An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

Predictive factors of visual function recovery after pituitary adenoma resection: a literature review and Meta-analysis.

AIM: To determine the dominant predictive factors of postoperative visual recovery for patients with pituitary adenoma. METHODS: PubMed, Google Scholar, Web of Science and Cochrane Library were searched for relevant human studies, which investigated the prediction of the postoperative visual recovery of patients with pituitary adenoma, from January 2000 to May 2017. Meta-analyses were performed on the primary outcomes. After the related data were extracted by two independent investigators, pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were estimated using a random-effects or a fixed-effects model. RESULTS: Nineteen studies were included in the literature review, and nine trials were included in the Meta-analysis, which comprised 530 patients (975 eyes) with pituitary adenoma. For the primary outcomes, there was a significant difference between preoperative and postoperative mean deviation (MD) values of the visual field (WMD -5.85; 95%CI: -8.19 to -3.51; P<0.00001). Predictive characteristics of four factors were revealed in this Meta-analysis by assigning the patients to sufficient and insufficient groups according to postoperative visual field improvements, including preoperative visual field defect (WMD 10.09; 95%CI: 6.17 to 14.02; P<0.00001), patient age (WMD -12.32; 95%CI: -18.42 to -6.22; P<0.0001), symptom duration (WMD -5.04; 95%CI: -9.71 to -0.37; P=0.03), and preoperative peripapillary retinal nerve fiber layer (pRNFL) thickness (OR 0.1; 95% CI: 0.04 to 0.23; P<0.00001). CONCLUSION: Preoperative visual field defect, symptom duration, patient age, and preoperative pRNFL thickness are the dominant predictive factors of the postoperative recovery of the visual field for patients with pituitary adenoma.

Quantitative analysis of retinal layers on three-dimensional spectral-domain optical coherence tomography for pituitary adenoma.

PURPOSE: To quantitatively investigate the characteristics of eyes with pituitary adenoma presented by three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) using three common indices, including thickness, optical intensity ratio, and optical intensity attenuation coefficient (OIAC). METHODS: The SD-OCT database of 38 patients with pituitary adenoma and 39 normal controls were included in the study. Quadrantal and average measurements of thickness, optical intensity ratio, and OIAC were calculated for macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL) combined with inner plexiform layer (IPL) (GCIPL) and/or the collective ganglion cell complex (GCC). The parameters of patients and controls were compared by unpaired t-test and Mann-Whitney U-test. The relationships between the optical intensity ratio and the thickness of mRNFL and GCIPL were evaluated by Pearson's correlation. Diagnostic performances of these indices were assessed using receiver operating characteristic (ROC) analysis. RESULTS: Significant decreases in thickness existed in the mRNFL and nasal GCC of patients compared with controls (p-values of 0.000 to 0.039). Optical intensity ratios in the relevant retinal layers of patients were almost all lower than those of controls. In patients, optical intensities were increased in the mRNFL but decreased in the GCIPL along with an increase of retinal thicknesses. The OIAC measurements were significantly higher in the upper quadrants and global average of the mRNFL in patients. The areas under the ROC curves (AUC) obtained by global average mRNFL thickness was significantly greater than that of the global average OIAC in the mRNFL (p = 0.0265). CONCLUSIONS: Thicknesses of the mRNFL and nasal GCC were significantly decreased in the retinas of patients with pituitary adenoma compared with controls. The differences of the optical intensity ratio and OIAC between patients and controls were not all statistically significant. Thickness was more sensitive than optical characteristics indices in distinguishing pituitary adenoma from controls.

Transforming growth factor-ß2 increases the capacity of retinal pigment epithelial cells to induce the generation of regulatory T cells.

