Clinical factors and predictors for spontaneous separation of epiretinal membranes.

PURPOSE: To investigate the clinical characteristics, imaging features, and predictive factors for spontaneous separation in patients with idiopathic or secondary ERM. METHODS: The overall cohort was divided into two subgroups: idiopathic ERM (28 eyes, 56%) and secondary ERM (22 eyes, 44%). Electronic records and multimodal imaging were reviewed. RESULTS: Among the 50 eyes included in this study, the self-separation of ERM occurred over a mean duration of 28.1 ± 25.3 months (median: 25.4 months). Compared with the secondary ERM group, the idiopathic group had a shorter interval to separation (idiopathic vs. secondary, 23.4 vs. 34.1 months, respectively; P = .01) and better vision at diagnosis (logMAR 0.094 vs. 0.224; P = .009) and after separation (logMAR 0.097 vs. 0.188; P = .01). Overall, in both subgroups, spontaneous ERM separation appeared to have been induced by posterior vitreous detachment (PVD) (P < .001). Multivariate analysis revealed that the self-separation interval (odds ratio [OR] 0.936) and IRF (OR 0.049) were significantly associated with complete ERM separation (all P < .05). Additionally, secondary ERM (OR 15.224) and lower initial best-corrected visual acuity (OR 267.589) were significantly associated with improvements in vision after self-separation (all P < .05). CONCLUSION: The self-separation of ERM appears to be induced by PVD development in most eyes. Owing to the possibility of complete spontaneous separation, surgical membrane peeling may be delayed by up to 28 months in eyes without PVD, regardless of whether the cause is idiopathic or secondary. Patients with secondary ERM may experience favorable visual improvement after self-separation despite having poor vision at diagnosis and IRF on OCT. KEY MESSAGES: What is known • An epiretinal membrane (ERM), the most prevalent retinal disease in adults, is less understood regarding clinical factors and the accurate mechanism of spontaneous separation. What is new • The separation of ERM appears to be induced by PVD development in most eyes. • Favorable vision outcomes were associated with secondary ERMs and lower initial visual acuity. • Complete ERM separation was associated with a shorter self-resolution interval and the absence of intraretinal fluid (IRF) in OCT imaging.

Vitreoretinal lymphoma: the importance of cerebral spinal fluid evaluation at initial diagnosis.

BACKGROUND/AIMS: To determine if patients with vitreoretinal lymphoma (VRL) and concomitant central nervous system lymphoma (CNSL) may present without brain MRI findings, but possess cerebrospinal fluid (CSF) suspicious for lymphoma. METHODS: This was a retrospective, single-centre, observational study evaluating patients with a diagnosis or suspicion of VRL seen at Memorial Sloan Kettering Cancer Center between 2006 and 2024. Patients were included if the final diagnosis was biopsy-proven CNSL and both MRI brain with and without contrast±CSF evaluation (obligatory for inclusion if MRI negative) were performed at the initial diagnostic workup. Patients were excluded if CNS disease treatment (brain, spine or CSF) preceded ocular disease. Patients with prior extra-CNS disease were included. Clinical records and radiographic imaging were retrospectively reviewed and relevant data were recorded for each patient. We evaluated the proportion of patients with MRI negative and CSF suspicious for lymphoma. Subgroup analysis included imaging features, pathology, treatment and disease course. RESULTS: We identified 65 patients. Of the 65 patients at the presentation of VRL, 30 had negative MRI brain and CSF, 16 had positive brain MRI and negative CSF and 8 had both positive MRI brain and CSF. 11 (16.9%) had CSF suspicious for lymphoma without positive findings on MRI of the brain. In this subgroup, the median age was 66 years (range 49-82) and 36% were female. 86% of these patients were asymptomatic neurologically. 73% underwent systemic treatment. At a mean 3 years follow-up, 91% of patients were living. CONCLUSION: In patients with suspected VRL, it is possible to have CSF test positive for lymphoma in the context of negative brain MRI. This suggests, when evaluating VRL patients for concomitant CNS disease, CSF evaluation leads to earlier detection and systemic treatment, even when MRI brain findings are negative. In our cohort, an absence of CSF evaluation in the context of negative brain MRI could have missed 16.9% of patients with CNS lymphoma.

