Bilateral Congenital Cataracts Research Articles

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy.

Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy and have also been reported in families with only a cataract phenotype. Dilated cardiomyopathy (DCM) is a disorder with a highly heterogeneous genetic etiology involving more than 60 causative genes, hindering genetic diagnosis. In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in NM_001289808.2:c.527A>G of CRYAB in one patient. The mutant alpha-B crystallin protein is predicted to have an extended strand with addition of 19 amino acid residues, p.(Ter176TrpextTer19), which may contribute to aggregation and increased hydrophobicity of alpha-B crystallin. The proband, diagnosed with DCM at age 32, had a history of bilateral congenital cataracts but had no evidence of myopathy or associated symptoms. He also has a 10-year-old child diagnosed with bilateral congenital cataracts with the same CRYAB variant. This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies.

Phenotypic comparison of a novel variant (p.P164R) and A founder mutation (c.748+1G&gt;A) in Warburg Micro syndrome

Warburg Micro syndrome is a rare autosomal recessive disease due to pathogenic variants found most commonly in the RAB3GAP1 gene. It is commonly seen in consanguineous marriages and is characterized by optic, neurologic, endocrinologic and some non-typical findings (cardiomyopathy, peripheral neuropathy). Here, we report two male patients from healthy consanguineous and non- consanguineous carrier parents, with homozygous variants of the RAB3GAP1 gene, presenting with bilateral congenital cataracts, hypogonadism, hypotonia and developmental delay. The first case had a novel variant and had colpocephaly as shown in his MRI brain, which has not been previously reported in the medical literature. The second case was thought to have a founder mutation for Turkey. In conclusion, there was no phenotypical difference between the novel and founder mutations. In Turkish patients suspected to have Warburg Micro syndrome, we recommend molecular testing for the detection of a founder mutation.

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

Hereditary hyperferritinemia cataract syndrome with iron deficiency : a case report

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. HHCS is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. In this case report, we aimed to present a young female patient with a history of cataracts in herself and her family members. Our patient had the dilemma of iron deficiency anemia and hyperferritinemia. As in our patient, patients with HHCS apply to many outpatient clinics and have difficulty in diagnosis. For this reason, we prepared our case to raise awareness.

From Bright to Brightness: Mastering the Management of Bilateral Congenital Cataracts

Congenital cataract is the leading cause of vision loss in newborns and children, and it is caused by an opacity of the eye's lens that occurs at birth or within the first few months of life. Congenital cataracts may develop as unilateral or bilateral. Around 50% of cases of it are considered as idiopathic. A 4-month-old boy was brought by his parents to the Department of Pediatric Ophthalmology and Strabismus in RSUD dr. Zainoel Abidin Banda Aceh with a chief complaint of a white spot on the patient’s right eye. The spot had appeared since birth and became more visible when he was 2 months old. The patient's overall condition was good. Both eyes' visual acuity was blink reflex. The ocular pressure in both eyes was normal. An ophthalmologic examination revealed a fully clouded right eye lens and aphakia in the left eye. The patient had undergone cataract surgery on his left eye on September 6th, 2023. He was diagnosed with Congenital Cataract Oculus Dexter (OD) and Aphakia Oculus Sinister (OS) before surgery. The patient underwent right eye cataract surgery with aspiration irrigation (AI), Primary Posterior Capsulotomy (PPC), and Anterior Vitrectomy (AV) without Intraocular Lens (IOL) implantation within the next two weeks. Following the surgery, the patient's visual function improved to fix and follow the object, the pupils looked round in both eyes, aphakia, and no membrane development. The patient was prescribed glasses for optical rehabilitation.

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

PP-19 Prenatal diagnosis of isolated bilateral congenital cataract

A X-linked nonsense APOO/MIC26 variant causes a lethal mitochondrial disease with progeria-like phenotypes.

APOO/MIC26 is a subunit of the MICOS complex required for mitochondrial cristae morphology and function. Here, we report a novel variant of the APOO/MIC26 gene that causes a severe mitochondrial disease with overall progeria-like phenotypes in two patients. Both patients developed partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. The patients died at an early age of 12 or 18 months. Exome sequencing revealed a mutation (NM_024122.5): c.532G>T (p.E178*) in the APOO/MIC26 gene that causes a nonsense mutation leading to the loss of 20 C-terminal amino acids. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells. We conclude that the novel mutation found in the APOO/MIC26 gene is a loss-of-function mutation impairing mitochondrial morphology and cristae morphogenesis.

Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing.

The present study aimed to identify the molecular etiology of non-syndromic congenital cataract (CC) using whole-exome sequencing (WES) analysis. In the present study, ophthalmologic results and pedigree analysis of the families of 12 patients with non-syndromic CC were evaluated. WES analysis was conducted after DNA was isolated from peripheral blood samples obtained from the patients. Twelve non-syndromic probands (10 males and 2 females) with bilateral CC were included in the study. Patient age ranged between 1 and 11months. WES analysis showed pathogenic/likely pathogenic variant in 7 (58%) of the 12 families and variant of unknown significance (VUS) in 5 (42%) of them. All the 13 different variants detected in 9 different CC-related genes were co-segregated with the disease. Autosomal dominant inheritance was found in 7 (58%) of the families and autosomal recessive inheritance was found in 5 (42%) of them. To the best of our knowledge, the present research is one of the limited numbers of studies in the Turkish population in which genetically heterogeneous non-syndromic CC was investigated using WES analysis. Novel variants that we identified in DNMBP, LSS, and WFS1 genes, which are rarely associated with the CC phenotype, have contributed to the mutation spectrum of this disease. Identifying the relevant molecular genetic etiology allows accurate genetic counseling to be provided to the families.

Infective Etiologies in Patients with Bilateral Congenital Cataract

Objective: To determine the frequency of positive Toxoplasma, Rubella, Cytomegalovirus, Herpes Simplex virus and Syphilis serology in patients with bilateral congenital cataract and their correlation with different type of cataracts and age groups.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Department of Pediatric Ophthalmology and Strabismus, Armed Forces Institute of Ophthalmology, Rawalpindi Pakistan, from May to Dec 2022.&#x0D; Methodology: Data was collected by a single investigator on Microsoft Excel sheet including patient’s age, gender, mode of delivery, consanguinity of parents, and type of congenital cataract, results of TORCH Screening and Presence or absence of amblyopia. TORCHS screening comprised of serum IgM and IgG levels for Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Simplex virus and Syphilis. &#x0D; Results: A total of 134 patients reported to our institute with bilateral congenital cataract during the study period. Out of them 56 patients had positive results of TORCH screening (41.7%) Out of total 56 patients with bilateral congenital cataract testing positive for TORCH, 30(53.6%) were male while 26(46.4%) were female. Age range was from 1-17 months (9.2±4.2 months).Lamellar cataract was the most common cataract type in our study sample 16(28.6%).&#x0D; Conclusion: In patients with bilateral congenital cataract positive TORCHS serology was most frequent. Serum Rubella IgM followed by Rubella IgG was positive in most cases. Most common age of presentation in our study was from 4-7 months. Furthermore, lamellar cataract followed by nuclear cataract was the commonest cataract type.

Clinical observation of spontaneous brain activity in children with congenital cortical cataract amblyopia

Objective: To investigate the characteristics of spontaneous brain activity in children with congenital cortical cataract amblyopia. Methods: A cross-sectional study was conducted. Twenty cases of unilateral congenital cortical cataract amblyopia (unilateral amblyopia group) and 14 cases of bilateral congenital cortical cataract amblyopia (bilateral amblyopia group) were enrolled from January 2022 to December 2022 at the First Affiliated Hospital of Zhengzhou University. Seventeen age and gender matched children with normal visual acuity were recruited as the healthy control group. Resting-state functional MRI (fMRI) was performed on all participants, and the amplitude of low-frequency fluctuations (ALFF) technique was used to analyze their spontaneous brain activities. The original ALFF value of each voxel was divided by the average ALFF value of the whole brain to obtain the standardized ALFF value (referred to as ALFF value), which reflected the intensity of spontaneous brain activity in different brain regions. General demographic data were compared using one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Comparison of ALFF values was conducted using one-way analysis of variance. Results: There were no significant differences in age, gender, distribution of amblyopic eye or non-dominant eye, and degree of refractive error among the three groups (all P>0.05). Compared to the healthy control group, the unilateral amblyopia group showed higher ALFF values in the right posterior lobe of the cerebellum (67 voxels, t=3.48) and left posterior lobe of the cerebellum (71 voxels, t=4.09), and lower ALFF values in the right postcentral gyrus (91 voxels, t=-3.91), right inferior parietal lobule (73 voxels, t=-4.88), right inferior frontal gyrus (78 voxels, t=-4.09), left inferior parietal lobule (556 voxels, t=-4.82), and left inferior frontal gyrus (122 voxels, t=-4.27) (all P<0.01). The bilateral amblyopia group showed higher ALFF values in the right insula (60 voxels, t=3.54), right Rolandic operculum (69 voxels, t=3.73), right posterior lobe of the cerebellum (54 voxels, t=3.43), and left posterior lobe of the cerebellum (143 voxels, t=3.69), and lower ALFF values in the left inferior frontal gyrus (99 voxels, t=-4.39), left postcentral gyrus (231 voxels, t=-4.28), and right inferior parietal lobule (54 voxels, t=-3.77) (all P<0.01). Compared to the unilateral amblyopia group, the bilateral amblyopia group showed higher ALFF values in the left middle frontal gyrus (52 voxels, t=3.15, P=0.029), left posterior lobe of the cerebellum (77 voxels, t=3.39, P=0.001), and right Rolandic operculum (53 voxels, t=3.59, P=0.007). Conclusion: Children with congenital cortical cataract amblyopia exhibit altered spontaneous brain activity in multiple brain regions, and there are differences in spontaneous brain activity changes between unilateral and bilateral amblyopia.

