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Studies of retinal ischemia/reperfusion indicate a disparity between the anatomical and functional results; while a large number of rod bipolar cells remain postischemia, there is a significant reduction in the amplitude of the scotopic b-wave of the electroretinogram (ERG). We investigated the alterations in photoreceptor-bipolar cell signaling following ischemia/reperfusion and suggest a mechanism for the decrease in b-wave amplitude. A cation channel probe (agmatine, 1-amino-4-guanidobutane, AGB) was used to assess cellular ion channel activity in neurochemically identified cells secondary to endogenous glutamate release or pharmacological manipulations. By applying the "neurochemical truth point" principle (Sun et al. [2007a] J Comp Neurol, this issue), we have been able to confirm the loss of specific subpopulations of neurons. ERG was used to assess gross retinal function, with parameters of the ERG model providing insight into changes in the phototransduction cascade and sensitivity of postreceptoral glutamate receptors. Following ischemia/reperfusion, rod bipolar cells maintained 2-amino-4-phosphonobutyric acid-responsive metabotropic glutamate receptors and displayed no change in sensitivity to flashes of light as assessed by ERG. Therefore, the loss in b-wave amplitude is likely due to alterations in photoreceptoral glutamate release detected as a change in postsynaptic AGB permeation into rod bipolar cells. Bipolar cell to amacrine cell signaling was also altered. The robust AGB entry into cholinergic amacrine cells was virtually absent in retinas that had undergone ischemia/reperfusion but remained in the AII amacrine cells. Such results suggest a loss of glutamate receptors and/or a change in receptor subunit expression in subpopulations of inner retinal neurons. Although many cells retain their characteristic neurochemical labeling following ischemia/reperfusion, caution should be used when assuming cells participate in functional retinal circuits based solely on the persistence of neurochemical labeling., (2007 Wiley-Liss, Inc)

Objective: To record intraocular pressure (IOP) of three different dog breeds following administration of one drop of 1% tropicamide., Animals: Three dog breeds -- Golden Retrievers (n = 20), Siberian Huskies (n = 20) and English Cocker Spaniels (n = 36) -- were studied., Procedure: IOPs were measured using a Tonopen following corneal anesthesia with a single drop of 0.5% proxymetacaine. A drop of 0.5% tropicamide was then administered bilaterally and a second IOP measurement was taken 30 min later (postdilation). The difference between the two measurements was considered as the effect of mydriasis on IOP., Results: Dogs had an average IOP of 14.9 +/- 3.2 mmHg, with 95% confidence limits ranging from 8 to 22 mmHg. There were significant differences between breeds (P < 0.006) with Siberian Huskies having higher IOPs (17.2 +/- 3.7 mmHg) than the other breeds (Spaniels: 14.2 +/- 2.8 mmHg, P < 0.01; Retrievers: 14 +/- 1.9 mmHg, P < 0.001). The majority (60%) of dogs displayed 5 mmHg or less in IOP change postmydriasis. Siberian Huskies showed the highest IOP levels, and also had the greatest variability with dilation., Conclusions and Clinical Relevance: Interbreed variability in effect of tropicamide of canine IOP is evident.

We have characterized the vascular, neuronal, and glial changes in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). Newborn Sprague-Dawley rats were exposed to either 80% +/- 2% oxygen to postnatal day P11 and then room air until P18 (ROP) or room air for the entire duration (controls). Retinal structure was examined under the light microscope and following postembedding immunocytochemistry in central, midperipheral, and peripheral regions. Müller cells were evaluated immunocytochemically with glial fibrillary acidic protein. The extent of vascularization was established histologically. ROP caused significant thinning of the inner cellular and plexiform layers, which became more pronounced in the peripheral inner nuclear layer of ROP animals (11.3% loss vs. 25.4% loss). Amacrine cell amino acid levels were particularly vulnerable in the peripheral retina; bipolar cells showed similar but less prominent changes. Müller cells had elevated glutamine levels and were most gliotic in the periphery. The vasculature extended to peripheral retinal regions at P18 in controls but not in ROP rats. The most striking pattern of change was evident in the midperipheral "transition zone" of ROP animals. Areas close to blood vessels showed neurochemical properties that were similar to those of the central retina, indicating a local protective effect of the inner retinal blood supply. We find that ROP produces complex vascular, neural, and glial changes that relate to the proximity of inner retinal blood vessels., ((c) 2007 Wiley-Liss, Inc.)

Symmetric flicker modulates about a background light level and effects no change in the time-average luminance. Rectified flicker is achieved by modulating a luminance-increment and results in both a flickering component and an increase in the time-averaged luminance (luminance-pedestal) above the adapting background light level. We studied the effect that changes in adapting light level and local luminance (within the area of the flickering target) have on thresholds. We measured thresholds for single and multiple cycles of flicker over a range of adapting light levels (Threshold versus Intensity paradigm) and defined their gain as a function of luminance-pedestal amplitude (Threshold versus Amplitude paradigm). The dynamics of symmetric and rectified flicker responses were determined using a Stimulus Onset Asynchrony paradigm. The data show rectified flicker thresholds differ from symmetric flicker thresholds due to two factors that can be contrast-dependent or contrast-independent: (1) local adaptation, which varies with stimulus duration and (2) surround interactions that depend on adapting light level. The dynamics of the thresholds for symmetric and rectified flicker stimuli suggest the detection mechanisms occur early in the visual pathways, involving the magnocellular pathway.

Purpose: To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult., Methods: In Sprague-Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl(2). Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS') was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl(2) administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats., Results: Comparing pre- and post-Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl(2) injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS'. ERG data did not show any effect of MnCl(2) on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time., Conclusions: MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.

