Pattern Of Visual Field Loss Research Articles

Local Glaucomatous Defects of the Circumpapillary Retinal Nerve Fiber Layer Show a Variety of Patterns of Progression.

The region of glaucomatous progression, seen on optical coherence tomography (OCT) images of the circumpapillary retinal nerve fiber layer (cRNFL), increases in width and depth in all eyes, but shows a variety of different patterns of loss across eyes. The purpose of this study was to examine the patterns of cRNFL loss secondary to glaucomatous progression in a region associated with the superior hemifield of the 24-2/30-2 visual field (VF). Twenty-four eyes (20 patients) with a diagnosis of glaucoma and evidence of progression on OCT had OCT disc cube scans on at least 3 separate visits (mean follow-up 7.4 y; range: 3.9 to 11.4). Circumpapillary b-scans were derived after enface images were aligned to assure that the study region (ie, 0 to -135 degrees, where 0 degree is 9 o'clock, on a right eye) coincided. Within this region, a region of progression (ROP) was defined based on the loss in cRNFL thickness between the first and subsequent visits. The width of the ROP was determined, along with the locations of its leading (close to fixation) and trailing edges. In addition, for each ROP, the location and depth at the point of maximal loss, total loss, and average remaining retinal nerve fiber layer were measured. The ROP proceeded both toward and away from fixation. Across eyes, the ROP varied widely in width (32 to 131 degrees, mean 82.7 degrees), location, and loss at point of deepest loss (22 to 99 μm, mean 52.9 μm), as well as total cRNFL loss. All eyes showed a widening and deepening of the ROP, but a variety of different patterns of progressive cRNFL loss. Thus, one should expect considerable variation in patterns of VF loss. Furthermore, conventional metrics (global or quadrant cRNFL thickness) do not fully depict the progressive changes that can be appreciated by inspecting OCT images.

Estimating Rates of Progression and Predicting Future Visual Fields in Glaucoma Using a Deep Variational Autoencoder

In this manuscript we develop a deep learning algorithm to improve estimation of rates of progression and prediction of future patterns of visual field loss in glaucoma. A generalized variational auto-encoder (VAE) was trained to learn a low-dimensional representation of standard automated perimetry (SAP) visual fields using 29,161 fields from 3,832 patients. The VAE was trained on a 90% sample of the data, with randomization at the patient level. Using the remaining 10%, rates of progression and predictions were generated, with comparisons to SAP mean deviation (MD) rates and point-wise (PW) regression predictions, respectively. The longitudinal rate of change through the VAE latent space (e.g., with eight dimensions) detected a significantly higher proportion of progression than MD at two (25% vs. 9%) and four (35% vs 15%) years from baseline. Early on, VAE improved prediction over PW, with significantly smaller mean absolute error in predicting the 4th, 6th and 8th visits from the first three (e.g., visit eight: VAE8: 5.14 dB vs. PW: 8.07 dB; P < 0.001). A deep VAE can be used for assessing both rates and trajectories of progression in glaucoma, with the additional benefit of being a generative technique capable of predicting future patterns of visual field damage.

Correlation of MRI Findings With Patterns of Visual Field Loss in Patients With Pituitary Tumors.

Compression of the optic chiasm by pituitary tumors typically results in bitemporal hemianopia, implying that nasal retinal fibers are preferentially damaged. The reason for this is not clear. One theory suggests that nasal fibers are selectively vulnerable simply because they cross each other. This study investigated the "crossing theory" by correlating visual field (VF) loss with chiasmal elevation and with the degree of eccentric compression on MRI scans. Our hospital database was searched to identify patients with a) chiasmal compression by a pituitary tumor; b) documented preoperative evidence of VF loss; and c) preoperative MRI scan performed within 1 month of VF testing. Temporality and bitemporality indices were derived from pattern deviation VF plots. Elevations of the central and peripheral parts of the chiasm were obtained from MRI scans, from which the eccentricity of compression was calculated. Temporality indices and hemifield loss were compared with central chiasmal elevation, and nasal hemifield loss in each eye was plotted against eccentricity. Eleven patients were suitable for analysis. The degree of bitemporal VF involvement was significantly correlated with elevation of the central chiasm (P = 0.004). However, there was minimal involvement of nasal VFs, and no demonstrable increase in nasal field loss with increasing eccentricity of compression. This study provides support for the crossing theory. These findings will inform further finite element models of chiasmal compression. A larger, prospective study is planned.

