A comparison of applanation tonometry using conventional reusable goldmann prisms and disposable prisms.

PURPOSE: To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GAT) and Tonosafe disposable prisms, and also to provide a comprehensive cost analysis of the use of both types of prisms METHODS: : In this prospective observational study, 198 eyes of 100 glaucoma patients had their IOPs measured by 5 consultant ophthalmologists. Data were analyzed using the Bland-Altman method of differences, and correlation was measured using the Pearson coefficient. An analysis of the cost incurred using the 2 methods over a 6-month period was performed. RESULTS: The majority were Chinese (82%), with a male preponderance (57%). The range of IOPs as measured by GAT was 4 to 34 mm Hg. Using the Bland-Altman method to compare GAT and disposable prisms, the bias was 0.2 mm Hg. Tonosafe overestimated the IOP by 0.2 mm Hg in the right eye and underestimated it by 0.2 mm Hg in the left eye. The Tonosafe IOP correlated well with GAT, with a Pearson coefficient of correlation(r) of 0.91 (P<0.0005) for the right eye and 0.92 (P<0.0005) for the left eye, respectively. For those with GAT IOP≥21 mm Hg (n=26), Tonosafe underestimated the IOP by 0.35 mm Hg. The cost incurred by Tonosafe prisms was approximately 8 times that of GAT, but the cost differential reverses when GAT had to be replaced after every 100 cycles of disinfection. CONCLUSIONS: We found a good correlation between Tonosafe prisms and conventional GAT in measuring the IOP. Tonosafe prisms may be of use, especially if the risk of transmission of infection is high. However, cost may limit its more widespread use.

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Spectral-domain optical coherence tomography of ß-zone peripapillary atrophy: influence of myopia and glaucoma.

PURPOSE: To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the ß-zone of peripapillary atrophy (PPA-ß) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Cross-sectional B-scan images of PPA-ß obtained with SD-OCT were evaluated in 100 eyes of 100 consecutive patients with POAG, regardless of intraocular pressure level, and in 100 eyes of 100 normal subjects. PPA bed configurations were classified, and associated factors were studied with multivariate analysis. RESULTS: In 147 eyes with PPA-ß (84 POAG and 63 normal eyes; P = 0.0012), the PPA bed was composed of straight (14 POAG and 27 normal eyes) or downward-curved (19 and 8 eyes) Bruch's membrane (BM) or of a downward-bending slope lacking BM (BM defect; 51 and 28 eyes). Multivariate analysis revealed that absence of POAG (odds ratio [OR], 0.36; P = 0.034) and less myopic refractive error (OR, 1.43; P = 0.009) were significantly associated with straight-BM-type, presence of POAG (OR, 5.74; P = 0.008) and less myopic refractive error (OR, 3.02; P < 0.001) with curved-BM-type, and myopic refractive error (OR, 0.34; P < 0.001) with BM-defect-type. Within the PPA-ß region, all retinal layers except for the nerve fiber layer frequently disappeared before reaching the disc edge, showing no significant intergroup difference (P > 0.05) between POAG and normal eyes. CONCLUSIONS: PPA bed configurations detected by SD-OCT were classified into three types. The lack of BM on the PPA bed was closely associated with myopia. The downward-curved appearance of BM may be related to the anatomic changes associated with glaucoma.

Central corneal thickness in Chinese subjects with primary angle closure glaucoma.

