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A very useful clinical vernier acuity or vernier alignment test has been developed in this and associated laboratories over a span of two decades. We seek to refine further this test, to seek internal inconsistencies and to optimize parameters used in a variety of devices and environments. Vernier testing, and many aspects of this work have been considered by numerous able scientists over a long time period (not reviewed here), but none have encountered conditions faced by this group, particularly in the developing world. The three point vernier alignment (acuity) threshold test (3Pt VeA test) employed here has broad applications; it can be used as a clinical test of vision status, for triage, and as a reference standard for vision testing (in general). As one example, if sufficient luminance is employed, the test is applicable in the presence of truly dense media disorders, even advanced leucomas, mature cataracts, intraocular bleeds, as well as combinations of these disorders, with or without a window to the retina. Only retinal and centrally-based neural disorders, eccentricity from fixation, and about 50% of hypermature cataracts affect outcomes. With minor alterations, this test can be employed to assess the visual field. An analysis of variance (ANOVA) was performed on a defined set of parameters, to enable us to understand better the special properties and requirements associated with this test. Results are not significantly altered between ages 10-94 years (not assessed here). Employing settings well above threshold for test spot detection and well separated individual test spots, changes in test spot luminance, or background luminance (or adaptation level), contrast, veiling glare, test spot size, clear and variously degraded images, seem not to affect meaningfully measured outcomes. If an observer can define well a center of gravity for each test spot viewed, he can align the three points with remarkable precision.

Ancient (in fact, first known) lenses (ca. 4600 years ago) mainly from the IVth and Vth Dynasties of Egypt had truly remarkable and unique optical properties. These were parts of equally fascinating eye structures. These structures were fabricated as separate assemblies for insertion into funerary statues during certain brief windows of time (roughly from 2620-2400 BC, and 1750-1700 BC). These "eyes" appear to follow the observer as he/she rotated in any direction about these statues. In this paper, by simple means, we have recreated the optical properties of these unique lenses in the laboratory in order to help understand their special properties.

The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines by the reactive oxidant H2O2, the proinflammatory cytokine TNF-alpha, and respiratory syncytial virus (RSV) is mediated in a cell type-specific manner involving different patterns of AP-1 and NF-kappaB binding activity. Our results demonstrate that H2O2 induction of IL-8 gene expression is linked with the selective binding of AP-1 to the IL-8 promoter, whereas TNF-alpha and RSV induction of IL-8 correlates with the activation of NF-kappaB binding. We propose that the differential activation and binding of inducible transcription factors to the promoter regions of chemokine genes provides a critical regulatory mechanism by which the CXC and CC chemokines can be selectively expressed in a cell type-specific and stimulus-specific manner. Such a regulatory mechanism of differential chemokine expression could critically influence the site-specific recruitment of distinct subsets of leukocytes to sites of inflammation and injury.

The geometrical center of the pupil has often been used as the reference axis in ocular wave-front aberration measurement. However, the geometrical center of the pupil may shift when the pupil size changes under different conditions. In particular, for subjective methods, defining the center of the pupil precisely during the actual measurement is not always practical. Furthermore, the geometrical center of the pupil may not define the chief ray of the ocular optics because of the Stiles-Crawford apodization effect, which has a peak location that often deviates from the geometrical center of the pupil. We present the coefficient transformation table of the Taylor polynomial up to the sixth order with respect to reference axis shift. We illustrate the effect of wave-front aberration change with reference axis shift with experimental data. This type of wave-front aberration change could be a true measurement error if there is an error in defining the reference axis. We also propose using the coaxially sighted corneal reflex as a better reference axis in aberration measurement.

Purpose: Surprisingly, an important characteristic of astigmatism has been overlooked by ophthalmic and clinical scientists. Apparently, refractive astigmatism is due largely to a form of high spatial frequency image distortion., Methods: Characteristic astigmatic image distortion can be minimized or eliminated by using a low-pass spatial filter (here, a ground glass plate was employed for this purpose). The ground glass is placed a short distance in front of a visual acuity chart, or it may be used with other tests, such as vernier acuity., Results: This test has been performed by us on large numbers of patients and test subjects. A clinician can try this test for himself/herself. Place a +2.00 D.C. (any axis) lens in front of the eye; the usual distortions will be observed. Locate the ground glass plate as described. The usual distortions associated with the conoid of Stürm will not be visible or will be virtually eliminated, although some image blur will remain., Conclusions: This technique has significance, e.g., in visual screening programs in developing nations, or in assessing patients with media disorders prior to ophthalmic surgery.

