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This study evaluated cone density (CD) in the macular region and assess macular perfusion in children with varying degrees of myopia. This was a prospective, cross-sectional, observational study. Children underwent confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT), and OCT angiography (OCTA) imaging. A built-in software was used to measure mean CD (cells/mm 2 ), retinal vessel density, choriocapillaris perfusion area, and choroidal thickness (CT). The study included 140 eyes from children categorized into four groups: emmetropia (31 eyes), low myopia (44 eyes), moderate myopia (31 eyes), and high myopia (34 eyes). The high myopia group exhibited significantly lower macular CD than the emmetropia group (P < 0.05). Additionally, the high myopia group showed thinner CT and higher choriocapillaris perfusion area in the macular region than the emmetropia group (all P < 0.01). Macular CD was significantly correlated with age, spherical equivalent, axial length, and CT (all P < 0.05). Generalized linear models revealed CT as the independent factor associated with macular CD (Wald χ2 = 9.265, P = 0.002). Children with high myopia demonstrate reduced CD in the macular region, accompanied by reduced CT. These findings may have important implications for future myopia prevention and management strategies., (© 2024. The Author(s).)

Purpose: To compare choroidal structural features in eyes with central macular atrophy related to Stargardt disease (STGD) and non-exudative age-related macular degeneration (AMD)., Methods: Twenty-five eyes of 25 Stargardt cases and 25 eyes of 25 non-exudative AMD cases were included in this retrospective study. Region Finder software was used to measure atrophic areas on blue-light fundus autofluorescence images centered on the macula. The total choroidal area (TCA), luminal area (LA), and stromal area (SA) were calculated using the ImageJ program and Niblack autolocal thresholding method. The choroidal vascularity index (CVI) was assessed., Results: The mean age was 59.4 ± 10.9 years in the STGD group and 68.1 ± 7.6 years in the non-exudative AMD group (P = 0.002). The mean macular atrophic area was 16.06 ± 10.61 mm2 in STGD and 11.73 ± 7.65 mm2 in non-exudative AMD (P = 0.171). The STGD group had significantly higher mean subfoveal choroidal thickness (184.0 ± 62.6 vs. 131.8 ± 62.4 µm), TCA (0.553 ± 0.201 vs. 0.406 ± 0.189 mm2), LA (0.344 ± 0.150 vs. 0.253 ± 0.124 mm2), and SA values (0.208 ± 0.062 vs. 0.153 ± 0.069 mm2) compared to the non-exudative AMD group (P = 0.004, P = 0.011, P = 0.023, and P = 0.004, respectively). However, CVI values did not differ significantly between the two groups (60.58 ± 7.4 vs. 61.93 ± 5.8%, P = 0.432). According to the results of the ANCOVA test, differences in mean SFCT, TCA, and SA persisted when the data were readjusted for age (P = 0.018, P = 0.035, and P = 0.017, respectively)., Conclusion: In non-exudative AMD with geographic atrophy, the reductions in the choroidal compartments are more pronounced than those in STGD. However, similar CVI values may suggest that controversy still exists regarding the role of choroidal compartmental changes in the development of atrophy., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

The choriocapillaris is a dense vascular bed in the inner choroid that supplies the photoreceptor cells and retinal pigment epithelium (RPE). While loss of choriocapillaris density has been described in association with age-related macular degeneration (AMD), whether these changes are primary or secondary to RPE degenerative changes in AMD has been debated. In this study we characterized choriocapillaris loss by quantifying "ghost" vessels in a series of 99 human donor maculae labeled with the UEA-I lectin, and found significant increases in early-intermediate AMD and a greater difference in geographic atrophy in areas with intact RPE. Eyes were genotyped at the CFH Tyr402His locus, and those homozygous for the His allele showed significantly more ghost vessels than those with other genotypes. When only non-AMD eyes were evaluated, His homozygotes had increased ghost vessel density but this trend did not reach statistical significance. These results support the notion that choriocapillaris death often precedes RPE degeneration in AMD and that this loss is an important therapeutic consideration for AMD., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on en face optical coherence tomography (OCT) images as bright lesions measuring at least 250 μm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 μm. Of the large hyperTDs ranging in size between 250 and 300 μm when first detected, only one was not persistent with a baseline GLD of 283 μm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE., Competing Interests: Declaration of competing interest Giovanni Gregori, Philip J. Rosenfeld and Ruikang K. Wang received research support from Carl Zeiss Meditec, Inc. Giovanni Gregori and the University of Miami co-own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr. Rosenfeld also received research funding from Gyroscope Therapeutics. He is also a consultant for Abbvie, Annexon, Apellis, Bayer Pharmaceuticals, Boehringer-Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech, Genentech/Roche, InflammX Therapeutics, Ocudyne, Regeneron Pharmaceuticals, and Unity Biotechnology. He also has equity interest in Apellis, InflammX, Ocudyne, and Valitor. Ruikang K. Wang received other financial support from Colgate Palmolive Company, Estee Lauder lnc, and is a consultant for Carl Zeiss Meditec. He also has several patents: US8, 750, 586, US8, 180, 134, US9, 282,905, US9, 759,544, US10, 354,378, US10, 529,061. The remaining authors have no disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Given the potential role of light and its wavelength on ocular growth, this study investigated the effect of short-term exposure to red, cyan and blue light on ocular biometry in humans., Methods: Forty-four young adults and 20 children, comprising emmetropes and myopes, underwent 2-h sessions of cyan (507 nm), red (638 nm) and broadband white light on three separate days via light-emitting glasses. Additionally, young adults were exposed to blue light (454 nm) on an additional day. Axial length (AL) and choroidal thickness (CT) were measured in the right eye before the light exposure (0 min), after 60 and 120 min of exposure and 30 min after light offset using an optical biometer and optical coherence tomographer, respectively., Results: Compared to broadband light, exposure to red light resulted in a significant increase in AL (mean difference between white and red light at 120 min, +0.007 mm [0.002]), but no significant change in CT, while cyan light caused a significant AL reduction (-0.010 mm [0.003]) and choroidal thickening (+0.008 mm [0.002]) in young adults (p < 0.05). Blue light caused a significant decrease of -0.007 mm (0.002) in young adult eyes at 60 min (p < 0.05). In children, cyan light led to a significant reduction in AL (-0.016 mm [0.004]) and strong sustained choroidal thickening (+0.014 mm [0.004]) compared to broadband light at 120 min (p < 0.05). The effects of cyan light on AL and CT were found to be stronger in myopic young adults and emmetropic children. The opposing effects of red and cyan light on ocular biometry were similar between the two age groups (p > 0.05)., Conclusions: Exposure to cyan light resulted in AL reduction and choroidal thickening in both young adults and children. Further research is needed to determine the application of these results in developing interventions for myopia control., (© 2024 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: To evaluate the optical coherence tomography-angiography (OCT-A) findings and choroidal vascularity index (CVI) of patients followed with a diagnosis of obsessive-compulsive disorder (OCD) by comparing them with the healthy control group (HCG)., Methods: This prospective study included 33 patients diagnosed with OCD and 32 HCG patients who followed up for at least 3 months. OCT-A images were obtained to evaluate the microvascular circulation, and enhanced HD line images were obtained for the CVI calculation of all patients., Results: Statistical analysis results revealed that the rates of superficial vascular density in the fovea region and deep vascular density in the parafovea region decreased in the OCD group compared to the HCG group ( P = 0.003 and P = 0.010, respectively). Subfoveal choroidal thickness values of the OCD group were lower than those of the HCG group ( P = 0.008). While total choroidal area and lumen area values were lower in the OCD group than in the HCG group ( P < 0.001 and P < 0.001, respectively); CVI values were similar in both groups ( P = 0.436)., Conclusion: The use of the OCT-A device, which is a non-invasive method for detecting retinal and choroidal changes in OCD cases, may provide insight into the pathogenesis of the disease., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions., Methods: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied., Results: CEUS analysis showed that the time-averaged estimated contrast was significantly higher ( p  = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM ( p  = 0.001 for CH cases and p  < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher ( p  = 0.032) for CH ( m  = 0.61) than for CM ( m  = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher ( p  = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM., Conclusions: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions.

