Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia.

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

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

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

High correlated color temperature artificial lighting impairs retinal pigment epithelium integrity and chloride ion transport: A potential mechanism for choroidal thinning.

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.

Role of NLRP3 Inflammasomes in Monocyte and Microglial Recruitments in Choroidal Neovascularization.

Although the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2RFPCx3cr1GFP dual-reporter mice and immunostaining techniques to confirm localization of NLRP3 inflammasomes in the laser-induced CNV (LCNV) lesions. Confocal microscopy was used to image and quantify LCNV volumes. MCC950 was used as NLRP3 inhibitor. ELISA and quantitative RT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1ß protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (-/-) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that red fluorescent protein (RFP)-positive monocyte-derived macrophages and GFP-positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post-laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2RFP-positive macrophages, Cx3cr1GFP-positive microglia, and other cells, resulting in an increase in total lesion size. NLRP3 (-/-) LCNV mice showed significantly increased lesion size compared with age-matched controls. Inhibition of NLRP3 resulted in decreased IL-1ß mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1ß.

Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline.

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.

[Circumscribed choroidal hemangioma and non-pigmented choroidal melanoma: clinical, instrumental and molecular genetic features]. / Otgranichennaya gemangioma i bespigmentnaya melanoma khorioidei: kliniko-instrumental'nye i molekulyarno-geneticheskie osobennosti.

Circumscribed choroidal hemangioma (CCH) and early non-pigmented choroidal melanoma (CM) have similar clinical, ultrasound and morphometric features, which in some cases makes their differential diagnosis difficult. There are few studies in the literature devoted to a comparative analysis of the molecular genetic features of CCH and non-pigmented CM, and the results of those studies are contradictory. PURPOSE: This study attempts to develop a method of non-invasive molecular genetic differential diagnostics of CCH and non-pigmented CM. MATERIAL AND METHODS: Based on the results of clinical and instrumental examination methods, 60 patients (60 eyes) with CCH (n=30) and non-pigmented CM (n=30) were included in this prospective study. The control group consisted of 30 individuals without intraocular tumors. Mutations in the GNAQ/GNA11 genes were determined by real-time PCR using the analysis of genomic circulating tumor DNA isolated from peripheral blood plasma. The average follow-up period was 12.1±1.8 months. RESULTS: The study revealed a significant association of mutations in exons 4 and 5 of the GNAQ/GNA11 genes with the presence of non-pigmented CM (27/30; 90%). These mutations were not detected in the group of patients with CCH. Mutations in exons 4 and 5 of the GNAQ/GNA11 genes were also not detected in the control group of healthy individuals. CONCLUSION: This study proposes a method of non-invasive and low-cost differential diagnostics based on molecular genetic analysis and detection of mutations in exons 4 and 5 of the GNAQ and GNA11 genes, which are specific for CM (90%).

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

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

[Predicting the effectiveness of organ-preserving treatment of choroidal melanoma using optical coherence tomography data]. / Prognozirovanie effektivnosti organosokhrannogo lecheniya melanomy khorioidei po dannym opticheskoi kogerentnoi tomografii.

Optical coherence tomography (OCT) is currently widely used for the diagnosis of choroidal melanoma (CM), but the problem of predicting the outcomes of planned CM treatment remains unsolved. PURPOSE: This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment. MATERIAL AND METHODS: OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account. RESULTS: Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction. CONCLUSION: When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.

Mast cells in human choroid and their role in age-related macular degeneration (AMD).

The role of mast cells in physiologic and pathological processes extends far beyond the allergy processes: they are involved in wound healing, chronic inflammation, and tumor growth. This short article emphasizes the role played by mast cells in age-related macular degeneration (AMD). Mast cells can induce angiogenesis and are present around Bruch's membrane during the early and late stages of choroidal neovascularization in AMD. Proteolytic enzymes released by mast cells lead to thinning of the choroid in AMD as well as degradation of vascular basement membranes and Bruch's membrane, which in turn could result in retinal pigment epithelial death and choriocapillaris degeneration in geographical atrophy and exudative AMD.

Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions.

PURPOSE: This study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion. METHODS: A retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography. RESULTS: The mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 µm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression. CONCLUSION: We observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.

Thinning of the retinal nerve fiber and choroidal layers in adolescents with anorexia nervosa: A controlled study.

PURPOSE: We aimed to evaluate retinal nerve fiber and choroidal layer alterations in adolescents with anorexia nervosa using spectral-domain optical coherence tomography. METHODS: Thirty patients with anorexia nervosa and 30 healthy adolescents aged 12-18 years were included in this study. Their age, sex, body mass index, anorexia nervosa type, disease duration, and spectral-domain optical coherence tomography data were recorded. RESULTS: Central macular thickness and retinal nerve fiber layer thickness in the temporal and inferior regions were significantly lesser in patients with anorexia than in healthy controls (p<0.05). Moreover, significant choroidal thinning around the foveal and subfoveal regions in patients with anorexia was observed (p<0.05). In addition, a statistically significant relation between the increase in disease duration and the thinning of the inferior retinal nerve fiber layer was detected (p<0.05). CONCLUSION: The retinal nerve fiber layer and choroidal layer thicknesses were lesser in patients with anorexia than in healthy controls. Screening for retinal indices might prevent the development of irreversible retinal pathologies in adolescents with anorexia nervosa. In addition, thinning of the retinal nerve fiber and choroidal layers could reflect structural or functional changes in the brain of adolescents with anorexia nervosa.

