Predicting Marfan Syndrome in Children With Congenital Ectopia Lentis: Development and Validation of a Nomogram.

Purpose: To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data. Methods: Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis. Results: Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created. Conclusions: The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes. Translational Relevance: The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

Ocular, cardiovascular, and genetic characteristics and their associations in children with Marfan syndrome and related fibrillinopathies.

PURPOSE: Congenital ectopia lentis (CEL) and heart abnormalities are common clinical symptoms in patients with Marfan syndrome (MFS) and related fibrillinopathies, which is caused by mutations in fibrillin-1 (FBN1) gene. This study aims to explore the ocular and cardiovascular characteristics and their association with genotype in children with MFS and related fibrillinopathies. METHODS: Seventy-nine children diagnosed with CEL and with FBN1 mutations confirmed via whole-exome sequencing were included for genotypes and phenotypes analysis. The axial length (AL), corneal curvature, and refractive status were included for ocular phenotypes analysis. The cardiovascular examination was performed by echocardiography, and aortic root Z score was calculated to evaluate the severity of aortic dilatation. The heart disorders were classified as aortic root dilatation, valvular disorders, and others. Both the ocular and cardiac manifestations were collected for comprehensive analysis and compared among patients with different genotypes, including the mutation involving cysteine substitution or mutation in different regions. RESULTS: In CEL children with FBN1 mutations, 77.2% patients could be diagnosed as MFS. It was observed that children with mutations in exons 22-42 had significant higher aortic root Z score (P = 0.003) and higher incidence of cardiovascular disorders (P = 0.004). Additionally, children with cysteine substitution mutations had significant higher aortic root Z score (P = 0.011), and the aortic root Z score was positively associated with axial length (AL) in children under 6 years old (P = 0.035). Those with long AL (≥ 26 mm) had significant higher incidence of valve disorders (P = 0.023). In addition, nearly half the children with CEL (46.8%) were diagnosed with cardiovascular disease for the first time. CONCLUSIONS: CEL children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42 or with long AL had higher risks of severe cardiovascular complications. Knowing the phenotype may help in anticipating severe cardiovascular disease in CEL patients.

A Modified Knotless Transscleral Intraocular Lens Fixation Technology for Congenital Ectopia Lentis.

INTRODUCTION: This study aimed to compare modified knotless transscleral suture fixation of intraocular lens (IOL) with traditional transscleral suture fixation for adolescents and young patients with congenital ectopia lentis (CEL). METHODS: This retrospective cohort study included 49 patients with CEL (60 eyes) who underwent surgery at the Zhongshan Ophthalmic Center. Improvements based on knotless Z-suture fixation technique were made to form a modified knotless method, in which thicker 8-0 polypropylene sutures were used, and double parallel scleral grooves were constructed behind the limbus instead of triangular lamellar scleral flaps to cover suture stitches. Modified knotless transscleral fixation of IOL was conducted on 30 eyes, and the other 30 eyes underwent traditional transscleral fixation surgery. Pre- and postoperative best-corrected visual acuity (BCVA), refractive error, astigmatism, other ocular parameters, and complications were statistically analyzed. RESULTS: For patients in the modified knotless group, the mean cylindrical refractive error and astigmatism at 1 month and 3 months postoperative were lower (all P < 0.05), and the mean IOL tilt degree was smaller at 3 months postoperative (3.21° ± 2.13° vs. 5.65° ± 3.66°, P = 0.032). The incidence of suture exposure in the modified knotless group was also lower than in the controls (0 vs. 16.7%, P = 0.026). No group differences were observed in mean BCVA, spherical equivalent, or other ocular biometric parameters between groups. CONCLUSION: Modified knotless technique was a valid method to achieve optimal IOL position and reduce postoperative astigmatism for adolescents and young patients with CEL. It effectively reduced the incidence of knot-related complications, greatly improved the postoperative comfort, and achieved aesthetic benefits.

Novel ADAMTSL4 gene mutations in Chinese patients with isolated ectopia lentis.

