UNASSIGNED: To report the clinical, tomographic, histopathological and genetic findings of a patient with brittle cornea syndrome and a novel mutation in the ZNF469 gene likely implicated in the development of this disorder.
UNASSIGNED: A 64-year-old man presented with a two-year history of worsening vision in both eyes. The patient and his son were examined by imaging and genetic analysis.
UNASSIGNED: The patient exhibited persistent ocular irritation, decreased vision, corneal epithelial defects and corneal stromal opacity. Confocal microscopy revealed that the anterior corneal stroma had a large amount of highly reflective and striated tissue. However, his son had no symptoms. Genetic analysis identified a heterozygous c.1781C > T:p.P594L variation in the ZNF469 gene.
UNASSIGNED: We reported a novel mutation in the ZNF469 gene (c.1781C > T:p.P594L) in a patient with brittle cornea syndrome from China, which enriched the spectrum of ZNF469 variants implicated in brittle cornea syndrome.

OBJECTIVE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity.
METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual.
RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications.
CONCLUSIONS: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

OBJECTIVE: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD).
METHODS: Retrospective interventional case series.
METHODS: Seventeen patients with RBCD (31 eyes, including 6 surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022. PTK or PKP was performed as the initial surgical procedure. Significant recurrence was determined when best spectacle-corrected visual acuity decreased at least 2 lines with increased opacity in the superficial cornea. Repeated PTK or PTK on the corneal graft (CG-PTK) was considered if patients could not endure poor vision due to significant recurrence. Recurrence depth and annual increase in thickness of the central cornea and subepithelial deposits were assessed by anterior segment optical coherence tomography.
RESULTS: The mean follow-up time was 12.8 ± 8.5 years (range, 2.0-25.5 years). The mean logMAR best spectacle-corrected visual acuity improved from 1.24 ± 0.48 preoperatively to 0.27 ± 0.09 postoperatively in the initial PTK group (13 eyes, P < .001), from 1.84 ± 0.69 to 0.40 ± 0.13 in the PKP group (12 eyes, P < .001), from 1.04 ± 0.46 to 0.30 ± 0.07 in the repeated PTK group (12 times in 7 eyes, P < .001), and from 1.29 ± 0.43 to 0.39 ± 0.11 in the CG-PTK group (7 times in 5 eyes, P = .001). The median significant recurrence time was 27 months (95% confidence interval 23.9-30.1), 96 months (84.1-107.9), 31 months (28.8-33.1), and 24 months (19.8-28.2), respectively (P < .001). The depth of superficial deposits located between the epithelium and the anterior stroma was approximately 115 µm (85-159 µm). The annual thickening of subepithelial deposits was 14 ± 2 µm after initial PTK, 7 ± 3 µm after PKP, 14 ± 3 µm after repeated PTK, and 30 ± 11 µm after CG-PTK, compared to 4 ± 2 µm in surgery-naïve eyes (P = .002, .515, .002, <.001). The thickness of the central cornea increased by 15 ± 2 µm, 7 ± 2 µm, 15 ± 3 µm, and 31 ± 10 µm per year in the 4 surgery groups, respectively, compared to 5 ± 2 µm in surgery-naïve eyes (P = .001, .469, .001, <.001).
CONCLUSIONS: Better visual acuity can be achieved after PTK than PKP for treatment of RBCD. The annual thickening of subepithelial deposits may approximate an increase in central corneal thickness. The superficial distribution of subepithelial deposits makes it feasible to perform repeated PTK, even on the corneal allograft, for recurrent RBCD.

暂无摘要。

BACKGROUND: Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs.
METHODS: Prepare solutions of chitosan acetate, carboxymethyl chitosan, and β-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections.
RESULTS: Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01).
CONCLUSIONS: In summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.