PURPOSE: To characterize central corneal thickness (CCT) in Chinese eyes with primary angle closure glaucoma (PACG). METHODS: CCT was measured by ultrasound pachymetry in PACG eyes and compared with primary open-angle glaucoma (POAG) eyes. POAG eyes were further subdivided into high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) for analysis. PACG eyes had glaucomatous optic neuropathy and visual field loss, an angle in which at least 180 degrees of angle in which the posterior trabecular meshwork was not visible, and raised intraocular pressure (IOP) and/or peripheral anterior synechiae. Both HTG (IOP >21 mm Hg) and NTG (IOP consistently <21 mm Hg) eyes had glaucomatous optic neuropathy with compatible visual field defects and open angles. Further comparison was made with CCT data of 1067 normal subjects previously enrolled in a population-based study. RESULTS: We enrolled 154 patients with PACG and 300 with POAG. Mean age of PACG patients was 68.1±8.3 years compared with 71.1±12.4 years in POAG patients (P=0.002). There was no difference in mean CCT of PACG eyes (541.28±33.95 µm) and POAG eyes (539.28±34.84 µm, P=0.56) or normal eyes of control subjects (536.74±31.08 µm) (P=0.07). However, mean CCT of NTG eyes (535.23±36.10 µm) was significantly lower than that of HTG eyes (543.44±33.10 µm, P=0.04), and HTG eyes had thicker CCT than normal eyes (P=0.01). CONCLUSIONS: PACG eyes had similar CCT as those with POAG or normal eyes in Chinese subjects.

Plateau iris in Asian subjects with primary angle closure glaucoma.

OBJECTIVE: To determine the prevalence of plateau iris in Asian eyes with primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM). METHODS: In this cross-sectional observational study, subjects older than 40 years with PACG who had a patent laser peripheral iridotomy underwent UBM in 1 eye. Ultrasound biomicroscopy images were qualitatively analyzed using standardized criteria. Plateau iris in a quadrant was defined by anteriorly directed ciliary body, absent ciliary sulcus, steep iris root from its point of insertion followed by a downward angulation, flat iris plane, and irido-angle contact. At least 2 quadrants had to fulfill these UBM criteria for an eye to be classified as having plateau iris. RESULTS: One hundred eleven subjects (70 from Singapore, 41 from Thailand) with PACG were recruited. The mean (SD) age was 65.6 (8.1) years, and 63.9% were female. Based on standardized UBM criteria, plateau iris was found in 36 of 111 eyes (32.4%; 95% confidence interval, 24.4%-41.6%). In these 36 eyes, quadrant-wise analysis showed 66.7% had plateau iris in 2 quadrants; 22.2%, in 3 quadrants; and 11.1%, in all quadrants. CONCLUSIONS: About 30% of PACG eyes with a patent laser peripheral iridotomy were found to have plateau iris on UBM, highlighting the importance of non-pupil block mechanisms in Asian individuals.

Stereotaxy for surgical navigation in orbital surgery.

PURPOSE: Image guidance has been used in neurosurgery with great success. The authors illustrate the use of stereotaxy and neuronavigation in the surgical management of a cranio-orbital tumor and for orbital decompresson in thyroid orbitopathy. METHODS: Stereotactic image guidance was used in the surgical management of 2 patients, one with a large left sphenoid wing meningioma causing proptosis and visual loss from orbital extension, and the other with disfiguring proptosis due to thyroid eye disease. Virtual reality simulation was used preoperatively in the first patient to visualize surgical corridors of approach to the tumor. RESULTS: The patients underwent successful orbital surgery aided by intraoperative neuronavigation. The sphenoidal wing meningioma was removed completely with no damage to adjacent orbital and intracranial tissues, and orbital decompression was successfully performed with good cosmetic improvement. CONCLUSION: Image-guided neuronavigation in our cases allowed for safe and precise surgery, with avoidance of complications.

Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese.