Effective Prediction of Drug Transport in a Partially Liquefied Vitreous Humor: Physics-informed Neural Network Modeling for Irregular Liquefaction Geometry.

As the medium for intravitreal drug delivery, the vitreous body can significantly influence drug delivery because of various possible liquefaction geometries. This work innovatively proposes a varying-porosity approach that is capable of solving the pressure and velocity fields in the heterogeneous vitreous with randomly-shaped liquefaction geometry, validated with a finite difference model. Doing so enables patient-specific treatment for intravitreal drug delivery and can significantly improve treatment efficacy. A physics-informed neural network (PINN) model is also established for the simulation, and three cases are used for validation. Despite limited information, the PINN model, together with the varying-porosity approach, captured fluid and drug transport in the partially liquefied vitreous. This opens the possibility for optimizing intravitreal drug delivery based on ultrasonography in clinical practice.

Negative impact of internal limiting membrane peeling in vitreous hemorrhage secondary to retinal vein occlusion with macular ischemia.

PURPOSE: To investigate the effect of internal limiting membrane (ILM) peeling on visual outcomes and postoperative epiretinal membrane (ERM) after pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) associated with retinal vein occlusion (RVO) with various degrees of macular ischemia. METHODS: We compared the outcomes of eyes that underwent vitrectomy with and without ILM peeling from 2012 to 2021 with a minimum follow-up of 6 months. RESULTS: 112 charts were analyzed, and 51 eyes met the inclusion criteria. There were 19 eyes with ILM peeling and 32 eyes with non-ILM peeling. Baseline characteristics did not differ significantly. The mean postoperative visual acuity significantly improved at 6 months compared with the mean preoperative visual acuity (P < 0.001). Visual improvement was significantly greater in the non-ILM peeling group(P < 0.05). Without ischemia within the arcade, there was no significant difference in the visual improvement. In patients with ischemia, the visual improvement in the ILM peeling group was significantly worse than that in the non-ILM peeling group. The incidence of postoperative ERM was significantly higher in the non-ILM peeling; however, there was no significant change in postoperative vision due to the presence of ERM. CONCLUSIONS: Vitrectomy either with or without ILM peeling results in visual improvement in patients with VH associated with RVO; however, it should be uniformly avoiding ILM peeling in cases with pre-existing macular ischemia, as it may significantly lead to a deterioration in visual outcomes. KEY MESSAGES: What is known Pars plana vitrectomy is effective for visual improvement in vitreous hemorrhage associated with retinal vein occlusion. The incidence of postoperative epiretinal membrane is variable depending on the surgical approach. What is new Avoiding ILM peeling in cases of macular ischemia during vitrectomy is crucial for better visual outcomes. Despite higher rates of epiretinal membrane post-surgery in non-ILM peeled eyes, their visual outcomes remain superior to those with ILM peeling.

A proof-of-concept study of a prototype needle that mitigates intraocular pressure rise following intravitreal injection.

