Ganglion Cell Displacement Research Articles

The effect of macular visual field test density on central structure-function concordance in glaucoma

ABSTRACT Clinical relevance Central visual field (VF) testing often requires focussed high-density test grids. The critical number of test locations for maximising structure-function concordance in the macula is not known. Purpose The aim of this work is to determine the impact of the number of test locations in the central VF on binarized structure-function concordance in glaucoma. Methods Humphrey Field Analyser (HFA) 10–2 test grid and Cirrus optical coherence tomography Ganglion Cell Analysis (GCA) results from one eye of 155 glaucoma patients were extracted. Following anatomical correction for retinal ganglion cell displacement, the pointwise results of the central 36 locations of the 10–2 pattern deviation map and their corresponding locations within the GCA deviation map were recorded. The number of test locations was systematically reduced from 36 (4 locations per step) and added from 1 (1 location per step) and binarized structure-function concordance (p < 0.05 for both) at each step was evaluated. Eleven test point subtraction and addition models were developed. Concordance rates (proportion) were plotted as a function of number of test locations, and were fitted using segmental nonlinear regression to identify the critical point of inflection at which concordance was maximised and discordance minimised. Results Subtractive and additive approaches returned two-way estimates of the critical number, with, on average 8–14 test locations being the range at which structure-function concordance was optimised in the present cohort across all models. A randomised approach to subtracting or adding test locations returned critical numbers that were similar to systematic and empirical models, suggesting that specific test location was not as critical in optimising structure-function concordance compared to the number of test locations. Conclusion There is a potential critical number (8–14) in macular visual field testing where binarized structure-function concordance is optimised, providing a framework for guiding the development of integrated macular test locations in VF testing for glaucoma.

Structurally enhanced perimetric examination

Aims/Purpose: To assess the use of structural data to guide perimetric examination.Methods: Two perimetric strategies were tested on ten healthy participants: standard ZEST with population‐based prior distributions and Structural‐ZEST (S‐ZEST), enhanced with OCT data to determine the starting parameters. Both strategies were tested twice, in random order. The Compass Automated Perimeter (CMP, iCare) was used to collect the perimetric data through the Open Perimetry Interface and bespoke Shiny user interface (UI). The UI was used to import the Spectralis SD‐OCT scans (Heidelberg Engineering, Germany) and align the OCT data with the fundus image captured by the CMP. A 10–2 grid was centred on the fovea of each participant, aligned with the fovea‐disc axis. The UI calculated the Ganglion Cell Layer (GCL) thickness corresponding to each test location, after accounting for ganglion cell displacement. The starting priors for S‐ZEST were modelled using an independent dataset of glaucoma and healthy subjects. Bland–Altman plots were used to quantify test–retest variability. Bootstrap was used to calculate confidence intervals (CIs) and p‐values to compare the widths of the 95%‐Limits of Repeatability (LoR). Correlation between GCL thickness and sensitivity (dB) and the difference in test duration was calculated using linear mixed effect models. Agreement was quantified with the mean difference between the results of the two strategies.Results: 95%‐LoRs for S‐ZEST of the two devices were similar (p = 0.829). The structure–function correlation was significant for both (p &lt; 0.001), and very similar between S‐ZEST (R2 = 0.24) and ZEST (R2 = 0.23). There was a small but statistically significant mean difference in sensitivity between S‐ZEST and ZEST (0.56 [0.35, 0.77] dB, p = 0.034). S‐ZEST was 2.7 [1.2, 3.5] min faster than ZEST (p &lt; 0.001).Conclusions: S‐ZEST significantly shortened testing time without reducing repeatability in healthy observers.

