Visual Performance of Scleral and Soft Contact Lenses in Normal Eyes

Home , Aberrations of the eye, Contact lens

THESIS

Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University

Alex Dominic Nixon

Graduate Program in Vision Science

The Ohio State University

2014

Master's Examination Committee:

Aaron Zimmerman, OD, MS, FAAO

G. Lynn Mitchell, MAS, FAAO

Dean VanNasdale, OD, PhD, FAAO, Advisor

Alex Dominic Nixon

2014

Abstract

The purpose of this study is to investigate whether scleral lenses have vision performance advantages compared to soft contact lenses in normal eyes. Previous studies reported that rigid contact lenses can increase or decrease optical aberrations of the eye depending on the quantity of aberrations at baseline.1 Soft contact lenses have generally increased optical aberrations compared to baseline. 2 3 Conclusions regarding optical quality with contact lenses have been inconsistent due to variability in study design, variability in contact lens parameters, differing lens fitting protocols, the specific measurements taken and the instruments used to take those measurements. This study will minimize variability due to rigid lens decentration and movement on eye by using a larger, more stable scleral design. The study will also include clinically relevant vision performance testing such as high contrast visual acuity, low contrast visual acuity, and contrast sensitivity. The hypothesis is that scleral lenses improve vision performance compared to soft contact lenses due to a reduction in optical aberrations of the eye.

14 subjects were fit with the Onefit P&A (Blanchard Lab, Manchester, NH) and

Air Optix Aqua or Air Optix for Astigmatism (Alcon, Ft. Worth, TX) contact lenses.

Measurements were taken at baseline and separate lens evaluation visits scheduled after completion of the contact lens fits. The order the contact lenses were worn was randomized and the lenses were worn for six hours prior to each lens evaluation visit. The primary outcomes were Bailey-Lovie high and low contrast visual acuity (10% ii

Michelson), MARS contrast sensitivity, and higher-order aberrations, measured with the

Complete Ophthalmic Analysis System (COAS). Secondary outcomes were scleral lens clearance and sodium fluorescein corneal epithelial staining. The corneal clearance was estimated using images from the Heidelberg Spectralis optical coherence tomographer.

There was no difference between the contact lenses in measurements of high contrast visual acuity (p=0.61), low contrast visual acuity (p=0.96), and contrast sensitivity (p=0.30). The Air Optix lenses had significantly reduced coma Z(3,1). The

Onefit P&A lenses had significantly reduced trefoil Z(3,3) (p=0.01) and spherical aberration Z(4,0) (p<0.01). The Onefit P&A lens tended to have lower root-mean-square

(RMS), but the trend was not statistically significant (p=0.51). The average Onefit P&A clearance after six hours of wear was 159 ± 64 microns. The average Onefit P&A settling after six hours of wear was 91.71 microns. Corneal epithelial staining was present following six hours of wear in 4/14 (29%) eyes wearing Air Optix lenses and 13/14

(93%) of eyes wearing Onefit P&A lenses.

The Onefit P&A rigid lenses do not appear to reduce aberrations in a population of normal eyes, consistent with previous studies.1,3 In addition, there was no detectable

difference between the Onefit P&A and Air Optix lenses in tests of visual performance

including high contrast visual acuity, low contrast visual acuity, and contrast sensitivity.

While rigid lenses may anecdotally offer improved optical quality, this population of

normal eyes with relatively low astigmatism did not demonstrate a clinically significant

difference. While Onefit P&A lenses offer promising improvements in comfort and

iii stability compared to traditional rigid lenses, the lens designs require further evaluation to ensure safety and to streamline the fitting process.

Acknowledgments

This work would not be possible without the guidance of my committee members,

help from fellow faculty members, and support from my wife.

I would like to show my greatest appreciation to my advisor, Dr. Dean

VanNasdale, for his dedication to my education and this study. I would like to thank

Professor G. Lynn Mitchell, who was a critical team member during the initial study

design and final statistical calculations. I would also like to thank Dr. Zimmerman, Dr.

Lai, Dr. Emch, Dr. Gardner and Dr. Rueff for their thoughtful comments and suggestions throughout the study.

Finally, I would like to thank my wife, Ashli Nixon. Without her, many of the opportunities that I am so grateful for would not have been possible.

Vita

June 2005 ...... Mount Vernon High School

2011...... B.S. The Ohio State University

2012...... O.D. The Ohio State University

2012 to present ...... Cornea and Contact Lens Advanced Practice

Fellow, College of Optometry, The Ohio

State University

Fields of Study

Major Field: Vision Science

Table of Contents

Abstract ...... ii

Acknowledgments...... v

Vita ...... vi

Fields of Study ...... vi

Table of Contents ...... vii

List of Tables ...... viii

List of Figures ...... ix

Chapter 1: Introduction ...... 1

Chapter 2: Methods ...... 24

Chapter 3: Results ...... 44

Chapter 4: Discussion ...... 65

References ...... 73

vii

List of Tables

Table 1: Eligibility criteria for the study...... 28

Table 2: Schedule of study visits and tests performed at each visit...... 30

Table 3: Subject characteristics at study baseline...... 45

Table 4: Average baseline values for vision performance and higher order aberrations. . 46

Table 5: Summary of high contrast visual acuity, low contrast visual acuity, and contrast sensitivity between the Onefit P&A and Air Optix lenses...... 49

Table 6: Summary higher-order aberrations with the Onefit P&A and Air Optix lenses. 51

Table 7: Summary of higher-order aberrations with the Onefit P&A and Air Optix lenses following removal of outliers...... 54

Table 8: Describes the presence of corneal staining after six hours of wear among the contact lenses tested...... 56

viii

List of Figures

Figure 1: Scleral lens demonstrating complete clearance of the central cornea...... 7

Figure 2: Large diameter, alignment fit, rigid lens...... 12

Figure 3: OCT cross-sectional image of a scleral lens fit with a bubble trapped beneath

the lens. The slit-lamp biomicroscope image shows the corresponding area of corneal

desiccation due to the non-motile bubble...... 13

Figure 4: Acceptable fit of the Air Optix Aqua on a patient's right eye...... 35

Figure 5: The fit and movement of the Air Optix Aqua being evaluated with the patient

looking up...... 36

Figure 6: Slit-lamp biomicroscope image of the evaluation of central clearance with

Onefit P&A...... 40

Figure 7: Slit-lamp biomicroscope image of the evaluation of peripheral corneal clearance with the Onefit P&A...... 41

Figure 8: Slit-lamp biomicroscope image of the evaluation of the edge alignment in the

Onefit P&A...... 42

Figure 9: OCT images of the Onefit P&A and anterior eye with the right eye looking

straight, left, right, up and down...... 43

Figure 10: Demonstration of RMS outlier identification in the Onefit P&A lens using a

stem and leaf plot...... 53

Figure 11: Demonstration of RMS outlier identification in the Air Optix lens using a stem

and leaf plot...... 53

Figure 12: Corneal epithelial staining near the temporal limbus in the right eye examined

using sodium fluorescein dye and a wratten filter. Note the pattern and location of the

staining...... 57

Figure 13: Corneal epithelial staining present inferiorly in an eye wearing the Air Optix

lenses examined using sodium fluorescein dye and a wratten filter. Note the pattern and

location of the staining...... 58

Figure 14: OCT cross-sectional image of the temporal eye and contact lens in the patient

from Figure 12...... 59

Figure 15: Slit-lamp biomicroscope image of the clearance in the temporal peripheral cornea in the patient from Figure 12...... 59

Figure 16: OCT cross-sectional images of the Onefit P&A lenses in the right eye of a

patient looking straight ahead and to the right, respectively. The image pairs demonstrate

the appearance before and after nearly seven hours of lens wear...... 60

Figure 17: Low magnification slit-lamp biomicroscope image of the Onefit P&A on eye

following nearly seven hours of wear...... 61

Figure 18: High magnification slit-lamp biomicroscope image of epithelial bullae in the

subject from Figure 17...... 62

Figure 19: High magnification slit-lamp biomicroscope image of epithelial bullae in a

Onefit P&A wearer...... 63

Figure 20: Slit-lamp biomicroscope imaging showing high magnification imaging of the epithelial bullae in the subject from Figure 17...... 64

Chapter 1: Introduction

Anterior Segment Anatomy

Successful contact lens wear is predicated on a safe relationship between the front surface of the eye and contact lens. Depending on the contact lens design, the lens may interact with multiple surfaces that make up the front of the eye and associated structures, including the cornea, conjunctiva, sclera and eyelids.