Purpose: This study aimed to evaluate the choroidal vascular characteristics of patients followed up with different headache diagnoses., Design: Prospective comparative study., Methods: This study included 21 patients with migraine with visual aura (MwA), 20 with migraine without aura, 29 patients experiencing episodic tension-type headache, and 30 healthy participants. The participants was performed refraction values, axial length, and intraocular pressure were examined. Choroidal thickness was determined in all participants with HD-line optical coherence tomography (OCT) in the subfoveal, nasal, and temporal quadrants 500 µm from the fovea. Using special image processing software, luminal area (LA), stromal area, total choroidal area, and choroidal vascular index (CVI) values were calculated in both macular and peripapillary regions. OCT was also used to perform peripapillary retinal nerve fiber layer (pRNFL) thickness and optic disc head measurements., Results: Spherical refraction, axial length, and intraocular pressure values did not significantly differ among the four groups with similar gender and age distributions ( P > 0.05). The LA values in both macular and peripapillary regions were found to be statistically significantly lower in the MwA group ( P = 0.007 and P = 0.005, respectively). There was no statistically significant difference among the groups in terms of the remaining choroidal area parameters or CVI values ( P > 0.05). The groups also did not show any significant difference in the pRNFL or optic disc head measurements performed in different quadrants ( P > 0.05)., Conclusion: While LA, one of the choroidal vascular parameters, was found to be lower in the MwA group in both the macular and peripapillary regions, there were no statistically significant differences between the groups in terms of the peripapillary or macular CVI values., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature Working Group criteria., Methods: Using the medical records of the patients, the authors reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on Standardization of Uveitis Nomenclature criteria and compared the result with the clinical diagnosis., Results: Of 100 eyes, 29 eyes (29%) were diagnosed as punctate inner choroidopathy and 15 eyes (15%) were diagnosed as MCP using Standardization of Uveitis Nomenclature criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed punctate inner choroidopathy eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using Standardization of Uveitis Nomenclature criteria., Conclusion: The existing diagnostic criteria showed limitations in capturing all clinical cases of punctate inner choroidopathy or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia could be considered to enhance diagnostic accuracy.

Purpose: To report a rare finding, choroidopathy, in herpes zoster ophthalmicus (HZO)., Methods: Report of two cases., Results: Multiple, well-defined, choroidal depigmented lesions were demonstrated in two cases of HZO on fundus color imaging, optical coherence tomography, fundus angiography, and indocyanine green angiography at 6 months., Conclusion: This report demonstrates a very rare, late finding of choroidal involvement in two HZO cases.

Purpose: To examine posterior ocular structures with optical coherence tomography (OCT) in individuals using a phosphodiesterase 5 inhibitor (PDI, tadalafil)., Method: This prospective study included 26 eyes of 26 patients who used 1 tablet of 5-mg tadalafil regularly every day for 1 month due to erectile dysfunction. The routine ophthalmological examinations of the participants were performed at the pre-tadalafil and post-tadalafil first-month visits. At both visits, OCT was used to measure the central retinal thickness (CRT), ganglion cell layer + inner plexiform layer (GCL + IPL) thicknesses, and peripapillary retinal nerve fiber layer (pRNFL; average and superior, temporal, inferior, and nasal quadrants) thicknesses. The disc area, rim area, average and vertical cup/disc ratio, and cup volume of the optic disc head were evaluated. Choroidal thickness was measured from five points: the subfoveal area and the nasal and temporal areas 500 and 1500 microns from the fovea. Choroidal vascular area values and choroidal vascular index (CVI) were calculated using a special binarization technique., Results: The mean age of the patients was 56 ± 8(range 34-72) years. No significant difference was detected in the CRT,GCL + IPL thicknesses,or pRNFL thicknesses in any of the quadrants before and after tadalafil use. The optic disc head measurements and choroidal thickness values measured from five points were similar between the two visits. The luminal choroidal area was 0.15 ± 0.04 mm 2 before tadalafil use and 0.17 ± 0.05 mm 2 after 1-month tadalafil use, with no statistically significant difference. The remaining choroidal vascular parameters, namely the stromal and total choroidal area and CVI values, were similar between the two visits., Conclusion: This study showed no significant change in the posterior ocular structures in individuals using tadalafil regular daily use for 1 month due to erectile dysfunction.

Purpose: To evaluate the association between quantitative parameters derived from volume analysis of optical coherence tomography (OCT) data and disease worsening in Vogt-Koyanagi-Harada disease (VKHD) and sympathetic ophthalmia (SO)., Methods: This retrospective study, conducted at Osaka University Hospital, employed swept-source OCT scans from patients diagnosed with VKHD or SO between October 2012 and January 2021. The choroidal vessel structure was segmented and visualized in three dimensions, generating quantitative vessel volume maps. Region-specific choroidal vessel volume (CVV), choroidal volume (CV), and vessel index (VI) were scrutinized for their potential correlation with disease severity., Results: Thirty-five eyes of 18 VKHD and 2 SO patient (8 females, 10 males) were evaluated. OCT-derived CVV maps revealed regional CV alterations in VKHD and SO patients. Two parameters, i.e. CV at 3- and 6-month follow-ups ( p  = 0.044, p  = 0.040, respectively, with area under the ROC curve of 0.70) and CVV at 6 months ( p  = 0.046, area under the ROC curve of 0.71), were significantly higher in recurrent VKHD and SO compared to effectively treated cases., Conclusions: The volume analysis of OCT images facilitates a three-dimensional visualization of choroidal alterations, which may serve as a reflection of disease severity in VKHD and SO patients. Furthermore, noninvasive initial CVV or CV measurements may serve as potential biomarkers for predicting disease recurrence in VKHD and SO.

