Evidence from several laboratories suggests that retinal neurons detect defocus and send a signal through the choroid to the sclera that controls axial elongation. In a "normal" visual environment, this mechanism matches the axial length to the focal plane. Imposed defocus in mammalian animal models increases axial elongation by increasing scleral extensibility, and produces an induced myopia. This may involve altered retinal signals that act to change levels of substances, like retinoic acid, in the choroid that, in turn, alter mRNA levels and protein levels in the sclera. In humans, exposure to an environment that produces a high level of retinal defocus may stimulate axial elongation and produce myopia.

As the mechanism by which the retina controls the size of the eye becomes clearer, several strategies for controlling myopia progression in humans are being examined. One approach is to use optical correction (progressive addition lenses, rigid gas-permeable contact lenses) to reduce defocus. Another approach is to use pharmacological agents (atropine, pirenzepine) to control myopia progression. The pharmacological approach may either provide a simulated retinal signal indicating low defocus or directly affect the scleral fibroblasts that produce the extracellular matrix that controls the eye's elongation. Time will tell whether any of these approaches is effective in preventing, or slowing the progression of, human juvenile myopia.

1. Definitions
   1. Aberration
   2. WFE
2. Quantification of Wavefront Error
   1. Sampling
   2. Zernike Polynomial
3. Effect of Various Zernike Modes on Acuity
   1. Mode Interactions
4. Problems with the Quantification of Optical Quality
   1. "I can read 20/20 but it is not as good as it used to be."
   2. The need for better metrics of visual performance

Aberrations in the human eye impose a major physical limit on spatial visual performance. Although scientists were well aware of the presence of aberrations in the eye, during most of the last century, this topic was restricted to research laboratories. Most of the methods to measure the ocular aberrations were tedious, involved long research hours and, in many cases, the attentive collaboration of the subjects. However, during the last years, this scenario changed dramatically since more accurate and comfortable methods to measure aberrations were developed. First, I will briefly summarize some of these techniques. Then, I will discuss how typical are the aberrations in the normal eye, and how they change for different conditions, such as pupil size, age, accommodation, retinal eccentricity, or refractive state. The type of aberrations appearing in abnormally pathological eyes will be also described.

In the second part of the presentation, I will concentrate on the sources, or location, of the ocular aberrations. The two main contributors to the eye's aberrations are the anterior surface of the cornea and the crystalline lens. How the aberrations of these two elements relatively contribute to the final retinal image quality constitutes a central problem in Physiological Optics. I will describe the experiments we performed to provide insight into this question. We estimated independently the aberrations of the complete eye, the cornea, and the lens. The aberrations of the entire eye were measured with a Hartmann-Shack wave-front sensor. The aberrations of the anterior surface of the cornea were computed from the corneal shape previously measured by videokeratography. These two sets of data allowed us to estimate the aberrations of the lens by subtraction of the corneal aberrations from that of the complete eye. In a complementary experiment, we measured the aberrations of the eye when the contribution of the anterior corneal surface to the aberrations was cancelled by immersing the eye in saline water using swimming goggles. The amount of aberrations for the internal ocular surfaces was larger than for the complete eye. This suggested that at least in some young eyes the internal surfaces compensates in part for the aberrations of the anterior surface of the cornea. This indicates a positive role of the lens for improving retinal image quality. However, as the corneal and lenticular aberrations change as a result of normal aging, this compensation effect fails to happen in most older eyes. This fact would explain the increment of aberrations found in normal older subjects; more a decoupling of the cornea and lens aberration than an increase of aberrations in each separate component.

Cataract and corneal refractive surgery are the most common ocular surgical procedures, and their popularity is increasing. During cataract surgery the crystalline lens is replaced by an intraocular lens (successfully eliminating the scattering produced by the lens). Current corneal refractive surgeries (such as LASIK surgery) successfully compensate for refractive errors (such as myopia, hyperopia or astigmatism). However, these techniques can still be greatly improved. In this talk, we will show the change of optical aberrations induced by these two types of surgeries, and the origin of these changes.

We measured the optical aberrations (corneal and total) before and after intraocular lens (IOL) implant and compared them to the ocular aberrations in a young control group. We found that 3rd and higher RMS wavefront errors (i.e. non-conventional aberrations) do not change significantly after cataract surgery, and it is seven times higher in post-cataract surgery eyes than in young, normal eyes. This increase is due to an increase in the corneal aberrations induced by the incision, aberrations of the IOL, tilt and decentration of the IOL, and lack of balance of corneal and internal aberrations. Ex vivo measurements in a model eye showed that IOL lenses has positive spherical aberration (increasing with the IOL power), similar to that measured in vivo. Tilts and decentrations are likely to produce the higher amounts of 3rd order aberrations found in the in vivo IOL's aberration measurements. Smaller incisions, lower (or negative) spherical aberration values and a better control of tilt and decentration would result in better optical performance of these intraocular procedures.

