Optic Disc Size Research Articles

A NEW MICROLENSING EVENT IN THE DOUBLY IMAGED QUASAR Q 0957+561

We present evidence for ultraviolet/optical microlensing in the gravitationally lensed quasar Q0957+561. We combine new measurements from our optical monitoring campaign at the United States Naval Observatory, Flagstaff (USNO) with measurements from the literature and find that the time-delay-corrected r-band flux ratio m_A - m_B has increased by ~0.1 magnitudes over a period of five years beginning in the fall of 2005. We apply our Monte Carlo microlensing analysis procedure to the composite light curves, obtaining a measurement of the optical accretion disk size, log {(r_s/cm)[cos(i)/0.5]^{1/2}} = 16.2^{+0.5}_{-0.6}, that is consistent with the quasar accretion disk size - black hole mass relation.

Estudo das correlações entre a área do disco óptico e as características geométricas e biomecânicas da córnea

PURPOSE: To correlate optic disc size geometry, corneal architecture and biomechanics. METHODS: Optic disc area and geometry was accessed by HRT III (Heidelberg Retina Tomography – Heidelberg eng), Pentacam (Oculus) was used for accessing IOP and corneal parameters and ORA (Ocular Response Analyze – Reichert) was utilized to access corneal biomechanical properties. Classification based DDLS (Disc Damage Likelihood Scale) scale from retinography was performed. Settings: Instituto de Olhos Renato Ambrósio. RESULTS: 244 eyes of 122 patients (75 female) were included. [...]

Correlation of Frequency-doubling Perimetry With Retinal Nerve Fiber Layer Thickness and Optic Disc Size in Ocular Hypertensives and Glaucoma Suspects

To determine the structure-function correlation using frequency-doubling technology (FDT) perimetry and optical coherence tomography (OCT) in glaucoma suspects, and analyze their relationship to optic disc size. Sixty eyes of 60 ocular hypertensive patients (OHT) and 54 eyes of 54 subjects with optic disc features suspicious of glaucoma (disc suspects) with normal visual fields on Standard Achromatic Perimetry were recruited. All subjects underwent FDT perimetry using the N-30 program, and the mean deviation (FDT-MD) and FDT-pattern SD were computed. Average and inferior retinal nerve fiber layer (RNFL) thickness and disc area were measured on Stratus OCT. Pearson correlation coefficient was calculated among all the measurements. In disc suspects, FDT-MD correlated significantly with RNFL thickness measurements (P<0.001; P=0.003) and disc area (P<0.001). There was no correlation with the vertical cup-disc area ratio (VCDR) and FDT indices. In OHT, FDT-MD correlated significantly with average RNFL thickness (P=0.038), and there was a significant negative correlation between FDT-MD and the VCDR (0.042). The FDT-pattern SD negatively correlated with RNFL thickness measurements (P=0.008; P=0.03). The disc area correlated significantly with the average and inferior average RNFL thickness measurements in both groups of patients (P=0.029 and P=0.007; P=0.013 and P=0.013, respectively). In OHT, optic discs with larger VCDR and thinner RNFL had lower FDT-MD values. In disc suspects, smaller-sized discs had thinner RNFL and lower values of FDT-MD. FDT perimetry and OCT seem to be useful adjuncts to detect these eyes, which might warrant close follow-up to eventually detect glaucoma by Standard Achromatic Perimetry.

Optic Disc Size and Other Parameters From Optical Coherence Tomography in Vietnamese-Americans

To investigate the optic disc parameters by optical coherence tomography (OCT) in Vietnamese with various types of glaucoma. Medical charts of Vietnamese and White patients within a single practice were reviewed. Disc and rim areas by OCT were compared among nonglaucoma controls, different types of glaucoma, and glaucoma suspect. The association of these parameters with demographic and ocular features was evaluated. Data from 1416 Vietnamese and 57 White patients were included. A larger mean disc area was observed in eyes with primary angle-closure glaucoma than in eyes with primary angle-closure and primary angle-closure suspect (both P<0.001). There was no association between disc size with central corneal thickness (P=0.051) and sex (P=0.155). Vietnamese patients with glaucoma and glaucoma suspicion had larger discs than diagnosis-matched Whites (P=0.043 and 0.021, respectively). Vietnamese patients with glaucoma seem to have larger optic discs than White patients. Central corneal thickness had no association with disc area in this study population.

