Congenital cataract associated with persistent fetal vasculature: findings from IoLunder2.

PurposeTo describe the frequency, characteristics, and treatment outcome of persistent fetal vasculature (PFV) in children undergoing surgery for congenital and infantile cataract in the first 2 years of life.Patients and methodsObservational population-based cohort study with case identification through active surveillance and standardised data collection via a national clinical network, the British Isles Congenital Cataract Interest Group (BCCIG).ResultsThe IoLunder2 cohort comprises 246 children undergoing surgery for bilateral and unilateral congenital and infantile cataract in the first 2 years of life. A total of 58/246 (24%) children had PFV (%): overall, 46/95 (46%) with unilateral cataract, and 12/141 (8%) with bilateral disease. Anterior segment vascular remnants were more common in bilateral than unilateral disease (75 vs 11%, P=0.01). At 1 year after surgery, 20% of children with bilateral PFV and 24% with unilateral had achieved normal vision for age within the operated eye. The prevalence of post-operative glaucoma was 9% (of children with bilateral disease) and 4% (unilateral).ConclusionPFV is significantly more common than previously reported, and outcomes are comparable to that for congenital and infantile cataract overall.

Long-term visual outcome after extraction of unilateral congenital cataracts.

BACKGROUND: Congenital cataract significantly impairs visual development. Although treatable, a good visual outcome is difficult to achieve, requiring prompt lensectomy and prolonged visual rehabilitation. PURPOSE: The aim of this study was to investigate whether useable visual acuity (VA) is a realistic goal in these patients. METHODS: A retrospective case review from a tertiary referral centre was performed. This study included children with unilateral congenital cataract who underwent cataract surgery with posterior capsulectomy and anterior vitrectomy. RESULTS: A total of 62 patients were identified. Of them, 32% of aphakic eyes had a final VA of 0.6 LogMAR or better (average 0.34+/-0.17). The average age at the time of surgery was 5.0+/-4.1 weeks. The remaining 68% had vision that was less than 0.6, with 27% having vision of <1.00. The group with vision less than 0.6 (68%) had an average age of 9.7+/-6.5 weeks at the time of surgery. One case (1.6%) achieved a VA of 0.0 and also had demonstrable stereoacuity (110 arc s). Manifest strabismus was present in 85% of cases. Glaucoma developed in 19% of patients and 31% discontinued the occlusion regime before the age of 4 years. In most of these cases, occlusion was ceased by the age of 2 years when testing revealed dense amblyopia in the aphakic eye even if good compliance had previously been achieved. In many cases, this coincided with the child becoming noncompliant with occlusion. CONCLUSIONS: More than two-thirds of children in our cohort did not develop acuity better than 0.6 LogMAR in their aphakic eye.

Cataract surgery and primary intraocular lens implantation in children < or = 2 years old in the UK and Ireland: finding of national surveys.

BACKGROUND: Current patterns of practice relating to primary intraocular lens (IOL) implantation in children < or =2 years old in the UK and Ireland are investigated. METHODS: National postal questionnaire surveys of consultant ophthalmologists in the UK and Ireland. RESULTS: 76% of 928 surveyed ophthalmologists replied. 47 (7%) of the respondents operated on children aged < or =2 with cataract. 41 (87%) of respondents performed primary IOL implantation, but 25% would not implant an IOL in a child under 1 year old. 88% of surgeons used limbal wounds, 80% manual capsulotomies, 98% posterior capsulotomies and 100% hydrophobic acrylic lenses. The SRK/T formula was most commonly used (70%). Exclusion criteria for primary IOL implantation varied considerably and included microphthalmos (64% of respondents), anterior and posterior segment anomalies (53%, 58%), and glaucoma (19%). DISCUSSION: Primary IOL implantation in children < or =2 has been widely adopted in the UK and Ireland. There is concordance of practice with regards to surgical technique and choice of IOL model. However, there is some variation in eligibility criteria for primary IOLs: this may reflect a lack of consensus on which children are most likely to benefit. Thus, there is a need for systematic studies of the outcomes of primary IOL implantation in younger children.