Objective: To investigate the levels of cytomegalovirus (CMV) infection and associated risk factors in corneal transplant recipients who experienced transplant failure. Methods: This was a case-control study. Clinical data from 576 cases (576 eyes) of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology, Peking University Third Hospital, due to corneal transplant failure from January 2016 to May 2022 were collected. Of these, 305 were male and 271 were female, with a median age of 44.0 (0.7, 91.0) years. The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery. Patients were divided into the CMV group (CMV DNA positive) and the control group (herpes virus DNA negative). The main research indicators included the CMV infection rate, clinical characteristics, and risk factors in corneal transplant recipients. Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information, systemic diseases, ocular lesions, ocular surgical history, and local and systemic medications. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each CMV infection risk factor. Results: The overall CMV infection rate was 21.9%(126/576), with annual rates ranging from 10.9% to 37.7% from 2016 to 2021. After applying inclusion and exclusion criteria, 378 patients were included in the control trial, with 126 in the CMV group and 252 in the control group. Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions [CMV group: 38 (30.2%), control group: 26 (10.3%)], local immune and inflammatory corneal lesions [CMV group: 46 (36.5%), control group: 40 (15.9%)], congenital corneal opacity [CMV group: 46 (36.5%), control group: 48 (19.0%)] total number of corneal transplants (CMV group: 178 times, control group: 276 times), corneal deep neovascularization crossing the graft [CMV group: 104 (82.5%), control group: 68 (27.0%)] and severe opacity [CMV group: 44 (34.9%), control group: 30 (11.0%)]. Binary logistic regression analysis showed that systemic immune-related corneal lesions (OR=4.044, 95%CI 1.810-9.033, P<0.001), local immune and inflammatory corneal lesions (OR=3.554, 95%CI 1.569-8.052, P=0.002), congenital corneal opacity (OR=2.606, 95%CI 1.216-5.589, P=0.014), total number of corneal transplants (OR=3.206, 95%CI 1.753-5.864, P<0.001), corneal deep neovascularization crossing the graft (OR=8.347, 95%CI 3.967-17.559, P<0.001), and severe opacity (OR=3.063, 95%CI 1.221-7.682, P=0.017) were independent risk factors for CMV infection after corneal transplant. Conclusions: CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure. CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses. Inflammatory corneal lesions associated with systemic or local immune abnormalities, congenital corneal opacity, and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant, increasing the risk of post-transplant CMV infection, leading to the infiltration of deep neovascularization and severe opacity in the cornea.
目的： 探讨角膜移植失败者巨细胞病毒（CMV）感染水平及危险因素。 方法： 病例对照研究。收集2016年1月至2022年5月因角膜移植失败于北京大学第三医院眼科再次行角膜移植手术患者的临床资料576例（576只眼），其中男性305例，女性271例，年龄为44.0（0.7，91.0）岁。依据角膜移植手术中房水或角膜组织病毒DNA的检测结果将患者分为CMV DNA阳性的CMV组和疱疹病毒DNA均为阴性的对照组，以CMV感染率、临床特征以及危险因素为主要研究指标，运用卡方检验和二元logistic回归分析比较两组患者在一般资料、合并全身病、眼部病变、眼部手术史和局部及全身用药等方面的差异，计算各CMV感染危险因素的比值比（OR值）及95%置信区间（CI）。 结果： 患者总体CMV感染率为21.9%（126/576），2016至2021年历年CMV感染率为10.9%~37.7%。根据纳入和排除标准，最终有378例患者被纳入对照试验，其中CMV组126例，对照组252例。两组之间差异存在统计学意义（P<0.05）的主要指标为全身免疫异常相关性角膜病变［CMV组：38例（30.2%），对照组：26例（10.3%）］、局部免疫及炎性角膜病变［CMV组：46例（36.5%），对照组：40例（15.9%）］、先天性角膜混浊［CMV组：46例（36.5%），对照组：48例（19.0%）］、总角膜移植次数（CMV组：178次，对照组：276次）、跨过植片的角膜深层新生血管［CMV组：104例（82.5%），对照组：68例（27.0%）］和严重混浊［CMV组：44例（34.9%），对照组：30例（11.0%）］。二元logistic回归分析结果显示，全身免疫异常相关性角膜病变（OR=4.044，95%CI：1.810~9.033，P<0.001）、局部免疫及炎性角膜病变（OR=3.554，95%CI：1.569~8.052，P<0.05）、先天性角膜混浊（OR=2.606，95%CI：1.216~5.589， P<0.05）、总角膜移植次数（OR=3.206，95%CI：1.753~5.864，P<0.001）、跨过植片的角膜深层新生血管（OR=8.347，95%CI：3.967~17.559，P<0.001）和严重混浊（OR=3.063，95%CI：1.221~7.682， P<0.05）是角膜移植后CMV感染的独立危险因素。 结论： 超过1/5的角膜移植失败者存在CMV感染。角膜移植后的CMV感染可能与免疫排斥反应及眼部炎性反应有关。全身或局部免疫异常相关的炎性角膜病变、先天性角膜混浊和多次角膜移植可能加剧了角膜移植围手术期的炎症因子水平，增加了移植后CMV感染的风险，进而导致了角膜深层新生血管的长入和严重混浊。.