Performance of Imaging Devices versus Optic Disc and Fiber Layer Photography in a Clinical Practice Guideline for Glaucoma Diagnosis

To compare the performance of Moorfields Regression Analysis (MRA) and optical coherence tomography (OCT) with that of photographic evaluation of the optic nerve head and retinal nerve fiber layer (RNFL) in the application of the Finnish Evidence-Based Guideline for Open-Angle Glaucoma (FEBG-OAG). Patients referred for glaucoma evaluation (n=312) and subjects selected from the general population (n=41) were included in the study. All subjects underwent ophthalmic evaluation, optic nerve head stereophotography, monochromatic RNFL photography, Heidelberg retina tomography, OCT, and laser polarimetry evaluation. The subjects were classified based on stereophotographic or MRA and OCT results by applying the FEBG-OAG. The specificity of the FEBG-OAG for detecting normal patients (stereophotography and imaging devices) was 78% (strict criteria) and 100% (liberal criteria). Agreement between the stereophotographic evaluation and evaluation based on MRA and OCT was 70.2%. Classification of subjects with similar management advice based on these evaluations had 70.5% agreement. Central corneal thickness was a confounding factor in glaucoma diagnosis. Large optic disc sizes played a major role in misleading the diagnosis compared to small discs. Central corneal thickness and large optic disc size are confounding factors in glaucoma diagnosis. Moorfields Regression Analysis and OCT allow for objective implementation of the FEBG-OAG compared to conventional stereophotographic evaluation of the neuroretinal structures.

Shrinkage of the Scleral Canal During Cupping Reversal in Children

The mechanism of cupping reversal seen after lowering intraocular pressure (IOP) in pediatric glaucoma is unknown. Theories include forward movement of the lamina cribrosa or shrinkage of a stretched scleral canal. Our study aimed to quantify changes in optic disc size occurring in children who had undergone glaucoma surgery. Retrospective, single-center, observational case series. Children undergoing incisional surgery for pediatric glaucoma at the University of California, Davis. The electronic charts of all patients with pediatric glaucoma were reviewed for the presence of RetCam digital optic nerve photographs (Clarity Medical Systems, Pleasanton, CA). Cases in which the photographs (baseline and follow-up after surgical intervention) were of sufficient quality were analyzed. The optic disc margin was outlined manually using ImageJ software. Inter-session changes in magnification were accounted for by drawing a control polygon joining 4 or 5 fixed landmarks (e.g., vessel crossings) to include a second larger area containing the optic nerve. The optic disc area (in pixels adjusted with the control polygon) was compared between baseline and follow-up images. Change in disc area between baseline and follow-up after surgery. We identified 29 eyes for which baseline and follow-up images were available for analysis. Fifteen eyes of 9 children showed clinically obvious cupping reversal. Fourteen eyes of 12 children showed no cupping reversal. Disc area decreased by 6.8% (95% confidence interval [CI], -10.0 to -3.3) in the obvious reversal group and increased by 4.3% (95% CI, +1.0 to +7.6) in the no reversal group after surgery (P < 0.0001; Student t test). Percent change in disc area is correlated to percent change in IOP (r=0.540; P=0.0025) and axial length (r=0.534; P=0.0028). When cupping reversal is clinically apparent after successful IOP-lowering surgery for congenital glaucoma, the scleral canal shrinks in area. In contrast, when cupping reversal is not observed, the scleral ring continues to enlarge, indicating ongoing stress on the optic nerve. Clinically obvious cupping reversal is less frequently observed in adults after surgery, which may reflect a lower elasticity of the scleral ring in adults compared with children. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Influence of Disc Size on Optic Nerve Head versus Retinal Nerve Fiber Layer Assessment for Diagnosing Glaucoma

