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Eye (London, England) Mar 2020
Topics: Corneal Diseases; Ectopia Lentis; Glaucoma; Humans; Iris
PubMed: 31391543
DOI: 10.1038/s41433-019-0544-6 -
Indian Journal of Ophthalmology Dec 2016This study aimed to evaluate the safety and efficacy of retropupillary fixation of an iris-claw intraocular lens (IOL; Verisyse polymethyl methacrylate IOL, Abbott...
PURPOSE
This study aimed to evaluate the safety and efficacy of retropupillary fixation of an iris-claw intraocular lens (IOL; Verisyse polymethyl methacrylate IOL, Abbott Medical Optics [AMO], Netherlands) for the surgical correction of aphakia in microspherophakic eyes without sufficient capsular support.
DESIGN
This was a prospective, interventional, noncomparative case series.
METHODS
This interventional case series comprised 17 eyes of 9 microspherophakic patients. Retropupillary fixation of the Verisyse iris-claw IOL (AMO) was performed in all cases. The surgical time was measured. Corrected distance visual acuity, astigmatism, intraocular pressure (IOP), tissue reaction, pigment dispersion, and stability of the IOL were studied 1 day, 3 days, 1 week, 2 weeks, 1 month, and 6 months postoperatively.
RESULTS
Eight patients had familial microspherophakia and one patient had Marfan's syndrome. Eighty-two percent of the cases achieved a visual acuity of 0.3 or better. There was no significant postoperative inflammatory reaction. Transient elevation of IOP was recorded in two cases in the 1st week only. One IOL developed disengagement of one of the haptics from the iris and was successfully re-engaged. All the other IOLs were well centered and stable. The mean surgical time was 18.0 ± 4.5 min.
CONCLUSIONS
Retropupillary fixation of an iris-claw IOL is a safe and effective procedure that provides early visual recovery. It is also a time-saving method for correcting aphakia in microspherophakic eyes without sufficient capsular support.
Topics: Adolescent; Adult; Aphakia; Corneal Diseases; Ectopia Lentis; Female; Follow-Up Studies; Glaucoma; Humans; Iris; Lenses, Intraocular; Male; Prospective Studies; Prosthesis Design; Refraction, Ocular; Time Factors; Visual Acuity; Young Adult
PubMed: 28112127
DOI: 10.4103/0301-4738.198844 -
Frontiers in Medicine 2022Weill-Marchesani syndrome 4 (WMS4) is caused by gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia,...
BACKGROUND
Weill-Marchesani syndrome 4 (WMS4) is caused by gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up.
CASE PRESENTATION
An 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G > A (p.Arg995Gln) and c.2254A > G (p.Ile752Val) in the gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient's myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present.
CONCLUSION
This case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.
PubMed: 36698805
DOI: 10.3389/fmed.2022.1021489 -
BMJ Case Reports May 2016The ocular manifestations of Marfan's syndrome (MS) range from ectopia lentis, microspherophakia, myopia, glaucoma and retinal detachment. Spontaneous scleral rupture is...
The ocular manifestations of Marfan's syndrome (MS) range from ectopia lentis, microspherophakia, myopia, glaucoma and retinal detachment. Spontaneous scleral rupture is a rare complication and recurrent scleral perforation is extremely rare. We report a rare case of a 26-year-old male with MS who had sequential recurrent spontaneous scleral rupture which required surgical repair. He suffered from a similar problem 4 years later in both eyes in a different location, with overlying thin cystic blebs and hypotony maculopathy. Surgical repair with preserved scleral donor patch graft and conjunctival autograft in one eye, and conjunctival advancement in the other eye was performed. This helped stabilise the eyes, and resulted in complete visual recovery in both eyes.
Topics: Adult; Autografts; Conjunctiva; Humans; Male; Marfan Syndrome; Rupture, Spontaneous; Sclera; Scleral Diseases; Treatment Outcome; Visual Acuity
PubMed: 27199441
DOI: 10.1136/bcr-2016-214764 -
Scientific Reports Jul 2020Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and...
Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.
Topics: ADAMTS Proteins; Anthropometry; Bodily Secretions; Brachydactyly; Canada; Female; Fingers; HEK293 Cells; Humans; Male; Mutation, Missense; Phenotype; Weill-Marchesani Syndrome; Exome Sequencing
PubMed: 32616716
DOI: 10.1038/s41598-020-66978-8 -
American Journal of Human Genetics Nov 2004Weill-Marchesani syndrome (WMS) is characterized by the association of short stature; brachydactyly; joint stiffness; eye anomalies, including microspherophakia and...
