ABSTRACT
Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK 'state of play' in the management of paediatric cataracts.
Subject(s)
Cataract Extraction , Cataract , Ophthalmology , Cataract/therapy , Child , Humans , United Kingdom/epidemiology , Vision Disorders/therapyABSTRACT
BACKGROUND: Pathogenic variants in the BCOR gene have been identified in males with X-linked recessive microphthalmia and in females with X-linked dominant oculofaciocardiodental (OFCD) syndrome. This latter condition has previously been regarded as rare but the increased availability of genetic testing in recent years has led to the identification of a greater number of patients. METHODS: We report the clinical and molecular findings in a series of 10 patients with pathogenic BCOR variants from 5 families, all seen in a single institution over a two year period. RESULTS: We emphasize the phenotypic variability in this cohort and the diverse genetic mechanisms involved which included point mutations and deletions of BCOR as well as the occurrence of gonadal and somatic mosaicism. CONCLUSION: In this report we demonstrate the novel findings of four newly identified variants in BCOR associated with an OFCD phenotype, and suggest that the frequency of this condition in females presenting with congenital cataract, including unilateral cataract, is more common than anticipated. We demonstrate the utility of screening for genetic causes of congenital cataract. Although gonadal mosaicism in OFCD had previously been reported, we demonstrate the presence of somatic mosaicism where BCOR mutations may only be detected in DNA from tissues other than blood such as buccal cells.
Subject(s)
Cataract/congenital , Cataract/diagnosis , Cataract/genetics , Heart Septal Defects/diagnosis , Heart Septal Defects/genetics , Microphthalmos/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/physiopathology , Cohort Studies , Databases, Genetic , Female , Genes, X-Linked , Humans , Infant , Infant, Newborn , Microphthalmos/diagnosis , Mosaicism , Oligonucleotide Array Sequence Analysis , Pedigree , Phenotype , Point Mutation , Rare Diseases/genetics , Sequence Analysis, DNA , Sequence DeletionABSTRACT
PurposeIn addition to environmental causes such as TORCH infection, trauma and drug or chemical exposure, childhood cataracts (CC) frequently have a genetic basis. They may be isolated or syndromic and have been associated with mutations in over 110 genes. We have recently demonstrated that next-generation sequencing (NGS), a high throughput sequencing technique that enables the parallel sequencing of multiple genes, is ideally suited to the investigation of bilateral CC. This study assesses the diagnostic outcomes of traditional routine investigations and compares this with outcomes of NGS testing.MethodsA retrospective review of the medical records of 27 consecutive patients with bilateral CC presenting in 2010-2012 was undertaken. The outcomes of routine investigations in these patients, including TORCH screen, urinalysis, karyotyping, and urinary and plasma organic amino acids, were collated. The success of routine genetic investigations undertaken over 10 years (2000-2010) was also assessed.ResultsBy April 2014, the underlying cause of bilateral CC had been identified in just one of 27 patients despite 44% (n=12) receiving a full 'standard' investigative work-up and 22% (n=6) investigations in addition to the standard work-up. Fifteen of these patients underwent NGS testing and nine (60%) of these received a diagnosis for their CC.ConclusionThe frequency of patients receiving a diagnosis for their CC after standard care and the time taken to diagnosis was disappointing. NGS testing improved diagnostic rates and time to diagnosis, as well as changing clinical management. These data serve as a baseline for future evaluation of novel diagnostic modalities.
