Isolated ectopia lentis with partial anterior dislocation and pupillary block: a case report.

BACKGROUND: Ectopia lentis is the dislocation of the natural crystalline lens and usually presents in the setting of trauma or other systemic diseases. Herein, we describe a case of an otherwise healthy four-year-old boy with isolated ectopia lentis whose partial lens dislocation was captured on a smartphone by the patient's father several days prior. CASE PRESENTATION: A four-year-old boy with no past medical, developmental, or trauma history presented with bilateral partial anterior lens dislocation with pupillary block. Initial ophthalmic evaluation two months prior was notable for uncorrected visual acuity at 20/100 OD, 20/250 OS, bilateral iridodenesis, and partially dislocated lenses inferonasally OD and inferiorly OS on slit lamp. Genetic testing found no abnormalities. Ten months later, the patient developed sudden onset of left eye pain. A dislocated lens and temporarily dilated left pupil were captured on a smartphone by the patient's father. He was evaluated 3 days later after a second episode and found to have hand motion vision OS, a fixed 8 mm left pupil with the crystalline lens subluxed into the pupil space and accompanying intraocular pressure OS of 40 mmHg. The lens was surgically removed with a limited anterior vitrectomy. Four and a half years after surgery, visual acuity was 20/125 OS with aphakic correction. The right eye eventually underwent prophylactic lensectomy and was 20/30 in aphakic correction. CONCLUSIONS: This report presents a unique presentation of isolated ectopia lentis with anterior lens dislocation and pupillary block and illustrates the role of smartphone photography in assisting in the triage of eye emergencies.

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.

[Structural and functional features of the eye in Marfan syndrome. Report 2. Changes in the anatomical complex of the lens]. / Strukturno-funktsional'nye osobennosti glaza pri sindrome Marfana. Soobshchenie 2. Izmeneniya anatomicheskogo kompleksa khrustalika.

Analysis of lens changes in Marfan syndrome (MS), in addition to assessing the position of the lens itself, should include the possibility of examining its supporting and accommodative components (ciliary zonule and ciliary body), or what can be called the entire anatomical complex of the lens. Optical methods of studying the structures of the anterior segment of the eye, due to iris opacity, allow only to analyze the state of the lens within the natural or medically enlarged pupil width. Visualization of the structures located behind the iris is possible with the use of radiation diagnostic methods, in particular ultrasound biomicroscopy (UBM). PURPOSE: This study assesses the state of the anatomical complex of the lens in MS using UBM. MATERIAL AND METHODS: The study was carried out on clinical material previously used by us to analyze changes in the fibrous membrane of the eye in MS. At the first stage, the main (19 patients with MS, 38 eyes) and the control (24 patients with myopia, 48 eyes) groups were formed for comparative evaluation. The formed groups were standardized according to the age of the patients and the axial length of the eye. At the second stage, patients with MS were divided into subgroups depending on the absence or presence of biomicroscopic signs of ectopia lentis (22 and 16 eyes, respectively). For UBM, an ultrasound linear sensor with a scanning frequency of 50 MHz was used (Aviso device, Quantel Medical, France). Various biometric UBM indicators were determined: lens thickness, diameter of the lens, lens-axial length factor, iris-lens angle, iris-lens contact distance, posterior chamber depth, length of the fibers of ciliary zonule, thickness of the ciliary body, sclera-ciliary process angle. RESULTS: There are changes in the anatomical complex of the lens as a whole in MS (in the lens itself, the ciliary zonule, and the ciliary body), which are characterized by an increase in lens thickness and a decrease in the diameter of the lens, an increase in the length of the fibers of the ciliary zonule and a decrease in the thickness of the ciliary body. At the same time, the displacement of the lens detected by optical biomicroscopy (ectopia lentis) can be considered as an advanced stage of changes in the anatomical complex of the lens. CONCLUSION: UBM provides the possibility of full-fledged visualization of all components of the anatomical complex of the lens in terms of both diagnostics, and monitoring of changes in MS. The question of the advisability of including this method in the algorithm for diagnosing ocular manifestations in order to verify the MS remains open. Possible obstacles may be, on the one hand, related to the need for special and expensive equipment, and on the other hand, the absence of a generally accepted «normal¼ values of UBM indicators of the anatomical complex of the lens.

[Structural and functional features of the eye in Marfan syndrome. Report 1. Changes in the fibrous tunic of the eye]. / Strukturno-funktsional'nye osobennosti glaza pri sindrome Marfana. Soobshchenie 1. Izmeneniya fibroznoi obolochki.