All contact lenses are positioned in front of the clear, dome-shaped cornea, the most anterior structure of the eye. The corneal diameter varies across individuals, with the average diameter being 12mm horizontally and 11mm vertically.4 The well-

delineated, stratified cornea is comprised of five layers, the most superficial of which is

the epithelium. Posterior to the epithelium is Bowman’s layer, the stroma, Descemet’s

layer, and the endothelium.4 Of the five layers, Bowman’s and Descemet’s layers act as

basement membranes and do not contribute to the overall function of the cornea in

contact lens wear.

The corneal epithelium consists of multiple layers of cells and is capable of

cellular regeneration. The turnover of these cells occurs relatively quickly and results in

a new layer of epithelium every seven to ten days.5 The new cells originate from stem

cells located in the corneal limbus, which serves as the junction between the cornea and

the adjacent sclera. The limbus is the sole location of the critical stem cell population required to replicate and replace the cells during normal cell cycling and wound healing. 1

The epithelium plays an additional role in the maintenance of the healthy ocular surface and corneal hydration. The epithelial cells are connected to one another by tight junctions, which form a protective barrier that prevents fluid uptake and infection in the healthy cornea.4

The stroma, the middle layer of the cornea, makes up 90% of the total corneal thickness.4 To maintain clarity, the stroma must have strict spacing of its collagen fibers and tight control of its level of hydration. Compromise to the corneal epithelium can cause excessive fluid uptake and alter the well-ordered alignment of stromal fibers, resulting in reduced transparency and visual function.4

The innermost layer of the cornea, the endothelium, is a single layer of cells responsible for regulating fluid exchange between the stroma and fluid in the anterior chamber of the eye. Endothelial cells do not replicate, and endothelial cell density decreases as a result of normal aging.4 Irreversible changes in the size and shape of endothelial cells, termed polymegathism and pleomorphism, respectively, can be worsened by chronic corneal swelling from low oxygen transmissibility contact lens wear.6

The cornea has been designed to maintain clarity and enable light transmission.

The cornea lacks a blood supply and its sensory nerves have no insulating myelin sheath, which allows the cornea to be free of vascular structures that would otherwise block or scatter light. Nutrients necessary for proper function and maintenance of the cornea diffuse from the fluid that fills the eye and from blood vessels within the corneal limbus.

In addition to the nutrients that drive metabolic functions, the cornea requires oxygen to

maintain its health and absorbs the oxygen from the ambient atmosphere.4 While the lack

of myelin enhances corneal clarity, it makes the cornea the most sensitive tissue in the

body.4 The non-myelinated corneal nerves make the eye susceptible to discomfort from contact lenses resting on its surface. Though the nerves are extremely sensitive to stimulation, repeated interaction with the cornea, occurring in long-term contact lens wear, can reduce corneal sensitivity.7

The conjunctiva is a thin, transparent tissue that is continuous with the corneal

epithelium and lines the white of the eye (bulbar conjunctiva) and inner portion of the

eyelids (palpebral conjunctiva). The conjunctiva is vascularized and has sensory nerves,

but the sensitivity is much less than that of the cornea.4 While contact lens wear has been

shown to increase signs of conjunctival compromise and hyperemia compared to non- contact lens wearers, the decreased conjunctival sensitivity results in fewer symptoms relative to similar findings in the cornea.8–10

The sclera is a thick, sturdy layer that is continuous with the corneal stroma at the

limbus. Unlike the corneal stroma, collagen fibers in the sclera branch and interweave

making it a whitish color. There is sensory innervation to the sclera, but the level of

sensitivity is less than the cornea.4

Contact Lens Designs

Contact lenses are broadly divided into two categories, soft and rigid, based on their composition. Contact lenses are soft, or flexible, if they are hydrated and a portion of their material is made up of water. The fundamental differences between soft and rigid lenses have implications for both comfort and visual performance.

Soft contact lenses make up nearly 90% of the global contact lens market.11 Soft

lenses can be custom designed by practitioners, but are most often commercially produced. The lenses are produced in limited curvatures and diameters that have been designed to fit the majority of eyes, with an average diameter near 14mm. Because of

their flexible nature, soft lenses conform to the contour of the eye, producing a small,

even tear layer between the corneal surface and posterior contact lens. The uniform

thickness of the tear layer, or tear lens, contributes little optical power to the overall

system. Soft lenses are often fit using in-office fitting sets that contain a single lens design in a variety of optical powers and may be dispensed on the day of the fitting. This simplifies the fitting process and makes it more efficient.

Unlike soft contact lenses, rigid contact lenses are customized from an infinite combination of curvatures, powers, and diameters. Traditionally, rigid lens designs have been smaller than the size of the cornea, promoting tear exchange beneath the lens and increasing oxygen supply to the cornea.12 Small rigid lens designs, ranging from 8-

9.5mm in diameter, were needed to ensure that the cornea received an adequate supply of

oxygen, considering the poor oxygen transmission of early contact lens materials.

Smaller diameter lenses tend to have more movement with each blink, increased lid

interaction, and are more likely to become dislocated, all of which decrease comfort.

The creation of more oxygen permeable rigid lens materials allowed for increased rigid lens size, improving centration and reducing lens movement and awareness.13 The

use of larger diameter, or intralimbal, rigid lenses improves comfort by promoting a lid attached fit and reducing upper lid interaction with the lens edge during the blink. In

adapted rigid lens wearers, a study found that larger diameter rigid lenses were

significantly more comfortable than smaller lenses with the same fitting relationship.14 15

While intralimbal lenses have improved initial comfort, they are still unable to match the

initial comfort of soft contact lenses.

Scleral lenses, one of the first types of contact lenses produced, are larger than the cornea and rest entirely on the sclera (Figure 1).16 Scleral lenses improve comfort relative

to intralimbal lenses by transferring the lens contact from the highly innervated cornea to

the less sensitive conjunctiva and sclera. This improves lens centration and stability by

resting on the more regular scleral contour and tucking underneath the eyelids to resist

interaction and movement with the blink. Although scleral lenses offer good comfort,

early scleral lens designs fell out of favor because the oxygen transmission of rigid lens

materials was insufficient to maintain corneal health and the lenses were time consuming

and difficult to fit. Modifications, such as fenestrations, were added to scleral lenses to

improve oxygen transmission. Fenestrations, holes in the lens, instead worsened the

fitting success by allowing bubbles underneath lenses and causing lenses to settle deeper

and more unpredictably onto the eye. More recently scleral lenses have grown in

5 popularity because of the improved safety profile created by hyper oxygen transmissible materials compared to their low oxygen transmission predecessors.17,18 Success in irregular corneas and ocular surface disease19–22 has moved the lenses from a last resort to popular recommendation and has caused scleral lenses to be considered for normal, astigmatic eyes. Leading contact lens trade publications recognize the trend in greater scleral lens use, noting “The scleral lens market continues to demonstrate ongoing dramatic growth. It is apparent that some of this growth in scleral lenses is a result of their successful crossover from a modality limited mainly to irregular cornea and dry eye patients to one that also includes the correction of healthy eyes, notably astigmatic and presbyopic patients.”23

While the support of scleral lens use is nearly unanimous, controversy remains regarding the appropriate diameter to design the lenses. Some contact lens practitioners prefer larger diameter scleral lenses because they allow the lens to completely vault the cornea, transferring the entire lens weight to the conjunctiva and sclera. The primary concern is lens compression near the limbus and the potential for damage to the epithelial stem cells. Others, however, prefer to use smaller diameter scleral lenses because the design reduces lens thickness, increases oxygen transmission and avoids the naturally toric shape of the peripheral sclera. The long-term ocular health ramifications of the differing lens designs are not well understood and are currently a source of debate.

Figure 1: Scleral lens demonstrating complete clearance of the central cornea.

Contact Lens Fitting Considerations

There are a number of parameters that are considered when fitting contact lenses,

among the most important being the optical power, the relationship of contact lens and

corneal diameters, the compatibility of the contact lens and corneal curvatures, and eyelid interaction with the contact lens.

