Two-year outcomes of intravitreal conbercept therapy for polypoidal choroidal vasculopathy.

BACKGROUND: This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. METHODS: Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. RESULTS: A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 µm to 278.31 ± 157.34 µm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). CONCLUSIONS: Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept.

DYNAMIC VIRAL LOAD MONITORING AND METAGENOMIC SEQUENCING IN ACUTE RETINAL NECROSIS CAUSED BY VARICELLA-ZOSTER VIRUS.

PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus-induced acute retinal necrosis and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9 × 10 7 (1.1 × 10 7 -1.1 × 10 8 ) copies/mL. The average duration of retinitis was 5 ± 3 weeks. The average time required to reach the inflection point was 4.2 ± 1.6 days. Time required to reach the inflection point was correlated with the duration of retinitis ( P = 0.025). Patients with varicella-zoster virus carrying the p.S715* variation in ribonucleotide reductase ( RNR ) subunit 1 gene had lower initial viral loads (median 1.3 × 10 7 copies/mL) than those without (median 1.1 × 10 8 copies/mL; adjusted P = 0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in patients with acute retinal necrosis. Loss-of-function variation in RNR gene might be correlated with lower virulence of varicella-zoster virus.

CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.

Retinal vascular leakage is a major event in several retinal diseases, including diabetic retinopathy (DR). In a previous study, we demonstrated that the aqueous humor concentration of Cystatin C (CST3), a physiological inhibitor of cysteine protease, is negatively correlated with the severity of diabetic macular edema. However, its function in the retina has not been clearly elucidated. In this study, we found a significant decrease in the aqueous humor concentration of CST3 with DR progression. Furthermore, we found that CST3 was expressed in retinal endothelial cells and that its expression was significantly downregulated in high glucose-treated human retinal microvascular endothelial cells (HRMECs) and the retinal vessels of oxygen-induced retinopathy (OIR) mice. Silencing CST3 expression resulted in decreased HRMEC migration and tubule formation ability. Exogenous addition of the CST3 protein significantly improved HRMEC migration and tubular formation. In-vivo experiments demonstrated that CST3 silencing induced retinal vascular leakage in WT mice, while its intravitreal injection significantly reduced retinal leakage in OIR mice. Mechanistically, CST3 promoted the expression of the downstream adhesion molecules, claudin5, VE-cadherin, and ZO-1, in retinal vascular cells by regulating the Rap1 signaling pathway. Therefore, this study revealed a novel mechanism by which CST3 improves retinal vascular function and provided evidence that it is a potential therapeutic target for retinal vascular leakage.

Multimodal Imaging of Bilateral Retinal Pigment Epithelial Immunoglobulin Light Chain Deposition in Patients with Systemic Immunoglobulin Light Chain Deposition.

OBJECTIVE: To describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DESIGN: A retrospective observational case series. PARTICIPANTS: We examined 6 eyes in 3 patients (1 with multiple myeloma, 1 with membranous nephropathy, and 1 with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch's membrane complex and acquired serous retinal detachment. METHODS: Fundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain OCT, swept-source OCT (SS-OCT), en face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. MAIN OUTCOME MEASURES: Multimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. RESULTS: Bilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch's membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and "angiographically silent" serous retinal detachment in patients with systemic immunoglobulin light chain deposition. CONCLUSIONS: We have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

The role of transforming growth factor beta in myopia development.

Myopia is widely recognized as an epidemic. Studies have found a link between Transforming Growth Factor-beta (TGF-ß) and myopia, but the specific molecular mechanisms are not fully understood. In this study, a monocular model in tree shrews (Tupaia belangeri) was established to verify the molecular mechanism of TGF-ß in myopia. The results indicated that there were significant changes in TGF-ßs during the treatment of myopia, which could enhance the refractive ability and axial length of the eye. Immunohistochemical staining, real-time fluorescent quantitative PCR, and immunoblotting results showed a significant upregulation of MMP2 and NF-κB levels, and a significant downregulation of COL-I expression in the TGF-ß treated eyes, suggesting that NF-κB and MMP2 are involved in the signaling pathways of TGF-ßs induced myopia and axial elongation. Moreover, the expression levels of IL-6, IL-8, MCP-1, IL-1ß, TNF-α, TAK1, and NF-κB in the retina were all significantly elevated. This indicates that TGF-ß stimulates the inflammatory response of retinal pigment epithelial cells through the TAK1-NF-κB signaling pathway. In conclusion, this study suggests that TGF-ß promotes the progression of myopia by enhancing intraocular inflammation.

