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.

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.

Progressively Decreased HCN1 Channels Results in Cone Morphological Defects in Diabetic Retinopathy.

Historically, diabetic retinopathy has been recognized as a vascular disease. Recent clinical evidence suggests the initiation of diabetic retinopathy with neuropathy rather than microangiopathy. However, the molecular mechanism that drives diabetic retinopathy-associated neuropathy remains mostly unexplored. Here, we reported progressive diabetic retinopathy defects in blood glucose levels, shortening of cone segments and uncoupled appearance of retinal vascular abnormalities from pdx1 +/- mutants zebrafish to glucose-treated pdx1 +/- mutants zebrafish of both sexes. Further single-cell transcriptomic analysis revealed cones as the most vulnerable retinal neuron type that underwent three developmentally progressive cell states (States 1-3), predominantly present in WT animals, pdx1 +/- mutants, and glucose-treated pdx1 +/- mutants, respectively. Mechanistically, the expression of hcn1 was progressively decreased in cones during its transition from State 1 to State 3. Furthermore, genetic hcn1 disruption resulted in similar cone segment defects found in the diabetic retinopathy model, suggesting the involvement of progressive hcn1 reduction in diabetic retinopathy-associated cone defects. Thus, our study provided a vertebrate retina model representing progressive diabetic retinopathy defects and further gained new mechanistic insights into the cone morphologic defects as an early neuropathy in diabetic retinopathy.SIGNIFICANCE STATEMENT We create a vertebrate retina model representing the progressive diabetic retinopathy-associated defects using zebrafish. Further systematic single-cell transcriptome analysis reveals two novel cell states of cones in response to different levels of higher glucose and the progressive decrease of HCN1 channels as a mechanism underlying cone defects in diabetic retinopathy.

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.

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.

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.

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.

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.

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.

Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats.

BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

Quantification of an oval optic disc in relation to myopic foveoschisis using swept-source optical coherence tomography.

BACKGROUND: To investigate the relationship between an oval optic disc and the occurrence of myopic foveoschisis (MF) using swept-source optic coherence tomography (SS-OCT). METHODS: Fifty eyes of 25 patients with unilateral MF were included in this retrospective observational study. The biometric features of the optic disc and peripapillary structures were evaluated using SS-OCT. RESULTS: The ovality index (OI) of the optic disc was significantly smaller (P = 0.003) and the optic disc tilt angle was greater (P = 0.023) in the eyes with MF than in the contralateral eyes. The optic disc tilt angle was significantly correlated with the OI (P = 0.000). Generalized estimating equation (GEE) model (linear regression) demonstrated that spherical equivalent refraction (P = 0.001), narrow macular staphyloma (P = 0.001) and the occurrence of MF (P = 0.026) were the independent factors associated with the OI. Narrow macular staphyloma was more frequent (P = 0.020) and the staphyloma was deeper (P = 0.006) in eyes with MF. GEE model (logistic regression) revealed that narrow macular staphyloma was the only independent factor related to the occurrence of MF (P = 0.013). CONCLUSIONS: An oval optic disc in eyes with MF resulted from the increased tilt around the vertical disc axis. The optic disc tilt was related to narrow macular staphyloma, which was the only independent factor associated with the occurrence of MF. The clinical relevance needs further exploration through longitudinal analysis.

Photocoagulation-associated spontaneous release of epiretinal membrane secondary to retinal vascular tumor: case series of 8 cases.

To evaluate the secondary epiretinal membrane (ERM) response after photocoagulation in retinal vascular tumor. This retrospective interventional case series included 8 patients (8 eyes) who were diagnosed with retinal vascular tumor and secondary ERM. All eyes were treated with photocoagulation and underwent comprehensive ophthalmologic examinations at baseline and at each follow-up. Of the 8 eyes with retinal vascular tumor and associated ERM, 4 eyes (50%) were von Hippel and 4 eyes (50%) were vasoproliferative tumor of the retina. The mean follow-up time was 12.63 ± 14.64 (range, 4-51) months. The BCVA in the eyes at baseline was 1.16 ± 1.10 logMAR (range, HM to 20/40). ERM located in the macular region in 100% of the eyes and led to CME with a mean central foveal thickness of 497.6 ± 147.7 µm (range, 294-736 µm) at presentation. After photocoagulation, the ERM spontaneously peeled in 7 of 8 eyes (87.5%), among which one case required surgical treatment due to complicating tractional retinal detachment. After ERM peeling without complications, 6 eyes recovered normal macular structure, with an improved BCVA in 5 eyes and a stable BCVA in 1 eye. Laser photocoagulation is necessary and effective treatment for retinal vascular tumor. After laser photocoagulation, retinal vascular tumor-related ERM spontaneously released in 75% of the cases, without complication and surgical intervention.