Programme choice for perimetry in neurological conditions (PoPiN): a systematic review of perimetry options and patterns of visual field loss

BackgroundVisual field loss occurs frequently in neurological conditions and perimetry is commonly requested for patients with suspected or known conditions. There are currently no guidelines for how visual fields in neurological conditions should be assessed. There is a wide range of visual field programs available and the wrong choice of program can potentially fail to detect visual field loss. We report the results of a systematic review of the existing evidence base for the patterns of visual field loss in four common neurological conditions and the perimetry programs used, to aid the design of future research and clinical practice guidelines.MethodsA systematic search of the literature was performed. The inclusion criteria required studies testing and/or reporting visual field loss in one or more of the target conditions; idiopathic intracranial hypertension, optic neuropathy, chiasmal compression and stroke. Scholarly online databases and registers were searched. In addition articles were hand searched. MESH terms and alternatives in relation to the four target conditions and visual fields were used. Study selection was performed by two authors independently. Data was extracted by one author and verified by a second.ResultsThis review included 330 studies; 51 in relation to idiopathic intracranial hypertension, 144 in relation to optic neuropathy, 105 in relation to chiasmal compression, 21 in relation to stroke and 10 in relation to a mixed neuro-ophthalmology population.ConclusionsBoth the 30–2 and 24–2 program using the Humphrey perimeter were most commonly reported followed by manual kinetic perimetry using the Goldmann perimeter across all four conditions included in this review. A wide variety of other perimeters and programs were reported. The patterns of visual field defects differ much more greatly across the four conditions. Central perimetry is used extensively in neurological conditions but with little supporting evidence for its diagnostic accuracy in these, especially considering the peripheral visual field may be affected first whilst the central visual field may not be impacted until later in the progression. Further research is required to reach a consensus on how best to standardise perimetry for neurological conditions.

Distribution and Rates of Visual Field Loss across Different Disease Stages in Primary Open-Angle Glaucoma

To identify patterns and rates of visual field (VF) loss in primary open-angle glaucoma (POAG) across different levels of severity. Retrospective, observational case series. Visual fields of 278 eyes of 139 patients with POAG (9 years of follow-up with ∼17 visits) from the Rotterdam Eye Hospital in The Netherlands were analyzed to identify patterns and rates of VF loss. Rate of VF decline for the entire VF, each region, and test point. Hemifield asymmetric rate if VF decline for each region and test point. Total deviation (TD) values were extracted from the Humphrey VF Analyzer (Carl Zeiss Meditec, Dublin, CA). Eyes were stratified into 3 glaucoma stages by means of the mean deviation (MD): better than-6 decibels (dB), worse than-6 dB and better than-12 dB, and worse than-12 dB. Each hemifield was divided into 5 regions according to the Glaucoma Hemifield Test (GHT): central, paracentral, nasal, and peripheral arcuates 1 and 2. Point-wise and region-wise asymmetric patterns of VF loss and rate of VF loss were identified by comparing the values in the superior hemifield and the inferior hemifield at each severity level using a generalized estimating equation. The mean age of the patients was 60.2±10.3 years (mean ± standard deviation [SD]). The rate of MD loss, for all eyes taken together, was-0.11 dB/year. In the cross-sectional analysis, in eyes in the early and moderate stages, central and peripheral arcuate 2 regions in the superior hemifield were worse than their inferior counterpart, whereas in the advanced stage all GHT regions in the superior hemifield were significantly worse than the corresponding regions in the inferior hemifield (P ≤ 0.05). In the longitudinal analysis, there was no significant difference in the rate of VF loss between the GHT regions in the superior and inferior hemifields. Our findings suggest that in POAG, VF damage is worse in the superior hemifield than in the inferior hemifield.

