Purpose:This study aims to examine the impact of adenosine monophosphate-activated protein kinase (AMPK) on corneal epithelial barrier function and energy metabolism. Methods:Corneal epithelial specific AMPK knockout mice were constructed to evaluate ocular surface phenotypes. In vitro experiments were performed using human corneal epithelial cells (HCECs) transfected with small interference RNA. Epithelial barrier function was assessed by analyzing apical junction complexes through immunofluorescence and Western blot in both in vivo and in vitro models. Changes in energy metabolism were evaluated by measuring oxygen consumption rate, mitochondrial dynamics protein expression, glucose uptake, and enzyme activity. Results:Increased corneal fluorescein sodium staining and irregularly shaped epithelial cells were observed in AMPK knockout mice. The staining patterns and protein levels of tight junction and adherens junction proteins, including ZO-1, occludin, and E-cadherin, were significantly impaired in the corneal epithelium of both knockout mice and AMPK knockdown HCECs. AMPK deficiency led to reduced oxidative phosphorylation, mitochondrial biogenesis, glucose uptake, and glycolysis in the corneal epithelium. Additionally, elevated inflammation was found in the corneal epithelium in the absence of AMPK. Conclusions:This study suggests that energy metabolism disruption plays a pivotal role in corneal barrier dysfunction, and elucidates the metabolic and biological functions of AMPKα in the corneal epithelium, which may serve as a potential therapeutic target for ocular surface diseases associated with compromised barrier function.
Purpose:Growing evidence indicates a strong association between obesity and keratoconus (KC), although the potential mediating factors remain largely unknown. This study aimed to explore the potential pathways through which corneal biomechanical and topographic parameters might link obesity and KC using structural equation modeling (SEM). Methods:This case-control study included 759 participants (363 patients with KC and 396 controls) from the Chinese Keratoconus (CKC) Cohort Study. Associations among body mass index (BMI), corneal biomechanical parameters, topographic parameters, and KC were analyzed using generalized linear regression models. SEM was used to construct latent variables for corneal biomechanical and topographic parameters. Three mediation models (single, parallel multiple, and serial multiple mediation) were used to examine the mediating roles of these parameters in the association between BMI and KC. Results:After adjusting for confounders, the odds ratio (OR) for BMI and KC was 1.14 (95% confidence interval [CI] = 1.07-1.22). All corneal biomechanical and topographic parameters showed significant associations with KC (P < 0.05). In the single mediation model, the indirect effect of corneal biomechanical parameters was 0.023 (95% CI = 0.002-0.045), whereas that of topographic parameters was 0.049 (95% CI = 0.023-0.073). The parallel multiple mediation model yielded a total indirect effect of 0.033 (95% CI = 0.013-0.053), with significant pathways through corneal biomechanical parameters (effect = 0.011, 95% CI = 0.000-0.022, 17.2% of total effect) and topographic parameters (effect = 0.022, 95% CI = 0.010-0.038, 35.4% of total effect). A serial mediation pathway was also identified, in which BMI correlated with corneal biomechanical parameters, which subsequently linked to topographic parameters and then KC (effect = 0.021, 95% CI = 0.002-0.039, 32.3% of total effect). Conclusions:Higher BMI was associated with KC. The association between BMI and KC may be partially explained by alterations in corneal biomechanical and topographic parameters, providing a statistical model for understanding potential underlying links in the disease. Translational Relevance:For patients with obesity, KC-related screening should be emphasized, and health management for patients with KC and obesity should be strengthened in clinical practice.