PURPOSE: Single nucleotide polymorphisms (SNPs) within the lysyl oxidase like-1 gene (LOXL1; rs1048661 and rs3825942) were found to confer risk to pseudoexfoliation glaucoma (XFG) through the pseudoexfoliation syndrome (XFS) in Nordic, Caucasian, and two Asiatic populations (Indian and Japanese). The prevalence (0.2%-0.7%) of XFS in the Chinese is considerably lower compared to Nordic populations. The aim of this study was to determine the association of LOXL1 in Chinese subjects with XFS/XFG. METHODS: Chinese subjects with clinically diagnosed XFS/XFG and normal controls were recruited. Genomic DNA was extracted, and the two LOXL1 SNPs (rs1048661 and rs3825942) were genotyped by bidirectional sequencing. Allele and genotype frequencies were compared between cases and unrelated controls using PLINK. Linkage disequilibrium (LD) calculations and haplotype association analysis were done using the Haploview package and WHAP package, respectively. RESULTS: Sixty-two Chinese patients (17 XFG and 45 XFS) and 171 Chinese controls were studied. The G allele of LOXL1 SNP rs3825942 was moderately associated (OR=10.97, p=0.0018) with pseudoxfoliation in the Chinese. The frequency of the G allele of rs1048661 was not significantly different in cases compared to controls (p=0.142) in the allelic association test. However, the genotype test showed marginal association for rs1048661 (p=0.030). Only three haplotypes were observed (T-G, G-G, and G-A) with G-G as a risk haplotype (p=0.0034) and G-A as a protective haplotype (p=0.00039). T-G, which was a risk haplotype in the Japanese, was not associated with XFG in the Chinese (p=0.124). CONCLUSIONS: Polymorphisms in LOXL1 confer risk to XFS/XFG in the Chinese. The lower incidence of XFS compared to other populations suggests additional genetic or environmental factors to have a major influence on the phenotypic expression of XFS in the Chinese. The G allele of rs3825942 has been shown to be associated with XFS/XFG in all populations studied to date.

Confirmation of the presence of uveal effusion in Asian eyes with primary angle closure glaucoma: an ultrasound biomicroscopy study.

OBJECTIVE: To confirm the presence of uveal effusion in the eyes of Asian patients with primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM). METHODS: In this observational case series, 70 patients with PACG (28 untreated patients with newly diagnosed PACG and 42 patients who had undergone previous laser iridotomy and were being monitored) and 12 patients with acute primary angle closure (APAC) were recruited. Eyes of patients with newly diagnosed PACG and APAC underwent UBM before and after laser iridotomy, whereas eyes of patients with treated PACG underwent UBM at enrollment. Uveal effusion was defined as a clear space between the choroid and sclera and was graded as follows: grade 0, none; grade 1, slitlike; grade 2, bandlike; and grade 3, obvious. RESULTS: Overall, uveal effusion was found in 11 of 70 eyes with PACG (15.7%; 95% confidence interval, 8.8%-26.2%) and in 3 of 12 eyes with APAC (25%; 95% confidence interval, 8.0%-53.4%). For patients with newly diagnosed PACG, uveal effusion was found in 4 of 28 eyes (14.2%; 95% confidence interval, 5.1%-32.1%) before laser iridotomy; 2 eyes had effusion after laser iridotomy. When present, the effusion was grade 1 in PACG eyes and grade 2 or 3 in APAC eyes. CONCLUSIONS: Uveal effusion was present in a significant proportion of Asian eyes with PACG and APAC, confirming a recent report of this finding.

Nasopharyngeal carcinoma with orbital involvement.

PURPOSE: To describe the clinical presentation of patients with nasopharyngeal carcinoma and orbital involvement. METHODS: A retrospective case series of 9 patients with nasopharyngeal carcinoma presenting with orbital involvement from March 2003 to April 2006 at the Singapore National Eye Centre were reviewed. The clinical profile, neuroradiologic evaluation, and clinical course of these patients were reviewed. RESULTS: There were 3 women and 6 men with stage T4 disease. The mean age was 49.2 years +/- 7.69 years (range, 37-57 years). The mean time from initial diagnosis of nasopharyngeal carcinoma to orbital involvement was 8.2 years (range, 0.8-29 years). One patient had no prior history of nasopharyngeal carcinoma. Four patients presented with an eyelid mass and 2 patients reported tearing. Other symptoms included diplopia, blurred vision, and protrusion of the eye. Imaging revealed tumor involvement of the orbital apex, inferior orbital fissures with intraconal spread, and infiltration of the lacrimal sac. The recurrences were confirmed histologically. Patients were treated with radiotherapy and/or chemotherapy. There were 3 deaths from advanced nasopharyngeal carcinoma during the follow-up period. The time interval from diagnosis of orbital involvement to death ranged from 8 months to 24 months. CONCLUSION: Ocular symptoms and signs may be the initial presentation of recurrent nasopharyngeal carcinoma. One must therefore be aware of possible tumor recurrence in patients with a prior history of nasopharyngeal carcinoma who present with symptoms of tearing or an eyelid mass, as this would enable prompt referral to the oncologist and otorhinolaryngologist.

Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a major cause of serosanguinous maculopathy in Chinese patients with age-related macular degeneration (AMD). Variants in the CFH and HTRA1/LOC387715 genes are strongly associated with AMD in Caucasians and Chinese. Variants in the C2 and BF genes have been found to confer a significantly reduced risk of AMD. This study was undertaken to determine whether these associations occur in Chinese patients with PCV. METHODS: Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV and normal control subjects were recruited from the Singapore National Eye Centre. Five single-nucleotide polymorphisms (SNPs) in the CFH gene, two each within the C2 and BF genes and two variants located in the LOC387715 and HTRA1 genes, were screened in all patients and control subjects. RESULTS: Seventy-two patients with PCV and 93 normal control subjects were studied. A significant association was noted with CFH variants rs3753394 and rs800292 among the PCV cases (P = 0.0015 and P = 0.0045, respectively). Individuals homozygous for the TT genotype of rs3753394 had a significantly higher risk (P = 0.0076) of PCV (OR = 4.29; 95% CI: 1.47-12.50) than those carrying a single copy of the T allele (P = 0.3210; OR = 1.69; 95% CI: 0.60-4.78), after adjustment for such risk factors as age and sex. The genotype frequencies of rs11200638 and rs10490924 in HTRA1 and LOC387715, respectively, were also found to be significantly different between patients with PCV and normal control subjects (P = 0.00032 and P = 0.003, respectively). The AA genotype of rs11200638 and TT genotype of rs10490924 conferred a 4.9-fold (95% CI: 1.85-12.95) and 4.89-fold (95% CI: 1.85-12.90) increased risk of PCV, respectively, after adjustment for age and sex. The Y402H variant of CFH (rs1061170) and the BF and C2 variants were not significantly different in patients and normal control subjects. CONCLUSIONS: The SNPs rs3753394 and rs800292 of CFH and rs11200638 of HTRA1 are significantly associated with the risk of PCV in Chinese patients.

Epibulbar osseous choristoma: a report of two cases.

Epibulbar osseous choristoma occurs rarely and is commonly mistaken for a dermoid or dermolipoma. We report two cases: an 8-year-old boy and a 79-year-old lady with epibulbar osseous choristomas where computed tomography showed an extraocular lesion in the temporal quadrant and diagnosis was confirmed by excision biopsy. The osseous component was adherent to the sclera in the young patient, while it was loosely attached to the surrounding tissue in the older patient. We believe that the 79-year-old lady is the oldest reported patient with an epibulbar osseous choristoma.

Association of LOXL1 gene polymorphisms with pseudoexfoliation in the Japanese.

PURPOSE: The single nucleotide polymorphisms (SNPs) rs1048661, rs3825942, and rs2165241 within the LOXL1 gene were recently found to confer risk of pseudoexfoliation glaucoma (XFG) through pseudoexfoliation syndrome (XFS) in Caucasians. The purpose of this study was to test this association in Japanese subjects with XFS/XFG. METHODS: Japanese subjects with clinically diagnosed XFS/XFG and normal control subjects were recruited. Genomic DNA was extracted and the three SNPs of the LOXL1 gene were genotyped by bidirectional sequencing. The association of individual SNPs with XFG/XFS was evaluated by using chi(2) and the Fisher exact test. RESULTS: Two hundred nine Japanese patients (106 XFG and 103 XFS) and 172 control subjects were studied. Strong associations were observed for all three SNPs of LOXL1 for XFS (odds ratio [OR] = 13.56, P = 3.39 x 10(-28) for allele T of rs1048661; OR = 10.71, P = 1.49 x 10(-7) for allele G of rs3825942; and OR = 4.55, P = 5.33 x 10(-4) for allele C of rs2165241) and XFG (OR = 25.21, P = 1.44 x 10(-34) for allele T of rs1048661; OR = 11.02, P = 1.40 x 10(-7) for allele G of rs3825942; and OR = 11.89, P = 4.76 x 10(-6) for allele C of rs2165241). The risk-associated alleles of rs1048661 and rs2165241 differed between the Japanese and Caucasians, whereas allele G of rs3825942 was associated with disease in both populations. Conditional analysis indicated that rs3825942 was not independent but correlated highly with rs1048661. The at-risk haplotype T-G-C was present at an approximately two times higher rate (94.7% vs. 50.6%, P = 4.22 x 10(-43)) in cases than in control subjects and conferred a 2.9-fold (95% confidence interval [CI], 2.357-3.464) increased likelihood of XFS. CONCLUSIONS: Polymorphisms in the LOXL1 gene confer risk to XFS/XFG in the Japanese, but there are different risk-associated alleles and haplotypes in the Japanese.