This study aims to evaluate the macular and the optic nerve head thickness and vascular profiles in KC patients and compare them with two groups of healthy emmetrope and subjects with myopic-astigmatism. This cross-sectional study was conducted at Khatam-Al-Anbia Eye Hospital between 2022 and 2023. Subjects aged 18 to 40 were prone to be included in the study. The participants in this study were grouped into three categories: emmetrope (E), myopic-astigmatic (MA), and keratoconus (KC). All participants underwent a comprehensive ocular examination, as well as macular and optic nerve head (ONH) optical coherence tomography angiography (OCTA). In this study, 143 subjects, 50 cases in the KCN group, 46 cases in the E group, and 47 cases in the MA group, enrolled. There was no difference between the three groups regarding age (p = 0.123) and gender (p = 0.632). The superficial and deep capillary densities at the fovea, parafovea, and perifovea were significantly lower in KC patients than in the control groups (p < 0.01). The radial peripapillary capillary (RPC)- all vessels' density is significantly lower in the KC group (p < 0.001). Besides, the choroidal vascularity index (CVI) and choroidal luminal area (CLA) were considerably higher in KC patients (p < 0.001). The macular and ONH vascular profile in KC patients significantly differs from the vascular profile of healthy controls. Further scientific evidence regarding the systemic implications of keratoconus on the vascular system would be desirable to understand the connections between KC and vascular disease., (© 2024. The Author(s).)

Background: We aimed to compare choroidal thickness (ChT) and retinal nerve fiber layer (RNFL) thickness in the affected and contralateral eyes of patients with Posner-Schlossman Syndrome (PSS) during acute, remission, and intermittent phases., Methods: This prospective observational study included 18 patients(36 eyes) diagnosed with PSS. These patients underwent a comprehensive ophthalmologic evaluation including slit lamp examination, visual acuity testing, intraocular pressure (IOP) measurement, and funduscopic examination, and assessment of RNFL thickness, macular thickness, and macular ChT. Patient data collected included gender, age, number of keratic precipitates (KPs), and number of episodes. Optical coherence tomography (OCT) was used to measure RNFL thickness, macular thickness, and macular ChT in both eyes during the acute, remission, and intermittent phases. The affected eye was compared with the unaffected eye at each phase., Results: In affected eyes, macular ChT was lower in the acute phase compared to the remission phase at N1500, N1000, N500, and subfoveal locations (allp < 0.05).The central macular recess ChT was also significantly thinner in the acute phase compared to the intermittent and remission phases. Age significantly correlated with ChT in the central recess (p = .024). Macular thickness was thinner during the acute phase in the affected eye (p = .048). The RNFL in the affected eye was thinner in the intermittent phase than in the acute phase at the inferior-temporal (p = .011) and global sectors (p = .044). During the acute phase, RNFL in the affected eye was thinner at the superior-nasal (p = .049), inferior-temporal (p = .003), and global (p = .041) sectors compared to the unaffected eye. In the intermittent phase, the affected eye's RNFL was thinner at the superior-nasal, inferior-temporal, inferior-nasal, and global sectors compared to the unaffected eye (allp < 0.05), while no difference was observed in both eyes at the nasal, superior-temporal, and temporal sectors. The number of episodes and age were significantly associated with RNFL thickness (p < .05)., Conclusion: This study demonstrated that in eyes affected by PSS, RNFL, macular ChT, and macular thickness thinned during the acute phase. The number of episodes and age are significant factors in the development of PSS., (© 2024. The Author(s).)

Objective: To investigate the change in choroidal components of patients with Graves' ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence tomography (OCT)., Methods: This cross-sectional study included 151 eyes of 90 patients with GO. Patients were grouped according to the clinical activity score (CAS) and disease severity. Total choroidal area (TCA), luminal area, stromal area (SA) and choroidal vascularity index (CVI) were acquired by image binarisation of the OCT. Ocular parameters between groups were compared using generalised estimating equations, accounting for intereye correlation and adjusting for relevant factors., Results: As for the included eyes, 104 eyes were inactive GO and 47 eyes were active GO. Local choroidal thicknesses were thicker in active GO than in inactive GO. TCA and SA were significantly larger in active GO than in inactive GO group (3.44±0.91 mm 2 vs 3.14±0.88 mm 2 , p=0.046; 1.16 (1.03-1.50) mm 2 vs 1.10 (0.96-1.27) mm 2 , p=0.002, respectively). CAS was positively correlated with TCA (r=0.171, p=0.036) and SA (r=0.172, p=0.035), and negatively associated with CVI (r=-0.174, p=0.032). In multiple regression models, age, diopter and intraocular pressure (IOP) exhibited significant correlations with the SA (β=-0.006, p=0.010; β=0.076, p<0.001; β=0.015, p=0.010, respectively)., Conclusions: Thickened choroid was observed in active GO compared with inactive GO. The proportional increase of SA was augmented as the disease activity progressed. Age, diopter and IOP were independent factors that affected choroidal area and components in patients with GO. Multicentre prospective cohort studies with a large sample size are still needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications., (© 2024. The Author(s).)

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10 -4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration., (© 2024. The Author(s).)

Purpose: To evaluate the peripapillary/parapapillary choroidal vascular parameters in the keratoconus (KC) and to determine the relationship between topography parameters and the peripapillary/parapapillary choroidal vascular parameters., Method: Ninety eyes of ninety patients with different stages of KC and 29 eyes of twenty-nine patients without KC were enrolled in the study. Patients with KC were divided into three groups according to the Amsler-Krumeich classification scale. The choroidal vasculature was assessed by choroidal vascular parameters [such as parapapillary choroidal microvascular density (pCMVd) and peripapillary choroidal vascularity index (pCVI)]. These parameters were also evaluated for correlation with other parameters., Result: The retinal nerve fibre layer thickness (RNFLT) of the superior-temporal area and the pCVI were decreased in group 3 compared to the control group (superiror-temporal RNFLT: 122.27 ± 21.43 vs 139.90 ± 21.7, p = 0.01 and pCVI: 67.04 ± 4.14 vs 69.99 ± 4.38, p = 0.04). The superior-temporal RNFLT was decreased in group 3 compared to group 2 (122.27 ± 21.43 vs 141.83 ± 25.58, p = 0.006). There was a negative correlation between pCVI and average simulated keratometry (mean sim K), but this association was weak (r = - 0.29 p = 0.001)., Conclusion: This study demonstrated that there may be changes in pCVI in patients with grade 3 KC and that there may be an association between pCVI and mean sim K. As KC grade increases, pCVI may decrease. Furthermore, pCVI may have a negative correlation with mean sim K., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Retinal neurovascular unit (NVU) is a multi-cellular structure that consists of the functional coupling between neural tissue and vascular system. Disrupted NVU will result in the occurrence of retinal and choroidal vascular diseases, which are characterized by the development of neovascularization, increased vascular permeability, and inflammation. This pathological entity mainly includes neovascular age-related macular degeneration (neovascular-AMD), diabetic retinopathy (DR) retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Emerging evidences suggest that the angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) signaling pathway is essential for the development of retinal and choroidal vascular. Tie receptors and their downstream pathways play a key role in modulating the vascular development, vascular stability, remodeling and angiogenesis. Angiopoietin 1 (Ang1) is a natural agonist of Tie2 receptor, which can promote vascular stability. On the other hand, angiopoietin 2 (Ang2) is an antagonist of Tie2 receptor that causes vascular instability. Currently, agents targeting the Ang/Tie signaling pathway have been used to inhibit neovascularization and vascular leakage in neovascular-AMD and DR animal models. Particularly, the AKB-9778 and Faricimab have shown promising efficacy in improving visual acuity in patients with neovascular-AMD and DR. These experimental and clinical evidences suggest that activation of Ang/Tie signaling pathway can inhibit the vascular permeability, neovascularization, thereby maintaining the normal function and structure of NVU. This review seeks to introduce the versatile functions and elucidate the modulatory mechanisms of Ang/Tie signaling pathway. Recent pharmacologic therapies targeting this pathway are also elaborated and summarized. Further translation of these findings may afford a new therapeutic strategy from bench to bedside., (© 2024. The Author(s).)