PURPOSE: To determine the feasibility of a prototype needle that enhances vitreous reflux (VR) to control intraocular pressure (IOP) in intravitreal injection (IVI). METHODS: We created an eye model to compare IVI using a standard 30-G needle with four different versions of a 30-G prototype needle with one to four surface grooves that enhanced VR. We injected 50, 70, and 100 µl saline through porcine sclera or 460-µm-thick rubber and measured the peak and 3-second pressure before we extracted the needle and measured the 10-second pressure. RESULTS: 50-µl injection through sclera with the standard needle resulted in mean (SD) pressure of 58.6 (3.8) mmHg at peak, 52.8 (4.7) mmHg at 3 s, and 39.6 (18.0) mmHg at 10 s. The prototype needle lowered the pressure; four grooves resulted in mean (SD) pressure of 29.4 (5.6) mmHg at peak, 22.0 (3.7) mmHg at 3 s, and 7.2 (6.6) mmHg at 10 s. 70-µl and 100-µl injections through sclera with the standard needle resulted in mean (SD) pressure of 68.8 (3.6) and 86.0 (6.0) mmHg at peak. Similar to 50-µl injection, the prototype needle lowered the pressure for 70-µl and 100-µl injections. At 10 s, we observed varying leakage at the injection site for sclera but not for rubber. CONCLUSIONS: The study provides proof of concept for a needle design for which surface grooves enhance VR and counteract the effect of IVI on IOP. The safety and efficacy of the prototype needle must be studied further in a clinical trial.

Is longer axial length protective of vision-threatening diabetic retinopathy across different ages? A multicenter cohort of 736 patients.

PURPOSE: Vision-threatening diabetic retinopathy (VTDR) included severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and clinically significant diabetic macular edema (DME). To compare the axial length (AL) and assess its influence on VTDR across different ages. METHODS: A retrospective cohort study. Medical chart review was performed in 736 consecutive patients with VTDR. The patients were divided into young (≤ 45 years) and elderly group (> 45 years) based on their age at the diagnosis of VTDR. After at least one year of standardized treatments, all eligible patients were followed up. The main outcome measures included the presence of tractional retinal detachment (TRD) involving foveal, final best-corrected visual acuity (BCVA), the development of neovascular glaucoma (NVG), and recurrent vitreous hemorrhage (VH) post-vitrectomy. ALs were compared between two age groups. The impact of AL on clinical outcomes was determined by logistic analyses after controlling for systemic parameters. RESULTS: The study included 144 patients ≤ 45 years and 592 patients > 45 years. Young patients had significantly longer AL than elderly participants (23.9 mm vs 23.0 mm, p < 0.001). Over a median follow-up of 25.9 months, a larger proportion of young patients developed TRD (34.7% vs 16.2%, p < 0.001) and recurrent VH (18.6% vs 10.3%, p = 0.040) than elderly patients. In elderly group, longer AL is an independent protective factor in preventing TRD (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4-0.7; P < 0.001). However, this beneficial effect was not observed in young patients. CONCLUSIONS: Young patients with VTDR exhibited significantly longer AL but more aggressive clinical signs with compromised prognosis. In elderly group, a longer AL independently reduced the risk of TRD, while this protective effect did not exist for young patients.

Flow Characterization in a Partially Liquefied Vitreous Humor.

The purpose of this study is to systematically examine the basic fluid dynamics associated with a fully liquid region within a porous material. This work has come about as a result of our investigation on the ocular fluid dynamics and transport process in a partially liquefied vitreous humor. The liquid is modeled as a sphere with Stokes flow while the surrounding infinite porous region is described by Brinkman flow. The development here provides basic three-dimensional axisymmetric results on flow characterization and also serves to evaluate the limits of validity of Darcy flow analysis for the same geometry. In the Darcy flow model, the liquid region is also treated as a porous region with a much higher permeability. Therefore, both liquid and porous regions are modeled by Darcy's law. Besides the analytical results from Brinkman-Stokes model, the simpler case of Darcy-Darcy flow for the same geometry has been provided. The results of both cases are compared and the differences between the two sets of results provide the range of validity of our computational model (Khoobyar et al. in J Heat Transf 144:031208, 2022). Some interesting fluid-dynamical aspects of the system are observed through the analysis. For the Darcy-Darcy system, the liquid region velocity is uniform throughout, as expected for potential flow. With the Brinkman-Stokes model, the liquid region has a paraboloidal profile with the maximum possible peak value of six times the far-field velocity in the porous medium. With the liquid region having a lower resistance, the flow tends to converge there for both models as it seeks the path of least resistance. As for the validation of the Darcy-Darcy model, it is a good approximation as far as the exterior flow is concerned. However, the liquid region flow profiles for the two models are different as noted. The current Brinkman-Stokes model has led to explicit analytical solutions for the flow field for both regions. This has permitted an asymptotic analysis giving deeper insight into the flow characterization.