A Baby Girl Born with Bilateral Congenital Cataract to A Mother with Unilateral Congenital Cataract Treated in Childhood

We hereby disseminate a case of a baby girl, who at ten months of age received MMR vaccine but was discovered to later have unilateral congenital cataract at eight years of age. At 25 years, she was married giving birth to a baby boy who had normal vision. Unfortunately, the second baby girl was detected to have bilateral cataract for which the baby at four months of age underwent lens aspiration and anterior vitrectomy of both eyes at a gap of one week. A month later a glass with bilateral +21 Diopters were prescribed. She is planned for intraocular lens implant at around four years of age. She is on currently on visual rehabilitation and treatment for amblyopia Learning lesson from this case being the fact that congenital cataract may run in family and may impart vision deprivation in the offspring; therefore, the importance of preconception counseling is important.

Autosomal recessive congenital cataract is associated with a novel 4-bp splicing deletion mutation in a novel C10orf71 human gene

Congenital cataract is one of the most genetically heterogeneous ocular conditions with different genes involved in its etiology. Here, we describe the analysis of a new candidate gene of a congenital bilateral cataract associated with polymalformative syndrome, moderate global developmental delay, microcephaly, axial hypotonia, intrauterine growth restriction and facial dysmorphism for two affected siblings. Molecular analysis included exome sequencing and genome wide homozygosity mapping revealed a region of homozygosity shared by the two affected siblings at 10q11.23. The new C10orf71 gene was included in this interval and direct sequencing of this gene revealed an already described homozygous c. 2123T > G mutation (p. L708R) for the two affected subjects. Interestingly, we revealed in contrast a 4-bp deletion on the 3'-splicing acceptor site of intron 3-exon 4, namely defined as IVS3-5delGCAA. The C10Orf71 gene expression analysis using RT-PCR showed an expression pattern in different fetal organs and tissues as well as in leukocytes and confirmed that the IVS3-5delGCAA deletion of the C10orf71 gene is a splicing mutation responsible for the shortening of the C10orf71 protein in the two related patients. The C10orf71 gene has not been described to date as associated to the autosomal recessive phenotype.

First Clinical Report of Two RAB3GAP1 Pathogenic Variant in Warburg Micro Syndrome.

Warburg micro (WARBM) syndrome is an autosomal recessive disease characterized by severe brain and eye abnormalities. Loss-of-function mutations in RAB18, RAB3GAP2, RAB3GAP1, or TBC1D20 can lead to this disease. Here, we present two unrelated WARBM syndrome patients who had an RAB3GAP1 c.559 C > T, (p.Arg187Ter) and c.520 C > T (p.Arg174Ter) homozygous state. Both patients had microcephaly, microphthalmia, microcornea, bilateral congenital cataracts, severe intellectual disability, and congenital hypotonia. Using the method of next-generation sequencing and sanger sequencing, we found two nonsense variations at the splice site in exon 7 of RAB3GAP1 in the WARBM syndrome patients. The mutations were predicted to cause the syndrome due to the early stop codon, and the patients had the WARBM1 syndrome. We present the first clinical report of two different unreported variants with RAB3GAP1 mutation in the literature.

