroid. However, remodeling of the choroidal drainage route via intervortex venous anastomosis appeared to compensate for the vortex vein congestion created in this model. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate and compare the discriminating ability of corneal elevation maps generated using a swept-source optical coherence tomography (SS-OCT) (SS-OCT ANTERION, Heidelberg Engineering, Heidelberg, Germany), which was estimated with different reference surfaces, to distinguish normal corneas from those with keratoconus and keratoconus suspect. Methods: A total of 126 eyes of patients, which comprised 43, 37, and 46 keratoconus, keratoconus suspects, and normal controls, respectively, were included in this study. The anterior and posterior elevations at the thinnest point under the best-fit sphere (BFS) and toric-ellipsoid (BFT), respectively, and other corneal parameters were measured using the SS-OCT. In addition, the receiver operating characteristic (ROC) curve analysis and cut-off value were calculated to evaluate the diagnostic ability of the corneal elevation values in differentiating keratoconus and keratoconus suspects from normal eyes. Results: The mean total keratometric and corneal elevation values were significantly higher in the keratoconus group than in the other groups. Pachymetric parameters exhibited the lowest values for keratoconus. In addition, ROC curve analyses showed a high accuracy of the thinnest point anterior and posterior BFT for both keratoconus and keratoconus suspects and normal controls (area under the ROC were 0.969 and 0.961, respectively). Furthermore, the optimal cut-off point of the posterior elevation at the thinnest point under BFT was 16.44 μm (sensitivity and specificity of 86% and 98%, respectively) for differentiating keratoconus from normal and keratoconus suspect eyes. Conclusions: The elevation map using the BFS and BFT references measured with the anterior segment SS-OCT is considered an effective indicator for keratoconus diagnosis. Therefore, the anterior segment SS-OCT can effectively differentiate keratoconus from suspected keratoconus and normal corneas by measuring parameters such as posterior and anterior elevations, pachymetry, and keratometry. [ABSTRACT FROM AUTHOR]

Purpose: There is abundant evidence on the benefits of physical activity on cardiovascular health. However, there are only few data on the acute effects of physical exercise on the retina and choroid. Our aim was the in vivo examination of chorioretinal alterations following short intense physical activity by spectral domain optical coherence tomography (SD-OCT). Methods: Twenty-one eyes of 21 healthy, young subjects (mean age 22.5 ± 4.1 years, 15 males and 6 females) were recruited. Macular scanning with a SD-OCT was performed before and following a vita maxima-type physical strain exercise on a rowing ergometer until complete fatigue. Follow-up OCT scans were performed 1, 5, 15, 30 and 60 minutes following the exercise. The OCT images were exported and analyzed using our custom-built OCTRIMA 3D software and the thickness of 7 retinal layers was calculated, along with semi-automated measurement of the choroidal thickness. One-way ANOVA analysis was performed followed by Dunnett post hoc test for the thickness change compared to baseline and the correlation between performance and thickness change has also been calculated. The level of significance was set at 0.001. Results: We observed a significant thinning of the total retina 1 minute post-exercise (-7.3 ± 0.6 μm, p < 0.001) which was followed by a significant thickening by 5 and 15 minutes (+3.6 ± 0.6 μm and +4.0 ± 0.6 μm, respectively, both p <0.001). Post-exercise retinal thickness returned to baseline by 30 minutes. This trend was present throughout the most layers of the retina, with significant changes in the ganglion cell–inner plexiform layer complex, (-1.3 ± 0.1 μm, +0.6 ± 0.1 μm and +0.7 ± 0.1 μm, respectively, p <0.001 for all), in the inner nuclear layer at 1 and 5 minutes (-0.8 ± 0.1 μm and +0.8 ± 0.1 μm, respectively, p <0.001 for both), in the outer nuclear layer–photoreceptor inner segment complex at 5 minute (+2.3 ± 0.4 μm, p <0.001 for all) and in the interdigitation zone–retinal pigment epithelium complex at 1 and 15 minutes (-3.3 ± 0.4 μm and +1.8 ± 0.4 μm, respectively, p <0.001 for both). There was no significant change in choroidal thickness; however, we could detect a tendency towards thinning at 1, 15, and 30 minutes following exercise. The observed changes in thickness change did not correlate with performance. Similar trends were observed in both professional and amateur sportsmen (n = 15 and n = 6, respectively). The absolute changes in choroidal thickness did not show any correlation with the thickness changes of the intraretinal layers. Conclusions: Our study implies that in young adults, intense physical exercise has an acute effect on the granular layers of the retina, resulting in thinning followed by rebound thickening before normalization. We could not identify any clear correlation with either choroidal changes or performance that might explain our observations, and hence the exact mechanism warrants further clarification. We believe that a combination of vascular and mechanic changes is behind the observed trends. [ABSTRACT FROM AUTHOR]

Background: Previous studies proposed possible applications of spectral-domain optical coherence tomography (SD-OCT) measurements in prognosticating pathologies observed in overweight/obesity, including ocular, vascular, and neurologic consequences. Therefore, we conducted a systematic review and meta-analysis to investigate the changes in the in SD-OCT measurements of the patients with higher body mass index (BMI) compared to normal weight individuals. Materials and methods: We conducted a systematic search on PubMed, Scopus, and Embase. The search results underwent two-phase title/abstract and full-text screenings. We then analyzed SD-OCT measurements differences in patients with high BMI and controls, and performed meta-regression, sub-group analysis, quality assessment, and publication bias assessment. The measurements included macular thickness, cup to disc ratio, ganglion cell-inner plexiform layer (GC-IPL) and its sub-sectors, RNFL and peripapillary RNFL (pRNFL) and their sub-layers, and choroidal thickness and its sub-sectors. Results: 19 studies were included in this meta-analysis accounting for 1813 individuals, 989 cases and 824 controls. There was an overall trend towards decreased thickness in high BMI patients, but only two measurements reached statistical significance: temporal retinal nerve fiber layer (RNFL) (Standardized mean difference (SMD): -0.33, 95% confidence interval (CI): -0.53 to -0.14, p<0.01) and the choroidal region 1.0 mm nasal to fovea (SMD: -0.38, 95% CI: -0.60 to -0.16, p<0.01). Conclusion: Some ocular layers are thinner in patients with higher BMI than the controls. These SD-OCT measurements might correlate with adverse events related to increased body weight and have prognostic abilities. As SD-OCT is a robust, rapid and non-invasive tool, future guidelines and studies are needed to evaluate the possibility of their integration into care of the patients with obesity. [ABSTRACT FROM AUTHOR]