Characteristics of posterior precortical vitreous pockets visualized by swept-source OCT and en face OCT.

To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 µm and 662.47 ± 326.39 µm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet's tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.

Impaired Visual Function in Posterior Vitreous Detachment Assessed With the Active-Learning Quantitative Contrast Sensitivity Function Test.

Introduction: To investigate whether there is visual function impairment in patients with posterior vitreous detachment (PVD) using the active-learning quantitative contrast sensitivity function test. Methods: In this cross-sectional study, contrast sensitivity was measured in eyes with PVD and eyes without PVD using the quantitative contrast sensitivity function algorithm on the Adaptive Sensory Technology platform. Outcomes included the area under the log contrast sensitivity function curve, contrast acuity, and contrast sensitivity thresholds at 1 to 18 cycles per degree (cpd). Snellen visual acuity (VA) was also measured. Mixed-effects multiple linear regression analyses were performed to evaluate the association between the presence of PVD and visual function, controlling for age and lens status. Results: The cohort comprised 232 healthy eyes of 205 participants; of these, 80 eyes of 69 patients had PVD. There was no significant association between VA and PVD presence. However, PVD was significantly associated with decreased contrast sensitivity thresholds at 1.5 cpd (ß, -0.058; P = .003) and 3 cpd (ß, -0.067; P = .004). Contrast sensitivity thresholds at lower (1 cpd) or higher (6, 12, 18 cpd) spatial frequencies did not significantly correlate with PVD presence. Even in the subgroup of symptomatic PVD eyes, VA was not significantly decreased, while quantitative contrast sensitivity function outcomes showed visual function deficits at low spatial frequencies (1.5 cpd and 3 cpd). Conclusions: Contrast sensitivity measured with the quantitative contrast sensitivity function test showed visual function deficits in eyes with PVD that would have been missed with VA testing alone. Incorporating this test in the retina clinic might offer a more comprehensive functional assessment of eyes with PVD, serving as an adjunct outcome metric in clinical decision-making.

In vitro ß-hydroxybutyrate stability evaluation in femoral blood and vitreous humor for integration into forensic toxicology practices.

Thanatological biochemistry has gained prominence in determining causes of death, especially when suspected fatal pathologies do not exhibit clear postmortem macroscopic and/or microscopic features, such as in cases of ketoacidosis. Indeed, in these cases, the measurement of ß-hydroxybutyrate (BHB) in femoral blood and/or vitreous humor is of particular importance. However, data on its in vitro stability remain scarce, especially in vitreous humor. In this context, the study reported here aims to assess the in vitro stability of BHB. BHB quantification was performed using a liquid chromatography coupled with tandem mass spectrometry method. To investigate BHB stability, two different postmortem matrices were considered: femoral blood and vitreous humor. These matrices were pooled, aliquoted and spiked with BHB at three different concentrations (50 mg/L, 100 mg/L, and 200 mg/L; n = 3). Initial BHB concentrations were established on day 1. Each sample was then divided into two aliquots for storage under two conditions: 20 °C and 4 °C. Analyses were performed on Day 3, 7, 14, and 28. The study revealed no significant degradation of BHB in femoral blood or vitreous humor over time (days 1-28), confirming the robustness and reliability of BHB measurement in these matrices as a postmortem biomarker of ketoacidosis under the tested temperature conditions (+4 °C or -20 °C). These results support a systematic integration of BHB measurement into the routine workflow of forensic toxicology laboratories.

The role of vitreous cortex remnants in secondary macular hole formation and spontaneous closure following vitrectomy for rhegmatogenous retinal detachment.

