The Chinese keratoconus (CKC) cohort study.

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%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.

Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

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.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

Machine learning analysis with the comprehensive index of corneal tomographic and biomechanical parameters in detecting pediatric subclinical keratoconus.

Background: Keratoconus (KC) occurs at puberty but diagnosis is focused on adults. The early diagnosis of pediatric KC can prevent its progression and improve the quality of life of patients. This study aimed to evaluate the ability of corneal tomographic and biomechanical variables through machine learning analysis to detect subclinical keratoconus (SKC) in a pediatric population. Methods: Fifty-two KC, 52 SKC, and 52 control pediatric eyes matched by age and gender were recruited in a case-control study. The corneal tomographic and biomechanical parameters were measured by professionals. A linear mixed-effects test was used to compare the differences among the three groups and a least significant difference analysis was used to conduct pairwise comparisons. The receiver operating characteristic (ROC) curve and the Delong test were used to evaluate diagnostic ability. Variables were used in a multivariate logistic regression in the machine learning analysis, using a stepwise variable selection to decrease overfitting, and comprehensive indices for detecting pediatric SKC eyes were produced in each step. Results: PE, BAD-D, and TBI had the highest area under the curve (AUC) values in identifying pediatric KC eyes, and the corresponding cutoff values were 12 µm, 2.48, and 0.6, respectively. For discriminating SKC eyes, the highest AUC (95% CI) was found in SP A1 with a value of 0.84 (0.765, 0.915), and BAD-D was the best parameter among the corneal tomographic parameters with an AUC (95% CI) value of 0.817 (0.729, 0.886). Three models were generated in the machine learning analysis, and Model 3 (y = 0.400*PE + 1.982* DA ratio max [2 mm]-0.072 * SP A1-3.245) had the highest AUC (95% CI) value, with 90.4% sensitivity and 76.9% specificity, and the cutoff value providing the best Youden index was 0.19. Conclusion: The criteria of parameters for diagnosing pediatric KC and SKC eyes were inconsistent with the adult population. Combined corneal tomographic and biomechanical parameters could enhance the early diagnosis of young patients and improve the inadequate representation of pediatric KC research.

A high body mass index strengthens the association between the time of eye rubbing and keratoconus in a Chinese population: a case control study.

BACKGROUND: Although body mass index (BMI) and eye rubbing are linked to an increased risk of keratoconus (KC), the interactive effect of eye rubbing and BMI on KC is largely unknown. This study aimed to evaluate the independent and interactive effects of BMI and eye rubbing on KC and to further explore the role of environmental factors on the occurrence of KC. METHODS: A total of 621 individuals (291 KC patients and 330 control individuals) were enrolled in this hospital­based study on KC patients in Central China after individuals missing BMI data were excluded. BMI was calculated as weight in kilograms divided by the square of height in meters. Data on eye rubbing was recorded through face-to-face interviews. Generalized linear regression models were used to analyze associations among BMI, eye rubbing and KC. Interaction plots were used to describe the interactive effects of BMI and eye rubbing on KC. RESULTS: The ß and 95% confidence interval (CI) were 0.923 (0.112, 1.733) (p = 0.026) and 3.356 (1.953, 4.759) (p < 0.001), respectively, for the effect of each 10 kg/m2 increase in BMI and each 1 min increase in eye rubbing on KC. The interaction of BMI and eye rubbing were positively correlated with KC (p < 0.001). CONCLUSION: These findings suggested that a high BMI aggravated the negative effect of eye rubbing on KC, implying that individuals with a high BMI may be more susceptible to exposure to eye rubbing, which is related to an increased risk of KC.

Accuracy of tomographic and biomechanical parameters in detecting unilateral post-LASIK keratoectasia and fellow eyes.

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.

Trio-based exome sequencing broaden the genetic spectrum in keratoconus.

