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**Aberrometry and the Tear Film — Understanding new methods —**

Good morning everyone. First, I would like to explain something about the language I will use. I can speak Japanese a little (conversational, simple), but it is difficult for me to give the entire presentation in proper Japanese. Therefore, I will basically give this presentation in English. However I may insert some words in Japanese to facilitate the explanation. Thank you for your patience. First, I would like to thank Dr. Shimuzu, Dr. Uozato for inviting me to speak at this meeting. I am always very happy to visit Japan, and I thank the International Refractive Society of Japan for giving me this wonderful opportunity. Aberrometry is a new method that has recently been used to evaluate the tear film. The purpose of this lecture is to present the basic principles of aberrometry and explain how it can be used to evaluate dry eye. Thomas O. Salmon, OD, PhD Northeastern State University, Oklahoma, USA

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**Northeastern State University**

I teach at Northeastern State University, in Oklahoma. We have enjoyed having many Japanese students come to study at our university, and for seven years I worked very closely with them as the faculty sponsor for the Japanese student’s association. This shows some of them at graduation time.

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**Today's lecture - overview**

Dry eye introduction Aberrometry basics Aberrometry and dry eye research My lecture is divided into 3 sections. I'll briefly introduce dry eye (A), and then present basic principles of aberrometry, which will be the bulk of this lecture (B). Finally, I'll mention how aberrometry has been used in dry eye research.

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**A. Introduction - Dry eye (DE)**

Prevalence ~15-30% Quality of life (QOL) More common among Women Elderly Contact lenses wearers Refractive surgery patients Computer users With some medications First, a few words about dry eye. Dry eye disease is a common condition, affecting 15-30% of the population according to various studies (TFOS Report, Ch. 6 Epidemiology). It negatively affects the quality of life (QOL) for many people and is a significant public health problem. Dry eye disease is more common among women, the elderly, contact lens wearers, refractive surgery patients, computer users and patients taking certain medications.

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**Diagnosis of DE Traditional clinical tests Subjective surveys**

Schirmer test Tear break-up time Corneal staining Slit lamp evaluation Subjective surveys Patient complaints Questionnaires Many clinical tests have been developed to diagnose and evaluate dry eye, such as the Schirmer test, tear break up time, corneal staining and slit lamp evaluation of the lids, cornea, conjunctiva and tear film. Subjective symptoms are also important, so a number of questionnaires have been developed for diagnosing dry eye disease.

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**Diagnostic dilemma DE test don’t agree**

Objective signs ≠ subjective symptoms Need for better tests New technologies Corneal topography Tear osmolarity Aberrometry OSDI Unfortunately, there is a diagnostic dilemma with dry eye disease. Clinical tests sometimes don’t agree with each other, and objective tests often don’t correlate with subjective symptoms. There is therefore a need for better diagnostic tests for dry eye. Some new technologies offer hope for better dry eye diagnosis. These include corneal topography, measurement of tear osmolarity and aberrometry. Drs. Maeda, Koh and others at Osaka University Medical School, have developed a method to evaluate dry eye using aberrometry, and I will describe their method in this talk. TearLab

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**B. Aberrometry basics What are aberrations?**

What do aberrometers measure? How do we interpret aberrometer data? Now let me move on to the main part of this lecture, which is a review of the basic principles of aberrometry. I will try to answer three basic questions. 1. What are aberrations? 2. What do aberrometers measure? 3. How do we interpret aberrometer data?

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**1. What are aberrations? Aberrations = refractive errors**

Lower order aberrations Sphere (myopia, hyperopia) Astigmatism Other refractive errors, they are the … Higher order (HO) aberrations Coma, trefoil, spherical aberration, … Aberrations have become important to clinical ophthalmology since the advent of refractive surgery, but some doctors and clinical staff are still unfamiliar with what they are. So the first question is, What are aberrations? The answer is simple: Aberrations are just refractive errors! The familiar refractive errors are sphere and astigmatism. Sphere includes myopia and hyperopia. These refractive errors are known as the lower order aberrations. But other refractive errors besides these exist . The other more complex refractive errors besides sphere and astigmatism are called higher order aberrations. There are many higher order aberration. Examples include coma, trefoil and spherical aberration, but there are also many others.