Circular RNA expression profile and functional analysis of circUvrag in light-induced photoreceptor degeneration.

BACKGROUND: Circular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA-expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light-induced photoreceptor apoptosis. METHODS: Sprague-Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light-induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT-PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin-eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry. RESULTS: We identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous-system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a-wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis. CONCLUSIONS: CircUvrag knockdown attenuated light-induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.

CORRELATIONS BETWEEN SUSPENDED HYPERREFLECTIVE MATERIAL WITH THE MACULAR MICROSTRUCTURE AND SPONTANEOUS CLOSURE OF FULL-THICKNESS MACULAR HOLES.

PURPOSE: To investigate the characteristics of spontaneously closed full-thickness macular holes (FTMHs) and to seek potential predictors for the spontaneous closure of FTMHs. METHODS: In this retrospective cohort study, the clinical data and optical coherence tomography images were reviewed from 19 eyes with spontaneously closed FTMHs (spontaneous closure group) and 37 control eyes with FTMHs that were delayed for nonmedical reasons, but ultimately required surgery (control group). The term, suspended hyperreflective material, was defined as hyperreflective material suspended within the FTMHs observed via optical coherence tomography; the presence of suspended hyperreflective material was evaluated in these eyes. RESULTS: The median time from diagnosis to spontaneous closure of the FTMHs was 13.7 (range, 2.4-32.4) weeks in the spontaneous closure group. The mean diameter of FTMHs in the spontaneous closure group was significantly smaller than that in the control group (191.68 ± 70.57 vs. 401.68 ± 162.19 µ m, P < 0.0001). The incidence of vitreomacular traction was higher in the spontaneous closure group compared with the control group (9/19 vs. 5/37, P = 0.009, odds ratio [95% confidence interval], 5.76 [1.56-21.21]); in seven of the nine eyes with vitreomacular traction from the spontaneous closure group, spontaneous vitreomacular traction separation and subsequent FTMH closure was observed. Suspended hyperreflective material was observed in nine eyes (47%) from the spontaneous closure group and three eyes (8%) from the control group ( P = 0.001, odds ratio [95% confidence interval], 10.20 [2.31‒45.02]). CONCLUSION: Smaller diameters, vitreomacular traction, and presence of suspended hyperreflective material may be suggestive of the potential for spontaneous closure of FTMHs.

Characteristics of Vitreoretinal Lymphoma in B-Scan Ultrasonography: A Case-Control Study.

PURPOSE: To explore the characteristics of vitreoretinal lymphoma (VRL) in B-scan ultrasonography. DESIGN: Single-center case-control study. PARTICIPANTS: A total of 106 eyes of 56 patients with biopsy-proven VRL and 86 eyes of 59 patients with uveitis were included. METHODS: B-scan ultrasonography of the included eyes was performed. Evaluated were the ultrasonographic signs as well as a special pattern termed centrifugal condensation, which refers to the peripherally hyperreflective appearance of the vitreous haze in ultrasonography. MAIN OUTCOME MEASURES: Posterior vitreous detachment, vitreoretinal adhesion, location of vitreous haze, thickening or occupying lesions of the retina, retinal detachment, and centrifugal condensation pattern of vitreous haze were evaluated through B-scan ultrasonography. The incidences of these signs were compared between the 2 groups; odds ratios (ORs) were calculated. RESULTS: The incidence of vitreoretinal adhesion in patients with VRL (6/106) was lower than in patients with uveitis (20/86; P = 0.001; OR: 0.195; 95% confidence interval [CI]: 0.073-0.522). The incidence of retinal thickening or occupying lesions in patients with VRL (21/106) was higher than that in patients with uveitis (1/86; P = 0.005; OR: 19.068; 95% CI: 2.455-148.265). The incidences of posterior vitreous detachment and retinal detachment were not significantly different between the 2 groups (P = 0.453 and P = 0.310, respectively). The centrifugal condensation pattern was more likely to be observed in patients with VRL (49/106) than in patients with uveitis (13/86; P < 0.001; OR: 4.831; 95% CI: 2.416-9.660). CONCLUSIONS: B-scan ultrasonography might help to provide clues for the suspicion of VRL. Thickening or occupying lesions of the retina and centrifugal condensation pattern of vitreous haze might be suggestive of VRL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Prognosis, Risk Factors, and Clinical Features of Intraocular Recurrence in Primary Vitreoretinal Lymphoma.