Reversal of Glaucoma Hemifield Test Results and Visual Field Features in Glaucoma

To develop a visual field (VF) feature model to predict the reversal of glaucoma hemifield test (GHT) results to within normal limits (WNL) after 2 consecutive outside normal limits (ONL) results. Retrospective cohort study. Visual fields of 44 503 eyes from 26 130 participants. Eyes with 3 or more consecutive reliable VFs measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm standard 24-2) were included. Eyes with ONL GHT results for the 2 baseline VFs were selected. We extracted 3 categories of VF features from the baseline tests: (1) VF global indices (mean deviation [MD] and pattern standard deviation), (2) mismatch between baseline VFs, and (3) VF loss patterns (archetypes). Logistic regression was applied to predict the GHT results reversal. Cross-validation was applied to evaluate the model on testing data by the area under the receiver operating characteristic curve (AUC). We ascertained clinical glaucoma status on a patient subset (n= 97) to determine the usefulness of our model. Predictive models for GHT results reversal using VF features. For the 16 604 eyes with 2 initial ONL results, the prevalence of a subsequent WNL result increased from 0.1% for MD <-12 dB to 13.8% for MD ≥-3 dB. Compared with models with VF global indices, the AUC of predictive models increased from 0.669 (MD ≥-3 dB) and 0.697 (-6 dB ≤ MD <-3 dB) to 0.770 and 0.820, respectively, by adding VF mismatch features and computationally derived VF archetypes (P < 0.001 for both). The GHT results reversal was associated with a large mismatch between baseline VFs. Moreover, the GHT results reversal was associated more with VF archetypes of nonglaucomatous loss, severe widespread loss, and lens rim artifacts. For a subset of 97 eyes, using our model to predict absence of glaucoma based on clinical evidence after 2 ONL results yielded significantly better prediction accuracy (87.7%; P < 0.001) than predicting GHT results reversal (68.8%) with a prescribed specificity 67.7%. Using VF features may predict the GHT results reversal to WNL after 2 consecutive ONL results.

Comparison of Threshold Saccadic Vector Optokinetic Perimetry (SVOP) and Standard Automated Perimetry (SAP) in Glaucoma. Part II: Patterns of Visual Field Loss and Acceptability.

PurposeWe compared patterns of visual field loss detected by standard automated perimetry (SAP) to saccadic vector optokinetic perimetry (SVOP) and examined patient perceptions of each test.MethodsA cross-sectional study was done of 58 healthy subjects and 103 with glaucoma who were tested using SAP and two versions of SVOP (v1 and v2). Visual fields from both devices were categorized by masked graders as: 0, normal; 1, paracentral defect; 2, nasal step; 3, arcuate defect; 4, altitudinal; 5, biarcuate; and 6, end-stage field loss. SVOP and SAP classifications were cross-tabulated. Subjects completed a questionnaire on their opinions of each test.ResultsWe analyzed 142 (v1) and 111 (v2) SVOP and SAP test pairs. SVOP v2 had a sensitivity of 97.7% and specificity of 77.9% for identifying normal versus abnormal visual fields. SAP and SVOP v2 classifications showed complete agreement in 54% of glaucoma patients, with a further 23% disagreeing by one category. On repeat testing, 86% of SVOP v2 classifications agreed with the previous test, compared to 91% of SAP classifications; 71% of subjects preferred SVOP compared to 20% who preferred SAP.ConclusionsEye-tracking perimetry can be used to obtain threshold visual field sensitivity values in patients with glaucoma and produce maps of visual field defects, with patterns exhibiting close agreement to SAP. Patients preferred eye-tracking perimetry compared to SAP.Translational relevanceThis first report of threshold eye tracking perimetry shows good agreement with conventional automated perimetry and provides a benchmark for future iterations.

The SCHEIE Visual Field Grading System.

ObjectiveNo method of grading visual field (VF) defects has been widely accepted throughout the glaucoma community. The SCHEIE (Systematic Classification of Humphrey visual fields-Easy Interpretation and Evaluation) grading system for glaucomatous visual fields was created to convey qualitative and quantitative information regarding visual field defects in an objective, reproducible, and easily applicable manner for research purposes.MethodsThe SCHEIE grading system is composed of a qualitative and quantitative score. The qualitative score consists of designation in one or more of the following categories: normal, central scotoma, paracentral scotoma, paracentral crescent, temporal quadrant, nasal quadrant, peripheral arcuate defect, expansive arcuate, or altitudinal defect. The quantitative component incorporates the Humphrey visual field index (VFI), location of visual defects for superior and inferior hemifields, and blind spot involvement. Accuracy and speed at grading using the qualitative and quantitative components was calculated for non-physician graders.ResultsGraders had a median accuracy of 96.67% for their qualitative scores and a median accuracy of 98.75% for their quantitative scores. Graders took a mean of 56 seconds per visual field to assign a qualitative score and 20 seconds per visual field to assign a quantitative score.ConclusionThe SCHEIE grading system is a reproducible tool that combines qualitative and quantitative measurements to grade glaucomatous visual field defects. The system aims to standardize clinical staging and to make specific visual field defects more easily identifiable. Specific patterns of visual field loss may also be associated with genetic variants in future genetic analysis.

