There is more to accommodation of the eye than simply minimizing retinal blur.

Eyes of children and young adults change their optical power to focus nearby objects at the retina. But does accommodation function by trial and error to minimize blur and maximize contrast as is generally accepted? Three experiments in monocular and monochromatic vision were performed under two conditions while aberrations were being corrected. In the first condition, feedback was available to the eye from both optical vergence and optical blur. In the second, feedback was only available from target blur. Accommodation was less precise for the second condition, suggesting that it is more than a trial-and-error function. Optical vergence itself seems to be an important cue for accommodation.

Accommodation to monochromatic and white-light targets.

PURPOSE: The objective of the current study was to compare accommodation to targets illuminated with monochromatic light from different regions of the visible spectrum with accommodation to white-light targets. METHODS: One of 10 marrow-band interference filters (430, 450, 470, 500, 530, 550, 570, 590, 630, and 670 nm) was used to produce monochromatic light from a tungsten-halogen source to illuminate a Maltese cross-target in Maxwellian view. Luminance of each monochromatic light was matched by minimum border photometry against a standard white light (3000 K) that was maintained at 200 cd/m2. Chromatic difference of focus of the eye was minimized for all monochromatic targets by the use of an achromatizing lens. A white-light target also was used, and the subject's eye was achromatized or the eye had normal chromatic aberration. The target was moved sinusoidally toward and away from the eye at a temporal frequency of 0.2 Hz over a 1 D amplitude (peak to peak). Accommodation was monitored continuously by an infrared recording optometer, and responses were Fourier analyzed to obtain gain and phase lag at the temporal frequency of stimulation. RESULTS: Accommodative gain was highest and phase lag was smallest when the target was illuminated by white light in the presence of normal chromatic aberration. The achromatized white-light gain of accommodation was statistically similar to the gain for monochromatic targets, indicating that the presence of chromatic aberration facilitates accommodation. Significant intersubject variability was present in the accommodative tracking ability to monochromatic targets. CONCLUSIONS: Accommodation to monochromatic targets is not as accurate as accommodation to a white-light target, and this effect is related to the presence of ocular longitudinal chromatic aberration for the white-light target.

Accommodation dynamics in divergence excess exotropia.

Objective recording of accommodation dynamics was performed in four patients with divergence excess exotropia (two true and two simulated) and in three visually normal control subjects. The accommodative peak velocity/amplitude relationship was normal in the exotropic patients and in the control subjects. Latency for decreasing accommodation was increased significantly, and overshoot frequency was decreased, in the divergence excess exotropes of the true variety, thus demonstrating slightly slowed accommodation dynamics in this diagnostic group. These subtle deviations in response dynamics reflect central rather than peripheral mechanisms.

Cytokine production in human and rat macrophages and dicatechol rooperol and esters.

The ability of dicatechol rooperol and esters to inhibit the production of cytokines in endotoxin-stimulated human alveolar macrophages, human blood monocyte/macrophages, histiocytic cell line U937, and rat alveolar macrophages was examined in vitro. Rooperol derivatives inhibited the production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 microM) than rooperol disulphate (IC50 in the range of 25-75 microM). The acetate esters also inhibited cytokine production in rat alveolar macrophages, whereas the sulphate had little effect. Rooperol and acetate esters, in the same concentration range, decreased the production of nitric oxide by rat alveolar macrophages stimulated by endotoxin. These concentrations of rooperol had no effect on cell viability, as indicated by incorporation of 14C-labelled leucine into macrophage proteins and their content of lactate dehydrogenase. The results obtained suggest that rooperol esters are potentially useful antiinflammatory agents.

Dioptric and non-dioptric stimuli for accommodation: target size alone and with blur and chromatic aberration.

The frequency response of the accommodative system (0.05-1 Hz) was determined for various combinations of stimuli: changing target size was presented alone, together with defocus blur, and with both defocus blur and chromatic aberration. A high-speed infrared optometer monitored accommodation while the subject viewed the target in a Badal optometer. Target size was varied sinusoidally and blur was provided by moving the target towards and away from the subject at the same frequency. Chromatic aberration was controlled by using either monochromatic (590 nm) or white (3300 K) light. The target was presented under open-loop conditions when size was the only stimulus. We find that besides the conventional dioptric stimuli, changes in target size that result in changes in apparent distance can have substantial effects on accommodation.

Stimuli for accommodation: blur, chromatic aberration and size.

