Prevalence of CYP1B1 mutations in Australian patients with primary congenital glaucoma.

Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified.

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.

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.

Visual improvement despite radiologically stable disease after treatment with carboplatin in children with progressive low-grade optic/thalamic gliomas.

BACKGROUND: The purpose of this study was to examine the clinical and radiologic response to carboplatin by children with progressive optic/thalamic gliomas. PATIENTS AND METHODS: Between July 1997 and July 1999, 12 consecutive children were treated with monthly carboplatin for progressive optic/thalamic gliomas. RESULTS: Five children have completed 12 cycles of carboplatin and five children are currently receiving treatment. Two children had progressive disease noted both clinically and radiologically. Nine children have stable radiologic disease and one child has had a partial radiologic response to chemotherapy. Eight children have had regular visual assessments. Four children (three with stable radiology and one with a partial radiologic response) have had improvement in their vision. Three children with radiologically stable disease have had no change in vision. One child has had deterioration in vision despite radiologically stable disease. CONCLUSIONS: The results suggest that the clinical response of optic/thalamic gliomas to carboplatin, as measured by visual acuity and visual fields, may be better than predicted by radiologic assessment. These data suggest that a prospective clinical study is warranted of the role of carboplatin in children with progressive optic/thalamic gliomas and visual impairment.

Tension pneumo-orbitus and pneumocephalus induced by a nasal oxygen cannula: report on two paediatric cases.

The present paper highlights the potential dangers of misplaced nasopharyngeal oxygen cannulae causing secondary pneumo-orbitus and pneumocephalus in two paediatric patients. While this complication is uncommon, early recognition allows prompt and appropriate intervention, with cessation of nasal oxygen, cannula removal, early investigation with computed tomography (CT) head/orbit scan and orbital or cranial decompression, if required. Early CT imaging identifies medial orbital or paranasal sinus fractures, the presence of sinusitis, associated intracranial air and assessment of the degree of orbital or intracranial tension. Antibiotics are not usually required for this type of clean injury unless pre-existing sinusitis is identified. In both cases, direct orbital decompression was performed with excellent results after identification of marked unilateral tense exophthalmos, delayed pupillary reactions to light and ophthalmopegia.

Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A.

A 16-year-old male developed night blindness 2 weeks after starting isotretinoin at a dose of 20 mg per day for cystic acne. He also had cystic fibrosis, complicated by hepatic cirrhosis. Despite long-term oral vitamin A supplementation, serum vitamin A levels were found to be 0.3 mumol/L (normal range 0.9-2.5 mumol/L). Oral vitamin A replacement was instituted with resolution of his visual symptoms in 6 months. Isotretinoin therapy was successfully continued with no deterioration in liver function. Isotretinoin has been reported to cause deterioration in night vision. In vitro evidence suggests isotretinoin may interfere with the processing of endogenous vitamin A in the retina. This case highlights the need for careful monitoring of serum vitamin A status in patients with malabsorptive states on isotretinoin therapy.

Adjunctive intra-operative local anaesthesia in paediatric strabismus surgery: a randomized controlled trial.

PURPOSE: The aim of the present study was to test the hypothesis that adjunctive local anaesthesia decreases postoperative pain, vomiting or length of stay in children having strabismus repair METHOD: A prospective, randomized, triple-armed clinical trial involving a treatment comparison between topical amethocaine, sub-conjunctival bupivacaine and, as a placebo, topical normal saline was performed. All treatments were given at the end of surgery before emergence from the anaesthetic. RESULTS: Overall, there was no statistically significant difference between outcome measures in the three trial groups. Using post hoc analysis there was a statistically significant difference between the groups receiving amethocaine and bupivacaine compared with the saline group in terms of the pain score at 120 min postoperatively. This difference has little clinical significance. CONCLUSIONS: Neither topical amethocaine nor subconjunctival bupivacaine makes a clinically significant difference to postoperative pain, emesis or length of stay. Moderate dose paracetamol per rectum alone appears to be effective analgesia for strabismus surgery, although it probably masked any small adjunctive effect of the topical anaesthesia used in the present trial.

