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).

Distribution of axial length in Chinese congenital ectopia lentis patients: a retrospective study.

BACKGROUND: Congenital ectopia lentis (CEL) usually leads to refractive error and may influence the axial length development. But few investigations have reported patient demographics and the distribution of axial length (AL) before surgery in Chinese pediatric patients with CEL. To describe the distribution of AL before surgery in CEL patients and its relationship with patients' demographics, such as age, Marfan syndrome, sex, and laterality. METHODS: This retrospective study reviewed 306 CEL patients from January 1, 2006 to December 31, 2015. One eye was randomly selected from each patient if both eyes were EL. The influences of Marfan syndrome, sex, and laterality to AL in different age subgroups were evaluated and compared. The differences of the AL between groups were assessed using the student t test or paired t-test. P-values less than 0.05 were considered statistically significant. RESULTS: Two hundred forty-seven eyes were enrolled. 58.3% of all the patients had binoculus EL, 70% of all the patients were male and 36% of all the patients were diagnosed with Marfan syndrome. The mean AL of EL patients was 25.1 ± 2.5 mm. There was no statistical difference in the AL between patients with and without Marfan syndrome, and in the AL between male and female patients. There was statistical difference in AL between the EL-affected eye and the unaffected eye in monocular EL patients younger than 12 years old. CONCLUSIONS: This study suggests that AL can be influenced by CEL, but the influence of CEL may be reduced after the age of 12 years old, which will likely provide a useful reference when considering the most appropriate time of surgery.

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.

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.

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.

Epidemiology of ectopia lentis and outcomes after surgery in a Danish population.

PURPOSE: To describe the causes of ectopia lentis (EL) and the outcomes after surgery in a Danish population. SETTING: The Eye Clinic Rigshospitalet and Kennedy Center in Copenhagen. DESIGN: Retrospective cohort study. METHODS: Medical records of patients with nontraumatic EL born after 1980 and seen at the Eye Clinic Rigshospitalet and Kennedy Center from 1983 to 2019 were reviewed. Clinical information regarding family history, comorbidities, genetic workup, ophthalmological examinations, and surgical history was retrieved. RESULTS: 72 patients (38 males), of whom 68 had bilateral EL (94.4%) were identified. Marfan syndrome (MFS) was found in 34 (47.2%) and biallelic variants in ADAMTSL4 in 4 (5.6%). Surgery was performed in 38 (52.8%) patients, 66 eyes, with a median age at the time of first eye surgery of 8.4 years (range 0.8 to 39.0 years) and a follow-up of 2.3 years (range 0 to 25.7 years). Intraocular lenses were implanted in 9 (23.7%) (11 eyes). Corrected distance visual acuity improved from 0.7 to 0.2 logMAR (median) in right eyes and from 0.7 to 0.3 logMAR in left eyes postoperatively. 21 patients (56.8%), 42 eyes, did not experience any surgery-related complications. 3 patients (3 eyes) experienced a perioperative tear in the posterior capsule. Temporary postoperative ocular hypertension was reported in 3 patients (7.9%) (3 eyes), and 2 patients (5.4%) (2 eyes) developed persistent ocular hypertension. There were no cases of postoperative retinal detachment. CONCLUSIONS: The main reason for EL was MFS. Surgery improved visual acuity, and postoperative ocular hypertension was the most common complication, whereas retinal detachment was not observed.

Incidence of retinal detachment after lens surgery in children and young adults with nontraumatic ectopia lentis.