BACKGROUND: Macular hole (MH) formation after rhegmatogenous retinal detachment (RRD) surgery is rare, and in most cases, additional surgical procedures are required to repair MH. Spontaneous closure of the MH is even rarer. In this study, we aimed to report a series of cases of spontaneous closure of the secondary MH and provide a review of the literature METHODS: We retrospectively collected the cases of secondary MH formation following vitrectomy in RRD patients followed by spontaneous closure. Ophthalmological data at presentation and during follow-up were collected and analyzed. RESULTS: We reported a total of three RRD patients aged 31,67,12 years, including two females and one male. The three patients underwent pars plana vitrectomy (PPV) with either silicone oil tamponade or air tamponade. Optical coherence tomography (OCT) revealed a second full-thickness MH formation with remnant vitreous cortex bridging in the macular region during early follow-up. Observations of the cases revealed subsequent remnant vitreous cortex traction remission and spontaneous closure of MH during follow-up, although with subsequent thin macular and abnormal macular structure. CONCLUSION: The progression of secondary MH formation in the cases may be related to vitreomacular traction (VMT) by the posterior vitreous cortex remnant after PPV, and the release of VMT may help the spontaneous closure of the MH after PPV for RRD.

Effect of Preoperative Glucocorticoid Application on Vitreous Parthanatos-Related Protein Expression in Patients with Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment.

PURPOSE: The protein concentrations of apoptosis inducing factor (AIF), macrophage migration inhibitory factor (MIF), interleukin-1ß (IL-1ß), poly ADP ribose polymerase-1 (PARP-1), poly (ADP-ribose) (PAR), α-synuclein (α-SYN), monocyte chemotactic protein­1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the vitreous of eyes with rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) were observed and analyzed. METHODS: A total of 57 patients' samples were included. 30 patients with RRD were set as the control group, 27 patients with RRDCD were set as the experimental group (16 patients with preoperative glucocorticosteroid (GC+) and 11 patients without preoperative glucocorticosteroid (GC-)). The levels of AIF, MIF, IL-1ß, PARP-1, PAR, α-SYN, MCP-1 and TNF-α in vitreous of patients in the control and experimental groups were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of AIF in the vitreous was higher in the RRD group (9.96 ± 2.78 ng/ml) than in the RRDCD (GC+) group (7.65 ± 2.13 ng/ml, p = 0.006),the RRDCD (GC+) group was lower than the RRDCD (GC-) group (10.28 ± 2.81 ng/ml) (p = 0.013). The concentration of MIF in vitreous fluid was lower in the RRDCD (GC+) group (61.21 ± 17.56 ng/ml) than in the RRDCD (GC-) group (74.30 ± 9.66 ng/ml, p = 0.039). In the experimental group, the protein concentration of MCP-1 in the RRDCD (GC+) group was higher in the preoperative PVR grading C (284.93 ± 54.96 ng/ml) grade than in the D grade (225.94 ± 24.05 ng/ml) (p = 0.050); The protein concentration of MIF was lower in the RRDCD (GC+) group of patients with an ocular axis of <26 mm (56.19 ± 6.99 ng/ml) than in those with an ocular axis of ≥26 mm (76.26 ± 26.60 ng/ml, p = 0.043). CONCLUSION: Low expression of Parthanatos-related proteins is present in the vitreous of patients with RRDCD (GC+), and preoperative treatment with glucocorticoids may reduce the expression of Parthanatos-related proteins.

Vitreoschisis-induced vitreous cortex remnants in proliferative vitreoretinopathy: A comprehensive review from basic research to clinical practice.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR.

Causal relationships between inflammatory cytokines and myopia: an analysis of genetic and observational studies.

