Optic Nerve Head Sectors Research Articles

Structural measurements and vessel density of spectral-domain optic coherence tomography in early, moderate, and severe primary angle-closure glaucoma.

To compare the macular ganglion cell-inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters, and retinal vessel density (VD) measured by spectral-domain optical coherence tomography (SD-OCT) and analyze the correlations between them in the early, moderate, severe primary angle-closure glaucoma (PACG) and normal eyes. Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis. PACG eyes were further separated into early, moderate, or severe PACG eyes using the Enhanced Glaucoma Staging System (GSS2). The GCIPL thickness, RNFL thickness, ONH parameters, and retinal VD were measured by SD-OCT, differences among the groups and correlations within the same group were calculated. The inferior and superotemporal sectors of the GCIPL thickness, rim area of ONH, average and inferior sector of the retinal VD were significantly reduced (all P<0.05) in the early PACG eyes compared to the normal and the optic disc area, cup to disc ratio (C/D), and cup volume were significantly higher (all P<0.05); but the RNFL was not significant changes in early and moderate PACG. In severe group, the GCIPL and RNFL thickness were obvious thinning with retinal VD were decreasing as well as C/D and cup volume increasing than other three groups (all P<0.01). In the early PACG subgroup, there were significant positive correlations between retinal VD and GCIPL thickness (except superonasal and inferonasal sectors, r=0.573 to 0.641, all P<0.05), superior sectors of RNFL thickness (r=0.055, P=0.049). More obvious significant positive correlations were existed in moderate PACG eyes between retinal VD and superior sectors of RNFL thickness (r=0.650, P=0.022), and temporal sectors of RNFL thickness (r=0.740, P=0.006). In the severe PACG eyes, neither GCIPL nor RNFL thickness was associated with retinal VD. The ONH damage and retinal VD loss appears earlier than RNFL thickness loss in PACG eyes. As the PACG disease progressed from the early to the moderate stage, the correlations between the retinal VD and RNFL thickness increases.

Choroidal microvasculature dropout is spatially associated with optic nerve head microvasculature loss in open-angle glaucoma

The presence of parapapillary choroidal microvasculature dropout (CMvD) may affect optic nerve head (ONH) perfusion in glaucoma patients, since parapapillary choroidal vessels provide vascular supply to the neighboring ONH. However, it remains to be determined whether the presence of parapapillary CMvD is associated with diminished perfusion in the nearby ONH. The present study investigated the spatial relationship between CMvD and ONH vessel density (ONH-VD) loss in open-angle glaucoma (OAG) eyes using optical coherence tomography angiography (OCT-A). This study included 48 OAG eyes with a single localized CMvD confined to the inferotemporal parapapillary sector and 48 OAG eyes without CMvD, matched for demographic and ocular characteristics. Global and regional ONH-VD values were compared between eyes with and without CMvD. The relationships between ONH-VD outcomes and clinical variables were assessed. ONH-VDs at the inferotemporal ONH sectors corresponding to the CMvD location were significantly lower in eyes with compared to those without CMvD. Multivariable linear regression analyses indicated that a lower inferotemporal ONH-VD was independently associated with CMvD presence and a greater CMvD angular extent (both P < 0.05). The localized presence of parapapillary CMvD in OAG eyes is significantly associated with ONH-VD loss in the neighboring ONH location, with a spatial correlation.

Improving Personalized Structure to Function Mapping From Optic Nerve Head to Visual Field.