Purpose: To determine whether there is an association between dietary omega-3 (omega-3) fatty acid intake, age, and intraocular pressure (IOP) caused by altered aqueous outflow., Methods: Sprague-Dawley rats were fed either omega-3-sufficient (omega-3(+)) or omega-3-deficient (omega-3(-)) diets from conception. The diets had 7% lipid content. The omega-3(+) diet contained safflower, flaxseed, and tuna oils (5.5:1.0:0.5), and the omega-3(-) diet contained safflower oil only. Intraocular pressure was measured at 5 to 40 weeks of age under light anesthesia (omega-3(+), n = 39; omega-3(-), n = 48). Aqueous outflow was determined at 45 weeks in a subgroup of animals (omega-3(+), n = 15; omega-3(-), n = 22) using pulsed infusion. Ciliary body tissues (n = 6 per group) were assayed for fatty acid content by thin-layer and gas-liquid chromatography in both diet groups., Results: Animals raised on omega-3(+) diets had a 13% decrease in IOP at 40 weeks of age (13.48 +/- 0.32 mm Hg vs. 15.46 +/- 0.29 mm Hg; P < 0.01). When considered as a change in IOP relative to 5 weeks of age, the omega-3(+) group showed a 23% decrease (P < 0.001). This lower IOP in the omega-3(+) diet group was associated with a significant increase (+56%; P < 0.001) in outflow facility and a decrease in ocular rigidity (-59%; P < 0.001). The omega-3(+) group showed a 3.3 times increase in ciliary body docosahexaenoic acid (P < 0.001)., Conclusions: Increasing dietary omega-3 reduces IOP with age because of increased outflow facility, likely resulting from an increase in docosanoids. This indicates that dietary manipulation may provide a modifiable factor for IOP regulation. However, further studies are needed to consider whether this can modify the risk for glaucoma and can play a role in treatment of the disease.

Purpose: To evaluate the recovery of retinal function after acute IOP elevation., Methods: The electroretinogram (ERG) was measured before, during, and after IOP increased to 50 and 70 mm Hg at different durations in anesthetized, dark-adapted rats (n = 5-7). Signals were collected for dim and bright flashes (-4.95 and 1.0 log cd . s/m(2)) and analyzed in terms of the photoreceptoral (P3), postreceptoral (P2), and inner retinal (negative scotopic threshold response [nSTR]) responses. Parameters (treatment/baseline, %) were compared across time by using repeated-measures ANOVA and t-tests. The rate of recovery was quantified with a logistic function and compared by bootstrap., Results: IOP spikes induce greater loss (P < 0.01) and slower recovery (P < 0.001) in the nSTR compared with the P2 and P3 responses. IOP spikes having common integral (pressure x duration, 2100 mm Hg x minutes) for insult gave significantly greater P2 and nSTR dysfunction at the higher pressure (70 vs. 50 mm Hg, nSTR reduced to -2.5% +/- 0.5% vs. 20.3% +/- 6.5%, P < 0.05). The higher pressure also produced significantly slower nSTR recovery (50% recovery time [t(0.5)] 70 vs. 50 mm Hg: 33.1 vs. 21.7 minutes; P < 0.05). At a given IOP (70 mm Hg), t(0.5) showed a linear relationship with duration (15 vs. 30 vs. 60 minutes' exposure: t(0.5) 16.7 vs. 33.1 vs. 63.2 minutes; P < 0.05) and integral., Conclusions: Ganglion cell function recovers slower than the outer retina after IOP insult, with peak IOP being the principle determinant of functional loss and recovery. For a fixed pressure, functional recovery is linearly related to exposure.

Purpose: The present study investigated retinal integrity in high myopia using spatial psychophysical tasks., Methods: Ten axial high myopes (-8.5 to -11.5 D) and 10 age-matched control subjects (+/-1.0 D) were recruited. All participants underwent clinical examination and ocular biometry and demonstrated no visible macular disease with visual acuities better than 6/12. Foveal summation thresholds were determined for white and S-cone-isolating spots of various diameters up to 5.4 degrees and spatial contrast sensitivity to luminance sine wave gratings (0.5-9.7 cyc/deg). Data were analyzed after correction for the magnification induced by eye size and correcting lens power., Results: Spatial summation for both white and S-cone-isolating spots showed a generalized loss of sensitivity at all spot sizes in myopes relative to control subjects (P = 0.01). Critical areas at maximum summation were significantly larger in myopes, for S-cone isolating spots only, after image size correction (P = 0.048). Sensitivity at maximum summation correlated negatively with vitreous chamber depth for both targets (P = 0.005). Sensitivities for S-cone and luminance spots also correlated (P < 0.001), indicating widespread dysfunction. Myopes displayed contrast sensitivity losses at high spatial frequencies (P

Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X(7) receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X(7) receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X(7) receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X(7) receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X(7) receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing.

Purpose: To examine photoreceptor function in diabetes in detail by evaluating photoreceptor light activation, deactivation of the photoresponse, and recovery of the photoreceptor after bleaching (dark adaptation) in rats made diabetic with streptozotocin (STZ)., Methods: Animals were assigned to treated and control groups. Light activation in rod photoreceptors was established using a paired-flash electroretinogram (ERG) protocol, and the leading edge of the a-wave was modeled with the mechanisms mediating phototransduction. Deactivation of the photoreceptor response was evaluated at three luminous exposures (1.4-2.2 log cd.m/s-2) using a variable interstimulus interval (ISI) paradigm. Dark adaptation was evaluated at 90-second intervals for 30 minutes after approximately 20% pigment bleach. At each time point, a paired-flash signal (1.4 log cd.s/m-2) was used to extract rod responses., Results: Diabetic animals showed decreased amplitudes of the photoreceptor response 12 weeks after diabetes induction. No difference was found in the rate of deactivation of the photoresponse in diabetic rats. Normalized amplitudes showed that diabetic animals had significantly faster dark adaptation (P<0.01) than did controls., Conclusions: Although photoreceptor activation was abnormal, deactivation was unaltered after 12 weeks of diabetes. The faster relative recovery found in diabetes after bleach, in the presence of normal pigment dynamics, may reflect a decrease in outer segment lengths.