The primary objective of a contact lens is to correct for refractive error, a condition affecting nearly 48.3 million people in the United States.24 Uncorrected

refractive error, where the eye focuses light in front of or behind the retina, can cause

symptoms of blurred vision, eyestrain, and headaches. Refractive error is clinically

measured using a subjective refraction, a series of forced choice two alternative questions

that compare a subject’s vision using a variety of refractive lens powers. Contact lenses

can be designed to correct for multiple types of refractive error including nearsightedness

(myopia), farsightedness (hyperopia), and astigmatism. Both soft and rigid lenses correct

for the myopic or hyperopic component of refractive error using a convex or concave

shape to produce specified amounts of optical power. The two lenses, however, take

differing approaches to correct the meridional differences in refractive error that cause

astigmatism. Rigid lenses use the tear lens to neutralize optical differences across the

corneal surface. The tear lens, depending on the relative shapes of the cornea and the

posterior contact lens surface, is not always uniform and may contribute plus or minus

optical power to the system. Because soft contact lenses drape across the eye, the tear

lens thickness is uniform and does not contribute optical power. As a result, nearly all of

the optical correction must be built into a soft contact lens itself. This requires soft

contact lenses to remain rotationally stable to align the optical power of the contact lens and the axis of the eye’s astigmatism. Contact lenses using the tear lens may be preferred by individuals with large amounts of astigmatism because they are not as dependent on rotational stability and vision is more stable.25,26

The size of the contact lens relative to the anatomical properties of the eye is also

a critical consideration in contact lens fitting. To estimate the corneal size, the diameter

of the iris is measured manually along the horizontal meridian, providing a clinical metric

known as the horizontal visible iris diameter (HVID). While slightly smaller than the

diameter of the cornea, the HVID is used as a surrogate marker for corneal diameter and

commonly referenced in contact lens fitting.13 Soft contact lens diameters are designed to

be larger than the HVID and cover the cornea entirely. Rigid contact lenses may be

designed smaller or larger than the HVID.

An additional consideration in contact lens fitting is the compatibility between the

curvatures of the contact lens and cornea. The corneal curvature is measured using

specialized clinical equipment such as a keratometer or corneal topographer. These

instruments use reflections from the corneal surface to indirectly determine the curvature

of the front corneal surface, which is recorded as the radius of curvature in millimeters.

The average central corneal curvature measurement is 7.80mm,27 with the central cornea being more curved than the peripheral cornea. In soft lenses, the base curve, or back surface curvature, is designed to fit the majority of eyes and may only be available in one

9 base curve. The base curve of a rigid contact lens is customized and must be selected to closely complement the shape of the cornea.13

The position and tension of the eyelids against the front surface of the eye also have considerable influence on the centration and movement of contact lenses. The influence is more pronounced in smaller diameter rigid lenses than for scleral and soft lenses. The lower eyelid generally rests along the lower edge of the limbus and the upper eyelid crosses the cornea near ten and two o’clock, covering the upper limbus.4 An upper eyelid that crosses at ten and two o’clock will tuck the small rigid lens beneath it and hold the lens stable between blinks. However, an eyelid that is positioned too high cannot hold the contact lens in place and interacts with the edge of the lens during each blink, causing lens awareness, irritation, or inflammation.

Physical Assessment of Contact Lens Fit

The fit of a soft contact lens is assessed using a slit-lamp biomicroscope. The assessment can be completed using white light only. The optimal fit of a soft lens is well- centered, completely covers the cornea by at least 0.5mm, and moves between 0.3 to

0.5mm with each blink.

The fit of a rigid contact lens is also commonly assessed using a slit-lamp biomicroscope. The ideal rigid lens fit, in most cases, is well-centered laterally and rests slightly superiorly on the cornea tucked beneath the upper eyelid (Figure 2). The shape of the lens, relative to the cornea, is assessed following instillation of sodium fluorescein dye. The visibility of sodium fluorescein is enhanced using blue light and a yellow filter

10 and the intensity of its glow offers a qualitative indication of the volume of tears, or clearance, between the back surface of the lens and the cornea. When the curvature of the lens closely matches that of the cornea, known as an alignment fit, the glow from the fluorescein dye is uniformly distributed beneath the lens. The periphery of the lens should have a band of clearance that is less than one millimeter in size.

More recently, imaging techniques have been used to visualize contact lens fitting relationships and have become complementary techniques to traditional contact lens fitting, in particular scleral lens fitting. Optical coherence tomography (OCT) using the

Heidelberg Spectralis (Heidelberg Engineering, Carlsbad, CA) produces high-resolution cross-sectional images of the eye without contact. OCT images capture the contact lens fit allowing for more accurate measurements of clearance in the central and peripheral cornea. In addition, OCT can provide information regarding the peripheral corneal shape and scleral shape that can be used to calculate the sagittal depth of the eye. Sagittal depth values, often notated on scleral lens diagnostic sets, can aid initial scleral lens selection and improve the efficiency and accuracy of the fitting process.28 Some OCT devices allow cross-sectional and two-dimensional images of the eye to be acquired simultaneously (Figure 3). This helps assess the physical relationship between the contact lens and ocular surface and allows for more precise object localization.

Figure 2: Large diameter, alignment fit, rigid lens.

Figure 3: OCT cross-sectional image of a scleral lens fit with a bubble trapped beneath the lens. The slit-lamp biomicroscope image shows the corresponding area of corneal desiccation due to the non-motile bubble.

Functional Assessment of Contact Lenses

Traditionally, the assessment of visual performance was limited to measurements of visual acuity, most commonly using high contrast charts with controlled lighting.

While high contrast visual acuity offers useful clinical data for refractive error calculation, it fails to detect and measure more subtle optical imperfections.29 Some of the optical imperfections, called aberrations, cause a reduction in vision quality that can be detected and quantified using low contrast visual acuity, contrast sensitivity, and wavefront aberrometry.30–32

Low contrast visual acuity may use the same letters and sizes as high contrast

visual acuity, but the letters will not be as dark. Low contrast visual acuity has been used

to detect subtle vision changes due to contact lens dryness, following refractive surgery

and in early stages of cataract formation.32–34

Contrast sensitivity testing uses letters that are all the same size, but vary in their level of darkness. Contrast sensitivity has also been used to detect subtle vision changes following refractive surgery and in early stages of cataract formation.32,34

Recently, techniques and instruments have been developed to more precisely

measure optical imperfections of the human eye and objectively quantify characteristics

of optical aberrations. The Shack-Hartmann wavefront sensor accomplishes this by using

a laser source that passes light through the optics of the eye. After passing through the

eye, the light returns and is collected by the instrument’s detector. The detector uses

deviations in the light path to quantify and categorize the optical properties of the eye.

The Shack-Hartmann wavefront sensor is considered by some to be superior to other

available methods because it provides a more complete map of the optical quality of the

eye, was quicker to use, and required less subjective input.35

The Complete Ophthalmic Analysis System (COAS, Wavefront Sciences Inc.) is

a commercially available Shack-Hartmann wavefront sensor capable of measuring optical aberrations and has been used to study the optical quality of the eye with and without contact lenses.36 The COAS was the first commercially available clinical aberrometer

using a Shack-Hartmann sensor to describe the wavefront of the eye and quantify

aberrations, most often as Zernike coefficients.37 The COAS has been clinically proven to

accurately measure refractive error and optical aberrations over a range greater than

typically seen in normal eyes.36

Optical aberrations are categorized into lower and higher-order aberrations

(HOAs). Lower-order aberrations, such as defocus and astigmatism, have a large impact on vision quality and are measured clinically during the subjective refraction. Higher- order aberrations also reduce quality of vision, but are not typically measured. The magnitude of ocular aberrations varies considerably across individuals at all ages,37,38 but remains highly correlated between the two eyes in the same individual.37 Ocular

aberrations increase as a function of normal aging, mostly due to changes in the

crystalline lens of the eye.39,40 The visual impact of higher-order aberrations depends on the quantity of the aberration, the type(s) of aberration(s) present, and the size of the aperture (pupil)41 in a complex relationship.42 To compare higher-order aberrations

between eyes or between contact lenses, the root mean square (RMS) is often reported to

paint a broad image of the optical system. While this helps describe the overall system

and can illustrate the differences between normal and abnormal eyes, the root mean

square (RMS) is not a good predictor of the quality of vision in normal eyes. The types of

aberrations present and interactions between aberrations have varying effects on visual

acuity.42

Optical Performance with Soft and Rigid Lenses

While the innovation of soft contact lens materials offered dramatic improvement compared to the comfort of rigid lenses, speculation remained that the soft contact lens designs were inherently flawed. Early crossover studies showed that although there was an overall preference to wear soft contact lenses, rigid lenses were preferred for their quality of vision and their ease of maintenance. 25,43 While the exact origin of the visual

deficit of soft contact lenses was not well understood, it was suspected that surface

dryness might contribute. Surface dryness was suspected because a significant reduction

in visual acuity of four lines was measured with soft lenses compared to rigid lenses

when blinking was suppressed. It was hypothesized that though the soft lenses could

dehydrate and cause surface dryness that contributed to light scatter.33

The first of several studies to provide a more comprehensive evaluation of vision

quality with contact lens wear was published in 2001.44 The report evaluated subjective

vision, high contrast visual acuity and wavefront aberrations in a group of four subjects

wearing soft contact lenses, rigid lenses and spectacles. The study found no significant

difference in high contrast visual acuity, however, three out of four subjects preferred the

vision offered by the rigid lens.44 While no affect on high contrast visual acuity was

detected, the authors suggested that higher-order aberrations may cause measureable changes in vision at lower levels of contrast.44