Review of cases presenting with microcephaly and bilateral congenital cataract in a paediatric cataract clinic.

PURPOSE: We reviewed all children presenting with microcephaly and bilateral congenital cataract in our paediatric cataract clinic, to identify their underlying diagnosis and clinical features that could help in early diagnosis of such conditions. METHODS: We screened our cataract database to collect data on all children presenting to our institute with cataract before 1 year of age for a period of 5 years (1997-2001) inclusive. We found 166 cases of cataract, of which 85 were bilateral. Of the 85 children with bilateral cataract, five also had microcephaly. The case notes of these five children were retrospectively reviewed for age at presentation, ocular and systemic examination findings, results of electro diagnostic testing, outcome of cataract surgery, and any additional investigation results. RESULTS: In our series, three children were diagnosed with early-onset Cockayne syndrome (CS2), one was diagnosed with Micro syndrome and one with Hallermann-Streiff syndrome. Electrodiagnostic testing was abnormal in four of the five cases, and growth failure was present in all five. There was a good outcome from surgery in the three children with CS2 and the child with Hallermann-Strieff. There was a poor outcome in the child with Micro syndrome. CONCLUSIONS: The presence of microcephaly in children presenting with bilateral cataracts in infancy is strongly suggestive of a syndromic cause. Early-onset Cockayne syndrome was the commonest underlying diagnosis in our series, but clinicians should be aware of other possibilities, and we discuss the differential diagnosis. Head circumference should be checked routinely in children with congenital cataract.

The achiasmia spectrum: congenitally reduced chiasmal decussation.

AIM: To describe the clinical spectrum of achiasmia, a congenital disorder of reduced relative decussation at the optic chiasm. METHODS: A retrospective case note and patient review of nine children (four boys). Achiasmia was defined by the combination of a characteristic asymmetry of the monocular visual evoked potential (VEP) response to flash and neuroimaging showing reduced chiasmal size. RESULTS: Three of the children had an associated skull base encephalocele with agenesis of the corpus callosum. In two patients achiasmia was associated with septo-optic dysplasia. Three patients had no neuroimaging abnormalities other than reduced chiasmal size and have no known pituitary dysfunction. One child had multiple physical deformities but the only brain imaging abnormality was reduced chiasmal size. CONCLUSIONS: Some children with disorders of midline central nervous system development, including septo-optic dysplasia and skull base encephaloceles, have congenitally reduced chiasmal decussation. Reduced relative decussation may co-exist with overall chiasmal hypoplasia. Children with an apparently isolated chiasmal decussation deficit may have other subtle neurological findings, but our clinical impression is that most of these children function well.

The telomere of human chromosome 1p contains at least two independent autosomal dominant congenital cataract genes.

AIMS: Multiple genetic causes of congenital cataract have been identified, both as a component of syndromes and in families that present with isolated congenital cataract. Linkage analysis was used to map the genetic locus in a six generation Australian family presenting with total congenital cataract. METHODS: Microsatellite markers located across all known autosomal dominant congenital cataract loci were genotyped in all recruited family members of the Tasmanian family. Both two point and multipoint linkage analysis were used to assess each locus under an autosomal dominant model. RESULTS: Significant linkage was detected at the telomere of the p arm of chromosome 1, with a maximum two point LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an estimated location score of 5.61 at marker D1S507. Haplotype analysis places the gene inside a critical region between D1S228 and D1S199, a distance of approximately 6 megabases. The candidate gene PAX7 residing within the critical interval was excluded by direct sequencing in affected individuals. CONCLUSION: This is the third report of congenital cataract linkage to 1ptel. The critical region as defined by the shared haplotype in this family is clearly centromeric from the Volkmann cataract locus identified through study of a Danish family, indicating that two genes causing autosomal dominant congenital cataract map to the telomeric region of chromosome 1p.

Management of intracorneal bleb after trabeculectomy for congenital glaucoma.