Ability of 24-2C and 24-2 Grids to Identify Central Visual Field Defects and Structure-Function Concordance in Glaucoma and Suspects

The purpose of this study was to compare the ability of the 24-2 test grid with that of the 24-2C test grid to measure visual field global indices, identify central visual field defects, and facilitate macular structure-function analysis with optical coherence tomography (OCT) scans in glaucoma suspects and glaucoma patients. Prospective, cross-sectional study. One eye from each of 100 glaucoma suspects and glaucoma patients (60 undergoing SITA-Faster [Zeiss Meditec] testing on 24-2 and 24-2C; 40 undergoing SITA-Standard [Zeiss Meditec] testing on 24-2 and SITA-Faster on 24-2C) were included in the study. Global visual field indices, test duration, and pattern deviation results were extracted. The deviation map from the Cirrus OCT (Carl Zeiss Meditec) Ganglion Cell Analysis (GCA) was extracted, and structure-function relationships were compared after correction of the visual field test stimulus location that stimulated the corresponding retinal ganglion cell. Global index results of the 24-2 grid were similar to those of the 24-2C grid, and both identified a comparable number of clusters of visual field defects. Centrally, the 24-2C grid identified more clusters of defects than the 24-2 grid, but this was not statistically significant. Although the 24-2C test locations resulted in more instances of structure-function concordance than the 24-2 locations, half the locations in the 24-2C grid fell close to or outside the GCA grid when corrected for ganglion cell displacement. The 24-2C returned global visual field indices similar to the 24-2 grid but tended to identify more clusters of central functional defects. Central structure-function concordance was better achieved using the 24-2C grid, but half of the visual field test locations did not coincide with the commonly used macular thickness scan.

Comparing Structure-Function Relationships Based on Drasdo's and Sjöstrand's Retinal Ganglion Cell Displacement Models.

PurposeTo compare structure-function relationships based on the Drasdo and Sjöstrand retinal ganglion cell displacement models.MethodsSingle eyes from 305 patients with glaucoma and 55 heathy participants were included in this multicenter, cross-sectional study. The ganglion cell and inner plexiform layer (GCIPL) thickness was measured using spectral domain optical coherence tomography. Visual field measurements were performed using the Humphrey 10-2 test. All A-scan pixels (128 × 512 pixels) were allocated to the closest 10-2 location with both displacement models using degree and millimeter scales. Structure-function relationships were investigated between GCIPL thickness and corresponding visual sensitivity in nonlong (160 eyes) and long (200 eyes) axial length (AL) groups.ResultsIn both the nonlong and long AL groups, compared with the no-displacement model, both the Drasdo and the Sjöstrand models showed that the structure-function relationship around the fovea improved (P < 0.05). The magnitude of improvement in the area was either comparable between the model or was larger for the Drasdo model than the Sjöstrand model (P < 0.05). Meanwhile, structure-function relationships outside the innermost retinal region that were based on the Drasdo and Sjöstrand models were comparable to or were even worse than (in the case of the Drasdo model) those obtained using the no-displacement model.ConclusionsStructure-function relationships evaluated based on both the Drasdo and Sjöstrand models significantly improved around the fovea, particularly when using the Drasdo model. This was not the case in other areas.

A spatial model of human retinal cell densities and solution for retinal ganglion cell displacement

A spatial model of human retinal cell densities and solution for retinal ganglion cell displacement

Evaluating the Usefulness of MP-3 Microperimetry in Glaucoma Patients

The purpose of the current study was to evaluate the test-retest reproducibility and structure-function relationship of the MP-3 microperimeter, compared against the Humphrey Field Analyzer (HFA). Design: Reliability and validity study. Institutional, or clinical practice. Thirty eyes of 30 primary open-angle glaucoma patients were enrolled. Visual fields (VF) were measured twice with the MP-3 and HFA instruments, using the 10-2 test grid pattern in both perimeters. Ganglion cell complex (GCC) thickness was measured using optical coherence tomography (OCT). Test-retest reproducibility was assessed using the mean absolute deviation (MAD) measure at all 68 VF test points, and also the intraclass correlation coefficient (ICC) of the repeated VF sensitivities. The structure-function relationship between VF sensitivities (measured with MP-3 or HFA) and GCC thickness (adjusted for the retinal ganglion cell displacement) was analyzed using linear mixed modeling. Reproducibility and structure-function relationship. The average measurement duration with the HFA 10-2 was 7minutes and 6 seconds (7m06s) ± 0m49s (mean ± standard deviation). A significantly (P< .001, paired Wilcoxon test) longer measurement duration was observed for the MP-3 test: 10m29s ± 2m55s. There were no significant differences in MAD and ICC values between HFA (MAD; 0.83 ± 0.69 dB and ICC: 0.89 ± 0.69, mean ± standard deviation) and MP-3 (MAD: 0.65 ± 0.67 dB and ICC: 0.89 ± 0.69). MP-3 VF sensitivities had a stronger structure-function relationship with GCC thickness compared to HFA. The MP-3 microperimeter has a similar test-retest reproducibility to the HFA but a better structure-function relationship.