Abstract #1397268: A Rare Case of Insulinomatosis in a 58-Year-Old Woman with Recurrent Symptoms of Hypoglycemia

Insulinomatosis is a rare cause of hyperinsulinaemic hypoglycaemia. The ideal management approach is not known. We present a case of recurrent hypoglycemia whose management was complicated by the pandemic. A 58-year-old woman with a family history of a mother who died of a pancreatic tumor and a personal history of congenital bilateral cataract, arterial hypertension, subclinical hypothyroidism, Child A liver cirrhosis, and subtotal pancreatectomy for hyperinsulinemic hypoglycemia in 2019 due to two insulinomas in the head and body of the pancreas. The pathological and immunohistochemical study was consistent with two pancreatic neuroendocrine tumors with Ki67: 1%, we did not have staining for insulin. She was discharged without episodes of hypoglycemia; 10 months after the operation, she presented a recurrence of neuroglycopenic symptoms during periods of fasting, which she controlled with a greater intake of food; furthermore, she recorded fasting capillary glycemia between 40-60mg/dl without symptoms. Due to the pandemic, she could not be evaluated at our center until 2022, when she was hospitalized for study. Hyperinsulinemic hypoglycemia was verified, imaging studies (CT, MRI, PET) did not show lesions in the remaining pancreatic tissue; On its own, endoscopic echocardiography described a 7-mm lesion adjacent to the splenic artery. The patient did not accept new surgery. The genetic study for MEN type 1 was negative. The subcutaneous octreotide test showed a glycemia value greater than 100mg/dL after its administration, so she was discharged with a fractionated diet and subcutaneous octreotide 25-50 ug at night. To date, she has not presented a clinical picture again. and biochemical hypoglycemia with adequate tolerance. Insulinomas are the most frequent pNETs (45%). About 10% are multiple, 10% are malignant, and 16% are associated with MEN1. Insulinomas are usually benign and managed surgically. Insulinomas that appear synchronously or metachronously, but are not associated with MEN1 are termed insulinomatosis. Diagnosis consists of documentation of hyperinsulinemic hypoglycemia, synchronous presence of β-cell micro- or macrotumors, or early recurrence of hyperinsulinemic hypoglycemia with new β-cell lesion in a history of prior insulinoma. Insulinomatosis is distinguished histologically by insulin-expressing monohormonal endocrine cell clusters (IMECCs) and tumor staining only for insulin, whereas MEN-1 associated insulinomas stain for multiple hormones. Regarding management, the first line is surgery, although in some cases total pancreatectomy did not result in a cure for hypoglycemia, so local or systemic treatment can be used (diazoxide, corticosteroids, somatostatin analogues, verapamil, and everolimus).

Endoplasmic Reticulum Stress and the Lysosomal Pathway Play Crucial Roles in the Progression of βB2-Crystallin Mutation-Induced Congenital Cataracts inMice.

Congenital cataract is a major cause of visual impairment and childhood blindness; however, its underlying mechanism remains unclear. Here, we aimed to identify the roles of endoplasmic reticulum stress (ERS), lysosomal pathway, and lens capsule fibrosis during the progression of βB2-crystallin mutation-induced congenital cataract in mice. BetaB2-W151C knock-in mice were generated using the CRISPR/Cas9 system. Lens opacity was assessed with a slit-lamp biomicroscopy and dissecting microscope. Transcriptional profiles of the lenses in W151C mutant and wild-type (WT) control mice were detected at 3 months of age. Immunofluorescence of lens anterior capsule was photographed with a confocal microscope. Real-time PCR and immunoblot were used to detect gene mRNA and protein expressions, respectively. BetaB2-W151C knock-in mice developed progressive bilateral congenital cataracts. At 2 to 3 months of age, lens opacity rapidly progressed to complete cataracts. Additionally, multilayered LEC plaques developed beneath the lens anterior capsule in homozygous mice at 3 months of age, and severe fibrosis was observed in the whole lens capsule at 9 months of age. Microarray analysis of whole genome transcriptomics and the validation results of real-time PCR revealed that genes of ERS, the lysosomal pathway, apoptosis, and cell migration and fibrosis were significantly upregulated in βB2-W151C mutant mice during the accelerated development of cataract. Moreover, the syntheses of various crystallins stagnated in βB2-W151C mutant mice. ERS, the lysosomal pathway, apoptosis, and fibrosis all contributed to the accelerated development of congenital cataract. The inhibition of ERS and lysosomal cathepsins may be promising therapeutic strategies for congenital cataract.