To explore and compare the influence of optic disc size on the diagnostic accuracy of retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) quantitative assessment. Observational, cross-sectional evaluation of diagnostic tests. We included 120 eyes from 50 normal subjects and 70 glaucomatous patients classified by the presence of a repeatable visual field defect for the analysis. The RNFL thickness was measured by scanning laser polarimetry with variable corneal compensator (GDx-VCC, Carl-Zeiss Meditec, Dublin, CA) and spectral-domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec, Inc). We obtained ONH imaging by means of confocal scanning laser ophthalmoscopy (HRT3; Heidelberg Engineering, GmbH, Dossenheim, Germany). Sensitivity and specificity for normative classifications, sensitivity at fixed specificity and area under the receiver operating characteristics curve (AUC) for continuous parameters. A logistic marginal regression model and coefficients of variation (CoV) have been used to test and quantify the influence of optic disc size on the diagnostic accuracy of the 3 technologies under investigation. Among continuous parameters average RNFL thickness for Cirrus HD-OCT, nerve fiber indicator for GDx-VCC and cup shape measure for the HRT3 showed the best diagnostic accuracy with an AUC of 0.97, 0.94, and 0.94, respectively. Among normative classifications, the highest sensitivity and specificity were found for OCT average RNFL thickness (75.8% and 94.7%), for GDx superior thickness (77.1% and 97.5%), for HRT3 Moorfields regression analysis result (89.4% and 73.7%) and for HRT3 GPS global (92.3% and 76.5%). The diagnostic performance of HRT3 parameters seemed to be significantly influenced by optic disc size, although the same was not true for Cirrus HD-OCT and GDx VCC. The most steady performers for each imaging device across disc size groups were Cirrus HD-OCT average thickness (CoV, 1.6%), GDx-VCC inferior thickness (CoV, 2.5%), and HRT3 GPS temporal and nasal (CoV, 21.4%). The diagnostic accuracy of quantitative RNFL assessment as performed by Cirrus HD-OCT and GDx-VCC is high and virtually unaffected or only minimally affected by the size of the optic disc and may provide more consistent diagnostic outcomes across small and large discs than ONH assessment as performed by HRT3.

Comparison of Automated Analysis of Cirrus HD OCT Spectral-Domain Optical Coherence Tomography with Stereo Photographs of the Optic Disc

To evaluate a new automated analysis of optic disc images obtained by spectral-domain optical coherence tomography (SD OCT). Areas of the optic disc, cup, and neural rim in SD OCT images were compared with these areas from stereoscopic photographs to represent the current traditional optic nerve evaluation. The repeatability of measurements by each method was determined and compared. Evaluation of diagnostic technology. One hundred nineteen healthy eyes, 23 eyes with glaucoma, and 7 glaucoma suspect eyes. Optic disc and cup margins were traced from stereoscopic photographs by 3 individuals independently. Optic disc margins and rim widths were determined automatically in SD OCT. A subset of photographs was examined and traced a second time, and duplicate SD OCT images also were analyzed. Agreement among photograph readers, between duplicate readings, and between SD OCT and photographs were quantified by the intraclass correlation coefficient (ICC), by the root mean square, and by the standard deviation of the differences. Optic disc areas tended to be slightly larger when judged in photographs than by SD OCT, whereas cup areas were similar. Cup and optic disc areas showed good correlation (0.8) between the average photographic reading and SD OCT, but only fair correlation of rim areas (0.4). The SD OCT was highly reproducible (ICC, 0.96-0.99). Each reader also was consistent with himself on duplicate readings of 21 photographs (ICC, 0.80-0.88 for rim area and 0.95-0.98 for all other measurements), but reproducibility was not as good as SD OCT. Measurements derived from SD OCT did not differ from photographic readings more than the readings of photographs by different readers differed from each other. Designation of the cup and optic disc boundaries by an automated analysis of SD OCT was within the range of variable designations by different readers from color stereoscopic photographs, but use of different landmarks typically made the designation of the optic disc size somewhat smaller in the automated analysis. There was better repeatability among measurements from SD OCT than from among readers of photographs. The repeatability of automated measurement of SD OCT images is promising for use both in diagnosis and in monitoring of progression.

Effect of Disease Severity and Optic Disc Size on Diagnostic Accuracy of RTVue Spectral Domain Optical Coherence Tomograph in Glaucoma

To evaluate the effect of disease severity and optic disc size on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain optical coherence tomography (SDOCT) in glaucoma. 110 eyes of 62 normal subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of glaucoma was based on visual field index (VFI) values from standard automated perimetry. Optic disc size was based on disc area measurement using the Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany). Influence of disease severity and disc size on the diagnostic accuracy of RTVue was evaluated by receiver operating characteristic (ROC) and logistic regression models. Areas under ROC curve (AUC) of all scanning areas increased (P < 0.05) as disease severity increased. For a VFI value of 99%, indicating early damage, AUCs for rim area, average RNFL thickness, and ganglion cell complex-root mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%, indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992, respectively. Optic disc size did not influence the AUCs of any of the SDOCT scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and specificity decreased in large optic discs. Diagnostic accuracies of RTVue scanning protocols for glaucoma were significantly influenced by disease severity. Sensitivity of the rim area increased in large optic discs at the expense of specificity.