PurposeMaps are required to relate visual field locations to optic nerve head regions. We compare individualized structure-to-function mapping (CUSTOM-MAP) to a population-derived mapping schema (POP-MAP).MethodsMaps were compared for 118 eyes with glaucomatous field loss, circumpapillary retinal nerve fiber layer (cpRNFL) thickness measured using spectral domain optical coherence tomography (OCT), and two landmarks: the optic nerve head (ONH) position relative to the fovea and the temporal raphe angle. Locations with visual field damage (total deviation < −6 dB) were mapped to 30° ONH sectors centered on the angle given by each mapping schema. The concordance between damaged function and damaged structure was determined per location for various cpRNFL damage probability levels, with the number of concordant locations divided by the total number of damaged field locations providing a concordance ratio per eye.ResultsFor the strictest concordance criteria (minimum cpRNFL thickness < 1% of normal), CUSTOM-MAP had higher mean concordance ratio than POP-MAP (60.5% c.f. 57.0% paired Wilcoxon, P = 0.005), with CUSTOM-MAP having a higher ratio in 43 eyes and POP-MAP having a higher ratio in 21 eyes. For all cpRNFL probability levels <20% of normal, more locations concorded for CUSTOM-MAP than POP-MAP. Inspection of the spatial patterns of differences revealed that CUSTOM-MAP often performed better in the arcuate regions, whereas POP-MAP had benefits inferior to the macula.ConclusionsAnatomic parameters required for individualized structure-function mapping are readily measured with OCT and can provide improved concordance for some eyes.Translational RelevancePersonalizing structure-function mapping may improve concordance between these measures. We provide a web-based tool for creating customized maps.

The Optimal Diameter for Circumpapillary Retinal Nerve Fiber Layer Thickness Measurement by SD-OCT in Glaucoma.

To evaluate the diagnostic power for glaucoma detection using circumpapillary retinal nerve fiber layer (cRNFL) thickness in 3 diameter sizes from the center of the optic nerve head (ONH) by spectral domain optical coherence tomography. In this cross-sectional study, case-control, 437 eyes diagnosed with glaucoma and 183 eyes of healthy controls underwent spectral domain optical coherence tomography of the ONH, visual field testing, and a clinical examination. cRNFL was measured by circular scans in 3.5 (C1), 4.1 (C2), and 4.7 mm (C3) distance from the center of the ONH. Receiver-operator characteristic analysis was used to assess diagnostic power to detect glaucoma; furthermore, patient-specific maximum localized damage was analyzed. In C1, mean global cRNFL was 70.03±18.2 μm in glaucomatous eyes and 93.46±9.9 μm in controls. Respectively, cRNFL in C2 was 61.39±14.9 and 80.43±8.4 μm as well as 55.25±12.8 and 70.70±6.7 μm in C3. Using receiver-operator characteristic analysis, the area under the curve (AUC) for cRNFL was 0.855 in C1, 0.850 in C2, and 0.843 in C3. Mean AUCs in ONH sectors ranged from 0.699 to 0.846 and did not exceed AUC of the best scoring global parameter. Comparing 3.5, 4.1, and 4.7 mm diameters for cRNFL measurement, the inner circle at 3.5 mm distance showed the highest AUC to differentiate glaucoma from healthy controls. However, levels of diagnostic power from wider circular scans were not significantly different and were comparable. Moreover, sectorial cRNFL measurements were nonsuperior. The use of the ONH sector with the highest localized damage seems not to increase diagnostic power.

Optimization Strategies for Bruch\u2019s Membrane Opening Minimum Rim Area Calculation: Sequential versus Simultaneous Minimization

To compare a simultaneously optimized continuous minimum rim surface parameter between Bruch’s membrane opening (BMO) and the internal limiting membrane to the standard sequential minimization used for calculating the BMO minimum rim area in spectral domain optical coherence tomography (SD-OCT). In this case-control, cross-sectional study, 704 eyes of 445 participants underwent SD-OCT of the optic nerve head (ONH), visual field testing, and clinical examination. Globally and clock-hour sector-wise optimized BMO-based minimum rim area was calculated independently. Outcome parameters included BMO-globally optimized minimum rim area (BMO-gMRA) and sector-wise optimized BMO-minimum rim area (BMO-MRA). BMO area was 1.89 ± 0.05 mm2. Mean global BMO-MRA was 0.97 ± 0.34 mm2, mean global BMO-gMRA was 1.01 ± 0.36 mm2. Both parameters correlated with r = 0.995 (P < 0.001); mean difference was 0.04 mm2 (P < 0.001). In all sectors, parameters differed by 3.0–4.2%. In receiver operating characteristics, the calculated area under the curve (AUC) to differentiate glaucoma was 0.873 for BMO-MRA, compared to 0.866 for BMO-gMRA (P = 0.004). Among ONH sectors, the temporal inferior location showed the highest AUC. Optimization strategies to calculate BMO-based minimum rim area led to significantly different results. Imposing an additional adjacency constraint within calculation of BMO-MRA does not improve diagnostic power. Global and temporal inferior BMO-MRA performed best in differentiating glaucoma patients.