A matrix method to do nonlinear calculations is described. This is possible only under the special condition when a transformation maps a zero vector onto a zero vector. Geometrical optics conform to this condition and hence matrix methods can be applied to calculate aberrations. Methods to reduce computational complexities using symmetry arguments are provided. The formalism is applied to study refraction by a conic surface. Aberration coefficients, up to fifth order, are obtained as functions of eccentricity and the latus rectum of the conic surface. The method can be used to model corneal aberrations.

A revised formulation of the image light distribution of an incoherent line source proposed by Steel [Rev. Opt. 31, 334-340 (1952)] is presented. Analytical and numerical results based on this new representation are given. We explicitly show that a major error in Steel's final expression generates singularities, thereby preventing convenient numerical computation.

Aim: To illustrate how the concept of ray vector fields can be used to demonstrate the elementary properties of thin lenses., Methods: Principles of matrix algebra are used., Results: Using simple geometry we give a generalization of Prentice's rule to include thick astigmatic lenses. Starting from the ray vector fields we show the connection between various representations of spherocylindrical lenses (Fourier representation, expansion in terms of the cross-cylinders). We suggest two clinical areas to which these concepts can be applied.

Contrast sensitivity has been shown to be affected in Alzheimer's disease (Ad). We investigated low contrast acuity and contrast sensitivity using clinical test charts in this patient population. Additionally, we tested patients with vascular dementia (vd) and mixed dementia (md), (Alzheimer' with vascular dementia). Contrast sensitivity was assessed using the Vistech VCTS 6500 test chart. Low contrast acuity was measured using the Regan charts at four contrast levels (96%, 50%, 25% and 11%). The patient population consisted of 19 Ad patients, 9 vd patients and 10 md patients. Reduction in acuity was found with contrast level in all cases. Regression lines were fit to the data and statistical analysis was performed. We did not find a statistically significant difference between the Ad and vd or md groups. We did, however, find a difference between the vd and md groups. We did find reduction in contrast sensitivity at all spatial frequencies when compared to the elderly normal. Correspondingly, we found a significant difference in acuity when compared with normal data at the four contrast levels tested. Acuity is reduced with contrast in all patient groups. Our contrast sensitivity results are similar to those reported in the literature. This study points out the importance of using simple clinical test charts and further underscores the idea that there is a primary visual deficit in Ad.

The spatial impulse response of a single variable-cross-section photoreceptor has been characterized assuming the incoming radiation to be an initial field propagating under confinement conditions inside the receptor. By application of Fourier analysis the total transfer function is determined. Both the outer and the inner segments are characterized as low-pass filters. The dependence of the transfer function on the modal parameter is analyzed.

With certain (but not all) vernier acuity (VeA) stimulus displays observers exhibit no or slight performance decrements with aging. Because three-point VeA test displays are much more easily applied experimentally and clinically, we examined visual performance on this task as a function of age. Ages of groups tested ranged from 20 to 70+ years (some individuals were 90+ years old). Eyes were examined monocularly. We tested three- and two-point sharply defined VeA arrays and a three-point ground-glass-degraded display (simulating a 20/100 nuclear cataract). Gap or feature separations were varied. Results obtained with the three-point display showed little alteration with age. Image degradation resulted in reduction in performance when small gap separations were used between the test points, but only slight decrements for large gap separations were recorded. The finding that performance with certain VeA targets is largely unaffected by age is confirmed and is expanded.