BACKGROUND: To characterise the phenotype and genetic defects of isolated ectopia lentis (IEL) and to determine the ADAMTSL4 gene mutation frequencies in a Chinese congenital ectopia lentis (CEL) cohort. METHODS: In total, 127 Chinese probands with a clinical CEL diagnosis were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to detect variants, and Sanger sequencing and bioinformatics analysis verified the pathogenic mutations. RESULTS: Overall, biallelic mutations in ADAMTSL4, involving 8 novel ADAMTSL4 mutations (c.21-2A>G, c.1174G>C, c.2169C>A, c.2236C>T, c.2263delG, c.2397C>A, c.2488dupC and c.2935T>C) were identified in 5 probands (5/127, 3.94%) with IEL. Additionally, four patients had combined congenital cataracts, and two patients had ectopia lentis et pupillae (ELP). One of eight mutations was a homozygous missense mutation, and the other seven mutations were compound heterozygous. These eight consisted of three missense (37.5%), three frameshift (37.5%), one stop-gain (12.5%) and one spicing mutation (12.5%). These mutations co-segregated with the IEL, and the substitution of amino acids greatly affected conserved residues. Most of the novel mutations were located in the thrombospondin type 1 (TSP1) domain, which ultimately alters the structure of the ADAMTSL4 protein. CONCLUSIONS: This study reported five IEL probands with eight novel mutations in the ADAMTSL4 gene. The clinical IEL phenotypes caused by these mutations were variable and complex. This study thus establishes the ADAMTSL4 gene mutation frequency and expands the gene's mutation spectrum to help recognise ADAMTSL4-related IEL clinical manifestations.

Longitudinal Changes of Axial Length and Associated Factors in Congenital Ectopia Lentis Patients.

Purpose: To investigate the longitudinal changes and associated factors of axial length (AL) in congenital ectopia lentis (CEL) patients. Methods: In this retrospective study, medical records of CEL patients were reviewed from January 2014 to December 2019 at the Zhongshan Ophthalmic (ZOC) in China. Patients were divided into the surgery group and the nonsurgery group. Data of refractive power, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) as well as ocular biometrics including AL, corneal curvature, white-to-white (WTW), and central corneal thickness (CCT) were collected at baseline and each follow-up visit. Multiple linear regression was performed to assess the potential associated factors for axial length growth in congenital ectopia lentis patients. Results: Compared with the nonsurgery group, the change rate of AL among children aged 3 to 6 years old was slower in the surgery group (0.443 ± 0.340 mm/year vs. 0.278 ± 0.227 mm/year, P < 0.05). However, no statistically significant difference for the change rate of AL was detected between the surgery group and the nonsurgery group (P > 0.05) among patients aged 7 years or older. For the surgery group, the results of the linear regression model showed that a higher change rate of AL was associated with younger age (older age: ß = -0.009, 95% CI: -0.014 to -0.003, and P=0.002) and worse baseline BCVA (logMAR) (ß = 0.256, 95% CI: 0.072 to 0.439, and P=0.007). As for the nonsurgery group, younger baseline age (older age: ß = -0.027, 95% CI: -0.048 to -0.007, and P=0.01) and longer baseline AL (ß = 0.073, 95% CI: 0.023 to 0.122, and P=0.006) were associated with a higher change rate of AL. Conclusions: The AL change rate was clearly associated with age both in the surgery group and in the nonsurgery group. Intervention strategies such as surgery should be performed earlier for CEL that meets the surgical criteria. Worse baseline BCVA and longer baseline AL are associated factors that would affect the growth rate of AL in the surgery and nonsurgery group, respectively.

Evaluation of Intraocular Lens Tilt and Decentration in Congenital Ectopia Lentis by the Pentacam Scheimpflug System.

Purpose: The purpose of this study was to quantify the characteristics of the tilt and decentration of the IOL after trans-scleral suture fixation surgery in congenital ectopia lentis (CEL) patients. Methods: The clinical characteristics of 70 CEL patients at Zhongshan Ophthalmic Center in China were retrospectively analyzed. The tilt and decentration of intraocular lens (IOL) were measured by using a Pentacam and compared between different axial length (AL) subgroups. The correlation between IOL tilt, decentration, and ocular characteristics was investigated using Spearman's correlation analysis. Results: The postoperative IOL position of CEL patients was mainly located nasally inferiorly. The average tilt of the IOL in CEL patients was less than 7° (for temporal: 2.21 ± 1.53°, for nasal: -1.84 ± 2.04°, for superior: 2.22 ± 2.18°, and for inferior: -1.70 ± 1.62°), and the average decentration of the IOL in CEL patients was larger than 0.4 mm (for temporal: 0.49 ± 0.38 mm, for nasal: -0.69 ± 0.46 mm, for superior: 0.72 ± 0.58 mm, and for inferior: -0.68 ± 0.54 mm). The decentration of CEL patients in the AL ≥ 26 subgroup was greater than those with AL < 24 mm and AL 24 to 26 mm subgroups (for superior: 0.72 ± 0.28 mm vs. 0.46 ± 0.25 mm and 0.48 ± 0.22 mm, all P < 0.05; for inferior: -0.94 ± 0.56 mm vs. -0.44 ± 0.26 mm and -0.44 ± 0.46 mm, all P < 0.05). IOL decentration was positively correlated with AL (for superior: r = 0.44, P=0.019; for inferior: r = 0.54, P=0.006). IOL tilt was positively correlated with AL on the superior side (r = 0.38, P=0.041). Conclusions: The extent of IOL decentration after trans-scleral suture fixation was great in CEL patients, and the IOL decentration in CEL patients was significantly associated with AL.