We investigated the frequency response of the accommodative system (0.05-1 Hz) using three stimuli: defocus blur, the effects of the chromatic aberration of the eye, and changing target size. A high-speed infrared optometer monitored accommodation while the subject viewed a target in a Badal optometer. Blur was provided by moving the target sinusoidally towards and away from the subject (1-3 D) and the size of the target was varied at the same frequency. Chromatic aberration was controlled by using either monochromatic (590 nm) or white light (3300 K). Gain and phase plots changed systematically as we varied the number of stimuli presented together. This suggests that besides defocus blur both chromatic aberration and changing size are involved in accommodative control.

Spatiotemporal transfer function of human accommodation.

We have investigated the spatiotemporal transfer function of human "reflex" accommodation. An accommodative mechanism that is sensitive to an intermediate temporal rate of retinal image contrast change is proposed as the basis of the fine focus control hypothesis. To test the proposed mechanism accommodative responses were monitored by a dynamic infrared optometer while the subject focused on sinusoidal gratings (0.98-10.5 c/deg) which were moving sinusoidally at temporal frequencies in the range of 0.05-0.80 Hz over a 0.50 or 2.00 D peak-to-peak amplitude. The accommodative responses were best at 3 and 5 c/deg at both amplitudes of target motion. This result does not support the proposed mechanism or the fine focus control hypothesis for "reflex" accommodation. Fitting the data with first-order response functions showed little evidence of prediction. In addition, a second experiment found that the profile of the accommodative gain function is not altered by instruction at spatial frequencies above 5 c/deg in this type of dynamic accommodation experiment. The use of sinusoidally moving accommodative blur targets, particularly with careful instruction, seems to discourage voluntary accommodation in investigations of "reflex" control mechanisms of accommodation.

Isolated short-wavelength sensitive cones can mediate a reflex accommodation response.

Both long- and middle-wavelength sensitive cones mediate the reflex accommodation signal but the contribution from the short-wavelength sensitive cones is unknown. A short-wavelength sensitive cone contribution could extend the range of the signed defocus signal from chromatic aberration. The aim was to determine whether isolated short-wavelength sensitive cones mediate reflex accommodation independently of long- and middle-wavelength sensitive cones. Accommodation was monitored continuously (eight subjects) to a sine-wave grating (3 cpd; 0.53 contrast) moving with a sum of sines motion in a Badal optometer. Two illumination conditions were used: a 'blue' condition that isolated short-wavelength sensitive cones, and a 'white' control condition that stimulated all three cone types. Of the eight subjects, two responded equally in the 'white' and 'blue' condition, four gave reduced responses in the 'blue' condition and two failed to respond in both conditions. The mean response in the 'blue' condition was reduced by 50% compared to the 'white' condition. Further analysis indicated that four of the eight subjects gave responses that were considerably greater than noise (S.D.>1.82) when short-wavelength sensitive cones were isolated. Some subjects can accommodate using only S-cones.

Stimulus and response AC/A ratios in intermittent exotropia of the divergence-excess type.

Objective infrared recording devices were used to measure simultaneously and continuously both accommodation and accommodative vergence to near stimuli in 4 subjects with intermittent exotropia of the divergence-excess type (2 simulated and 2 true). In addition standard clinically determined stimulus accommodative convergence to accommodation (AC/A) ratios were measured. Results showed the mean group response AC/C ratio to be 5.9/1 (range 4.5-8.0/1) with no differences between true and simulated divergence-excess. Similar AC/A ratios were found after 45 minutes of monocular occlusion. Our results clearly demonstrate relatively normal response AC/A ratios in these subjects. Thus, contrary to what is believed by many clinicians, the reduced ocular deviation at near compared with distance vision cannot be attributed primarily to an abnormally high AC/A ratio. We believe than fusional convergence after-effects and/or proximal convergence effects contribute to inflate the clinically determined stimulus AC/A ratios.

Changing size (looming) as a stimulus to accommodation and vergence.

Changing size (looming) produces changes in accommodation and vergence. Dynamic responses of vergence and accommodation to sinusoidal looming of a Maltese cross were recorded with an SRI dual-Purkinje-image eyetracker and optometer. The ratio of these two motor responses was compared with the response accommodative convergence/accommodation (AC/A) ratio and convergence accommodation/convergence (CA/A) ratio determined from sinusoidal variations of blur and disparity respectively. The response to changing size was found to be more similar to the AC/A ratio than the CA/C ratio. In addition, when a changing disparity or changing blur stimulus was combined with a changing size stimulus, the response phase lags of accommodation and vergence were decreased. In addition, the CA/C ratio was increased when changing size was added to changing disparity, but the AC/A ratio was unaltered when changing size was added to changing blur. These results indicate that changing size is stimulating accommodation directly and vergence secondarily through an AC/A crosslink.