Progression of transsynaptic retinal degeneration with spectral-domain optical coherence tomography

PurposeTo illustrate the progression of retrograde transsynaptic retinal degeneration using spectral-domain optical coherence tomography (SD-OCT). ObservationsA 60 year-old man with a stroke was followed over a 17-month period using SD-OCT of the macula, ganglion cell layer (GCC), and retinal nerve fiber layer. Transsynaptic retinal degeneration progressed over this time. Conclusions and importanceRetrograde transsynaptic retinal degeneration may occur in patients with homonymous visual field loss caused by post-geniculate neurologic disease. This is best detected as homonymous thinning of the retina, corresponding to the pattern of visual field loss, using SD-OCT of the GCC and macula. The retinal changes occur at a variable time following the onset of neurologic disease.

Glaucoma: the retina and beyond.

Over 60 million people worldwide are diagnosed with glaucomatous optic neuropathy, which is estimated to be responsible for 8.4 million cases of irreversible blindness globally. Glaucoma is associated with characteristic damage to the optic nerve and patterns of visual field loss which principally involves the loss of retinal ganglion cells (RGCs). At present, intraocular pressure (IOP) presents the only modifiable risk factor for glaucoma, although RGC and vision loss can continue in patients despite well-controlled IOP. This, coupled with the present inability to diagnose glaucoma until relatively late in the disease process, has led to intense investigations towards the development of novel techniques for the early diagnosis of disease. This review outlines our current understanding of the potential mechanisms underlying RGC and axonal loss in glaucoma. Similarities between glaucoma and other neurodegenerative diseases of the central nervous system are drawn before an overview of recent developments in techniques for monitoring RGC health is provided, including recent progress towards the development of RGC specific contrast agents. The review concludes by discussing techniques to assess glaucomatous changes in the brain using MRI and the clinical relevance of glaucomatous-associated changes in the visual centres of the brain.

Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic

ABSTRACTPurpose: To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns.Materials and Methods: For each of 16 previously identified VF loss patterns (“archetypes,” denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10–20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test.Results: 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often ≥ 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often < 0.7 among eyes representative of AT1 (no focal defect; p < 0.001) and AT2 (superior defect; p = 0.027), which was also associated with ptosis (p < 0.001). AT12 (temporal hemianopia) was associated with history of stroke (p = 0.022). AT11 (concentric peripheral defect) trended toward association with trial lens correction > 6D (p = 0.069).Conclusions: Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.

Pattern of Visual Field Loss in Primary Angle-Closure Glaucoma Across Different Severity Levels

To investigate the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) across different severity levels and to assess hemifield differences within each severity level. Cross-sectional study. Three hundred four patients diagnosed with PACG were recruited from glaucoma clinics at a Singapore hospital. Point-wise total deviation values were recorded from the static automated perimetry (Swedish interactive threshold algorithm standard program 24-2; Humphrey model 750 [Carl Zeiss Meditec, Dublin, CA]) printouts. Patients were excluded if they had unreliable VFs (fixation losses >33% and false-positive responses >15%), had undergone only 10-2 VF testing, had VF defects not typical of glaucoma, or had undergone cataract extraction. Mild, moderate, and severe VF loss were defined by a mean deviation of-6.00 dB or more,-6.01 to-12.00 dB, and-12.01 dB or less, respectively. Each hemifield was divided into regions according to glaucoma hemifield test sectors. The average mean deviation (MD) of each region was obtained using total deviation values. Between- and within-hemifield differences of the regions across the severity levels. After excluding ineligible cases, 249 patients with PACG were included in the analysis. Mean age of the patients was 65.7±8.6 years, with a 1:1 gender ratio. The number of patients who had mild, moderate, and severe VFs was 72 (28.9%), 78 (31.3%), and 99 (39.8%), respectively. For between-hemifield comparisons, all regions in the superior hemifield had worse MDs compared with their counterparts in the inferior hemifield across the severity spectrum. Likewise, for within-hemifield comparisons, MDs of the regions gradually worsened with increasing distance from the fixation point. In this group of clinic-based PACG patients, the superior hemifield was found to be affected more severely than the inferior hemifield, and the differences between them increased with worsening disease severity. The damage was consistently more pronounced in the nasal area.