PURPOSE: To determine the incidence of retinal detachment after lens surgery in children and young adults with nontraumatic ectopia lentis. SETTING: Population-based claims data. DESIGN: Population-based retrospective cohort study. METHODS: Patients with nontraumatic ectopia lentis aged 30 years or younger who had undergone lens surgery with or without intraocular lens (IOL) implantation and had 1 year or greater continuous enrollment after lens surgery were included in the Optum deidentified Clinformatics Data Mart Database (2003 to 2019) and IBM MarketScan Databases (2007 to 2016). Both databases were assessed for sex, age, etiology of ectopia lentis, IOL implantation, and postoperative retinal detachment separately. Univariate and multivariate analyses were conducted to identify the risk factors for postoperative retinal detachment. RESULTS: Among a total of 298 eyes (210 patients), IOL implantation was coupled with lens surgery in 151 eyes (49.8%) that underwent lens surgery for nontraumatic ectopia lentis. The median follow-up was 32 months in aphakic eyes and 29 months in pseudophakic eyes. Patients undergoing IOL implantation were older at the time of lens surgery (median age: no IOL, 6 years; IOL, 16 years; P < .001). Retinal detachment developed in 13 patients (14 eyes [4.7%]) 14 eyes (4.7%). Older age was the baseline characteristic that correlated most closely with the risk for retinal detachment (P = .05). CONCLUSIONS: The rate of retinal detachment was similar with or without IOL implantation after lens surgery for nontraumatic ectopia lentis in children and young adults.

Humphrey visual fields and optical coherence tomography findings in patients with the Axenfeld-Rieger syndrome: a case series.

INTRODUCTION: Axenfeld-Rieger syndrome is characterized by clinical characteristics including: ocular, craniofacial, dental, umbilical, and other systemic abnormalities. Previous studies have reported that the Axenfeld-Rieger syndrome (ARS) occurs in one out of 200,000 patients. PURPOSE: To study patients with the ARS in a sub-urban community in Puerto Rico. PATIENTS AND METHODS: We conducted a non-concurrent study of 17,800 patients. Of these, 57 patients had the syndrome. Every patient had a comprehensive ophthalmology evaluation. RESULTS: A frequency of 320 per 100,000 was found in the studied population. Using Humphrey's visual field analyzer, we found a mean deviation of less than -2.00 dB in 56.4 and 60.5 percent of the right and left eye respectively. OCT evaluation of the optic nerve rim showed glaucomatous changes in 29.2 and 41.7 percent of the right and left eyes respectively. OCT evaluation of the retinal nerve fiber layer showed glaucomatous changes in 20.8 and 16.7 percent of the right and left eyes respectively. CONCLUSION: The frequency of patients with the syndrome in Puerto Rico is higher than in other populations reported in the literature. Also, the percent of patients with glaucoma is higher than previously reported. A relationship between hemochromatosis and ARS has not been previously described. Further studies will elucidate the genetics of Axenfeld-Rieger syndrome in Puerto Rico.

Management of cataracts and ectopia lentis in children: Practice patterns of pediatric ophthalmologists in India.

PURPOSE: To analyze the current practice patterns of Indian pediatric ophthalmologists in the management of lens anomalies. This study was conducted in a tertiary eye care hospital and involved an online questionnaire survey for practicing pediatric ophthalmologists in India. METHODS: A questionnaire was devised by the authors, which included the various options available for the management of lens anomalies in children. The questionnaire was sent to each of them using an online portal. Commercial software (Stata ver. 13.1; StataCorp, College Station, TX, USA) was used for statistical analysis. RESULTS: In unilateral cataracts in children aged <6 months, 85.42% of surgeons did not prefer to insert an intraocular lens (IOL). In the age group of 6-12 months, almost half of them preferred to insert an IOL. In the age group of 12-24 months and> 24 months, 92.63% and 88.54%, respectively, preferred to insert an IOL. In bilateral cataracts, in children aged <6 months, 91.84% of surgeons did not prefer to insert an IOL, whereas in the age group of 6-12 months, 69.39% did not prefer to insert an IOL. In the age group of 12-24 months and> 24 months, 80.61% and 90.82%, respectively, preferred to insert an IOL. Seventy-four percent of surgeons preferred to use a single-piece hydrophobic acrylic IOL. CONCLUSION: The management of lens anomalies by pediatric ophthalmologists in India varies with laterality and appears to be comparable to that followed worldwide.