Chromatic aberration and ocular focus: Fincham revisited.

Longitudinal chromatic aberration of the eye (LCA) produces "color fringes" at edges that specify focus. Fincham [(1951) British Journal of Ophthalmology, 35, 381-393] concluded that these chromatic effects were important for accommodation, but most investigators disagree. We monitored accommodation in 25 subjects while they viewed a sinusoidally moving target (1.5-2.5 D at 0.2 Hz) in a Badal optometer. The target was monochromatic (590 nm with 10 nm bandwidth), or white (3000 K) with LCA normal, neutralized or reversed. Sensitivity to the effects of LCA is profound and widespread. Gain decreases substantially and phase-lag increases when LCA is eliminated, and reversing the aberration severely disrupts accommodation. The ordered arrangement of spectral foci produced by LCA seems to be a fundamental aspect of the stimulus for "reflex" accommodation.

Accommodation responds to changing contrast of long, middle and short spectral-waveband components of the retinal image.

We simulated the effects of longitudinal (axial) chromatic aberration and defocus on contrast of the long-, middle- and short-wavelength components of the retinal image to determine whether the effects of chromatic aberration are sufficient to drive accommodation. Accommodation was monitored continuously while subjects (12) viewed a 3 c/deg white sine-wave grating (0.92 contrast) in a Badal stimulus system. The contrasts (amplitudes) of the red, green and blue components of the white grating changed independently to simulate a grating oscillating from 1 D behind the retina to 1 D in front of the retina at 0.2 Hz. Subjects responded strongly to the chromatic simulation but poorly to a luminance control. The results support the hypothesis that focus is specified by the contrast of spectral-wavebands of the retinal image, and that conventional color mechanisms, monitoring chromatic contrast at luminance borders (1-8 c/deg), mediate the signals that specify dioptric vergence.

Accommodation without feedback suggests directional signals specify ocular focus.

Accommodation was monitored continuously under open-loop conditions while subjects viewed a sinusoidally oscillating sine-wave grating (0.2 Hz; +/- 1 D; 2.7 c/d; 0.56 contrast) in a Badal optometer. The target was illuminated by monochromatic light (590 nm) or white light (3000 K) with longitudinal chromatic aberration (LCA) normal, doubled, neutralized and reversed. Subjects (12) accommodated well in white light with LCA normal and doubled (mean gains = 0.85 and 0.94), gain was reduced in the neutralized condition (0.54), in monochromatic light (0.43), and especially when LCA was reversed (0.30). The results suggest that accommodation responds to changes in the relative contrast of spectral components of the retinal image and perhaps to the vergence of light.

Inhibitory effect of di-catechol rooperol on VCAM-1 and iNOS expression in cytokine-stimulated endothelium.

Induced expression of vascular cell adhesion molecule-1 (VCAM-1) and of nitric oxide synthase (iNOS) is believed to play a role in the pathogenesis of atherosclerosis, asthma, as well as other inflammatory disorders. In the current study we examined the effect of the di-catechol rooperol [(E)-1,5-bis (3',4'-dihydroxyphenyl) pent-4-en-1-yne] on the process of microvascular endothelial cell (MME) activation by TNF-alpha and IFN-gamma. We show that rooperol decreases VCAM-1 and iNOS mRNA levels in cytokine-activated MME with subsequent inhibition of VCAM-1 membrane expression as measured by adhesion of P815 cells to MME monolayers, and NO production, as reflected in the nitrite concentration in culture medium. The properties of rooperol now described suggest that rooperol may be an anti-inflammatory agent useful in the treatment of several inflammatory disorders.

beta-Glucosidase activity in fetal bovine serum renders the plant glucoside, hypoxoside, cytotoxic toward B16-F10-BL-6 mouse melanoma cells.