We investigated the mechanisms by which H2O2 increases intercellular adhesion molecule 1 (ICAM-1; CD54) expression in endothelial cells. The H2O2-induced increase in ICAM-1 mRNA was inhibited by actinomycin D, by the antioxidant N-acetylcysteine, and by 3-amino-benzamide (which blocks oxidant-induced AP-1 activity), but not by pyrrolidine dithiocarbamate (which blocks oxidant-induced NF-kappa B activity). Nuclear run-on and transient transfections of ICAM-1 promoter constructs indicated that H2O2 stimulated ICAM-1 gene transcription by activation of a distinct region of the ICAM-1 promoter. The H2O2-responsive element was localized to sequences between -981 and -769 (relative to start codon). Located within this region are two 16-base pair repeats, each containing binding sites for the transcription factors AP-1 and Ets. A similar composite AP-1/Ets element isolated from the macrophage scavenger receptor gene conferred H2O2 responsiveness to a minimal promoter. Mutation of the 16-base pair repeats within the ICAM-1 promoter prevented H2O2-induced DNA binding activity, and their deletion abrogated the H2O2-induced transcriptional activity. In contrast, TNF alpha induced ICAM-1 transcription via activation of promoter sequences between -393 and -176, a region with C/EBP and NF-kappa B binding sites. The results indicate that H2O2 activates ICAM-1 transcription through AP-1/Ets elements within the ICAM-1 promoter, which are distinct from NF-kappa B-mediated ICAM-1 expression induced by TNF alpha.

Problem: If changes are made to the optics of the eye (e.g., intraocular lens implants, contact lenses, etc.) how will they affect performance on clinical tests of vision?, Method: A phenomenological method is presented based on in vitro optical transfer function (OTF) and a simple model of human threshold detection., Results: The model is used to predict and the results are compared with clinical data (acuity, contrast sensitivity) obtained from pseudophakic patients implanted with a multifocal intraocular lens (IOL). A good qualitative agreement is found with the clinical data., Significance: This model predicts the relative change in clinical performance for a given change in the optical components of the human eye. This simple phenomenological model permits numerical prediction of clinical tests and is easily calculable.

Purpose: To introduce the concept of the ray vector field and apply it to a problem in ophthalmic optics., Methods: Matrix and linear algebra are used to relate ray vector fields and a representation of thin spherocylindrical lenses., Results: Equations were derived relating ray vector fields and a particular coordinate system recommended previously. The method is illustrated with a simple example from ophthalmic optics, namely, addition of spherocylindrical lenses. We also illustrate the method by considering two spherocylinders separated by a distance., Conclusions: Ray vector fields are intuitively simple and can be used to solve complex ophthalmic optics problems.

Purpose/background: Many visual functions change with age. Hyperacuity vernier thresholds, however, seem to remain practically invariant with age., Methods: We critically review reports on age-related changes in hyperacuity thresholds and present new data using two and three-point vernier hyperacuity thresholds., Results: It appears as though the vernier (two dot or two line) alignment hyperacuity thresholds are not sensitive to age., Significance: Based on these studies we propose that hyperacuity (vernier) thresholds be used as a benchmark, or a gold standard for aging studies. This measurement can serve as a valuable control and reference for other clinical studies of aging.

Purpose: Investigate photoreceptor orientation and alignment in an observer with a simple coloboma of the iris and no retinal involvement., Method: Using a psychophysical procedure, extensive measurements of the Stiles-Crawford functions of the first kind (SCE I) were obtained from this observer., Results: In this observer, the usual center-of-the-exit-pupil-of-the-eye alignment tendency of photoreceptors (inferred from the peaks of the SCE I functions) is absent. The inferred orientation of photoreceptors at numerous retinal loci tested lies outside the pupil, opposite the direction of the downwardly displaced pupil center., Conclusions: These results add support to previous suggestions that nonphototropic forces such as retinal tractional forces should be considered as an integral part of the mechanism(s) subserving human photoreceptor alignment in both normal and anomalous observers.

We describe a methodology to predict the outcome of clinical tests caused by changes made to the optical elements of the human eye. This formalism, called the expected visual outcome model, is based on in vitro measurements of the optical transfer function and takes into account a simple model of human threshold performance. The clinical tests under consideration are high-contrast visual acuity and contrast sensitivity. Using the expected visual outcome, we describe a useful performance index called the predicted visual acuity graph, which can be measured clinically. The theoretical results are compared with visual function measured in patients with pseudophakic (multifocal and monofocal) implants.