The Proportion of Individuals Likely to Benefit from Customized Optic Nerve Head Structure–Function Mapping

Interindividual variance in optic nerve head (ONH) position, axial length, and location of the temporal raphe suggest that customizing mapping between visual field locations and ONH sectors for individuals may be clinically useful. Herein we quantify the proportion of the population predicted to have structure-function mappings that markedly deviate from "average," and thus would benefit from customized mapping. Database study and case report. Population database of 2836 eyes from the Beijing Eye Study and a single case report of an individual with primary open-angle glaucoma. Using the morphometric fundus data of the Beijing Eye Study for 2836 eyes and applying a recently developed model based on axial length and ONH position relative to the fovea, we determined for each measurement location in the 24-2 Humphrey (Carl Zeiss Meditec, Dublin, CA) visual field the proportion of eyes for which, in the customized approach as compared with the generalized approach, the mapped ONH sector was shifted into a different sector. We determined the proportion of eyes for which the mapped ONH location was shifted by more than 15°, 30°, or 60°. Mapping correspondence between locations in visual field space to localized sectors on the ONH. The largest interindividual differences in mapping are in the nasal step region, where the same visual field location can map to either the superior or inferior ONH, depending on other anatomic features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. Anatomically customized mapping shifts the map markedly in approximately 12% of the general population in the nasal step region, where visual field locations can map to the opposite pole of the ONH than conventionally considered. Early glaucomatous damage commonly affects this region; hence, individually matching structure to function may prove clinically useful for the diagnosis and monitoring of progression within individuals.

Enhancing Structure–Function Correlations in Glaucoma with Customized Spatial Mapping

To determine whether the structure-function relationship in glaucoma can be strengthened by using more precise structural and functional measurements combined with individualized structure-function maps and custom sector selection on the optic nerve head (ONH). Cross-sectional study. One eye of each of 23 participants with glaucoma. Participants were tested twice. Visual fields were collected on a high-resolution 3° × 3° grid (164 locations) using a Zippy Estimation by Sequential Testing test procedure with uniform prior probability to improve the accuracy and precision of scotoma characterization relative to standard methods. Retinal nerve fiber layer (RNFL) thickness was measured using spectral-domain optical coherence tomography (OCT; 4 scans, 2 per visit) with manual removal of blood vessels. Individualized maps, based on biometric data, were used. To customize the areas of the ONH and visual field to correlate, we chose a 30° sector centered on the largest defect shown by OCT and chose visual field locations using the individualized maps. Baseline structure-function correlations were calculated between 24-2 locations (n = 52) of the first tested visual field and RNFL thickness from 1 OCT scan, using the sectors of the Garway-Heath map. We added additional data (averaged visual field and OCT, additional 106 visual field locations and OCT without blood vessels, individualized map, and customized sector) and recomputed the correlations. Spearman correlation between structure and function. The highest baseline correlation was 0.52 (95% confidence interval [CI], 0.13-0.78) in the superior temporal ONH sector. Improved measurements increased the correlation marginally to 0.58 (95% CI, 0.21-0.81). Applying the individualized map to the large, predefined ONH sectors did not improve the correlation; however, using the individualized map with the single 30° ONH sector resulted in a large increase in correlation to 0.77 (95% CI, 0.47-0.92). Using more precise visual field and OCT measurements did not improve structure-function correlation in our cohort, but customizing the ONH sector and its associated visual field points substantially improved correlation. We suggest using customized ONH sectors mapped to individually relevant visual field locations to unmask localized structural and functional loss.