PURPOSE: To investigate the clinical features, risk factors, and prognosis of the intraocular recurrence in primary vitreoretinal lymphoma (PVRL). DESIGN: Retrospective case-control study. PARTICIPANTS: Ninety-seven eyes of 51 patients diagnosed with PVRL between December 2011 and January 2021 were enrolled in this study. Fourteen patients among them had experienced intraocular recurrence. METHODS: Data on demographic and ophthalmic characteristics, results of diagnostic tests, treatments, and prognosis of intraocular recurrence and nonrecurrence for PVRL patients were collected and compared. Multivariate logistic regression was used to identify independent risk factors. Receiver operating characteristic curves were used to determine the cutoff values. MAIN OUTCOME MEASURES: Clinical features and risk factors. RESULTS: Fourteen (19 eyes) of 51 PVRL patients had intraocular recurrences, resulting in a recurrence rate of 27.5% over a mean follow-up period of 42.5 months. No difference was observed in central nervous system lymphoma (CNSL) relapse rate (54.3% vs. 64.3%, P = 0.52) or median time to CNSL (36.5 months; 95% confidence interval [CI], 24.6-48.3 vs. 37.3 months; 95% CI, 24.8-49.8; P = 0.78) between intraocular nonrecurrence and intraocular recurrence groups. Furthermore, there were no statistically significant differences in the survival outcomes, such as mortality (28.6% vs. 29.7%, P = 1.00) and median overall survival (70.8 months; 95% CI, 54.0-87.7 vs. 59.2 months; 95% CI, 44.8-73.6; P = 0.30), between these 2 groups. Younger onset age (odds ratio [OR] 0.90; 95% CI, 0.84-0.98; P = 0.010), isolated PVRL (OR, 35.3; 95% CI, 2.08-600.0; P = 0.014), and no history of intravitreal chemotherapy (OR, 7.72; 95% CI, 1.37-43.6; P = 0.021) were identified as independent risk factors for intraocular recurrences. Of the patients with intraocular recurrence, 23.6% were asymptomatic and were diagnosed during routine follow-up. The rate of interleukin-10 (IL-10)/interleukin-6 > 1 was significantly lower than that at diagnosis (43.8% vs. 92.3%, P = 0.008). However, the rate of IL-10 ≥ 50 pg/mL was high (81.3%) and not significantly different from that at diagnosis (92.3%, P = 0.61). CONCLUSIONS: This study did not identify an impact of intraocular recurrence on CNS manifestations or survival outcomes in patients with PVRL. Younger patients have a higher risk of intraocular recurrence, and combined systemic and intravitreal chemotherapy may reduce intraocular recurrence. Regular ophthalmic follow-up and IL-10 testing are recommended to detect intraocular recurrence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes of Secondary Intracapsular Intraocular Lens Implantation in Patients following Rhegmatogenous Retinal Detachment.