Objective: This study aims to explore the causal relationship between inflammatory markers and myopia through the use of bidirectional Mendelian randomization (MR) and myopia animal models. Methods: The authors utilized data from a comprehensive and publicly accessible genome-wide association study (GWAS) for our analysis, which includes 460 536 European ancestry control subjects and 37 362 myopia patients. Utilizing a two-sample Mendelian randomization analysis framework, 27 inflammatory markers were investigated as exposure variables with myopia serving as the outcome variable. Nine MR analysis techniques were employed, with inverse-variance weighting (IVW) as the principal MR analysis method. Heterogeneity was assessed using Cochrane's Q test. The identification of single-nucleotide polymorphisms (SNPs) and outliers linked to myopia was achieved via MR-PRESSO. The expression of interleukin-2 (IL-2) in the vitreous of guinea pigs subjected to experimentally induced form-deprivation myopia (FDM) was examined. Results: Elevated concentrations of IL-2 and IL-2ra were found to be associated [IVW estimate odds ratio (OR): 1.003, 95% CI: 1.001-1.005, P=0.001] and strongly associated (IVW estimate OR: 1.002, 95% CI: 1.000-1.003, P=0.049) with an increased risk of myopia, respectively. Conversely, lower levels of C-reactive protein (CRP) (IVW estimate OR: 0.996, 95% CI: 0.994-0.999, P=0.002) and tumour necrosis factor alpha (IVW estimate OR: 0.995, 95% CI: 0.994-0.996, P<0.001) were robustly linked to a heightened risk of myopia. IL-2 expression was notably upregulated in the vitreous of guinea pigs with experimentally induced FDM. Conclusions: Elevated levels of inflammatory factors, especially IL-2 and IL-2ra, have a potential causal relationship with myopia susceptibility, providing new insights into the pathogenesis of myopia.

Case report: Characterizing of free-floating pigmented vitreous cyst using swept-source optical coherence tomography.

Aim: A free-floating vitreous cyst is a rare eye disease. This study aimed to find diagnostic imaging methods and imaging features for vitreous cysts. Methods: This article presents a case report along with a literature review of published cases of vitreous cysts. The case report describes a highly myopic 60-year-old woman with a pigmented, free-floating vitreous cyst in her right eye. A search of the PubMed database using the keywords "vitreous cyst" was performed to identify other cases reported in the literature and to summarize the imaging methods used to diagnose and visualize vitreous cysts and the imaging features of vitreous cysts. Results: A thorough ophthalmic examination was performed in the present case, including slit-lamp photography, B-scan ultrasound, broad line fundus imaging, spectral-domain optical coherence tomography (SD-OCT), and ultra-wide field SS-OCT. The literature review revealed the imaging methods used in previously reported cases of vitreous cysts in which ultra-wide field SS-OCT has the advantages of wide scanning depth and high imaging clarity. Conclusion: SS-OCT has an advantage over SD-OCT in providing intuitive morphological characteristic images for the diagnosis of posterior vitreous cysts. The comprehensive assessment of multimodal imaging examinations, including SS-OCT, is of significant value for the diagnosis and differential diagnosis of vitreous cysts.

Synthetic vitreous fibers (SVFs): adverse outcome pathways (AOPs) and considerations for next generation new approach methods (NAMs).