Purpose: Overactivation of the mineralocorticoid receptor (MR) pathway is proinflammatory and contributes to the pathogenesis of diabetic retinopathy and of age-related macular degeneration. Excess of aldosterone, the specific MR ligand, is known to stimulate the production of proinflammatory cytokines and chemokines in extrarenal tissues and cells. In the RPE/choroid complex, aldosterone upregulated genes encoding proteins of the inflammatory response and downregulated genes encoding proteins involved in synaptic activity and neurotransmitters. Yet, cortisol, which is the main MR ligand in the eye, is a potent anti-inflammatory endogenous glucocorticoid. The aim of the present work was to better understand the role of MR activation in retinal inflammation either by acute injection of aldosterone or overexpression of the receptor., Methods: We first analyzed the retinal transcriptomic regulation induced by acute intraocular injection of aldosterone in the rat. Then, we used a transgenic rat overexpressing human MR (hMR) to also conduct retinal transcriptomic analysis as well as histological evaluation of the retina, retinal pigment epithelium and choroid., Results: Our results show that acute intravitreal injection of aldosterone is highly proinflammatory, upregulating pathways related to microglial activation, oxidative stress, cell death, and downregulating pathways related to glial/neuronal cells activity and proper neurotransmission. On the other hand, hMR overexpression mediates a low-grade inflammation in the retina, associated with notable choroidal inflammation and choroidal neuropathy., Conclusions: Consequences of hMR overexpression or aldosterone-injection on retinal transcriptome reveal very distinct pathological mechanisms, with only a few common genes regulated, most of them not being regulated in the same way. Although aldosterone is highly proinflammatory in the retina, MR overactivation in its physiologic milieu mediates a low-grade inflammation in the neural retina.

Purpose: To investigate the long-term effects of repeated low-level red light (RLRL) therapy on the axial length (AL), spherical equivalent (SE), and choroidal parameters., Methods: Two hundred eight myopic eyes were recruited. The RLRL group included 100 eyes, whereas the control group included 108 eyes. Throughout the one-year follow-up period, changes in AL and SE were recorded for both groups. The RLRL group underwent additional choroidal imaging, and changes in choroidal thickness (CT), choroidal vascularity (CV), and choriocapillaris luminal area (CLA) were assessed before and after RLRL therapy., Results: During the follow-up period, the changing trends in AL and SE differed significantly between the RLRL and control groups. In the RLRL group, AL decreased at three and six months (both P < 0.05) and returned to pretreatment values at 12 months (P = 0.453). In contrast, AL increased significantly throughout the follow-up period (three, six, and 12 months) in the control group (all P < 0.001). The SE increased significantly during the entire follow-up period in the RLRL group (all P < 0.001), whereas it decreased significantly in the control group (all P < 0.05). Regarding choroidal parameters, significant improvements were observed in CT, CV and CLA throughout the follow-up period (all P < 0.05), and changes in most choroidal parameters were significantly correlated with changes in AL and SE during the follow-up period (all P < 0.05). Furthermore, AL, SE, and most choroidal parameters showed significant correlations between changes at three and 12 months (all P < 0.05)., Conclusions: RLRL therapy significantly improved choroidal blood perfusion and circulation, which may explain the observed slowing or reversal of myopia progression in the RLRL group. Thus RLRL therapy may be a novel and effective method for controlling myopia. Furthermore, the short-term effect of photobiomodulation therapy (i.e., changes at three months) can be used to predict the long-term effects (i.e., changes at 12 months)., Translational Relevance: In this study, RLRL therapy showed a significant control effect on the development of axial length and spherical equivalent. RLRL therapy also promoted the choroidal blood perfusion and circulation. RLRL therapy could be a novel and effective method for myopia control.

Purpose: The mechanisms underlying a myopia control strategy using scattering lenses are unclear. Therefore, this study investigates the short-term effects of scatter lenses on central and peripheral choroidal thickness and axial length, which serve as a biomarker in myopia progression research., Methods: In total, 23 participants underwent a 60-minute lens wear phase each to five lens conditions: medium peripheral scattering, high peripheral scattering, medium full-field scattering, high full-field scattering and control (clear lens). Central and peripheral choroidal thickness, foveal axial length, and central visual acuity were measured before and after each lens wear condition., Results: Peripheral choroidal thickening was found after the lens wear phase of the medium peripheral scattering condition (+3.91 ± 5.37 µm, P = 0.04), revealing a significant difference to the control lens condition (P = 0.004), most pronounced in the superior peripheral retina (+1.95 ± 10.74 µm, P = 0.02). In the central retina, significant choroidal thickening was only found in the nasal part after exposure to medium full-field scattering (+3.91 ± 11.72 µm) compared to the control condition (P = 0.001). High peripheral and full-field scattering conditions did not significantly affect central or peripheral choroidal thickness. Visual acuity was significantly reduced in the full-field scattering conditions compared to control and peripheral scattering lenses, with no improvement after 60-minute lens wear. Axial length did not differ significantly after 60-minute exposure to any scattering lens condition or when compared to the control lens., Conclusions: The results indicate a local retinal contrast detection mechanism signals the choroid to thicken peripherally after adaptation to medium peripheral scattering but not high peripheral scattering or full-field scattering at all, while central thickening was only significant nasally after exposure to medium full-field scattering. This emphasizes the importance of the peripheral retina and the level of contrast reduction in the context of myopia research., Translational Relevance: This finding gives insight into the mechanism behind the myopia control strategy inducing peripheral scattering.