Evidence suggests that the psychophysically determined Stiles-Crawford effect of the first kind (SCE) reflects waveguide properties of human photoreceptors. The peak of the SCE data set is assumed to reflect the principal alignment tendencies, and the spread (e.g., rho value, the curvature or width at half-height) is assumed to reflect the directionality (i.e., interreceptor differences in alignment) of the population of photoreceptors being tested. As such, disruption of the normal SCE can be used and/or has been used (1) to document early natural history of retinal pathology involving the photoreceptors, (2) to provide a firm rationale for therapeutic intervention, and (3) to provide a method for monitoring therapies designed to alter the natural course of retinal-disease processes. We report large-sample norms for foveal SCE peak location and spread (horizontal peak location, nasal 0.51 +/- 0.72, horizontal rho value 0.047 +/- 0.013, vertical peak location, superior 0.20 +/- 0.64, vertical rho value 0.053 +/- 0.012), compare these norms with values determined in other laboratories, and discuss the various mathematical forms used for the empirical description of SCE data sets.

In many experimental situations one has to work with suitable optical corrections for ocular elements which have been eliminated (lens in aphakia, for example). Analysis of the optics of the total system (eye plus correction and other optical elements) shows substantial changes in the positions of the cardinal points. These changes are meaningful and must be taken into account in subsequent analysis. We discuss the pertinent optical considerations and show as an example the results of measurements of the Stiles-Crawford effect of the first kind in an aphakic subject with spectacle and contact lens correction.

In the presence of one or two intraocular lenses (IOL's; pseudophakic corrections) or in the presence of naturally occurring or developmental anisometropia (due to a tumescent cataract) some induced or residual refractive aniseikonia is usually encountered. We wish to call this problem to the attention of the optometric practitioner. We provide a discussion of the resultant aniseikonia and simple rules of thumb for management of such patients with refractive aniseikonia. Aniseikonia in these patients may be less important than once had been suggested, but certainly it is more significant than it is currently being considered. Use of personal computers to calculate this aniseikonia makes appropriate correction relatively easy and readily applicable.

Responses to hyperacuity stimuli are processed in quite a different manner by the central nervous system than many other stimuli such as resolution targets or increment threshold stimuli. With increased attention being paid to visual response in aging individuals, it is important to study how these response paradigms are affected by age. In this analysis, otherwise normal observers 20 to 85 years of age were studied. The hyperacuity gap test was used. As defined, this is a vernier test using a two-point test array. This particular format was chosen because the resultant data are less distorted by image blur, scatter, and astigmatism than other designs we have studied. The gap or feature separation between the two small targets (which were aligned vertically) was increased logarithmically using octave steps and the hyperacuity threshold (setting variance) was measured for each step. No systematic variation of vernier hyperacuity threshold was found with increasing age within the range of ages or gaps tested. This is important because it can serve as a valuable control and reference for other clinical studies of aging.

The Hill length-tension curve of a muscle fibre is not linear. This had led us to investigate the behaviour of a model muscle sarcomere. The muscle is modelled as an oscillator of mass m subject to a nonlinear restoring force, a periodic external driving force and friction. We have found that this simple, idealized model exhibits spontaneous symmetry breaking and transition to chaos via a period doubling sequence. This result suggests that the nonlinearity in the length-tension curve of a muscle fibre could be responsible for irregular temporal behaviour and muscle tremor.

We have developed a new technique for quantification of metamorphopsia using a simplified and modified Amsler grid. Furthermore, the technique used is a bisection task, a form of hyperacuity determination. This allows for very fine assessments of metamorphopsia even in the presence of cataracts.

Three visual manifestations of Gilles de la Tourette syndrome (TS), a neuropsychiatric disorder, have been previously reported. In this paper we report anomalies in the measured kinetic paracentral visual field of TS patients and their family members. We found that 96% of TS patients exhibited paracentral kinetic visual field defects (nasal and temporal steps, enlargement, "ringing," and/or baring of the blind spot). Ninety-three percent of fathers of TS children and, surprisingly, about 80% of mothers exhibit these characteristic visual field anomalies. Sample data and examples of family studies are reported.

Dopamine may play a role in form-deprivation myopia in chickens. Anomalies of the dopaminergic system are believed to be responsible for manifestations of symptoms in Tourette Syndrome (TS), a neuropsychiatric disorder. Visual anomalies have been identified in TS. In this paper, refractive error in people suffering from TS is compared with available population studies. Refractive errors in TS are found to be similar to those in the normal population.