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

Background: We develop the logic for a stimulus that can evaluate cone-dependent spatial summation and detail the modelling and interpretation of thresholds obtained with this stimulus., Methods: Fifteen observers participated, including two young normals tested extensively in control experiments, and a clinical trial based on four observers with age-related macular degeneration (AMD), four age-similar controls and five young observers. Monocular spatial summation functions were measured with contrast-modulated Gabor targets that approximated the optimal visual contrast detector. Thresholds were returned from a yes/no adaptive psychophysical algorithm. By fine titration along the size domain it was demonstrated that the spatial summation of normal observers can be adequately described by a two-component model. A reduced set of variables are proposed for clinical applications and the model was applied to data derived using these variables in persons with AMD and age-similar controls., Results: We do not find a significant age-related loss of contrast sensitivity in our normal group. On the other hand, persons with early AMD exhibited a 0.41 log unit loss of sensitivity (P=0.04) from age-similar controls, without any change in their maximum summation area (A(max))., Conclusions: The nature of the spatial summation is consistent with the interpretation that early AMD produces a decrease in cone input to post-receptoral mechanisms in the absence of neural remodelling.

We demonstrate that cathode-ray-tube (CRT) monitors commonly used as stimulus generators in visual neuroscience produce signal artefacts. This arises from two factors, one being the finite time needed for the raster scan of the CRT to cross the receptive field being stimulated, and the other being the restraint imposed by the impulse response of the phosphor itself. Together these factors result in smearing or blurring that manifests as high frequency noise, distorting the desired signal applied by the investigator. Our analysis identifies those conditions that promote these artefacts and we describe methods for their minimisation. We suggest that a monitor frame rate >/=100 Hz provides a reasonable trade-off between refresh and the generators of high frequency noise.

Purpose: To investigate the onset of retinal neural dysfunction in the streptozotocin (STZ)-induced diatebic rat., Methods: A cohort of 20 Sprague-Dawley rats were randomly assigned to treatment (STZ 50 mg/kg, n = 10) and control (citrate buffer, n = 10) groups and observed for 12 weeks. Diabetes was confirmed by blood glucose (>15 mmol/L) and HBA(1c) (>7.0%). Treated animals received 2 to 3 U insulin daily. Retinal function was monitored using paired-flash electroretinograms (ERGs) at baseline and various time points between 2 days and 12 weeks after treatment, to allow isolation of rod and cone components. Protocols compared photoreceptor and inner retinal responses (rod and cone) at each time point., Results: Losses in the function of rod photoreceptors and the inner retina were seen 2 days after STZ injection, with recovery in some components by 4 weeks and a secondary loss of function at 12 weeks. Some inner retinal responses (cone response and rod oscillatory potentials (OPs) remained consistently depressed over the entire 12 weeks., Conclusions: Retinal neural dysfunction was observed as early as 2 days after STZ injection. These acute changes reflect either STZ toxicity or hyperglycemia as a result of pancreatic compromise. Consistent loss over the 12 weeks of the cone response and OPs suggests a vulnerability of the inner retina to STZ-related effects. The 12-week losses in function of retinal neurons are consistent with a generalized diabetic neuropathy, since impaired function developed simultaneously in both inner and outer retinal neurons.

We have employed fos-tau-LacZ (FTL) transgenic mice to examine functional activation in the visual areas of the nervous system. The FTL mice express the marker gene lacZ in neurons and their processes following many different stimuli, and allow the imaging of activation from the level of the entire brain surface through individual neurons and their projections. Analysis of FTL expression in the retinas of mice following diurnal exposure to light shows that bipolar cells, specific classes of amacrine cells, ganglion cells, and a dense network of processes in the inner plexiform layer are functionally activated. In animals deprived of light, there is almost no activity in the retina. In the lateral geniculate nucleus (LGN), light exposure appears responsible for FTL expression in dorsal nuclei, but not for expression in the ventral nuclei or the intergeniculate leaflet. In the superficial layers of the superior colliculus, FTL expression is highly dependent on light exposure. Similarly, light exposure is required for FTL expression in primary visual cortex (area 17), but some expression remains in area 18 of dark-adapted animals. Finally, using mice with one or both eyes missing, we have determined which parts of the visual system are dependent on the presence of a functional connectivity from the eye. These data demonstrate the usefulness of the FTL mice to map functional activation within the entire visual system. Furthermore, we can capture visual activation in a conscious animal. Our findings give an insight into the architecture of activity within the retina and throughout the visual system.

Purpose: To compare static and flicker perimetry outcomes in patients with early age-related macular degeneration (AMD)., Methods: Perimetry was performed in the central visual field of one eye of each of 25 patients with good visual acuity (> 6/12) and early AMD using static and flickering targets. These results were compared with data obtained from a single eye of 34 age-matched control subjects, 33 of whom were retested at 1 to 3 months after their initial visits., Results: In all cases, patients with early AMD had greater mean defects for flickering than static targets, returning a significantly larger group average in response to flicker (4.3 +/- 0.6 dB) than to static (1.8 +/- 0.6 dB; P < 0.005). Greater pattern defect losses were also present in AMD-affected eyes with flicker compared with static perimetry (P < 0.02). These give a higher diagnostic sensitivity for flicker (68% vs. 42%, P < 0.05) at 90% specificity. Sensitivity can be increased to 84% +/- 6% (specificity 92% +/- 4%) if the criterion for failure is a more than 10-dB loss in the foveal region (1 degrees -3 degrees )., Conclusions: Flickering targets expose foveal deficits in early AMD better than do static targets. Flicker perimetry is an easy, short procedure that may be useful for monitoring the progression of AMD., (Copyright Association for Research in Vision and Ophthalmology)