[The estimation of functional results after surgical treatment for ectopia lentis in children]. / Ocena wyników czynnosciowych po leczeniu operacyjnym przemieszczonej soczewki u dzieci.

PURPOSE: To review the visual outcome of planned pars plana lensectomy and vitrectomy with posterior chamber intraocular lens implantation for ectopia lentis in children. MATERIAL AND METHODS: Between 1997-2002, 116 eyes were operated because of lens subluxation, mainly because of decreased visual acuity (<0.4). Lens subluxation was associated with homocystinuria in 4 patients (8 eyes), Marfan's syndrome in 30 (54 eyes), congenital simple ectopia lentis in 16 (31 eyes), post trauma in 6 (6 eyes), and congenital ectopia lentis and pupillae in 9 (17 eyes). Time of observation ranged between 1 to 6 years (mean 3.4). RESULTS: After surgery, we achieved best-corrected visual acuity improvement in 89%. Unsatisfactory visual results were due to amblyopia (9 eyes), complications of retinal detachement surgery (3 eyes), uveitis (2 eyes), glaucoma (1 eye). CONCLUSIONS: Pars plana lensectomy, vitrectomy and scleral-fixated IOL implantation give quick and good functional results. To achieve these results, visual rehabilitation and amblyopia treatment is necessary.

Ocular findings in 87 adults with Ghent-1 verified Marfan syndrome.

PURPOSE: To study ocular characteristics in 87 patients with verified Marfan syndrome (MFS) based on the Ghent criteria from 1996 (Ghent-1). METHODS: The position of the lens was noted by observing the eye in different gaze directions in maximal mydriasis during slit lamp examination. Ectopia lentis (EL) was classified as subluxated (dislocation slightly backwards) or luxated (vertical or horizontal displacement). Corneal curvature, axial length (AL), corneal diameter, central corneal thickness, anterior chamber depth, lens thickness, condition of the iris, intraocular pressure, spherical equivalent and visual acuity were also investigated. RESULTS: EL was found in 108 eyes (62.1%). Of the 68 phakic eyes with EL, 43 (63.2%) had subluxation. Mean AL was 24.80 ± 2.57 mm, and the AL was above 23.5 mm in 65.3%. Mean keratometry (K) in phakic eyes was 41.79 ± 1.70 diopters (D), and the K value was <41.5D in 46.8%. Iris hypoplasia was found in 3.4%. Myopia above 3D occurred in 38.4% of the phakic eyes. Mean binocular logMAR was 0.10 ± 0.32. Only five patients (5.7%) had a logMAR more than 0.5. These 5 patients had EL, and 4 of them were amblyopic. CONCLUSION: In this strictly defined MFS group fulfilling the Ghent-1 criteria, the prevalence of EL was 62.1%. In many cases, the dislocation of the lens was subtle. On average, the corneas were flattened and the globe length was increased. Only a few patients were visually impaired. Children with MFS should have a thorough follow up to avoid amblyopia.

Lens surgery in infancy and childhood.

The medical records of 224 children who had lens surgery performed at the Hospital for Sick Children during the 10-year period 1978-88 were reviewed. There were 12 children with ectopia lentis; these patients achieved a mean postoperative acuity of 0.68 (6/8.8), and no operative or postoperative complications were noted. Two hundred and twelve children had lens surgery for cataracts or for retrolental abnormalities with a clear lens. Children with bilateral congenital cataracts achieved a mean acuity in the better eye of 0.32 (6/18). In a series of carefully controlled unilateral congenital cataracts the visual results were poor. The postoperative complication rate for cataract and clear lens surgery was 4.6%. Because visual results are probably better with early surgery we emphasise that every newborn baby should be tested for media opacities.

Strabismus in pediatric lens disorders.