Weill-Marchesani syndrome (WMS) is characterized by the association of short stature; brachydactyly; joint stiffness; eye anomalies, including microspherophakia and ectopia of the lenses; and, occasionally, heart defects. We have recently mapped a gene for the autosomal recessive form of WMS to chromosome 19p13.3-p13.2, in a 12.4-cM interval. Here, we report null mutations in a member of the extracellular matrix protease family, the gene encoding ADAMTS10, a disintegrin and metalloprotease with thrombospondin motifs. A total of three distinct mutations were identified in two consanguineous families and in one sporadic WMS case, including one nonsense mutation (R237X) and two splice mutations (1190+1G-->A and 810+1G-->A). ADAMTS10 expression studies using reverse-transcriptase polymerase chain reaction, northern blot, and dot-blot analyses showed that ADAMTS10 is expressed in skin, fetal chondrocytes, and fetal and adult heart. Moreover, electron microscopy and immunological studies of the skin fibroblasts from the patients confirmed impairment of the extracellular matrix. We conclude, therefore, that ADAMTS10 plays a major role in growth and in skin, lens, and heart development in humans.
Topics: ADAM Proteins; ADAMTS Proteins; Abnormalities, Multiple; Actins; Base Sequence; Blotting, Northern; Child; DNA Primers; Dwarfism; Extracellular Matrix Proteins; Eye Abnormalities; Fibroblasts; Gene Components; Gene Expression; Genes, Recessive; Humans; Immunoblotting; Metalloendopeptidases; Microscopy, Electron; Molecular Sequence Data; Mutation; Pedigree; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Syndrome
PubMed: 15368195
DOI: 10.1086/425231 -
Matrix Biology : Journal of the... Jan 2021Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular...
Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular fibers that centers and suspends the lens in the eye. LTBP-2 has been implicated previously in the development of extracellular microfibrils, although its exact role remains unclear. Here, we analyzed the three-dimensional structure of the ciliary zonule in wild type mice and used a knockout model to test the contribution of LTBP-2 to zonule structure and mechanical properties. In wild types, zonular fibers had diameters of 0.5-1.0 micrometers, with an outer layer of fibrillin-1-rich microfibrils and a core of fibrillin-2-rich microfibrils. LTBP-2 was present in both layers. The absence of LTBP-2 did not affect the number of fibers, their diameters, nor their coaxial organization. However, by two months of age, LTBP-2-depleted fibers began to rupture, and by six months, a fully penetrant ectopia lentis phenotype was present, as confirmed by in vivo imaging. To determine whether the seemingly normal fibers of young mice were compromised mechanically, we compared zonule stress/strain relationships of wild type and LTBP-2-deficient mice and developed a quasi-linear viscoelastic engineering model to analyze the resulting data. In the absence of LTBP-2, the ultimate tensile strength of the zonule was reduced by about 50%, and the viscoelastic behavior of the fibers was altered significantly. We developed a harmonic oscillator model to calculate the forces generated during saccadic eye movement. Model simulations suggested that mutant fibers are prone to failure during rapid rotation of the eyeball. Together, these data indicate that LTBP-2 is necessary for the strength and longevity of zonular fibers, but not necessarily for their formation.
Topics: Animals; Cilia; Ectopia Lentis; Eye; Fibroblasts; Humans; Latent TGF-beta Binding Proteins; Longevity; Mice; Mice, Knockout; Microfibrils; Ocular Physiological Phenomena; Saccades; Tensile Strength; Viscoelastic Substances
PubMed: 33039488
DOI: 10.1016/j.matbio.2020.10.002 -
American Journal of Ophthalmology Case... Dec 2022To report a case of congenital ciliary body cysts causing microspherophakia, ectopia lentis, and secondary angle closure glaucoma in an infant.
PURPOSE
To report a case of congenital ciliary body cysts causing microspherophakia, ectopia lentis, and secondary angle closure glaucoma in an infant.
OBSERVATIONS
A 16-month-old male was found to have bilateral ciliary body cysts associated with zonular laxity or absence causing microspherophakia and ectopia lentis as demonstrated on multimodal imaging. Additionally, the patient had secondary angle closure glaucoma which was likely multi-factorial related to both lens abnormalities and anterior displacement of the iris from the cysts themselves. The patient underwent lensectomy and cyst removal which resulted in intraocular pressure stabilization and visual rehabilitation.