PURPOSE: Congenital glaucoma is a well-recognized entity that can occur in the presence of anterior segment dysgenesis. Trabeculectomy is an accepted intervention in the management of congenital glaucoma. The surgical technique as well as complications is well described. METHODS: This is a case report of a 3-month-old girl with anterior segment dysgenesis and glaucoma. She was referred post-trabeculectomy with persistent corneal opacity to be considered for penetrating keratoplasty and was found to have intrastromal corneal bleb. RESULTS: Ultrasound biomicroscopy confirmed communication of the corneal bleb with the anterior chamber, and the bleb was treated by autologous blood injection at the trabeculectomy site, under acetazolamide cover. CONCLUSIONS: We present evidence suggesting that abnormal structure was the etiologic basis for corneal bleb formation and describe our management of this previously unreported complication of trabeculectomy.

Is early surgery for congenital cataract a risk factor for glaucoma?

AIMS: To estimate the risk of aphakic glaucoma after lensectomy for congenital cataract and its association with surgery within the first month of life. METHOD: A retrospective case notes review was conducted of all patients who had lensectomy for congenital cataract during their first year of life at Great Ormond Street Hospital between 1994 and 1997. Patients with pre-existing glaucoma, anterior segment dysgenesis, and Lowe syndrome were excluded. The risk of aphakic glaucoma after surgery was estimated using Kaplan-Meier survival analysis. RESULTS: 80 patients, undergoing 128 lensectomies were eligible. Of these, six patients (nine eyes) were lost to follow up. Based on eye count, the risk of glaucoma by 5 years after lensectomy was 15.6% (95% CI 10.2 to 23.4). Based on patient count, the 5 year risk of glaucoma in at least one eye following bilateral surgery was 25.1% (95% CI 15.1 to 40.0). The incidence of glaucoma remained at a constant level for the first 5 years after surgery. After early bilateral lensectomy, within the first month of life, the 5 year risk of glaucoma in at least one eye was 50% (95% CI 27.8 to 77.1) compared to 14.9% (95% CI 6.5 to 32.1) with surgery performed later (log rank test, p = 0.012). There was no significant difference (Kolmogorov-Smirnov test: unilateral lensectomy p = 0.587, bilateral lensectomy p = 0.369) in 5 year visual outcomes between eyes operated before and after 1 month of age. CONCLUSION: Bilateral lensectomy during the first month of life is associated with a higher risk of subsequent glaucoma than with surgery performed later. The reason for this is unclear but it may be prudent, in bilateral cases, to consider delaying surgery until the infant is 4 weeks old. As the incidence of glaucoma is similar for each year after surgery, long term glaucoma surveillance is mandatory.

Early proximal tubular dysfunction in Lowe's syndrome.

The early diagnosis of Lowe's syndrome can be difficult. Urinary excretion of retinol binding protein (RBP) and the lysosomal enzyme N-acetyl-glucosaminidase (NAG) were significantly increased in boys with Lowe's syndrome. Measurement of these urine parameters is recommended in suspected cases.

Investigation of crystallin genes in familial cataract, and report of two disease associated mutations.

AIMS: Mutations of seven crystallin genes have been shown to cause familial cataract. The authors aimed to identify disease causing crystallin mutations in paediatric cataract families from south eastern Australia. METHODS: 38 families with autosomal dominant or recessive paediatric cataract were examined. Three large families were studied by linkage analysis. Candidate genes at regions providing significant LOD scores were sequenced. Single stranded conformational polymorphism (SSCP) analysis was used to screen five crystallin genes in the probands, followed by direct sequencing of observed electrophoretic shifts. Mutations predicted to affect the coding sequence were subsequently investigated in the entire pedigree. RESULTS: A LOD score of 3.72 was obtained at the gamma-crystallin locus in one pedigree. Sequencing revealed a P23T mutation of CRYGD, found to segregate with disease. A splice site mutation at the first base of intron 3 of the CRYBA1/A3 gene segregating with disease was identified by SSCP in another large family. Five polymorphisms were also detected. CONCLUSIONS: Although mutations in the five crystallin genes comprehensively screened in this study account for 38% of paediatric cataract mutations in the literature, only two causative mutations were detected in 38 pedigrees, suggesting that crystallin mutations are a relatively rare cause of the cataract phenotype in this population.