Macular SD-OCT Outcome Measures: Comparison of Local Structure-Function Relationships and Dynamic Range

PurposeWe tested the hypothesis that the macular ganglion cell layer (GCL) thickness demonstrates a stronger structure-function (SF) relationship and extends the useful range of macular measurements compared with combined macular inner layer or full thickness.MethodsNinety-eight glaucomatous eyes and eight normal eyes with macular spectral domain optical coherence tomography (SD-OCT) volume scans and 10-2 visual fields were enrolled. Inner plexiform layer (IPL), GCL, macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full thickness (FT) measurements were calculated for 8 × 8 arrays of 3° superpixels. Main outcome measures were local structure-function relationships between macular superpixels and corresponding sensitivities on 10-2 fields after adjusting for ganglion cell displacement, dynamic range of measurements, and the change point (total deviation value where macular parameters reached measurement floor).ResultsMedian (interquartile range [IQR]) mean deviation was −7.2 (−11.6 to −3.2) dB in glaucoma eyes. Strength of SF relationships was highest for GCIPL, GCL, GCC, and IPL (ρ = 0.635, 0.627, 0.621, and 0.577, respectively; P ≤ 0.046 for comparisons against GCIPL). Highest SF correlations coincided with the peak of GCL thickness, where the dynamic range was widest for FT (81.1 μm), followed by GCC (65.7 μm), GCIPL (54.9 μm), GCL (35.2 μm), mRNFL (27.5 μm), and IPL (20.9 μm). Change points were similar for all macular parameters (−7.8 to −8.9 dB).ConclusionsGCIPL, GCL, and GCC demonstrated comparable SF relationships while FT, GCC, and GCIPL had the widest dynamic range. Measurement of GCL did not extend the range of useful structural measurements. Measuring GCL does not provide any advantage for detection of progression with current SD-OCT technology.

Structure-Function Relationship in Glaucoma Using Ganglion Cell-Inner Plexiform Layer Thickness Measurements.

To evaluate the structure-function relationship between ganglion cell-inner plexiform layer (GCIPL) thickness at the macula and 10-2 standard automated perimetry (SAP) in glaucoma and to evaluate the relationship using a recently proposed linear model. In a cross-sectional analysis, structure-function relationship was determined in 50 glaucomatous eyes (40 patients, mean deviation: -15.4 ± 7.5 dB) and 21 control eyes (13 subjects, mean deviation: -3.4 ± 3.0 dB), which had undergone 10-2 SAP and GCIPL imaging on the same day. Functional loss was derived from total deviation numerical values on 10-2 SAP and calculated on both a linear (reciprocal of Lambert) and a decibel scale after accounting for the retinal ganglion cell displacement at the macula. Strength of relationship was reported as coefficient of determination (R2) of the linear regression models fitted to the data separately for different sectors. The relationship was also evaluated using a linear model. The R2 for the associations between GCIPL thickness sectors and the corresponding sector SAP total deviation values ranged from 0.19 (for superonasal GCIPL sector) to 0.60 (for average GCIPL thickness) when functional loss was calculated on the decibel scale and 0.16 (for superonasal sector) to 0.54 (for inferior sector) on the linear scale. All associations were statistically significant (P < 0.05). The linear model fitted the data reasonably well. Significant structure-function associations were found between GCIPL thickness measurements at the macula and the functional loss measured on 10-2 SAP in glaucoma. Best fit was found for the inferior and average GCIPL sector thickness. The linear model was useful to study the structure-function relationship.

Relationship between macular inner retinal layer thickness and corresponding retinal sensitivity in normal eyes.