'Wet' age-related macular degeneration (AMD) is characterized by pathologic choroidal neovascularization (CNV) that destroys central vision. Abundant evidence points to inflammation and immune cell dysfunction in the progression of CNV in AMD. Mast cells are resident immune cells that control the inflammatory response. Mast cells accumulate and degranulate in the choroid of patients with AMD, suggesting they play a role in CNV. Activated mast cells secrete various biologically active mediators, including inflammatory cytokines and proteolytic enzymes such as tryptase. We investigated the role of mast cells in AMD using a model of CNV. Conditioned media from activated mast cells exerts proangiogenic effects on choroidal endothelial cells and choroidal explants. Laser-induced CNV in vivo was markedly attenuated in mice genetically depleted of mast cells (Kit W-sh/W-sh ) and in wild-type mice treated with mast cell stabilizer, ketotifen fumarate. Tryptase was found to elicit pronounced choroidal endothelial cell sprouting, migration and tubulogenesis; while tryptase inhibition diminished CNV. Transcriptomic analysis of laser-treated RPE/choroid complex revealed collagen catabolism and extracellular matrix (ECM) reorganization as significant events correlated in clusters of mast cell activation. Consistent with these analyses, compared to wildtype mice choroids of laser-treated mast cell-deficient mice displayed less ECM remodelling evaluated using collagen hybridizing peptide tissue binding. Findings herein provide strong support for mast cells as key players in the progression of pathologic choroidal angiogenesis and as potential therapeutic targets to prevent pathological neovascularization in 'wet' AMD., (© 2024. The Author(s).)

Objective: To use ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) to evaluate the choroidal features of neovascular age-related macular degeneration (nAMD) and type 1 macular neovascularization (MNV) attributable to central serous chorioretinopathy (CSC)., Method: A cross-sectional research was carried out to examine patients with type 1 MNV due to CSC (50 eyes) and nAMD (98 eyes) utilizing UWF SS-OCTA examinations. The scan procedure covered a vertical 20 mm × horizontal 24 mm region with 9 subfields. A typical set of 68 healthy eyes was used for comparison. The effects of different diagnoses on choroidal parameters were assessed using covariance tests, using gender and age as variables., Results: The research showed that all choroidal characteristics were age-related (all p < 0.05). The calculated marginal averages of choroidal thickness (ChT) and choroidal volume (CV) in the central area were substantially lower in the nAMD group than in the CSC group and the normal group after age differences were taken into account (all p < 0.05). In both the superotemporal and temporal areas, the CSC group had a greater choroidal vascular index (CVI) compared to the nAMD group (p < 0.05). Additionally, the CSC group had a greater temporal area choriocapillaris density (CCD) than the nAMD group (p < 0.05)., Conclusion: At the choroidal level, type 1 MNV due to CSC and nAMD may be distinguished by UWF SS-OCTA. Compared to the nAMD affected eyes, the CSC affected eyes had increased ChT, CV, CVI, and CCD in several areas. The two diseases could be distinguished based on ChT and CV., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Stargardt disease (SD) is a common inherited macular dystrophy. It exhibits a high degree of phenotypic and genotypic heterogeneity. Yellow-white flecks are often found in the posterior pole in the early stages of the disease with a reduction in central vision from foveal atrophy as it progresses. A characteristic dark choroid appearance is seen on fundus fluorescein angiography (FFA) in many cases, with occasional reports of choroidal neovascular membranes. We report a series of four Nigerian patients, with varied presentations diagnosed with SD in our facility. One patient had good vision, while the other three had variable degrees of reduced vision. All patients had macular atrophy and flecks, while three patients had a dark choroid appearance on FFA and one patient developed a choroidal neovascular membrane in one eye., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO 3 ), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO 3 -treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO 3  injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO 3 -treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To explore size, growth, and topographic distribution of choroidal nevi in children to gain insights into choroidal nevogenesis., Design: Retrospective consecutive case series using pediatric clinic - and population-study data, comparing to adult data., Methods: Clinical data from Cole Eye Institute (CEI) database (December 2005-January 2023) was derived from a retrospective consecutive case series of 20 children (< 20 years) with choroidal nevi. For population data, 48 children from previously reported pooled data of the participants of the Sydney Pediatric Eye Disease Study, Sydney Myopia Study, Sydney Childhood Eye Study, and Sydney Adolescent Vascular and Eye Disease Study were included. Fundus photographs were reviewed and the locations of 18 choroidal nevi seen at CEI with widefield imaging were mapped on a radial scatter plot. For comparison, 100 consecutive adults with choroidal nevi were identified from CEI database. Main outcomes were size, growth, and topographic distribution of choroidal nevi., Results: The median largest basal diameter was 1.6 mm (range 0.4-4.2) in children. Most choroidal nevi (75%) remained stable, and 16% demonstrated growth at follow-up. The mean growth rate was calculated as 0.12 mm/year (range 0.10-0.15). Malignant transformation was not noted during childhood. All secondary changes (drusen, orange pigment, and subretinal fluid) associated with choroidal nevi in children were less common than those in adults (p < .05). Choroidal nevi in children were located significantly more posterior than in adults. The median distance to fovea was 2.1 mm (range 0.5-8.5) in children and 5.1 mm (range 0.4-16) in adults (p < .0001)., Conclusions: The onset and growth of choroidal nevi in children suggest active choroidal nevogenesis in childhood. A posterior topographic distribution may support the developmental framework for migration and maturation of choroidal melanoblasts., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to compare choroidal thickness in juvenile open angle glaucoma (JOAG) and healthy controls using spectral domain optical coherence tomography (SD-OCT) and study its correlations., Methods: In this case-control study, 56 eyes of 28 JOAG patients and an equal number of controls were recruited. SD-OCT was used to measure the choroidal thickness (ChT), in the macular region at 5 locations: subfoveal, 1500 µm and 3000 µm nasal and temporal to the foveal center, and in the peripapillary region at 6 locations: up to 1500 µm, nasal and temporal to the disc, respectively. The ChT and its correlations with age, intraocular pressure, cup-to-disc ratio, central corneal thickness, mean deviation, and axial length were studied., Results: The average macular ChT in JOAG was 306.30 ± 56.49 µm vs. 277.12 ± 64.68 µm in controls. The average peripapillary ChT in JOAG was 197.79 ± 44.05 µm vs. 187.24 ± 38.89 µm in controls. The average total ChT (p = 0.042), the average macular ChT (p = 0.022), the subfoveal ChT (p = 0.022), the ChT 1500 µm (p < 0.001), and 3000 µm temporal to the fovea (p = 0.002) were significantly thicker in the JOAG group. In the JOAG group, the average macular ChT had a significant negative correlation with age, whereas axial length was positively correlated with the average peripapillary ChT., Conclusions: In this South Asian cohort of JOAG, the average total ChT, average macular ChT, subfoveal ChT, and ChT at 1500 µm, and 3000 µm temporal to the fovea were significantly thicker when compared to healthy controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To compare the choroidal thickness (CT) and choroidal vascularity index (CVI) values in ocular rosacea (OR) patients across skin subtypes of the disease and healthy controls., Methods: This prospective study included 90 eyes of 90 mild-moderate OR patients with different skin subtypes (30 phymatous, 30 papulopustular and 30 erythematotelangiectatic) and 30 eyes of 30 age-gender matched healthy volunteers. After obtaining the enhanced depth imaging optical coherence tomography images, the CT was measured at subfoveal, 1500 μm nasal and 1500 μm temporal to the fovea, and the CVI was calculated using Image J software in the subfoveal, nasal and temporal areas., Results: There was no CT significant difference between OR patients and healthy controls in all regions (p > 0.05). CVI values of OR patients were found to be significantly lower in the subfoveal, nasal and temporal regions compared to healthy controls (p = 0.02, p = 0.01, p = 0.01, respectively). No CT difference was detected between the subtypes and healthy controls in all regions (p > 0.05). Subfoveal-CVI was significantly lower in the phymatous subtype than the other subtypes and controls (p < 0.05), while nasal and temporal-CVI were significantly lower in the phymatous and papulopustular subtypes than the erythematotelangiectatic subtype and controls., Conclusion: Our study demonstrated no difference between rosacea skin types and healthy controls in terms of CT. Phymatous and papulopustular subtypes were more likely to be affected by chronic inflammation with having lower CVI in most of the regions. Further studies are needed to investigate the association of inflammatory factors with CVI in OR., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p < 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder., Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: In addition to sensorineural hearing loss, Waardenburg Syndrome (WS) may present with variable pigmentation of skin and choroid, which may simulate other life-threating conditions (e.g. melanoma)., Case Report: Two siblings ostensibly presented with unilateral choroidal pigmentary abnormalities concerning for choroidal tumour. Serial ophthalmic examination documented no lesion growth (base or height) whilst the apparent syndromic features (i.e. iris hypochromia, profound sensorineural hearing loss, SNHL), family history (autosomal dominant inheritance) and positive genetic testing (pathogenic MITF variant) led to a revised diagnosis of Waardenburg Syndrome type 2A., Conclusion: Sectoral preservation of choroidal pigmentation in WS is rarely associated with choroidal malignancy. Awareness of syndromic features (e.g. SNHL) and access to genetic testing may facilitate early accurate diagnosis (i.e. allay concern for malignancy), enable treatment of modifiable features (e.g. SNHL) and identify other affected relatives.