The group expected that the soft contact lens would conform to the corneal shape and maintain the baseline level of higher-order aberrations, while the rigid lens would

neutralize corneal aberrations and reduce overall aberrations. Aberrometry measurements

showed that the rigid lens reduced astigmatism and higher-order aberrations compared to both the baseline and soft contact lens values. Contrary to their hypothesis, the higher- order aberrations of the cornea were not maintained when soft lenses were worn, differing significantly from baseline.44 Although higher-order aberrations were reduced with the rigid lenses, the subjective visual preference for the rigid lens may have had other influences. Both spectacle and rigid contact lenses had the potential to correct all astigmatism present, assuming the astigmatism was from the cornea. However, only one subject wore a soft contact lens that corrected for the astigmatism.44

A 2003 study sought to further investigate the effect of GP lenses on corneal and

total ocular aberrations in four long-term GP wearers, finding a reduction in RMS higher-

order aberrations by a factor of two.45

Another 2003 study evaluated the wavefront aberrations of 27 myopic subjects while wearing a soft contact lens, a GP lens, and uncorrected using a psychophysical ray- tracing technique. The soft and GP contact lenses used were spherical and were not designed for astigmatism correction.2

The wavefront aberrations in the contact lens wearing eyes were different, either

higher or lower, compared to the natural eye. The average RMS values for soft lens

17 wearing eyes were significantly greater than those wearing rigid lenses. The mean RMS values for the GP wearers were the smallest, but were not significantly reduced from baseline. While rigid lenses generally reduced wavefront aberrations compared to the natural optics of the eye, the effect of contact lenses on wavefront aberrations varied from eye to eye. The most significant difference in wavefront aberrations was found when astigmatism, a lower-order aberration, was included in the calculation of total aberrations.

The authors concluded that a contact lens (soft or rigid) could induce or reduce wavefront aberrations depending on the initial corneal aberrations present.2 Though vision was once again better with rigid lenses compared to soft, the soft contact lenses were unable to correct for astigmatism.2

A 2006 study evaluated the affect of soft contact lenses on HOAs in a group of 15 myopic subjects. The analysis showed that soft contact lenses for myopia significantly increase the RMS. Although coma, trefoil, and spherical aberration were not significantly different, the trend existed that values with the soft contact lenses were higher than baseline.3

A 2007 study further investigated the effects of rigid lenses on wavefront aberrations. Myopic subjects were fit with spherical GP lenses using a lid-attached fitting method to minimize lens decentration and movement with each blink.1 There was no significant difference in total wavefront aberrations, coma, trefoil or spherical aberration in eyes with GP lenses compared to baseline measurements. There appeared to be a trend present when the population was separated based on the mean total aberrations present at baseline. In the group with lower wavefront aberrations, the rigid lens caused a

significant increase in aberrations from 0.23 to 0.35um (p=0.006). In contrast, the group

with higher baseline aberrations showed a decrease in total aberrations with rigid lens wear from 0.45 to 0.29um (p=0.068).1.The amount of baseline aberrations present did not

have an effect on the high contrast visual acuity with rigid contact lens wear, however,

and the authors suggested that higher-order aberrations may cause measureable changes in vision at lower levels of contrast.1

The study demonstrated that the changes in wavefront aberrations with rigid lens

wear were dependent on the amount of aberrations present at baseline. The reduction in

ocular aberrations with rigid lens wear was only significant when the initial aberrations

were high. When the initial aberrations were low, there was an increase in the total

aberrations with GP lens wear.1 This confirmed that there are situations where the

aberrations of the eye’s crystalline lens compensate for those of the cornea, leaving few

net aberrations, and a rigid lens could disrupt the balance of the whole eye’s aberrations.

2,44,45

A 2012 multi-site, crossover, randomized study enrolled 40 subjects with

astigmatism to evaluate the clinical performance of a new large diameter rigid lens, the

Onefit P&A, compared to a soft lens, the Biofinity Toric. The study was sponsored by

Blanchard Lab, the contact lens manufacturer that produces the Onefit P&A lens. The

rigid lens used in this study, unlike previous studies, was a scleral lens that would

improve centration and stability compared to smaller rigid lenses. Stability is important

because rigid lens decentration can induce tilt, defocus, astigmatism, coma, and trefoil,

commonly measured optical aberrations.46 The study found no statistically significant

difference in high contrast or low contrast visual acuity between the contact lenses. In

addition, there was no significant difference in comfort and both lenses averaged nearly

12 hrs/day of wear. Subjectively, 75% of patients preferred the vision in the Onefit P&A,

and nearly 53% of subjects chose to continue wearing the lens instead of the Biofinity

Toric. Although the survey showed that the Biofinity Toric was easier to use and subjects

were more likely to recommend it, the study demonstrated that the scleral lens was a

reasonable alternative to the soft lens in astigmatic patients.47

The effect of rigid lenses on visual performance and HOAs has been studied, but

the study designs and conclusions are inconsistent 44. These conflicting findings may be

attributable to variability in study design, variability in contact lens parameters, differing

lens fitting protocols, the specific measurements taken and the instruments used to take

those measurements. There is anecdotal evidence that newer large-diameter scleral gas

permeable lenses have comfort and visual performance advantages, but limited

information from published studies exists on the ability of scleral lenses to improve comfort, and provide superior and more stable optical quality compared to soft contact

lens designs.

Ocular Health Complications from Contact Lens Wear

While modern contact lens wear is generally safe, the eye is still susceptible to

complications related to hypoxia, mechanical irritation, infection and inflammation.

Manifestations of corneal hypoxia include corneal vascularization, epithelial

microcysts, epithelial vacuoles, and epithelial bullae. These complications have been

reduced considerably in the advent of more oxygen permeable materials, however, there

is still concern that scleral lenses may result in hypoxic complications due to the large

oxygen diffusion distance of the lens thickness and post-lens tear layer. Scleral lenses are designed to be 2-3 times thicker than their soft lens counterparts and offer little tear exchange, leading to theoretical concern for corneal hypoxia and accumulation of metabolic waste from the cornea that could lead to an inflammatory response.48

Corneal vascularization is a generally asymptomatic response, likely secondary to

corneal hypoxia,49 edema,50 and chronic, low-level inflammation.51 The maximum

acceptable level of contact lens-induced vascularization is 0.5mm inward from the limbus.6 Vascularization in contact lens wear is often self-limiting with removal of the

hypoxic or inflammatory stimulus, which can reduce the extent of vascularization within

one month.52

Epithelial microcysts are 5-30 micron, gray spheres that are indicative of metabolic stress and are most often seen in wearers of low oxygen transmissibility contact lenses, especially those that wear their lenses overnight.6 Microcysts generally

cause few, if any, symptoms and have no affect on vision. It is thought that the

microcysts are dead corneal cells that were ingested by neighboring cells,53

demonstrating that the epithelium is not replicating and turning over as it should.6

Prognosis for recovery is good if the hypoxic stimulus is removed, however, the number of microcysts may increase before they resolve.54

Epithelial vacuoles and bullae occur secondary to excessive or persistent

epithelial edema. The two are similar in their gaseous composition, but differ in their

relative size and shape. While vacuoles appear as 5-30 micron spheres, bullae are larger

and more oblong in shape.55 Although far less common, bullae are more problematic

because they may represent more chronic epithelial edema.6 While these are not usually

associated with discomfort, epithelial edema may cause visual complications, such as

haloes in vision. 6

Corneal staining describes the uptake of sodium fluorescein dye into corneal

epithelial cells that are damaged or missing. The presence of corneal staining is common,

especially in contact lens wearers, and has been reported to occur in as many as 19.5% of

soft contact lens wearers. Although corneal staining is frequently found, it is generally

low grade and clinically insignificant.56 Practitioners often use the location, density, and

depth of the corneal staining to determine its severity and potential etiology.

The most serious complications of contact lens wear are corneal infection and

contact lens associated infiltrative keratitis (CLAIK). Corneal infection occurs rarely in

both rigid and soft lens modalities, with 1.1 per 10,000 rigid and 3.5 per 10,000

developing microbial keratitis with daily wear.57 Corneal infections are most commonly

bacterial, although they can be fungal in nature. CLAIK occur slightly more frequently,

but tend to resolve more quickly and cause less long-term damage.