Keratoconus (KC) is a complex corneal disorder with genetic factors involving in its pathogenesis. The genetic etiology of KC has not been fully elucidated. In this study, we aimed to expand the genetic spectrum in KC by trio-based exome sequencing. Trio-based exome sequencing was conducted in 20 patients with KC and their unaffected parents to broaden the genetic spectrum of the disease. With a series of filtering criteria, de novo, recessive homozygous, and compound heterozygous variants in candidate genes were identified, and the candidate genes were classified for further analysis. Finally, we identified 60 variants in 32 candidate genes through trio-based exome sequencing. Among the candidate genes, 10 genes (ARHGEF10, ARHGEF17, ASPM, FLNA, NDRG1, NEB, PLS3, STARD8, SYNE1, TTN) were classified as cytoskeleton-related genes, 4 genes (COL28A1, SDK1, STAB1, TENM2) were classified as cell adhesion-related genes, and 18 genes (APLP2, BCORL1, CCNB3, FOXN1, FUT8, GALNT10, HEPH, HHIP, HMGB3, HS6ST2, JADE3, KIAA0040, MCF2L, MYOF, QRICH2, RPS6KA6, SMARCA1, TNRC6A) were classified into other genes group. Additionally, the candidate rare deleterious variants in TTN were highly repeated in 25% trios. In conclusion, the study provided new insights into the genetic spectrum of KC which might underlie the genetic etiology for the disease. The findings would improve our understanding of pathogenesis in KC and provide critical clues to future functional validation.

Correlations among Corneal Biomechanical Parameters, Stiffness, and Thickness Measured Using Corvis ST and Pentacam in Patients with Ocular Hypertension.

Background: To preliminary explore the correlations among corneal biomechanical parameters, stiffness, and thickness in patients with ocular hypertension (OHT) before and after treatment with topical antiglaucoma medications. Methods: This was a retrospective study that included 35 eyes with newly diagnosed OHT. Axial length (AL), apical corneal thickness, and minimum corneal thickness were measured using Pentacam. The lengths, velocities, and times of the first and second corneal applanations (A1L, A1V, A1T, A2L, A2V, and A2T, respectively); the highest concavity radius; highest concavity peak distance (PDHC); highest concavity deformation amplitude (DAHC); highest concavity time (HCT); pachymetry (PACH); stress-strain index (SSI); stiffness parameter-A1 (SP-A1); deformation amplitude ratio (DA ratio); integrated radius (IR); Ambrosio's relational thickness horizontal (ARTh); corneal biomechanical index; noncorrected intraocular pressure (IOPnct); and biomechanically corrected IOP (bIOP) values were measured using the corneal visualization Scheimpflug technology (Corvis ST/CST). Results: After 5 weeks of treatment, Goldman applanation tonometer-IOP, IOPnct, bIOP, PACH, A1T, A2V, SSI, SP-A1, and ARTh decreased, but A1V, A2T, PDHC, DAHC, DA ratio, and IR increased significantly (all p < 0.05). SP-A1 and A1T were positively associated with premedication IOP and IOP changes, whereas A1V, A2T, PDHC, and IR were negatively associated (all p < 0.05). DAHC and DA ratio had significantly negative correlations with IOP variations. PDHC was found to be positively correlated with AL (p < 0.05). A positive relationship was noted between SP-A1 and HCT before medication (p < 0.05). Conclusions: SP-A1 was significantly and consistently associated with IOP. HCT might be correlated with SP-A1. SP-A1 and CST parameters could serve as potential biomarkers for evaluating OHT treatment efficacy.

Effect of myopia and astigmatism deepening on the corneal biomechanical parameter stress-strain index in individuals of Chinese ethnicity.

Purpose: To investigate the differences in corneal biomechanical parameter stress-strain index (SSI) among different degrees of myopic eyes in Chinese individuals and to analyze the relevant factors of the SSI. Methods: This study analyzed the right eyes of 240 participants (240 eyes) aged 18-34 years. The participants were divided into low-, moderate-, high-, and ultra-high myopia groups according to their spherical equivalent (SE), with 60 eyes included in each group. Spherical, cylinder, and SE were measured via automatically integrated optometry. Intraocular pressure (IOP) was measured using a non-contact tonometer. AL was measured using an IOLMaster device. Corneal curvature and central corneal thickness (CCT) were measured using a Pentacam. SSI and biomechanical corrected IOP (bIOP) were measured via corneal visualization Scheimpflug technology (Corvis ST). The statistical analyses included one-sample Kolmogorov-Smirnov tests and normal distribution histogram methods, Levene variance homogeneity tests, Pearson's correlation analyses, multiple linear stepwise regression analyses, one-way ANOVA, and LSD t-tests. Results: The mean (±SD) age of the 240 participants was (24.97 ± 4.16) years. The SSI was positively correlated with spherical, cylinder, SE, CCT, IOP, and bIOP and negatively correlated with K1 and AL (r = 0.475, 0.371, 0.497, 0.169, 0.291, 0.144, -0.154, and -0.464, respectively; all p < 0.05), but were not correlated with age, K2, or Km (all p > 0.05). Multiple linear regression analysis performed with SSI as the dependent variable, and spherical, cylinder, K1, CCT, and IOP as independent variables produced the following regression equation: SSI = 0.989 + 0.017 spherical + 0.042 cylinder +0.018 IOP (R 2 = 0.402, F = 31.518, p < 0.001). The SSI values in the low-, moderate-, high-, and ultra-high myopia groups were 0.945 ± 0.135, 0.940 ± 0.128, 0.874 ± 0.110, and 0.771 ± 0.104, respectively. The values decreased sequentially, and the differences between pairs were statistically significant (all p < 0.05), except for that between the low- and moderate-myopia groups (p > 0.05). Conclusion: SSI decreased with increasing myopia and astigmatism in the Chinese participants. The SSI was significantly lower in high and ultra-high myopia, especially ultra-high myopia. These findings indicate that increased corneal elasticity may be related to the pathogenesis of high and ultra-high myopia.