Purpose: To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography., Methods: SLE patients with disease duration < 10 years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated., Results: Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9 years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21 years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups., Conclusions: This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate changes in the choroid using the choroidal vascularity index (CVI) and choroidal thickness (ChT) in patients with ocular (OBD) and non-ocular Behçet disease (non-ocular BD)., Methods: Sixty-eight OBD patients, 40 non-ocular BD patients, and 40 healthy control subjects were included. ChT was measured using optical coherence tomography (OCT) in enhanced-depth imaging (EDI) mode (EDI-OCT; sub-foveal ChT at 1000 μm, nasal ChT at 1000 μm temporal ChT). The CVI value (%) was calculated by dividing the luminal area by the sub-foveal total choroidal area., Results: The mean sub-foveal ChT (297 ± 68 µm), nasal ChT (261 ± 66 µm), and temporal ChT (272 ± 68 µm) in eyes with OBD and the mean sub-foveal ChT (286 ± 31 µm), nasal ChT (266 ± 29 µm), and temporal ChT (269 ± 32 µm) in eyes with non-ocular BD were significantly decreased compared with those regions in healthy control subjects (333 ± 69, 301 ± 75, and 312 ± 70 µm, respectively). Additional subgroup analysis was performed for active OBD, inactive OBD, non-ocular BD, and the control group, and in pairwise comparisons, the CVI value was significantly decreased in both active (64.3 ± 3.1) and inactive OBD groups (64.2 ± 4.5) compared with healthy control subjects (67.2 ± 3.6; p = 0.026 and p < 0.001, respectively). There was no significant difference between non-ocular BD (65.9 ± 3.4) and control subjects (67.2 ± 3.6) for CVI measurements (p > 0.05)., Conclusions: Decreased CVI values in OBD suggest that uveitis affects the choroidal vasculature and that perfusion is affected by uveitis, whereas systemic inflammation in non-ocular BD does not affect them. In addition, the choroid in uveitis is affected by the chronicity of the disease rather than disease activity. ChT measurements and CVI values may be a novel and robust prognosticating biomarker to evaluate choroidal vasculature and to monitor disease progression in OBD patients because EDI-OCT is a non-invasive imaging modality. However, CVI does not seem to be a biomarker for monitoring of disease activity or treatment efficacy., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients., Methods: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroidal vascular index. Patients were categorized into a high-dose group if their pioglitazone dose was 30 mg or more per day, and a low-dose group if it was 15 mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location., Results: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone (6.70 and 13.65 µm, respectively) in all subjects. When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both high-dose group (4.48 and 0.84 µm, respectively) and low-dose groups (6.85 and 21.45 µm, respectively), with a greater change observed in the low-dose group (p < 0.05). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00 and 13.15 µm, respectively) and nasal regions (6.43 and 19.24 µm, respectively), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53 µm, p < 0.05). The largest increase in choroidal thickness was observed in the nasal side., Conclusions: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.

Competing Interests: Footnotes and Disclosures The authors have no proprietary or commercial interest in any materials discussed in this photo essay. Funding: Prithvi Ramtohul is supported by The Philippe Foundation.

Background: Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks., Aims: To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA., Methods: This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA., Results: Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease., Conclusions: This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Injuries to the retinal pigment epithelium (RPE) trigger immune responses, orchestrating interactions within the innate and adaptive immune systems in the outer retina and choroid. We previously reported that interleukin 17 (IL-17) is a pivotal signaling molecule originating from choroidal γδ T cells, exerting protective effects by mediating functional connections between the RPE and subretinal microglia. In this current study, we generated mice with aryl hydrocarbon receptor (AhR) knockout specifically in IL-17-producing cells. These animals had deficiency in IL-17 production from γδ T cells, and exhibited increased sensitivity to both acute and chronic insults targeting the RPE. These findings imply that IL-17 plays a crucial role as a signaling cytokine in preserving the homeostasis of the outer retina and choroid., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiyang Cai reports was provided by The University of Oklahoma Health Sciences Center. Jiyang Cai reports was provided by The University of Oklahoma Health Sciences Center. Jiyang Cai reports a relationship with The University of Oklahoma Health Sciences Center that includes: Jiyang Cai has patent pending to NA. NA If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To explore the efficacy of CLS-TA, a proprietary suprachoroidal injectable suspension of triamcinolone acetonide, in noninfectious uveitis (NIU) with macular edema (ME), categorized by anatomic subtype., Methods: Patients diagnosed with ME associated with NIU of any etiology and anatomic subtype were eligible for the phase 3 PEACHTREE trial of CLS-TA. Post-hoc analyses were performed, stratified by discrete anatomic subtype of uveitis (anterior, intermediate, posterior, and panuveitis.)., Results: Across all anatomic subtypes at 24 weeks, patients receiving CLS-TA at baseline and week 12 demonstrated mean increases in BCVA ranging from +12.1 to +15.9 letters, mean central subfield thickness (CST) improvement ranging from -120.1 µm to -189.0 µm, and IOP changes ranging from +0.5 to +3.1 mmHg. Overall, reports of adverse events were similar among subtypes., Conclusions: Irrespective of the uveitic anatomic subtype among patients treated for ME associated with NIU, a clinical benefit in participants treated with CLS-TA was demonstrated, with a comparable safety profile.