PURPOSE: To evaluate the prevalence and types of strabismus in children with cataract and ectopia lentis. METHODS: The authors retrospectively evaluated 860 children treated in the ophthalmological department of Children's Hospital "Agia Sophia" during the past decade. Their medical files with reference to strabismus prevalence, correlation between the time of strabismus occurrence and lens extraction surgery, and type of strabismus were studied. RESULTS: Of the 822 children with cataract, 337 had congenital cataract and 485 had acquired cataract. Strabismus occurred in 199 (24.2%) patients; 113 (56.8%) patients had esotropia and 86 (43.2%) patients had exotropia. Of the 38 children with ectopia lentis, strabismus occurred in 5 (13.2%); 1 patient had esotropia and 4 patients had exotropia. There is no significant difference in the time of appearance of strabismus in relation to the cataract operation, whereas there is a significant difference in ectopia lentis, although this may be a result of the small sample size. The incidence of strabismus is higher in patients with unilateral cataracts (27.4%) than in those with bilateral cataracts (19.6%). Strabismus occurred more frequently in patients with congenital cataracts (30.3%) than in acquired cases (20%), with esotropia being more common in congenital cataracts (76.5%) and exotropia more common in acquired cataracts (63.9%). CONCLUSION: The authors believe it is imperative that great attention should be given to ocular alignment in addition to management of refractive error and intense amblyopia therapy during long-term follow-up.

Marfan syndrome and other systemic disorders with congenital ectopia lentis. A Danish national survey.

In order to elucidate demographic and nosologic characteristics of Marfan syndrome (MS) and other systemic disorders associated with congenital ectopia lentis (ECL) in Denmark, a register of affected persons was established in a nationwide retrospective study. Three hundred and forty patients with MS (180M, 160F) were registered. By January 1, 1993, the estimated prevalence rate of MS was 4.6/100,000. An estimated average birth rate of 0.96/10,000 live born was found. The mean age at death was decreased (38 +/- 18 y) mainly due to cardiovascular complications. Correspondingly, a median cumulative probability of survival of 57 y (males) and 58 y (females) was found. Only seven patients with ECL as manifestation of other systemic disorders were diagnosed in the material, i.e. three patients with homocystinuria, two patients with Weill-Marchesani syndrome, and another 2 patients with sulphite oxidase deficiency. In a further 122 cases with ECL a nosologic diagnosis could not be established due to unavailable or insufficient information. This group may comprise patients with MS and other systemic disorders as well as patients with non-systemic ECL. In retrospect, the differential diagnostic activity for patients with congenital ectopia lentis has been insufficient during the last few decades and a common protocol for diagnosis, control and treatment of ECL is needed.

Congenital ectopia lentis. A Danish national survey.

PURPOSE: To elucidate demographic and nosologic characteristics of congenital ectopia lentis (ECL) in Denmark. METHODS: A register of affected persons was established based on information provided from medical records and files in a nation-wide retrospective study, the Danish ECL-study. RESULTS: Three hundred and ninety-six cases (197 males, 199 females) with ECL were included in the study. By January 1st, 1993, the estimated prevalence rate of ECL was 6.4/100,000. The estimated average point prevalence rate at birth 1976-85 was 0.83/10,000 live born. Only in 69% of the cases (274/396) was a nosologic classification possible, based on preexisting information about familial occurrence, systemic and ocular findings: Marfan syndrome was found in 68.2% of these (187/274), ectopia lentis et pupillae in 21.2%, simple dominant ectopia lentis in 8.0%, homocystinuria in 1.1%, sulfite oxidase deficiency and Weill-Marchesani syndrome in 0.7% each. In the remaining 31% (122/396) a nosologic diagnosis could not be established. CONCLUSION: The majority of affected persons have congenital ectopia lentis as a manifestation of a systemic disease. It is therefore essential to evaluate ECL patients systemically with a general physical examination, a metabolic screening, and an echocardiography as a minimum, in order to make a nosologic diagnosis and to prevent potentially life-threatening systemic complications.