The present study investigated the underlying mechanism of the induction of regulatory T cells (Tregs) by retinal pigment epithelial (RPE) cells and the characteristics of these Tregs. Human RPE cells were cultured in the presence or absence of transforming growth factor-ß 2 (TGF-ß2), and reverse-transcription quantitative PCR was performed to determine the mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear factor erythroid 2-related factor (Nrf2). Supernatants of RPE cell cultures were added to CD4+ T cells to induce Tregs. The RPE-induced Tregs were purified by two-step magnetic cell sorting. The natural Tregs were isolated from the peripheral blood mononuclear cells of healthy volunteers. Purified CD4+ CD25- T cells (2 x 10(5)/well) were cultured alone or with Tregs (various densities, natural or RPE-induced). The proliferation of CD4+ CD25- T cells was determined by 3H-thymidine incorporation. After 24 h of stimulation with TGF-ß2, the mRNA expression of IDO in RPE cells was upregulated. The highest level of IDO mRNA expression was reached after 72 h of stimulation with TGF-ß2. However, the Nrf2 mRNA expression was slightly decreased after 24 h of stimulation with TGF-ß2 and significantly increased after 48-72 h of TGF-ß2 stimulation. Increased levels of CD25 expression were observed on CD4+ T cells exposed to supernatants of RPE cell cultures treated with TGF-ß2 and recombinant interleukin-2. The RPE-induced Tregs were more effective at suppressing the proliferation of CD4+ CD25- T cells compared with native Tregs. These findings suggested that IDO may be a signaling protein in RPE cells which is implicated in the induction of Tregs. RPE-induced Tregs have the potential to be applied for immunotherapy for ocular inflammatory diseases.

Tolerogenic dendritic cells suppress murine corneal allograft rejection by modulating CD28/CTLA-4 expression on regulatory T cells.

Anterior chamber-associated immune deviation (ACAID) is initiated when dendritic cells (DCs) capture intraocular antigen and induce regulatory T cells (Tregs) in the spleen. We investigated whether DCs could be used as an immunotherapy to prevent murine corneal allograft rejection by inducing Tregs. Bone marrow-derived DCs (BMDCs) were differentiated with transforming growth factor-ß2 (TGF-ß2) in the presence of donor-derived allopeptide in vitro (TGFß2-DCs), and adoptively transferred to BALB/c mice. Three days later a corneal allograft transplant was carried out. Graft rejection, as well as the number and the phenotype of splenic Tregs, were determined after transplant. CD86, CD80, CD40 were present, and MHC class II expression were significantly reduced on TGFß2-DCs compared to BMDCs not exposed to TGF-ß2. TGFß2-DCs increased the number of splenic Tregs (CD4(+)CD25(+)) in recipient mice prior to transplant by modulating CD28/CTLA-4 expression. These induced Tregs suppressed proliferation of CD4(+)CD25(-) T cells ex vivo. TGFß2-DCs delayed corneal allograft rejection and TGFß2-DC recipient mice had significantly more splenic Tregs expressing Foxp3 and CTLA-4, but fewer CD28+ Tregs. Expression of GITR, CD69, and CD45RB were similar in TGFß2-DC and control mice. Therefore, the phenotype of TGFß2-DCs suggests they are tolerogenic DCs (tolDCs). In vivo, these cells increased the number and function of Tregs by modulating CD28/CTLA-4 expression. The suppressor Tregs induced by TGFß2-DCs may be involved in the induction of ACAID, which helps to suppress corneal allograft rejection. Our results provide proof of principle for the use of tolDCs as immunotherapy during transplant.

Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1α.

Concerns were increasingly raised that several types of cancers overexpressed the nuclear factor erythroid 2-related factor 2 (Nrf2), which contributed strikingly to cancer biological capabilities and chemoresistance. However, the role of Nrf2 in the tumor vascular biology had yet to be mechanistically determined. Here, we investigated the involvement of Nrf2 in glioblastoma (GB) angiogenesis in hypoxia. First, we detected the overexpression of Nrf2 and correlated its protein level with microvessel density (MVD) in human GB tissues. Then, we established the stable RNAi-mediated Nrf2-knockdown cells and mimicked hypoxic condition in vitro. The knockdown of Nrf2 inhibited cell proliferation in vitro and suppressed tumor growth in mouse xenografts with a concomitant reduction in VEGF expression and MVD. Similar antiangiogenic effects were documented in endothelial tube formation assays. The downregulation of Nrf2 in glioma cells led to much lower accumulation of HIF-1α protein and limited expression of VEGF and other HIF-1α target genes in mimicking hypoxia. Mechanistic investigations suggested that HIF-1α degradation during hypoxia could be attributed to reduced mitochondrial O2 consumption in Nrf2-inhibited cells. It can be concluded that Nrf2, with its capacity for affecting the protein level of HIF-1α expression, has good reasons to be considered as a critical transcription factor for controlling glioma angiogenesis.

Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model.

NF-E2-related factor 2 (Nrf2) is a pivotal transcription factor of cellular responses to oxidative stress and recent evidence suggests that Nrf2 plays an important role in cancer pathobiology. However, the underlying mechanism has yet to be elucidated, particularly in glioma. In the present study, we investigated the role of Nrf2 in the clinical prognosis, cell proliferation and tumor growth of human glioblastoma multiforme (GBM). We detected overexpression of Nrf2 protein levels in GBM compared to normal brain tissues. Notably, higher protein levels of Nrf2 were significantly associated with poorer overall survival and 1-year survival for GBM patients. Furthermore, we constructed the plasmid Si-Nrf2 and transduced it into U251MG cells to downregulate the expression of Nrf2 and established stable Nrf2 knockdown cells. The downregulation of Nrf2 suppressed cell proliferation in vitro and tumor growth in mouse xenograft models. We performed immunohistochemistry staining to detect the protein levels of Nrf2, Ki-67, caspase-3 and CD31 in the xenograft tumors and found that the expression levels of Nrf2 and Ki-67 were much lower in the Si-Nrf2 group compared to the Si-control group. In addition, the number of caspase-3-positive cells was significantly increased in the Si-Nrf2 group. By analysis of microvessel density (MVD) assessed by CD31, the MVD value in the Si-Nrf2 group decreased significantly compared to the Si-control group. These findings indicate that the knockdown of Nrf2 may suppress tumor growth by inhibiting cell proliferation, increasing cell apoptosis and inhibiting angiogenesis. These results highlight the potential of Nrf2 as a candidate molecular target to control GBM cell proliferation and tumor growth.

Ocular siderosis.

Ocular siderosis refers to intraocular iron deposition in ocular tissues caused by the long-time retention of penetrating iron-containing foreign bodies, commonly leading to a series of characteristic alterations and severe disorder of visual function. Ocular siderosis, rarely seen in the clinic, can cause irreversible retinal injuries and visual function damage and can even affect the appearance of the eyeballs. These effects significantly decrease the quality of life of patients and lead to poor prognosis. This study summarizes ocular siderosis with respect to pathogenesis, clinical manifestations, diagnosis, treatment, and sequelae, with the aim of assisting clinicians in the diagnosis and treatment of ocular siderosis.

Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population.

OBJECTIVE: The angiotensin-converting enzyme (ACE) gene has been implicated in the development of diabetic retinopathy (DR). However, the results have been conflicting. In this study, we performed a meta-analysis to assess the association of insertion/deletion (I/D) polymorphism in the ACE gene with DR in the Chinese population. METHODS: Published literature from PubMed, CNKI, CBM and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. RESULTS: Seventeen studies (1039 cases and 1185 controls) for I/D polymorphism in the ACE gene were identified. The results suggested that I/D polymorphism D allele might increase the risk of DR (DD vs. II: OR = 1.73, 95% CI 1.19-2.51; DD+ID vs. II: OR = 1.41, 95% CI 1.16-1.72; DD vs. ID+II: OR = 1.55, 95% CI 1.13-2.12). Subgroup analyses based on the type of DR showed that the effect size was statistically significant for proliferative DR (PDR) (DD vs. II: OR = 2.67, 95% CI 1.53-4.64; DD+ID vs. II: OR = 1.86, 95% CI 1.18-2.93; DD vs. ID+II: OR = 2.22, 95% CI 1.38-3.55), but not for background DR (BDR) (DD vs. II: OR = 1.38, 95% CI 0.85-2.25; DD+ID vs. II: OR = 1.40, 95% CI 0.98-2.02; DD vs. ID+II: OR = 1.15, 95% CI 0.74-1.79). CONCLUSION: The results indicated that I/D polymorphism in the ACE gene was associated with PDR, but not with BDR in the Chinese population.