Marfan syndrome (MS) is an orphan hereditary connective tissue disease associated with a mutation in the FBN1 gene, which pathological manifestations are characterized by polysystemic involvement. The fibrillin-1 protein is an integral component of the sclera and cornea of the eye, and in MS its structure is distrubed. PURPOSE: This study assesses potential structural and functional changes in the cornea and sclera of a patient with MS. MATERIAL AND METHODS: Two groups were formed, comparable in the axial length of the eye and age: the main group - 19 patients (38 eyes) with a verified diagnosis of MS, and the control group - 24 patients (48 eyes) with myopia of varying degrees. The results obtained from MS patients were analyzed depending on the absence or presence of ectopia lentis. In addition to measuring the basic ophthalmological parameters (refraction, axial length, visual acuity), topographic keratometry, anterior segment optical coherence tomography, and ocular response analyzer were used for structural and functional assessment of the cornea and sclera. RESULTS: In MS there was a statistically significant increase in the radius of curvature and a decrease in corneal refraction in the central zone compared to the control group. There were no significant differences in central corneal thickness, but there was a significant decrease in the thickness of the sclera in the limbal zone compared to the control group. There were no statistically significant changes in corneal hysteresis and corneal resistance factor in MS. CONCLUSION: This study confirmed the previously obtained data on the tendency of the optical power to reliably decrease in MS (flattening of the cornea). This symptom can be considered as a compensatory factor affecting clinical refraction, while the decrease in the thickness of the sclera - as the main reason for aaxial length elongation in MS. There were no clear patterns of dependence of the changes in the cornea and sclera analyzed in this study on the presence or absence of ectopia lentis. Changes in the lens, perhaps, should be regarded only as one of the potential components of the ocular symptom complex in MS.

Biometric and corneal characteristics in marfan syndrome with ectopia lentis.

PURPOSE: To describe the biometric and corneal characteristics of patients with Marfan Syndrome (MFS) and ectopia lentis. STUDY DESIGN: Observational, descriptive, prospective study. Subjects Individuals with MFS with ectopia lentis (EL). METHODS: Fourty-four eyes of 23 patients underwent Scheimpflug analysis using the Pentacam (Oculus, Wetzlar, Germany), axial length (AL) using the IOL master 700 (Carl Zeiss AG, Oberkochen, Germany), endothelial cell count (ECC) using the CEM-350 (NIDEK, Maihama, Japan) and corneal biomechanics evaluation with the Ocular Response Analyzer: ORA (Reichert Ophthalmic Instruments, Buffalo, New York, USA) and Corvis (Oculus, Wetzlar, Germany). Statistical analysis was performed using IBM SPSS Statistics 25.0. RESULTS: The direction of lens subluxation was most frequently supero-nasal 40.9% (18/44). Mean keratometry (Km) was 40.22±1.76 Diopters (D); mean corneal astigmatism was 1.68±0.83 D; total corneal aberrometric root mean square (RMS) was 2.237±0.795µm; higher-order aberrations (HOAs) RMS were 0.576±0.272µm; mean AL was 25.63±3.65mm; mean ECC was 3315±459cell/mm2; mean CBI was 0.13±0.24, mean TBI was 0.31±0.25, mean posterior elevation was 4.3±4.5µm; mean total corneal densitometry was 16.0±2.14 grayscale units (GSU). CONCLUSION: Increased axial length, flatter and thicker corneas with higher regular astigmatism, normal densitometry, normal corneal biomechanical indices and normal posterior elevation were observed in Marfan patients with EL.

Longitudinal changes of refractive error in preschool children with congenital ectopia lentis.