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**These aberrations are …**

not … but rather … chromatic aberrations monochromatic aberrations Seidel aberrations coma spherical aberration oblique astigmatism field curvature Petzval Zernike aberrations trefoil Z(4,-4), Z(4,-2) … Others I should clarify that aberrometers measure monochromatic aberrations only. They do not measure chromatic aberration. You may have heard of the Seidel aberrations, such as coma, spherical aberration or oblique astigmatism. The are used in optical engineering for rotationally symmetric man-made optical systems. But clinical aberrometers do not use the Seidel system. Rather, they use the Zernike system to analyze aberrations of the eye. Some Zernike aberrations have the same names as their Seidel counterparts. For example, coma or spherical aberration. But the Zernike aberrations are a little different from the Seidel aberrations.

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**Summary 1 Aberrometry basics What are aberrations?**

Aberrations = refractive errors Lower order = sphere & astigmatism Higher order = other more complex abs Monochromatic aberrations Pupil size = critical parameter! This completes the first main point: What are aberrations? They are refractive errors. The human eye can have many different kinds of refractive errors. Sphere and astigmatism are called the lower order aberrations, but there are many other more complex aberrations. They are known as the higher order aberrations. Also, whenever you do aberrometry you must record pupil size, because it is a critical parameter.

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**2. What do aberrometers measure?**

Refractive errors Similar to autorefractors Sphere, astigmatism, … & Higher order aberrations The next basic questions is, What do aberrometers measure?” Since aberrations are just refractive errors, aberrometers are instruments that measure refractive errors. But we already have instruments that measure refractive errors. They are autorefractors. What is the difference between an aberrometer and an autorefractor? The main difference is that autorefractors only measure lower order aberrations, but aberrometers measure lower and higher order aberrations. That is, aberrometers provide a more complete measurement of refractive errors compared to autorefractors. Here’s a picture of one clinical aberrometer, the COAS, which is one of the popular aberrometers used in eye research. Notice that it looks like an autorefractor. COAS

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**Aberrometry ≠ corneal topography**

Wavefront Whole eye optics HD autorefraction Corneal topography Corneal surface shape HD keratometry Aberrometers present their data as a wavefront maps, like the one on the left. When I teach students about aberrometry, they sometimes confuse wavefront maps (left) for corneal topography maps (right). But wavefront maps are not the same as corneal topography maps! Aberrometers measure optics of the whole eye. That is what is displayed in a wavefront map. Corneal topographers measure only the anterior corneal surface, so corneal topography maps show the shape of the anterior cornea only. You could say that aberrometry is like high-definition autorefraction, and corneal topography is like high definition keratometry. So, just as autorefraction is ≠ to keratometry, aberrometry is ≠ to corneal topography. Autorefraction ≠ keratometry

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**What do aberrometers measure?**

Optical wavefronts exciting the eye Single pass through all the eye's optics Perfect wavefront = flat What, specifically, do aberrometers measure? An aberrometer projects a beam of light into the eye, which focuses to a point on the retina, as shown by the ret dot in this figure. Light from the point source is reflected off the retina and is then emitted from the eye. It travels outward, through the eye’s optics, and is measured by the aberrometer. Aberrometers measure the shape of an optical wavefront that has passed through the eye’s optics. If the eye were perfectly aberration-free, the wavefronts exiting the eye would be perfectly flat, as represented by the vertical red lines in this figure. Any refractive errors present in the eye would cause distortions in the wavefront’s shape. If we analyze the wavefront’s shape, we can know all the refractive errors, that is, all the aberrations present in the eye.

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**In an aberrated eye … refractive errors distort the wavefronts.**

Analyze wavefront shape to learn which refractive errors caused the distortion. This illustrates an eye with a simple refractive error—myopia. Instead of exiting the eye as flat wavefronts, the wavefronts are distorted. If we can analyze the wavefront’s shape, then we can determine which refractive errors were present in the eye. That is, we can know which refractive errors caused that particular wavefront distortion. myopia

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**Video courtesy of Alcon**

This video, which I borrowed from Alcon, illustrates the principle of a Shack-Hartmann aberrometer, which is the most commonly used type of aberrometer. Video courtesy of Alcon

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**Color maps, surface plots**

Recall that an aberration-free eye would have a perfectly flat wavefront. If the wavefront has any distortion, we know that is must have some kind of refractive error. By measuring the wavefront distortions we can determine which refractive errors are present in the eye. The wavefront measured by an aberrometer can be presented as a color map (left), or as a surface plots (right).