Accuracy of intraocular lens power formulas for eyes with scleral-sutured intraocular lenses in congenital ectopia lentis.

PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculation formulas in eyes with congenital ectopia lentis (CEL) that underwent scleral-fixated IOL implantation. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Retrospective consecutive case-series study. METHODS: 158 eyes from 158 patients diagnosed from December 12, 2017, to November 16, 2020, with CEL and undergoing a lensectomy and scleral fixation of a Rayner 920H or 970C model IOL were retrospectively reviewed. The prediction errors (PEs) of the spherical equivalent of 8 formulas, Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), Haigis, Hoffer Q, Holladay 1, Kane, Hill-RBF 3.0, and SRK/T, were compared. RESULTS: For CEL patients with scleral-sutured IOL, all 8 formulas yielded myopic PEs without constant optimization. After such optimization, the performance of each formula ranked by median absolute error (MedAE) from the lowest to highest in diopter (D) was as follows: SRK/T (0.47), EVO (0.48), Kane (0.52), BUII (0.53), Hoffer Q (0.58), Holladay 1 (0.59), Haigis (0.61), and Hill-RBF 3.0 (0.62) formulas. The EVO and SRK/T formulas had the highest prediction accuracy concerning the percentage of cases within ±0.50 D and ±1.00 D range of PE in eyes that experienced scleral-sutured IOL surgery, respectively. CONCLUSIONS: All formulas before constant optimization produced myopic PEs. After optimization, the SRK/T and EVO formulas had the lowest MedAE and the highest percentage of PE in the range within ±0.50 D for CEL patients with scleral-sutured IOL implantations.

CHARACTERISTICS OF THE FOVEAL MICROVASCULATURE IN CHILDREN WITH MARFAN SYNDROME: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate the characteristics of foveal microvasculature in children with Marfan syndrome (MFS). METHODS: Ninety eyes from 45 MFS patients and 76 eyes from 38 healthy individuals of age-matched, sex-matched, and axial length-matched were enrolled. Characteristics of the superficial capillary plexus including the vessel density, perfusion density, and foveal avascular zone were analyzed by optical coherence tomography angiography. RESULTS: The vessel density and the circularity index of the foveal avascular zone were significantly decreased in the MFS group compared with the controls (P = 0.017 and P = 0.004 respectively). In MFS group, the central vessel density (P = 0.003) and perfusion density (P = 0.001) were negatively correlated with the best-corrected visual acuity. The foveal avascular zone area was correlated with the aortic diameters (P = 0.001) and the paratemporal perfusion density was correlated with the ejection fraction (P = 0.003). Moreover, the paratemporal perfusion density and the circularity index of foveal avascular zone were found to be correlated with the aortic Z-score (P < 0.001 and P = 0.003 respectively). CONCLUSION: Retinal microvascular decrease and its correlation with best-corrected visual acuity and cardiac functions were observed in the MFS group. The optical coherence tomography angiography may help to characterize the underlying pathophysiology features of MFS and enable early detection and prevention of vascular changes in MFS.

Endoscopy-guided in vivo evaluation of ciliary sulcus location in children with ectopia lentis.