Cataract in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD).

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare metabolic disorder that can lead to acute encephalopathy, liver disease, cardiomyopathy, rhabdomyolysis, and long-term complications involving the eye and peripheral nerves. LCHADD is a peroxisome biogenesis disorder (PBD). Except for the series presented by Tyni and colleagues (Ophthalmology 1998;105:810-824), which described visually insignificant lens opacities in association with LCHADD, previous ophthalmic papers have only reported retinal complications. We report on one case with progressive asymmetrical cataract. The more mildly affected eye had a similar morphology to that previously reported and the more severely affected eye had an unusual morphology we believe is unique to LCHADD. We discuss the range of ophthalmic presentations in our cases and in the literature. The variability of the severity of ocular complications, even between eyes in one individual, makes it difficult to test the effectiveness of therapeutic options upon the ophthalmic complications.

Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus.

PURPOSE: To determine a gene locus for a family with a dominantly inherited vestibulocerebellar disorder characterised by early onset, but not congenital nystagmus. DESIGN: Observational and experimental study. METHODS: We carried out a phenotypic study of a unique four generation family with nystagmus. We performed genetic linkage studies including a genome wide search. RESULTS: Affected family members developed vestibulocerebellar type nystagmus in the first two years of life. A higher incidence of strabismus was noted in affected members. Haplotype construction and analysis of recombination events linked the disorder to a locus (NYS4) on chromosome 13q31-q33 with a lod score of 6.322 at theta=0 for D13S159 and narrowed the region to a 13.8 cM region between markers D13S1300 and D13S158. CONCLUSIONS: This study suggests that the early onset acquired nystagmus seen in this family is caused by a single gene defect. Identification of the gene may hold the key to understanding pathways for early eye stabilisation and strabismus.

Aetiology of congenital and paediatric cataract in an Australian population.

BACKGROUND/AIM: Paediatric cataract is a major cause of childhood blindness. Several genes associated with congenital and paediatric cataracts have been identified. The aim was to determine the incidence of cataract in a population, the proportion of hereditary cataracts, the mode of inheritance, and the clinical presentation. METHODS: The Royal Children's Hospital and the Royal Victorian Eye and Ear Hospital have a referral base for almost all paediatric patients with cataracts in south eastern Australia. The database contains cases seen over the past 25 years. The medical histories of these patients were reviewed. RESULTS: 421 patients with paediatric cataract were identified, which gives an estimated incidence of 2.2 per 10,000 births. Of the 342 affected individuals with a negative family history, 50% were diagnosed during the first year of life, and 56/342 (16%) were associated with a recognised systemic disease or syndrome. Unilateral cataract was identified in 178/342 (52%) of sporadic cases. 79 children (from 54 nuclear families) had a positive family history. Of these 54 families, 45 were recruited for clinical examination and DNA collection. Ten nuclear families were subsequently found to be related, resulting in four larger pedigrees. Thus, 39 families have been studied. The mode of inheritance was autosomal dominant in 30 families, X linked in four, autosomal recessive in two, and uncertain in three. In total, 178 affected family members were examined; of these 8% presented with unilateral cataracts and 43% were diagnosed within the first year of life. CONCLUSIONS: In the paediatric cataract population examined, approximately half of the patients were diagnosed in the first year of life. More than 18% had a positive family history of cataracts. Of patients with hereditary cataracts 8% presented with unilateral involvement. Identification of the genes that cause paediatric and congenital cataract should help clarify the aetiology of some sporadic and unilateral cataracts.

Hermansky-Pudlak syndrome: infrequent bleeding and first report of Turkish and Pakistani kindreds.