Variants of BEST1 and CRYBB2 cause a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy: case report

BackgroundBest vitelliform macular dystrophy (BVMD), caused by pathogenic variants of the BEST1 gene, has not been reported in association with cataracts and ocular malformations. We reported a case with a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy.Case presentationA six-year-old girl manifested photophobia and a poor visual behavior. A thorough ophthalmic examination revealed the patient to have bilateral microphthalmia, microcornea, congenital cataract, and Best vitelliform macular dystrophy (BVMD). Whole exome sequencing (WES) identified one variant in the BEST1 and one variant in CRYBB2 genes: c.218 T > G p.(Ile73Arg) and c.479G > C p.(Arg160Pro). The first variant was inherited from the proband’s father, who was diagnosed with subclinical BVMD, while the second was a de novo variant. A minigene assay showed that c.218 T > G in BEST1 did not affect pre-mRNA splicing.ConclusionsThis case suggests that the complex ocular phenotype comprising BVMD and congenital cataract with microphthalmia cannot be explained by variation in one gene but is caused by variants in BEST1 and CRYBB2. This case highlights the importance of general clinical evaluation and comprehensive genetic testing for diagnosing complex eye diseases.

Congenital Cataract and Narrow CSP: A Clue to Prenatal Diagnosis of RAB3GAP1-Associated Warburg Micro Syndrome

AbstractWarburg Micro Syndrome (WMS) is an autosomal recessive disorder characterized by intellectual disability, bilateral congenital cataracts, microphthalmia, and brain anomalies. We report an 18-week fetus presenting with bilateral congenital cataract and narrow cavum septum pellucidum. Patient was counselled about the possible etiologies ranging from infectious to chromosomal and single gene etiologies. Invasive testing for genetic analysis was done to determine etiology and establish prognosis. A previously reported homozygous frameshift mutation was identified in RAB3GAP1 gene leading to diagnosis of WMS. This case highlights the role of detailed fetal sonography and genetic testing to prognosticate pregnancies. Also WMS should be suspected in fetuses presenting with bilateral congenital cataract with or without brain anomalies.

Incidence of and risk factors for suspected and definitive glaucoma after bilateral congenital cataract surgery: a 5-year follow-up

AimsTo report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year follow-up.MethodsSecondary analysis of a prospective longitudinal cohort...

Nystagmus in Children - a Survey

Nystagmus describes an involuntary, periodic movement of one or both eyes. About 1/600 children and adolescents have nystagmus, most of them idiopathic infantile nystagmus (IIN), also called "congenital nystagmus", which can be caused by mutations in the FRMD7 gene. Other frequent forms of nystagmus are latent nystagmus, which is usually associated with infantile strabismus, and nystagmus associated with albinism. Sometimes difficult to distinguish in young infants is a sensory nystagmus, where a defect in the visual system reduces vision and causes nystagmus. Causes include retinal dystrophies, congenital stationary night blindness and structural ocular defects including optic nerve hypoplasia or dense bilateral congenital cataracts. Unilateral nystagmus can be the sign of an anterior visual pathway lesion. Seesaw nystagmus may be associated with suprasellar and mesodiencephalic lesions and - rarely - with retinal dystrophies.The ophthalmology plays a key role in identifying the form of nystagmus. Children with new onset nystagmus, with spasmus nutans, with vertical or unilateral nystagmus and those with seesaw nystagmus require neurologic evaluation including imaging of the brain.The treatment of nystagmus depends on the underlying cause. Even minor refractive errors should be corrected, contact lenses offer advantages over glasses.Gabapentin and memantine, possibly also carbonic anhydrase inhibitors, are effective in treating IIN, nystagmus in albinism and sensory nystagmus. Nevertheless, pharmacologic treatment of nystagmus is rarely used in children; the reasons are the limited effects on vision, the need for lifelong therapy, and potential side effects. Eye muscle surgery (Anderson procedure, Kestenbaum procedure) can correct a nystagmus-related anomalous head posture. The concept of "artifical divergence" of Cüppers may help to decrease nystagmus intensity in patients whose nystagmus dampens with convergence. The four-muscle-tenotomy, which involves disinsertion and reinsertion of the horizontal muscles at the original insertion of both eyes, has a proven but limited positive effect on visual acuity.