BACKGROUND: Congenital ectopia lentis (CEL) is a hereditary eye disease which severely impacts preschool children's visual function and development. This study aimed to evaluate the longitudinal changes in spherical equivalent (SE) refractive error in preschool children with CEL. METHODS: A retrospective cohort study was conducted at Zhongshan Ophthalmic Center, Guangzhou, China. Medical records of CEL patients under 6-year-old who were diagnosed with Marfan syndrome at the initial visit from January 2014 to March 2022 were collected and were divided into surgery and non-surgery groups. Mean change rate of SE in the two groups was evaluated, and the potential associated factors of SE change rate were investigated by mixed-effect regression model. RESULTS: A total of 94 preschool patients from 14 provinces of China were included. Among the 42 children of the surgery group, the mean age with standard deviation (SD) was 5.02 ± 0.81 years and patients experienced a myopic shift of -0.05 ± 0.09 D/month in average. The mean age with SD of the 52 children of the non-surgery group was 4.34 ± 1.02 years, and the mean myopic shift was -0.09 ± 0.14 D/month. The mixed-effect regression model identified that higher degree of myopia at baseline was associated with slower myopic shift both in surgery (ß = 0.901, 95% CI: 0.822 ~ 0.980, P < 0.001) and in non-surgery group (ß = 1.006, 95% CI: 0.977 ~ 1.034, P < 0.001) in CEL patients. Surgical treatment (ß = 2.635, 95% CI: 1.376 ~ 3.894, P < 0.001) was associated with slower myopic shift in all participants CEL patients. CONCLUSIONS: Myopic progression was slower in the surgery group than in the non-surgery group of CEL. Preschool CEL patients who met the surgical indication are suggested being performed with timely surgery to slow down the myopic progression.

Clinical and Genetic Landscape of Ectopia Lentis Based on a Cohort of Patients From 156 Families.

Purpose: To extend the mutation spectrum and explore the characteristics of genotypes and ocular phenotypes in ectopia lentis (EL). Methods: Variants in all 14 reported EL-associated genes were selected from in-house data sets as well as literature review, and available clinical data were analyzed. Results: Likely pathogenic variants in three genes were identified in 156 unrelated families with EL from the in-house cohort, of which 97.4% resulted from variants in FBN1, whereas the remaining were caused by variants in ADAMTSL4 (1.3%) and LTBP2 (1.3%). A comparative analysis of the in-house data and literature review suggested several characteristics: (1) a higher proportion of cysteine involvement variants in FBN1, either variants introducing or eliminating cysteine, and an earlier diagnosis age were presented in our cohort than in published literature; (2) the axial length (AL) and refractive error increased more rapidly with age in preschool EL children than normal children, and the increased rate of AL was slower in patients with surgery than those without surgery; (3) aberrant astigmatism was common in EL; and (4) worse vision and earlier onset age were observed in patients with non-FBN1 variants (all P < 0.05). Conclusions: Variants in FBN1 are the predominant cause of EL, with the most common cysteine involvement variants. Early-stage EL manifests refractive error but gradually converts to axial myopia through defocus introduced by lens dislocation. Aberrant astigmatism is a suggestive sign of EL. Non-FBN1 variants cause early-onset and severe phenotypes. These results provide evidence for early diagnosis as well as timely treatment for EL.

Ocular Involvement and Treatment Pattern in Korean Patients with Marfan Syndrome: A Population-Based Study.

PURPOSE: This study aimed to investigate the incidence and prevalence of, and treatment patterns for ocular complications in Korean patients with Marfan syndrome. METHODS: Incidence and prevalence of Marfan syndrome was calculated from 2010 to 2018, based on data from the Korean National Health Insurance Service (KNHIS). Diagnosis codes (for cataract, ectopia lentis, retinal detachment, etc.) and surgery reimbursement codes (lensectomy, phacoemulsification, buckling, vitrectomy, etc.) in the patients with Marfan syndrome were retrieved by complete enumeration of the data. RESULTS: The annual prevalence of Marfan syndrome adjusted by age and sex was gradually increased from 2.44 per 100,000 in 2010 to 4.36 per 100,000 in 2018. The age group of 10-19 years showed the highest prevalence. The prevalence of ectopia lentis was 21.7%, of whom 43.0% underwent surgeries. Surgery for RD was performed in 253 (14.1%) of 2044 patients during the study period. CONCLUSION: Although the most prevalent ophthalmologic manifestation was ectopia lentis, total prevalence rate of RD was more than 10% in the study period; thus, regular fundus examination is recommended for the patients with Marfan syndrome.

Postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome.