We assessed the effect of the in vivo application of monocarboxylate transport inhibitors on retinal function and amino acid immunocytochemistry. We wanted to determine the impact that altered aerobic metabolite availability has on retinal function and the characteristics of amino acid shunting into metabolic pools. Electroretinograms were collected from anaesthetized rats at various times after intravitreal injection of the monocarboxylate transport inhibitors alpha-cyano-4-hydroxycinnamate (4-CIN; 2 micro L, 0.1-10 mm) or p-(dipropylsulphamoyl)benzoic acid (probenecid; 1-10 mm). Changes in retinal function were compared with quantitative amino acid immunocytochemical changes in retinas harvested 20 and 40 min after either 4-CIN or vehicle treatment. The injection of 4-CIN resulted in a dose-dependent reduction of the ON-bipolar cell P2 wave amplitude (20-80%) and delay in its implicit time. The phototransduction sensitivity was mildly reduced whereas the ON-bipolar cell P2 sensitivity was unaffected. Probenecid induced functional changes similar to those observed with 4-CIN. We also mapped the amino acid alterations within specific cell classes induced by 4-CIN application. All neurones displayed a reduced glutamate content averaging 48%; reduced GABA (31%) and glycine (28%) were found within amacrine cells and glutamine was reduced in all cell classes except photoreceptor and Müller cells. All cell classes in the retina demonstrated increases in aspartate (57%), whereas leucine (24%) and ornithine (21%) were only significantly increased in photoreceptor and bipolar cells. The reduction in glutamate immunolabelling in specific retinal cell classes was mirrored by an increase in aspartate levels at these locations. In addition, attenuated glutamine immunolabelling also closely matched the spatial pattern observed for glutamate. Our immunocytochemical analysis provides evidence that monocarboxylate transport inhibition induces a shift in the equilibrium of glutamate transamination reactions involving aspartate throughout the retina whereas photoreceptor and bipolar cells also use glutamate transamination reactions involving ornithine and leucine. The distribution pattern of glutamine secondary to monocarboxylate inhibition suggests that this amino acid is a major precursor for glutamate throughout the retina.

Purpose: To test the proposal that inhibiting monocarboxylate transport in the rat retina results in altered retinal function measured using the electroretinogram (ERG) and to evaluate the efficacy of exogenous metabolic substrates to restore any functional deficit., Methods: Full-field white-flash ERGs were measured after monocarboxylate transport inhibition with intravitreal injection of alpha-cyano-4-hydroxycinnamic acid (4-CIN, 10 mM), and functional recovery was assessed after the introduction of various exogenous metabolic substrates (10 mM): lactate, pyruvate, alpha-ketoglutarate, alanine, succinate, and glutamine. The efficacy of glutamine as a metabolic substrate was also considered in the presence of phosphate-activated glutaminase inhibition (6-diazo-5-oxo-norleucin, 10 mM) or aminotransferase inhibition (aminooxyacetic acid, 10 mM). Pyruvate and alanine recovery was also assessed after aminooxyacetic acid application., Results: 4-CIN application resulted in an increased phototransduction amplitude but a mild reduction of gain. A greater reduction of postreceptoral b-wave and oscillatory potential amplitudes (80%) was observed, along with delayed implicit times (35 ms). Partial recovery of b-wave amplitudes was achieved with exogenous lactate (24%), pyruvate (27%), alpha-ketoglutarate (27%), alanine (25%), and succinate (26%), whereas glutamine provided 62% recovery. However, none of the substrates improved phototransduction gain. Both 6-diazo-5-oxo-norleucin and aminooxyacetic acid completely suppressed the glutamine-induced b-wave recovery. Aminooxyacetic acid also abolished the b-wave recovery from 4-CIN afforded by pyruvate and alanine., Conclusions: The greater loss of the b-wave and oscillatory potentials may reflect preferential routing of amino acid carbon skeletons to oxidative metabolic pathways, which in turn reduces glutamate availability for neurotransmission between photoreceptors and ON-bipolar cells. The reduction in log S provides evidence that inhibition of monocarboxylate transport produced some metabolic dysfunction in the rat.

Purpose: To investigate the accuracy and precision of threshold estimates returned by two Bayesian perimetric strategies, staircase-QUEST or SQ (a Swedish interactive threshold algorithm [SITA]-like strategy) and ZEST (zippy estimation by sequential testing), and to compare these measures with those of the full-threshold (FT) algorithm., Methods: A computerized visual field simulation model was developed to compare the performance (accuracy, precision, and number of presentations) of the three algorithms. SQ implemented aspects of the SITA algorithm that are in the public domain. The simulation was tested by using standard automated perimetry (SAP) visual field data from 265 normal subjects and 163 observers with glaucomatous visual field loss and by exploring the effect of response variability and response errors on algorithm performance., Results: SQ was faster than FT or ZEST, with a comparable mean error when simulating field tests on patients. Point-wise analysis revealed similar error and standard deviation of error as a function of threshold for FT and SQ. If the initial estimate of threshold for either procedure was incorrect, the means and standard deviations of the error increased markedly. ZEST produced more accurate thresholds than did the other two strategies when the initial estimate was removed from the true threshold., Conclusions: When simulated patients made errors, the accuracy and precision of sensitivity estimates were poor when the initial estimate of threshold either overestimated or underestimated the true threshold. This was particularly so for FT and SQ. ZEST demonstrated more consistent error properties than the other two measures.

We wanted to determine the characteristics associated with electrophysiological and neurochemical changes secondary to ischemic insult as well as correlate these electrophysiological and neurochemical changes. A Ganzfeld source was used to elicit electroretinograms in anesthetized adult Sprague-Dawley rats. Following baseline recordings, one eye was removed for control quantitative amino acid immunocytochemistry, and ischemic insult was induced by cervical dislocation. Following the induction of ischemia, a single electroretinogram signal was collected at 1, 2, 4, 6, 8, 16, 32 or 64 min, after which the eye was removed for immunocytochemistry. The post-receptoral b-wave was undetectable after 1 min post-ischemia, whereas phototransduction declined more gradually and persisted for up to 16 min post-mortem. Both phototransduction saturated amplitude and sensitivity decayed with a similar time course (tc=3.06 (2.73, 3.48) versus 3.29 (2.61, 4.62)min). Significant elevation of amino acid neurotransmitter levels was not observed until 6 min post-mortem. Between 8 and 16 min post-ischemia, glutamate and GABA were significantly accumulated in neurons and Müller cells (p<0.05). Beyond 16 min, the neurotransmitter elevation in neurons and Müller cells was relatively attenuated. Aspartate immunoreactivity was significantly elevated at 4 and 6 min post-ischemia in neurons, prior to a change in any other amino acid. Moreover, of the amino acids assessed the post-ischemic change in aspartate immunoreactivity showed the best correlation with phototransduction decay (r2=0.68). Our findings show that complete impairment of phototransduction coincides with the accumulation of amino acid neurotransmitter. The correlation of aspartate immunoreactivity and phototransduction provides evidence of heightened glutamate oxidation during ischemic insult.