Background: Foveal hypoplasia is characterized by the persistance of inner retinal layers at the macular center. We evaluated using spectral-domain optical coherence tomography (SD-OCT) morphological parameters of the macular center of eyes with foveal hypoplasia and describe the presence of hyporeflective zones in the Henle fiber layer (HFL) of eyes with high-grade foveal hypoplasia. Methods: Eyes with foveal hypoplasia were classified into two groups: high-grade foveal hypoplasia with thick inner retinal layers at the macular center (thickness above 100 μm; 16 eyes of 9 subjects) and low-grade foveal hypoplasia with thinner inner retinal layers at the macular center (thickness below 100 μm; 25 eyes of 13 subjects). As comparison, SD-OCT images of normal control eyes (n = 75) were investigated. Results: Eyes with foveal hypoplasia displayed shorter central photoreceptor outer segments (POS), a thinner central myoid zone, and a thicker central HFL compared to control eyes. Eyes with high-grade foveal hypoplasia also displayed a thinner central outer nuclear layer (ONL) compared to eyes with low-grade foveal hypoplasia and control eyes. There was a negative correlation between the thicknesses of the central ONL and HFL in eyes with foveal hypoplasia; however, the total thickness of both ONL and HFL was similar in all eye populations investigated. Visual acuity of subjects with foveal hypoplasia was negatively correlated to the thickness of the central inner retinal layers and positively correlated to the length of central POS. In contrast to central POS, the length of paracentral POS (0.5 and 1.0 mm nasal from the macular center) was not different between the three eye populations investigated. The paracentral ONL was thickest in eyes with high-grade foveal hypoplasia and thinnest in control eyes. Hyporeflective zones in the HFL were observed on SD-OCT images of eyes with high-grade foveal hypoplasia, but not of eyes with low-grade foveal hypoplasia and control eyes. OCT angiography images recorded at the level of the HFL of eyes with high-grade foveal hypoplasia showed concentric rings of different reflectivity around the macular center; such rings were not observed on images of eyes with low-grade foveal hypoplasia and control eyes. Conclusions: It is suggested that the hyporeflective zones in the HFL of eyes with high-grade foveal hypoplasia represent cystoid spaces which are surrounded by Henle fiber bundles. Cystoid spaces are likely formed because there are fewer Henle fibers and a thinner central ONL despite an unchanged thickness of both ONL and HFL. Cystoid spaces may cause the concentric rings of different reflectivity around the macular center in the HFL of eyes with high-grade foveal hypoplasia. [ABSTRACT FROM AUTHOR]

Purpose: To analyze choroidal structure using subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) in Macular Telangiectasia (MacTel) type 2. Methods: Medical records of 43 eyes with MacTel type 2 and 30 sex and age-matched healthy eyes were retrospectively reviewed. Their SFCT and CVI were measured using the SS-OCT scan passing through the central fovea and image binarization. The difference in baseline SFCT and CVI from each group and their yearly changes up to second year of follow up were analyzed. The baseline characteristics of the groups were also compared. Results: The baseline characteristics, including CVI and SFCT, of the MacTel group and the control group were not significantly different, except for BCVA. The mean CVI of MacTel group were 64.59 ± 2.92%, 63.76 ± 2.67%, and 62.97 ± 2.74% (p < 0.001) whereas that of control group were 63.33 ± 2.45%, 63.04 ± 2.46%, and 63.43 ± 2.25% (p = 0.636) at baseline, 1 and 2 years, respectively. The mean SFCT of MacTel group were 324.65 ± 89.65μm, 326.14 ± 93.11μm, and 322.65 ± 91.77μm (p = 0.436), whereas that of control group were 304.30 ± 51.86 μm, 300.86 ± 52.64μm, and 298.55 ± 53.71μm (p = 0.275) at baseline, 1 and 2 years, respectively. Conclusion: CVI decreases at a faster rate in MacTel type 2 in comparison with healthy subjects. This may suggest possible choroidal involvement in the progression of MacTel type 2. [ABSTRACT FROM AUTHOR]

PurposeThis study investigated the gene expression of TGFβ isoforms and their receptors in chick retina, retinal pigment epithelium (RPE), and choroid and the effects of short-term imposed optical defocus.MethodsThe expression of TGFβ isoforms (TGF-β1, 2, 3) and TGFβ receptors (TGFBR1, 2, 3) was examined in the retina, RPE, and choroid of young White-Leghorn untreated chicks (19 days-old). The effects on the expression of the same genes of monocular +10 and -10 D defocusing lenses, worn for either 2 or 48 h by age-matched chicks, were also examined by comparing expression in treated and untreated fellow eyes. RNA was purified, characterized and then reverse transcribed to cDNA. Differential gene expression was quantified using real-time PCR.ResultsAll 3 isoforms of TGFβ and all 3 receptor subtypes were found to be expressed in all 3 ocular tissues, with apparent tissue-dependent differences in expression profiles. Data are reported as mean normalized expression relative to GAPDH. Sign-dependent optical defocus effects were also observed. Optical defocus did not affect retinal gene expression but in the RPE, TGF-β2 expression was significantly up-regulated with +10 D lenses, worn for either 2 h (349% increase ± 88%, p < 0.01) or 48 h (752% increase ± 166%, p < 0.001), and in the choroid, the expression of TGF-β3 was up-regulated with -10 D lenses, worn for 48 h (147% increase ± 9%, p < 0.01).ConclusionsThe effects of short term exposure to optical defocus on TGFβ gene expression in the RPE and choroid, which were sign-dependent and isoform specific, provide further supporting evidence for important roles of members of the TGFβ family and these two tissues in local signal cascades regulating ocular growth.