OBJECTIVE: To assess a new method to measure the distance of the needle passage from the ciliary sulcus to the corneal limbus anterior border (CTC) in eyes with ectopia lentis directly in vivo via endoscopy and to further evaluate the correlations among the CTC, age, automated horizontal white-to-white distance (WTW), and ocular axial length (AL). METHODS: The WTW and AL were measured using an optical biometer. An intraocular endoscope was used during transscleral suture fixation of posterior chamber intraocular lenses to identify the true location of the ciliary sulcus. Linear regression analysis was used to assess the correlation between the CTC and other ocular biological parameters, including age, WTW, and AL. RESULTS: Thirty eyes of 30 children with ectopia lentis were evaluated. A statistically significant correlation was found between age and the CTC. The CTC could be predicted by the equation CTC = 0.1313 × Age + 0.9666. No statistically significant correlations were found between CTC and WTW, CTC and AL, WTW and AL, or WTW and age. CONCLUSION: Endoscopy is useful for precisely suturing intraocular lens haptics in the real ciliary sulcus. Age can be used as an equivalent parameter for prediction of the true ciliary sulcus location.

Characteristics of Corneal Higher-Order Aberrations in Congenital Ectopia Lentis Patients.

Purpose: The purpose of this study was to investigate the characteristics of corneal higher-order aberrations (HOAs) in patients with congenital ectopia lentis (CEL). Methods: Clinical characteristics and HOAs of 60 patients with CEL and 75 healthy controls at Zhongshan Ophthalmic Center in China were retrospectively analyzed. The Q value and the corneal HOAs in the CEL group and the controls were measured by using Pentacam and compared value between the CEL and control groups. The correlation between HOAs and age was investigated using the Pearson correlation analysis. Results: The Q value of anterior corneal surface in the CEL group was larger than that in the controls (-0.41 ± 0.17 vs. -0.32 ± 0.13, P = 0.001); the total corneal horizontal coma in the CEL group were larger than that in the controls (0.24 ± 0.18 vs. -0.05 ± 0.14, P < 0.001); both the primary spherical aberrations of the anterior and total corneal surface were lower in the CEL group than that in the controls (for anterior corneal surface: 0.15 ± 0.08 vs. 0.27 ± 0.08 µm, P < 0.001; for total corneal surface: 0.10 ± 0.09 vs. 0.23 ± 0.09 µm, P < 0.001), the anterior and total corneal horizontal coma were negatively associated with age, whereas the anterior and total corneal spherical aberrations were positively associated with age in patients with CEL. Conclusions: Patients with CEL had higher corneal horizontal coma and lower corneal vertical coma primary spherical aberrations than healthy controls. Translational Relevance: These findings are informative for the clinical managements in patients with CEL.

Mutation spectrum and genotype-phenotype correlations in Chinese congenital ectopia lentis patients.

PURPOSE: To identify the spectrum and frequency of mutations in congenital ectopia lentis (CEL) and to investigate the correlations between genotype and clinical phenotype in Chinese CEL patients. METHODS: Ninety-three participants with CEL were enrolled from March 2017 to April 2020. Ocular and systemic examinations were performed for each included patient. Genomic DNA from the included patients was analysed by whole-exome sequencing to detect mutations. Clinical manifestations were compared for different mutation subgroups. RESULTS: Gene mutations were detected in 79 patients. Sixty-five were FBN1-associated, and most were related to Marfan syndrome (MFS). The FBN1 mutations mainly consisted of missense mutations (49/65) and were concentrated in the 5' region. Probands with missense mutations tend to show high corneal astigmatism (χ2 = 3.98, P = 0.046) and severe lens dislocation (t = 2.90, P = 0.006) compared to premature termination codon (PTC) mutations. CONCLUSIONS: Most Chinese CEL patients were identified as having FBN1 mutations. Those with missense mutations commonly showed severe ocular phenotypes; therefore, reinforced follow-up and long-term observation are required. These correlations implicated the crucial role of missense and cysteine-involving mutations in ocular phenotypes, which might be explained by dominant-negative and nonsense-mediated mRNA decay (NMD).

Genotype variant screening and phenotypic analysis of FBN1 in Chinese patients with isolated ectopia lentis.