Purpose: To consider how aerobic and anaerobic metabolic processes limit posthypoxemic decay in retinal function, measured by electroretinogram (ERG)., Methods: The hypothesis that lowering metabolic demand would prolong endogenous metabolic stores was tested by comparing the rate of ERG decay in rats in dark- (n = 5) versus light-adapted (15 minutes, 112 cd/m(2), n = 5) conditions and with serial versus single (n = 5 at each of seven time points) light stimulation. Postmortem hypoxemia was induced by cervical dislocation. Glucose (10 and 100 mM) and glutamine or lactate (100 mM) were injected into the vitreous 10 minutes before hypoxemic insult, to consider glycolytic-oxidative versus oxidative metabolism, respectively., Results: Lowering the metabolic drain by light adaptation or serial stimulation significantly improved the photoreceptoral saturated amplitude during the first 5 to 7.5 minutes after postmortem hypoxemia. Increasing substrate availability with exogenous glucose preloading delayed the loss of the photoreceptoral response, thereby extending the delay constant from 4.8 to 10.9 minutes. Postreceptoral amplitudes were not improved by any exogenous substrate. Providing glucose at 5 minutes after hypoxemia provided no benefits. Similar to glucose, glutamine and lactate loading significantly delayed photoreceptoral decay over the first 7.5 minutes, after which time glucose was the more effective substrate., Conclusions: The postmortem decay of photoreceptoral function reflects depletion of both endogenous oxygen and carbon substrate reserves. The findings provide evidence that a transition between aerobic and anaerobic metabolism occurs after approximately 8 minutes of complete hypoxemia.

Purpose: To evaluate cone visual function of subjects with age-related maculopathy (ARM)., Methods: Cone thresholds in 16 patients with ARM and 14 age-matched control subjects were compared. All subjects had visual acuity of 6/12 or better in the studied eye. A range of contrast thresholds were measured to evaluate diverse aspects of cone visual function under steady state conditions (spatiotemporal, color and luminance, and photopic sensitivity) or after bleaching (adaptation dynamics)., Results: ARM produced a diffuse loss across all cone steady state visual functions in 31% to 44% of subjects. The adaptation time constant of cone recovery was significantly prolonged in most (69%) ARM eyes. A cross-correlational analysis found adaptational kinetics to be independent of other steady state losses, with cone photopigment regeneration being the most affected visual function in ARM (chi(2) = 4.03, P < 0.05)., Conclusions: The results show that cone-adaptational kinetics are affected in ARM more so than are steady state thresholds. Given that cone recovery is easy to examine in a clinical setting, this test may provide a useful index of photopic function in patients with ARM.

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n-3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n-3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n-3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n-3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.

Aims: We consider the nature of retinal dysfunction in streptozotocin rats and assess the functional benefits of administering an angiotensin enzyme inhibitor or an inhibitor of advanced glycation end product formation., Methods: Sprague-Dawley rats (n=44) were randomly assigned to control (C=12, C(p)=4, C(a)=4) and diabetic groups (Streptozotocin, D=24). Diabetes was diagnosed based on a range of physiological and biochemical parameters at 4, 8 and 12 weeks. Streptozotocin animals were administered insulin daily (4 units protophane). Animals were treated with either an Angiotensin Converting Enzyme inhibitor (perindopril, C(p)=4, D(p)=8) or an inhibitor of advanced glycation end product formation (aminoguanidine, C(a)=4, D(a)=8). Dark-adapted electroretinograms were measured on anaesthetized animals at 12 weeks following streptozotocin treatment. Photoreceptoral and inner retinal responses were extracted, modelled and compared using ANOVA., Results: Streptozotocin injection increased blood glucose, glycosylated haemoglobin, fluid intake and urine volume, whereas body weight was decreased. Perindopril treatment produced improvements (p<0.05) in all indices, whereas aminoguanidine therapy produced some improvement in blood glucose and water intake. Streptozotocin rats showed losses of photoreceptoral-P3 (-27%), postreceptoral-P2 (-15%) and oscillatory potential (-19%) amplitudes of a similar magnitude. Perindopril therapy returned photoreceptoral and inner retinal function to within control limits. However, aminoguanidine treatment gave no significant functional improvement., Conclusions: Our findings provide evidence for a selective neuropathy in diabetes with a primary photoreceptoral lesion. Treatment with perindopril, an angiotensin converting enzyme inhibitor, ameliorates the neuropathy.

Purpose: To evaluate and compare the functional and perceived benefits of wearing coloured lenses by patients with age-related macular degeneration (ARMD)., Method: Ten subjects with early ARMD and five elderly controls wore a selection of NoIR wrap-around coloured lenses (yellow 29.7% light transmission, orange 22.9%, red 16.8% and grey 10.3%), each for a duration of 7 days. Contrast sensitivity, colour vision, visual acuity, the effect of glare and peripheral sensitivity were measured for each lens and compared with a control (no lens) condition. Subjective ratings of visual performance were also scored., Results: Compared with the no filter condition, red and grey lenses reduced contrast sensitivity whereas yellow and orange lenses increased contrast sensitivity. These objective changes were supported by subjective ratings in subjects with ARMD. Grey lenses reduced the loss of contrast sensitivity usually suffered in the presence of glare, whereas visual acuity and peripheral sensitivity decreased with red lenses. Colour vision became distorted with red lenses in control subjects, but was relatively unaffected by the use of coloured lenses in subjects with ARMD., Conclusions: The subjective benefit of coloured lenses appears to be due to a minor enhancement of contrast sensitivity.

We investigated the effect that spatially coincident luminance increments (luminance pedestals) have on flicker thresholds at several eccentricities and target sizes. Luminance pedestals elevated flicker amplitude-thresholds more when stimuli were presented eccentrically, both at low (4 Hz) and high (20 Hz) temporal frequencies. Altering the size of the eccentric stimulus failed to equate central and eccentric thresholds at all pedestal amplitudes. Comparisons with flicker thresholds at various background luminances suggests that the increase in luminance-pedestal flicker thresholds peripherally is due to increased suppressive rod-cone interactions, increased effectiveness of luminous contrast on edge-sensitive flicker mechanisms, as well as increased gain in the light adaptation response.