The scientific aims of this study are to quantify fitting characteristics, vision performance and optical quality differences between two fundamentally dissimilar contact lens designs, scleral gas permeable lenses and soft contact lenses. The study will include clinically relevant vision performance testing such as high contrast visual acuity, low contrast visual acuity, and contrast sensitivity. This study also will attempt to provide insight into potential tradeoffs between the vision performance, comfort, and ocular health impact of each contact lens design. The hypothesis is that scleral lenses improve vision performance compared to soft contact lenses in normal eyes due to a reduction in optical aberrations of the eye.

Chapter 2: Methods

Design

This study used a prospective, randomized, crossover design. Each subject was fit into scleral contact lenses, Blanchard Onefit P&A (Blanchard Lab, Manchester, NH),

as well as soft contact lenses, Air Optix Aqua or Air Optix for Astigmatism (Alcon, Fort

Worth, TX). Following completion of both fittings, the order the subjects wore the

contact lenses was randomized. The original study design intended to have the subjects

wear the first pair of lenses for two weeks and return for objective and subjective testing

of visual performance. Subjects were scheduled to have a one week washout in between

wearing periods, during which time they could return to their habitual vision correction.

Following the washout period, each subject repeated the wearing process with the

alternative set of contact lenses.

During the fitting process, widespread corneal staining was observed in eyes

wearing the Onefit P&A lenses for greater than six hours. The epithelial compromise in

an annular pattern appeared linked to bearing of the Onefit lens based on corresponding

OCT images that indicated peripheral corneal touch. Reasonable attempts were made to

resolve the epithelial damage and resulted in as many as five lens orders for a single

patient. The changes to lens parameters included increases to the lens diameter and

steepening of the base curve. To prevent additional complications from persistent limbal

epithelial damage, the wearing time for each contact lens during the data collection 24

period was reduced from two weeks to six hours on a single day. An amended IRB

protocol was filed and approved with the adjusted wearing schedule and all subjects were

re-consented.

The protocol was amended before any subjects began the designated two week

wearing periods. The final study design, which was consistent for all subjects, included a

six hour wearing period on a single day that concluded with objective testing of visual

performance. The subjects were scheduled to repeat the process with the alternative set of

contact lenses at least one week after the initial wearing period.

Sample Size

Nineteen subjects were recruited and fifteen subjects were enrolled in this study,

all between the ages of 18 and 40 years. All participants had normal ocular health and visual acuity was correctable to 20/20 as measured by high contrast visual acuity. The total number of participants expected for statistically significant results was derived using data from previous studies. Previous studies evaluating similar metrics of optical quality and performance have included 15 subjects and were able to show significant differences in visual performance. A recruitment target of 20 subjects was used to

allow for attrition of up to five subjects, while retaining the ability to detect clinically meaningful changes in HOAs, high contrast visual acuity, low contrast visual acuity and contrast sensitivity. Subjects that could not be successfully fit in both lens designs were

excluded from the study.

Recruitment

Recruitment was performed by sending an e-mail script, approved by The Ohio

State University Institutional Review Board, to existing list-serves within the College of

Optometry. Subjects were primarily recruited from OSU students, faculty, and staff.

All subjects were consented using a form approved by The Ohio State University

Institutional Review Board, which adheres to the Tenets of the Declaration of Helsinki.

All risks and benefits were presented to the subjects, and subjects were given time to ask questions and consider his or her participation in the research. Subjects were instructed that they could withdraw from the study at any time without consequence. If

the subject elected to participate and time permitted, the initial fitting was performed on

the date of consent. If there was not sufficient time or the subject preferred additional

time to consider participation, he/she was scheduled for a separate fitting appointment.

Rationale for Eligibility Criteria

The eligibility criteria are listed in Table 1 and include ocular health, age, visual

acuity and refractive error limitations, further described below.

Ocular Health and Visual Acuity: These criteria exist to assure that the subjects were healthy and to minimize confounding data that may affect the validity of the results.

Age: Persons under the age of 18 were excluded from the study to avoid use of children.

The recruitment was capped at 40 years to limit normal aging changes that degrade the

optical quality and performance of the eye, which may confound our data.58,59

Gender: There were no criteria for exclusion based on gender. However, females who

were pregnant or planning to become pregnant were unable to be enrolled. Pregnancy

can cause vision changes, contact lens intolerance, and refractive changes that could

confound our results.60

Refractive Error: Subjects were eligible to be enrolled in the study with any refractive error correctable with both sets of contact lenses.

Corneal Astigmatism: These criteria exist to minimize uncorrected astigmatism with the

Onefit P&A lenses. The Onefit P&A lenses cannot have correction for astigmatism built into the lens, and instead rely on the tear lens and corneal astigmatism to correct vision.

The corneal astigmatism had to be within 0.75D of the astigmatism from the baseline refraction to minimize residual astigmatism. In addition, the total corneal astigmatism had to be less the 2.50D because of limitations by both contact lenses.

Subjects must be free from eye diseases or any other conditions that Ocular Health would prevent him/her from wearing contact lenses.

Subjects must be between 18 and 40 Age years old at the time of the baseline examination.

Either gender may be included. However, females who are pregnant Gender or planning to become pregnant will be excluded due to variable refractive error.

Subjects must have visual acuity of 20/20 or better with habitual Visual Acuity correction or following refraction at the eligibility visit.

Subjects refractive error must be between +6.00D and -10.00D Refractive Error sphere and up to -2.50D of astigmatism

May be up to 2.50D and must be Corneal Astigmatism within 0.75D of the cylinder power in the subject’s refraction.

Table 1: Eligibility criteria for the study.

Research Methods and Activities

At the baseline examination, qualification for entry to the study was confirmed by reviewing ophthalmologic records. Assuming qualifying data and good ocular health, the subject was fit with pairs of scleral and soft contact lenses and randomly assigned to

order of lens wear (e.g. some patients first wore scleral lenses while the remaining

patients first wore soft contact lenses).

The fit and prescription of the contact lenses were evaluated using a slit-lamp

examination including topical ophthalmic fluorescein dye, Spectralis OCT and anterior

segment imaging, keratometry measurements to look for lens flexure, and refraction.

Multiple visits were required to finalize the fit and prescription of the contact lenses,

consistent with standard clinical protocol.

There were two additional lens evaluation visits, one for each pair of contact

lenses. At each visit, the fit and vision with the contact lenses were evaluated using a slit-

lamp examination, the COAS, high and low contrast visual acuity (Bailey-Lovie Chart),

and contrast sensitivity (MARS chart). In addition, Spectralis anterior segment OCT was

performed while the scleral lenses were worn. The schedule of study visits and testing is

listed in Table 2.

CL CL CL Lens 1 Lens 2 Consent (60 min) Fitting Dispense Follow-up Evaluation Evaluation (60 min) (60 min) (30 min) (60 min) (60 min) Review of Exam x Records High Contrast x x x x x x Visual Acuity Slit Lamp Exam x x x x x x Refraction x Autorefraction x x x Topography x x x Visual Performance (Low Contrast VA x x x and Contrast Sensitivity) COAS x x x

OCT Imaging x x x x x x if scleral only if scleral only Randomization x *

Table 2: Schedule of study visits and tests performed at each visit. *Randomization performed when both contact lens prescriptions have been finalized

Primary Outcome Measures

The primary outcome measures for this study evaluated the objective visual

performance of the Onefit P&A lenses compared to the Air Optix Aqua or Air Optix for

Astigmatism lenses. The clinical testing used to evaluate the quality of vision included

high contrast visual acuity, low contrast visual acuity and contrast sensitivity. The

subjects’ higher order aberrations were also measured using the COAS.

Visual acuity was measured using Bailey-Lovie high and low contrast (10%

Michelson) visual acuity charts (Precision Vision, La Salle, IL). This chart has shown good reliability in clinical testing and utilizes a logarithmic scale for ease of calculations. The low contrast chart can be used to detect more subtle changes in visual performance and has been shown to correlate best with wavefront aberration metrics.29,34 Visual acuity was measured using logMAR and compared using a paired t-

test.

The MARS chart was used to measure contrast sensitivity for the study. Contrast

sensitivity has been shown to be reduced due to wavefront aberrations in normal eyes

and following refractive surgery.32,34 The MARS charts have been demonstrated to

perform as well as the Pelli-Robson contrast sensitivity chart, but are easier to operate,

more durable and less expensive to purchase.61 Contrast sensitivity was measured letter

by letter and compared using a paired t-test.