This study aimed to evaluate the correlation between ophthalmologic factors and the serologic indicator soluble fms-like tyrosine kinase 1 (sFlt-1): placental growth factor (PlGF) ratio in patients with preeclampsia using optical coherence tomography (OCT) and OCT angiography (OCT-A). A total of 52 pregnant patients (104 eyes) diagnosed with preeclampsia were recruited during their hospital stay. The associations between the sFlt-1/PlGF ratio and chorioretinal measurements, including the choroidal thickness (CT), foveal avascular zone, vascular density, and ganglion cell layer+ were evaluated. Central and nasal subfield CT of the left eye (p = 0.039; p = 0.010) and nasal subfield CT of the right eye (p = 0.042) were lower in the high sFlt-1/PlGF ratio group (≥38). Pearson's correlation test showed a negative correlation between the sFlt-1/PlGF ratio and central subfield CT; however, this was not statistically significant (p = 0.648). Linear regression analysis revealed a significant association between the sFlt-1/PlGF ratio and central subfield CT (β coefficient, -6.66; p = 0.01) and between sFlt-1 and central subfield CT (β coefficient, -5.65; p = 0.00). Thus, an increase in the sFlt-1/PlGF ratio resulted in a decrease in central subfield CT. [ABSTRACT FROM AUTHOR]

Background: Gaucher's disease is associated with a high variety of structural and functional abnormalities in the eye, which do not always affect visual acuity. The purpose of this study was to analyse ocular features in Spanish patients with Gaucher's disease type I, and to investigate their possible correlation with phenotypic and burden parameters of this entity. Methods: This cross-sectional observational study compared parameters belonging to 18 eyes from 9 Spanish patients with Gaucher's disease Type I with 80 eyes from 40 healthy controls. Complete ophthalmological examination included choroidal and retinal thickness maps with swept source optical coherence tomography. Systemic analysis included genotype, plasmatic biomarkers, [ferritin, chemokine ligand 18 (CCL18) and chitotriosidase (ChT)] and severity scoring systems results ["Gaucher Disease Severity Score Index Type I" (GauSSI-I) and "Gaucher disease severity scoring system" (GD-DS3)]. Results: Nine subjects (18 eyes) were cases (female: 55.5%, mean age 45 years; male: 44.5%, mean age 36 years) and 40 subjects (80 eyes) were controls (female: 49%, mean age 50 years; male: 51%, mean age 55 years). There were no statistically significant differences when comparing ocular parameters (visual acuity; axial length, refractive errors, corneal parameters, lens, retinal and choroidal thickness) between case and control subjects (p>0.05). A statistically significant moderate correlation was observed between lower retinal thickness and choroidal quadrants thickness and greater disease severity scores. A lower central retinal thickness also correlates with higher biological plasmatic levels, and has a statistically significant association with the most affected patient with genotype N370S/Del 55pb. Conversely, higher pachymetry involves a more severe plasmatic concentration of biomarkers. Conclusions: Our results suggest that pachymetry, and retinal and choroidal thickness, are associated with burden biomarkers and disease severity index scores in Spanish patients with Gaucher's disease Type I. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in choroidal vascular structure and aqueous cytokine levels in eyes with vitreoretinal lymphoma (VRL) after intravitreal methotrexate (MTX) treatment. Methods: In this retrospective study, VRL patients who visited our hospital between October 2018 and July 2020 were reviewed. Aqueous samples were obtained before treatment and at clinical resolution after intravitreal MTX therapy. Interleukin (IL)-6 and IL-10 levels and the IL-10-to-IL-6 ratio were evaluated. Swept-source optical coherence tomographic images were obtained along with the aqueous samples. Subfoveal choroidal thickness (SFCT), total vascular area of the choroid (TCA), stromal area (SA), luminal area (LA), and choroidal vascularity index (CVI) were assessed. Results: Twelve patients were enrolled (female:male—5:7). The mean age (± standard deviation) at diagnosis was 60.9±8.5 years. In the 16 eyes diagnosed with VRL, values of SFCT, TCA, LA, and SA significantly decreased after treatment (all p-values <0.05). Additionally, the aqueous cytokine IL-10 level and IL-10-to-IL-6 ratio were significantly decreased (p = 0.001 and p = 0.003, respectively). The choroidal structure in the non-treated fellow eyes did not show any significant difference. There were no further changes in SFCT, TCA, LA, or CVI that occurred during maintenance therapy. For clinical remission, the patients received 7.7±5.5 intravitreal MTX injections. The required number of injections for clinical remission was positively correlated with best-corrected visual acuity, IL-10, and IL-6 levels in the active phase (p = 0.035, p = 0.009, and p = 0.031, respectively). Conclusion: Eyes with active VRL exhibited choroidal thickening with increased vascular and stromal areas that decreased after remission following MTX treatment. Higher aqueous IL-10 and IL-6 levels and lower visual acuity in the active phase may indicate the number of injections required for remission; this should be considered in the treatment of patients with VRL. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the structure of the choriocapillaris in healthy eyes by using averaged en face images acquired using swept source optical coherence tomography angiography and to examine the changes in the macular profile in relation to age, sex, axial length, and choroidal thickness. Methods: This prospective, cross-sectional study included 81 eyes of 81 subjects without ophthalmologic or systemic diseases who underwent a full ophthalmologic examination, including 3 × 3-mm macular optical coherence tomography angiography. Four to nine choriocapillaris en face images were registered and averaged. The averaged images were then binarized and analyzed. Results: The averaged choriocapillaris images showed a continuous capillary meshwork, whereas the unaveraged images had a granular appearance. The mean total area and size of flow voids were 0.99 ± 0.20 mm2 and 567.8 ± 201.5 μm2, respectively, and these values correlated positively with age (p = 0.002, R = 0.336 and p = 0.026, R = 0.247, respectively). Age-related gains in the mean total area and flow void size were 4.20 × 10−3 mm2 and 3.07 μm2 per year, respectively. However, the mean total area and flow void size had no significant correlation with axial length, subfoveal choroidal thickness, or sex. Conclusions: Multiple averaged en face swept source optical coherence tomography angiography is more effective than a single optical coherence tomography angiography scan for better visualizing the choriocapillaris. The total area and size of flow voids within a 3 × 3-mm macular area positively correlated with age. This technique can be useful for investigating the changes arising in macular diseases. [ABSTRACT FROM AUTHOR]