Subject(s)
Cataract/diagnosis , Cataract/genetics , Eye Proteins/genetics , High-Throughput Nucleotide Sequencing , Mutation , Cataract/congenital , Child , Child, Preschool , DNA Mutational Analysis , Female , Genetic Testing , Humans , Infant , Infant, Newborn , Karyotype , Male , Retrospective StudiesABSTRACT
We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX) mutations, a rare cause of Kabuki syndrome (KS2, MIM 300867) and report, for the first time, germ-line missense and splice-site mutations in the gene. We demonstrate that less than 5% cases of Kabuki syndrome are due to KDM6A mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by KMT2D (previously called MLL2) mutations, KS2 patients are characterized by hypotonia and feeding difficulties during infancy and poor postnatal growth and short stature. Unlike KS1, developmental delay and learning disability are generally moderate-severe in boys but mild-moderate in girls with KS2. Some girls may have a normal developmental profile. Speech and cognition tend to be more severely affected than motor development. Increased susceptibility to infections, join laxity, heart, dental and ophthalmological anomalies are common. Hypoglycaemia is more common in KS2 than in KS1. Facial dysmorphism with KDM6A mutations is variable and diagnosis on facial gestalt alone may be difficult in some patients. Hypertrichosis, long halluces and large central incisors may be useful clues to an underlying KDM6A mutation in some patients.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Face/abnormalities , Genes, X-Linked , Hematologic Diseases/diagnosis , Hematologic Diseases/genetics , Histone Demethylases/genetics , Mutation , Nuclear Proteins/genetics , Vestibular Diseases/diagnosis , Vestibular Diseases/genetics , Amino Acid Substitution , Child , Child, Preschool , Exons , Facies , Female , Gene Order , Genetic Association Studies , Humans , Male , Mutation Rate , Phenotype , Reproducibility of Results , Sequence Analysis, DNAABSTRACT
PURPOSE: To describe the anterior segment optical coherence tomography (AS-OCT) characteristics of patients with ocular manifestations of mucopolysaccharidoses type I (Hurler), II (Hunter), and VI (Maroteaux-Lamy). METHODS: Prospective, observational study of nine consecutive patients with variants of mucopolysaccharidosis (MPS) attending the Paediatric Ophthalmology service at Manchester Royal Eye Hospital, UK. All patients underwent Visante AS-OCT imaging as part of their ophthalmic assessment. RESULTS: Ocular involvement tended to be symmetrical. Angle-to-angle distance was significantly lower in MPS VI than in MPS I (P=0.04). Anterior chamber depth, angle opening distance, trabecular-iris space area, and scleral spur angle tended to be lower in MPS VI than in MPS I, but did not reach statistical significance. Corneal thickness in the central 0-2 mm zone was greater in MPS VI than in MPS I, approaching but not attaining statistical significance (P=0.07). The 2-5 and 5-7 mm zones were significantly thicker in MPS VI than MPS I (P=0.04, P=0.04). There was no difference in corneal thickness between MPS I and MPS VI in the peripheral 7-10 mm zone (P=0.57). Measurements of the patient with MPS II resembled the mean values of the MPS I group. CONCLUSION: AS-OCT is valuable in quantifying anterior segment pathology in MPS. It suggests more crowded anterior segments and greater corneal thickness in patients with MPS VI than MPS I. AS-OCT is useful in evaluating the risk and mechanism of glaucoma in MPS patients, and may improve our assessment of the efficacy of systemic treatment.
Subject(s)
Anterior Eye Segment/pathology , Mucopolysaccharidosis II/diagnosis , Mucopolysaccharidosis I/diagnosis , Mucopolysaccharidosis VI/diagnosis , Tomography, Optical Coherence , Adolescent , Child , Child, Preschool , Corneal Pachymetry , Female , Humans , Male , Prospective StudiesABSTRACT
PURPOSE: To explore the role of intralesional steroid injections (ILSI) and oral steroids in the management of periocular hemangioma of infancy (HOI). METHODS: In this retrospective study, treatment options studied were observation, ILSI, and oral steroids. All children received adjunctive amblyopia treatment if required. The main indications for treatment were cosmetic, worsening astigmatism, and visual axis obscuration. Success was defined as complete HOI regression before the age of 5 years (cosmetic group), reduction of astigmatism of at least 1 diopter cylinder (DC) (astigmatism group), or no evidence of amblyopia at the last follow-up (visual axis obscuration group). RESULTS: Twenty-four of 41 children (58.5%) had amblyopia at presentation. Eighteen children formed the observation group, 17 children received ILSI, and 6 children received oral steroids. Successful outcome was achieved in all except 2 patients in the cosmetic group and 6 of 7 in the visual axis obscuration group. Mean astigmatic correction of all cases was 1.65 ± 1.34 DC before treatment and 0.91 ± 1.17 DC after treatment, the change being statistically significant (P < .001). CONCLUSION: Observation appears to be a highly effective strategy if coupled with amblyopia therapy, especially for mild cases. Intralesional and oral steroids appear to be equally effective for lesions requiring treatment, but their exact role cannot be clearly determined in the presence of a spontaneously resolving lesion.