The COAS is a Hartmann-Shack wavefront aberrometer that has been used in previous studies evaluating higher order aberrations.36,39 The wavefront was quantified

using the Zernike system. For each value, five measurements were collected and the

average was used for analysis. Individual aberrations through the fourth order, the most

influential HOAs, and the RMS were compared using a paired t-test.

Secondary Outcome Measures

Heidelberg Spectralis anterior segment OCT images were taken at baseline and

at Onefit P&A evaluations. The Spectralis does not provide quantitative distance

measurements in the current anterior segment software, so lens clearance in the Onefit

P&A lenses was measured with a millimeter ruler and compared to the central thickness

of the lens, a known parameter. The use of OCT imaging to evaluate the clearance and

edge alignment in scleral lens fits has been previously described.28 The amount of clearance present over the peripheral cornea and alignment of the lens edge were evaluated by collecting images with the eyes looking up, down, left and right. Scleral lens settling was calculated by comparing the clearance at the lens evaluation visit to the clearance present when the same set of lenses was initially dispensed. These values were not collected on the same day, but were compared assuming a consistent clearance was present each time the same set of lenses was inserted.

The presence of corneal staining was assessed using sodium fluorescein dye at the data-collecting visit for each contact lens. Each subject was asked to wear the lenses for six hours prior to the visit, with staining assessed following roughly an hour of vision testing. The presence of staining was recorded as present or not present, but not

32 graded with a specific scale. If staining was present, photo-documentation was attempted if time permitted.

Statistical Methods

Statistical analysis was performed using SPSS software (IBM, Armonk, NY). The level used to determine statistical significance was p=0.05. All statistical comparisons were completed using data from the right eye only. Stem and leaf plots and histograms were used to detect outliers. The data were compared using paired t-tests.

Fitting Procedures

All contact lenses were fit by Dr. Alex Nixon, Dr. Nixon has considerable experience with both contact lens modalities during his optometric education and in his current position as an Advanced Practice Fellow in Cornea and Contact Lenses at the

Ohio State University College of Optometry (OSUCO).

Air Optix Aqua and Air Optix for Astigmatism

The Air Optix Aqua and the Air Optix for Astigmatism (Lotrafilcon B) can be used to fit patients requiring vision correction due to refractive error. Air Optix for

Astigmatism is made from the same material with an analogous design to the Air Optix

Aqua, but has additional parameters for correction of refractive astigmatism. These complementary lenses were specifically chosen for this study for their high anecdotal success rate. Patients not requiring astigmatic correction, or requiring small amounts of

astigmatic correction, can be adequately corrected with the Air Optix Aqua lens.

Subjects requiring astigmatic correction of 0.75 diopter or more were fit into Air Optix

for Astigmatism.

The Air Optix Aqua and the Air Optix for Astigmatism are each only available in

one base curve and diameter. The size and shape of each lens have been optimized to fit

the majority of eyes. The appropriate prescriptions were selected based on each subject’s

refractive error as measured by subjective refraction at the baseline examination. The

contact lens prescriptions were adjusted to correct for the distance between the eye and

the refracting lenses, which may cause the power of the contact lenses to differ slightly

from the spectacle lenses.

The contact lenses were evaluated for vision, position and movement after

allowing adequate time to settle (Figure 4-5). Rotation in the Air Optix for Astigmatism lenses that degraded vision was compensated for with lens parameter adjustments, specifically cylinder axis, until optimum visual acuity was achieved. The contact lens powers were assessed by performing a subjective refraction and an autorefraction over the lenses. The powers were adjusted to minimize refractive error and maximize visual acuity.

Figure 4: Acceptable fit of the Air Optix Aqua on a patient's right eye.

Figure 5: The fit and movement of the Air Optix Aqua being evaluated with the patient looking up.

Onefit P&A

The Onefit P&A lenses were fit using a diagnostic fitting set available from

Blanchard Lab. All lenses in the fitting set were 14.6mm in diameter and had a 300

micron center thickness. The initial base curve was selected to be 0.30mm steeper than the flattest meridian of the cornea, as recommended by the manufacturer. If a subject’s

eyes were similar in shape and required the same trial fitting lens, a lens with a base

curve one step steeper was inserted on the left eye to streamline the bilateral lens

assessment.

The characteristics of the fit were evaluated by measuring the central clearance

(Figure 6), the clearance in the peripheral cornea (Figure 7) and the lens edge alignment

(Figure 8) using a slit lamp biomicroscope. The lenses at the initial fit were filled with saline and fluorescein prior to insertion to facilitate the fitting assessment. Heidelberg

Spectralis was also used to acquire more accurate fitting characteristics (Figure 9).

After insertion, the goal was to have a 1:1 ratio of the clearance to the contact lens

thickness, or 300 microns, at the tallest corneal point (Figure 6). If a 1:1 ratio was not

present, the base curve could then be adjusted, either steeper or flatter, to obtain the

desired clearance. A one step (0.10mm) base curve change would adjust the clearance by

30 microns. The clearance of the lens was also evaluated near the corneal limbus (Figure

7). Clearance at the limbus was verified using a commercially available anterior segment

OCT (Heidelberg Spectralis) to acquire high-resolution, cross-sectional imaging of the lens and cornea. In subjects where clearance was insufficient in the periphery or corneal

37 staining was present, lenses were ordered with a larger diameter (14.9mm) and/or a steeper base curve per the manufacturer’s instructions.

The lens edge alignment relative to the conjunctiva is an important consideration in large diameter gas permeable lens fitting. Peripheral curves that are steep relative to the conjunctiva can impinge on the tissue near the lens edge, affecting the local superficial vascular flow. Conversely, lenses that are flat in the periphery may allow bubbles to be introduced beneath the lens or may interact with the eyelids causing discomfort and intolerance. The fit of the Onefit edge was evaluated by monitoring for changes in vessel course or caliber indicative of restricted blood flow (Figure 8). If the lens edge was too steep or too flat, the edge curvature was adjusted based on the manufacturers recommendations. The relationship between the peripheral lens and the conjunctiva was also assessed with cross sectional OCT imaging (Figure 9). Due to the limited lateral and axial range of the Heidelberg Spectralis, the images of the peripheral lens were acquired separately with the subject in various gazes by having the subjects look to the right, left, up or down. Similar to optical power verification in a soft lens, the final power of the Onefit lenses was determined by performing a subjective refraction and an autorefraction with the lenses on the eye.

At Onefit P&A dispense and lens evaluation visits, the fitting characteristics of the Onefit lenses were evaluated using the standardized methods previously described.

The main difference at the lens evaluation visits was that fluorescein was not introduced beneath the lens, but was used after the lens was removed to look for signs of corneal compromise. The expected central lens clearance at the evaluation visits was less than the

initial fitting because the lens had settled into the softer conjunctival tissue. The average

amount of settling following eight hours of wear was previously reported to be 98

microns, and ranged from 70 to 180 microns.62 The ideal clearance of the Onefit P&A following settling is approximately 175 microns. The clearance throughout the cornea and the edge fit were further evaluated using OCT imaging. The lenses were then removed and sodium fluorescein dye was inserted to look for signs of corneal compromise, consistent with standard gas permeable lens fitting practices. Punctate staining near the limbus is indicative of scleral lens bearing and requires a fit adjustment to reduce bearing on the cornea and improve corneal health. Over-refraction and auto-

refraction were performed at each follow-up to determine whether the lens power was correct and remained consistent following lens settling. If uncorrected astigmatism was present, the lens was evaluated for flexure by assessing front curvature changes using the keratometry readings from the autorefraction. Flexure was addressed by steepening the base curve and increasing the center thickness of the lens, based on the manufacturer’s

recommendations.

Figure 6: Slit-lamp biomicroscope image of the evaluation of central clearance with Onefit P&A.

Figure 7: Slit-lamp biomicroscope image of the evaluation of peripheral corneal clearance with the Onefit P&A.

Figure 8: Slit-lamp biomicroscope image of the evaluation of the edge alignment in the Onefit P&A.

Figure 9: OCT images of the Onefit P&A and anterior eye with the right eye looking straight, left, right, up and down.

Chapter 3: Results

Subject Characteristics

The study initially enrolled a total of 15 subjects. Of the 15 subjects, one was

excluded because adequate fit and vision with the Onefit P&A lens could not be

achieved. Four males and 10 females were enrolled and included in the final analysis.