Pathological changes in rabbit retina and its relationship with glutamic acid after injuries from high-speed bullets.

PURPOSE: To observe the pathological changes in rabbit retinas and the measure of glutamic acid levels in the vitreous body after suffering from high-speed bullet injuries. METHODS: Rabbits eyeball contusion models were established with high-speed bullets, i.e., the rabbits eyes were shot with a fixed air rifle at a speed of 90m/s (using plastic bullets, weighing 0.20122g, on average). Retinal tissues treated with HE staining and were prepared for light microscopy examination and glutamate levels were tested at different points in time after the injury. RESULTS: Edema, exudation, hemorrhage, and rupture were evident in rabbit retinas following bullet injuries. Meanwhile, glutamate levels gradually increased as time proceeded. CONCLUSION: Visual impairment is related with retinal damages after high-speed bullet injuries. Increased glutamate concentration serves as a potential factor for aggravating retinal injuries.

Peripheral ophthalmic artery aneurysm.

Generally speaking, the term "ophthalmic aneurysms" refers to carotid-ophthalmic aneurysms, which arise from the internal carotid artery (ICA) wall at or around the origin of the ophthalmic artery (OA). In contrast, aneurysms arising from the OA stem or its branches, separate from the ICA are called peripheral OA aneurysms (POAAs). POAAs are a rare entity, which clinical features and natural course are not fully understood. A comprehensive literature review of reported aneurysms involving each segment of the OA was undertaken. The demographics, aetiology, clinical manifestations and treatment of reported POAAs are discussed. Of 35 retrieved cases, ten involved the intracranial segment, two were fusiform aneurysms in the optic canal, 17 arose from the intraorbital segment, and 6 involved either the lacrimal or the anterior ethmoidal branches. In 34 cases, clinical details were available; 18 patients experienced moderate to severe visual impairment including blindness, while seven patients had improvement in visual acuity as a result of surgical treatment. The present clinical review reveals that aneurysms of the OA stem and lacrimal branch are potentially threatening to visual acuity, while intracranial segment and anterior ethmoidal aneurysms can rupture and cause subarachnoid or intraparenchymal haemorrhage. Surgical intervention is mandatory in symptomatic cases to prevent visual deterioration or treat aneurismal rupture; alternatively, for small incidental POAAs "watchful waiting" may be indicated.

[Effect of seawater soaking on corneal epidermis injury].

PURPOSE: Use slit lamp microscope and optical microscope to observe the changes in corneal tissue after corneal epidermis injury and the effect of seawater soaking on the healing of cornea after explosive injury. METHOD: Corneal epidermis were scraped on 20 eyes of 10 adult grey rabbits. For each rabbit, the right eye was in experiment and the left one was for comparison. After the injury, the experimental eyes were soaked in seawater for 30 minutes and the comparable eyes were soaked in 0.9% sodium chloride injection for the same time. All eyes were underwent slit lamp examinations, fluorescein dyeing, and ultrasonic cornea thickness metering on the corneas before the injury and 1, 3, 5, 7, 10 days after the injury respectively. At the same time, 2 rabbits were killed and the eyes were examined with pathology. The cornea thickness numbers were compared using self-comparison t test and grouping t test. Result after scraping the whole corneal epidermis, slit lamp microscope examination found that the corneas were edema and turbidity, the experimental eyes were stricter than the comparable eyes. The corneas of the experimental eye were vascularized 10 days after the injury. Fluorescein dyeing showed that more apparent pigmentation was found on the experimental eyes than that on the comparable ones. Comparative examination under the optical microscope showed that the corneal tissue of the experiment eyes changed distinctly, its inflammation is patency and healing was delayed and the vascularization degree became high after the injury. Cornea thickness of the experimental eyes became apparently thicker than that of the comparable eyes. The difference was statistically significant. CONCLUSION: Seawater soaking will have bad effects on the healing of the corneal epidermis injury.