Purpose: To validate the clinical performance of two new efficient threshold-estimation procedures for frequency-doubling technology (FDT) perimetry in both visually normal individuals and patients with glaucomatous visual field loss., Methods: Forty-one normal subjects (mean age, 48.3 +/- 11.6 years) and 50 patients with glaucomatous visual field loss (mean age, 72.7 +/- 10.0 years) were tested. Some of these participants were retested within a 3-month period. FDT perimetry was performed on a color monitor driven by a visual-stimulus-generating video board, with stimulus parameters designed to closely mimic those of the commercial FDT test. Visual field sensitivity was measured using three procedures: a modified binary search (MOBS) identical with the one used in the commercial FDT device, a rapid efficient binary search (REBS), and a procedure the uses Bayesian methods (zippy estimation of sequential testing; ZEST). The selection of optimum parameters for REBS and ZEST were based on results from previous simulations., Results: Both ZEST and REBS were 40% to 50% faster than MOBS. All three methods produced similar visual field sensitivity measures, with 95% of the differences occurring between +/-2 dB for normal subjects and +/-3 dB for glaucoma patients. Test-retest performance was similar for all three procedures., Conclusions: The test time for full-threshold FDT perimetry can be approximately halved, by using either the ZEST or REBS procedure, without affecting the accuracy or reliability of the measurements. These findings in normal subjects and patients with glaucoma provide clinical confirmation of our previous investigations of these test strategies that use computer simulation.

Purpose: To consider whether growth restriction secondary to chronic placental insufficiency results in postnatal deficits in retinal structure and function., Methods: Chronic placental insufficiency was induced just before midgestation in guinea pigs through unilateral ligation of the uterine artery. Eight weeks after birth, electroretinograms were recorded from prenatally compromised (PC, n = 6) and control (n = 15) animals. Data were collected for b-wave amplitude and implicit time, also the modeled receptoral (P3) response and oscillatory potentials were extracted. After electroretinography, retinas were prepared for structural analysis (PC, n = 6; control, n = 7). A separate cohort of PC (n = 8) and control (n = 9) animals underwent tyrosine hydroxylase immunoreactivity (TH-IR, dopaminergic neurons) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry (neuronal nitric oxide synthase, nNOS)--these being markers of amacrine cell subpopulations., Results: Electroretinography revealed two PC guinea pigs with marked changes to saturated receptoral amplitude (Rm(P3)), sensitivity (log S) and postreceptoral waveforms. Grouped PC data revealed significantly reduced Rm(P3), whereas log S was not affected. The b-wave amplitudes were normal, but b-wave implicit times were delayed (P < 0.05) in PC animals. Amplitudes and peak times of oscillatory potentials were also significantly reduced and delayed (P < 0.05). Morphologic analysis revealed significant reductions in all cellular and plexiform (synaptic) layers in both the central (P < 0.05) and peripheral (P < 0.05) retina in PC animals. The outer retina, which contains the photoreceptors and the outer plexiform layer was particularly affected. The reduced growth of plexiform layers suggests a reduction in the growth of the neuropile in PC animals compared with control animals. The total number (P < 0.03) and density (P < 0.05) of TH-IR neurons was reduced, whereas the total number and density of nNOS-positive amacrine cells was not significantly different between PC and control animals., Conclusions: Chronic placental insufficiency results in morphologic and functional alterations to the retina. Electroretinogram deficits in PC animals indicated both inner and outer retinal anomalies. Such affects could contribute to the visual impairments reported in very-low-birth-weight children, some of whom are growth restricted.

Purpose: To develop new test procedures for frequency-doubling technology (FDT) perimetry that improve performance beyond those currently used., Methods: Two novel threshold estimation procedures were evaluated: a rapid, efficient binary search technique (REBS) and a maximum-likelihood estimation (ZEST) procedure. A computerized visual field simulation model was developed to determine the accuracy and efficiency of these procedures. This model was constructed using previously derived characteristics of FDT perimetry from both normal observers (n = 506) and those with glaucomatous visual field loss (n = 352). The computer simulation program was used to determine the best parameters for the two new procedures and the effect of variability and response errors on algorithm performance. Comparisons were made to the performance of the modified binary search (MOBS) procedure used in the current commercial implementation of the FDT perimeter., Results: Both the optimized REBS and ZEST procedures approximately halved the time required for FDT threshold testing without loss of accuracy or reproducibility., Conclusions: With suitable parameter choices, comparable performance was achieved using either ZEST or REBS. Simulation results indicate that accurate thresholds can be measured with an optimized ZEST or REBS procedure in approximately half the time required by traditional estimation methods.

This paper considers the recommendation that Oscillatory Potentials (OP) be extracted by filtering in the frequency domain. This recommendation presumes that filtering isolates OPs from other ERG waveforms. However, we show that the leading edge of the a-wave has substantial frequency overlap with the OP spectrum at high intensities and that it contaminates these wavelets in the frequency domain. We propose a method of signal conditioning that removes a-waves prior to filtering. When this is done, the OPs show a bimodal distribution in the frequency domain that is well approximated by two Gaussians having means (+/-std. dev.) of 91.0 +/- 14.6 Hz and 153.1 +/- 17.1 Hz. This implies that two functions can be used to model the OPs in the time domain. However, we show that as most of the power of the Fourier spectrum (74%) is contained in a single Gaussian, a reasonable OP model can be derived by using a single function in the time domain. We test such a model on humans (n=5) and pigmented (n=14) and albino (n=14) guinea-pigs and show that it provides excellent fits to data across a range of flash exposures. Furthermore, changes in OP amplitude and timing between strains of guinea-pigs are easily detected with this model. We show that there is no statistical justification for making the model more complex by including multiple functions. Such paramatisation of the OP envelope provides a valuable and intuitive description of the OP waveforms in the time domain. The model provides an excellent description of OPs obtained with the current paradigm, however the single gaussian model may be deficient under stimulus conditions which produce highly asymmetric OP envelopes.