We measured corneal and total aberrations in patients before and after LASIK surgery (both for myopia and hyperopia). The standard laser procedure induced aberrations in most subjects (average increase of 3rd and higher order RMS) by a factor of 2. The largest change occurred for spherical aberration. Myopic LASIK induced positive spherical aberration, and hyperopic LASIK induced negative spherical aberration. These changes are well correlated to the amount of pre-op ametropia, and with degradation of visual performance (CSF) Combination of corneal and total measurements are important to understand individual changes, and shed light into possible corneal biomechanical effects. Corneal ablation algorithms should be optimized to avoid aberration induction, before attempting a cancellation of natural ocular aberrations.

Significance: Cataract surgery with IOL implantation is the most commonly performed surgical procedure in patients over 60 years old in the United States. Approximately 2 million patients in the US will undergo cataract surgery and IOL implantation this year. While this procedure has undergone numerous refinements over the past 25 years, certain problems remain. In particular, calculations of IOL power are sometimes imprecise because of improper pre-operative measurements, post-operative astigmatism from irregular wound healing, or variability in placement of the IOL.

In addition to imprecise IOL power determinations post-operative, uncorrected visual acuity is often limited by pre-existing astigmatism. Recently, Staar Surgical (Monrovia, CA) introduced a toric IOL that corrects pre-existing astigmatic errors. The IOL comes in only 2 toric powers (2.0, 3.5 Diopters) and the axis must be precisely aligned at surgery. Other than surgical repositioning, there is no way to adjust the IOL's axis, which may shift post-operatively. Furthermore, individualized correction of astigmatism is limited by unavailability of multiple toric powers. An additional problem with using pre-existing astigmatic errors to gauge axis and power of a toric IOL is the unpredictable effect of the cataract wound on final refractive error. After the refractive effect of the cataract wound stabilizes, there can be a shift in both magnitude and axis of astigmatism, minimizing the corrective effect of a toric IOL. A means to post-operatively adjust (correct) astigmatic refractive errors after cataract surgery would be very desirable.

Growing interest in phakic IOLs for refractive correction of high myopia has accentuated the need for greater precision in IOL power determination. Because of the need to ablate excessive corneal tissue to correct large refractive errors, posterior chamber, iris fixated, or anterior chamber phakic IOLs provide better optical quality than excimer laser surgery (LASIK, PRK). While phakic IOLs are not associated with disabling optical aberrations, optimization of this refractive therapy remains limited by imprecision in IOL power selection (11-13).

An additional unexpected need for improved precision in IOL power determination has recently emerged. Eyes undergoing corneal refractive procedures (approximately 1 million/year US) that subsequently develop cataracts are problematic when estimating pseudophakic IOL power. Corneal topographic alterations induced by refractive surgery create imprecision in keratometric measurements (14-16). Several series of patients who have had refractive surgery (PRK, LASIK, radial keratotomy) and then required subsequent cataract surgery demonstrate surprisingly large hyperopic errors in IOL power determination. As the number of myopic patients who have undergone refractive surgery increases and these patients age, difficulty in accurately predicting IOL power will become an increasingly significant clinical problem. The ability to address this problem with non-invasive post-operative IOL adjustability would be especially valuable in refractive surgery patients, many of whom are accustomed to spectacle-free vision.

The Solution: Therefore, despite advances in cataract and refractive surgery, imprecise IOL power determination remains an important clinical problem to address. For the first time, Calhoun Vision's light adjustable silicone IOL materials will provide a means to precisely and non-invasively adjust IOL power post-operatively, after the refractive status of the eye has stabilized. Calhoun's adjustable silicone formulations are a platform technology, useful in both pseudophakic and phakic IOLs.

The method proposed to achieve this is akin to holography and is pictorially displayed in Figure 1.

The application of the appropriate wavelength of light onto the central optical portion of the light adjustable lens (LAL) polymerizes the macromer in the exposed region, thereby producing a difference in the chemical potential between the irradiated and non-irradiated regions. To re-establish thermodynamic equilibrium, unreacted macromer and photoinitiator diffuses into the irradiated region. As a consequence of the diffusion process and the material properties of the host silicone matrix, the LAL will swell producing a concomitant decrease in the radius of curvature of the lens. This process may be repeated if further refractive change in the LAL is desired or an irradiation of the entire lens may be applied consuming the remaining, unreacted macromer and photoinitiator. This action has the effect of effectively "locking" in the refractive power of the LAL. It should be noted that it is possible to induce a myopic change by irradiating the edges of the LAL to effectively drive macromer and photoinitiator out of the central region of the LAL, thereby increasing the radius of curvature and decreasing the power of the LAL.

