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.

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.

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.

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.

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.

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.

Exosomal MicroRNA Profiling in Vitreous Humor Derived From Pathological Myopia Patients.

Purpose: Pathologic myopia (PM) is one of the primary causes of blindness. This study aims to explore the possible relations between the composition of microRNA in vitreous exosomes of patients with PM and the progression of myopic maculopathy. Methods: Vitreous humor (VH) samples were collected from patients undergoing retinal surgery. A total of 15 and 12 VH samples were obtained from patients with PM and control, respectively. The PM group was divided into PM-L (G2) and PM-H groups (G3 and G4) in order to explore differentially expressed microRNAs (DEMs) that account for the relatively poor prognosis in G3 and G4 myopic maculopathy. A Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to find the persistently altered key microRNAs in myopic maculopathy progression. The Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were used. Results: High purity exosomes were extracted from the vitreous fluid of patients with PM and control. The top five downregulated DEMs of PM-H versus PM-L can reflect the tendency of deterioration of PM-H myopic maculopathy. MiR-143-3p and miR-145-5p, which were found in WGCNA, may participate in the development of myopic maculopathy. These microRNAs all relate to the insulin resistance pathway. Conclusions: This is the first study to explore the relations between the progression of myopic maculopathy and vitreous exosomal microRNAs. Vitreous exosomal miR-143-3p and miR-145-5p can be considered biomarkers for patients with PM, and the vitreous exosomal DEM associated with PM-H may represent alarming signals of myopic maculopathy deterioration.

Secondary in-the-bag Intraocular Lens Implantation in Aphakic Eyes After Vitrectomy and Silicone Oil Tamponade for Rhegmatogenous Retinal Detachment.

PURPOSE: To describe a novel technique for capsular bag reopening and secondary in-the-bag intraocular lens (IOL) implantation in aphakic eyes after vitreoretinal surgery and intraocular tamponade. METHODS: We enrolled 14 eyes of 14 patients who underwent primary vitreoretinal surgery with silicone oil tamponade for rhegmatogenous retinal detachment between September 2018 and September 2019. The novel technique was used for capsular bag reopening and foldable single-piece IOL implantation. Patients were followed up at least 24 weeks with routine ophthalmic examinations, corneal endothelial cell density, and IOL tilt and decentration measurement. RESULTS: The procedure was successfully completed in 13 cases; in one case, because of posterior capsular tear, the IOL was implanted with ciliary sulcus fixation. After a mean follow-up of 48.8 ± 14.8 (range, 24.9-65.9) weeks, the best-corrected visual acuity (before 20/76 Snellen, 0.63 ± 0.23 logarithm of the minimum angle of resolution equivalent and after 20/35 Snellen, 0.32 ± 0.32 logarithm of the minimum angle of resolution equivalent; P = 0.001) and spherical equivalent (before +8.22 ± 4.08, after -2.39 ± 1.77 D; P < 0.001) improved, intraocular pressure (before 15.93 ± 4.40, after 16.25 ± 4.25 mmHg; P = 0.743) remained unchanged. The IOL was well centered with a mean horizontal and vertical tilt of 0.5070 ± 0.3319° and 0.4652 ± 0.3465°, respectively, and decentration of 0.1705 ± 0.1334 mm and 0.1712 ± 0.1576 mm, respectively. CONCLUSION: With this technique, capsular bag reopening and secondary in-the-bag IOL implantation could be achieved in most cases with satisfactory visual outcome and IOL position.

Silicone oil residual after vitrectomy for rhegmatogenous retinal detachment.

OBJECTIVE: To explore the presence of residual emulsified silicone oil (SO) droplets in patients with rhegmatogenous retinal detachment (RRD) and their possible risk factors. METHODS: Patients who underwent primary pars plana vitrectomy with SO injection for RRD and SO removal at the same eye centre were included. Approximately 10 weeks after SO removal, B-scan ultrasonography was performed, and using ImageJ, the silicone oil index (SOI) was measured, and its possible correlations with other clinical factors were explored. RESULTS: A total of 101 eyes were included. Residual SO particles were found in all the patients (100%), and the mean SOI was 4.04% ± 5.16% (range 0.06%-19.88%). Multiple linear regression revealed that, among all the clinical factors, axial length (AL) and ocular hypertension (intraocular pressure (IOP) > 21 mmHg or the use of antiglaucoma medications) before SO removal were positively and significantly associated with the SOI (all P < 0.05). Patients with ocular hypertension after SO removal had a higher SOI, a longer SO duration, a higher IOP before SO removal and a longer AL than those without (all P < 0.05). CONCLUSIONS: Patients with a larger AL and higher IOP before SO removal were more prone to have more residual SO droplets, which might in turn lead to an elevated IOP. In these eyes, thorough irrigation or repeated fluid-air exchange might be necessary.

SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways.

BACKGROUND: Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved. METHODS: In the all trans retinal (atRAL)-induced oxidative stress model, we used the vector of lentivirus to knockdown the expression of SHP-1 in ARPE-19 cells. CCK-8 assay, Annexin V/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis. RESULTS: We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes. CONCLUSIONS: These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal diseases including AMD.

Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions.

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Cell-Free DNA Sequencing of Intraocular Fluid as Liquid Biopsy in the Diagnosis of Vitreoretinal Lymphoma.

Purpose: To seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value. Methods: The study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500µl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500µl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes. Results: CfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013). Conclusions: The improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL.

PERIVASCULAR FLOWER-BUD-LIKE LESIONS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH VITREORETINAL LYMPHOMA.

PURPOSE: To describe perivascular flower-bud-like lesions (PFBLs) as novel characteristics of vitreoretinal lymphoma on en face optical coherence tomography (OCT) angiography. METHODS: A retrospective chart review was performed on 23 consecutive patients (35 eyes), who had biopsy-proven vitreoretinal lymphoma between January 2018 and March 2021. En face OCT angiography images were analyzed before and after intervention. PFBLs were initially identified on midretinal slabs of en face OCT angiography, and were further characterized by other imaging modalities. RESULTS: Perivascular flower-bud-like lesions were detected in 12 eyes (34.3%) of 8 patients, of which 8 eyes had best-corrected visual acuity of 20/40 or better. In 10 of the 12 eyes, PFBLs were detected within 6 months of symptom onset. On en face OCT angiography, PFBLs presented as punctate points or confluent bands surrounding retinal vessels, with arterial and venous involvement. In 4 of the 12 eyes, arteries were mainly affected. On OCT B-scans, PFBLs commonly appeared as hyperreflective full-thickness intraretinal lesions that colocalized with subretinal pigment epithelium deposits (3 eyes, 25%) and retinal pigment epithelium irregularities (4 eyes, 33.3%). However, PFBLs could not always be identified on other imaging modalities such as fundus photographs and fundus fluorescein angiography. In all eyes with follow-up, PFBLs attenuated or resolved months after receiving chemotherapy or diagnostic vitrectomy. CONCLUSION: PFBLs are characteristic imaging findings of vitreoretinal lymphoma and may facilitate an early diagnosis of vitreoretinal lymphoma, which would in turn lead to more timely and effective treatment.

MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway.

Aberrant neovascularization in the retina is an important threat to vision and closely related to several retinal diseases, such as wet form of age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. However, the pathogenesis remains largely unknown. MicroRNAs (miRNAs) have been demonstrated to play critical regulatory roles in angiogenesis. Therefore, we aimed to identify the key miRNAs that regulate retinal neovascularization and elucidate the potential underlying mechanisms. In the present study, we performed RNA sequencing of microRNAs in the retina and found that miR-375 was significantly downregulated in the retina of oxygen-induced retinopathy mice. In retinal microvascular endothelial cells (RMECs), overexpression of miR-375 inhibited cell proliferation and angiogenesis. Conversely, inhibition of miR-375 had the opposite effects. Moreover, our results showed that miR-375 negatively regulated the protein expression of JAK2 by inhibiting its translation. The promoting effects of anti-miR-375 on cell proliferation and angiogenesis were attenuated by an inhibitor of STAT3. These results indicate that miR-375 mitigates cell proliferation and angiogenesis, at least in part, through the JAK2/STAT3 pathway in RMECs, which implies an important underlying mechanism of retinal angiogenesis and provides potential therapeutic targets for retinal microangiopathy.