This study reports the outcomes of a secondary IOL implantation technique in patients that suffered from rhegmatogenous retinal detachment combined with a cataract, which included reopening the capsular bag, enabling secondary intracapsular intraocular lens (IOL) implantation. We included consecutive cases with rhegmatogenous retinal detachment (RRD) treated with vitrectomy and silicone oil tamponade, and subsequent secondary IOL implantation during silicone oil removal between September 2019 and June 2022. Demographics, pre- and postoperative clinical data, and complications were collected. Visual and refractive outcomes and IOL position were evaluated. Thirty eyes were included and followed up for a mean of 24.2 ± 5.06 months. Compared with the preoperative values, no significant changes were observed in the intraocular pressure (p = 0.170) and endothelial cell density (p = 0.336); however, the best-corrected visual acuity (Snellen: 20/83 vs. 20/38; logMAR: 0.66 ± 0.23 vs. 0.37 ± 0.32; p < 0.001) and spherical equivalent (p < 0.001) improved significantly. The mean prediction error (ME) was -0.45 ± 0.68 D (-1.9-0.54 D), and the mean absolute prediction error (MAE) was 0.62 ± 0.52 D (0.01-1.9 D). The macula-on subgroup demonstrated significantly better refractive outcomes than the macula-off subgroup (ME, p = 0.046; MAE, p = 0.008). The IOL was well positioned, with a mean horizontal and vertical tilt and decentration of 0.53 ± 0.49° and 0.21 ± 0.16 mm, and 0.54 ± 0.45° and 0.22 ± 0.16 mm, respectively. Secondary intracapsular IOL implantation provided a good and stable IOL position and satisfactory refractive outcomes, and is a feasible treatment option for patients with RRD.

Metabolomic Profiling of Aqueous Humor from Pathological Myopia Patients with Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC-MS and 1457 metabolites using LC-MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings.

Comparison of Clinical Profiles, Demographics, and Surgical Outcomes of 25-Gauge Vitrectomy for Proliferative Diabetic Retinopathy in Young Adults with Type 1 or Type 2 Diabetes.

Purpose: Proliferative diabetic retinopathy (PDR) is a leading cause of poor vision in young adults. This study sought to evaluate the clinical characteristics and outcomes of primary vitrectomy for PDR in young adults. Patients and Methods: Medical data were retrospectively collected at a large ophthalmology hospital in China. We analyzed data for 99 patients (140 eyes) aged <45 years with T1D or T2D who underwent primary vitrectomy for PDR-related complications. Results: There were 18 patients with T1D and 81 patients with T2D. The proportion of males was significantly greater than that of females in both groups. The T1D group had a longer duration of diabetes (P = 0.008), younger age at primary vitrectomy (P = 0.049), and lower body mass index (P < 0.001) than the T2D group. The proportion of eyes with rhegmatogenous retinal detachment (RRD) was greater but the proportion of eyes with traction retinal detachment (TRD) was lower in the T1D group than in the T2D group. The final best-corrected visual acuity (BCVA) improved or remained stable in 100% and 85.3% of eyes and decreased in 0% and 14.7% of eyes in the T1D and T2D groups, respectively. After surgery, the incidence of postoperative complications was significant greater in the T2D group than in the T1D group (P = 0.045). Factors influencing the final visual acuity included preoperative BCVA in both groups, the duration of diabetes (P = 0.031) and preoperative FVP (P = 0.004) in the T1D group, and preoperative RRD (P < 0.001) and postoperative NVG (P < 0.001) in the T2D group. Conclusion: In this retrospective study, young adults with T2D who underwent vitrectomy had worse final visual acuity and more complications than young adults with T1D.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Assessment of Silicone Oil Emulsification: A Comparison of Currently Applied Methods.

Purpose: To compare ultrasound biomicroscopy (UBM), Coulter counter, and B-scan ultrasonography in the evaluation of silicone oil (SO) emulsification. Methods: Patients who underwent primary pars plana vitrectomy with SO tamponade for rhegmatogenous retinal detachment and SO removal were included. UBM images were acquired before the SO removal, and B-scan images were taken after removal. The number of droplets in the first and last 2 mL of washout fluid was analyzed using a Coulter counter. The correlations between these measurements were analyzed. Results: Thirty-four eyes received both UBM and Coulter counter analysis for the first 2 mL of washout fluid, and 34 underwent B-scan and Coulter counter analysis of the last 2 mL washout fluid. The mean UBM grading was 26.41 ± 9.71 (range: 1-36); the mean SO index obtained with B-scan was 5.25 ± 5.00% (range: 0.10-16.49%), and the mean number of SO droplets was 1.26 ± 2.45 × 107/mL and 3.34 ± 4.22 × 106/mL in the first and last 2 mL of washout fluid, respectively. There were significant correlations between UBM grading and SO droplets in the first 2 mL and between B-scan grading and SO droplets in the last 2 mL (all P < 0.05). Conclusions: UBM, Coulter counter, and B-scan ultrasonography could all be used in the evaluation of SO emulsification, and their findings were comparable.