Predictors of Normal Optic Nerve Head, Retinal Nerve Fiber Layer, and Macular Parameters Measured by Spectral Domain Optical Coherence Tomography

To evaluate the effects of signal strength, age, sex, optic disc size, and axial length on the normal optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular measurements with spectral domain optical coherence tomography (SD-OCT). In an observational, cross-sectional study, 119 eyes of 60 normal subjects of Indian origin underwent ONH, RNFL, and macular imaging with SD-OCT during the same visit. Linear mixed-modeling methods were used to evaluate the effects of signal strength, age, sex, optic disc area, and axial length on ONH, RNFL, and macular measurements. ONH rim measurements increased and cup measurements decreased with increasing signal strengths. For a 10-unit increase in signal strength, total rim area increased by a mean of 0.1 mm(2). ONH measurements also increased with increasing optic disc size. Rim measurements decreased and cup measurements increased with increasing axial length. None of the predictors influenced RNFL measurements. Macular inner retinal thickness decreased by a mean of 1.7 μm and macular full retinal thickness decreased by an average of 3.4 μm for every decade's increase in age. Sex did not influence any of the measurements. Signal strength, optic disc size, and axial length had a significant effect on ONH measurements, whereas age had a significant effect on macular measurements. None of the predictors evaluated influenced the RNFL measurements. These predictors should be considered when evaluating change in the structural measurements in glaucoma over time.

The influence of axial length on retinal nerve fibre layer thickness and optic-disc size measurements by spectral-domain OCT

BackgroundTo evaluate the influence of axial length on measurements of the retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) parameters in healthy subjects.MethodsUsing Cirrus HD-OCT, RNFL thickness...

Heritability of optic disc diameters: a twin study

To assess the relative influence of genetic and environmental factors on optic disc size and cup/disc ratio in healthy eyes. A sample of 55 monozygotic and 50 dizygotic healthy twin pairs aged 20-46, all having the same sex within pairs (47 pairs were male) had optic discs measured from colour fundus photographs according to the Wisconsin Protocol. Structural equation modelling was used to estimate the relative contribution of genetic and environmental factors to the phenotype. Disc dimensions did not vary significantly by age or sex. After adjusting for age and sex, additive genetic factors (i.e. heritability) explained 77% (95% CI: 65-85%) of variation of vertical disc diameters, whereas estimated unshared environmental effect was 23% (95% CI: 15-35%). For vertical cup diameters, heritability accounted for 70% (95% CI: 55-80%) and environmental factors 30% (95% CI: 20-45%). For cup/disc ratio, additive genetic and unshared environmental factors explained 66% (95% CI: 48-77%) and 34% (95% CI: 23-52%) of the variations, respectively. In this healthy twin sample, we found that three quarters of the variations in vertical optic disc and optic cup diameters were attributable to genetic influence.

Correlation Between Peripapillary Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Parameters Using Spectral Domain Optical Coherence Tomography

To evaluate correlation between peripapillary retinal nerve fiber layer thickness (RNFL) and optic nerve head (ONH) parameters in normal participants using Spectral domain optical coherence tomography (OCT). Sixty-five eyes of 65 healthy participants aged 13-79 years underwent ONH analysis and peripapillary RNFL thickness measurements using spectral domain OCT. The RNFL measurements were correlated with the data obtained with ONH analysis. The average and quadrant RNFL thickness did not show correlation with optic disc area. A positive correlation was found between average RNFL thickness and rim area (r=0.425, P=0.000) and negative correlation between average RNFL thickness and cup area (r=-0.249, P<0.046). In our study, peripapillary RNFL thickness as measured by OCT did not show correlation with optic disc size. Despite a shorter distance between optic disc and circular scan margin, larger discs did not show a thicker RNFL. Interindividual variability of disc area probably minimizes the effect of various ONH size on RNFL thickness measurement.

