Faculty Bibliography

PURPOSE: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). METHODS: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those >/=5 kilobases (kb) in size and interrogated by >/=5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. RESULTS: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. CONCLUSIONS: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.

PURPOSE: To determine the intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer thickness measures using handheld optical coherence tomography (OCT) in sedated children with optic pathway gliomas and/or neurofibromatosis type 1 (NF1). DESIGN: Prospective longitudinal cohort study. METHODS: Children with sporadic optic pathway gliomas and/or NF1 who had >/=2 volumes acquired over the macula using handheld OCT during sedation for clinically indicated magnetic resonance imaging were eligible for the intra-visit cohort. Children with repeat handheld OCT imaging within 6 months were eligible for the inter-visit cohort. Total retinal thickness and ganglion cell-inner plexiform layer thickness were measured using custom-designed automated segmentation software. Reproducibility was compared across average and anatomic quadrant by calculating the coefficient of variation (CV) and intraclass correlation coefficient (ICC). RESULTS: Forty-two subjects (median age 5.4 years, range 0.8-12.7 years) contributed 45 eyes to the intra-visit cohort. Thirty-one subject eyes had normal vision and 14 had abnormal vision (decreased visual acuity and/or visual field). Average and quadrant ganglion cell-inner plexiform layer measures demonstrated CVs 0.935). The superior quadrant CV differed between subjects with (4.4%) and without (2.1%) vision loss (P < .05). Twenty-five subject eyes were eligible for the inter-visit cohort, demonstrating CVs from 1.6% to 5.2%. Inter-visit ICCs were excellent (0.955-0.995). DISCUSSION: Handheld OCT imaging in sedated children with optic pathway gliomas produces highly reproducible measures of ganglion cell-inner plexiform layer thickness.

PURPOSE: To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) measures using handheld optical coherence tomography (OCT) in sedated children. DESIGN: Prospective cross-sectional and longitudinal study. METHODS: Children undergoing sedation for a clinically indicated magnetic resonance imaging for an optic pathway glioma and/or neurofibromatosis type 1 (NF1) had multiple 6 x 6 mm volumes (isotropic 300 x 300 or nonisotropic 1000 x 100 samplings) acquired over the optic nerve. Children with 2 handheld OCT sessions within 6 months were included in the intervisit cohort. The intra- and intervisit coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for the average and anatomic quadrant circumpapillary RNFL thickness. RESULTS: Fifty-nine subjects (mean age 5.1 years, range 0.8-13.0 years) comprised the intravisit cohort and 29 subjects (mean age 5.7 years, range 1.8-12.7 years) contributed to the intervisit cohort. Forty-nine subjects had an optic pathway glioma and 10 subjects had NF1 without an optic pathway glioma. The CV was comparable regardless of imaging with an isotropic and nonisotropic volume in both the intra- and intervisit cohorts. The average circumpapillary RNFL demonstrated the lowest CV and highest ICC compared to the quadrants. For the intervisit cohort, the average ICC was typically higher while the CV was typically lower, but not statistically different compared to the other quadrants. DISCUSSION: Circumpapillary RNFL measures acquired with handheld OCT during sedation demonstrate good intra- and intervisit reproducibility. Handheld OCT has the potential to monitor progressive optic neuropathies in young children who have difficulty cooperating with traditional OCT devices.