Purpose: To assess choroidal vasculature changes in eyes with branch retinal vein occlusion (BRVO) and macular edema (ME) using the choroidal vascularity index (CVI) and evaluate the effectiveness of CVI as a prognostic biomarker. Methods: 35 patients with monocular BRVO and ME were analyzed retrospectively. Luminal and stromal areas in choroids of swept-source optical coherence tomography were calculated using the image binarization technique. The CVI was calculated as the ratio of the luminal to total choroidal area. The CVI of BRVO and ME eyes were compared with that of the unaffected fellow and post anti-vascular endothelial growth factor (VEGF) injected eyes. A regression analysis was performed on the choroidal parameters, logMAR visual acuity (VA) two years post disease onset and central macula thickness (CMT). Results: The CVI of BRVO and ME eyes was significantly lower than the fellow and post-injected eyes (p<0.05). The regression analysis showed a strong association between two years after logMAR VA and the CVI of fellow eyes (R2 = 0.433, p<0.001). Remarkable correlations were observed in the CVI and subfoveal choroidal thickness of BRVO and ME eyes (R2 = 0.189, 0.155, respectively, p<0.05). The CMT of diseased eyes were also significantly associated with the CVI of unaffected fellow eyes (R2 = 0.113, p<0.05). Conclusions: The alteration of CVI in BRVO and ME suggests that choroidal vasculature might be affected by extracellular fluid shift and VEGF changes. The fellow eye CVI could be a useful supplementary prognostic biomarker. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the differences in the choroidal biomarkers between two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes with chronic central serous chorioretinopathy (CSC). Materials and methods: Enhanced depth imaging optical coherence tomography (EDI-OCT) was done in eyes with FIPED correlated to chronic CSC, fellow eyes, and also in healthy eyes from gender- and age-matched subjects. Eyes with FIPED were classified into two subgroups based on optical coherence tomography angiography (OCTA) findings: vFIPED and aFIPED. Different choroidal biomarkers such as subfoveal choroidal thickness (SFCT), total choroidal area (TCA), and choroidal vascular index (CVI) were compared between the groups. Results: Forty-four eyes from 42 patients with chronic CSC and FIPED along with 40 eyes from 20 healthy subjects were included. OCTA identified vascularization in 14 eyes in the FIPED group (31.8%). Mean SFCT was higher in the FIPED group compared to two other groups (p = 0.005). In comparison to patients with aFIPED, patients with vFIPED had lower SFCT (p = 0.003) and higher CVI (p = 0.020) based on multivariate analysis. Conclusions: It seems that measurement of CVI along with SFCT may help to differentiate aFIPED from vFIPED in patients with CSC. Further longitudinal studies would be required to confirm the clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Purpose: We sought to evaluate changes of mean peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) over 12 months in patients with unilateral central retinal vein occlusion (CRVO). Methods: Our retrospective, observational study included 19 patients with treatment-naïve, unilateral CRVO who completed at least 12 months of follow-up period. Mean PCT and mean SFCT in CRVO-affected eyes and unaffected contralateral eyes were measured at each follow-up visit, and then compared. Differences between baseline and 12 months (ΔSFCT and ΔPCT) and percentage changes (ΔSFCT or ΔPCT/baseline×100%) were determined. We also investigated the predictive factors for visual outcome in the CRVO-affected eyes. Results: In the CRVO-affected eyes, mean PCT was 146.7±41.9 μm at baseline, and 106.5±24.2 μm at 12 months (P < 0.001). Mean PCT of the contralateral eyes was 129.8±42.6 μm at baseline and 124.6±39.7 μm at 12 months (P = 0.089). Mean SFCT of CRVO-affected eyes was 225.8±77.9 μm at baseline, and 199.4±66.6 μm at 12 months (P = 0.009). Mean SFCT of the contralateral eyes was 218.4±83.0 μm at baseline, and 208.4±78.1 μm at 12 months (P = 0.089). Δ PCT was -41.6±25.3 μm in the CRVO-affected eyes, and -5.2±5.8 μm in the contralateral eyes (P<0.001). % PCT was -24.9±14.0% in the CRVO-affected eyes, and -4.0±0.4% in the contralateral eyes (P = 0.001). Δ SFCT was -26.4±24.6 μm in the CRVO-affected eyes, and -9.5±16.7μm in the contralateral eyes (P = 0.016). % SFCT was -10.4±9.8% in the CRVO-affected eyes, and -3.4±6.4% in the contralateral eyes (P = 0.015). Among the various factors, BCVA at baseline (β = 0.797, P = 0.001) and % SFCT (β = 0.712, P = 0.001) were significantly associated with visual outcome at 12 months in the CRVO-affected eyes. Conclusion: Both peripapillary and subfoveal choroidal thickness reduced significantly over 12 months in the CRVO-affected eyes, but not in the contralateral eyes. In addition, the absolute reduction amount and reduction ratio of PCT and SFCT were significantly greater in the CRVO-affected eyes than the contralateral eyes. [ABSTRACT FROM AUTHOR]

