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.

[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.

Comparison of macular changes and visual outcomes between femtosecond laser-assisted cataract surgery and conventional phacoemulsification surgery for high myopic cataract patients.

BACKGROUND: To evaluate differences in log MAR best-corrected visual acuity (BCVA) improvement and postoperative central foveal thickness (CFT) and choroidal thickness (CT) changes between conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS) for high-myopia cataracts. METHODS: This was a retrospective and observational study. One hundred and two eyes of 102 patients with high-myopia cataracts were examined. CPS was performed in 54 eyes, and FLACS was performed in 48 eyes. All eyes underwent logMAR BCVA, CFT and CT of three different sectors preoperatively and one week and six months postoperatively. RESULTS: The logMAR BCVA improved significantly after surgery in both groups (both P < 0.001), but no difference was observed in BCVA improvement between the groups (P = 0.554). Moreover, no significant differences were reflected in the changes in CFT, nasal 1 mm CT or temporal 1 mm CT between the two groups, and only subfoveal choroidal thickness (SFCT) in the CPS group decreased significantly compared with that in the FLACS group at any postoperative time (P = 0.003 and 0.026). AL, preoperative logMAR BCVA, and CT of the three regions exhibited a notable correlation with postoperative BCVA (all P < 0.05) according to univariate logistic regression analysis. However, only the AL, preoperative logMAR BCVA and SFCT remained significant in the multivariate model. Postoperative logMAR BCVA revealed a positive correlation with AL and preoperative logMAR BCVA but a negative correlation with SFCT. CONCLUSIONS: FLACS was not superior to CPS in improving BCVA but had less impact on SFCT in the treatment of high-myopia cataracts. Eyes with a longer AL, worse preoperative logMAR BCVA and thinner SFCT had a high risk of worse postoperative BCVA.

[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.

Histologic correlates of "Choroidal abnormalities" in Neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.

Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.

Purpose: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Methods: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery. Results: RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Conclusions: Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.

One-year visual and anatomical outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration after prior brolucizumab treatment.

This single-center retrospective cohort study analyzed the 1-year real-world treatment outcomes of 63 consecutive eyes (of 60 patients) with neovascular age-related macular degeneration (nAMD) that were switched from intravitreal brolucizumab (IVBr) to intravitreal faricimab (IVF) and managed on a treat-and-extend regimen with discontinuation criteria. After the switch, patients opted to continue IVF, to switch back to IVBr, or receive photodynamic therapy (PDT). Thirty-eight patients continued IVF, 16 patients were switched back to IVBr, 2 patients received PDT, and 4 patients paused treatment. Best-corrected visual acuity (BCVA), central subfield thickness (CST), subfoveal choroidal thickness (sf-CT), and injection intervals were compared immediately before and 1 year after the initial IVF. Whereas there was no change in BCVA and CST; 0 [- 0.0969 to 0.125, P = 0.58], - 1.5 [- 27.8 to 13.5, P = 0.11] µm, respectively, sf-CT decreased significantly; - 19.5 [- 45.5 to 7.75, P = 0.015] µm. The patients switched back showed no significant change in sf-CT. The injection interval extended significantly in the IVF continuation and the switch-back group (2.0 and 3.0 weeks, respectively; [P = 0.0007 and 0.0078]) in eyes with a pre-switching interval of less than 12 weeks. Faricimab shows promise as a safe and effective alternative to brolucizumab for treating nAMD.

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.

New suture probe canaloplasty combined with suprachoroidal collagen implantation.

PURPOSE: To present the modified surgery technique of new suture probe canaloplasty with a specially prepared monofilament 4.0 polypropylene suture combined with suprachoroidal drainage (ScD) and collagen sheet implantation for non-penetrating glaucoma surgery. METHODS: Prospective study with a twelve months follow-up. A standard 4/0 polypropylene suture (ProleneTM by Ethicon; thickness: approximately 250 m) is cut and shaped with an ophthalmic knife (MANI® Crescent Knife, Mani Inc 8-3 Kiyohara Industrial Park, Utsunomiya, Tochigi 321-3231, Japan) to create a blunt end without sharp or compressed edges. This improves suture probe canaloplasty by providing a more stable and smoother probing device. Schlemm's canal is prepared using the standard technique of canaloplasty with suprachoroidal drainage. Then, instead of using the canaloplasty microcatheter or the previously published 6/0 double-helix suture, Schlemm's canal is probed with the blunt ending of the 4/0 Prolene suture. After successful 360-degree probing, a doubled 10/0 polypropylene tension suture is threaded through the tip of the 4/0 suture. The 4/0 suture is then pulled back and the 10/0 tension sutures are tied at both ends to tension Schlemm's canal. A special collagen sheet (Ologen®) is placed in suprachoroidal space, and the scleral flap is firmly sewed. RESULTS: 115 eyes were included in this prospective study. In 113 cases the Schlemm's canal could completely be probed with the suture probe and canaloplasty with ScD and collagen sheet implantation succeeded. In two cases the intervention was transformed to 360-degree suture trabeculotomy due to an intraoperative cheese-wiring. Twelve months after successful new suture probe canaloplasty with ScD and Collagen Implantation the IOP had decreased by 37.1% (from 21.6 ± 6.0 mmHg with 3.3 different IOP lowering eye drops to 13.5 ± 3.5 mmHg with 1.0 eye drops). 16 Patients did not achieve sufficient IOP levels and underwent 360-degree suture trabeculotomy during the follow-up. One patient had to be treated with further glaucoma surgery to achieve a sufficient IOP level. Complications were hyphema, postoperative IOP elevation and transient hypotony. No serious or sight-threatening complications occurred. CONCLUSION: New suture probe canaloplasty with ScD and collagen sheet implantation yields the opportunity to conduct a cost-effective canaloplasty easier and less complicated than with the previously described method with the twisted 6/0 suture. The safety profile and IOP lowering effect is comparable. In cases where complete probing fails, there is still the opportunity to switch to suture trabeculotomy over the majorly probed part of Schlemm's canal. The pressure lowering effect of the deep sclerectomy with ScD and suprachoroidal collagen sheet implant seems to have an additional impact on the sufficient pressure lowering procedure.

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.

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

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

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

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

Diagnostic and therapeutic considerations in patients with bilateral diffuse uveal melanocytic proliferation.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP). METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process. RESULTS: BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones. CONCLUSIONS: BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy.

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.

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

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

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.

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

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