Lack of association between interleukin-1 gene cluster polymorphisms and glaucoma in Chinese subjects.

PURPOSE: A recent study identified single nucleotide polymorphisms (SNPs) within the IL-1 gene cluster at chromosomal locus 2q13 that were associated with reduced risk for primary open-angle glaucoma (POAG) in whites. The purpose of this study was to investigate the association between IL-1 SNPs and glaucoma in Chinese patients with either POAG or primary-angle closure glaucoma (PACG). METHODS: Patients with POAG with a mean IOP without treatment that was consistently <21 mm Hg on diurnal testing were classified as having normal-tension glaucoma (NTG) and those with higher IOP were classified as having high-tension glaucoma (HTG). Subjects with PACG had at least 180 degrees of angle closure on gonioscopy. Genotypes were determined by polymerase chain reaction and restriction digest enzymes at the following loci: IL1A (-889C/T), IL1B (+3953C/T), and IL1B (-511C/T). The association of individual SNPs with glaucoma was evaluated by using chi(2) testing. Haplotype analysis was performed with the PHASE program, with haplotype frequency estimated for combined cases and controls, assuming Hardy-Weinberg equilibrium (HWE) of haplotypes. RESULTS: Of the Chinese subjects studies, 194 had POAG (94 NTG and 100 HTG), 125 had PACG, and 79 were normal control subjects. There was no significant difference in IL-1 SNP or allele frequencies for in subjects with POAG or PACG compared with control subjects, or between NTG and HTG. None of the common haplotypes showed any significant difference between the HTG, NTG, PACG, and normal control subjects. CONCLUSIONS: This study did not find an association between IL-1 gene cluster polymorphisms and glaucoma in this sample of Chinese subjects.

Peripapillary atrophy after acute primary angle closure.

AIM: To determine the changes in peripapillary atrophy after episodes of acute primary angle closure (APAC). METHODS: Prospective observational study of 40 eyes in 38 patients of predominantly Chinese ethnicity. The mean (SD) intraocular pressure at the time of presentation was 51.7 (12) mm Hg (median, 55 mm Hg) and the mean duration of the symptoms was 37.7 (69.4) hours. A laser iridotomy was undertaken 3.2 (8.4) days after the APAC episode, leading to normalisation of intraocular pressure in all cases. Colour optic disc photographs taken at 2 and 16 weeks after APAC were examined morphometrically. Peripapillary atrophy was divided into alpha and beta zones. RESULTS: Comparing measurements at baseline with week 16, the minimum width of the alpha zone (0.013 (0.056) v 0.016 (0.001) arbitrary units; p = 0.23), the maximum width of the alpha zone (1.11 (1.31) v 1.31 (0.79) arbitrary units; p = 0.22), the minimum width of the beta zone (0.030 (0.122) v 0.033 (0.166) arbitrary units; p = 0.93), and the maximum width of the beta zone (0.62 (0.94) v 0.73 (0.98) arbitrary units; p = 0.42) did not vary significantly. The mean cup to disc ratio increased from 0.56 (0.05) to 0.62 (0.07) (p<0.0001) at the end of follow up. CONCLUSIONS: The alpha and beta zones of peripapillary atrophy did not enlarge markedly in patients after APAC, despite an enlargement of the optic cup during a follow up of four months.