SHP-1 suppresses endotoxin-induced uveitis by inhibiting the TAK1/JNK pathway.

We investigated how Src-homology 2-domain phosphatase-1 (SHP-1) regulates the inflammatory response in endotoxin-induced uveitis (EIU), and the signalling pathways involved. One week after intravitreal injection of short hairpin RNA targeting SHP-1 or SHP-1 overexpression lentivirus in rats, we induced ocular inflammation with an intravitreal injection of lipopolysaccharide (LPS). We then assessed the extent of inflammation and performed full-field electroretinography. The concentrations and retinal expression of various inflammatory mediators were examined with enzyme-linked immunosorbent assays and Western blotting, respectively. SHP-1 overexpression and knockdown were induced in Müller cells to study the role of SHP-1 in the LPS-induced inflammatory response in vitro. Retinal SHP-1 expression was up-regulated by LPS. SHP-1 knockdown exacerbated LPS-induced retinal dysfunction and increased the levels of proinflammatory mediators in the retina, which was abrogated by a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). SHP-1 overexpression had the opposite effects. In Müller cells, the LPS-induced inflammatory response was enhanced by SHP-1 knockdown and suppressed by SHP-1 overexpression. SHP-1 negatively regulated the activation of the transforming growth factor-ß-activated kinase-1 (TAK1)/JNK pathway, but not the nuclear factor-κB pathway. These results indicate that SHP-1 represses EIU, at least in part, by inhibiting the TAK1/JNK pathway and suggest that SHP-1 is a potential therapeutic target for uveitis.

Ferrostatin-1 attenuates ferroptosis and protects the retina against light-induced retinal degeneration.

Degenerative retinal diseases, including age-related macular degeneration, are serious diseases that may lead to irreversible retinal neuron damage and permanent vision impairment. There are currently no effective treatments for these diseases due to our incomplete understanding of the underlying pathological mechanisms. Ferroptosis, a newly identified iron-dependent mode of cell death, is implicated in various diseases. However, it is unknown whether ferroptosis is involved in light-induced retinal degeneration. In this study, we found that light exposure significantly reduced the viability of photoreceptor cells in vitro and induced pro-ferroptotic changes, including iron accumulation, mitochondrial shrinkage, glutathione depletion, increased malondialdehyde (MDA), and decreased protein expression of SLC7A11 and GPX4. The effects of light exposure on ferroptosis were attenuated by ferrostatin-1. Consistently, the results of in vivo studies demonstrated that ferrostatin-1 protected against light-induced ferroptosis. And it exerted therapeutic effects by inhibiting neuroinflammation and prevented the effects of light exposure on the structure and function of the retina. The findings reveal an important role of ferroptosis in the pathogenesis of light-induced retinal degeneration and suggest that ferroptosis may be a novel treatment target for preventing retinal degeneration.

Synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model.

Purpose: To explore synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model. Methods: Sprague-Dawley rats were euthanized 1 h, 1 day, 3 days, 7 days, and 14 days after being exposed to intense blue light for 24 h. Hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate changes in the outer nuclear layer (ONL). Transmission electron microscopy (TEM) was applied to observe the ultrastructural changes in the synapses between the photoreceptors and second-order neurons. Western blotting was conducted to evaluate specific proteins, including postsynaptic density-95 (PSD-95), metabotropic glutamate receptor 6 (mGluR6), synapsin I, and synaptophysin. Immunofluorescence of CD11b and PKC-α or mGluR6 was used to explore the spatial relationships between microglial processes and synaptic elements. Immunoelectron microscopy of PSD-95 was performed to further confirm its engulfment of synaptic materials. Results: H&E and TUNEL staining showed that the thickness of the ONL decreased markedly, and the number of apoptotic photoreceptors peaked at day 1. TEM revealed darkened photoreceptor terminals and that ribbons of them were floating in the cytoplasm, coinciding with the downregulation of PSD-95 and mGluR6. Downstream synaptic protein synapsin I and synaptophysin exhibited upregulation in the inner plexiform layer. Activated microglia migrated to the outer retina, and their processes were found in close proximity to synapses in the outer plexiform layer under light and electron microscopy levels. Double immunostaining of CD11b and mGluR6 showed colocalization. PSD-95-immunoreactive electron-dense materials were observed inside the microglia suggesting engulfment of synaptic components. Conclusions: The study showed that there are early synaptic impairment and late compensatory changes in downstream synapses in this photic injury model. Activated microglia touched and directly engulfed synaptic materials. Microglia may play a role or a partial role in synaptic changes.