Enhanced Structure-Function Relationship in Glaucoma With an Anatomically and Geometrically Accurate Neuroretinal Rim Measurement

To evaluate the structure-function relationship between disc margin-based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruch's membrane opening-based horizontal rim width (BMO-HRW), minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFLT) obtained with spectral-domain optical coherence tomography (SD-OCT), and visual field sensitivity. We examined 151 glaucoma patients with CSLT, SD-OCT, and standard automated perimetry on the same day. Optic nerve head (ONH) and RNFL with SD-OCT were acquired relative to a fixed coordinate system (acquired image frame [AIF]) and to the eye-specific fovea-BMO center (FoBMO) axis. Visual field locations were mapped to ONH and RNFL sectors with fixed Garway-Heath (VF(GH)) and patient-specific (VF(PS)) maps customized for various biometric parameters. Globally and sectorally, the structure-function relationships between DM-RA and VF(GH), BMO-HRW(AIF) and VF(GH), and BMO-HRW(FoBMO) and VF(PS) were equally weak. The R(2) for the relationship between DM-RA and VF(GH) ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRW(AIF) and VF(GH) ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure-function relationships with BMO-MRW(AIF) and with BMO-MRW(FoBMO) were obtained. The R(2) between BMO-MRW(AIF) and VF(GH) ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRW(FoBMO) and VF(PS) ranged from 5% (nasal) to 25% (inferotemporal). The structure-function relationship with RNFLT was not significantly different from that with BMO-MRW, regardless of image acquisition method. The structure-function relationship was enhanced with BMO-MRW compared with the other neuroretinal rim measurements, due mainly to its geometrically accurate properties.

Sectoral variations in the distribution of axonal cytoskeleton proteins in the human optic nerve head

Axonal cytoskeleton proteins are intrinsically related to retinal ganglion cell (RGC) health and disease. This study quantifies and documents the sectoral distribution of axonal cytoskeleton proteins in the different laminar compartments of the normal human optic nerve head (ONH). Nine human eyes were used (mean age of 46.9 ± 3.7 years). Coronal sections of the prelaminar, anterior lamina cribrosa, posterior lamina cribrosa and retrolaminar regions were examined using immunohistochemical and confocal microscopy techniques. The axonal cytoskeleton was studied using antibodies to neurofilament light (NFL), neurofilament medium (NFM), neurofilament heavy (NFH), phosphorylated NFH (NFHp), microtubule associated protein-1 (MAP-1) and tubulin. Axonal cytoskeleton intensity was quantified in a standardized manner and comparisons were made within and between laminar regions. The intensity of NFM, NFH and NFHp is significantly greater in the nasal and peripheral sectors of the prelaminar, anterior lamina cribrosa and posterior lamina cribrosa regions. There is no significant difference in the distribution of NFL, tubulin and MAP-1 proteins between sectors in any laminar region. The intensity of all axonal cytoskeleton proteins in unmyelinated laminar regions is greater than the retrolaminar region. The distribution of all cytoskeleton proteins in the myelinated, retrolaminar region of the optic nerve appears to be relatively even. The distribution of axonal cytoskeleton proteins may have relevance for understanding the vulnerability of distinct ONH sectors to intraocular pressure- and ischaemia-mediated damage. The findings in this study may be important for understanding patho-physiological mechanisms involved in glaucomatous and ischaemic optic neuropathy.