Purpose: Establishing the reliability of a new method to check the mean retinal and choroidal reflectivity and using it to find retinal and choroid changes in amblyopia. Methods: Design: Retrospective case-control. Population: 28 subjects of which 10 were healthy controls (20 eyes): 8 with refractive errors, 1 with strabismus, and 1 with both. 18 patients with unilateral amblyopia included: 7 anisometropic, 6 isoametropic, 1 strabismic, and 4 combined. Mean participants' age: 13.77 years ± 10.28. Observation procedures: SD-OCT and ImageJ. Main outcome measure: mean reflectivity of retinal and choroid layers. Amblyopic, fellow, and healthy eyes were compared. Results: The method of measuring reflectivity is good to excellent reliability for all regions of interest except the fourth. The mean reflectivity of the choriocapillaris and Sattler's layer in amblyopic eyes were significantly lower than in healthy eyes (p = 0.003 and p = 0.008 respectively). The RNFL reflectivity was lower than that of fellow eyes (p = 0.025). Post-hoc pairwise comparisons showed statistically significant differences between amblyopic and healthy eyes for choriocapillaris (p = 0.018) and Sattler's (p = 0.035), and between amblyopic and fellow eyes for RNFL (p = 0.039). Conclusion: A decrease in reflectivity of the choriocapillaris and Sattler's in amblyopic compared to healthy eyes, and a decrease in reflectivity of the RNFL in the amblyopic compared to fellow eyes, indicate that the pathophysiology is partly peripheral and might be bilateral. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA) Design: Prospective, cross-sectional study. Methods: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation. Results: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%. Conclusions: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully. [ABSTRACT FROM AUTHOR]

Drusen are known to be the important hallmark to predict the development of age-related macular degeneration (AMD). The prevalence of drusen is lower in Asians compared with Caucasians so that the role of signs constituting early AMD is not well established in Asian populations as in Western countries. In this study, we retrospectively investigated clinical characteristics and 5-year incidence of neovascular AMD (nAMD) in the fellow eye of unilateral nAMD patients. Of 296 consecutive unilateral nAMD patients who had been followed up more than 5 years, 170 typical AMD, 119 polypoidal choroidal vasculopathy, and 7 retinal angiomatous proliferation were included. To examine factors associated with nAMD occurrence in the fellow eye, drusen and pigmentary abnormality in the fellow eye were classified into 4 categories; Category 1: no or small drusen < 63 μm (37.2%), Category 2: 63–125 μm medium drusen or pigmentary abnormality (22.2%), Category 3: large drusen > 125 μm (25.0%), Category P: pachydrusen (15.5%). The mean sub-foveal choroidal thickness (SFCT) was Category 1: 276 μm, Category 2: 308 μm, Category 3: 246 μm, and Category P: 302 μm, respectively. Of note, SFCT in Category 2 and Category P was significantly larger than those of Category 3. Finally, the 5-year incidence of nAMD in the fellow eye was 32/296 (10.8%); Category 1: 0/110 (0%), Category 2: 12/66 (18.2%), Category 3: 20/74 (27.0%), and Category P: 0/46 (0%). Thus, signs of intermediate AMD (large drusen) as well as those of early AMD, especially the pigmentary abnormality, may contribute to development of bilateral nAMD in Japanese patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. Methods: This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. Results: The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p<0.001; 67.3% vs. 40.9%, p = 0.017, respectively), but the choroidal vascularity index (CVI) showed a significantly lower value (60.7±2.0% vs. 61.7±2.5%; p = 0.047). The presence of reticular pseudodrusen was related with the duration from baseline to development of fellow eye neovascularization (p = 0.038). Conclusion: Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To diagnose central serous chorioretinopathy (CSC) by deep learning (DL) analyses of en face images of the choroidal vasculature obtained by optical coherence tomography (OCT) and to analyze the regions of interest for the DL from heatmaps. Methods: One-hundred eyes were studied; 53 eyes with CSC and 47 normal eyes. Volume scans of 12×12 mm square were obtained at the same time as the OCT angiographic (OCTA) scans (Plex Elite 9000 Swept-Source OCT®, Zeiss). High-quality en face images of the choroidal vasculature of the segmentation slab of one-half of the subfoveal choroidal thickness were created for the analyses. The 100 en face images were divided into 80 for training and 20 for validation. Thus, we divided it into five groups of 20 eyes each, trained the remaining 80 eyes in each group, and then calculated the correct answer rate for each group by validation with 20 eyes. The Neural Network Console (NNC) developed by Sony and the Keras-Tensorflow backend developed by Google were used as the software for the classification with 16 layers of convolutional neural networks. The active region of the heatmap based on the feature quantity extracted by DL was also evaluated as the percentages with gradient-weighted class activation mapping implemented in Keras. Results: The mean accuracy rate of the validation was 95% for NNC and 88% for Keras. This difference was not significant (P >0.1). The mean active region in the heatmap image was 12.5% in CSC eyes which was significantly lower than the 79.8% in normal eyes (P<0.01). Conclusions: CSC can be automatically diagnosed by DL with high accuracy from en face images of the choroidal vasculature with different programs, convolutional layer structures, and small data sets. Heatmap analyses showed that the DL focused on the area occupied by the choroidal vessels and their uniformity. We conclude that DL can help in the diagnosis of CSC. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT).MethodsA cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses.ResultsOverall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P

