Cryopreservation in Ophthalmology

Amniotic membranes (AMs) and corneas are critical materials in ocular surface reconstruction. AM has specific structures (e.g., basement and two types of cells with stemness characteristics: amniotic epithelial cells and amniotic mesenchymal cells), which contribute to its attractive physical and biological properties that make it fundamental to clinical application. The corneal endothelial cell is a vital part of the cornea, which can influence postoperative vision directly. However, widespread use of fresh AM and cornea has been limited due to their short use span and safety concerns. To overcome these concerns, different preservation methods have been introduced. Cryopreservation is distinguished from many preservation methods for its attractive advantages of prolonged use span, optimally retained tissue structure, and minimized infection risk. This review will focus on recent advances of cryopreserved AM and cornea, including different cryopreservation methods and their indications in ophthalmology

Zinner syndrome: a case report and literature review

Objective To investigate the key issues of clinical diagnosis and treatment of Zinner syndrome and reduce the misdiagnosis rate. Methods Clinical data of 1 case of Zinner syndrome were retrospectively analyzed. Zinner syndrome cases presenting hematuria， frequent urination and dysuria as initial manifestations were retrieved from PubMed， CNKI， Wanfang Data and Chongqing VIP until November 2022 by using the searching words of Zinner syndrome， renal agenesis and seminal vesicle cyst. Clinical characteristics， developmental characteristics and treatment methods were summarized. Results The 46-year-old male patient was admitted to the hospital because of “bladder space-occupying lesion for more than 8 years， hematuria with dysuria for 1 week”， and was diagnosed with Zinner syndrome by imaging examination. He successfully underwent “transurethral cystoscopy + transrectal pelvic mass puncture biopsy”， and was discharged from the hospital at postoperative 2 d. The patient was advised to continually receive anti-infection treatment after discharge. According to literature review， 16 cases of Zinner syndrome presenting with hematuria， dysuria and other urinary symptoms as the first manifestations were collected. All patients developed abnormalities in the urinary system by imaging examination. Surgical resection and puncture biopsy were the main treatment methods. Among 8 patients receiving follow-up， 7 cases did not recur， and 1 suspected recurrent case underwent puncture biopsy. Conclusions Zinner syndrome is mainly manifested with imaging characteristics of unilateral seminal vesicle cyst， ipsilateral renal agenesis and ipsilateral ejaculatory duct obstruction triad. Ultrasound， CT scan， and MRI are important diagnostic tools for Zinner syndrome. Laparoscopic seminal vesicle cystectomy can reduce the risk of recurrence

A Robust and Powerful Set-Valued Approach to Rare Variant Association Analyses of Secondary Traits in Case-Control Sequencing Studies

In many case-control designs of genome-wide association (GWAS) or next generation sequencing (NGS) studies, extensive data on secondary traits that may correlate and share the common genetic variants with the primary disease are available. Investigating these secondary traits can provide critical insights into the disease etiology or pathology, and enhance the GWAS or NGS results. Methods based on logistic regression (LG) were developed for this purpose. However, for the identification of rare variants (RVs), certain inadequacies in the LG models and algorithmic instability can cause severely inflated type I error, and significant loss of power, when the two traits are correlated and the RV is associated with the disease, especially at stringent significance levels. To address this issue, we propose a novel set-valued (SV) method that models a binary trait by dichotomization of an underlying continuous variable, and incorporate this into the genetic association model as a critical component. Extensive simulations and an analysis of seven secondary traits in a GWAS of benign ethnic neutropenia show that the SV method consistently controls type I error well at stringent significance levels, has larger power than the LG-based methods, and is robust in performance to effect pattern of the genetic variant (risk or protective), rare or common variants, rare or common diseases, and trait distributions. Because of the SV method’s striking and profound advantage, we strongly recommend the SV method be employed instead of the LG-based methods for secondary traits analyses in case-control sequencing studies

SVSI: Fast and Powerful Set-Valued System Identification Approach to Identifying Rare Variants in Sequencing Studies for Ordered Categorical Traits: SVSIfor Genetic Association Studies