Persistent infra-orbital nerve hyperaesthesia after blunt orbital trauma.

BACKGROUND: Hyperaesthesia involving the infra-orbital nerve is rarely associated with orbital floor fracture. METHODS: An 11-year-old boy and a 34-year-old man had persistent and severe hyperaesthesia in the distribution of the infra-orbital nerve 12 and 26 months, respectively, after blunt orbital trauma. RESULTS: Surgical decompression of the infra-orbital nerve resulted in rapid and complete resolution of the hyperaesthesia in both cases. CONCLUSION: Persistent hyperaesthesia of the infra-orbital nerve is another indication for exploration of the orbital floor following blunt orbital trauma.

Identification of the lower end of the nasolacrimal duct with a fibre-optic light 'pipe'.

PURPOSE: To report a method of identifying the lower end of the nasolacrimal duct when more usual methods have failed. METHODS: A vitreoretinal fibre-optic light pipe was used to identify the lower end of the nasolacrimal duct in a child with unusual congenital nasolacrimal duct obstruction. RESULTS: This intraluminal light source enabled easy cut down onto the 'blind' end of the lacrimal drainage apparatus and subsequent intubation with silicone tubing to overcome the obstruction. CONCLUSION: This technique may prove useful in the rare cases in which it is not possible to identify the lower end of the nasolacrimal duct with a probe and nasal endoscope alone.

Ocular migraine in an eight-year-old girl.

BACKGROUND: A case of ocular migraine in an eight-year-old girl is presented. This is believed to be the youngest reported patient with ocular migraine. CONCLUSION: The choroid was noted to darken during an episode of visual loss, suggesting choroidal ischaemia as the cause of the visual loss.

Severe epistaxis--an unusual complication of lacrimal probing.

Severe epistaxis after combined nasolacrimal duct probing and cardiac catheterisation in a one-year-old child is reported. The epistaxis followed streptokinase infusion given as treatment for femoral artery thrombosis secondary to cardiac catheterisation and necessitated nasal packing and blood transfusion. The authors recommend that probing not be undertaken in conjunction with another procedure if anticoagulant and/or thrombolytic agents are likely to be required.

Retinal findings after head trauma in infants and young children.

BACKGROUND: Many authorities believe that the finding of retinal hemorrhages in a child younger than 3 years of age with a history of head trauma, in the absence of an obvious cause for the injury, is pathognomonic of child abuse. To date, no studies have examined the prospective retinal examination of children who have had head trauma. The authors undertook such a study because the presence of retinal hemorrhage from any head trauma in children may have medicolegal diagnostic significance in differentiating accidental from nonaccidental trauma. METHODS: Seventy-nine children younger than 3 years of age, each of whom experienced head injury, underwent an ophthalmologic assessment, which included a dilated funduscopic examination. RESULTS: Seventy-five children sustained accidental head injuries and had normal funduscopic examinations. Three children had nonaccidental head injuries and all were found to have varying degrees of retinal hemorrhages. One child, with a normal fundus examination, had injuries that were of indeterminate cause. CONCLUSION: The finding of retinal hemorrhages in a child with a head injury suggests a nonaccidental cause.

Screening for fungal endophthalmitis in children at risk.