Vitamin A (retinol) is vital for the normal development and function of many tissues in the body including the eye. The purpose of this project was to characterize the retinal anatomy and function of the transthyretin (TTR) null mouse. Mice lacking TTR have been constructed by homologous recombination. Immunocytochemistry was performed to localize short and mid-long wavelength cone opsins as well as morphological examination of the entire retina in wild-type and TTR null mice. Visual function was assessed using the electroretinogram (ERG) and resulting waveforms were analysed in terms of receptoral and postreceptoral components. Retinal morphology of the TTR null mouse was normal. In addition, short and mid-long wavelength cone opsins were localized normally in both TTR null and wild-type retinae. Consistent with these findings, TTR null mice show no anomalies of receptoral (P3) nor post-receptoral (b-wave) ERG components compared with wild-type mice. The results suggest that although circulating plasma levels of retinol and retinol binding protein (RBP) are extremely low, this reduction has little effect on the retinal structure or function of the TTR null mouse. These data are consistent with the existence of mechanisms for the transport of retinol to the retina independent of the classical retinol-RBP-TTR complex., ((C) 2001 Academic Press.)

By systematically manipulating the luminance of a flickering spot and the area immediately surrounding it, we investigated why thresholds from flickering stimuli that cause a change in average luminance are elevated relative to those from stimuli with no luminance change. Threshold elevation resulted from local light adaptation and from temporal-frequency-specific interactions between the spot and its surround: at low frequencies, the contrast between the spot and the surround elevated thresholds, whereas at high frequencies, dark adaptation within the surround elevated thresholds. Our findings suggest that two common ways of determining temporal sensitivity may give markedly different outcomes.

BACKGROUND: The retinal response to flickering stimuli (steady state ERG) recruits many retinal elements and is a sensitive indicator of early retinal dysfunction. This study reports the post-natal maturation of the steady state ERG response in guinea pigs. METHODS: The steady state ERG response to flickering stimuli (0.6 to 20 Hz) was recorded from dark adapted (more than 12 hrs) English Shorthair guinea pigs (n = 7) using flashes that produced rod and cone dominated responses. Temporal sensitivity functions and critical fusion frequencies (CFF) were derived over a range of ages from postnatal day (PND) 1 to 45. RESULTS: Guinea pig rod and cone temporal sensitivity functions show shape characteristics and CFF similar to humans. Furthermore, the post-natal development of the guinea pig temporal characteristics is also similar to that of humans - they are present at birth and mature rapidly post-natally. The time-course of CFF maturation is similar for rod and cone mediated responses. CONCLUSIONS: These data show that the temporal response and its maturation in the guinea pig retina is similar to that in humans. Therefore, we propose that the guinea pig is a particularly useful animal model to study retinal disease in early childhood.

INTRODUCTION: Psychophysical methods are used in clinical settings to obtain estimates of visual performance. Such methods should be fast and accurate, yet robust to the corrupting effects of false responses. METHODS: In this paper, we develop these concepts and investigate the efficiency of two maximum likelihood methods (bestPEST and ZEST) for use in clinical applications. The performance of both methods will depend on whether a criterion-free paradigm (alternate forced choice) is adopted. RESULTS: Our data show that the number of trials needed to obtain reliable thresholds with a yes/no paradigm can be as few as six to eight, provided no false responses are given within the first few trials. In addition, we show that the reliability and short-term variability of the endpoint of the methods is compatible with clinical applications. CONCLUSION: We show that a yes/no maximum likelihood method using a small number of presentations will yield reliable and accurate estimates of threshold in a clinical setting.

Retinal neurons are generated in overlapping growth spurts with ganglion cell and cone populations peaking sooner than rod and bipolar cell numbers. As such the functional development of the inner and outer retinal components and elements within these strata (rods vs. cones) may differ. We considered the postnatal development of the postreceptoral components of the ERG (P2, oscillatory potentials) in the guinea pig. ERGs were also evaluated across albino and pigmented strains in order to consider the role that pigmentation has for functional development. Electroretinograms were collected on postnatal days PDI to PD60 (n = 4-7 per time point). The postreceptoral P2 amplitude and implicit time was extracted (digital subtraction of modelled P3 and filtering, 0.5-49 Hz). Intensity-response relationships were described using Naka-Rushton functions whose parameters were compared using a nonparametric bootstrap. Oscillatory potentials (OPs) were extracted following signal conditioning and filtering to remove the a- and b-waves and were described using a Gabor function. OP response parameters were compared using repeated measures ANOVA. Postreceptoral P2 amplitudes mature soon after birth (PD10-PD12). Oscillatory potentials show a similar postnatal amplitude development (PD10-PD12) but a later maturation in timing (PD20) compared with the postreceptoral waveform. All components (P3, P2, and OPs) declined at the same relative rate with age after PD12. Albino animals gave larger, faster, and more sensitive waveforms at all ages but showed the same age-related trends as did pigmented animals. Early development of inner retinal synapses in guinea pigs may underlie the rapid postnatal maturation of their postreceptoral response. These appear to be constrained by the development of receptoral responses. All components declined at the same rate suggesting either a change in the photoreceptoral response or changes to ocular impedance with age.

The mechanisms underlying the adaptive response for achromatic impulses seen on achromatic fields were investigated. Foveal thresholds were measured for a static probe-impulse under two conditions of adaptation. Thresholds were obtained under gain-clamped conditions after observers had reached steady-state adaptation and with a probe-flash paradigm. It was found that thresholds isolated on steady-state fields cannot be modelled using a single mechanism. Likewise, the probe-flash condition failed to reflect the response of a single mechanism. Both threshold functions showed distinct breaks occurring at about the same field luminance (approximately 1.0 log cd/m2). Optimum data fits required the incorporation of two mechanisms implying the existence of independent processes mediating detection. Chromatic isolation confirmed that differential adaptation had been unmasked in the long- and medium-wavelength sensitive cone inputs to the achromatic channel.

The contribution of rods and cones to the scotopic electroretinogram (ERG) of small animals is unclear, with a recent report suggesting that the mouse has no cone a-wave. The present study considered the contribution of cones to the ERG of the rat. Dark-adapted Long Evans rats (n = 4) had ERG signals collected following a single flash, which stimulated rods and cones (mixed response), or a twin-fash paradigm (short interstimulus interval, 1 s), which isolated cone responses. Rod signals were derived by digital subtraction of the cone signal from the mixed rod/cone ERG. The rat a-wave was found to be dominated by rod responses but cone responses contributed substantially (45%) to post-receptoral waveforms (b-wave) at higher light levels.