By using p-nitrophenyl-beta-D-glucopyranoside as substrate, beta-glucosidase activity was observed in fetal bovine serum (FBS). This activity could be inhibited by heat inactivation of the serum. Gel chromatography of FBS indicated the presence of beta-glucosidase activity with an apparent molecular mass of 29 kDa. In McCoy's 5A medium supplemented with non-heat inactivated FBS, the diglucoside hypoxoside ([E]-1,5-bis[4'beta-D-glucopyranosyloxy-3'-hydroxyphenyl]pent-4-en - 1-yne) showed cytotoxicity toward B16-F10-BL-6 mouse melanoma cells. In incubations where the media were supplemented with FBS previously heat inactivated at 56 degrees C for 1 h or more, no cytotoxicity was observed in the presence of hypoxoside. The aglucone of hypoxoside, rooperol ([E]-1,5-bis[3',4'-dihydroxyphenyl]pent-4-en-1-yne), showed cytotoxicity regardless of whether the serum was heat inactivated or not. The kinetics of the heat inactivation of the beta-glucosidase activity in FBS coincided with the loss of apparent cytotoxicity of hypoxoside. High performance liquid chromatography analysis showed that rooperol could be generated by incubation of hypoxoside in non-heat inactivated FBS, but that this ability was lost in serum that was heat inactivated for 1 h or longer. Newborn bovine serum did not contain any beta-glucosidase activity whereas it was found in three different commercial sources of FBS. This observation is of practical importance because conventional heat inactivation of FBS at 56 degrees C for 30 min was not sufficient to inactivate the beta-glucosidase activity completely.

The effect of cognitive demand on accommodation.

An optometer (infared recording retinoscope) was used to monitor the accommodation of subjects (N = 40, ages 20 to 30 years) to determine whether an increase in cognitive demand would result in an increase in the level of their accommodation. When the subjects in the experimental group (N = 20) changed from reading 2-digit numbers at 40 cm to adding the numbers, with no change in the visual stimulus, the average level of accommodation increased in 75% of the subjects--the mean level of accommodation increased 0.28 D (P < 0.01). Subjects in the control group (N = 20) showed no significant change in accommodation. The increase in accommodation is attributed to an increase in cognitive damand.

Infrared recording retinoscope for monitoring accomodation.

An optometer (infrared recording retinoscope) that provides high resolution measurements of accommodative changes of the eye has been developed. The instrument employs the principle of retinoscopy to monitor changes in the refractive state of the eye. Infrared radiation is scanned across the eye to provide a moving retinal source as in retinoscopy. An electro-optical system replaces the observer in determining the direction and amount of apparent motion in the pupil of the patient. The optometer is sensitive to accommodative changes of 0.12 D over a range of 12 D. The response of the instrument is faster than the most rapid changes of accommodation, and measurements are unaffected by pupil changes or by small eye movements.

Luminance changes of the fundus reflex.

A recording retinoscope was developed to measure the luminance of the fundus reflex during problem-solving tasks. 10 students were used as subjects. The luminance of the reflex was recorded while the subjects read 5 passages of graded reading material and performed an addition task. A reversal design was used to determine the effects of pupil changes and accommodation on changes in the luminance of the reflex. Relatively large changes in the luminance of the reflex were recorded. These were due to accommodation. The subjects' comprehension of the reading material did not appear to affect the luminance of the reflex in the manner predicted by previous studies. However, a change in task from simple reading material to an addition task appeared to increase the luminance of the reflex.

Brightness changes during book retinoscopy.

Book retinoscopy involves the observation of fundus reflex changes that are said to be related to the reading levels or interpretive levels at which persons are functioning. Recent investigations have shown that increasing the cognitive demand on a person can result in accomodative changes in his eye that increase the luminance of the fundus reflex. Since the ability of observers to distinguish such changes is not known, this experiment was designed to determine the minimum detectable increase in luminance. The experiment involved a 2-alternative forced-choice procedure in which observers were required to indicate during which of 2 designated intervals the reflex from a schematic eye became brighter. The luminance of the reflex had to increase by at least 11% beforeit could be detected. A reduction in the lag of accommodation and dilation of the pupil probably account for the changes observed during book retinoscopy.

The effect of accommodative changes on the brightness of the fundus reflex.

This paper demonstrates how accommodation and refractive changes affect the brightness of the reflex observed during retinoscopy. The amount of light entering the peephole of the retinoscope was monitored while accommodation was varied. The light entering the peephole reaches a maximum when the far-point of the eye is co-incident with the retinoscope and drops when the far-point moves behind or in front of the retinoscope. A reduction in the accommodative lag during book retinoscopy would result in brightening of the reflex along with a shift in the "against" direction.