The average age of the subjects was 27.29 years, ranging from 22 to 37. All eyes were healthy and free from eye disease that would limit vision or contraindicate contact lens wear. All subjects wore contact lenses at baseline, with 13 out of 14 subjects habitually wearing soft contact lenses and one subject wearing rigid corneal lenses. The average spherical equivalent refractive error at baseline was -4.97D ± 2.44D. The average flat keratometry value was 43.48D (7.76mm) ± 1.28D. The average amount of corneal astigmatism was 0.59D ± 0.38D. The average amount of astigmatism in the subjective refraction at baseline was 0.48D ± 0.39D. These values are listed in Table 3.

Subject Characteristics

N Minimum Maximum Mean Std. Deviation

Age 14 22 37 27.29 5.47 Spherical Equivalent 14 -1.13 -10.63 -4.97 2.44 Flat K 14 40.62 46.00 43.48 1.28 Corneal Astigmatism 14 0.13 1.40 0.59 0.38 Refractive Astigmatism 14 0.00 1.30 0.48 0.39

Table 3: Subject characteristics at study baseline.

Baseline Vision Testing

Bailey-Lovie high contrast visual acuity, low contrast visual acuity and MARS

contrast sensitivity were performed on each participant with their habitual refractive

correction. The average high contrast visual acuity at baseline was -0.04 ±0.10 logMAR.

The average low contrast visual acuity at baseline was 0.25 ± 0.41 logMAR. The MARS

contrast sensitivity at baseline was 1.77 ± 0.03 log CS. One subject’s high contrast visual

acuity, low contrast visual acuity, and contrast sensitivity data were omitted because

baseline values were not documented.

Optical aberrations were also measured at baseline using the COAS. The mean trefoil Z(3,-3) value was 0.09 ± 0.24 microns. The mean coma Z(3,1) was 0.00 ± 0.23

microns. The mean coma Z(3,-1) was -0.12 ± 0.32 microns. The mean trefoil Z(3,3) value

was -0.21 ± 0.33 microns. The mean spherical aberration Z(4,0) value was -0.18 ± 0.19

microns. The mean RMS value was 0.26 ± 0.15 microns. These data are summarized in

Table 4.

Baseline Vision Testing

N Mean Std. Deviation

HC Baseline 13 -0.07 0.04

LC Baseline 13 0.14 0.05

CS Baseline 13 1.77 0.03

Z(3,-3) 14 0.10 0.25

Z(3,1) 14 0.01 0.24

Z(3,-1) 14 -0.11 0.33

Z(3,3) 14 -0.23 0.34

Z(4,0) 14 -0.19 0.19 0.15 RMS 14 0.26

Table 4: Average baseline values for vision performance and higher order aberrations.

Effect of Order of Lens Wear

Subjects were randomly assigned to each testing order. Group 1 wore the Air

Optix Aqua lenses initially, while group 2 first wore the Onefit P&A lenses. To test for the effect of order, the difference between the response of each lens was calculated and a two-sample t-test was used to compare the differences. The analyses found no effect of testing order (p>0.22).

High and Low Contrast Visual Acuity

The average high contrast visual acuity for the Onefit P&A and Air Optix lenses were -0.10 ± 0.06 and -0.11 ± 0.05 logMAR, respectively. No significant difference in high contrast visual acuity was detected between the lenses (P =0.61). These data are summarized in Table 5.

The average low contrast visual acuity for the Onefit P&A and Air Optix lenses were 0.17 ± 0.11 and 0.17 ± 0.10 logMAR, respectively. No significant difference in low contrast visual acuity was detected between the lenses (P =0.96). These data are summarized in Table 5.

MARS Contrast Sensitivity

The average MARS contrast sensitivity for the Onefit P&A and Air Optix lenses were 1.79 ± 0.02 and 1.78 ± 0.03 log CS, respectively. No significant difference in

47 contrast sensitivity was detected between the lenses (P =0.30). These data are summarized in Table 5.

Visual Performance Statistics

Mean N Std. P (2-tailed) Deviation HC Onefit -0.10 14 0.06 0.61 Pair 1 HC Air Optix -0.11 14 0.05 LC Onefit 0.17 14 0.11 0.96 Pair 2 LC Air Optix 0.17 14 0.10 CS Onefit 1.79 14 0.02 0.30 Pair 3 CS Air Optix 1.78 14 0.03

Table 5: Summary of high contrast visual acuity (HC), low contrast visual acuity (LC), and contrast sensitivity (CS) between the Onefit P&A and Air Optix lenses.

Aberrations

The average coma values Z(3,-3) for the Onefit P&A and Air Optix lenses were

0.08 ± 0.13 and 0.07 ± 0.23 microns, respectively. No significant difference was detected between the lenses (P =0.89). The average coma values Z(3,3) for the Onefit P&A and

Air Optix lenses were -0.01 ± 0.20 and -0.19 ± 0.32 microns, respectively. The difference between the lenses was statistically significant (P =0.01). These data are summarized in

Table 6.

The average trefoil values Z(3,1) for the Onefit P&A and Air Optix lenses were

-0.21 ± 0.19 and -0.05 ± 0.23 microns, respectively. The difference between the lenses was statistically significant (P =0.04). The average trefoil values Z(3,-1) for the Onefit

P&A and Air Optix lenses were -0.23 ± 0.19 and -0.35 ± 0.42 microns, respectively. No

49 significant difference was detected between the lenses (P =0.28). These data are summarized in Table 6.

The average spherical aberration values Z(4,0) for the Onefit P&A and Air Optix lenses were -0.11 ± 0.21 and 0.06 ± 0.23 microns, respectively. The difference between the lenses was statistically significant (P <0.01). These data are summarized in Table 6.

The average RMS for the Onefit P&A and Air Optix lenses were 0.24 ± 0.18 and

0.28 ± 0.10 microns, respectively. No significant difference was detected between the lenses (P =0.51). These data are summarized in Table 6.

Higher Order Aberrations

Mean Median N Std. Deviation P (2-tailed)

Z(3,-3) Onefit 0.08 0.11 14 0.13 0.89 Pair 1 Z(3,-3) Air Optix 0.07 0.07 14 0.23 Z(3,3) Onefit -0.01 -0.04 14 0.20 0.01 Pair 2 Z(3,3) Air Optix -0.19 -0.21 14 0.32 Z(3,1) Onefit -0.21 -0.19 14 0.19 0.04 Pair 3 Z(3,1) Air Optix -0.05 -0.06 14 0.23 Z(3,-1) Onefit -0.23 -0.18 14 0.19 0.28 Pair 4 Z(3,-1) Air Optix -0.35 -0.38 14 0.42 Z(4,0) Onefit -0.11 -0.09 14 0.21 <0.01 Pair 5 Z(4,0) Air Optix 0.06 0.04 14 0.23 RMS Onefit 0.24 0.20 14 0.18 0.51 Pair 6 RMS Air Optix 0.28 0.27 14 0.10

Table 6: Summary of higher-order aberrations with the Onefit P&A and Air Optix lenses after six hours of wear.

Data Outliers

The presence of outliers may have had a significant impact on the results of the study (Figures 10-11). The outliers were detected using stem and leaf plots, and they were suspected to be influential because of the relatively large difference between the mean and median values for each group (Table 6). While the mean values for the Air

Optix lenses approximated the median values, the mean values for the Onefit lenses tended to be larger than the median values. This trend indicates that, due to small sample size, the mean values for the Onefit lenses may have been shifted significantly higher because of an outlier. This shift would increase the difference between the Onefit and Air

Optix values and may result in spurious statistically significant findings. These outliers were most significant in the HOA measurements and were not present in vision performance testing.

Figure 10: RMS outlier identification in the Onefit P&A lens using a stem and leaf plot.

Figure 11: RMS outlier identification in the Air Optix lens using a stem and leaf plot.

Aberrations with Outliers Removed

The average trefoil values Z(3,-1) for the Onefit P&A and Air Optix lenses were -

0.19 ± 0.15 and -0.37 ± 0 .43 microns, respectively. No significant difference was detected between the lenses (P =0.12). The value for the Onefit P&A lens was slightly reduced while the Air Optix value became slightly more negative. These data are summarized in Table 7.

The average RMS for the Onefit P&A and Air Optix lenses were 0.19 ± .08 and

0.25 ± .07 microns, respectively. No significant difference was detected between the lenses (P =0.07). The RMS values for both the Onefit P&A and Air Optix lenses were reduced, but the RMS for the Onefit P&A was reduced more than for the Air Optix lenses. These data are summarized in Table 7.