Purpose: To analyze ocular biometric parameters alterations of the posterior pole and choroidal abnormalities in patients with neurofibromatosis type 1 (NF1) by adopting multimodal imaging, especially focusing on the role of novel diagnostic devices like swept-source optical coherence tomography angiography (SS-OCTA). Methods: In this prospective, case-controlled study, patients with NF1 and age-matched control subjects were quantitatively analyzed by using multimodal imaging. All the subjects underwent confocal scanning laser ophthalmoscopy (SLO), SS-OCT and SS-OCTA examinations. Results: SS-OCT analysis revealed a lower macular retinal nerve fiber layer (RNFL) thickness in patients with NF1 compared with those with suspected NF1 (95.0±15.9 vs 109.7±11.3 μm; P = 0.001) and control subjects (106.8±14.4 μm, P = 0.003). Retinal thickness was significantly lower in NF1 patients compared to those with suspected NF1 (280.7±23.0 vs 304.2±15.3 μm; P < 0.001) and control subjects (298.7±23.8 μm, P = 0.003). The mean vascular flow area of the SCP was significantly higher in patients with NF1 (42.6±2.2%) and suspected NF1 (43.1±2.5%) compared to control subjects (41.0±2.0%; respectively, P = 0.017 and P = 0.002). In the second choroidal layer, the flow area was significantly lower in patients with NF1 compared to control subjects (45.4±4.8 vs 49.0±4.0%,; P = 0.011). Conclusions: Retinal thicknesses alterations and choroidal nodules are described as ocular manifestations in patients with NF1. In addition, OCTA could represent an important novel advanced imaging technique, capable of detecting early altered retinal and choroidal vascular flow area in patients with NF1. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Choroidal metastases (CM) are the most common intraocular malignancies. With longer survival rates for cancer patients, CM will be increasingly encountered. We evaluated clinical and ultrasonographic (US) characteristics of CM in order to identify diagnostic biomarkers that correlate with the primary tumor site. Methods: The medical records of all patients with CM evaluated at the Ocular Oncology Unit between February 2010 and March 2020 were analyzed. Results: 82 eyes of 70 patients were included. The primary cancer site was lung in 26 patients (37%), breast in 23 (33%), kidney in 9 (13%), gastrointestinal in 5 (7%), thyroid in 5 (7%), parathyroids and prostate respectively in 2 (3%). Fifty-five patients (78%) had other systemic metastases at the time of ocular diagnosis. Ten (14%) patients had no history of primary cancer. Bilateral CM were found in 20 patients (29%); fifty-six eyes (68%) had a single CM. The epicenter of CM was predominantly macula (43 eyes, 52%). The mean thickness was 4,1 mm (range 1,8–12,3). US structure was inhomogeneous in 67 eyes (82%). Reflectivity was mainly medium (39%) and medium-low (39%). In particular, CM from lung cancer showed lower reflectivity than those from the breast (p = 0,02). CM deriving from lung cancer were typically dome-shaped, whereas CM originating from breast were characteristically plateau shaped (p = 0,02). Seventy-four (91%) eyes presented fluid on optical coherence tomography. Conclusion: We significatively found that CM from lung cancer generally appear dome-shaped with medium-low internal reflectivity, whereas those from breast cancer typically present a plateau appearance and higher internal reflectivity. Though it is hard to identify the site of the primary tumor relying exclusively on clinical and US aspects, morphology and internal reflectivity can be considered as diagnostic biomarkers. Thus, the origin of the primary tumor can be suspected by integrating a constellation of findings. [ABSTRACT FROM AUTHOR]

Purpose: A smoking habit can cause various health problems encompassing retinal diseases including central serous chorioretinopathy (CSC). The aim of the current study was to investigate the effect of smoking on the choroidal structure in patients with CSC. Methods: The choroidal vascular index (CVI) was calculated using the binarized OCT images. Baseline parameters (age, refractive error [SE], subfoveal choroidal thickness [SFCT] and CVI) were compared between smokers and non-smokers using Wilcoxon rank sum test. Moreover, the associations between SFCT and the baseline parameters were analyzed using a multivariate linear regression followed by the AICc model selection. Results: Among 75 CSC patients, 45 patients were smokers and 30 patients were non-smokers. No significant differences in age and SE were seen between the smoking group and the non-smoking group. A significant difference in the SFCT was seen between two groups (382.0 ± 68.2 μm in the smoking group vs. 339.3 ± 52.3 μm in the non-smoking group, p = 0.0038), while no significant difference was observed in the CVI (p = 0.32). The optimal model for SFCT included the variables of age, SE and past history of smoking among the baseline parameters. Additionally, increased pack years was associated with increased SFCT. Conclusion: Cigarette smoking was associated with an increased SFCT in patients with CSC. Thicker choroid in smoking CSC patients may be an important modulator of the disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the retinal nerve fiber layer (RNFL) and macular thicknesses and identify systemic risk factors for thinning of these layers in patients with metabolic syndrome (MetS). Methodology: A cross-sectional observational study was performed on patients diagnosed with MetS and compared to normal controls. All patients underwent ophthalmic and anthropometric examination, serological and biochemical blood investigations; and ocular imaging using spectral-domain optical coherence tomography. Patients with ocular pathology were excluded. Unpaired t-test was used to compare mean thickness between the two groups. One-way ANOVA with Bonferroni correction for multiple comparisons was used to compare mean thickness between different tertiles of MetS parameters, and a generalized estimating equation was used to correct for inter-eye correlation and to assess association between mean thickness and covariates. Results: Two hundred and forty-eight eyes from 124 participants (1:1 ratio of MetS patients to controls) were included. Age ranged between 30 to 50 years old, and mean age was 40 ± 6.6 years. RNFL thickness was lower globally (93.6 ± 9.9 μm vs 99.0 ± 9.3, p<0.001) and in the inferior (124.5 ± 17.5 μm vs 131.0 ± 16.4 μm, p = 0.002), superior (117.2 ± 16.0 μm vs 126.3 ± 14.4 μm, p<0.001) and temporal (65.5 ± 10.2 μm vs 69.5 ± 9.8, p = 0.002) sectors in MetS patients compared to controls. Only the central (237.0 ± 14.0 μm vs 243.6 ± 18.0 μm, p = 0.002) and inferior parafoveal (307.8 ± 20.9 vs 314.6 ± 14.6, p = 0.004) area of the macula was significantly thinner. The inferior RNFL sector had the most difference (mean difference = 9.1 μm). The Generalized Estimating Equation found that, after adjusting for age, diastolic blood pressure, BMI, HDL and obesity; the number of MetS components and elevated triglyceride levels were independent risk factors for reduced thickness in global RNFL (β = -4.4, 95% CI = -7.29 to -1.5, p = 0.003) and inferior parafovea (β = -6.85, 95% CI = -11.58 to -2.13, p = 0.004) thickness respectively. Conclusion: RNFL thinning was seen more than macula thinning in MetS patients, suggesting RNFL susceptibility to neurodegeneration than the macula. A higher number of metabolic components and elevated triglyceride levels were independent risk factors for retinal thinning in this group of patients. [ABSTRACT FROM AUTHOR]