Inhibition of NF-κB ameliorates aberrant retinal glia activation and inflammatory responses in streptozotocin-induced diabetic rats.

Background: To determine the anti-inflammatory effects of IMD-0354, a specific NF-κB blocker, on glial cells in rats with streptozotocin (STZ)-induced diabetic retinopathy (DR). Methods: The following four groups of rats were used: control, control + IMD-0354, STZ, and STZ + IMD-0354. After six weeks of STZ injection, diabetic rats and nondiabetic control rats received IMD-0354 (30 mg/kg) or an equal volume of 4% dimethyl sulfoxide (DMSO) in phosphate-buffered saline intraperitoneally for six consecutive weeks. The following four groups of primary rat retinal microglia and Müller cells were used: control (5 mM), control + IMD-0354, high glucose (20 mM), and high glucose + IMD-0354. The effects of IMD-0354 on nuclear factor-κB (NF-κB) activation, oxidative stress strength, expression of inflammatory cytokines and VEGF (vascular endothelial growth factor), activation of glial cells, and apoptosis of neuron cells were evaluated by immunohistochemistry, oxidative stress assays, western blot, enzyme linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining respectively. Results: Nuclear translocation of NF-κB was markedly increased in diabetic rat retina and high glucose treated glial cells. Systemic administration of IMD-0354 significantly inhibited NF-κB activation in both diabetic rat retina and high glucose treated glial cells, ameliorated oxidative injury, inflammatory responses, VEGF production and glial cell activation, and protected neurons from apoptosis. Conclusions: Our findings indicated that NF-κB activation is acritical step in the abnormal reactivity of glial cells in STZ-induced diabetic rats. Inhibition effect of IMD-0354 on NF-κB activation may represent a promising therapeutic strategy for DR via a variety of mechanisms, including inflammation reduction and glial cells regulation.

Longitudinal Analysis of Ocular Manifestation and Interleukin During Intravitreal Treatment of Vitreoretinal Lymphoma With Methotrexate.

PURPOSE: To explore the trend of ocular manifestations and interleukin (IL) during the treatment of vitreoretinal lymphoma (VRL) and to evaluate the potential effects of different intravitreal administration schedules on the therapeutic response. DESIGN: Interventional comparative nonrandomized clinical study. METHODS: Patients diagnosed with VRL between January 2011 and January 2022 were included. Intravitreal methotrexate (MTX) injections consisting of induction, consolidation, and maintenance were scheduled. At baseline and each visit, ocular manifestations and IL in aqueous humor were recorded. Effects of the variations (eg, frequency and number) in the injection schedule on the therapeutic response were analyzed. RESULTS: Fifty-eight eyes of 33 patients were treated with intravitreal MTX chemotherapy. A mean ± standard deviation of 9 ± 3 injections were given; 52 eyes achieved complete remission (CR). IL-10, keratic precipitates, and subretinal lesions correlated well with the course of treatment (all P < .001). Initial injection given twice weekly was correlated with a higher rate of CR (36/36) than given once weekly or less frequently (16/22; P = .011). Ocular progression occurred in 13 eyes of 8 patients. The completion of schedule was correlated with PFS (induction + consolidation + maintenance: 547 [335-874] days; induction + consolidation: 355 [322-831] days; induction only: 147 [116-187.5] days; P < .001). IL-10 >50 pg/mL was a feasible threshold for the detection of ocular relapse (sensitivity 100.0%, specificity 95.1%). CONCLUSION: Keratic precipitates, subretinal lesions, and IL-10 could serve as indicators for therapeutic response. Intensive initial administration and adequate injection numbers would help to improve the response and prognosis. IL-10 >50 pg/mL could help detect ocular relapse.

Case report: Sympathetic ophthalmia after vitrectomies in a patient with Von Hippel-Lindau syndrome.