Isolated ectopia lentis (IEL) can lead to blindness as result of severe complications, such as retinal detachment and secondary glaucoma. Pathogenic variants in the fibrillin 1 (FBN1) gene are a common cause of IEL. The aim of the present study was to investigate the frequency of pathogenic FBN1 variants in twelve probands with IEL and to evaluate their associated phenotypes. Systemic clinical examination of the twelve probands indicated that all had bilateral EL with a median age at diagnosis of three years. High myopia was the most common feature among the probands (83.3%; 10/12 cases). No extraocular symptoms (either cardiovascular or skeletal) were observed among these patients. Genomic DNA was extracted from peripheral blood leukocytes from all patients for targeted exome sequencing. Seven heterozygous missense variants in FBN1 were identified by bioinformatics analysis and further verified using Sanger sequencing. The seven variants were all classified as pathogenic after segregation analysis on available family members according to the American College of Medical Genetics and Genomics standards and guidelines. Of the seven variants, three were novel, namely c.2179T>C, c.2496T>G and c.3346G>C. The remaining four, namely c.184C>T, c.367T>C, c.1879C>T and c.4096G>A have been reported in previous studies. The seven pathogenic variants were identified in 8/12 (66.7%) probands with IEL. These results expand the variant spectrum of the FBN1 gene as well as the understanding of the molecular pathogenesis of IEL.

Fluid-jet technique to polish the posterior capsule for phacoemulsification surgeries: efficacy and safety evaluation.

PURPOSE: To compare the efficacy and safety of a fluid-jet technique with capsular polish in reducing residual lens fibers (RLFs) in phacoemulsification surgery. SETTING: Single center. DESIGN: Prospective nonrandomized comparative study. METHODS: Patients receiving phacoemulsification were included. Consecutive eligible patients alternately underwent either removal of RLFs on the posterior capsule using capsular polish after irrigation and aspiration, and before intraocular lens (IOL) implantation, or RLF removal using a fluid-jet technique after IOL implantation. Posterior capsular images were used to quantify RLFs. Visual parameters were evaluated at 1 day, 1 week, and 1 year postoperatively. The proportion of capsule occupied by posterior capsule opacification (PCO) (area %) and incidence of protocol-driven laser posterior capsulotomy were recorded at 1 year in masked fashion. RESULTS: Seven hundred forty eyes were allocated to polishing (n = 370) or fluid-jet technique (n = 370). Polishing required 70.4 ± 17.5 seconds and fluid-jet 32.2 ± 9.9 seconds (P ≤ 0.001). Compared with the polishing group, capsular area occupied by RLFs in the fluid-jet group was significantly smaller (3.5% vs 0.5%, P = .031) at the end of surgery. One day postoperatively, the fluid-jet group had more desirable corrected distance visual acuity, objective scattering index, and Strehl ratio (all P < .05). PCO area percentage did not differ between groups (6.5% vs 4.5%, P = .252) 1 year postoperatively, but incidence of posterior capsulotomy was lower in the fluid-jet group (3.2% vs 0.8%, P = .019). CONCLUSIONS: Fluid-jet removed RLFs effectively and had lower incidence of postoperative capsulotomy than capsular polishing.

What hinders congenital ectopia lentis patients' follow-up visits? A qualitative study.

OBJECTIVES: The aim of our study is to give insight into congenital ectopia lentis (CEL) patients' care-seeking behaviour and explore the factors affecting their follow-up visits. DESIGN: Cross-sectional study; in-depth and face-to-face semistructured interview. SETTING: A large-scale ophthalmology hospital in China. PARTICIPANTS: 35 patients with CEL and their parents from May 2017 to August 2017. MAIN OUTCOME MEASURES: Themes and categories. The interviews were audio-recorded, transcribed verbatim, coded and analysed using grounded theory. Data collection was closed when new themes did not emerge in subsequent dialogues. RESULTS: The factors affecting the timely visits included insufficient awareness of CEL, shame on hereditary disease, lack of effective doctor-patient communication, lack of reliable information online and daily stressors. CONCLUSION: Continuing medical education of severe and rare disease, reforming the pattern of medical education, constructing an interactive platform of the disease on the internet and improving healthcare policy are effective ways to improve the diagnosis and treatment status of CEL in China.

Incidence of and Risk Factors for Suspected Glaucoma and Glaucoma After Congenital and Infantile Cataract Surgery: A Longitudinal Study in China.