The correlation between standard automated perimetry (SAP) sensitivity and macular inner retinal layer thickness in eyes with glaucoma is well known. We examined whether the corresponding correlation is also significant in normal eyes. One eye of each of 195 normal subjects was included. The average thickness of the macular ganglion cell-inner plexiform layers (GCIPL) and the macular retinal nerve fiber layer/GCIPL (ganglion cell complex, GCC) in four regions with 0.6-mm-diameter circular area corresponding to the four central test points of the Humphrey Field Analyzer 24-2 test program, adjusted for ganglion cell displacement, were measured using spectral-domain optical coherence tomography (SD-OCT) and correlated to the mean SAP sensitivity (in 1/Lambert scale) at the corresponding test points with a multiple regression analysis using age, refraction, disc size, sex, and laterality of the eye as other explanatory variables. In normal eyes, GCIPL and GCC thickness (in micrometers) showed significant correlation to SAP sensitivity in corresponding areas, with partial regression coefficients of 0.0016 (P = 0.036) and 0.0022 (P = 0.023), respectively. Other significantly correlated factors were age and GCIPL (-0.18, P = 0.000), age and GCC (-0.20, P = 0.000), and refraction and GCIPL (0.92, P = 0.012). Similar analyses at each of the four test points yielded essentially the same results, although partial correlation coefficients were not always significant. A thicker macular GCIPL or GCC was weakly but significantly associated with higher SAP sensitivity in the corresponding macular region in normal eyes.

The length of Henle fibers in the human retina and a model of ganglion receptive field density in the visual field

An experimental study of lateral displacement of ganglion cells (GCs) from foveal cones in six human retinas is reported. At 406–675 μm in length, as measured in radially oriented cross-sections, Henle fibers are substantially longer than previously reported. However, a new theoretical model indicates that the discrepancies in these reports are mainly due to meridional differences. The model takes into account the effects of optical degradation and peripheral ON/OFF asymmetry and predicts a central GC:cone ratio of 2.24:1. It provides estimates of cumulative counts and GC receptive field density at 0°–30° along the principal meridians of the visual field.

Degenerative leiomyopathy in children. A clinico-pathological study

The syndrome of degenerative leiomyopathy (DL) causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. We report on a clinico-pathologic study of 18 children seen over a 15-year period. All patients came from the same geographic area. Mean age at presentation was 9.5 years with mean duration of symptoms 4.3 years. The youngest infant was 6 months old. Eighteen children presented with progressive abdominal distention and infrequent stooling; 11 had intermittent diarrhoea and 9 colicky abdominal pain. Gross colonic gaseous distention was noted with proximal extension into the small bowel in 9 and into the stomach and oesophagus in 4. The rectosphincteric reflex was present in all 7 patients studied with anorectal manometry. The diagnosis, confirmed on full-thickness rectal biopsy, showed characteristic features distinguishing it from chronic idiopathic intestinal pseudo-obstruction, progressive systemic sclerosis, and mixed connective-tissue disease of childhood. The bowel was dilated, thin-walled, and on microscopy showed smooth-muscle degeneration and necrosis with replacement fibrosis of muscular layers, displacement of ganglion cells, mild increase in numbers and thickness of nerve fibres, mild inflammatory change, and medial fibrosis of small muscular arteries. Immunohistochemical studies were within normal limits. One child died; 14 have been maintained with a combination of prokinetic agents, low-residue diet, laxatives, and enemas; and 3 patients did not respond to this medical therapy on short-term follow-up. Nine children required surgical intervention — 2 diagnostic laparotomies, 4 volvulus, and 3 adhesive bowel obstructions. Four of these required subsequent surgical procedures. DL is a distinctive entity with a classical clinical and histologic picture whose exact etiology is still obscure, Exploratory laparotomy should be avoided.