Optic Disc Damage Staging System

To evaluate the optic disc damage staging system (ODDSS); a new clinical method of optic disc (OD) classification based on OD size, neural rim (NR) loss severity and localization. Accuracy, reproducibility, and reliability were studied. Agreement of ODDSS with the Heidelberg-Retina-Tomograph (HRT) results was evaluated. One eye of 68 consecutive open-angle glaucoma (POAG) patients and 40 controls underwent standard automated perimetry (SAP), HRT-II, and OD examination using the ODDSS classification by 3 independent graders in this prospective cross-sectional study. Sensitivity, specificity, and area under the receiver operating characteristic curve (AROC) in discriminating between normal and POAG eyes were determined for ODDSS and HRT parameters. ODDSS intraobserver and interobserver agreement and agreement with HRT-Moorfield-Regression-Analysis (MRA) were assessed. ODDSS sensitivity ranged from 72.0% to 89.7%; specificity ranged from 92.5% to 100%. Differences between AROCs for ODDSS (0.89 to 0.94) and for the best-performing HRT parameter (Vertical Cup/Disc Ratio 0.88) were not statistically significant. ODDSS interobserver agreement ranged from 0.33 to 0.78; intraobserver agreement ranged from 0.53 to 0.89. Agreement with HRT-MRA ranged from 0.50 to 0.87. ODDSS is a new method for assessing, recording, and sharing information about the clinical OD appearance. Our preliminary results show that it provides good sensitivity and specificity in glaucoma detection. The interobserver and intraobserver agreement ranged from fair to good.

Laminar and Prelaminar Tissue Displacement During Intraocular Pressure Elevation in Glaucoma Patients and Healthy Controls

To determine the response of the anterior lamina cribrosa and prelaminar tissue to acute elevation of intraocular pressure (IOP) in glaucoma patients and healthy subjects. Prospective case-control series. Patients with open-angle glaucoma (n = 12; mean age ± standard deviation [SD], 66.8 ± 6.0 years), age-matched healthy controls (n = 12; mean age ± SD, 67.1 ± 6.2 years), and young controls (n = 12; mean age ± SD, 36.1 ± 11.7 years). One eye was imaged with spectral-domain optical coherence tomography to obtain 12 high-resolution radial scans centered on the optic disc. Imaging was repeated at precisely the same locations with an ophthalmodynamometer held perpendicular to the globe via the inferior lid to raise the IOP. A line joining Bruch's membrane opening in 4 radial scans was used as reference in the baseline and elevated IOP images. The vertical distance from the reference line to the anterior prelaminar tissue surface and anterior laminar surface was measured at equidistant points along the reference line in the 2 sets of images. The difference between the 2 sets of corresponding measurements were used to determine laminar displacement (LD) and prelaminar tissue displacement (PTD). Laminar displacement and PTD. Intraocular pressure elevation among patients, age-matched controls, and young controls was similar (mean ± SD, 12.4 ± 3.2 mmHg). The mean ± SD LD and PTD were 0.5 ± 3.3 μm and 15.7 ± 15.5 μm, respectively. The LD was not statistically different from 0 (P = 0.366), but PTD was (P < 0.001). The mean ± SD LD was similar among the groups (-0.5 ± 3.7 μm, 0.2 ± 2.0 μm, and 2.0 ± 3.6 μm, respectively; P = 0.366), whereas the mean ± SD PTD was different (6.8 ± 13.7 μm, 20.8 ± 17.5 μm, and 19.6 ± 11.8 μm, respectively; P = 0.045). In all subjects, the PTD was greater than LD. In multivariate regression analyses, LD was negatively associated with optic disc size (P = 0.007), whereas PTD was positively associated with the degree of IOP elevation (P = 0.013). In glaucoma patients and controls, the anterior laminar surface is noncompliant to acute IOP elevation. Acute optic disc surface changes represent compression of prelaminar tissue and not laminar displacement.