Multifractal Analysis of Choroidal SDOCT Images in the Detection of Retinitis Pigmentosa.

The aim of this paper is to investigate whether a multifractal analysis can be applied to study choroidal blood vessels and help ophthalmologists in the early diagnosis of retinitis pigmentosa (RP). In a case study, we used spectral domain optical coherence tomography (SDOCT), which is a noninvasive and highly sensitive imaging technique of the retina and choroid. The image of a choroidal branching pattern can be regarded as a multifractal. Therefore, we calculated the generalized Renyi point-centered dimensions, which are considered a measure of the inhomogeneity of data, to prove that it increases in patients with RP as compared to those in the control group.

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

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

Neuroretinal degeneration in a mouse model of systemic chronic immune activation observed by proteomics.

Blindness or vision loss due to neuroretinal and photoreceptor degeneration affects millions of individuals worldwide. In numerous neurodegenerative diseases, including age-related macular degeneration, dysregulated immune response-mediated retinal degeneration has been found to play a critical role in the disease pathogenesis. To better understand the pathogenic mechanisms underlying the retinal degeneration, we used a mouse model of systemic immune activation where we infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13. Here, we evaluated the effects of LCMV infection and present a comprehensive discovery-based proteomic investigation using tandem mass tag (TMT) labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Changes in protein regulation in the posterior part of the eye, neuroretina, and RPE/choroid were compared to those in the spleen as a secondary lymphoid organ and to the kidney as a non-lymphoid but encapsulated organ at 1, 8, and 28 weeks of infection. Using bioinformatic tools, we found several proteins responsible for maintaining normal tissue homeostasis to be differentially regulated in the neuroretina and the RPE/choroid during the degenerative process. Additionally, in the organs we observed, several important protein pathways contributing to cellular homeostasis and tissue development were perturbed and associated with LCMV-mediated inflammation, promoting disease progression. Our findings suggest that the response to a systemic chronic infection differs between the neuroretina and the RPE/choroid, and the processes induced by chronic systemic infection in the RPE/choroid are not unlike those induced in non-immune-privileged organs such as the kidney and spleen. Overall, our data provide detailed insight into several molecular mechanisms of neuroretinal degeneration and highlight various novel protein pathways that further suggest that the posterior part of the eye is not an isolated immunological entity despite the existence of neuroretinal immune privilege.

Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration.

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.

Choroidal and central macular thickness before and after treatment in post fever retinitis.

PURPOSE: To study the choroidal thickness (CT) and central macular thickness (CMT) in post-fever retinitis (PFR) and their correlation with visual acuity and treatment. METHODS: A retrospective, observational study of patients presenting with PFR from 2013 to 2021 and with spectral domain optical coherence tomography (SD-OCT) (Heidelberg®, SpectralisTM, Heidelberg, Germany) images were included. The CT and CMT were measured at presentation and at the final visit. The CT was measured subfoveally and at points 2000 µm superior, inferior, medial, and lateral from the fovea using the caliper tool. RESULTS: Seventy-nine eyes of 65 patients were included for this study. The mean age was 39.03 (±16.00) years with female preponderance of 53.84% (n = 35). Mean follow-up duration was 30 days. Mean CT at presentation and at follow-up was 254.12 µm and 241.51 µm, respectively. CT was decreased in majority of the eyes 67.1% (n = 53) from their baseline value. Mean CMTs at presentation and final visit were 454.8 µm and 223.7 µm, respectively. Best corrected visual acuity had a positive correlation with CMT (r = 0.340; P = 0.002) and negligible correlation with CT. A significant decrease in the mean CT was noted in patients who received doxycycline either alone or in combination with a steroid as compared to those who did not receive any treatment (P < 0.001). The significance of which is unknown presently. CONCLUSION: CMT has a greater role in determining the final visual outcome than CT. CT can be reduced post-treatment with no effect on vision.

Assessing acute nicotine impact on choroidal thickness: a randomized, double-blinded study comparing smoking cessation aids, including nicotine gum and electronic cigarettes.

PURPOSE: To explore whether differences in choroidal thickness arise from nicotine consumption in healthy young individuals, specifically comparing the effects of nicotine gum to electronic cigarette (vaping), while maintaining a consistent 4 mg nicotine dosage. METHODS: In a randomized double-blinded prospective cross-sectional study, 20 healthy participants (mean age ± standard deviation: 23 ± 2.36 years) were randomly assigned to either the nicotine gum or vaping group. Choroidal thickness (ChT) measurements were conducted using optical coherence tomography (OCT) (Topcon 3D OCT-1 Maestro System) at baseline, 30, and 60 min after ingesting 4 mg of nicotine, with ChT measurements taken from five different horizontal areas. RESULTS: Neither the nicotine delivery method (gum or vaping) demonstrated a statistically significant impact on ChT mean scores among subjects in the five measured areas at baseline, 30, and 60 min (p > 0.05). However, significant differences were observed in ChT mean scores within subjects across the five areas (F (1.83, 72) = 36.43, p < 0.001), regardless of other study factors such as group, time, and visit (p > 0.05). A statistically significant interaction was identified between the factors of area and time concerning participants' ChT mean scores when stratified by the type of smoking (tobacco, vaping, and dual) (p = 0.003). CONCLUSION: The results of this study revealed that nicotine, up to particular concentration of 4 mg, does not have a statistically significant vasoconstrictive effect on choroidal thickness, regardless of the delivery method, within the examined group. These findings offer valuable insights into the relationship between nicotine intake and choroidal dynamics in young adults.

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model.

Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.