UNASSIGNED: To investigate the clinical characteristics and factors associated with herpes simplex virus keratitis.
UNASSIGNED: Patients with herpes simplex virus keratitis who came to our hospital from January 2018 to June 2022 were selected and divided into a good prognosis group and a poor prognosis group according to their prognosis. The clinical data of the two groups were compared, and univariate/multivariate logistic regression was used to analyze the factors influencing the poor prognosis of herpes simplex virus keratitis.
UNASSIGNED: A one-way analysis of variance showed that, compared with the good prognosis group, the poor prognosis group had more elderly patients and a longer course of disease, and the difference was statistically significant (p < 0.05). There were significant differences in the types of patients between the two groups (p < 0.05). Univariate logistic regression analysis also showed that age (≥65 years) (OR: 1.557, 95%CI: 1.081-2.183, p < 0.05), course of disease (> 7 months) (OR: 1.303, 95%CI: 1.003-1.829, p < 0.05), epithelial type (OR: 2.321, 95%CI: 1.198-4.321, p < 0.05), and stromal type (OR: 2.536, 95%CI: 1.672-3.871, p < 0.05) were risk factors for poor prognosis. Multivariate logistic regression analysis showed that age (≥65 years) (OR: 1.656, 95%CI: 1.168-2.357, p < 0.05) and course of disease (> 7 months) (OR: 1.461, 95%CI: 1.031-2.001, p < 0.05) were independent risk factors for the prognosis of herpes simplex keratitis.
UNASSIGNED: The clinical symptoms of herpes simplex virus keratitis include corneal opacity, corneal posterior elastic layer folds, corneal infiltration, posterior corneal mass, corneal edema, and ocular pain. Age and course of disease are important factors in the prognosis of herpes simplex virus keratitis.

OBJECTIVE: The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ-forming hydrogel and study its effects on preventing corneal stromal opacity.
METHODS: The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca 2+ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC-hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation.
RESULTS: The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) ( P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups ( P < 0.05). The MSC-hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2\'-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation.
CONCLUSIONS: The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.

BACKGROUND: The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity.
METHODS: Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed.
RESULTS: Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003).
CONCLUSIONS: This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.