To evaluate the efficacy of screening ophthalmologic examinations in high-risk children, we reviewed the medical records for all patients hospitalized from 1985 through 1989 at The Hospital for Sick Children, Toronto, Ontario, who underwent ophthalmological consultation to rule out endogenous fungal endophthalmitis (n = 176). The patients were divided into groups: Group 1 (n = 47), those with deep-tissue fungal infection, and Group 2 (n = 129), those at risk for invasive fungal disease. Group 2 was subdivided further into two subgroups: Group 2a (n = 48), those with evidence of superficial fungal colonization (positive fungal culture) but no deep-tissue involvement, and Group 2b (n = 81), those with no evidence of fungal colonization (negative fungal culture). Of these 176 patients, 7 were diagnosed with endogenous fungal endophthalmitis: 6 from Group 1, 1 from Group 2a, and 0 from Group 2b. We found a significant association between the development of endogenous fungal endophthalmitis and the status of the fungal culture result (P less than .005). The odds ratio indicated the risk of endogenous fungal endophthalmitis in Group 1 patients with deep-tissue infection was at least 19 times that of Group 2 at-risk patients. The risk of endogenous fungal endophthalmitis in Group 1 patients was at least 7 times that of Group 2a colonized patients and 12 times that of Group 2b patients with no positive fungal culture. Our study confirms the necessity of careful dilated ophthalmoscopic examination in patients with invasive fungal disease and suggests screening for those at-risk patients with superficial fungal colonization.(ABSTRACT TRUNCATED AT 250 WORDS)

A matched comparison of single and triple incision techniques for the surgical treatment of carcinoma of the vulva.

Thirty-two patients with invasive squamous cell carcinoma of the vulva (SCC) undergoing radical vulvectomy or radical local excision with bilateral superficial groin node dissection using a triple incision technique (TI) were matched for new FIGO stage, lymph node status, size of lesion, and site of lesion with patients with SCC undergoing traditional radical vulvectomy with en bloc bilateral groin (but not pelvic) node dissection using a single incision (SI) technique. Average operative time (134 min: 191 min), blood loss (424 ml: 733 ml), and hospital stay (9.7 days: 17.2 days) were significantly less in the TI group. After SI 6/32 (19%) patients and after TI 1/32 (3%) patients experienced complete breakdown of the groin wounds. There was no significant difference in overall survival (P = 0.56) or disease-free survival (P = 0.53) between the two groups. There was no significant difference in survival between the two groups by lesion size or by FIGO (1989) stage. Disease recurred in six patients after SI compared with seven after TI (P = 0.75). There were no skin bridge recurrences in the TI group. Two patients in each group had isolated vulvar recurrences and all four were successfully treated by local excision. These data indicate that outcome following TI surgery is essentially equal to that of SI in early-stage disease but major morbidity is much reduced.

Retinal haemorrhage in accidental head trauma in childhood.

Twenty-five children (age range 1.2-14.5 years) who sustained accidental head injury requiring admission to hospital were prospectively examined for evidence of retinal haemorrhage. In no case were retinal haemorrhages detected. It is suggested that accidental head injury seldom results in retinal haemorrhage and that the finding of retinal haemorrhage in a child with a head injury should prompt suspicion of abuse.

Heterotopic brain tissue in the orbit: case report.

A case of heterotopic brain tissue within the orbit is reported. Previously reported cases of this condition are reviewed, with particular reference to the pathogenesis and visual outcome.

The incidence of pneumoconiosis, mesothelioma and other respiratory cancer in men engaged in mining and milling crocidolite in Western Australia.

Previous employees of a mining company, engaged in mining of crocidolite at Wittenoom Gorge in Western Australia between 1943 and 1966, have been traced to determine their incidence of asbestos-related diseases. Of 6200 male employees, 220 (3.5%) have developed pneumoconiosis and 26 have developed pleural mesothelioma. No cases of peritoneal mesothelioma have been identified. Prior to 1978, 60 men had died from respiratory cancer other than mesothelioma, compared with 38.25 expected from the mortality experience of all Western Australian males. The incidence of pneumoconiosis and mesothelioma and the mortality from other respiratory cancer all increased with duration of employment, interval from first employment, and level of occupational exposure, indicating a strong relationship between intensity of asbestos exposure and these diseases. The mortality ratio for respiratory cancer, excluding mesothelioma (1.57), was nearly twice that for all nonrespiratory causes of death, suggesting a two-fold increase in mortality from respiratory cancer compared with all Western Australian males. Variation of mortality from respiratory cancer by duration of employment and occupational exposure suggests that at least 30% of respiratory cancer deaths other than mesothelioma may be due to asbestos exposure. The major part of this excess is accounted for by respiratory cancer occurring in men with previously diagnosed pneumoconiosis.