Individualized Structure–Function Mapping for Glaucoma: Practical Constraints on Map Resolution for Clinical and Research Applications

We have developed customized maps that relate visual field and optic nerve head (ONH) regions according to individual anatomy. In this study, we aimed to determine feasible map resolution for research use, and to make a principled recommendation of sector size for clinical applications. Measurement variability in fovea-ONH distance and angle was estimated from 10 repeat OCT scans of 10 healthy people. Errors in estimating axial length from refractive error were determined from published data. Structure-function maps were generated, and customized to varied clinically-plausible anatomical parameters. For each parameter set (n = 210), 200 maps were generated by sampling from measurement/estimation error distributions. Mapped 1° sectors at each visual field location from each parameter set were normalized to difference from their mean. Variation (90% ranges) in normalized mapped sectors represents the precision of individualized maps. Standard deviations of repeated measures of fovea-ONH distance and angle were 61 μm and 0.97° (coefficients of variation 1.3% and 12.0%, respectively). Neither measure varied systematically with mean (Spearmans's ρ = 0.26, P = 0.47 for distance, ρ = -0.31, P = 0.39 for angle). Variation (90% ranges) in normalized mapped sectors varied across the visual field and ranged from 3° to 18° when axial length was measured accurately, and from 6° to 32° when axial length was estimated from refractive error. The 90% ranges represent the minimum feasible ONH sector size at each visual field location. For clinical use an easily interpretable scheme of 30° sectors is suggested.

Structure–Function Mapping: Variability andConvictionin Tracing Retinal Nerve Fiber Bundles and Comparison to a Computational Model

We evaluated variability and conviction in tracing paths of retinal nerve fiber bundles (RNFBs) in retinal images, and compared traced paths to a computational model that produces anatomically-customized structure-function maps. Ten retinal images were overlaid with 24-2 visual field locations. Eight clinicians and 6 naïve observers traced RNFBs from each location to the optic nerve head (ONH), recording their best estimate and certain range of insertion. Three clinicians and 2 naïve observers traced RNFBs in 3 images, 3 times, 7 to 19 days apart. The model predicted 10° ONH sectors relating to each location. Variability and repeatability in best estimates, certain range width, and differences between best estimates and model-predictions were evaluated. Median between-observer variability in best estimates was 27° (interquartile range [IQR] 20°-38°) for clinicians and 33° (IQR 22°-50°) for naïve observers. Median certain range width was 30° (IQR 14°-45°) for clinicians and 75° (IQR 45°-180°) for naïve observers. Median repeatability was 10° (IQR 5°-20°) for clinicians and 15° (IQR 10°-29°) for naïve observers. All measures were worse further from the ONH. Systematic differences between model predictions and best estimates were negligible; median absolute differences were 17° (IQR 9°-30°) for clinicians and 20° (IQR 10°-36°) for naïve observers. Larger departures from the model coincided with greater variability in tracing. Concordance between the model and RNFB tracing was good, and greatest where tracing variability was lowest. When RNFB tracing is used for structure-function mapping, variability should be considered.

An Anatomically Customizable Computational Model Relating the Visual Field to the Optic Nerve Head in Individual Eyes

To present a computational model mapping visual field (VF) locations to optic nerve head (ONH) sectors accounting for individual ocular anatomy, and to describe the effects of anatomical variability on maps produced. A previous model that related retinal locations to ONH sectors was adapted to model eyes with varying axial length, ONH position and ONH dimensions. Maps (n = 11,550) relating VF locations (24-2 pattern, n = 52 non-blind-spot locations) to 1° ONH sectors were generated for a range of clinically plausible anatomical parameters. Infrequently mapped ONH sectors (5%) were discarded for all locations. The influence of anatomical variables on the maps was explored by multiple linear regression. Across all anatomical variants, for individual VF locations (24-2), total number of mapped 1° ONH sectors ranged from 12 to 90. Forty-one locations varied more than 30°. In five nasal-step locations, mapped ONH sectors were bimodally distributed, mapping to vertically opposite ONH sectors depending on vertical ONH position. Mapped ONH sectors were significantly influenced (P < 0.0002) by axial length, ONH position, and ONH dimensions for 39, 52, and 30 VF locations, respectively. On average across all VF locations, vertical ONH position explained the most variance in mapped ONH sector, followed by horizontal ONH position, axial length, and ONH dimensions. Relations between ONH sectors and many VF locations are strongly anatomy-dependent. Our model may be used to produce customized maps from VF locations to the ONH in individual eyes where some simple biometric parameters are known.