Background: Sympathetic ophthalmia (SO) is a rare but sight-threatening uveitis, and most observations have been made after typical manifestations occur. This report focuses on the choroidal changes detected by multimodal imaging at the presymptomatic stage of SO, which is implicated in the early recognition of SO. Case presentation: A 21-year-old woman suffered from decreased vision in the right eye and was diagnosed with retinal capillary hemangioblastomas associated with Von Hippel-Lindau syndrome. The patient underwent two 23-G pars plana vitrectomies (PPVs), soon after which typical signs of SO manifested. SO resolved quickly after the oral administration of prednisone and remained stable during the follow-up of more than 1 year. The retrospective analysis revealed preexisting bilaterally increased choroidal thickness, dots of flow void on the choroid, and choriocapillaris en-face slabs in optical coherence tomography angiography (OCTA) after the first PPV, which were all reversed by corticosteroid treatment. Conclusion: The case report highlights the involvement of the choroid and choriocapillaris at the presymptomatic stage of SO after the first inciting event. Abnormally thickened choroid and flow void dots suggested that SO had started and an ensuing surgery would run the risk of exacerbating SO. OCTA scanning of both eyes should be ordered routinely for patients with a history of trauma or intraocular surgeries, especially before the next surgical intervention. The report also suggests that non-human leukocyte antigen gene variation may also regulate the progression of SO, which requires further laboratory investigations.

The Role of Widefield Optical Coherence Tomography Angiography in the Diagnosis and Management of Acute Vogt-Koyanagi-Harada Disease.

PURPOSE: We explore the choroid vasculature changes of acute Vogt-Koyanagi-Harada (VKH) disease using widefield optical coherence tomography angiography (OCTA). METHODS: In this retrospective, observational, longitudinal study, 16 patients with acute VKH disease (32 eyes, mean age: 42.19 ±13.66 years) were measured using widefield OCTA. RESULTS: In this study, we first described the multiple dark foci in choriocapillaris and Sattler's layer in the panoramic montage of the five 12x12mm images in 30 eyes (93.8%) of acute VKH disease. OCTA follow-up in these 30 eyes demonstrated the diminished size and number of these dark foci in choriocapillaris and Sattler's layer after the initiation of treatment. CONCLUSIONS: Widefield OCTA enables noninvasive identification of characteristics of flow void at the level of superficial choroidal vessels in the acute phase and may be a novel valuable tool for diagnosis and monitoring of disease progression in VKH disease in the future.

Multipurpose ultrasonographic characteristics of primary uveal MALT lymphoma.

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.

Clinical Characteristics and Surgical Outcomes of Complications of Proliferative Diabetic Retinopathy in Young versus Older Patients with Type 2 Diabetes.

Purpose: Proliferative diabetic retinopathy (PDR) is a leading vision-threatening disease. In this study, we investigated the clinical features of PDR and the surgical outcomes of its complications in patients with type 2 diabetes (T2D). Patients and Methods: We retrospectively reviewed the medical data of patients with T2D who underwent vitrectomy for PDR between January 2016 and June 2021. The patients were divided into two groups by age (young patients, < 45 years; older patients, ≥ 45 years). Results: There were 149 eyes (100 patients) in the young patient group and 315 eyes (256 patients) in the older patient group. The proportion of males and the proportion of patients requiring binocular surgery were much higher in the young patient group than in the older patient group (P = 0.005 and P < 0.001, respectively). In the young patient group, 26.2% of eyes had active fibrovascular proliferation compared with only 11.4% in the older patient group (P < 0.001). The final best-corrected visual acuity (BCVA) was significantly improved relative to the preoperative BCVA in both groups (P < 0.001). After surgery, there were no significant differences in the incidence of postoperative neovascular glaucoma (NVG) or recurrent vitreous hemorrhage (VH) between the two groups. The incidence of postoperative recurrent retinal detachment was higher in the young patient group (P = 0.033). The risk factors associated with the visual outcomes in the young patient group included preoperative BCVA (P < 0.001), renal diseases (P = 0.001), postoperative NVG (P < 0.001), and recurrent VH (P = 0.028). Conclusion: In this retrospective study, young patients who underwent vitrectomy for PDR had more severe clinical characteristics before vitrectomy. However, vitrectomy (combined with cataract surgery when necessary) achieved better final visual outcomes in young patients than in older patients with T2D.