Purpose:Studies have shown that eye rubbing is associated with increased risk of keratoconus (KC). However, the potential mediating roles between eye rubbing and KC remain largely unknown. Hence, this study aims to explore the mediating roles of two specific factors, namely, the inverse of the stiffness parameter at the first applanation (-SPA1) and maximal corneal keratometry (Kmax) values, in the relationship between eye rubbing and KC. Methods:A total of 395 patients with KC and 396 controls from the Chinese keratoconus (CKC) cohort study were included in this case-control analysis. The Spearman correlation and generalized linear regression models were used to analyze the associations between the time of eye rubbing, -SPA1, Kmax, and KC. Furthermore, three mediation models (individual, parallel multiple, and serial multiple) were utilized to investigate the mediating roles of -SPA1 and Kmax in the relationship between eye rubbing and KC. Results:After adjusting for confounding factors, the odds ratio and 95% confidence interval (CI) for the time of eye rubbing, -SPA1, and Kmax in relation to KC were 1.02 (1.01, 1.04), 1.16 (1.12, 1.19), and 3.86 (2.52, 5.92), respectively. The individual mediation model indicated that the indirect effects of -SPA1 and Kmax were 0.084 and 0.056, respectively. The parallel multiple mediation model showed a total indirect effect of 0.081 for -SPA1 and Kmax. Additionally, the serial multiple mediation model (time of eye rubbing → -SPA1 → Kmax → KC) indicated that following -SPA1, Kmax partially mediated the relationship between the time of eye rubbing and KC with a total indirect effect of 0.024 (95% CI: 0.016-0.042), accounting for 14.5% of the total effect (time of eye rubbing on KC), while no significant indirect effect was found for Kmax alone. Conclusions:The individual, parallel multiple, and serial multiple mediation analyses consistently demonstrated the mediating roles of -SPA1 and Kmax in linking the duration of eye rubbing to KC. Notably, the serial mediation pathway (time of eye rubbing → -SPA1 → Kmax → KC) exhibited a significant indirect effect. These findings confirm and complement the theoretical framework linking eye rubbing to KC, providing a reference for further exploration of the pathogenesis of KC.
In this Inside Story, a student describes his experiences after receiving a diagnosis of keratoconus at age 16 years.
To compare the suitability of the Standard Patient Evaluation of Eye Dryness (SPEED) and the Ocular Surface Disease Index (OSDI) among Chinese college students, and to further validate the SPEED questionnaire by using the OSDI in a non-clinical sample. This cross-sectional study involved 1,084 students from Nanyang Medical College, aged 18 to 21 years. The students completed the OSDI and SPEED questionnaires to assess dry eye symptoms. The correlation between the scores of the two questionnaires was analyzed to assess criterion validity. Based on the OSDI scores, a receiver operating characteristic curve was constructed to determine the area under the ROC curve and the cut-off point for evaluating the diagnostic threshold of the SPEED questionnaire. The Cronbach’s alpha values for the OSDI and SPEED questionnaires were 0.943 and 0.911, respectively. Notably, only 281 participants (25.92
Purpose:Keratoconus (KC) is a corneal disorder characterized by progressive corneal protrusion and thinning. Our previous studies have demonstrated that genetic factors influence KC occurrence. The purpose of this study was to explore the genetic model of KC from the perspective of genetic epidemiology. Methods:A total of 157 KC families, including 157 KC probands and their 445 first-degree relatives, from the Chinese Keratoconus (CKC) Cohort Study were included in present study. The genetic model of KC was evaluated by three genetic epidemiological analyses, including the Penrose method, simple segregation analysis, and complex segregation analysis, where the complex segregation analysis was conducted using the Statistical Analysis for Genetic Epidemiology package. Results:The 157 KC families included 181 affected individuals, 384 unaffected individuals, and 37 unknown individuals. There are 24 individuals diagnosed with KC among the 445 first-degree relatives. The relative frequency calculated by the Penrose method was 33.188, which was close to 1/√q. In addition, the segregation ratio calculated by the simple segregation analysis was 0.046, which was less than 1/4. Furthermore, all the hypotheses of Mendelian, nontransmission and environmental model were rejected by complex segregation analysis. These results fully showed that KC is a disease of multifactorial inheritance. Conclusions:This study identified that KC followed a pattern of multifactorial inheritance, which is helpful to provide initial guidance for prevention and management of the disease and points out a research direction for future research.
NLRP3 proteins mainly act as inflammasome core components in cytosol, but was sparsely recorded to translocate into nuclei in some conditions, such as in human simplex virus (HSV)-infected corneas, in SV40 T-Ag-immortalized human corneal epithelial cell (HCEC) line, or during differentiation of naïve T cells. This study was designed to define whether or how SV40 T-Ag transfection per se caused NLRP3 translocation. It was demonstrated that infection of primary human corneal epithelial cells with lentivirus coding for SV40 T-Ag induced NLRP3 proteins' translocation into nuclei. Pull-down of NLRP3-containing complexes in HCEC nuclear proteins followed by mass spectrometry revealed 285 nuclear proteins interacting with NLRP3 proteins. Clustering analysis of these proteins showed that "RNA binding", "Nucleocytoplasmic transport" and "Viral carcinogenic pathway" were among the enriched molecular function terms or KEGG pathways. Structural modeling showed significant but differential affinities between NLRP3 proteins and histone subunits. Systemic Evolution of Ligands by EXponential enrichment (SELEX) was utilized to define DNA motifs potentially bound by NLRP3 proteins in vitro, and in-depth analysis of SELEXed motifs confirmed that the genes harboring those motifs were significantly associated with transcription and RNA processing. This study demonstrated that during the process of SV40 T-Ag-mediated corneal cell immortalization, NLRP3 proteins translocated into nuclei and behaved like a transcription factor. Besides confirming NLRP3 proteins' novel functions in non-immune cells or tissues like cornea, these findings also shed light on the mechanisms of virus-mediated immortalization or viral induced carcinogenesis.