Purpose: To evaluate interictal visual dysfunction in persons with migraine in terms of spatiotemporal selectivity and location within the visual pathways., Methods: The vision of a group of 15 persons who had experienced migraine with aura was compared with that of 15 normal age-matched control subjects. A range of thresholds was measured to evaluate precortical (background modulation, contrast thresholds for static, and moving stimuli), area V1 (orientation discrimination and motion discrimination thresholds), and higher order (global dot motion thresholds) visual processes. Testing was performed centrally and at 10 degrees in the superior visual field. For each of the tests, the spatial and temporal parameters of the stimuli were selected to bias detection toward either parvocellular or magnocellular visual mechanisms., Results: No defects were found for parvocellular processes. Significant (P: < 0.05) losses were apparent with the temporal background modulation method (16 Hz), orientation discrimination (0.5 cyc/deg), and global dot motion tasks., Conclusions: Both cortical and precortical visual dysfunction were identified in migraine group 7 days after the headache. This loss was selective for targets with temporal modulation of approximately 16 Hz.

This study considered whether the dynamics of flicker adaptation can be explained in terms of probability summation over time between independent ON- and OFF-processors. Foveal thresholds were measured for flickering probes, and for static ON- and OFF-probes that have durations consistent with the flicker duty cycle. Thresholds were obtained using a probe-flash stimulus onset asynchrony paradigm. The outcome of the experiment suggests that flicker thresholds are lower than the component ON- and OFF-thresholds, and that the flicker response can be predicted by assuming probability summation between the ON- and OFF-mechanisms.

We investigated the relationship between stimulus duration and flicker thresholds when flickering stimuli were presented on luminance pedestals. Mean-modulated flicker thresholds remained constant with changes in stimulus duration. However, flicker presented on a luminance pedestal gave masking at short durations, decaying exponentially to stable thresholds with time. These stable thresholds were elevated when compared with the mean-modulated condition. The lowest threshold in a stimulus onset asynchrony function predicted the threshold obtained from a luminance-pedestal flicker stimulus of the same duration. This suggests that luminance-pedestal flicker thresholds are determined by the most detectable cycle in a multiple cycle stimulus. We find that the 800 ms stimulus duration used in the Medmont M600 perimeter (Medmont, Camberwell, Australia) is suitable to determine stable flicker thresholds.

The background modulation method has been proposed as a useful test of early visual mechanisms [Biol. Cybern. 37, 77 (1980); Biol. Cybern. 47, 173 (1983)]. The task involves measuring detection thresholds for a luminous spot (increment) drifting over a spatially or temporally modulated background. The study explores the nature of the detecting mechanism in terms of spatial and temporal filters for both spatial and temporal background modulations. In both cases we find that thresholds can be explained by spatial contrast cues generated by the moving spot and that their spatiotemporal characteristics suggest detection by magnocellular processes.

BACKGROUND: Glaucoma manifests mostly in the elderly, who frequently have otherocular changes that frustrate clear visualisation of the optic nerve head or nerve fibre layer. In the past, a large or asymmetric cup/disc ratio has been used to indicate the possibility of glaucoma. In this paper, I will argue that cup/disc ratios alone have poor sensitivity to glaucoma, and a more sophisticated approach is needed to make the earliest diagnosis. METHODS: This paper reviews the literature and describes the changes that occur at the optic nerve head and in the peripapillary region as a consequence of glaucomatous optic neuropathy (GON). RESULTS: The concept of 'risk factors' is developed to help screen for glaucoma. Glaucoma suspects require a full clinical investigation (visual field, IOP, assessment of anterior chamber, disc features and nerve fibres) and need to be monitored annually. For future reference, they should have their disc features recorded by instrumental methods or with photography at an early age. As no single sign provides the perfect diagnostic marker for the disease, clinicians need to examine for a group of signs before making the diagnosis. A clinical logic is developed in this paper to enhance the detection of glaucoma. CONCLUSION: Adoption of a protocol similar to that detailed in this paper will enhance the early and reliable detection of glaucoma.

Purpose: To characterize the visual fields of subjects with migraine headaches using static and temporal modulation perimetry., Methods: Sixteen subjects with migraines (15 with aura, 1 without) and 15 nonheadache controls were tested. Perimetry was conducted 7 days after the offset of a headache with both static and temporally modulated targets using the Medmont M-600 automated perimeter (Medmont Pty Ltd., Camberwell, Victoria, Australia). Flicker thresholds were measured using the autoflicker test, which varies flicker rate with eccentricity. A subset of four subjects with migraines (3 with aura, 1 without) had the temporal tuning characteristics of their loss evaluated using fixed temporal frequencies (4, 6, 9, 12, and 16 Hz)., Results: Field losses were identified with temporal modulation perimetry in 11 of 16 migraine subjects. The majority of these losses occurred in the presence of normal static thresholds (8/11). The deficits displayed temporal tuning, being greatest for higher temporal frequencies (> or =9 Hz). None of the subjects revealed deficits typical of cortical lesions. The migraine-without-aura subject displayed a selective loss to temporally modulated stimuli, which was consistent with the aura group. This defect altered over time, decreasing for 30 to 40 days but remaining, to a smaller extent, for up to 75 days after the headache event., Conclusions: Visual dysfunction that is selective for temporally modulated targets occurs in migraine subjects. The migrainous pattern of dysfunction shares some features with that identified in early stages of glaucoma and raises the possibility for a common precortical vascular involvement in these two conditions.

We investigated the interactions between flicker thresholds and luminance pedestals using threshold versus contrast (TvC) and method of constant stimuli paradigms. High amplitude luminance pedestals were found to elevate flicker thresholds, but low amplitude luminance pedestals were unable to reduce flicker thresholds. Luminance pedestals elevated flicker thresholds more at low temporal frequencies. A simple model based on local light adaptation was able to capture the general form of the TvC functions. Our results suggest that flicker thresholds derived in the presence of a luminance pedestal (luminance-pedestal flicker) may vary from those obtained by modulating about a mean luminance (mean-modulated flicker).