PRéCIS:: The overall incidence of postoperative suspected glaucoma and glaucoma after congenital cataract surgery is low; however, the identification of the associated risk factors helps to monitor susceptible individuals and to provide real-time surveillance and timely intervention. PURPOSE: Pediatric patients who have undergone surgery for congenital or infantile cataracts have a risk of developing suspected glaucoma and glaucoma, but the current evidence does not address our understanding of the incidence and associated risk factors of suspected glaucoma/glaucoma for application in clinical standard care. Therefore, this study investigated the incidence of and risk factors for suspected glaucoma/glaucoma in patients who have undergone surgery for congenital/infantile cataracts. METHODS: This study used a prospective cohort of 241 eyes from 241 patients who were 10 years of age or younger and who had undergone congenital/infantile cataract surgeries and were recruited from January 2011 to December 2016 at the Zhongshan Ophthalmic Center. Pediatric patients who underwent cataract surgery were classified into 2 groups according to intraocular lens (IOL) implantation. The patients' baseline characteristics and the incidence and risk factors for suspected glaucoma/glaucoma were assessed. RESULTS: The incidence of suspected glaucoma after cataract surgery was 10.70% [26 of 241 eyes; 95% confidence interval (CI), 6.88%-14.70%]. The rate of suspected glaucoma developing into glaucoma was 26.92% (7 of 26 eyes; 95% CI, 9.87%-43.97%), and the incidence of glaucoma was 2.90% (7 of 241 eyes; 95% CI, 0.79%-5.03%). Our study revealed that the incidence of suspected glaucoma/glaucoma in patients who did not receive IOL implantation was 13.91% (21 of 151 eyes; 95% CI, 8.39%-19.42%), and the incidence in patients who received IOL implantation was 5.56% (5 of 90 eyes; 95% CI, 8.23%-10.28%). The preoperative central corneal thickness (hazard ratio, 1.003; 95% CI, 1.001 to 1.004; P=0.004) and a family history of congenital cataracts (hazard ratio, 2.314; 95% CI, 1.004-5.331; P=0.049) were significant risk factors in patients without IOL implantation. Patient age at the time of cataract surgery was not a statistically significant risk factor for the development of suspected glaucoma/glaucoma in patients without IOL implantation. CONCLUSIONS: Identification of the incidence of and risk factors for suspected glaucoma/glaucoma may help clinicians monitor susceptible individuals and provide timely surveillance and interventions in a clinical setting. Age at the time of cataract surgery was not a risk factor for suspected glaucoma/glaucoma in patients without IOL implantation, and this may allow the timing window for pediatric cataract surgery to be expanded and support new insights into the optimal timing of surgery for standard care.

Increased prevalence of parent ratings of ADHD symptoms among children with bilateral congenital cataracts.

AIM: To investigate the behavioral and psychological disorders and the prevalence of parent ratings of attention deficit hyperactivity disorder (ADHD) symptoms among children with bilateral congenital cataracts (CCs). METHODS: This cross-sectional study investigated children with bilateral CC aged 3-8y (CC group) using Conners' Parent Rating Scale-48 (CPRS-48) from July to December 2016. The abnormal rates of psychological symptoms in CC children and normal vision (NV) children were compared using the Chi-square test. The scores of CC children were compared with those of NV children and the Chinese urban norm using the independent samples t-test and one-sample t-test, respectively. RESULTS: A total of 262 valid questionnaires were collected. The ratio of CC children to NV children was 119:143. The overall rate of psychological symptoms in CC children was 2.28 times higher than that in NV children (46.22% vs 20.28%, Pearson's χ 2=20.062; P<0.001). CC children showed higher scores for conduct problems, learning problems, impulsiveness/hyperactivity, anxiety, and hyperactivity index than NV children and the Chinese urban norm, particularly between the ages of 3 and 5y. Furthermore, male children aged between 6 and 8y showed a higher impulsive/hyperactive score than females of the same age (t=6.083, P<0.001). CONCLUSION: Children with bilateral CCs have a higher rate of ADHD symptoms than children with NV. This study provides clinical evidence that screening for psychological symptoms and particularly for ADHD symptoms in children with bilateral CC are recommended for an early diagnosis and timely treatment.

Expression of transforming growth factor ß and matrix metalloproteinases in the aqueous humor of patients with congenital ectopia lentis.