Keratoconus is a progressive blinding eye disease that characterized by corneal thinning and protrusion,which accompanied with irregular astigmatism and impaired visual acuity.The irregular astigmatism of early keratoconus can be corrected by spectacles.For the irregular astigmatism of moderate to severe keratoconus,spectacles are no longer suitable,and contact lenses are the best choice for patients to restore vision.There are various types of contact lenses,making the selection very difficult.In addition,trying on lenses for a long time will increase the discomfort and overall feeling of patients,and greatly increase the workload of doctors.Thus,the article aims to summarize and discuss the classification of contact lenses,the application of contact lenses in different types of keratoconus,the complications of contact lens,and the current status and prospect of contact lenses,with a view to understanding the management and clinical application of contact lenses in keratoconus patients and to further improving the application value of contact lenses in keratoconus.
Purpose:Keratoconus (KC), characterized by progressive corneal protrusion and thinning, is a complex disease influenced by the combination of genetic and environmental factors. The purpose of this study was to explore potential gene‒environment interaction between the calpastatin (CAST) gene and eye-rubbing in KC. Methods:A case-only study including 930 patients (676 patients with eye-rubbing and 254 patients without eye-rubbing) from the Chinese Keratoconus (CKC) cohort study was performed in the present study. Genotyping of single nucleotide polymorphism (SNP) was conducted using the Illumina Infinium Human Asian Screening Array (ASA) Beadchip. The gene‒environment interactions between CAST gene and eye-rubbing were analyzed using PLINK version 1.90. The interactions between CAST genotypes and eye-rubbing were analyzed by logistic regression models. The SNP-SNP-environment interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Results:Three SNPs in CAST gene, namely, rs26515, rs27991, and rs9314177, reached the significance threshold for interactions (defined as P < 2.272 × 10-3). Notably, the minor alleles of these three SNPs exhibited negative interactions with eye-rubbing in KC. The results of logistic regression models revealed that the minor allele homozygotes and heterozygotes of rs26515, rs27991, and rs9314177 also exhibited negative interactions with eye-rubbing. Furthermore, GMDR analysis revealed the significant SNP-SNP-environment interactions among rs26515, rs27991, rs9314177, and eye-rubbing in KC. Conclusions:This study identified rs26515, rs27991, and rs9314177 in CAST gene existed gene-environment interactions with eye-rubbing in KC, which is highly important for understanding the underlying biological mechanisms of KC and guiding precision prevention and proper management.
OBJECTIVE:Keratoconus (KC) is a condition characterized by progressive corneal steepening and thinning. However, its pathophysiological mechanism remains vague. We mainly performed literature mining to extract bioinformatic and related data on KC at the RNA level. The objective of this study was to explore the potential pathological mechanisms of KC by identifying hub genes and key molecular pathways at the RNA level.METHODS:We performed an exhaustive search of the PubMed database and identified studies that pertained to gene transcripts derived from diverse corneal layers in patients with KC. The identified differentially expressed genes were intersected, and overlapping genes were extracted for further analyses. Significantly enriched genes were screened using "Gene Ontology" (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) analysis with the "Database for Annotation, Visualization, and Integrated Discovery" (DAVID) database. A protein-protein interaction (PPI) network was constructed for the significantly enriched genes using the STRING database. The PPI network was visualized using the Cytoscape software, and hub genes were screened via betweenness centrality values. Pathways that play a critical role in the pathophysiology of KC were discovered using the GO and KEGG analyses of the hub genes.RESULTS:68 overlapping genes were obtained. Fifty genes were significantly enriched in 67 biological processes, and 16 genes were identified in 7 KEGG pathways. Moreover, 14 nodes and 32 edges were identified via the PPI network constructed using the STRING database. Multiple analyses identified 4 hub genes, 12 enriched biological processes, and 6 KEGG pathways. GO enrichment analysis showed that the hub genes are mainly involved in the positive regulation of apoptotic process, and KEGG analysis showed that the hub genes are primarily associated with the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathways. Overall, the matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin-endoperoxide synthase 2 were the potential important genes associated with KC.CONCLUSION:Four genes, matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin endoperoxide synthase 2, as well as IL-17 and TNF pathways, are critical in the development of KC. Inflammation and apoptosis may contribute to the pathogenesis of KC.