Fiber dimension, durability/dissolution, and biopersistence are critical factors for the risk of fibrogenesis and carcinogenesis. In the modern era, to reduce, refine, and replace animals in toxicology research, the application of in vitro test methods is paramount for hazard evaluation and designing synthetic vitreous fibers (SVFs) for safe use. The objectives of this review are to: (1) summarize the international frameworks and acceptability criteria for implementation of new approach methods (NAMs), (2) evaluate the adverse outcome pathways (AOPs), key events (KEs), and key event relationships (KERs) for fiber-induced fibrogenesis and carcinogenesis in accordance with Organization for Economic Co-operation and Development (OECD) guidelines, (3) consider existing and emerging technologies for in silico and in vitro toxicity testing for the respiratory system and the ability to predict effects in vivo, (4) outline a recommended testing strategy for evaluating the hazard and safety of novel SVFs, and (5) reflect on methods needs for in vitro in vivo correlation (IVIVC) and predictive approaches for safety assessment of new SVFs. AOP frameworks following the conceptual model of the OECD were developed through an evaluation of available molecular and cellular initiating events, which lead to KEs and KERs in the development of fiber-induced fibrogenesis and carcinogenesis. AOP framework development included consideration of fiber physicochemical properties, respiratory deposition and clearance patterns, biosolubility, and biopersistence, as well as cellular, organ, and organism responses. Available data support that fiber AOPs begin with fiber physicochemical characteristics which influence fiber exposure and biosolubility and subsequent key initiating events are dependent on fiber biopersistence and reactivity. Key cellular events of pathogenic fibers include oxidative stress, chronic inflammation, and epithelial/fibroblast proliferation and differentiation, which ultimately lead to hyperplasia, metaplasia, and fibrosis/tumor formation. Available in vitro models (e.g. single-, multi-cellular, organ system) provide promising NAMs tools to evaluate these intermediate KEs. However, data on SVFs demonstrate that in vitro biosolubility is a reasonable predictor for downstream events of in vivo biopersistence and biological effects. In vitro SVF fiber dissolution rates >100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo SVF fiber clearance half-life less than 40 or 50 days were not associated with fibrosis or tumors in animals. Long (fiber lengths >20 µm) biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. In vitro fiber dissolution assays provide a promising avenue and potentially powerful tool to predict in vivo SVF fiber biopersistence, hazard, and health risk. NAMs for fibers (including SVFs) may involve a multi-factor in vitro approach leveraging in vitro dissolution data in complement with cellular- and tissue- based in vitro assays to predict health risk.

The Gly103Arg variant in hereditary transthyretin amyloidosis.

Background: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited systematic disease primarily affecting the peripheral and autonomic nervous system, heart, eyes and kidney. Over 140 variants have been identified worldwide, with the Gly103Arg variant reported exclusively in China. This variant is characterized by early onset eye manifestations, making accurate and timely diagnosis difficult. Therefore, we conducted a case study and literature review to investigate the clinical characteristics of the Gly103Arg variant in hereditary transthyretin amyloidosis. Methods: We identified three patients and an asymptomatic carrier in a four-generation family by sequencing the TTR gene. The proband underwent a lumbar puncture, electromyography, abdominal fat biopsy, among other tests. Case reports of Gly103Arg variant were retrieved through a literature search for an analysis of clinical characteristics. Results: The study included clinical data of 44 patients. Our literature review collected data on 41 patients and the present report supplied 3 patients with the Gly103Arg variant. The mean age at onset was 39.1 ± 4.27 years (range 30-47 years) with a female ratio of 52.3%. All cases were reported in China, predominantly in southern regions, especially Yunan and Guizhou Provinces. The initial manifestation was blurred vision, except for one case presenting with numbness in the upper extremities. All of them had vitreous opacity; 17 cases had peripheral neuropathy,6 cases had autonomic neuropathy, and 3 cases had cardiopathy. No disease-related deaths have been reported to date. Conclusion: The Gly103Arg variant is unique to the Chinese population, frequently occurring in southern China. The main clinical manifestations are blurred vision, vitreous opacity, and neuropathy, with cardiopathy being rare. ATTRv should be considered if a patient diagnosed with CIDP does not respond to related therapy. Abdominal fat biopsy is a convenient and accurate diagnostic method.

Impact of microorganism virulence on endophthalmitis outcomes.