For genetic association studies that involve an ordered categorical phenotype, we usually either regroup multiple categories of the phenotype into two categories (“cases” and “controls”) and then apply the standard logistic regression (LG), or apply ordered logistic (oLG) or ordered probit (oPRB) regression which accounts for the ordinal nature of the phenotype. However, these approaches may lose statistical power or may not control type I error rate due to their model assumption and/or instable parameter estimation algorithm when the genetic variant is rare or sample size is limited. Here to solve this problem, we propose a set-valued (SV) system model, which assumes that an underlying continuous phenotype follows a normal distribution, to identify genetic variants associated with an ordinal categorical phenotype. We couple this model with a set-valued system identification algorithm to identify all the key system parameters. Simulations and two real data analyses show that SV and LG accurately controlled the Type I error rate even at a significance level of 10−6 but not oLG and oPRB in some cases. LG had significantly smaller power than the other three methods due to disregarding of the ordinal nature of the phenotype, and SV had similar or greater power than oLG and oPRB. For instance, in a simulation with data generated from an additive SV model with odds ratio of 7.4 for a phenotype with three categories, a single nucleotide polymorphism with minor allele frequency of 0.75% and sample size of 999 (333 per category), the power of SV, oLG and LG models were 70%, 40% and <1%, respectively, at a significance level of 10−6. Thus, SV should be employed in genetic association studies for ordered categorical phenotype

Research progress of TRPV4 in ocular pathophysiological function

Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed

Incomplete handwritten Dongba character image recognition by multiscale feature restoration

Abstract Incomplete handwritten Dongba character often appears in heritage documents and its recognition is significant for heritage and philology. However, all previous methods always suppose that a complete Dongba character is used as input, and thus fail to achieve satisfactory performance when applied to incomplete Dongba character recognition. In this paper, an end-to-end network (DB2RNet) is proposed for incomplete handwritten Dongba character image recognition by multiscale feature restoration. Specifically, we first develop datasets that contain different levels of incomplete Dongba characters. A restoration module is proposed to restore the input incomplete Dongba character, and then a recognition module is employed to recognize Dongba character. By introducing an inter-module residual connection between the restoration module and recognition module, the DB2RNet can strengthen feature information transmission and boost the recognition performance. In addition, novel multiscale feature blocks are introduced, which can provide more effective texture and contextual information transmission for Dongba character image restoration, and thus yielding better restoration effects and better recognition results. Extensive experiments are conducted on Dongba character, Chinese character and Oracle character datasets and validate the effectiveness, superiority and robustness of our methods. Experiments results demonstrate that our proposed DB2RNet achieves competitive Dongba character restoration and recognition performance and outperforms the current state-of-the-art methods

Intravitreal Conbercept Injection with and without Grid Laser Photocoagulation in the Treatment of Diffuse Diabetic Macular Edema in Real-Life Clinical Practice

Purpose. To evaluate the efficacy of intravitreal conbercept (IVC) plus modified grid laser photocoagulation (MGP) versus IVC alone for treatment of diffuse diabetic macular edema (DDME). Methods. In this retrospective study, 51 DDME patients were treated with either IVC alone (IVC group) or IVC plus MGP (combined group) with 12 months of follow-up. The clinical records of those patients were reviewed. Results. 26 patients (31 eyes) received IVC alone and 25 patients (30 eyes) received combined therapy. At month 12, the mean best-corrected visual acuity (BCVA) letter score improvement was 9.1±4.5 and 7.5±4.2 in the IVC group and the combined group and the mean central retinal thickness (CRT) reduction was 145.1 ± 69.9 μm and 168.5±53.6 μm, respectively. There was no statistically significant difference of improvement in BCVA (P=0.164) and decrease in CRT (P=0.149) between the two groups. The mean number of injections delivered was significantly higher (P<0.001) in the IVC group (5.6 ± 0.8 per eye) than in the combined group (3.3±1.2 per eye). Conclusions. IVC alone or combined with MGP appeared to be effective for treatment of DDME, achieving the similar clinical efficacy. Moreover, MGP helps to reduce the number of injections

Trends and Hotspots Concerning Macular Hole between 2002 and 2021: A 20-Year Bibliometric Study