Keratoconus is a blinding corneal disease characterized by central or paracentral corneal thinning and conical ectasia, and usually happens in adolescence. Currently, the etiology of keratoconus is unclear. Multiple studies have identified an association between genetics, eye rubbing, allergic diseases, ultraviolet exposure and keratoconus. Recently, several studies identified that sex hormones also played important roles in the pathogenesis of keratoconus. The disturbance of sex hormones may increase the risk of occurrence and progress of keratoconus. This review aims to summarize the pathophysiological effects of sex hormones on the cornea, clarify the effects of sex hormones on keratoconus and its related inflammatory or immune mechanisms, and explore the role of sex hormones in the early diagnosis and treatment of keratoconus, providing reference and help for clinical work.
Purpose:Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases. Methods:A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90. Results:Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km. Conclusions:In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.
The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40
Transforming growth factor β1 (TGF-β1) drives corneal fibroblasts to differentiate into corneal myofibroblasts and plays a key role in corneal fibrosis. However, the role of LIM and cysteine-rich domains-1 (LMCD1) in TGF-β1-induced corneal myofibroblast differentiation and corneal fibrosis remains elusive. Thus, this study aimed to investigate the expression, regulatory mechanism, and role of LMCD1 in TGF-β1-induced corneal myofibroblast differentiation and corneal fibrosis. The expression of LMCD1 in TGF-β1-stimulated corneal fibroblasts was found to be upregulated through mRNA sequencing, quantitative PCR (qPCR), and Western blotting. Moreover, LMCD1 was identified to be upregulated in a mouse model of corneal fibrosis via qPCR and Western blotting. Additionally, our results demonstrated that the increase in LMCD1 expression induced by TGF-β1 in corneal fibroblasts was primarily regulated by the SMAD3 signaling pathway. Furthermore, LMCD1 knockdown significantly inhibited TGF-β1-induced corneal fibroblast-to-myofibroblast differentiation and simultaneously activated SMAD3, JNK, and p38 by promoting TGF-β1 transcription. These findings collectively suggest that LMCD1 could upregulate alpha-smooth muscle actin (α-SMA) expression and downregulate TGF-β1 expression in corneal myofibroblast differentiation. Consequently, upregulation of LMCD1 expression could potentially serve as a strategy to mediate the TGF-β1 signaling pathway in corneal myofibroblast differentiation and corneal fibrosis, laying a theoretical reference for corneal fibrosis and contributing to the development of effective therapeutic strategies for corneal fibrosis.