Purpose: OCT-angiography (OCT-A) offers a non-invasive method to visualize retinochoroidal microvasculature. As glaucoma disease affects retinal ganglion cells in the macula, macular microcirculation is of interest. The purpose of the study was to investigate regional macular vascular characteristics in patients with ocular hypertension (OHT), pre-perimetric primary open-angle glaucoma (pre-POAG) and controls by OCT-A in three microvascular layers. Material and methods: 180 subjects were recruited from the Erlangen Glaucoma Registry, the Department of Ophthalmology, University of Erlangen and residents: 38 OHT, 20 pre-POAG, 122 controls. All subjects received an ophthalmological examination including measurements of retinal nerve fibre layer (RNFL), retinal ganglion cell layer (RGC), inner nuclear layer (INL), and Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW). Macular vascular characteristics (vessel density, VD, foveal avascular zone, FAZ) were measured by OCT-A (Spectralis OCT II) in superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Results: With age correction of VD data, type 3 tests on fixed effects showed a significant interaction between diagnosis and sectorial VD in SVP (p = 0.0004), ICP (p = 0.0073), and DCP (p = 0.0003). Moreover, a significance in sectorial VD was observed within each layer (p<0.0001) and for the covariate age (p<0.0001). FAZ differed significantly between patients' groups only in ICP (p = 0.03), not in SVP and DCP. For VD the AUC values of SVP, ICP, and DCP were highest among diagnostic modalities (AUC: 0.88, 95%-CI: 0.75–1.0, p<0.001). Conclusion: Regional reduced macula VD was observed in all three retinal vascular layers of eyes with OHT and pre-POAG compared to controls, indicating localized microvascular changes as early marker in glaucoma pathogenesis. [ABSTRACT FROM AUTHOR]

Pachychoroid spectrum diseases have been described as a new clinical entity within the spectrum of macular disorders. "Pachychoroid" is defined as choroidal thickening associated with dilated outer choroidal vessels often showing retinal pigment epithelium (RPE) degeneration. Although various clinical studies on the pachychoroid spectrum diseases have been conducted, the pathophysiology of pachychoroid has yet to be fully elucidated. In this study, we attempted to establish a mouse model of pachychoroid. We sutured vortex veins in eyes of wild type mice to imitate the vortex vein congestion in pachychoroid spectrum diseases. Fundus photography and ultra-widefield indocyanine green angiography showed dilated vortex veins from the posterior pole to the ampulla in eyes after induction of choroidal congestion. Optical coherence tomography and tissue sections presented choroidal thickening with dilatation of choroidal vessels. The RPE-choroid/retina thickness ratios on the tissue sections in the treated day 1 and day 7 groups were significantly greater than that in the control group (0.19±0.03 and 0.16±0.01 vs. 0.12±0.02, P<0.05 each). Moreover, immunohistochemistry using RPE flatmount revealed focal RPE degeneration in the treated eyes. Furthermore, inflammatory response-related genes were upregulated in eyes with choroidal congestion induction, and macrophages migrated into the thickened choroid. These results indicated that vortex vein congestion triggered some pachychoroid features. Thus, we have established a choroidal congestion mouse model by suturing vortex veins, which would potentially be useful for investigating the pathophysiology of pachychoroid spectrum diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the change in axial length (AxL) and choroidal thickness (ChT) in response to continuous and alternating episodes of monocular myopic and hyperopic defocus. Methods: The right eye of sixteen young adults was exposed to 60 minute episodes of either continuous or alternating myopic and hyperopic defocus (+3 DS & -3 DS) over six separate days, with the left eye optimally corrected for distance. During alternating defocus conditions, the eye was exposed to either 30 or 15 minute cycles of myopic and hyperopic defocus, with the order of defocus reversed in separate sessions. The AxL and ChT of the right eye were measured before, during and after each defocus condition. Results: Significant changes in AxL were observed over time, dependent upon the defocus condition (p < 0.0001). In general, AxL exhibited a greater magnitude of change during continuous than alternating defocus conditions. The maximum AxL elongation was +7 ± 7 μm (p = 0.010) in response to continuous hyperopic defocus and the maximum AxL reduction was -8 ± 10 μm of (p = 0.046) in response to continuous myopic defocus. During both 30 and 15 minute cycles of alternating myopic and hyperopic defocus of equal duration, the effect of opposing blur sessions cancelled each other and the AxL was near baseline levels following the final defocus session (mean change from baseline across all alternating defocus conditions was +2 ± 10 μm, p > 0.05). Similar, but smaller magnitude, changes were observed for ChT. Conclusions: The human eye appears capable of temporal averaging of visual cues from alternating myopic and hyperopic defocus. In the short term, this integration appears to be a cancellation of the effects of the preceding defocus condition of opposite sign. [ABSTRACT FROM AUTHOR]