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**Total & higher order maps**

Most aberrometer display two color maps. One shows the total aberrations of the eye (left) and a map of the higher order aberrations only (right). The total aberration map on the left includes sphere and astigmatism. The right map shows only the higher order aberrations. Total aberrations Higher order aberrations

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**A wealth of information**

Metrics of optical quality MTF PSF Strehl ratio … Estimate visual performance Simulate vision Design optical corrections MTF An aberrometer captures a wavefront of light that has passed through the eye’s optics, and displays it as a wavefront map. But it can also provides much additional information about the eye’s optics. An aberrometer measurement allows us to compute Metrics of the eye’s optical quality, such as the modulation transfer function (MTF) or points spread function (PSF) It can provide metrics of visual performance. It allows us to simulate vision for that eye, and It allows us to design optical corrections for the eye’s aberrations. Simulated vision

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**Simulated retinal images**

This is a view of the Northeastern State University College of Optometry, where I work. The left photo simulates how this scene would look for an emmetrope, and the right shows simulated vision for a patient who had myopia and astigmatism. Emmetropia Myopia + astigmatism

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**Summary 2 Aberrometry basics What are aberrations?**

What do aberrometers measure? Wavefronts that have passed through the eye's optics. Distortions caused by refractive errors Lower and higher order aberrations Much other information To review, I have been discussing basic principles of aberrometry. I answered the questions, “What are aberrations?” and “What do aberrometers measure?” To summarize the second main point, aberrometers are simply high-definition autorefractors that measure both lower and higher order refractive errors. They do this by measuring wavefronts of light that have passed through the eye’s optics. By analyzing the wavefront distortions, we can know which refractive errors are in that eye. Aberrometers provide a wealth of information about the eye’s optics.

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**3. How to interpret the wavefront?**

Each refractive error (aberration) causes one particular wavefront shape. The aberrometer provides us with a pretty map of the eye’s wavefront error, but what does it mean? How can we know the refractive errors by looking at the map? Next I will explain how we analyze and interpret the wavefront. Each refractive error causes a particular kind of wavefront distortion. Three examples are shown here. If an eye had only myopia, it would have a wavefront like the one on the the left. If it had only astigmatism, the wavefront would look like the one in the middle. If it had only trefoil, it would look like the one on the right. sphere astigmatism trefoil

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Zernike analysis Most eyes, however, don’t have just a single refractive error. They have have a mix of aberrations that cause complex wavefront shapes such as the one in the upper left. By just examining a complex wavefront such as this, it is difficult to know the specific refractive errors in this eye, because they all are mixed together. That's where Zernike analysis helps us. Zernike analysis mathematically breaks down any wavefront into its component aberrations, each of which causes a particular kind of wavefront distortion. So applying Zernike analysis to this particular wavefront, we find that it contains a mix of these specific aberrations: sphere, astigmatism, trefoil, coma, spherical aberration and others.

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Zernike analysis is based on a system of mathematically defined wavefront shapes that can be arranged into a hierarchy like this. At the top are the simplest wavefronts shapes, and as you go down the Zernike pyramid the wavefront shapes become more complex. In this hierarchy, each row is referred to as a Zernike order. The numbers on the left indicate the Zernike order, 0, 1, 2, 3, 4, 5. I have highlighted the 2nd order because these three aberrations are the ones we routinely correct clinically—sphere and astigmatism. Sphere is in the middle and astigmatism is broken down into two refractive errors, 45/135 astigmatism and 90/180 astigmatism. The aberrations contained in Orders 3 and below are collectively known as the higher-order aberrations (dashed box). Each of these aberrations is identified by two numbers, a subscript (n) and a superscript (m), as shown here. The subscript (n) tells you the Zernike order (row) and the superscript (m) numbers the aberration within that order. Negative numbers identify aberrations on the left side and positive numbers identify aberrations on the right side of the pyramid.

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**Common higher order aberrations**

Z(3,-3) Z(3,-1) Z(3,1) Z(3,3) Oblique trefoil Vertical coma Horizontal coma Horizontal trefoil Z(4,0) Here are examples of some relatively common higher order aberrations. All aberrations in the Zernike system can be identified by number, but the most common ones also have names, such as shown here. Spherical aberration

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**A clinical aberrometer provides data such as this for each measurement**

A clinical aberrometer provides data such as this for each measurement. It includes the sphere, cylinder and axis for this eye. It also displays a higher order aberration wavefront map (here) and then lists the higher order aberrations. It identifies each aberration by its number, and then for each it gives a coefficient. The Zernike coefficient tells you how much of each aberration is present. The Zernike coefficients are listed in units of micrometers (µm) and can have either a positive or negative sign. Additional important information includes the pupil size, total RMS and higher-order RMS values. Whenever you specify a Zernike Rx, you must include the pupil size. The Zernike coefficients are specific for one pupil size. If you change the pupil size, the coefficients will change. The RMS values describe the magnitude of combined aberrations, as I will explain soon.