Objective: To investigate the long-term outcomes of corneal grafts after penetrating keratoplasty(PK) for congenital corneal opacity(CCO) in children aged 0 to 5 years and the related influencing factors. Methods: It was a retrospective series case study. Data of 39 children (55 eyes) who underwent PK surgery due to CCO in the keratology Department of Beijing Tongren Hospital from April 2014 to April 2018 and were followed up for more than 30 months were collected. Among them, there were 17 males (43.6%) and 22 females (56.4%). The age at operation was (16.2±13.3) months, and the follow-up time was (46.4±13.8) months. Clinical data such as basic information, preoperative diagnosis, operation age, operation method and postoperative complications were recorded. The corneal graft transparency was analyzed according to preoperative diagnosis, corneal neovascularization area, age at surgery, monocular or binocular surgery interval, primary surgery type and further surgery, and postoperative complications were observed. Results: At 12 months, 24 months and the last follow-up after PK, 78.2% (43/55), 70.9% (39/55) and 58.2% (32/55) of the affected eyes had clear corneal grafts, respectively.There was no statistical significance between Peters anomaly and sclerocornea (P>0.05), while the extent of neovascularization in the limbus had a significant effect on corneal graft transparency, and graft opacity was more likely to occur in patients with vessel area exceeding 2 quadrants (P<0.05).The highest corneal graft transparency was found in children aged 1 to 3 years 80.8%(21/26) (P<0.05), followed by children younger than 6 months (7/15).The translucency rate of the corneal graft was higher in patients undergoing unilateral surgery than in those undergoing bilateral surgery (P<0.05).Translucency of corneal graft was higher in children with simple surgery than with combined surgery (P<0.05), however, cataract surgery after PK had no significant effect on corneal graft transparency (P>0.05).The postoperative complications mainly included immune rejection in 19 eyes (34.5%), complicated cataract in 13 eyes (23.6%), glaucoma in 7 eyes (13.2%), persistent corneal epithelial defect in 7 eyes (13.2%). Conclusions: After PK in children with CCO, the transparent rate of corneal grafts decreases gradually with time, but the long-term translucency of corneal grafts can still be obtained. The range of corneal neovascularization, age at the time of surgery, whether the surgery was binocular and whether the surgery was combined had an effect on the transparency of corneal graft.
目的： 探讨0~5岁儿童先天性角膜混浊（CCO）行穿透性角膜移植术（PK）后远期效果以及植片存活的相关影响因素。 方法： 回顾性系列病例研究。收集2014年4月至2018年4月因CCO就诊于北京同仁医院角膜病科行PK术并坚持随访30个月以上的患儿资料39例（55只眼）。其中男性17例（43.6%），女性22例（56.4%），手术时年龄为（16.2±13.3）个月，随访时间为（46.4±13.8）个月。记录患儿的基本信息、术前诊断、手术年龄及手术方式、术后并发症等临床资料。按照术前诊断、角膜新生血管面积、手术时年龄段、单眼还是双眼接受手术以及双眼手术的间隔时间、初次手术形式及进一步手术情况分别对其角膜植片透明情况进行分析，并观察术后并发症情况。 结果： PK术后12、24个月及末次随访时，角膜植片透明的患眼分别占78.2%（43/55）、70.9%（39/55）和58.2%（32/55）。Peters异常与角膜巩膜化患儿术后角膜植片透明率的差异无统计学意义（P>0.05），而角膜缘新生血管范围对角膜植片的透明率有明显影响：血管范围超过2个象限者的角膜植片更易出现混浊（P<0.05）。1~3岁患儿角膜植片透明率80.8%（21/26）最高（P<0.05），其次是6个月以内的患儿（7/15）。单眼手术较行双眼手术者角膜植片透明率更高（P<0.05）。单纯手术较联合手术患儿术后角膜植片透明率更高（P<0.05），但PK术后再行白内障摘除手术对角膜植片透明率无明显影响（P>0.05）；术后主要并发症包括免疫排斥反应19只眼（34.5%），并发性白内障13只眼（23.6%），眼压升高7只眼（13.2%），持续性角膜上皮缺损7只眼（13.2%）。 结论： CCO患儿行PK术后角膜植片透明率随时间延长逐渐下降，但仍可获得较高的远期角膜植片透明率。角膜新生血管范围、手术时年龄、是否双眼手术及是否联合手术对角膜植片透明率有影响。.