Background: Macular hole (MH) can severely impair central vision. Although it can be treated with vitrectomy surgery, avoiding recurrence and improving visual acuity are still priorities to be addressed. This study aims to reveal the trends and hotspots about MH. Methods: The Web of Science Core Collection (WOSCC) was used to perform a bibliometric analysis investigating trends of MH research from 2002 to 2021. We evaluated the details of associated regions, institutions, authors, and journals. To construct and overlay network visualizations, VOSviewer software was used. Results: In total, 1518 publications were collected. Our analysis showed that MH research is becoming increasingly relevant, with Japan achieving the largest number of publications (291), largest number of citations (7745 in total), and highest h-index value (48). Retina published the most publications on this topic, totaling more than the next two journals combined. An analysis of keyword co-occurrence was evaluated, highlighting several novel keywords of interest, such as flap technique, transplantation, epiretinal proliferation (EP), foveal microstructure, and retinal sensitivity. Conclusions: Details on MH research were uncovered by comprehensively analyzing the global trends and hotspots over the past two decades, presenting valuable information for future MH research. Japan, the USA, and China hold leading positions in research on this topic. Amendable surgical methods are a potential focus for improving prognosis

Regression of mature corneal lymphatic vessels by intracorneal ranibizumab injection

Objective: Ranibizumab is a Fab fragment of a recombinant, humanized, monoclonal anti-vascular endothelial growth factor (VEGF) antibody. This study analyzes the possibility of regressing lymphangiogenesis and hemangiogenesis by intracorneal ranibizumab injection. In addition, the effect of ranibizumab on corneal endothelial cells (CECs) of mice is also studied. Methods: Hemangiogenesis and lymphangiogenesis were induced in female BALB/c mice using the murine model of suture-induced inflammatory neovascularisation. The treatment group received an intracorneal injection of ranibizumab (controls: phosphate buffered saline (PBS)). Corneas were excised at different time points (1 day, 5 days, and 10 days) after the injection, and corneal whole mounts were stained with CD31, LYVE-1, and alizarin red S to quantify hemangiogenesis, lymphangiogenesis, and corneal endothelium. The morphology was analyzed by using the image analysing programme Cell boolean AND F and Image J image analysis programme, respectively. Results: In accordance with our previous findings, lymphatic vessels and blood vessels could be reduced after an intracorneal ranibizumab injection: One day after the injection, lymphatic vessels were reduced by 18% (P = 0.4), blood vessels were reduced by 22% (P = 0.083); after 5 days and 10 days, lymphatic vessels were reduced by 50% (P = 0.002) and 63% (P 0.05). Conclusions: This study is the first to demonstrate that the intracorneal ranibizumab injection is a novel technique to specifically induce regression of corneal lymphatics and blood vessels without affecting corneal endothelial cells

Identification of Novel Endogenous Anti(lymph)angiogenic Factors in the Aqueous Humor

PURPOSE. The avascular cornea is in direct contact with aqueous humor (AqH). Here we investigate whether AqH exerts anti(lymph) angiogenic effects and thereby may contribute to corneal (lymph) angiogenic privilege. METHODS. Using the murine model of suture-induced inflammatory corneal hem-and lymphangiogenesis, the potential anti(lymph) angiogenic effect of AqH was analyzed by applying murine AqH as eyedrops. Anti(lymph) angiogenic effects were measured using morphometric analysis of flat mounts stained with CD31 as panendothelial and LYVE-1 as specific lymphatic endothelial marker. The potential antilymphangiogenic effect of immunomodulatory factors contained in AqH such as vasoactive intestinal peptide (VIP) and alpha-melanocyte stimulating hormone (alpha-MSH) was analyzed in lymphatic and blood vascular endothelial cell proliferation assays in vitro. RESULTS. Topically applied AqH significantly inhibited corneal hemangiogenesis and even more so lymphangiogenesis in vivo and directly in vitro. The immunoregulatory factors VIP and alpha-MSH significantly inhibited lymphatic endothelial cell proliferation in vitro. Depletion of VIP or alpha-MSH from AqH diminished its anti-hem-and lymphangiogenic potential. CONCLUSIONS. Aqueous humor exerts significant antilymphangiogenic effects in vivo. This is at least partially mediated by the known immunomodulatory factors VIP and alpha-MSH present in the AqH. Therefore, AqH not only contributes to corneal lymphangiogenic privilege and is a new tool to identify novel endogenous regulators of lymphangiogenesis but also may have therapeutic applications