Hermansky-Pudlak syndrome (HPS) is a rare disorder characterised by oculocutaneous albinism, a bleeding tendency, and lipofuscinosis. This retrospective study reviews the clinical history and haematological features of 23 cases of HPS. Information was gathered from patient notes and by direct interview. Thirteen of the 23 children were of Turkish origin, 12 being members of four kindreds from the Turkish/Kurdish border. Four children originated from Pakistan. Haemorrhage was uncommon; two experienced significant bleeding (intracranial and retinal haemorrhage in one and menorrhagia in another), and twelve minor symptoms. Results of laboratory evaluation of platelet function were not predictive of bleeding; in particular the PFA-100 analyser was not sensitive to the HPS defect. The most sensitive test of platelet fuction was quantitation of platelet nucleotides. The occurrence of Turkish and Pakistani kindreds with HPS is novel and follow up for long term complications described in Puerto Rican patients as well as genetic analysis is ongoing.

Albinism.

Albinism is a heterogeneous group of conditions having in common a hereditary error of melanin metabolism resulting in misrouting of optic nerve fibers during embryogenesis, underdevelopment of the neuroretinas, and in varying degrees of hypopigmentation of eyes, skin, and hair.

Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder involving hearing loss, branchial defects, ear pits and renal abnormalities. Oto-facio-cervical (OFC) syndrome is clinically similar to BOR syndrome, with clinical features in addition to those of BOR syndrome. Mutations in the EYA1 gene (localised to 8q13.3) account for nearly 70% of BOR syndrome cases exhibiting at least three of the major features. Small intragenic deletions of the 3' region of the gene have also been reported in patients with BOR syndrome. We have developed a fluorescent quantitative multiplex polymerase chain reaction for three 3' exons (7, 9 and 13) of the EYA1 gene. This dosage assay, combined with microsatellite marker analysis, has identified de novo deletions of the EYA1 gene and surrounding region in two patients with complex phenotypes involving features of BOR syndrome. One patient with OFC syndrome carried a large deletion of the EYA1 gene region, confirming that OFC syndrome is allelic with BOR syndrome. Microsatellite analysis has shown that comparison of the boundaries of this large deletion with other reported rearrangements of the region reduces the critical region for Duane syndrome (an eye movement disorder) to between markers D8S553 and D8S1797, a genetic distance of approximately 1 cM.

Outcome of lens aspiration and intraocular lens implantation in children aged 5 years and under.

AIMS: To determine the visual outcome and complications of lens aspiration with intraocular lens implantation in children aged 5 years and under. METHODS: The hospital notes of all children aged 5 years and under, who had undergone lens aspiration with intraocular lens implantation between January 1994 and September 1998, and for whom follow up data of at least 1 year were available, were reviewed. RESULTS: Of 50 children who underwent surgery, 45 were eligible based on the follow up criteria. 34 children had bilateral cataracts and, of these, 30 had surgery on both eyes. Cataract was unilateral in 11 cases; thus, 75 eyes of 45 children had surgery. Cataracts were congenital in 28 cases, juvenile in 16, and traumatic in one case. The median age at surgery was 39 months (range 11-70 months). Follow up ranged from 12-64 months (median 36 months). Of 34 children with bilateral disease, 25 (73.5%) had a final best corrected visual acuity of 6/12 or better, while seven (20.5%) achieved 6/18 or less; in one child the vision improved from UCUSUM to CSM but another, who had only one eye operated on, was unable to fix or follow with this eye preoperatively or 2 years postoperatively. Of 11 children with unilateral cataract, five (45.5%) had a final best corrected visual of 6/12 or better, and six (54.5%) 6/18 or less. A mild fibrinous uveitis occurred in 20 (28.2%) eyes in the immediate postoperative period, but resolved with topical steroids. One child had a vitreous wick postoperatively requiring surgical division. Glaucoma, endophthalmitis, or retinal detachment have not been observed so far in any patient postoperatively. CONCLUSION: From this series the authors suggest that, in children aged 5 years and under, lens aspiration with intraocular lens implantation is a safe procedure, with a good visual outcome in the short term. Further studies are needed to investigate these outcomes in the long term.