Subject(s)
Amblyopia , Hemangioma, Capillary , Amblyopia/therapy , Astigmatism , Hemangioma, Capillary/drug therapy , Humans , Injections, Intralesional , Retrospective StudiesSubject(s)
Glaucoma/diagnosis , Intraocular Pressure , Tonometry, Ocular/methods , Child , Child, Preschool , Female , Humans , Male , Surveys and Questionnaires , United KingdomABSTRACT
AIM: Neurofibromatosis type I (NFI) is a phakomatosis that affects approximately 1 per 3000 live births. About 15% children with NFI develop optic pathway glioma (OPG). The Neurofibromatosis UK society recommend annual ophthalmic screening to identify those children who may have OPG affecting vision and refer for investigation and treatment as necessary. METHODS: We undertook a retrospective audit with three aims: (1) to elicit if departmental screening practice of children with NFI for OPG meets current guidelines, (2) to document the age at which tests of visual function are useful in the diagnosis and screening of OPG, and (3) to document the contribution eye screening has made to the diagnosis of OPG. RESULTS: A total of 37 children were identified from the clinic register. Overall 43% children met the criterion for an appropriate number of screening episodes. All the children met the visual acuity and optic disc assessment criteria; 84% met the pupil-testing criterion. No child was mature enough to perform visual fields or colour vision testing. CONCLUSION: Further education is required to encourage patients to attend eye clinic for screening as the majority of patients failing to reach the standard were due to non-attendances. No OPGs were detected during 128 screening episodes over approximately 7 years of screening. The authors question the usefulness of including visual field and colour vision assessment in the protocol for this age group.
Subject(s)
Diagnostic Techniques, Ophthalmological , Neurofibromatosis 1/diagnosis , Optic Nerve Glioma/diagnosis , Child , Child, Preschool , Clinical Audit , Female , Humans , Infant , Male , Neurofibromatosis 1/complications , Optic Nerve Glioma/etiology , Retrospective Studies , Vision Screening/methods , Visual Acuity , Visual Pathways/pathologySubject(s)
Eyelid Neoplasms/drug therapy , Glucocorticoids/therapeutic use , Hemangioma/drug therapy , Neurocutaneous Syndromes/drug therapy , Prednisolone/therapeutic use , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/drug therapy , Eyelid Neoplasms/diagnosis , Female , Hemangioma/diagnosis , Humans , Infant , Magnetic Resonance Imaging , Neurocutaneous Syndromes/diagnosisSubject(s)
Chromosomes, Human, Pair 17 , Retina/pathology , Retinal Drusen/genetics , Ring Chromosomes , Adult , Humans , Male , Retinal Drusen/pathologyABSTRACT
Congenital and infantile cataracts produce deprivation amblyopia and can thus cause lifelong visual impairment. Successful management is dependent on early diagnosis and referral for surgery when indicated. Accurate optical rehabilitation and postoperative supervision are essential.The timing of surgery and its relationship to the duration of deprivation is important. Unilateral congenital cataract surgery within 6 weeks of birth produces the best outcomes. The equivalent 'latent' period for bilateral visual deprivation may be longer at around 10 weeks. Visual deprivation has a significant impact on the development of fixation stability. Major form deprivation, even after early surgery, leads to nystagmus. This is mostly manifest latent nystagmus (MLN). The latent period for fixation stability may be as short as 3 weeks. Preoperative congenital nystagmus (CN) can convert to more benign MLN after surgery. Infantile IOL implantation is becoming increasingly accepted. A satisfactory long-term refractive result requires that allowance be made for childhood axial growth and myopic shift. In a series of 25 infants (33 eyes) implanted before 12 months of age, the mean myopic shift at 12 months was 4.83 D. This increased to 5.3 D in infants implanted before 10 weeks. The initial desired refractive outcome following IOL implantation is thus hypermetropia, with the degree dependent on the age of the child. Glaucoma or ocular hypertension is a common complication following paediatric cataract surgery. Microphthalmia and surgery in early infancy are risk factors. Tonometry results may be influenced by the increased corneal thickness seen in aphakic and pseudophakic children. The long-term prognosis of eyes with aphakic glaucoma is not necessarily poor but intraocular pressure control may require three or more medications. Surgical intervention appears to be necessary in over a quarter of eyes. Posterior capsule opacification (PCO) is common in infants undergoing primary lens implantation. Primary capsulotomy and anterior vitrectomy reduce the risk of PCO. In the absence of anterior vitrectomy, primary posterior capsulotomy does not prevent visual axis opacification. Further developments will continue to be driven by clinical research. The prevention of capsule opacification and cellular proliferation may in future be achieved by the use of devices to specifically target epithelial cells at surgery.