Independent and interactive effects of eye rubbing and atopy on keratoconus.

Purpose: To evaluate the independent and interactive effects of eye rubbing and atopy on keratoconus (KC) in central China. Methods: A total of 330 KC patients and 330 controls were recruited in the case-control study. Eye rubbing and history of atopy were recorded through face-to-face interviews. The association between KC and eye rubbing, atopy, interactive effects of eye rubbing and atopy were analyzed by logistic regression, and the odds ratios (OR), relative excess risk due to interaction (RERI), attributable proportion (AP), synergy (S) index, and 95% confidence intervals (95% CI) were calculated. Results: A total of 228 patients (69.09%) had an eye rubbing history, and 53 (16.06%) had an atopy history in the KC group, which were both higher than that in the control group (p<0.001). Eye rubbing and atopy were positively associated with KC in multivariate analysis, with ORs (95% CIs) of 15.11 (10.02, 22.80) and 5.30 (2.59, 10.84), respectively. Compared to non-eye rubbing and non-atopy eyes, the risk for eye rubbing coexisted with atopy was 52.31 (12.25, 223.35). No significant associations were found between KC and multiplicative interaction (p=0.608). The RERI, AP, and S values were 32.89 (-43.35, 109.14), 0.63 (0.05, 1.21), and 2.79 (0.56, 13.96), respectively, with no significant association between additive interaction and KC. No significant associations were found between eye rubbing, atopy and the severity of KC (p>0.05). Conclusion: Eye rubbing and atopy were separately positively associated with KC, and there was a strong impact of coexistent eye rubbing and atopy on KC in China. Further multi-center and cohort study need to be conducted to explore the role of eye rubbing and atopy in the occurrence and development of KC.

Distribution of pediatric keratoconus by different age and gender groups.

Purpose: To evaluate the distribution of pediatric keratoconus patients and the disease severity based on different age and gender groups in China. Materials and methods: A total of 446 keratoconus eyes in 266 pediatric patients from January 2019 to January 2022 were included in the cross-sectional study. The clinical findings and severity of keratoconus were recorded and Kruskal-Wallis test, chi-squared test, and Cochran-Mantel-Haenszel (CMH) test were used to compare the parameters between different gender and age groups. Results: The male/female ratio was 353/93 (3.8:1), and the median age was 16 years (range: 6-17 years). Male patients were statistically younger than female patients (P = 0.041). The male/female ratio decreased with age (P for trend = 0.011). The distribution of the topographic keratoconus classification (TKC) stage was significantly different between gender and age groups (all P < 0.05). Male patients had a higher ratio of advanced keratoconus eyes (TKC ≥ 3) than female patients (P < 0.001), and CMH analysis indicated that being a male was a risk factor for advanced keratoconus after controlling for age (odds ratio: 2.581, P < 0.001). Conclusion: Male keratoconus patients were younger, with a higher ratio of advanced keratoconus than female patients in the Chinese pediatric patients evaluated. Multicenter studies with larger sample sizes are necessary in the future.

Bacterial Keratitis Following Small Incision Lenticule Extraction.