We evaluate the ocular effects of proton beam therapy (PBT) in a single institution, in Korea, and identify factors contributing to decreasing visual acuity (VA) after PBT. A total of 40 patients who received PBT for choroidal melanoma (2009‒2016) were reviewed. Dose fractionation was 60‒70 cobalt gray equivalents (CGEs) over five fractions. Complete ophthalmic examinations including funduscopy and ultrasonography were performed at baseline and at 3, 6, and 12 months after PBT, then annually thereafter. Only patients with at least 12 months follow-up were included. During the follow-up, consecutive best-corrected visual acuity (BCVA) changes were determined, and univariate and multivariate logistic regression analyses were performed to identify predictors for VA loss. The median follow-up duration was 32 months (range: 12‒82 months). The final BCVA of nine patients was > 20/40. The main cause of vision loss was intraocular bleeding, such as neovascular glaucoma or retinal hemorrhage. Vision loss was correlated with the tumor size, tumor distance to the optic disc or fovea, maculae receiving 30 CGEs, optic discs receiving 30 CGEs, and retinas receiving 30 CGEs. Approximately one-third of PBT-treated choroidal melanoma patients with good pretreatment BCVA maintained their VA. The patients who finally lost vision (VA < count fingers) usually experienced rapid declines in VA from 6‒12 months after PBT. Tumor size, tumor distance to the optic disc or fovea, volume of the macula, and optic discs or retinas receiving 30 CGEs affected the final VA. [ABSTRACT FROM AUTHOR]

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4(216), which represses VEGF promoter activity. The TEAD4(216) isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4(216) protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4(216) isoform can competitively repress the stimulatory activity of the TEAD4(434) and TEAD4(148) enhancers. Synthesis of the native VEGF(165) protein and cellular proliferation is suppressed by the TEAD4(216) isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4(216) isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases.

The clinical course of age-related macular degeneration (AMD) is related to choroidal conditions, and can be determined by the evaluation of the central choroidal thickness (CCT). The aim of this study was to determine the association between the axial length (AL) and choroidal thickness in AMD by measuring these parameters in patients with and without AMD. Seventy eyes of 70 patients (34 men and 36 women; age, 64–88 years; mean age, 77.0 ± 6.5 years) who underwent cataract surgery from February 2015 to March 2020 at the Department of Ophthalmology, Keio University School of Medicine were retrospectively analyzed. The AMD group (29 patients, 29 eyes) included eyes with early AMD, whereas the control group (41 patients, 41 eyes) included those without ocular diseases other than cataract. Optical coherence tomography images were used to measure the CCT and the choroidal vessel diameter (CVD). The IOL Master was used to measure the AL. The results revealed that mean CCT was greater in the AMD group (238.3 ± 108.3 μm) compared with the age-matched control group (187.2 ± 66.8 μm) (p = 0.03). The CCT was negatively correlated with AL in the overall sample (r = -0.42, p = 0.001), the AMD group (r = -0.42, p = 0.02), and the control group (r = -0.42, p = 0.006). Note that all eyes with CCT > 350 μm were included in the AMD group. CCT and CVD were positively correlated in the overall sample (r = 0.76, p < 0.001) as well as in the individual groups (AMD: r = 0.82, p < 0.001; control: r = 0.76, p = 0.004). Given that CCT is an important parameter for predicting the prognosis of subfoveal diseases, routine evaluation of AL may be valuable for a better understanding of the pathogenesis of AMD. [ABSTRACT FROM AUTHOR]

We aimed to evaluate choroid structural changes using swept-source optical coherence tomography (SS-OCT) following hemodialysis initiation in diabetic and nondiabetic patients with end-stage kidney disease (ESKD). In this multicenter, prospective, cross-sectional study, diabetic (DM group; 30 eyes; 16 patients) and nondiabetic patients (NDM group; 30 eyes; 15 patients) with ESKD were evaluated after hemodialysis initiation. SS-OCT findings were analyzed using a manual delineation technique and binarization method before the first and last hemodialysis sessions, conducted approximately 2 weeks apart. Subfoveal choroidal thickness changes and mean large choroidal vessel layer thickness were significantly greater in the DM group (−13.3% ± 2.5% and −14.5% ± 5.2%, respectively) than the NDM group (−9.5% ± 3.1% and −9.2% ± 3.4%, respectively; p = 0.049 and p = 0.02, respectively). Binarized SS-OCT analysis revealed that the mean subfoveal choroidal area was significantly larger in the DM group (−21.9% ± 6.5%) than the NDM group (−17.2% ± 5.9%; p = 0.032). The change ratio in mean luminal area values was significantly greater in the DM group (−27.7% ± 8.7%) than the NDM group (−17.7% ± 5.8%; p = 0.007). The DM group exhibited substantial changes in the choroidal layer, possibly reflecting choroidal vascular disorders caused by diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate long-term treatment response after intravitreal bevacizumab injections (IVBIs) for central serous chorioretinopathy (CSC). Methods: This retrospective, interventional study investigated the medical records of 45 eyes of 44 patients with CSC who underwent IBVIs and completed at least 2-year follow-up period. Complete resolution (CR) was defined as complete resolution of subretinal fluid at least 3 months after the last IVBI. Thick-choroid CSC was defined as mean subfoveal choroidal thickness more than 300.0 μm. The main outcome measure was long-term treatment outcome after IVBIs in patients with CSC. Results: Thirty-five patients (79.5%) were male, and their mean age was 45.5 ± 9.6 years. The mean follow-up period was 35.1 ± 11.5 months. Twenty-two eyes (48.9%) had acute CSC, and 40 eyes (88.9%) achieved CR. Twenty eyes (50.0%) developed recurrence, the mean number of IVBIs to achieve the first CR was not significantly different between eyes with and without recurrences (2.6 ± 1.6 vs. 2.9 ± 1.9; P = 0.658). Thick-choroid CSC was significantly difference between the eyes with and without recurrence (17 eyes, 85.0% vs. eyes, 50.0%; P = 0.020). Among the baseline characteristics, serous pigment epithelial detachment (B = - 2.580, P = 0.032) and thick-choroid (B = 1.980, P = 0.019) were significantly associated with recurrence. Conclusion: Eyes with CSC treated with IVBI and achieving complete resolution of subretinal fluid have 50% chance of recurrence in the long term. Thinner choroid and serous pigment epithelial detachment appear protective for recurrences. [ABSTRACT FROM AUTHOR]

High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6, SCO2, CCDC102B, BLID, chromosome 15q14, and COL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed that COL8A1 SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 of chromosome 15q14 also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population. [ABSTRACT FROM AUTHOR]