[Lamellar corneal graft certosina for corneal perforation].

PURPOSE: To explore the treatment of corneal perforation, lamellar corneal graft cetosina was performed in patients with corneal perforation by operation of eliminating foreign body in deep cornea. METHODS: Five patients with operation of eliminating foreign body in deep cornea were treated with lamellar corneal graft certosina from 1999 to 2002. These five cases were all offered 1-week conservative therapy but without curative effect. The period of postoperative follow-up was 1 year. RESULTS: All five cases were healed, and attained satisfying anterior chamber. The inflammation of each anterior pole of eye was controlled quickly. The visual acuity was all improved quickly. The visual acuity was 0.15-1.0 (mean: 0.51) after one year follow-up. Slit-lamp examination showed translucence slight cloudy in the areas of corneal operation. The rest areas of cornea were transparent. No corneal neovascular and fore-and-aft iris conglutination appeared. There was no obvious change by the keratometer and corneal topography. CONCLUSION: Lamellar corneal graft certosina is an effective method for patients with corneal perforation due to operation of eliminating foreign body in deep cornea.

Study on retinal ganglion cell apoptosis after explosive injury of eyeballs in rabbits.

PURPOSE: To explore the pathological changes of retinal ganglion cell apoptosis and its relation to the value of glutamate concentration in vitreous body after explosive injury of eyeballs in the rabbits. METHOD: Similar explosive injury models of eyeballs in 10 adult grey rabbits were made. The rabbits were killed on scheduled time. The retinal tissues of studied eyes and control eyes were obtained for the pathological examination with TUNEL method respectively. The value of glutamate in vitreum of injured eyes was measured and was compared with that of contralateral eyes. Statistical comparison analysis on the experiment data was performed. RESULT: The value of glutamate in vitreum of injured eyes was significantly higher than that of contralateral eyes in all rabbits in the study. A lot of TUNEL positive cells were observed in the injured eyes. It suggested that apoptosis of the retinal ganglion cells took place. CONCLUSION: We speculate that apoptosis of the retinal ganglion cells is perhaps among the causes resulting in damage of visual function after explosive injury of eyeballs and that the increasing of the value of glutamate in vitreum possibly associated with apoptosis of the retinal ganglion cells.

Effect of seawater soaking on explosive cornea injury.

OBJECTIVE: To observe the changes in corneal tissue after explosive corneal injury and the effect of seawater soaking on the healing of cornea after explosive injury with the help of optical microscope. METHODS: Make 10 similar explosive injury models of rabbit's eyeball using 10 adult grey rabbits. For each rabbit, both eyes are artificially injured through explosion; its right eye is the comparison eye and after the injury the left eye is soaked in seawater for 30 minutes. (Conduct slit lamp examinations, fluorescein dyeing, and ultrasonic cornea thickness metering on the corneas at intervals, that is, before the injury, 1, 2, 3, 4, 5, 7, 9, 12, 15 days after the injury respectively. Examine the corneas under the optical microscope and make comparisons. RESULTS: The corneal thickness of the experiment eye becomes apparently thicker than that of the comparison eye after the injury. The corneal clouding of the former apparently aggravates compared with the latter. The healing of corneal epithelium in the injured eye is slower compared with that in the comparison eye. Comparative examination under the optical microscope shows: after the injury, the corneal tissue of the experiment eye changes distinctly, its healing is delayed and the vascularization degree becomes high in corneal stroma. CONCLUSION: Scars and vascularization of various degrees will appear in corneal stroma after explosive injuries. Seawater soaking will have bad effects on the healing of the cornea injured in explosions.