Objective:To compare the fitting effect between rig gas-permeable contact lens (RGPCL) and scleral lenses (SLs) in moderate and severe keratoconus eyes.Methods:A cross-sectional study was performed.Fifty-two eyes of 42 keratoconus patients were recruited in Henan Eye Hospital from September 2022 to September 2023.Based on steep keratometry (Ks) value, patients were divided into moderate stage (48 D≤Ks<55 D, 28 eyes) and severe stage (Ks≥55 D, 24 eyes). RGPCL and SLs were fitted normatively in all eyes.Fluorescein staining and anterior segment optical coherence tomography were performed under a slit lamp.The distance between the central and lateral centers of the lenses and the cornea, the centering of the lenses, the mobility of the lenses and the peripheral fit of the lenses were observed.Best corrected visual acuity (BCVA) converted to logarithmic minimum angle of resolution, comfort score, wetness score and clarity score were recorded.Differences in the above parameters of each patient between RGPCL and SLs wear were compared.The improvement of the above parameters after RGPCL and SLs wear was compared in moderate and severe patients.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]-04). Written informed consent was obtained from each patient before any medical examination.Results:After RGPCL wear, the mean BCVA, comfort, wetness, and clarity score were 0.19(0.10, 0.30), 5.5(3.0, 7.0) points, 7.0(5.0, 8.0) points and 7.0(4.0, 8.0) points, respectively.After SLs wear, the mean BCVA, comfort score, wetness score and clarity score were 0.10(0.00, 0.10), 8.0(8.0, 9.0) points, 8.0(8.0, 9.0) points and 8.0(6.0, 9.0) points, respectively.Compared with RGPCL wear, the BCVA, comfort score, wetness score and clarity score of SLs were significantly improved ( Z=-5.887, -6.064, -5.705, -5.516; all at P<0.001). There was a moderate positive correlation between BCVA and Kmax after SLs wearing ( rs=0.519, P<0.001), and had a moderate negative correlation with TCT ( rs=-0.535, P<0.001). There was a moderate positive correlation between the clarity score of the SLs and TCT ( rs=0.303, P=0.029). In the moderate and severe subgroup analysis, BCVA, comfort score, wetness score and clarity score were significantly improved after SLs wear compared to RGPCL (all at P<0.05). In addition, the clarity score was significantly improved in severe keratoconus compared to moderate keratoconus ( Z=-3.100, P=0.002). Conclusions:In patients with moderate to severe keratoconus, RGPCL can improve BCVA to a limited extent.SLs can significantly improve patients' comfort, wetness and visual clarity while improving their BCVA.
Background The purpose of this study was to map the publishing trend on CXL research and explore the research hotspots. Methods A bibliometric analysis was performed using the Web of Science Core Collection to investigate the publishing trend on CXL research. VOSviewer was used to build the knowledge map to visualise the number of annual publications, distribution of countries and institutions, international cooperation, author productivity, source journals and research hotspots in the field of CXL. Results A total of 2061 peer-reviewed articles on CXL research were collected from 2001 to 2020, and the annual research production increased over time. The United States was the country with the largest number of published articles, and the University of Zurich was the most active institution. Hafezi F published the largest number of articles on CXL, while Cornea was the journal with the largest number of studies on CXL. The most frequently cited references mainly focus on CXL in the treatment of keratoconus. The keywords were divided in 5 categories: 1) CXL mechanism, 2) ectasia diseases and refractive surgery, 3) corneal biomechanics, 4) efficacy evaluation, 5) treatment of infectious keratitis. Conclusion The quantity and quality of articles on CXL were evaluated using bibliometric techniques by extracting the data from the Web of Science Core Collection. The research hotspots could provide insights on CXL research, providing valuable information for clinicians to perform research in this field and find potential partners.
SMAD3 downregulation is documented in transforming growth factor β1 (TGF-β1)-induced corneal fibroblasts differentiation to myofibroblasts ("fibroTOmyoDiff") or corneal wound healing. However, the exact regulatory mechanism of TGF-β1/SMAD3 pathway in this context remains unclear. Here, we investigated the role and related mechanism of SMAD3 down-regulation in TGF-β1-induced human corneal fibroTOmyoDiff. By detecting expression changes of SMAD family during this process, we demonstrated that SMAD3 protein expression was dramatically decreased in the process and the decrease occurred mainly in SMAD3 gene transcription. Furthermore, SMAD3 overexpression using lentivirus infection and knockdown using sgRNA lentivirus infection or siRNAs revealed that SMAD3 overexpression enhanced TGF-β1-induced corneal fibroTOmyoDiff and vice versa. In addition, specific siRNAs and inhibitors targeting particular signaling pathway were used to figure out the intracellular signaling pathway regulating SMAD3, and the result showed that the decease of SMAD3 induced by TGF-β1 stimulation in human corneal fibroblasts (HCFs) was strikingly prevented by SMAD4 knockdown or p38 signaling inhibitor SB203580 treatment. Collectively, these results demonstrate that, in TGF-β1 induced corneal fibroTOmyoDiff, down-regulation of SMAD3 expression regulated by SMAD4 and p38 signaling pathways forms a negative feedback loop of TGFβ signaling to avoid excessive activation of the signaling, which suggest that SMAD3 may be a key target for corneal fibrosis treatment.