Visual recovery following emergent orbital decompression in traumatic retrobulbar haemorrhage.

INTRODUCTION: Acute retrobulbar haemorrhage is a potentially sight-threatening condition, and can follow retrobulbar anaesthesia or trauma to the orbit. Acute loss of vision can occur with retrobulbar haemorrhage and is reversible if the condition is recognised and treated early. CLINICAL PICTURE: We report a case of acute retrobulbar haemorrhage following orbital trauma in a 78-year-old Chinese lady. TREATMENT: The patient was on follow-up for a mature cataract in the right eye and had been scheduled for cataract surgery. The patient presented to the emergency department with acute loss of vision in the right eye, severe proptosis and tense periorbital haematoma after she hit her right face following a fall. Computed tomography scans revealed fractures of the floor, lateral and medial walls of the right orbit as well as retrobulbar and periorbital haematoma. There was marked proptosis and tenting of the globe with stretching of the optic nerve. Emergent lateral canthotomy and cantholysis was performed at the emergency department. The patient subsequently underwent surgical evacuation of the orbital haematoma. OUTCOME: The patient's vision in the right eye recovered from no perception of light to light perception over the next few days. After a month of follow-up, the patient underwent right cataract surgery, and her best corrected visual acuity was 6/12 part. CONCLUSION: In severe acute retrobulbar haemorrhage, prompt surgical evacuation of the haematoma can reverse visual loss.

Orbital metastatic tumour as initial manifestation of asymptomatic gastric adenocarcinoma.

INTRODUCTION: Metastatic orbital tumour from gastric cancer is rare. Patients with metastatic disease may present initially to the ophthalmologist with symptoms from metastases instead of from the primary cancer. CLINICAL PICTURE: We report a case, with clinicopathological correlation, of metastatic gastric adenocarcinoma presenting first in the orbit with diplopia. Computed tomography and magnetic resonance imaging of the orbit showed a well-defined enhancing right intraconal tumour. TREATMENT AND RESULTS: Excisional biopsy was performed and histopathology confirmed a metastatic adenocarcinoma. Focused gastrointestinal screening revealed an otherwise asymptomatic Stage IV gastric adenocarcinoma. Chemotherapy was initiated with good tumour response. CONCLUSION: Early biopsy of unusual orbital tumours is critical as orbital metastases may be the initial manifestation of an asymptomatic primary. Histopathological diagnosis can aid localisation of the primary tumour and allow prompt treatment to be instituted.

Characterization of Bietti crystalline dystrophy patients with CYP4V2 mutations.

PURPOSE: Mutations of the CYP4V2 gene, a novel family member of the cytochrome P450 genes on chromosome 4q35, have recently been identified in patients with Bietti crystalline dystrophy (BCD). The aim of this study was to investigate the spectrum of mutations in this gene in BCD patients from Singapore, and to characterize their phenotype. METHODS: Nine patients with BCD from six families were recruited into the study. The 11 exons of the CYP4V2 gene were amplified from genomic DNA of patients by polymerase chain reaction and then sequenced. Detailed characterization of the patients' phenotype was performed with fundal photography, visual field testing, fundal fluorescein angiography, and electroretinography (ERG). RESULTS: Three pathogenic mutations were identified; two mutations, S482X and K386T, were novel and found in three patients. The third mutation, a previously identified 15-bp deletion that included the 3' splice site for exon 7, was found in all nine patients, with six patients carrying the deletion in the homozygous state. Haplotype analysis in patients and controls indicated a founder effect for this deletion mutation in exon 7. Clinical heterogeneity was present in the patients. Compound heterozygotes for the deletion in exon 7 seemed to have more severe disease compared to patients homozygous for the deletion. There was good correlation between clinical stage of disease and ERG changes, but age did not correlate with disease severity. CONCLUSIONS: This study identified novel mutations in the CYP4V2 gene as a cause of BCD. A high carrier frequency for the 15-bp deletion in exon 7 may exist in the Singapore population. Phenotype characterization showed clinical heterogeneity, and age did not correlate with disease severity.