Purpose: To describe the development of bacterial keratitis after small incision lenticule extraction in 5 patients and to explore its appropriate therapies. Methods: We retrospectively summarized the clinical treatments of five patients with postoperative bacterial infection after small incision lenticule extraction, who were referred to our hospital from 2019 to 2021. Results: Five male patients had undergone bilateral SMILE in the local hospital due to myopia aged from 18 to 26 years. The onset of keratitis during 1-3 days postoperatively and four of them were severe infection (2 bilateral, 2 unilateral). In five cases, 1 patient (1 eye) who was infected mild keratitis after SMILE was treated with only topical antibiotics; the others who respond poorly to topical antibiotics require surgical treatment, which 1 patient (1 eye) infected necrotic mass of the corneal cap was scraped and irrigated with antibiotic, and 3 patients (5 eyes) were treated by converting the cap to flap, curetting the necrotic tissue and irrigating with the antibiotic solution. In all patients, the duration from onset to resolution was 1-5 weeks. The final uncorrected visual acuity was above 20/32. Conclusion: Owing to the upward popularity of refractive surgery, the incidence of keratitis after SMILE should not be ignored. Early diagnosis and timely treatment of post-SMILE keratitis are essential. For severe keratitis that fails to respond to topical antibiotics, the corneal cap should be opened as a flap.

Heritability of Corneal Parameters in Nuclear Families With Keratoconus.

Purpose: This study aimed to investigate the heritability of corneal parameters obtained by Pentacam in nuclear families with keratoconus (KC). Methods: A total of 82 patients with KC and their biological parents (n = 164) were recruited in the current study. All subjects underwent corneal tomography with Pentacam. Family units were analyzed to calculate the heritability of corneal parameters by linear mixed effects model using the R statistical software. Results: The pachymetry at apex, pupil, and thinnest point were all significantly heritable at 43.26%, 42.63%, and 43.09%, respectively. The heritability of flat meridian keratometry, steep meridian keratometry, and mean keratometry in the anterior surface were 10.36%, 9.05%, and 10.21%, respectively, and that of flat meridian keratometry, steep meridian keratometry, and mean keratometry in the posterior surface were 8.44%, 9.67%, and 9.06%, respectively. The posterior radius of curvature had higher heritability in comparison with anterior radius of curvature (19.16% vs. 14.37%). Moreover, among combined topometric indices, the heritability of index of vertical asymmetry was the highest (19.49%), and that of central keratoconus index was the lowest (6.64%). Conclusions: The present study demonstrated a substantial heritability of corneal parameters in nuclear families with KC. The pachymetric indices are heritable and may be suitable as KC endophenotypes, suggesting a necessity to discover the genes associated with corneal thickness in KC. Translational Relevance: The pachymetric indices are heritable and may be suitable as KC endophenotypes, indicating that the pachymetric indices might be a corneal characteristic to predict the occurrence of KC.

A Hospital-Based Study on the Prevalence of Keratoconus in First-Degree Relatives of Patients with Keratoconus in Central China.

Purpose: The present study investigated the prevalence of keratoconus (KC) among first-degree relatives of KC patients in Central China. Methods: From July 2018 to March 2022, 661 first-degree relatives of 384 KC patients were included in the present study. Corneal tomography, uncorrected distance visual acuity, manifest refraction with corrected distance visual acuity, intraocular pressure, slit-lamp microscopy, and fundus examination were performed. The diagnosis of KC was based on the Belin/Ambrosio enhanced ectasia total deviation value (BAD-D value) on the Pentacam® system (Oculus GmbH). BAD-D value <1.6 was diagnosed as healthy, 1.6≤ BAD-D value <2.6 was diagnosed as suspected KC, and BAD-D value ≥2.6 was diagnosed as KC. Results: The present study included 337 (50.98%) female and 324 (49.02%) male subjects. The prevalence of KC and suspected KC in first-degree relatives was 8.77% (n = 58) and 29.05% (n = 192), respectively. The prevalence of KC was 9.70% among parents and 7.23% among siblings. Conclusions: The higher prevalence of KC among first-degree relatives of patients with KC suggests that first-degree relatives of KC are at high risk of developing KC.

A Bibliometric Analysis of 100 Most-Cited Articles on Corneal Cross-Linking.