Keratoconus (KC) is a multifactorial disease in which genetic factors played important roles in its pathogenesis. The purpose of the current study was to identify the key candidate genes and pathways in Chinese patients with KC through bioinformatics analysis. Totally, we identified 71 candidate genes by analyzing the results of whole exome sequencing on 51 Chinese patients with KC, combining with previous reports on differential expression at transcription and protein levels in KC. Gene enrichment analysis with GeneCodis demonstrated that two significantly enriched terms including 21 genes in biological process (BP) were detected, and six significantly enriched terms containing 14 genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were discovered. The STRING was utilized to construct the protein-protein interaction (PPI) network of identified genes. The result showed that a PPI network consisted of 14 nodes with 14 edges was constructed, and two gene modules were obtained. Eight hub genes (LAMB3, LAMA3, LAMA1, ITGA6, ITGA3, COL6A3, COL6A2, and COL6A1) were identified as key candidate genes for KC by cytoHubba in Cytoscape. Functional enrichment analysis with ClueGO and CluePedia indicated that the ECM-receptor interaction was the key pathway accounted for KC. The findings might provide novel insights on the genetic basis of KC.
目的 探讨圆锥角膜患者进行角膜胶原交联(CXL)术后无菌性角膜炎的临床特点、治疗及愈后.方法 回顾性系列病例研究.选择2018年1月至2020年9月河南省立眼科医院屈光手术中心281例(387眼)圆锥角膜患者,其中行CXL术后发生无菌性角膜炎的患者为炎症组(9例11眼),选取同期CXL术后无并发症的圆锥角膜患者为对照组(23例30眼),比较炎症组与对照组患者的年龄、性别、平坦角膜曲率(K1)、陡峭角膜曲率(K2)、散光(Astig)及最薄点角膜厚度(TCT)的差异.采用多因素Logistic回归分析无菌性角膜炎发生的影响因素.结果 CXL术后发生无菌性角膜炎患者9例11眼,发生率为2.84%,均发生在去上皮CXL术后.9例11眼均于术后1周内出现无菌性角膜炎,1眼同时累及角膜中央区、旁中央区及周边部,1眼累及旁中央区,其余9眼均位于角膜周边部.炎症组与对照组患者的年龄、性别、K1、K2、Astig及TCT差异均无统计学意义(均为P>0.05).经皮质类固醇激素治疗,预防性使用抗生素滴眼可以取得良好效果.Logistic回归分析结果显示,年龄、性别、K1、K2、Astig及TCT均不是无菌性角膜炎发生的危险因素(均为P>0.05).结论 圆锥角膜患者行CXL后无菌性角膜炎常见于去上皮CXL患者中,一般发生在术后早期,病灶多在角膜周边部,以皮质类固醇激素为主的治疗可以取得良好效果.
Background: Patients with unilateral post-LASIK keratectasia (KE) have clinical ectasia in one eye but not in the fellow eye. As serious complications, these cases are rarely reported but are worth investigating. This study aimed to explore the characteristics of unilateral KE and the accuracy of corneal tomographic and biomechanical parameters to detect KE and distinguish fellow eyes from control eyes.Methods: The study analyzed 23 KE eyes, 23 KE fellow eyes, and 48 normal eyes from age- and sex-matched patients who had undergone LASIK. The Kruskal–Wallis test and further paired comparisons were performed to compare the clinical measurements of the three groups. The receiver operating characteristic curve was used to evaluate the ability to distinguish KE and fellow eyes from the control eyes. Binary logistic regression with the forward stepwise method was performed to produce a combined index, and the DeLong test was used to compare the discriminability difference of the parameters.Results: Males accounted for 69.6% of patients with unilateral KE. The duration between corneal surgery and the onset of ectasia ranged from 4 months to 18 years, with a median time of 10 years. The KE fellow eye had a higher posterior evaluation (PE) value than the control eyes (5 vs. 2, p = 0.035). Diagnostic tests showed that PE, posterior radius of curvature (3 mm), anterior evaluation (FE), and Corvis biomechanical index–laser vision correction (CBI-LVC) were sensitive indicators for distinguishing KE in the control eyes. The ability of PE to detect the KE fellow eye from the control eye was 0.745 (0.628 and 0.841), with 73.91% sensitivity and 68.75% specificity at a cut-off value of 3. The ability of a combined index, constructed using PE and FE, to distinguish fellow eyes of KE from controls was 0.831 (0.723 and 0.909), which was higher than that of PE and FE individually (p < 0.05).Conclusion: The fellow eyes of patients with unilateral KE had significantly higher PE values than control eyes, and a combination of PE and FE enhanced this differentiation in a Chinese population. More attention should be paid to the long-term follow-up of patients after LASIK and to be wary of the occurrence of early KE.