CONCLUSIONS AND IMPORTANCE
Congenital ciliary body cysts are a rare cause of lens abnormalities and secondary angle closure glaucoma in children. Information regarding genetic underpinnings or systemic associations is limited.
PubMed: 36275188
DOI: 10.1016/j.ajoc.2022.101723 -
BMC Medical Genetics May 2018Microspherophakia is a rare autosomal recessive eye disorder characterized by small spherical lens. It may present as an isolated finding or in association with other...
BACKGROUND
Microspherophakia is a rare autosomal recessive eye disorder characterized by small spherical lens. It may present as an isolated finding or in association with other ocular and/or systemic disorders. This clinical and genetic heterogeneity requires the study of large genes (ADAMTSL4, FBN1, LTBP2, ADAMTSL-10 and ADAMTSL17). The purpose of the present study is to identify the genetic cause of this pathology in a consanguineous Spanish family.
METHODS
A clinical exome sequencing experiment was executed by the TruSight One® Sequencing Panel (TSO) from Illumina©. Sanger sequencing was used to validate the NGS results.
RESULTS
Only the insertion of an adenine in exon 36 of the LTBP2 gene (c.5439_5440insA) was associated with pathogenicity. This new mutation was validated by Sanger sequencing and segregation analysis was also performed. Haplotype analyses using the polymorphic markers D14S1025, D14S43 and D14S999 close to the LTBP2 gene indicated identity by descent in this family.
CONCLUSION
We describe the first case of a microspherophakia phenotype associated with a novel homozygous mutation in the LTBP2 gene in a consanguineous Caucasian family by means of NGS technology.
Topics: Adult; Consanguinity; Corneal Diseases; Ectopia Lentis; Exons; Female; Genetic Association Studies; Genetic Predisposition to Disease; Glaucoma; High-Throughput Nucleotide Sequencing; Humans; Iris; Latent TGF-beta Binding Proteins; Male; Mutagenesis, Insertional; Mutation; Pedigree; Point Mutation; Sequence Analysis, DNA; Spain; White People
PubMed: 29751740
DOI: 10.1186/s12881-018-0590-0 -
The British Journal of Ophthalmology Dec 2022To identify the mutation spectrum and genotype-phenotype correlations of () mutations in a Chinese cohort with congenital ectopia lentis (EL).
AIMS
To identify the mutation spectrum and genotype-phenotype correlations of () mutations in a Chinese cohort with congenital ectopia lentis (EL).
METHODS
Patients clinically suspected of congenital zonulopathy were screened using panel-based next-generation sequencing followed by multiplex ligation-dependent probe amplification. All the probands were subjected to thorough ocular examinations. Molecular and clinical data were integrated in pursuit of genotype-phenotype correlation.
RESULTS
A total of 131 probands of mutations from unrelated families were recruited. Around 65% of the probands were children younger than 9 years old. Overall, 110 distinct mutations were identified, including 39 novel ones. The most at-risk regions were exons 13, 2, 6, 15, 24 and 33 in descending order of mutation frequency. The most prevalent mutation was c.184C>T (seven, 5.34%) in the coding sequence and c.5788+5G>A (three, 2.29%) in introns. Missense mutations were the most frequent type (103, 78.63%); half of which were distributed in the N-terminal regions (53, 51.46%). The majority of missense mutations were detected in one of the calcium-binding epidermal growth factor-like domains (62, 60.19%), and 39 (62.90%) of them were substitutions of conserved cysteine residues. Microspherophakia (MSP) was found in 15 patients (11.45%). Mutations in the middle region (exons 22-42), especially exon 26, had higher risks of combined MSP (OR, 5.51 (95% CI 1.364 to 22.274), p=0.017).
CONCLUSIONS
This study extended the knowledge of the mutation spectrum and provided novel insights into its clinical correlation regarding EL and MSP in the Chinese population.
Topics: Humans; Ectopia Lentis; Fibrillin-1; Fibrillins; Marfan Syndrome; Microfilament Proteins; Phenotype; Mutation; Genotype; China; DNA Mutational Analysis
PubMed: 34281902
DOI: 10.1136/bjophthalmol-2021-319084