It is well known that transforming growth factor ß (TGFß), which is able to stimulate multiple intracellular signaling pathways, exerts an important role in Marfan syndrome, although the effects of TGFß on congenital ectopia lentis (CEL) have yet to be fully elucidated. In the present study, the expression levels of TGFß and matrix metalloproteinases (MMPs) were investigated in the aqueous humor of patients with ectopic lentis who differed in terms of the severity of the disease. A total of 17 CEL patients with 21 eyes (aged 12.76±9.37 years) and 12 congenital cataract (CC) patients with 17 eyes (aged 6.82±9.18 years) were randomized in the present study. The levels of active TGFß and MMPs in the aqueous humor were analyzed with Luminex xMAP® technology by using commercially available Bio­Plex Pro™ Human MMP and TGFß assays. The distance from the lens edge to the pupil edge and the white to white corneal diameter (i.e. the horizontal distance between the borders of the corneal limbus) were measured, and the ratio was calculated as the degree of lens dislocation. The association between TGFß and MMP levels and the degree of lens dislocation was analyzed using Spearman's correlation test. Compared with the patients with CC, the level of TGFß2 in the patients with CEL was increased significantly. Specifically, the level of TGFß2 in the CEL patients was 855.19 pg/ml (744.33, 1,009.24), whereas it was 557.08 (438.24, 692.71) pg/ml in the CC patients (P<0.001). In addition, it was noted that the levels of MMP­2 and ­10 in the aqueous humor of the patients with CEL were higher compared with those in the CC patients, although this increase did not reach the level of statistical significance. Notably, the levels of MMP­8 and ­9 in the aqueous humor of patients with CEL were significantly lower compared with those in the CC patients (P=0.014 and P=0.002, respectively). Furthermore, a marginal correlation was identified between the severity of ectopic lentis and the levels of TGFß2 in the aqueous humor (r2=0.379; P=0.003) of the patients with CEL. Taken together, these results demonstrated that a significant correlation existed between high levels of aqueous humor TGFß2 and the severity of ectopia lentis in patients with CEL. In addition, aqueous humor TGFß2 levels in the CEL patients were significantly higher compared with those in CC patients.

Diagnostic Efficacy and Therapeutic Decision-making Capacity of an Artificial Intelligence Platform for Childhood Cataracts in Eye Clinics: A Multicentre Randomized Controlled Trial.

BACKGROUND: CC-Cruiser is an artificial intelligence (AI) platform developed for diagnosing childhood cataracts and providing risk stratification and treatment recommendations. The high accuracy of CC-Cruiser was previously validated using specific datasets. The objective of this study was to compare the diagnostic efficacy and treatment decision-making capacity between CC-Cruiser and ophthalmologists in real-world clinical settings. METHODS: This multicentre randomized controlled trial was performed in five ophthalmic clinics in different areas across China. Pediatric patients (aged ≤ 14 years) without a definitive diagnosis of cataracts or history of previous eye surgery were randomized (1:1) to receive a diagnosis and treatment recommendation from either CC-Cruiser or senior consultants (with over 5 years of clinical experience in pediatric ophthalmology). The experts who provided a gold standard diagnosis, and the investigators who performed slit-lamp photography and data analysis were blinded to the group assignments. The primary outcome was the diagnostic performance for childhood cataracts with reference to cataract experts' standards. The secondary outcomes included the evaluation of disease severity and treatment determination, the time required for the diagnosis, and patient satisfaction, which was determined by the mean rating. This trial is registered with ClinicalTrials.gov (NCT03240848). FINDINGS: Between August 9, 2017 and May 25, 2018, 350 participants (700 eyes) were randomly assigned for diagnosis by CC-Cruiser (350 eyes) or senior consultants (350 eyes). The accuracies of cataract diagnosis and treatment determination were 87.4% and 70.8%, respectively, for CC-Cruiser, which were significantly lower than 99.1% and 96.7%, respectively, for senior consultants (p < 0.001, OR = 0.06 [95% CI 0.02 to 0.19]; and p < 0.001, OR = 0.08 [95% CI 0.03 to 0.25], respectively). The mean time for receiving a diagnosis from CC-Cruiser was 2.79 min, which was significantly less than 8.53 min for senior consultants (p < 0.001, mean difference 5.74 [95% CI 5.43 to 6.05]). The patients were satisfied with the overall medical service quality provided by CC-Cruiser, typically with its time-saving feature in cataract diagnosis. INTERPRETATION: CC-Cruiser exhibited less accurate performance comparing to senior consultants in diagnosing childhood cataracts and making treatment decisions. However, the medical service provided by CC-Cruiser was less time-consuming and achieved a high level of patient satisfaction. CC-Cruiser has the capacity to assist human doctors in clinical practice in its current state. FUNDING: National Key R&D Program of China (2018YFC0116500) and the Key Research Plan for the National Natural Science Foundation of China in Cultivation Project (91846109).