This talk will center on a discussion of the mechanism and principles of the induced refractive change, the optical characterization of the refractive change in-vitro, and will finish up with a discussion of the latest in-vivo results.

Purpose: Recent technology developments have made measurement of wavefront aberrations of higher order than defocus and astigmatism clinically feasible. For many patients, particularly those with pathologies that alter the shape of the corneal surface, higher order aberrations play a significant role in the quality of their retinal image. The goal of this series of studies was to determine the capability of current technologies in correcting higher order wavefront aberrations in the human eye with contact lenses.

Method: A Hartmann-Shack wavefront sensor was used to measure the wavefront of a series of patients identified as having demonstrable higher order aberrations from previous studies. Five images were collected from the dilated eye while fixating at infinity. The average wavefront aberration was calculated as a Zernike polynomial expansion up to 5th order for a 7.2mm optic zone. The data was transferred via modem to a remote manufacturing location and converted into lathing instructions for a 3-axis CNC lathe. The front and back surfaces of the lens were created via diamond turning without polishing, and shipped back to Rochester. Lenses were fit to the dilated eye and fitting and wavefront results were again recorded, along with high and low contrast visual acuities.

Results: Control of individual Zernike co-efficients could be demonstrated using this technique, along with an overall reduction in higher order RMS. Clinical results and technical challenges discovered during this series of studies will be discussed.

Three-dimensional topography of perfused vascular structures is possible via confocal laser scanning if intravascular fluorescence. The lateral resolution is given by the spot site of the scanning laser beam (optimally 10 _m at the retina). The axial resolution, however, depends on the accuracy if detection of the surface if the fluorescent structure, which is typically one order of magnitude higher (30 _m at the retina) than the confocal resolution. The vascular structure is stained with an appropriate fluorescent dye prior to the investigation using standard systemic dye injection.

Confocal scanning if the fluorescence in planes if different depths within the vascular structure under investigation leads to a three-dimensional data set. Signal processing includes passive eye tracking, lateral averaging and axial determination of surface of the fluorescent structure.

The potential of this new technique is demonstrated by showing the topography of physiological vessel structures as well as of selected vascular diseases such as cone dystrophy, RPE detachment, choroidal haemangioma and retinal laser coagulation.

Confocal laser angioscopic fluorescence topography (CLAFT) measures the three-dimensional surface structure of functional (perfused) vasculature and surrounding leakage. CLAFT may help to diagnose and quantify status and time course of vascular disease.

Adaptive Optics (AO) is not rocket science. As with many technologies, it is rather easy to describe the principle but can be remarkably difficult to build a usable, and hence useful, AO system for a particular application.

In this talk, I shall start by reviewing the principles and some of the history of AO. Adaptive Optics is proving to be spectacularly successful in groundbased astronomy, and this community is moving to a new phase of AO requiring multiple wavefront sensors and deformable mirrors, and laser guide stars, in order to expand the field of view and the sky coverage. Astronomical AO is also spectacularly expensive. I will discuss why this is so, as understanding why astronomical AO systems are so expensive will help us build much lower cost systems for vision science and other applications.

In the second part of this talk, I shall discuss some of the issues that need to be considered when building an AO system for vision science. In particular, I shall discuss the error budget, some potential problems in wavefront sensing, and some of the possible technologies for wavefront sensing and wavefront correction. I hope that this talk will serve as an introduction to the later talks that focus on specific AO systems for vision science.

We are constructing an en-face coherence gated camera equipped with adaptive optics (AO) for imaging single cells in the living human retina. The high-axial resolution of coherence gating combined with the high-transverse resolution of AO provides a powerful imaging tool whose image quality can surpass either methodology performing alone. The AO system relies on a 37-actuator Xinetics mirror and a Shack-Hartmann wavefront sensor running at up to 22 fps. The coherence gate is based on a free-space Michelson interferometer that employs a superluminescent diode for illuminating the retinal tissue; voice coil and piezo-electric translators for controlling the optical path length of the reference channel; and a scientific-grade 12-bit CCD array for recording 2-D retinal interferograms. En-face slices of retinal tissue and test objects are obtained using a four-step (l/4) phase shift method. Reconstructions as short as 7 milliseconds have been achieved to mitigate eye motion blur. The axial width and dynamic range of the camera's point spread function were measured at 10-15 microns and 40 dB, respectively.

Early results suggest that a coherence gated adaptive optics camera should substantially improve our ability to detect single cells in the retina over the current state-of-the-art AO retina cameras, including conventional flood illumination and confocal scanning laser ophthalmoscopes. To our knowledge, this is the first effort to combine coherence gating and adaptive optics.