Background: Highly cited papers are expected to have high-quality data that significantly contribute to the body of knowledge. The study aimed to evaluate the characters of the 100 most-cited articles on corneal cross-linking (CXL) through a bibliometric analysis. Materials and Methods: The Web of Science database was searched to identify papers published from 1950 to 2020. A bibliometric analysis of the top 100-cited articles was conducted in the current study. The citation differences between basic research, clinical research, and reviews were compared by Kruskal-Wallis test. The association between citations and publication year was evaluated by Spearman correlation analysis. The VOSviewer software was used to create networks of co-authorship and keywords map. Results: The median values of the number of citations, citations/year since publication, and citations since 2013 were 101, 9.5, and 11.92, respectively. A total of 61% of articles were clinical research. The citations since 2013 of clinical research were lower than basic research and the reviews (all p < 0.001). The publication year was positively correlated with the number of publications (r = 0.665, p = 0.013), and the total number of citations decreased for basic research (r = -0.447, p = 0.017), and clinical research (r = -0.433, p < 0.001). The J REFRACT SURG publishes the highest number of articles. The corresponding authors were predominantly from the Italy (N = 17), Germany (N = 16), and United States (N = 15). Spoerl Eberhard has the highest number of citations and total link strength with 15 articles. Extensive collaboration existed among the main core nodes containing "cross-linking (N = 45)," "riboflavin (N = 44)," and "ultraviolet A (UVA) (N = 42)." Conclusion: The present study focused on the comprehensive analysis of the top 100-cited articles on the CXL research, providing insight into research developments over the past decades.

A bibliometric analysis of the top 100 most-cited articles on keratoconus.

PURPOSE: To explore the characteristics of the top 100 most-cited articles on keratoconus research. METHODS: The Web of Science database was searched to identify papers published from 1950 to 2020. A bibliometric analysis of the top 100 most-cited articles was conducted in the current study. The Kruskal-Wallis test was conducted to test the citation differences between basic research, clinical research, and reviews. The Spearman correlation analysis was used to investigate the association between citations and publication year. The VOSviewer software was used to create networks of co-authorship and keywords map. RESULTS: The median values of the number of citations, citations/year since publication, and citations since 2013 were 186.5, 13.90, and 11, respectively. A total of 79% of articles were clinical research. Reviews exhibited a higher value of citations/year since publication and citations since 2013 than basic research (all P < 0.05). The number of publications, total number of citations, citations/year since publication and citations since 2013 on the top 100 most-cited articles list increased with an increase in the publication year in three article types (all P < 0.05). The Journal of Cataract and Refractive Surgery had the highest number of articles. There were 37 articles from the USA. Rabinowitz, YS was the most-cited author with the greatest total link strength. Extensive collaboration existed among the main core nodes containing "cross-linking," "refractive surgery," and "penetrating keratoplasty." CONCLUSIONS: The present study focused on the comprehensive analysis of the top 100 most-cited articles on keratoconus research, providing insight into keratoconus research developments over the past decades.

Salzmann nodular degeneration in posterior keratoconus: a case report.

BACKGROUND: To report an unusual case of salzmann nodular degeneration (SND) in posterior keratoconus (PKC) after a corneal penetrating injury. CASE PRESENTATION: A 56-year-old woman presented with a history of recurrent light sensitivity, foreign body sensation, and tears after a corneal penetrating injury 20 years ago. The patient was diagnosed with SND accompanying with PKC by slit-lamp microscope, anterior segment optical coherence tomography (OCT), and corneal tomography. A combined therapy of medication (0.1% sodium hyaluronate eye drops, recombinant bovine basic fibroblast growth factor eye drops, and 0.1% fluorometholone eye drops) and bandage contact lens could not relieve the latest episode. A phototherapeutic keratectomy (PTK) treatment (laser ablation depth: 15 µm; treatment zone: 7.5 mm) was performed to remove nodules and smooth the surface. The best spectacle-corrected visual acuity improved from 20/63 preoperatively to 20/40 postoperatively. No SND relapse and corneal ectasia were recorded at follow-up 12 months later. CONCLUSIONS: This is the first known, reported case of SND accompanying with PKC after corneal trauma. The PTK is a safe and effective option for SND with PKC.

A Case Report of Gemella haemolysans Keratitis After Refractive Surgery.

PURPOSE: Systematic review of Gemella haemolysans infection associated with ophthalmology, and to summarize the clinical characteristics of Gemella haemolysan s keratitis after refractive surgery. METHODS: Case report and literature review. RESULTS: We report an 18-year-old man who developed corneal infection after Trans-PRK, and the culture results of lesion specimens confirmed G. haemolysans keratitis. He was treated with fortified topical antibiotics, and clinical improvement was noted shortly after treatment. Resolution of keratitis was achieved at 1 month. Then, a systematic review of the reported cases of ocular G. haemolysans infection was conducted. We summarized clinical manifestations of G. haemolysans infection in cornea. CONCLUSION: We reported a case of G. haemolysans keratitis infection after refractive surgery, and reviewed the literature of ocular G. haemolysans infection.