PURPOSE: To evaluate the postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome (MFS). SETTING: Zhongshan ophthalmic center, Guangzhou, China. DESIGN: Retrospective cohort study. METHODS: Medical data of patients diagnosed with ectopia lentis and MFS that underwent surgery younger than 8 years were collected. Refractive errors and ocular biometric parameters were collected preoperatively and at each follow-up visit. Patients were stratified into groups according to age at surgery, and only the eye operated on first was selected. Multivariate analysis was performed to determine the association between refractive shift and potential risk factors. RESULTS: In total, 54 eyes of 54 patients were enrolled. The median age at surgery was 6.21 years (interquartile range [IQR], 5.25 to 6.85), and the median follow-up was 2.0 years (IQR, 1.2 to 2.8 years). At age 8 years, patients demonstrated a median myopic shift ranged from -1.75 diopters (D) (IQR, -2.75 to -1.00 D) for the 4-year-old group to -0.13 D (IQR, -0.50 to -0.06 D) for the 7-year-old group. Multivariate analysis showed that greater myopic shift was associated with younger age at surgery ( P = .004), male sex ( P = .026), and shorter preoperative axis length ( P = .005). CONCLUSIONS: A tendency toward increasing postoperative myopic was demonstrated in children with ectopia lentis and MFS, with the greatest myopic shift in the younger age groups. If the goal is to reach emmetropia by age 8 years, the immediate postoperative hypermetropic targets should be 1.75 D for age 4 years, 1 D for age 5 years, 0.5 D for age 6 years, and 0 to 0.25 D for age 7 years.

Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome.

Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based data-independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation-related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.

A novel ADAMTSL4 compound heterozygous mutation in isolated ectopia lentis: a case report and review of the literature.

BACKGROUND: Congenital ectopia lentis is characterized by dislocation of the lens caused by partial or complete abnormalities in the zonular fibers. It can be caused by either systemic diseases or isolated ocular diseases. Gene detection techniques can provide valuable information when an etiological diagnosis is challenging. Herein, we report the case of a six-year-old girl with a confirmed diagnosis of isolated ectopia lentis caused by a compound heterozygous ADAMTSL4 gene mutation. CASE PRESENTATION: The patient was a 6-year-old Chinese Han girl with strabismus in the right eye. Slit lamp examination revealed that the lens in the right eye was opacified and dislocated, without an ectopic pupil. Gene detection demonstrated the presence of a compound heterozygous mutation in the ADAMTSL4 gene [c. 2270dupG (p.Gly758Trpfs *59) and c. 2110A > G (p.Ser704Gly)], and the diagnosis of isolated ectopia lentis was confirmed. She underwent lens extraction, and a sutured scleral-fixated posterior chamber intraocular lens (IOL) was placed in the right eye. The best-corrected visual acuity was 0.1 one month postoperatively. CONCLUSION: Gene detection plays a crucial role in diagnosing disorders with similar symptoms, such as isolated ectopia lentis and Marfan syndrome. In this study, we used whole exons sequencing to diagnose isolated ectopia lentis and identified the variant c.2110A > G (p.Ser704Gly), which may be associated with the development of ectopia lentis and early-onset cataract in the patient. These pathogenic gene mutations have significant implications for the genetic diagnosis of congenital ectopia lentis, treatment, surveillance, and hereditary and prenatal counseling for the patient and their family members.

Evaluation of functional vision and eye-related quality of life in children with congenital ectopia lentis: a prospective cross-sectional study.

OBJECTIVES: This study aims to evaluate the effect of congenital ectopia lentis (CEL) on functional vision and eye-related quality of life (ER-QOL) in children and their families using the Paediatric Eye Questionnaire (PedEyeQ). DESIGN: A questionnaire survey administered via in-person interviews of patients with CEL and their parents. PARTICIPANTS: 51 children with CEL and 53 visually normal controls accompanied by 1 parent completed the survey questionnaires for the study from March 2022 to September 2022. OUTCOME MEASURES: PedEyeQ domain scores. Functional vision and ER-QOL of children and their families were evaluated by calculating and comparing the Rasch domain scores of the PedEyeQ. RESULTS: PedEyeQ domain scores were significantly worse with CEL compared with controls (p<0.01 for each), with the exception of the Proxy Social domain among children aged 0-4 years (p=0.283). Child PedEyeQ greatest differences were in the functional vision domain (5-11 years, -20 points (95% CI -27 to -12)) and frustration/worry domain (12-17 years, -41 (95% CI -37 to -6)). Proxy PedEyeQ greatest differences were in the functional vision domain (0-4 years, -34 (95% CI -45 to -22)) and frustration/worry domain (5-11 years, -27 (95% CI -39 to -14); 12-17 years, -37(95% CI (-48 to -26))). Parent PedEyeQ greatest difference was in the 'worry about child's eye condition' (-57 (95% CI (-63 to -51))). CONCLUSIONS: In this study, children with CEL had reduced functional vision and ER-QOL compared with controls. Parents of children with CEL also experience reduced quality of life.