Phenotypic differences in normal vs high tension glaucoma.

Normal tension glaucoma (NTG) and high tension open angle glaucoma (HTG) are associated with characteristic patterns of optic nerve findings and corresponding patterns of visual field loss. In the past, clinicians viewed NTG and HTG as distinct entities, with separate underlying pathophysiologies and often different clinical presentations and courses. Literature review. Optic nerve and visual field findings in NTG have been reported to be dissimilar to those in HTG. In more recent years, however, there has been increasing recognition of the shared features NTG and HTG. There is now a trend to consider these two entities as part of a spectrum of glaucoma with overlapping pathophysiology and clinical characteristics.

Comparison of visual field defects between newly detected chronic simple glaucoma and normotensive glaucoma

Objective : To study and compare the visual field defects in subjects with newly detected primary open angle glaucoma and normotensive glaucoma using HUMPHREY FIELD ANALYSER 30-2 swedish interactive thresholding algorithm(SITA) standard technique and to establish specific visual field loss patterns in each group and establish varied pathomechanisms. Methods: A prospective study 37 eyes of 25 patients with normal tension glaucoma(NTG) and chronic simple glaucoma(CSG). Patients were subjected to visual field testing using HUMPHREY FIELD ANALYSER(HFA) 30-2, SITA(Swedish interactive thresholding algorithm) standard method. Results: There was significant preponderance of early visual field defects in patients with NTG in comparison to patients with CSG (64% compared to 32.4%). Strong statistical differences were found in number of patients with scotomas falling with 6 degrees of central fixation (p<_0.001) in NTG comparing with CSG. Conclusion : results suggest that field defects between chronic simple and normotensive glaucoma do not differ in most aspects except for those in NTG group being closer to fixation and should not be used to underline different pathomechanisms in the two groups.

Recognizing patterns of visual field loss using unsupervised machine learning.

Glaucoma is a potentially blinding optic neuropathy that results in a decrease in visual sensitivity. Visual field abnormalities (decreased visual sensitivity on psychophysical tests) are the primary means of glaucoma diagnosis. One form of visual field testing is Frequency Doubling Technology (FDT) that tests sensitivity at 52 points within the visual field. Like other psychophysical tests used in clinical practice, FDT results yield specific patterns of defect indicative of the disease. We used Gaussian Mixture Model with Expectation Maximization (GEM), (EM is used to estimate the model parameters) to automatically separate FDT data into clusters of normal and abnormal eyes. Principal component analysis (PCA) was used to decompose each cluster into different axes (patterns). FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results, recruited from a university-based, longitudinal, multi-center, clinical study on glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1 contained 94% normal fields (94% specificity) and clusters 2 and 3 combined, contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA successfully separated FDT fields from healthy and glaucoma eyes and identified familiar glaucomatous patterns of loss.

Visual acuity and pattern of visual field loss at presentation in pituitary adenoma

Our purpose was to analyse the demographics, prevalence and pattern of visual field defects in patients with pituitary adenoma. We prospectively recruited 103 consecutive patients (206 eyes) presenting to a neurosurgical unit with pituitary adenoma. Ophthalmological examination and standard automated perimetry (Humphrey, 24-2 threshold) was performed. Severity of visual field defects was also assessed. The mean population age was 53.9years (standard deviation=15). Visual loss was the most common reason for presentation (39%) followed by endocrine abnormality (21%) and headache (15%). Patients with endocrine abnormality on presentation were 10.9years younger than those presenting with visual loss (p=0.001). Bitemporal defects were the most prevalent pattern (n=22, 41%) followed by homonymous defects (n=7, 13%). Of the patients with visual field loss, 33% had unilateral visual field defects. The mean visual acuity in those with bitemporal defects was 6/7.5 with half of these patients having 6/6 vision in both eyes. In conclusion, the majority of patients with pituitary adenoma have visual acuity better than 6/7.5 despite having visual field defects. While a bitemporal pattern of visual field loss is the most common, a significant proportion of patients had unilateral and altitudinal defects. Assessment of the visual field is essential to rule out chiasmal compression.