Data on goldfish rod and cone fragments were obtained before and after a strong bleach by using a Zeiss Jamin-Lebedeff infrared interference microscope and computer image processing techniques. The receptor fragments were fractured in the inner segment and were immersed in goldfish aqueous humor medium. On bleaching we found that: (1) there is a small increase in rod diameter. This effect is of the same magnitude reported earlier in Rana pipiens outer segments (Vision Res 1973; 13:171). (2) There is an inferred decrease in rod refractive index. (3) There is a decrease in cone width. (4) There is a slight increase in inferred cone refractive index. These data are presented.

Subjects can accurately discriminate small changes in the relative position of features within a pattern. Simple patterns (intersected line segments) can undergo magnification and a variety of transformations without significantly affecting the discrimination thresholds. Features to be localized and compared need not be similar. We suggest that such relative position discriminations could support complex object identification.

Ensemble averaging after pre-editing of surface EMG potentials has enabled construction of underlying controller signals from stereotyped head movements. Carefully controlled, intended time-optimal movements by trained, actively participating human subjects have been found to yield repeatable, multi-pulse controller signals. Also, adaptive changes in these horizontal head movements in response to added viscous loads showed further causal relationships between movement dynamics and EMG signals from left and right splenius muscles. These experimental results are a base from which modeling studies can be performed to explicate the neurological control strategies used in the performance of this class of movements.

Apparent motion was investigated as a stimulus for optokinetic nystagmus (OKN) and self-motion perception (vection). Apparent motion was stimulated by stroboscopically illuminating vertical stripes on the interior of a large drum that rotated about the observer at 20, 40 and 60 deg/sec. We determined threshold stroboscopic frequencies (f) for the appearance of smooth continuous apparent motion and measured responses of pursuit, OKN, optokinetic after nystagmus (OKAN) and vection, to stroboscopic frequencies at, above and below f. Pursuit occurred for all of these stimuli. However OKN, OKAN and vection only occurred for frequencies equal to or greater than the threshold for continuous apparent motion. Our results suggest that pursuit can occur as a response to apparent motion generated by both small and large image displacements, while OKN and vection are responses to apparent motion generated by small image displacements only. These results suggest that different afferent sources are utilized for the control of pursuit and of the slow phase of OKN.

Contrary to previously published studies, monocular light exclusion did not alter the shape of the Stiles-Crawford function in a substantial manner in four subjects who were patched in this laboratory for one full week. In order to rule out methodological differences, an experimenter from each of the two sets of experiments (current and prior) patched one eye for 1 week, then tested each other. For one subject, there was little effect of patching. For the other, patching had a measurable effect, but it was different from that originally reported. However, the much larger, symmetrical broadening of the Stiles-Crawford function reported in earlier studies was not replicated. A testable working hypothesis to explain the earlier results is discussed.

The optical matrices for modified schematic eyes are derived. The primary modification is to replace the usual isoindicial or bi-indicial crystalline lens with a polyindicial lens so as to more closely approximate the living human lens. Further modifications are made to simulate the accommodated state. The use of optical matrices to solve an optometric problem is demonstrated.

An exact formulation of the electromagnetic field striking an optical waveguide is presented and compared with the decomposition relationship used in the literature. The expression for the critical angle is derived as a natural consequence of this formulation. Equations for the total fraction of power confined within a waveguide are derived and analyzed for the special case of absorbing waveguides. An explicit expression is derived for the fraction of energy confined within a waveguide supporting two sets of modes.

Opacities in the cornea, crystalline lens, and vitreous may make conventional measurements of retinal/visual function of little value. Here, we present two psychophysical hyperacuity tests that are designed to detect and quantify retinal distortions even in the presence of substantial opacities. One test makes use of a two-dot vernier display in which directional bias as well as vernier acuity can be estimated. The second test is a multi-dot hyperacuity bisection task, which resembles a simplified Amsler grid test. By varying the spatial parameters of these stimuli, metamorphopsia may be quantified. The method is applicable both in clear and occluded ocular media.