Purpose: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism., Methods: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed, including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) at baseline and after laser therapy., Results: In 3 of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross-sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA. The development of this sign was suggestive of active leakage into the subretinal space displacing overlying subretinal hyperreflective material (SHRM) and suggestive of a reversal of RPE pump function. All 6 cases were treated with focal laser to directly target the intense leakage points with remarkable resolution of the fluid due to destruction of the RPE cells mediating reversal of pump function., Conclusions: Unlike chronic CSCR in which degenerative changes of the RPE lead to oozing of fluid into the subretinal space, in acute forms of CSCR including bullous CSCR, there are focal leaks of the RPE that actively drive fluid into the subretinal space suggestive of RPE pump reversal. We propose that pachychoroid disease causes increased hydrostatic pressure and increased resistance to the RPE pump, thereby triggering a reversal in pump function. Understanding this concept can have therapeutic implications., (Published by Elsevier Inc.)

To investigate long-term treatment outcomes of polypoidal choroidal vasculopathy (PCV) with classic type leakage and to compare the outcomes with those of PCV without classic type leakage. This retrospective study included 153 patients diagnosed with PCV and treated with anti-vascular endothelial growth factor (VEGF). Patients showing classic type leakage on fluorescein angiography were included in the classic type leakage group (N = 40, 26.1%), and those without classic type leakage were included in the occult group (N = 113, 73.9%). The best-corrected visual acuity (BCVA) at baseline and 24 months, changes in BCVA, incidence of fibrosis, and lesion reactivation after initial loading injections were compared between the two groups. There was no significant difference in the baseline BCVA between the classic type leakage group (mean logarithm of minimal angle of resolution 0.67 ± 0.53[Snellen equivalents = 20/93]) and the occult group (0.55 ± 0.49[20/70])(P = 0.639). In addition, the BCVA at 24 months (0.44 ± 0.53[20/55] vs. 0.38 ± 0.41[20/47])(P = 1.000), changes in BCVA (0.22 ± 0.42 improvement[2.2 lines] vs. 0.16 ± 0.36 improvement[1.6 lines]) (P = 0.366), and lesion reactivation (P = 0.787) did not differ between the two groups. The incidence of fibrosis was higher in the classic type leakage group (37.5%) than in the occult group (14.2%) (P = 0.002). Although the incidence of fibrosis was higher in PCVs with classic type leakage, the overall treatments were not significantly different between PCVs with and without classic type leakage. In addition, substantial visual improvement was noted at 24 months, suggesting that PCVs with classic type leakage can be effectively treated with anti-VEGF therapy., (© 2024. The Author(s).)

The retina is composed of neuronal layers that include several types of interneurons and photoreceptor cells, and separate underlying retinal pigment epithelium (RPE), Bruch's membrane, and choroid. Different regions of the human retina include the fovea, macula, and periphery, which have unique physiological functions and anatomical features. These regions are also unique in their protein expression, and corresponding cellular and molecular responses to physiological and pathophysiological stimuli. Skeie and Mahajan analyzed regional protein expression in the human choroid-RPE complex. Mitogen-Activated Protein Kinase (MAPK) signaling pathways have been implicated in responses to stimuli such as oxidative stress and inflammation, which are critical factors in retina diseases including age-related macular degeneration. We, therefore, analyzed the Skeie and Mahajan, 2014, dataset for regional differences in the expression of MAPK-related proteins and discussed the potential implications in retinal diseases presenting with regional signs and symptoms. Regional protein expression data from the Skeie and Mahajan, 2014, study were analyzed for members of signaling networks involving MAPK and MAPK-related proteins, categorized by specific MAPK cascades, such as p38, ERK1/2, and JNK1/2, both upstream or downstream of the respective MAPK and MAPK-related proteins. We were able to identify 207 MAPK and MAPK-related proteins, 187 of which belonging to specific MAPK cascades. A total of 31 of these had been identified in the retina with two proteins, DLG2 and FLG downstream, and the other 29 upstream, of MAPK proteins. Our findings provide evidence for potential molecular substrates of retina region-specific disease manifestation and potential new targets for therapeutics development.