Comparison of Pattern and Evolution of Visual Field Defects between Non Diabetic and Diabetic Patients with Primary Open Angle Glaucoma

Visual field defects pattern in diabetic patient with glaucoma is different from patients with glaucoma alone. Inferior visual field defects are more common in patients of primary open angle glaucoma with diabetes and superior visual field defects are more common in patients of open angle glaucoma alone. These superior defects may result from less structural support to the nerve fibre in the inferoperipheral region of the lamina cribrosa. It is stated that a vascular factor, attributable to diabetes, may influence glaucomatous optic nerve damage, thus creating a difference in the pattern of visual field loss in patients with primary open angle glaucoma.

Glaucoma: A Disease of Early Cellular Senescence

Coexistent with the age-related increase in the prevalence of glaucoma is the age-related decrease in anterior segment outflow facility. That is, the resistance to fluid flow across the trabecular meshwork (TM) increases with age in a linear fashion, and begins at a fairly young age. 11 This decreased outflow facility is largely responsible for the elevated IOP that is encountered in Western populations with increasing age. Markers of cellular senescence are found in the TM of patients with primary open-angle glaucoma (POAG) to a much greater degree than in age-matched controls. It is thought that aging of these cells leads to their decreased function and therefore a consequent decreased outflow facility. 12 It is hypothesized that aging failure of the normal, regulatory proteolytic systems in the TM may be responsible for the observed pathophysiological alterations of the outflow pathway that may contribute to glaucoma. 13 Along with the decreased function of the outflow apparatus with age is a decreased population of retinal ganglion cells (RGCs) in the retina. The RGC is the pivotal cell in the retina that electrically couples the retina with the brain; it is the cell that is primarily damaged by glaucoma. Pathological studies have shown a steady attrition of RGCs with normal aging, starting at a young age, in the amount of approximately 5000 cells per year. 14 Given that the average RGC population is approximately 1 million in the human eye, and that an individual can lose approximately half of that population before significant visual dysfunction occurs, every person would normally develop glaucoma by the age of 100! Glaucomatous loss of RGCs can be viewed as a premature aging effect, causing the typical and unique optic neuropathy that clinicians diagnose as glaucoma, and the consequent characteristic patterns of visual field loss. Clinical studies have also shown a decrease with age in the thickness of the nerve fiber layer in normal individuals. 15 The nerve fiber layer carries the axons of the RGCs to the optic nerve, where they exit the laminar cribrosa and connect to their targets in the central nervous system. Biomechanical factors within the optic nerve head have been hypothesized to play a central role in RGC physiology, and contribute to the optic neuropathy of aging and glaucoma. 16 The posterior sclera of old monkeys is significantly stiffer than that of younger individuals and leads to lower strains with the higher stresses associated with elevated levels of IOP. This agerelated stiffening of the sclera significantly influences the biomechanical properties of the optic nerve head and may contribute to age-related susceptibility to glaucomatous optic nerve damage. 17 Similar changes occur in humans, which may be an important underpinning of the age relationship with glaucoma. 18

Association of CAV1/CAV2 Genomic Variants with Primary Open-Angle Glaucoma Overall and by Gender and Pattern of Visual Field Loss

The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Case-control study. We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.

Modeling the Patterns of Visual Field Loss in Glaucoma

A computer model was developed to test the assumption that diffuse neural loss can result in the field loss pattern characteristic of glaucoma. The anterior visual pathways comprised the retinal ganglion cells, and their axons up to the optic nerve head (ONH) were modeled in a computer program. Axon resistance to stress was accounted for depending on the location on the ONH, taking into consideration the presence or absence of vessels in the area. Damage patterns were applied to the axons at the ONH, and the corresponding dendritic fields were removed accordingly. A visual field was extracted and represented on a gray scale after a predetermined stage of damage was reached. Two patterns of damage were considered, a diffuse damage produced by randomly removing fibers and an ordered anteroposterior elimination. Random damage never rendered a pattern loss. Ordered centrifugal fiber loss may produce a radial pattern more conspicuous when the vessels are endowed with a protective role. In both cases, scotomas tend to be detectable earlier in more peripheral locations, attributable to the increasing size of the receptive fields with eccentricity. The model shows that pattern loss typical of glaucoma cannot be solely the result of a random loss of fibers. Anteroposterior damage of the ONH can explain radial progression of scotomas if a protective role is introduced for the central vessels.