AIMS: To determine the impact of microorganism virulence on visual outcomes in endophthalmitis. METHODS: Retrospective, multicentre cohort study of patients presenting with endophthalmitis between 2006 and 2021. A literature review was conducted to divide cultured microorganisms into low and high virulence subcategories. RESULTS: 610 eyes with endophthalmitis were recruited from New Zealand, the UK and Israel. The median age was 69.4 years. The median visual acuity was hand movements at presentation and 20/120 at the final follow-up. Severe visual loss (≤20/200) occurred in 237 eyes (38.9%) at the final follow-up. The culture-positive rate was 48.5% (296 eyes). Highly virulent microorganisms were associated with a 4.48 OR of severe visual loss at the final follow-up (p<0.001) and a 1.90 OR of developing retinal detachment or requiring enucleation or evisceration during the follow-up period (p=0.028). Oral flora were observed in 76 eyes (25.7%), and highly virulent microorganisms were observed in 68 eyes (22.9%). Highly virulent microorganisms were more likely to be found after glaucoma surgery (15 eyes, 34.9%) and vitrectomy (five eyes, 35.7%) compared with intravitreal injections (two eyes, 2.9%) and cataract surgery (22 eyes, 24.2%). On multivariate analysis, the following were associated with poorer visual outcomes: poor presenting vision (p<0.001), glaucoma surgery (p=0.050), trauma (p<0.001), oral microorganism (p=0.001) and highly virulent microorganism (p<0.001). CONCLUSION: This is the first classification of microorganisms into high and low virulence subcategories that demonstrate highly virulent microorganisms were associated with poor visual outcomes and increased likelihood of retinal detachment and enucleation.

Anterior Chamber Flare as a Non-Invasive Assessment of Intraocular Immune Status and Ocular Complications in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman's rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME.

Liquid Biopsy for Proliferative Diabetic Retinopathy: Single-Cell Transcriptomics of Human Vitreous Reveals Inflammatory T-Cell Signature.

Purpose: Current therapies for proliferative diabetic retinopathy (PDR) do not specifically target VEGF-independent, cell-type-specific processes that lead to vision loss, such as inflammatory pathways. This study aimed to identify targetable cell types and corresponding signaling pathways by elucidating the single-cell landscape of the vitreous of patients with PDR. Design: Case series. Subjects: Vitreous and peripheral blood obtained from 5 adult patients (6 eyes) undergoing pars plana vitrectomy for vision-threatening PDR. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on vitreous cells obtained from diluted cassette washings during vitrectomy from 6 eyes and peripheral blood mononuclear cells (PBMCs, n = 5). Droplet-based scRNA-seq was performed using the Chromium 10x platform to obtain single-cell transcriptomes. Differences in tissue compartments were analyzed with gene ontology enrichment of differentially expressed genes and an unbiased ligand-receptor interaction analysis. Main Outcome Measures: Single-cell transcriptomic profiles of vitreous and peripheral blood. Results: Transcriptomes from 13 675 surgically harvested vitreous cells and 22 636 PBMCs were included. Clustering revealed 4 cell states consistently across all eyes with representative transcripts for T cells (CD2, CD3D, CD3E, and GZMA), B cells (CD79A, IGHM, MS4A1 (CD20), and HLA-DRA), myeloid cells (LYZ, CST3, AIF1, and IFI30), and neutrophils (BASP1, CXCR2, S100A8, and S100A9). Most vitreous cells were T cells (91.6%), unlike the peripheral blood (46.2%), whereas neutrophils in the vitreous were essentially absent. The full repertoire of adaptive T cells including CD4+, CD8+ and T regulatory cells (Treg) and innate immune system effectors (i.e., natural killer T cells) was present in the vitreous. Pathway analysis also demonstrated activation of CD4+ and CD8+ memory T cells and ligand-receptor interactions unique to the vitreous. Conclusions: In the first single-cell transcriptomic characterization of human vitreous in a disease state, we show PDR vitreous is primarily composed of T cells, a critical component of adaptive immunity, with activity and proportions distinct from T cells within the peripheral blood, and neutrophils are essentially absent. These results demonstrate the feasibility of liquid vitreous biopsies via collection of otherwise discarded, diluted cassette washings during vitrectomy to gain mechanistic and therapeutic insights into human vitreoretinal disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.