Purpose: Insomnia is a common psychiatric disorder that has oxidative and degenerative effects on the brain. It is thought that the brain's processes affect the retina through their synaptic connections. However, the effects of sleep disorders on the retina and choroid are not fully understood. We aimed to investigate the impact of insomnia on retinal nerve fiber layer (RNFL), central foveal thickness, retinal layers, and choroidal thickness., Methods: The right eye of 16 healthy controls and 15 patients with insomnia complaints for 3 months, no history of psychiatric drug use, and an Insomnia Severity Index (ISI) score of 15 or higher were included in the study. The retinal layers and RNFL analyses were performed using optical coherence tomography (OCT), and choroidal layers were analyzed using enhanced depth imaging OCT., Results: Nasal and temporal ganglion cell complex thicknesses were significantly lower in patients with insomnia compared to the controls (97 μm vs. 111 μm P = 0.004; 94 μm vs. 105 μm P = 0.012, respectively). A significant negative correlation was detected between the ISI score and global RNFL thickness (rho, P = 0.03) Additionally, pachychoroid-like vascular structures were observed in choroidal images., Conclusion: These changes in the retina and the choroid layers due to insomnia may be precursors to retinal degenerative conditions, such as age-related macular degeneration that may occur in the future. Multicenter studies including more patients are needed to demonstrate the importance of quality sleep for eye health., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Pachychoroid spectrum disease (PSD) involves various chorioretinal pathologies associated with increased choroidal blood flow. Theoretically, PSD could worsen after cataract surgery since the choroidal thickness tends to increase after surgery. Therefore, we evaluated the prevalence of asymptomatic PSD in patients who underwent cataract surgery and compared the clinical characteristics according to the presence of PSD. The subretinal fluid (SRF) development risk was evaluated using the Cox proportional hazard model. Of 924 eyes, 184 (19.9%) showed asymptomatic PSD. Patients with asymptomatic PSD were older, predominantly male, hyperopic, and showed thicker choroid (P < 0.001, 0.001, < 0.001, and < 0.001). Seven (3.8%) of 184 eyes with asymptomatic PSD developed SRF. The Cox proportional hazard model showed that the flat, irregular pigment epithelial detect (FI-PED; HR 37.337, 95% CI 3.880-359.9300, P = 0.002) was the sole indicator for the SRF development after adjustment of age, sex, and axial length. The SRF-developed PSD group experienced a profound and prolonged increase in the choroidal thickness (P = 0.001, 0.002, and 0.002 at 1, 3, and 12 months). Meticulous preoperative evaluation for FI-PED and postoperative monitoring for choroidal thickness would predict SRF development after cataract surgery in eyes with asymptomatic PSD., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study aims to assess the disparities in choroidal thickness and optic disc parameters between individuals diagnosed with chronic gout and an age- and gender-matched control cohort., Methods: This cross-sectional study involved 30 gout patients receiving treatment at the Rheumatology clinic, alongside 30 healthy control individuals matched for age and gender. A comprehensive ophthalmological assessment, encompassing visual acuity measurement, intraocular pressure evaluation, slit-lamp biomicroscopy, and dilated fundus examination, was conducted for all participants. Peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and subfoveal choroidal thickness (SFCT) were quantified utilizing Spectral Domain Optical Coherence Tomography., Results: The mean age within the study group was 54.53 ± 9.43 years, while the control group's mean age was 53.20 ± 10.36 years. In both the gout and control cohorts, there were 28 men and 2 women. No significant differences were observed in age and gender between the groups. Gout patients manifested thinner RNFL and GCC across all quadrants; however, statistically significant thinning was only evident in the nasal and inferior quadrants for RNFL. Despite a thinner SFCT observed in gout patients compared to controls, this discrepancy did not attain statistical significance., Conclusion: Chronic phase gout patients may display alterations in optic disc and macular parameters, alongside potential variations in choroidal thickness. Nevertheless, more controlled studies encompassing a larger participant pool are imperative to substantiate our findings., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To evaluate the changes of choroidal thickness (CT) and blood flow related to myopia, and its effects of vascular endothelial growth factor (VEGFA) on choroidal vessels in myopia. Subjects were included and divided into emmetropia (EM), non-high myopia (Non-HM) and high myopia (HM) groups. we measured choroidal thickness (CT), choriocapillaris vessel density (VD), and VEGFA content in tears in humans (137 subjects for CT, VD and 84 for tear) and detected the role of VEGFA in the choroid in form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs were divided into control and FDM groups, and the expression changes of choroidal vessels and VEGFA were observed and compared using immunohistochemistry and Western blotting. Twenty-one guinea pigs were divided into control, FDM + Vehicle and FDM + Conbercept groups. The changes of diopter, axis length and choroidal vessels after intravitreal injection of Conbercept were observed. There were significant differences in CT and VD among the three groups (p < 0.05). VEGFA levels in tears were significantly lower in the myopic groups, with a decreasing trend from EM to Non-HM to HM. The choroidal vascular area fraction of FDM decreased compared to the control group. FDM guinea pigs exhibited reduced choroidal vasculature and significant downregulation of VEGFA expression. Following intravitreal injection of conbercept, the FDM + Conbercept group showed greater myopia, longer axial length, and lower choroidal vascular area fraction compared to the control group. VEGFA may participate in the regulation of choroidal blood vessels and blood flow in the progression of myopia. The reduction in VEGFA may accelerates the progression of myopia., (© 2024. The Author(s).)

Purpose: To describe choroidal thickness measurements using a sequential deep learning segmentation in adults who received childhood atropine treatment for myopia control., Design: Prospective, observational study., Methods: Choroidal thickness was measured by swept-source optical coherence tomography in adults who received childhood atropine, segmented using a sequential deep learning approach., Results: Of 422 eyes, 94 (22.3 %) had no previous exposure to atropine treatment, while 328 (77.7 %) had received topical atropine during childhood. After adjusting for age, sex, and axial length, childhood atropine exposure was associated with a thicker choroid by 32.1 μm (95 % CI, 9.2-55.0; P = 0.006) in the inner inferior, 23.5 μm (95 % CI, 1.9-45.1; P = 0.03) in the outer inferior, 21.8 μm (95 % CI, 0.76-42.9; P = 0.04) in the inner nasal, and 21.8 μm (95 % CI, 2.6-41.0; P = 0.03) in the outer nasal. Multivariable analysis, adjusted for age, sex, atropine use, and axial length, showed an independent association between central subfield choroidal thickness and the incidence of tessellated fundus (P < 0.001; OR, 0.97; 95 % CI, 0.96-0.98)., Conclusions: This study demonstrated that short-term (2-4 years) atropine treatment during childhood was associated with an increase in choroidal thickness of 20-40 μm in adulthood (10-20 years later), after adjusting for age, sex, and axial length. We also observed an independent association between eyes with thicker central choroidal measurements and reduced incidence of tessellated fundus. Our study suggests that childhood exposure to atropine treatment may affect choroidal thickness in adulthood., Competing Interests: Declaration of Competing Interest Dr Jost B. Jonas has disclosed European patent EP 3 271 392, JP 2021–119187, and US 2021 0340237 A1: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia. Dr Audrey Chia has disclosed royalties from Myopine. Dr Leopold Schmetterer has disclosed consultancy fee from Thea Pharma., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This study aims to define the characteristics of acquired vitelliform lesions (AVLs) in patients with intermediate age-related macular degeneration (iAMD)., Design: Retrospective, observational, cross sectional study., Subjects: This study included 217 eyes with AVLs associated with iAMD, and an equivalent number of control patients., Methods: OCT scans were evaluated for qualitative and quantitative parameters at both the eye and lesion level. Eye-level parameters included the presence of: hyporeflective core drusen, intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits, macular pachyvessels, central retinal thickness, and central choroidal thickness. Lesion-level qualitative parameters included the presence of ellipsoid zone (EZ) and external limiting membrane disruption overlying the AVL, IHRF overlying the AVL, AVL overlying drusen, pachyvessels under the AVL, a solid core within AVL, and AVL location. Lesion-level quantitative characteristics included AVL height and width, AVL distance from the fovea, and sub-AVL choroidal thickness., Main Outcome Measures: The primary outcomes assessed included the frequency of IHRF, the presence of macular pachyvessels, central choroidal thickness, and the dimensions (both height and width) of AVLs., Results: Comparing the AVL and control groups, the frequency of IHRF (AVL: 49.3% vs. control: 26.3%) and macular pachyvessels (37.3% vs. 6.9%) was significantly higher in the AVL case group, and the central choroidal thickness (256.8 ± 88 μm vs. 207.1± 45 μm) was thicker in the AVL group. Acquired vitelliform lesions located over drusen, with overlying IHRF, or situated subfoveally, and AVL lesions with EZ disruption were found to have a greater lesion height and width compared with AVL lesions lacking these characteristics (P value < 0.001 for all). Additionally, a significant negative correlation was observed between the distance from the fovea and AVL height (Spearman rho: -0.19, P = 0.002) and width (Spearman rho: -0.30, P = 0.001)., Conclusions: This study represents the largest reported cohort of AVL lesions associated with iAMD. Novel findings include the higher frequency of pachyvessels in addition to the presence of a thicker choroid in these eyes, as well as the greater height and width of AVL closer to the foveal center. These findings may offer insights into pathophysiologic mechanisms underlying the development of AVL., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)