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**Sample COAS printout COAS**

This shows a printout from a COAS aberrometer, which is the instrument I use. It shows a color map for both total (left) and higher order aberrations (right). It has a table of Zernike coefficients for 2nd, 3rd and 4th order aberrations. It also lists the pupil size (7.23 mm), spectacle Rx and RMS values for total and higher order aberrations. At the bottom it shows the simulated image of a 20/200 (0.1) visual acuity letter E for this eye. COAS

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**RMS wavefront error A useful summary statistic**

Magnitude of combined Zernike modes Can be used for any combined aberrations Examples Vertical + horizontal coma = total coma RMS Third order RMS Higher order RMS Total RMS I referred to RMS wavefront error. Now I will explain what it means. The Zernike coefficients give the sign and magnitude of each individual aberration, but sometimes we want to know how bad combined aberrations are. For example, “How bad are the total aberrations of an eye?” The RMS wavefront error tells the magnitude of combined aberrations for any combination. The RMS wavefront error is easy to compute. As shown in the equation, you simply square the Zernike coefficients, add them together, and compute the square root of the sum. You can do this for any combination of aberrations. For example you can compute the RMS for total coma from the Zernike coefficients for vertical and horizontal coma Likewise you could compute the RMS for all the third order aberrations combined, all higher order aberrations combined, or for all the lower and higher order aberrations combined (total RMS).

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Reference norms Journal of Cataract and Refractive Surgery, December Downloadable data Keyword search: “Zernike norms” The aberrometer provides us with a wavefront map and Zernike coefficients, but that’s still not enough for clinical diagnosis. How can we know if the Zernike coefficients or RMS values are good or bad? In order to evaluate the wavefront data, you must compare it to normal values. Prior to 2006 there were no readily available reference norms for aberrometry. This made it difficult for doctors to interpret aberrometer data. In December 2006, the Journal of Cataract and Refractive Surgery published a study that complied a standard set of reference norms based on data from 2,560 normal eyes. The article and data tables are available for downloading from my web site. You can also find it by searching the internet using keywords "Salmon, Zernike."

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**Summary 3 Aberrometry basics What are aberrations?**

What do aberrometers measure? How do we interpret aberrometer data? Zernike coefficient for each aberration ± µm, … specify pupil size! RMS wavefront error – combined aberrations Diagnose by comparing data to norms In summary, we can interpret aberrometer data as shown here. First, the basic data provided by an aberrometer are the Zernike coefficients. Zernike coefficients indicate the sign (±) and magnitude, in microns, of each aberration for one particular pupil size. If the eye were perfect, all the coefficients would be equal to zero. However, every eye has some aberrations. RMS wavefront error tells us the magnitude of combined aberrations. How do you diagnose the aberrometer data? That is, how can you tell if the eye has good or bad optics? To do so you must compare the Zernike coefficients to normal values.

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**C. Aberrometry in DE research**

Tear film - many functions Nutrition, wetting, comfort The eye's primary refracting surface DE -> tear film ∆s -> optical effects Example: DE -> blurred vision Aberrometry – can be used to evaluate DE Finally, in the last part of my talk, I’d like to describe how aberrometry can be used to evaluate dry eye. The tear film provides many important functions for the eye. It provides nutrients and wetting, which are critical to the health and comfort of the eye. But it also serves an important optical function. It is the front refracting surface of the eye, and is in fact, the most important refractive surface in the eye. Dry eye disrupts the tear film and this in turn disrupts the eye’s optics. Dry eye patients sometimes notice this as blurred vision associated with dry eye. Since aberrometry allows us to measure the eye's optics in detail, it also provides a way to indirectly evaluate dry eye.

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**Serial aberrometry Tear film - constantly changing over time**

Evaporation, blinking, gravity, eye movement, etc. Important to measure changes as a function of time Koh & Maeda's method: Serial aberrometry Since the tear film is constantly changing due to evaporation, blinking and other factors, it is important to measure the tear film over time. Drs. Koh, Maeda and others at Osaka University Medical School developed a serial aberrometry method to evaluate changes in the tear film over time.