Subject(s)
Cataract Extraction/methods , Cataract/congenital , Cataract/complications , Amblyopia/etiology , Cataract Extraction/adverse effects , Glaucoma/etiology , Humans , Infant , Infant, Newborn , Lens Implantation, Intraocular/methods , Nystagmus, Pathologic/etiology , Time Factors , Vision Disorders/etiologyABSTRACT
BACKGROUND: Intraocular lens (IOL) implantation is becoming increasingly accepted as a primary procedure in infants. AIM: To evaluate the accuracy of IOL power calculation, the rate of myopic shift and the refractive outcome after primary IOL implantation in infants aged <12 months at the time of cataract surgery. METHOD: A retrospective case review of 25 patients (8 with bilateral cataracts and 17 with unilateral cataracts) who underwent cataract surgery with primary IOL implantation at <12 months of age. Outcomes measured were actual early postoperative refraction, lens power calculation error, myopic shift and refractive outcome. RESULTS: In 83% of cases, actual postoperative refraction was within 2 dioptres (D) of the target refraction. Lens power calculation error did not depend on axial length, age at surgery or target refraction. Mean (SD) myopic shift was 5.43 (3.7) D in the first 12 months after surgery, but was significantly greater when surgery was performed at <10 weeks of age. CONCLUSION: This study demonstrates that IOL power can be calculated with reasonable accuracy in infants using current formulas. Factors such as age at the time of surgery, axial length, whether surgery is unilateral or bilateral, and the presence of systemic pathologies do not seem to influence the accuracy of lens power calculation or myopic shift up to 36 months of age.
Subject(s)
Cataract/physiopathology , Lens Implantation, Intraocular/standards , Lenses, Intraocular/standards , Refraction, Ocular/physiology , Age Factors , Cataract Extraction , Female , Humans , Infant , Infant, Newborn , Male , Myopia/etiology , Myopia/physiopathology , Refractive Errors/etiology , Refractive Errors/physiopathology , Retrospective StudiesABSTRACT
PURPOSE: To introduce and describe two methods of grading the severity of infantile cataracts, and thereby propose a useful clinical guide for early surgical intervention. METHODS: Thirty-three subjects, aged 1 week to 8 years, participated in the study. Twenty-two were evaluated soon after birth (1 week), and 11 in childhood (3-8 years). All had isolated infantile cataracts, of which 16 were bilateral and 17 unilateral. Nine cataract types were examined; nuclear (n = 9), lamellar (n = 9), posterior lenticonus (n = 4), persistent hyperplastic primary vitreous (n = 4), posterior polar (n = 3) and single cases of total, cortical, sutural and anterior polar. Grading the infantile cataracts was performed subjectively based on the cataract morphology, density and position using an 11-point (0-10) ordinal scale. Objective measures of the cataracts were performed by scanning and then digitising photo-slit lamp images to provide cataract intensity profiles. Subjects without cataracts acted as controls. RESULTS: Subjective gradings of 0 and 10 were assigned to the clear, cataract-free lens and the total cataract, respectively. Fixed grades of 1 (anterior polar, sutural) and 6 (posterior polar) were assigned to the three remaining cataracts with static morphologies. The five cataracts which were all progressive were given grading ranges, reflecting the initial and likely final morphological states. Objective measures were found to be valuable in indicating the exact position and relative density of the cataract, as well as accurately defining boundaries. CONCLUSIONS: The magnitude and severity of infantile cataracts can be usefully characterised by an 11-point ordinal subjective grading scale. Although subjective grading alone is satisfactory, it can be greatly assisted by objective measures, particularly in the documentation of cataract progression. Cataracts assigned grades 1-4 were considered minor obstructions to vision and therefore not candidates for early surgery. Cataracts graded 5 and above were considered major visual defects, and ideally should be removed early in life.