Influence of Diabetes and Diabetic Retinopathy on the Performance of Heidelberg Retina Tomography II for Diagnosis of Glaucoma

To determine whether diabetes and diabetic retinopathy (DR) affect the performance of the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) algorithms for glaucoma detection. This population-based survey was conducted among Malays in Singapore who were a 40 to 80 years of age. Diabetes was defined as self-report of a physician's diagnosis, use of diabetic medication, or a random blood glucose level ≥11.1 mmol/L. Retinal photographs were graded for DR according to the modified Airlie House classification system. The diagnosis of glaucoma was based on International Society for Geographical and Epidemiologic Ophthalmology criteria. The sensitivity and the false-positive rates were calculated for the Moorfields regression analysis [MRA]; the linear discriminant functions (LDFs) by Mikelberg (Mikelberg-LDF), Burk (Burk-LDF), and Bathija (Bathija-LDF); and the support vector machine (SVM). A total of 1987 persons without diabetes (including 86 with glaucoma) and 524 with diabetes (including 26 with glaucoma) were analyzed. The presence of diabetes had no influence on both the sensitivities and false-positive rates for all HRT algorithms. In the multivariate analyses adjusting for optic disc size, the presence of DR was significantly associated with the higher false-positive rates for Burk-LDF and Bathija-LDF (P < 0.05), but not with the false-positive rates for MRA, Mikelberg-LDF, and SVM. Diabetes does not affect the performance of HRT II for diagnosis of glaucoma, but the presence of DR may be a source of false-positive test results.

Optic Nerve Head (ONH) Topographic Analysis by Stratus OCT in Normal Subjects: Correlation to Disc Size, Age, and Ethnicity

To study optic nerve head (ONH) topography parameters measured by Stratus optical coherence tomography (OCT) in normal subjects and to analyze ONH data for differences in relation to disc size, ethnicity, and age. Three hundred sixty-seven normal subjects underwent Stratus optical coherence tomography ONH measurement using the fast optic disc scan protocol software package 3.0. Only ONH scans meeting specific qualification criteria were included for data analysis ensuring appropriate scan quality and reliability. ONH topographic parameters of qualified scans were analyzed for differences in regards to optic disc size, age, and ethnicity. Two hundred and twelve qualified ONH scans were included for data analysis. Mean disc area was 2.27+/-0.41 mm and optic cup area, rim area, and horizontal integrated rim width increased with disc size, whereas vertical integrated rim area did not. Vertical integrated rim area, horizontal integrated rim width, and rim area decreased and cup area increased with age. Mean optic disc area was larger in African-Americans as compared with Hispanics or Whites and this difference was statistically significant. Optic cup area, rim area, and horizontal integrated rim width correlated to disc size. Vertical integrated rim area, horizontal integrated rim width, rim area, and cup area, changed with age. African-American optic discs had larger disc area measurements as compared with Whites optic discs and this difference was statistically significant.

OPA1 Mutations Associated with Dominant Optic Atrophy Influence Optic Nerve Head Size

To analyze the influence of OPA1 gene mutations on the optic nerve head (ONH) morphology in patients with dominant optic atrophy (DOA). Cross-sectional study. Twenty-eight patients with DOA from 11 pedigrees, which were positive for the presence of OPA1 gene mutations, and 56 age-matched control subjects, were enrolled. The ONH of DOA patients was studied by optical coherence tomography and compared with an age-matched control group of 56 individuals. ONH area, and vertical and horizontal diameters. The ONH analysis of DOA patients showed a significantly smaller optic disc area (P<0.0001), vertical (P = 0.018), and horizontal (P<0.0001) disc diameters, compared with controls. Stratification of the results for the single OPA1 mutation revealed normal ONH area with 2 mutations, whereas the only missense mutation linked to a "DOA plus" phenotype had the smallest ONH measurements. The DOA patients carrying OPA1 gene mutations present, as a group, a significantly smaller ONH compared with the range of size observed in a control population; this feature may be mutation specific. This observation suggests that OPA1 is involved in shaping the anatomic conformation of the ONH in patients with DOA. The relevance of OPA1 in regulating apoptosis and modeling the eye development has been recently shown by others. Thus, mutations in the OPA1 gene may determine the previously unrecognized feature of a smaller optic disc size and this in turn may have relevance for DOA pathogenesis. Furthermore, OPA1 gene polymorphic variants may contribute to the normal variability of ONH size in the general population.

Genome-wide association identifies ATOH7 as a major gene determining human optic disc size

Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P = 6.2 × 10−10, near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P = 3.4 × 10−10. Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P = 1.3 × 10−10 to 4.3 × 10−11, top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P = 1.5 × 10−7, in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P = 0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls.

Influence of optic-disc size on parameters of retinal nerve fibre analysis as measured using GDx VCC and ECC in healthy subjects

BackgroundTo date, there is no knowledge on the impact of optic-disc size on the retinal nerve fibre layer (RNFL) as measured with GDx VCC or GDx ECC. Since the size...