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**Tear film aberrometry research**

1994 Liang Aberrometry of the human eye JOSAA 1999 Thibos, Hong Tear film break up OVS 2006 Koh, Maeda Normal tears film over time IOVS 2008 Dry eye changes over time Cornea Contact lens wetting ECL 2009 Burger, Head Artificial tears CEO This table lists a few of the scientists who did pioneering work in aberrometry and more specifically, dry-eye aberrometry. In 1994 Liang described a new method he developed to measure higher order aberrations of the human eye, using the Shack-Hartmann principle. In 1999 Thibos and Hong recognized that aberrometry could be used to evaluate the tear film, and they demonstrated this by measuring aberrations of eyes before and after tear break up. More recently, Koh and Maeda and others developed a serial aberrometry method to evaluate normal eyes (2006), dry eyes (2008), and contact lens wetting (2008). I have listed only a few of their papers here. After reading about Koh’s method, in 2009, Burger, Head and myself used serial aberrometry to evaluate artificial tears on the eye.

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**Pioneers in dry-eye aberromery**

Three pioneers in dry-eye aberrometry, Drs. Liang, Thibos and Koh are shown here. Dr. Junzhong Liang Dr. Larry Thibos Dr. Shizuka Koh

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**Contact lens wetting (Koh, et al.)**

Blink Blink (sec) 1 2 3 4 5 6 7 8 9 Etafilcon A Etafilcon A with PVP I thank Dr. Koh, for sending me this figure from one of her papers. It shows changes in aberrations and vision over time for two contact lenses that have different wetting properties. Koh S. Effect of Internal Lubricating Agents of Disposable Soft Contact Lenses ... Contact Lenses. Eye Cont Lens 2008;34:100-5. 34

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**Serial aberrometry (Koh's method)**

Every 1 sec, for 60 sec, blink every 10 sec For each eye, ~60 measurements in 1 minute ~60 HO RMS values Plot HO RMS as a function of time Fluctuation index (FI) & Stability index (SI) This summarizes the procedure that I used in a study of soft contact lens wetting. It is based on Koh’s serial aberrometry method. We set the aberrometer to make one measurement every second for 60 seconds. We prompted subjects to blink once every 10 seconds. This provided a series of sequential aberrometer measurements. Each of the measurements provided a single higher order RMS value. I then did the following analysis: I plotted changes in higher order RMS values (60) as a function of time. Then, for each plot, I computed a fluctuation index (FI) and then a stability index (SI) as defined by Koh. HO RMS ∆ over time RMS FI SI 60 measurements

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**This video shows an example of timed blinks during serial aberromery.**

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**blink blink blink 1 2 3 4 5 6 7 8 9 ->**

> blink blink blink This figure shows ~50 successive wavefront maps from one serial aberrometry session. ->

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Change HO RMS with time This plot, from a serial aberrometry session, shows changes in higher order RMS over 60 seconds. In this study, we evaluated surface wetting of two different contact lenses, as shown by the red and yellow curves. The gradual increase in HO RMS over time indicated an increase in aberrations, which we attributed to drying and tear-film break up.

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**Fluctuation Index (FI), Stability index (SI)**

This figure illustrates the definitions for the fluctuation (FI) and stability indices (SI), which were developed by Koh. Fluctuation index (FI) To calculate the FI, we must first, Compute the standard deviation for the higher order RMS values within each blink interval (red arrows). Repeat for each blink interval (six in one minute). Then compute the mean of these these 6 standard deviation values. Note that one set of 60 measurements produces one FI value. The FI describes variability of the HO RMS values between blinks. Stability index (SI) To calculate the SI, we must, 1. Compute the slope for the higher order RMS values within each blink interval (yelloiw lines). Then compute the mean of these these slope values. Note that one set of 60 measurements produces one SI value. This describes stability of the HO RMS values between blinks.

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**Summary 4 Need for better diagnostic tests for dry eye**

Dry eye -> tear film -> changes in the eye's optics Serial aberrometry - measures changes over time Applications Normal tear dynamics Dry eye diagnosis Contact lens wetting Artificial tears Others Final, to summarize my lecture today, There is a need for better tests to help doctors diagnose dry eye. Dry eye alters the tear film and thereby changes the eye's optics. Since serial aberrometry can measure subtle changes in the eye's optics over time, it can be used to study conditions that affect the tear film. Several studies have used it to study normal tear dynamics, the tear film in dry-eye patients, contact lens surface wetting and artificial tear. There are certainly many other useful clinical applications of this technology.

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ご清聴ありがとうございました Finally, I’ll close with this photo of the JNSU soran bushi team, which is a group of Japanese students at Northeastern State University whom I supervised. Thank you very much for your kind attention. ご清聴ありがとうございました。

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