Whole mitochondrial genome analysis in Chinese patients with keratoconus.

Purpose: Keratoconus (KC) is a corneal disorder characterized by corneal ectasia, progressive corneal thinning, and conical protrusion. This study aimed to elucidate the mitochondrial gene profile in Chinese patients with KC, analyze the mitochondrial haplogroup and heteroplasmy, and further explore the association between mitochondrial genes and KC. Methods: Mitochondrial sequencing was conducted on 100 patients with KC and 100 matched controls. Haplogroup analysis was conducted with logistic regression analysis. The heteroplasmy was analyzed with ANOVA (ANOVA) and Student t test. Sequence kernel association tests (SKATs) were performed to analyze the association between mitochondrial genes and KC. Mtoolbox, Mitoclass.1, and APOGEE were used to estimate the impact of the identified variants in protein-coding genes. PON-mt-tRNA was used to annotate the impact of the variants in tRNA. RNAstructure was used to predict the secondary structures of native and mutated tRNAs. Results: We identified 689 variants in patients with KC and 725 variants in controls (with 308 variants shared by both). The mitochondrial haplogroups exhibited no statistically significant differences between the two groups. Based on the heteroplasmy analysis, the number of heteroplasmic variants in the complete mitochondrial genome, RNA coding regions, and noncoding regions were statistically significantly different in the KC cases and controls (p<0.05). The heteroplasmic levels of the m.16180_16182delAA, m.16182insC, and m.14569 G>C variants in the KC cases were statistically significantly higher than those in the controls (p<0.05). The SKAT analysis showed that the COX3 and TRNH genes were statistically significantly associated with KC (p<0.05). Among the nine variants of COX3 included in the SKAT analysis (m.9300G>A, m.9316T>C, m.9327A>G, m.9355A>G, m.9468A>G, m.9612G>A, m.9804G>A, m.9957G>A, and m.9966 G>A), m.9612G>A was predicted to be deleterious by Mtoolbox. The m.9316T>C, m.9327A>G, m.9355A>G, m.9612G>A, m.9804G>A, and m.9957G>A variants were predicted to be damaging by Mitoclass.1. The m.9355A>G and m.9804G>A variants were predicted to be pathogenic by APOGEE. All identified variants located in TRNH (m.12153C>T, m.12178C>T, and m.12192G>A) were predicted to be neutral by the PON-mt-tRNA website. Conclusions: This study presents the mitochondrial gene profile of Chinese patients with KC and demonstrated that the COX3 and TRNH genes were associated with KC.

A hospital-based study on clinical data, demographic data and visual function of keratoconus patients in Central China.

China is a populous country but lacks epidemiological data on keratoconus (KC). The present study aimed to investigate the clinical data, demographic data, and visual function (VF) data of KC patients in Central China. A total of 524 KC eyes in 307 KC patients (217 bilateral and 90 unilateral) from Henan Eye Hospital were included in the current study. Demographic and VF data were assessed with questionnaires administered by well-trained staff during face-to-face interviews. Visual acuity value was examined by a qualified optometrist, and the clinical data were measured by professional clinicians. The distributions of sex, residence and education level of KC patients were compared by Chi-square tests, and the ratios of people wearing glasses and rigid gas permeable (RGP) lenses were compared by McNemar tests. General linear models/Chi-squared tests were used to compare the clinical and demographic data according to KC severity. Spearman's correlation analysis was used to test the associations between the data and KC severity. The mean age at diagnosis was 20.98 ± 6.06 years, and males had a higher ratio of KC than females (P < 0.001). Patients in rural areas had a higher rate of KC than those in urban areas (P = 0.039), and the proportion of KC patients with a higher education level (above high school) was high (P < 0.001). A total of 68.40% of the patients reported eye rubbing and 3.52% had a positive family history. The percentage of people wearing glasses was higher than that of patients wearing RGP lenses (P < 0.001). The total VF score of KC patients was 69.35 ± 15.25. The thinnest corneal thickness (TCT) and stiffness parameter at the first applanation (SP-A1) values were inversely correlated with KC severity (P < 0.05). The mean, steep, and max keratometry (Km, Ks and Kmax) values, the RGP lens use and keratoplasty were positively correlated with KC severity (all P < 0.05). The total VF score of the eye with better VA decreased as the severity increased (r = - 0.21, P = 0.002). The present study comprehensively describes various associated features of KC patients from a tertiary hospital in Central China, providing a reference for understanding the characteristics of KC patients in China.