Further study of the outward displacement of retinal ganglion cells during optic nerve regeneration, with a note on the normal cells of dogiel in the adult frog

In a previous study we observed massive retinal ganglion cell death in adult Rana pipiens after periods of optic nerve regeneration, and reported that large numbers of the surviving cells had become displaced bodily into the inner plexiform layer of the affected eye (Scalia et al.: Brain Research 344:267-280, 1985). The outwardly displaced cells could be identified as retinal ganglion cells because they could be back-filled with horseradish peroxidase (HRP) injected into the regenerated optic nerve. Quantitative observations on the abnormal outward displacement of ganglion cells are reported here. Parallel observations on normally displaced ganglion cells (cells of Dogiel) are also reported to clarify the distinctions between these two classes of cells. For the present work, injections of HRP of varying size were placed in the optic tectum bilaterally in 3 normal frogs and 9 frogs sustaining unilateral optic nerve regeneration. Most injections were centered at loci mapping the middle region of the nasal retina. The retinas were examined as flat-mounts and in-section. In 8 other frogs sustaining optic nerve regeneration, the HRP was administered bilaterally directly to the optic nerves in the orbit. Ganglion cells were labeled by retrograde transport of the HRP in the retinal ganglion cell layer in both the normal and affected eyes in areas topographically isomorphic with the tectal areas subtended by the injections. In the normal eyes, the orthotopic ganglion cells formed a strict monolayer, and virtually no cells existed in the inner plexiform layer. In the retinas sustaining optic nerve regeneration, the retinal ganglion cells abnormally displaced into the inner plexiform layer were also labeled topographically in correspondence with the injection sites. The abnormally displaced cells comprised 5.5% of the total population of surviving neurons in the retinal ganglion cell and inner plexiform layers. The mean outward dislocation of the displaced cells, as measured in one frog surviving optic nerve crush for 8 weeks, was 69.9 +/- 2.4% of the distance across the inner plexiform layer, which itself was uniformly 14.3 +/- 0.39 microns thick. Cells of Dogiel, which were embedded within the inner nuclear layer, were also labeled when the injections of HRP spread to include the area of representation of the optic disc. The labeled cells were restricted to a dorsal, peripapillary locus capping the optic disc. Therefore, some cells of Dogiel project to the tectum normally, but only from the central retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Loss and displacement of ganglion cells after optic nerve regeneration in adult Rana pipiens

After studying pathway selection in the brain of Rana pipiens during unilateral optic nerve regeneration, several frogs were allowed to survive for lengthy periods for use in the present investigation. Retina flat-mounts were prepared from both eyes at 42–50 weeks postoperation. In some cases, HRP was infiltrated into both optic nerves prior to sacrifice to assist in identifying retinal ganglion cells. All specimens showed reduced cell-densities in the ganglion cell layer of the eye that had sustained the nerve regeneration. In addition, many ganglion cells were displaced, abnormally, into the inner plexiform layer, and the normally-situated cells formed irregular bands and islands in some parts of the retina. Cell-counts showed an apparently time-related change in neuron number ranging from a loss of 41% compared with the unaffected eye at 42 weeks, to losses as great as 71% at 50 weeks. The probable number of displaced amacrine cells in the ganglion cell layer, assumed to be unaffected by the experiment, was estimated at a maximum of 16%. Possible factors underlying the loss and displacement of ganglion cells are discussed.

Postembryonic development of the optic lobes of Phormia regina meigen (diptera: Calliphoridae)

The postembryonic development of the optic lobes of Phormia regina Meigen was studied using reduced silver nerve stains. The ganglion cells of the optic cortices are formed from 2 neuroblast aggregates located within the optic lobes, the inner and outer optic anlagen. The lamina and medulla are formed by the outer optic anlage; and the lobula and lobula plate by the inner optic anlage. One isolated neuroblast was observed to participate in the development of the lobula. The neuropiles and cortices of the lamina, medulla and lobula plate are formed with discrete spatial and temporal orientations, resulting from the distal displacement of ganglion cells from their site of proliferation. In regard to the lamina, medulla and lobula plate, ganglion cells and neuropile located distal to the site of ganglion cell production are older and more differentiated than those located more proximally. The displacement of ganglion cells also results in specific directions of formation for the lamina, medulla and lobula plate and the formation of the first optic chiasma. The lamina forms in a posterior-to-anterior direction; the medulla and lobula plate in a medial-to-lateral direction. The first optic chiasma forms because the lamina and medulla form in opposite directions and the fibers extending between them cross-over one another and form a chiasma.