Initial screening for occult congenital ectopia lentis based on ocular biological parameters in preschool children.

BACKGROUND: This study aimed to identify an initial screening tool for congenital ectopia lentis (CEL) by comparing ocular biological parameters in children with myopia. METHODS: A retrospective case-control study was conducted at one tertiary referral centre, from October 2020 to June 2022. Axial length (AL), corneal curvature (CC), refractive astigmatism (RA), corneal astigmatism (CA), internal astigmatism (IA), the difference between the axis of RA and CA [AXIS(RA-CA)], white-to-white corneal diameter (WTW), and axial length-corneal radius ratio (AL/CR) were compared in 28 eyes of CEL patients, and 60 eyes of myopic patients matched for age and refraction. The spherical equivalent of each eye was < -3.00 D. Area under the curve (AUC) of the receiver operating characteristic curves were calculated. RESULTS: The differences in RA, AL, mean keratometry (Kmed), maximum keratometry (Kmax), minimum keratometry (Kmin), CA, IA, AXIS(RA-CA), WTW, and AL/CR between the CEL and myopic groups were statistically significant (p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001; p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). In logistic regression analysis RA, IA, AXIS(RA-CA), and AL/CR were significantly associated with CEL (p < 0.05). AUCs for RA, IA, AXIS(RA-CA), and AL/CR were 0.694, 0.853, 0.814, and 0.960, respectively. AUCs for AL/CR in SE< -6.00 D subgroup was 0.970, and 0.990 in -6.00 D ≤ SE < -3.00 D group. An AL/CR < 3.024 was the optimal cut-off point differentiating the CEL and control groups (sensitivity, 92.9%; specificity, 88.30%). CONCLUSIONS: A smaller AL/CR could identify CEL in children with myopia. An AL/CR cut-off value of 3.024 may be the most sensitive and specific parameter for the differential diagnosis of CEL in patients with mild to high myopia.

Incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis.

PURPOSE: To investigate the population-based incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis. METHODS: Patients newly diagnosed with Marfan syndrome in Olmsted County, Minnesota, from January 1, 1976, through December 31, 2005, were identified through medical records review. Outcome measures were Marfan incidence, de novo mutation rate, risk of ectopia lentis. RESULTS: Marfan syndrome was identified in 17 patients during the 30-year period, yielding an incidence of 0.52 per 100,000 people/year (95% CI, 0.27-0.77). Mean age at diagnosis was 24.4 years (range, 1.7 year to 51.3 years). Nine patients (53%) were female. Of the 17, 5 (29%) were new mutations, with a calculated mutation rate of 3.8 ± 1.7 × 10-5. Four (24%) were diagnosed with ectopia lentis, including 3 at the time of their Marfan diagnosis. Of the 14 patients at risk for developing ectopia lentis after being diagnosed with Marfan syndrome, 1 (7%) developed it during a mean follow-up of 9 years (range, 0-6.4). Twelve (71%) were diagnosed with dilated ascending aorta during a mean follow-up of 13.2 years (range, 6.7 months to 28.9 years). CONCLUSIONS: Incidence and de novo mutation rate of Marfan syndrome in this population-based cohort was higher than prior reports. Ectopia lentis, whose prevalence in North America has not been reported previously, occurred in approximately one-fourth of study patients and more commonly around the time of initial Marfan diagnosis.

[Endocapsular fixation of intraocular lens in patients with ectopia lentis and Marfan syndrome (case study)]. / Endokapsulyarnaya fiksatsiya intraokulyarnoi linzy pri ektopii khrustalika na fone sindroma Marfana (klinicheskoe nablyudenie).

Modern trends in advancement of phaco surgery techniques in patients with ectopia lentis (including patients with Marfan syndrome) are characterized by the transition from complete removal of the lens (lensectomy) to aspiration of the lens substance and attempts to preserve and reposition the capsular bag. This case study analyzes the results of surgical treatment of bilateral ectopia lentis in a 6-year-old patient with Marfan syndrome. The specifics of microinvasive phaco surgery consisted in capsular bag preservation and endocapsular fixation of the intraocular lens. The article presents the results of ophthalmological observation over a seven-year period.

Characteristics and genotype-phenotype correlations in ADAMTS17 mutation-related Weill-Marchesani syndrome.

Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. This study aims to investigate the characteristics and genotype-phenotype correlations of WMS with ADAMTS17 mutations. WMS patients with ADAMTS17 variants were identified by whole-exome sequencing from 185 patients with EL. All the included patients underwent comprehensive ocular and systemic examinations. ADAMTS17 variants were reviewed from included patients, published literature, and public databases. Bioinformatics analysis, co-segregation analysis, species sequence analysis, and protein silico modeling were used to verify the pathogenic mutations. A total of six novel ADAMTS17 mutations (c.1297C > T, c.2948C > T, c.1322+2T > C, c.1716C > G, c.1630G > A, and c.1669C > T) were identified in four WMS probands in our EL cohort (4/185, 2.16%). All probands and their biological parents presented with apparent short stature compared with the standard value. In particular, one child was detected with valvular heart disease, which has not previously been reported in patients with ADAMTS17 mutations. Conserved residues were greatly affected by the substitution of amino acids caused by these six mutations. Short stature could be considered a clue for EL patients with ADAMTS17 mutations, and much more attention needs to be paid to heart disorders among these patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.

Visual prognosis and complications of congenital ectopia lentis: study protocol for a hospital-based cohort in Zhongshan Ophthalmic Center.

INTRODUCTION: Congenital ectopia lentis (CEL) is a rare ocular disease characterised by the dislocation or displacement of the lens. Patients with mild lens dislocations can be treated with conservative methods (eg, corrective eyeglasses or contact lenses). In contrast, patients with severe CEL usually require surgical management. However, few studies have focused on the visual prognosis and complications in conservative and surgical management of patients. This study aims to investigate the prognosis and complications in patients with CEL with conservative and surgical management, which is vital for CEL management, especially the choice of surgical timing and surgical method. METHODS AND ANALYSIS: A cohort study will be conducted at Zhongshan Ophthalmic Center. We plan to recruit 604 participants diagnosed with CEL and aged ≥3 years old. Patients with mild lens subluxation and stable visual conditions will be included in the non-surgical group and follow-up at 1, 2 and 3 years after enrolment. Patients with severe lens subluxation who accept CEL surgery will be included in the surgical group. Different surgical techniques, including phacoemulsification, in-the-bag intraocular lens implantation (with or without capsular tension ring) and trans-scleral fixation, will be used depending on the severity of dislocation. Patients will be followed up at 3 months, and 1, 2 and 3 years postoperatively. Over a 5-year follow-up period, patients will receive a detailed ocular examination, including optometry, biological measurement, specular microscopy, ultrasound biomicroscopy, anterior segment and posterior segment optical coherence tomography (OCT), OCT angiography, echocardiography and questionnaires on vision-related quality of life. The primary outcome is the change of best-corrected visual acuity and the incidence of complications in both groups. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Zhongshan Ophthalmic Center (number: 2022KYPJ207). Study findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05654025.

Traboulsi syndrome without features of Marfan syndrome caused by a novel homozygous ASPH variant associated with a heterozygous FBN1 variant.

BACKGROUND: Traboulsi syndrome is a rare disease clinically characterized by facial dysmorphism, abnormal spontaneous filtering blebs, ectopia lentis (EL) and multiple anterior segment abnormalities. MATERIAL AND METHODS: An 18-year-old female was referred to the Emergency Service of Hospital São Geraldo (HSG) claiming decreased right eye (RE) visual acuity associated with ocular pain that was noticed approximately 2 months earlier. She underwent a complete ophthalmic and physical examination including hands, ankle, wrist and chest X-ray, abdominal ultrasound, echocardiogram and genetic analysis (whole-exome sequencing). RESULTS: The ophthalmic examination revealed a high myopia with spherical equivalent of - 9.50 D and best corrected visual acuity (BCVA) of 20/60 in RE and - 9.25 D with BCVA of 20/30 in the left eye (LE). Slit-lamp examination showed normal conjunctiva in both eyes (BE) and a superior-temporal cystic lesion in RE and nasal in LE; the flat anterior chamber in BE with the transparent crystalline lens touches the central corneal endothelium in the RE. Fundoscopy suggested glaucoma as the cup/disc ratio was 0.7, although the intraocular pressure (IOP) was 10 mmHg in BE without medication. Validation of data from whole exome demonstrated a novel splicing homozygous pathogenic variant (PV) (c.1765-1G>A) of the ASPH gene as well as a heterozygous variant of unknown significance (VUS) of the FBN1 gene (c.6832C>T). CONCLUSION: We here report a novel splice-affecting homozygous pathogenic variant in the ASPH gene that was detected in a Brazilian patient with clinical features of Traboulsi syndrome.