Subject(s)
Cataract/pathology , Child , Child, Preschool , Female , Humans , Image Processing, Computer-Assisted/methods , Infant , Infant, Newborn , Lens, Crystalline/pathology , Male , Ophthalmoscopy/methods , Photography/methods , Severity of Illness IndexABSTRACT
AIMS: The mucopolysaccharidoses (MPS) are a heterogeneous group of rare disorders characterised by accumulation of glycosaminoglycans within multiple organ systems. This study aimed to determine the prevalence and severity of ocular complications in patients with MPS. METHODS: Clinical ophthalmic features and electrodiagnostic results of 50 patients with a diagnosis of MPS were retrospectively reviewed. RESULTS: A total of 79% of MPS IH patients had a visual acuity of less than 6/12 equivalent in their better eye, compared to 44% of MPS IH/S and 25% of MPS VI patients. In total, 16% of MPS IH and 25% of MPS IH/S had severe corneal opacification, compared to 38% of MPS VI patients. 16% of MPS IH patients had optic atrophy; 21% of MPS VI patients had mild disc swelling, 29% had markedly swollen discs, and 14% had optic atrophy. One patient with MPS IH, one with MPS IH/S and six with MPS VI had ocular hypertension. One MPS VI patient had glaucoma that required topical therapy. Nine patients with MPS IH had electrodiagnostic evidence of retinopathy, as did one MPS VI patient. CONCLUSIONS: Ocular complications causing significant reduction in vision are common in MPS. The majority of MPS I and MPS VI patients have corneal opacification, which can lead to difficulties in diagnosis and monitoring of glaucoma, optic disc changes, and retinopathy.
Subject(s)
Eye Diseases/etiology , Mucopolysaccharidoses/complications , Adolescent , Adult , Child , Child, Preschool , Corneal Opacity/etiology , Female , Follow-Up Studies , Humans , Infant , Male , Mucopolysaccharidosis I/complications , Mucopolysaccharidosis VI/complications , Ocular Hypertension/etiology , Optic Atrophy/etiology , Papilledema/etiology , Retrospective Studies , Vision Disorders/etiology , Visual AcuityABSTRACT
AIM: To report outcomes and identify factors affecting surgical response for constant esotropia using 'hang-back' bimedial rectus recession. STUDY TYPE: Retrospective case series analysis. METHODS: Patients managed by a single surgeon over a 4-year study period were categorized into esotropia types: infantile, partially accommodative, nonaccommodative and secondary esotropia. Postoperative alignment was compared between types, and regression modelling used to examine factors predicting surgical response. RESULTS: In all, 95% (18/19) of children with partially accommodative esotropia achieved postoperative deviation <15 prism dioptres from orthotropia, compared to 56% (15/27) of children with infantile esotropia, 69% (11/16) of children with non-accommodative esotropia and all (2/2) of those with secondary esotropia. Surgical response (Delta/mm recession performed) increased with the magnitude of both preoperative deviation (P<0.001) and anisometropia (P<0.001); the effect of deviation on surgical response was reduced by amblyopia (P=0.02). Age at surgery was statistically associated (P=0.002) but had negligible clinical effect on response. CONCLUSIONS: Surgical response to hang-back recession may be partially predicted by preoperative factors.
Subject(s)
Esotropia/surgery , Oculomotor Muscles/surgery , Accommodation, Ocular , Age Factors , Age of Onset , Amblyopia/complications , Anisometropia/complications , Child, Preschool , Esotropia/complications , Humans , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
A three-generation family presenting with ocular developmental abnormalities, including anterior segment dysgenesis and coloboma, associated with brachydactyly and clinodactyly is presented. Several conditions incorporating ocular and bony limb abnormalities have been described. However, we believe that this family manifests a previously undescribed syndrome due to autosomal dominant or possibly x-linked inheritance with variable expression.