Proinflammatory and angiogenesis-related cytokines in vitreous samples of highly myopic patients.

PURPOSE: To determine the concentrations of vitreous proinflammatory cytokines and angiogenesis-related growth cytokines in highly myopic (HM) patients and controls. METHODS: Vitreous humor (VH) was obtained from patients during vitrectomy for rhegmatogenous retinal detachment (RRD), myopic retinoschisis (MRS), idiopathic epiretinal membrane (ERM), or macular hole (MH). High myopia was defined as an axial length (AL) of ≥26.0 mm and a spherical equivalent refractive error more negative than -6.0 D. A multiplex fluorescent-bead-based immunoassay was employed to measure the levels of 29 designated cytokines. The results were compared across groups. RESULTS: Seventy-eight VH samples were collected from 78 patients (36 HM versus 42 controls). Vascular endothelial growth factor (VEGF) was significantly higher in the VH samples from HM patients than in those from the controls. Five inflammation-related factors, interferon γ (IFN-γ), interleukin 6 (IL6), IFN-γ-induced protein 10 (IP-10), eotaxin, and macrophage inflammatory protein 1α (MIP-1α), were significantly higher in the HM group than in the control group. The vitreous concentrations of well-known angiogenic growth factors monocyte chemoattractant protein 1 (MCP1) and IL5 were significantly elevated in the VH samples from HM patients. CONCLUSIONS: Proinflammatory cytokines and angiogenic growth factors were elevated in the VH of HM patients, suggesting that an elevated inflammatory status and higher levels of angiogenic factors are present in eyes with HM.

CLINICAL FEATURES OF FLAT IRREGULAR PIGMENT EPITHELIAL DETACHMENT ASSOCIATED WITH CHOROIDAL NEOVASCULARIZATION IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To describe the multimodal imaging characteristics of flat irregular pigment epithelial detachment (FIPED) in patients with chronic central serous chorioretinopathy and determine the risk factors for vascularized FIPED and to explore the activity of vascularized FIPED before and after half-dose photodynamic therapy. METHODS: Multimodal imaging data of 185 eyes of 155 consecutive patients with chronic central serous chorioretinopathy included spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Optical coherence tomography angiography was available for 56 eyes. Flat irregular PED was classified into two types based on indocyanine green angiography or optical coherence tomography angiography findings: avascular FIPED and vascularized FIPED. RESULTS: The avascular FIPED and vascularized FIPED were detected in 127 (68.6%) and 42 (22.7%) eyes, respectively. Age (P = 0.001), visual acuity (P = 0.048), subfoveal choroidal thickness (P = 0.032), height (P < 0.001) and width (P < 0.001) of FIPED, choriocapillary thickness (P = 0.015), and maximum vessel diameter (P = 0.009) beneath the FIPED were significantly different between avascular and vascularized FIPEDs. Old age was an independent risk factor for vascularized FIPED. On optical coherence tomography angiography, all vascularized FIPEDs manifested the pattern of mature choroidal neovascularization (CNV). After half-dose photodynamic therapy, vascularized FIPED remained stable without the reaccumulation of subretinal fluid at the last follow-up. CONCLUSION: In chronic central serous chorioretinopathy, vascularized FIPED was closely associated with Type I CNV. Old age was an independent risk factor for vascularized FIPED. Vascularized FIPED is suggested as "quiescent" CNV, and half-dose photodynamic therapy may be recommended as the first-line therapy in chronic central serous chorioretinopathy complicated with quiescent CNV, except when the activity of CNV becomes evident.

COMPARISON OF THE INTERNAL LIMITING MEMBRANE INSERTION TECHNIQUE AND THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE WITH VITRECTOMY TO TREAT MACULAR HOLE-ASSOCIATED RETINAL DETACHMENT.