Sector-Based Analysis with the Heidelberg Retinal Tomograph 3 Across Disc Sizes and Glaucoma Stages: A Multicenter Study

To investigate the ability of sectorial analysis using the Heidelberg Retinal Tomograph 3 (HRT3) to discriminate between healthy and glaucomatous eyes and to determine whether this is affected by disc size and glaucoma severity. Multicenter, cross-sectional evaluation of diagnostic tests. Two hundred thirty-three eyes from 137 normal subjects and 96 glaucoma patients classified by the presence of a repeatable visual field defect. Participants underwent imaging with the HRT3, and the diagnostic accuracy of stereometric parameters, Moorfields regression analysis (MRA), and glaucoma probability score (GPS) were analyzed sectorially by glaucoma stage and optic disc size. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristics curve (AUC). Of stereometric parameters, the cup-to-disc area ratio of the inferotemporal sector had the largest AUC (AUC, 0.74). Both MRA and GPS algorithms showed the best diagnostic accuracy in the inferotemporal sector, with a sensitivity and specificity of 63% and 88% for MRA and 80% and 62% for GPS, respectively. In small discs, sectorial MRA analysis had higher diagnostic accuracy than the global optic nerve head (ONH) analysis (sensitivity of 70% and specificity of 82% in the inferonasal sector), and these findings were confirmed in very large discs (sensitivity of 74% and specificity of 85% in the inferotemporal sector). Similarly, stereometric parameters discriminated better sectorially rather than globally, with different parameters giving the best results in different optic disc size subgroups. MRA sensitivity was weak in the early-glaucoma stage, with slightly higher figures if considered sectorially rather than globally. GPS diagnostic accuracy was very consistent across ONH sectors in each disc size and glaucoma stage subgroup, with no single sector demonstrating better diagnostic accuracy than the global analysis. Heidelberg Retinal Tomograph 3 sectorial analysis showed moderate diagnostic performance and may offer potential advantages over global analysis in the clinical diagnostic process. Small discs are classified more accurately by examining the inferonasal sector, whereas larger discs are classified more accurately by examining the inferotemporal sector. Neither HRT parameters nor classification algorithms seem to be good at the earlier stage of the disease. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Combining Ganglion Cell Topology and Data of Patients with Glaucoma to Determine a Structure–Function Map

To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P < 0.05) correlation coefficient within 40 degrees of the angle predicted by GROW for each location was computed. Before correlation, both functional and structural data were normalized by either normative data or the fellow eye in each participant. The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P < 0.001) when both field and rim area data were normalized with the fellow eye. A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data.

Evaluation of the Structure-Function Relationship in Glaucoma

While glaucoma is evaluated on the basis of structural and functional test results, the spatial relationship between structure and function is not well defined. This study produces a topographical map to demonstrate how sectors of the optic nerve head (ONH) are related to locations in the visual field, using empiric cross-sectional patient data. One hundred nine subjects with healthy eyes and 166 subjects with diagnosed or suspected glaucoma (one test per patient) were evaluated using a retina tomograph and white-on-white standard automated perimetry (SAP). The tomograph ONH images were divided into 36 sectors; and the sector rim areas normalized to account for changes in the total rim area. These were then correlated with SAP thresholds. For each visual field location, a map was produced indicating the strength of correlation between the normalized sector rim areas and thresholds. The highest correlation between a sector's normalized rim area and a SAP location's sensitivity was 0.520. Twenty-seven of the 52 non-blind spot SAP locations exhibited a correlation greater than 0.2 with at least one ONH sector. Locations in the superior hemifield were usually best correlated with the polar inferior temporal sectors of the ONH; locations in the inferior hemifield were usually best correlated with the polar superior temporal sectors of the ONH. A map relating regions of the ONH to SAP test locations has been produced. This map may be useful in elucidating the structure-function relationship, particularly for cases of localized glaucomatous loss.