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yes / We have read with interest the recent article by Sponsel et al.1 There is much evidence that glaucomatous damage occurs at the optic nerve head,2 and therefore we were surprised by the authors' conjecture that there may be a central mechanism that preserves the binocular visual field in advanced glaucoma.

no / Purpose 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). Design Cross-sectional study. Participants One eye of each of 23 participants with glaucoma. Methods 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. Main Outcome Measures Spearman correlation between structure and function. Results 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). Conclusions 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.

yes / Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

yes / Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

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Despite that the RGC axons closely associated with astrocytes, the role of astrocytes in RGC regeneration was uncertain. In view of this, the effect of cultured adult astrocytes on RGC regeneration through an extensive ON lesion segment was studied. Adult ON astrocytes were prepared by sub-culturing of cells migrating out of ON explants. A small hole in the ON was punctured by 27G needle and about 0.5 to 1.0mul (1000 cells) cultured astrocytes was injected into the extensive ON lesion segment. We found that cultured adult astrocytes promoted significant RGC axon regeneration in the extensive ON lesion. / Finally, co-transplantation of intravitreal PN followed by transplantation of astrocytes into the extensive lesion has a synergistic effect on the regrowth of RGC axons, as indicated by the maximum distance achieved by regenerating axons and integrated intensity of staining of the CTB-labeled axons. Transplanatation of VPN+AST, VPN+NAST and NPN+AST as 3.9, 2.5 and l.9 times more potent in inducing regeneration than that of NPN+NAST as shown by integrated intensity measurement. However, co-transplantation of PN and astrocytes could not enhance RGC survival. (Abstract shortened by UMI.) / In this study, we have established an extensive lesion paradigm to study the behavior of injured retinal ganglion cell (RGC) axons after ON crush in adult golden hamster. We found that RGC axons regenerated in the extensive lesion for 406.8mum at 1 week post-crush to 1174.0mum at 4 weeks post-crush. RGC axons were able to regenerate the entire lesion segment but they terminated precisely at the interface between the lesion and the distal segment of the ON. Regrowing axons were intimately associated with astrocytes which repopulated the lesion segment. Repopulated oligodendrocytes were scattered in the lesion segment and myelin debris was significantly decreased in the lesion segment with time. / It is commonly believed that central nervous system (CNS) neurons are unable to regenerate after injury. Recently, there have been several lines of evidence showing that damaged CNS neurons can undergo axonal regeneration under appropriate conditions. Since the retina and optic nerve (ON) are regarded as part of the CNS, therefore, they are used as a model to study CNS regeneration. / Kong Wai Chi. / "July 2005." / Adviser: Y.P. Cho. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3616. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 96-115). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

[Truncated abstract] Formation and consolidation of the retinotectal projection during optic nerve regeneration has been associated with two major interlinked processes. Initially, retinal ganglion cell (RGC) axons are guided by molecular guidance cues, such as the Eph receptor tyrosine kinases and their ligands, the ephrins, to their approximately correct location and form a coarse topographic map in the optic tecum. Such axon guidance occurs in the absence of neural activity and is considered to be activity-independent. The second process involves glutamatergic excitation, whereby correctly located connections are strengthened by correlated neural activity, whilst removing inappropriately located ones thereby sharpening the topography.The second process is considered to be activitydependent. Here, a number of experiments were undertaken to further examine the interrelationships of activity-dependent and independent processes with respect to functional outcomes. Two models of optic nerve regeneration were studied. In goldfish, following optic nerve crush, regeneration is successful. … In goldfish, guidance along the medio-lateral tectal axis may occur through preordering of axons prior to entering the tectum via the appropriate medial and lateral brachium, with EphA/ephrin-A then guiding axons over the rostral-caudal axis establishing gross topography. The increase in involvement of NMDA-mediated transmission during the period of activity-dependent refinement consolidated the role of this receptor in synapse plasticity. However what triggers NMDA-mediated activity to increase is still largely unresolved, although as the factors governing receptor trafficking during development and synaptic plasticity become better understood, these can be applied to the period of plasticity associated with regenerating axons. And finally, as GABAergic inhibition appears to suppress activity-dependent refinement, means of overcoming this inhibition through 4 such methods as visual training or pharmacological intervention may have significance for mammalian regeneration.