PURPOSE: To compare the anatomical and functional outcomes of macular hole (MH)-associated retinal detachment after vitrectomy with the internal limiting membrane (ILM) insertion technique or the inverted ILM flap technique. METHODS: In this retrospective observational study, we reviewed the medical records of 49 eyes with MH-associated retinal detachment that underwent vitrectomy with the ILM insertion (26 eyes) or ILM flap (23 eyes) technique. RESULTS: The MH closure rate at 12 months was greater in the ILM flap group versus the ILM insertion group (95% vs. 73%, respectively, P = 0.059). The postoperative best-corrected visual acuity (BCVA) at 12 months was significantly better in the ILM flap group (P = 0.014). All eyes (100%) showed an improvement in the BCVA of ≥0.3 logarithm of the minimum angle of resolution (15 Early Treatment Diabetic Retinopathy Study letters) in the ILM flap group versus 20 eyes (77%) in the ILM insertion group (P = 0.026). The preoperative BCVA and the ILM flap technique were significantly correlated with the postoperative BCVA (P = 0.028 and 0.027, respectively) and BCVA improvement (≥0.3 logarithm of the minimum angle of resolution [15 Early Treatment Diabetic Retinopathy Study letters]; P = 0.003 and 0.026, respectively). CONCLUSION: The inverted ILM flap technique was more effective in improving the postoperative BCVA in patients with MH-associated retinal detachment when compared with the ILM insertion technique. The preoperative BCVA and the ILM flap technique were independent prognostic factors for visual outcomes in patients with MH-associated retinal detachment.

CLINICAL FEATURES, DIAGNOSTIC SIGNIFICANCE, AND PROGNOSIS OF VITREORETINAL LYMPHOMA IN YOUNG PATIENTS.

PURPOSE: To investigate the clinical features, diagnostic approaches, and outcomes of young patients with vitreoretinal lymphoma. METHODS: Fifty-one vitreoretinal lymphoma patients (97 eyes) referred to the Eye and ENT Hospital of the Fudan University from 2011 to 2020 were grouped based on their onset age (age ≤50 years and age >50 years). Complete eye examinations, evaluation of systemic conditions, and biological analysis of intraocular fluids were performed. RESULTS: Young patients accounted for 31.4% (n = 16) of the cohort. More eyes had retinal/subretinal pigment epithelial infiltration (20 [64.5%] vs. 23 [34.8%]; P = 0.018) in young patients than in elderly ones. The mutation rate of Myeloid Differentiation Factor 88 gene (MYD88) was significantly lower in young patients than in elderly ones (5 [50%] vs. 21 [91.3%]; P = 0.016). The median time to new onset of central nervous system lymphoma was significantly shorter in young patients (11.7 vs. 36.2 months; P = 0.012). However, mean overall survival did not differ between the 2 groups (64.9 vs. 57.5 months; P = 0.871). CONCLUSION: Early diagnosis and central nervous system evaluation are crucial for young vitreoretinal lymphoma patients with rapid central nervous system involvement. Meanwhile, young vitreoretinal lymphoma patients have some unique features, including more retinal/subretinal pigment epithelial infiltrations and lower MYD88 mutation rates.

Vitrectomy for laser-induced full-thickness macular hole.

BACKGROUND: To report the structure and visual outcomes of pars plana vitrectomy (PPV) for laser-induced full-thickness macular holes (MHs). METHODS: This retrospective study enrolled 10 patients who underwent vitrectomy for MHs caused by laser injury. Best corrected visual acuity (BCVA), macular spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA) were used for assessment. RESULTS: Four patients were injured by unexpected expose of an yttrium aluminum garnet (YAG) laser, and six patients were accidentally injured by a handheld laser. The MH minimum diameters (MDs) ranged from 55 to 966 µm (mean = 548.00 ± 286.10 µm), and BCVA ranged from 20/400 to 20/50 (mean = logMAR 0.87 ± 0.29) preoperatively. All 10 eyes underwent PPV, internal limiting membrane (ILM) peeling, and gas tamponade. All eyes demonstrated closure of the MH with different degrees of discontinuity of the outer layer of the retina, and four eyes exhibited serious retinal pigment epithelium (RPE) destruction. Postoperative BCVA values were significantly improved (mean = logMAR 0.55 ± 0.33; P = 0.032, t = 2.234). The mean BCVA of the destroyed RPE group was significantly worse than that of the non-destroyed RPE group both before and after surgery (P = 0.019; Wilcoxon signed rank test). Further, OCTA indicated choroidal ischemia in the laser-induced MHs. CONCLUSION: Vitrectomy can be successful in closing laser-induced full-thickness MHs and improving visual acuity. However, If RPE/choroid is involved in laser damage in addition to the outer retinal layer, this may indicate poor visual prognosis.