Accommodative amplitude decreases with age, not with aging. The decrease is largely completed by age 40 years; only minor residual accommodation is present in most subjects after the mid-40s. Dynamical measurements show the accommodative response of subjects over 30 years of age to be significantly slowed (time constants of accommodation increases). Accommodation amplitude is less than 3 D by 30 years of age. Thus prepresbyopia is a sign of continual development, not of deterioration of the accommodative mechanism. Accommodation, or the change of clear vision with change in lens power, has been studied by many distinguished scientists including Descartes and Thomas Young. Helmholtz's "Theory of Accommodation" is a dual, indirect, active theory. There are both lenticular, including lens and capsule, and also extralenticular mechanisms, comprised of the zonule of Zinn or suspensory ciliary ligament and the ciliary muscle itself. The ciliary muscle does not act directly on the lens but indirectly through its action on the zonule of Zinn. Active contraction of the ciliary muscle, a unified muscle, produces accommodation; relaxation of the ciliary muscle permits relaxation of accommodation.

The presence of visual field anomalies was measured using Goldmann kinetic perimetry in twelve patients, age 7 to 39 with Gilles de la Tourette syndrome. Refraction to the cupola was carefully controlled. The visual acuity of the group was good to excellent. Visual field alterations were prechiasmal, generally non-symmetric, and best described as arcuate defects, steps, baring of the blind spot and enlargement of the blind spot. Central fields were most commonly affected, i.e., I/2e to I/1B isopters. There was no evidence of glaucoma in any of the patients although two patients exhibited keratoconus and another one manifested moderate to high astigmatism. Visual involvement other than ocular and lid tics have not been reported in Tourette syndrome. This research represents clear evidence of additional physical components in this condition. Automated visual field measurements are not recommended in this population because of the presence of non-predictable tic and vocal behavior (both may result in head/eye movements). Suppression of tic behavior can be very fatiguing. (Eight of twelve of the patients reported exhibited signs of marked fatigue during testing.)

There is a tendency for the posterior chamber intraocular lens to tilt about the points of insertion. This is found clinically and in postmortem studies of eyes that have had intraocular lenses surgically implanted. One end is often located in the lens capsule and the other end is located in the ciliary sulcus. The possibility of anteroposterior displacement also exists. Using a modified Gullstrand schematic model eye, we have computed the amount of spherical and cylindrical errors that are induced due to the tilt and/or displacement of the intraocular lens. If a cylindrical error of approximately 90 degrees from the axis of insertion (lens plus haptic loops) and/or axis of tilt is detected, further careful investigation is warranted.

We present here numerical estimates of the density and flux of energy based on physical parameters associated with the absorption properties of certain types of absorbing optical waveguides. These results are based on a theoretical formalism established previously for the initial field incident upon the entrance pupil of an absorbing optical waveguide. Based on these results, the mechanisms of confined energy transmission and possible cross talk between neighboring waveguides are discussed. Some comments on the behavior of Bessel functions with complex arguments are also included in the discussion.

The Stiles-Crawford effect of the first kind (SCE I), discovered in 1933, represented a major breakthrough in our understanding of retinal physiology and the modern beginning of the science of photoreceptor optics. The current status of knowledge in this area is briefly reviewed. A study is presented of a white adult female observer with aniridia, clear media, only traces of nystagmus, rather good visual acuity, and good fixation. It is shown that this individual exhibits approximate alignment of her photoreceptors with the center of the retinal sphere, clear evidence of side lobes on functions, and surprisingly steep SCE I functions. The implications of these findings are considered.

A simple mathematical proof for the constancy of the shape factor in the analysis of the psychophysically determined Stiles-Crawford data is presented.

Stiles-Crawford (SCE) functions are determined using an increment threshold procedure. The customary technique requires considerable time to obtain a full SCE function and in many situations, both clinical and experimental, it is imperative that the SCE function be evaluated at many retinal loci in as short a time as possible. We have been using two different variants of the standard method, one requiring a very limited number of threshold settings at five fixed entry points in the entrance pupil (5-point method) and in the other, thresholds are determined at only three preselected entry points (3-point method). The time required to obtain a complete SCE function is the order of 5 to 8 min using either method. Comparison and statistical evaluation of the techniques are presented.