Higher Order Aberrations

Mean N Std. Deviation P (2-tailed)

Z(3,-1) Onefit -0.19 13 0.15 0.12 Pair 3 Z(3,-1) Air Optix -0.37 13 0.43 RMS Onefit 0.19 12 0.08 0.07 Pair 6 RMS Air Optix 0.25 12 0.07

Table 7: Summary of higher-order aberrations with the Onefit P&A and Air Optix lenses after six hours of wear, following removal of outliers.

Scleral Lens Settling

The average amount of clearance present at the contact lens dispense was 251.14

± 60.48 microns. The average amount of clearance present at the lens evaluation visit was

159.43 ± 64.39 microns. The average amount of settling that occurred, comparing the two measures, was 91.71 microns.

Corneal Compromise

At the lens evaluation visit, 13 out of 14 eyes wearing the Onefit P&A lenses showed corneal staining present compared to 4 out of 14 eyes wearing the Air Optix lenses (Table 8, Figures 12-20). In addition to showing signs of epithelial compromise, the eyes wearing the Onefit P&A lenses also showed signs of epithelial edema through the presence of epithelial bullae. The epithelial bullae were primarily visible using fluorescein dye and presented as localized, pebble-like areas of negative fluorescein staining in the peripheral cornea. The bullae were best imaged using retroillumination or with fluorescein dye, but were rarely visible with direct white light. In all, epithelial bullae were photo documented in six eyes. There were no cases of epithelial bullae in the

Air Optix lenses. However, residual epithelial bullae secondary to the Onefit P&A lenses were able to be imaged in one eye at the second lens evaluation visit which took place one week after the bullae were first imaged.

Corneal Epithelial Staining

Present Absent Total

Air Optix 4 10 14

Onefit P&A 13 1 14

Table 8: Describes the presence of corneal staining after six hours of wear among the contact lenses tested.

Figure 12: Corneal epithelial staining near the temporal limbus in the right eye examined using sodium fluorescein dye and a Wratten filter. Note the pattern and location of the staining.

Figure 13: Corneal epithelial staining present inferiorly in an eye wearing the Air Optix lenses examined using sodium fluorescein dye and a Wratten filter. Note the pattern and location of the staining.

Figure 14: OCT cross-sectional image of the temporal eye and contact lens in the patient from Figure 12.

Figure 15: Slit-lamp biomicroscope image of the clearance in the temporal peripheral cornea in the patient from Figure 12.

Figure 16: OCT cross-sectional images of the Onefit P&A lenses in the right eye of a patient looking straight ahead and to the right, respectively. The image pairs demonstrate the appearance before and after nearly seven hours of lens wear.

Figure 17: Low magnification slit-lamp biomicroscope image of the Onefit P&A on eye following nearly seven hours of wear.

Figure 18: High magnification slit-lamp biomicroscope image of epithelial bullae in the subject from Figure 17.

Figure 19: High magnification slit-lamp biomicroscope image of epithelial bullae in a Onefit P&A wearer.

Figure 20: Slit-lamp biomicroscope imaging showing high magnification imaging of the epithelial bullae in the subject from Figure 17.

Chapter 4: Discussion

Vision Performance

We hypothesized that the Onefit P&A rigid lens would provide better vision

performance than the Air Optix soft lens secondary to changes in higher order

aberrations2,44,45. Because high contrast visual acuity is a gross measure of visual

function, it was expected that the two lens designs would perform similarly with respect

to this metric. As a more specific indicator of visual performance, we predicted

differences between low contrast visual acuity and/or contrast sensitivity between the

lens modalities, particularly if residual aberrations between the lens types differed. Poorer

contrast sensitivity performance in the modality with the highest residual HOAs would be

consistent with previous studies evaluating post-refractive surgery and early cataract

patients, who exhibited reduced contrast sensitivity prior to high contrast visual acuity

loss.30,31,58 In this study we found no significant difference in vision performance

between the rigid and soft lens on any of the vision performance tests.

Although there were no significant findings with respect to vision performance,

there is limited data that use low contrast visual acuity or contrast sensitivity to quantify

the quality of vision with contact lenses. Previous studies of higher-order aberrations with

contact lenses did not use any vision testing beyond high contrast visual acuity.1,2,26,45

The lack of significance found in this study is consistent with a 2012 American Academy of Optometry (AAO) poster presentation comparing the Onefit P&A to the Biofinity 65

Toric lenses. The study found that although there was no difference in the subjects’ low contrast visual acuity, nearly 75% of the astigmatic subjects subjectively preferred the vision of the Onefit P&A.63

The refractive error of our study population likely influenced the visual

performance in the Onefit P&A lens. The subjects participating in this study had naturally

low levels of corneal astigmatism, based on corneal topography data, with low overall

refractive astigmatism. The 2012 AAO poster enrolled subjects with astigmatism from

0.75 to 2.75D.63 In this study population, the average refractive astigmatism was just

under 0.50D, with many subjects having completely spherical refractions. This implies

that the the optics of the cornea and the internal optics of the eye offset and eliminate

refractive astigmatism. Applying a rigid contact lens to the eye can create a tear lens that

upsets this balance and may induce astigmatism. This residual astigmatism in the Onefit

lens could explain why the rigid lenses used in this study, despite the trend to lower

HOAs, failed to offer significantly better visual performance. It is also possible that the

vision performance in the Onefit P&A lenses was limited by hazy vision secondary to

corneal epithelial edema.64 This would have been less likely, however, because the

epithelial edema present in the Onefit P&A lenses was always localized to the corneal

periphery, outside of the visual axis.

Higher-Order Aberrations

The higher-order aberrations of the contact lenses on-eye were evaluated using the COAS, a clinical aberrometer. The hypothesis was that the higher-order aberrations

would be decreased with the Onefit P&A lenses relative to the Air Optix lenses.

Compared to the baseline higher-order aberration levels, neither lens was statistically better. The Onefit P&A lenses averaged RMS aberrations that were equal to or slightly

lower than the baseline aberrations. The Air Optix lenses averaged RMS aberrations that

were generally greater than the baseline aberrations. These statistics support previous

findings demonstrating that rigid lenses do not seem to reduce higher-order aberrations

compared to baseline when the baseline aberrations are low, 1,26 and that soft lenses may

increase higher-order aberrations compared to baseline.3

This study supports the theory that rigid lenses may offer superior optical quality,

but the difference in optical quality may not be clinically significant, especially in

subjects with low levels of astigmatism. The initial data review showed significant

differences in trefoil, coma and spherical aberration. The Onefit P&A lens showed

significantly lower levels of trefoil and spherical aberration, with the spherical aberration

remaining similar to baseline levels. Comparatively, the Air Optix lenses caused a shift

from negative to positive spherical aberration. Although the Air Optix lenses had higher

levels of trefoil and spherical aberration, they showed a statistically lower level of coma.

While these differences were numerically significant, they are unlikely to be clinically meaningful because they did not translate into an effect on the subjects’ visual performance.

There were numerical outliers in the data for both the Onefit P&A and Air Optix groups that warranted further investigation. The outlier corrected calculation maintained the previous statistical significance in trefoil, coma and spherical aberration and the RMS

p-value trended towards significance (Table 4). It is possible that the statistical power of

the RMS values was limited by the sample size. While the sample size calculations prior to the study projected the need for 15 subjects to reach significance, the single exclusion due to an inadequate fit in the Onefit P&A and the two statistical outliers, one for each

contact lens modality, reduced the population for the RMS calculation to just 12.

Corneal Compromise

The presence of corneal staining and epithelial edema with the Onefit P&A lenses was an unanticipated result that caused significant concern with respect to the ocular health of the study population and resulted in significant revisions to the study protocol.

The signs of corneal disruption associated with the Onefit P&A lens were present at a

much higher frequency than what was observed in the Air Optix lenses (Table 8). The

positive and negative corneal staining, consistent with physical interactions between the

cornea and the lens, have not been documented previously for the Onefit P&A. The

corneal staining pattern in the Onefit P&A had a characteristic distribution, localized to

the outer 2mm of the cornea, the most critical location for corneal healing and site of the

epithelial stem cells. While the corneal disruption was highly visible with sodium

fluorescein dye following removal of the contact lens, it was virtually undetectable while

the contact lens was on the eye and patients were minimally symptomatic. Any symptoms

reported by subjects in the Onefit P&A lens were minimal and almost exclusively limited

to complaints of dryness or hyperemia, which are not uncommon symptoms of normal

contact lens wear.

The subtle nature of the corneal changes associated with the Onefit P&A lens

limited our ability to document these changes while the lenses were on the eye. Only one

anterior segment photograph was taken through the lens where epithelial bullae or staining were identified, despite efforts in multiple patients. The difficulty viewing the compromise in the peripheral cornea may have been due to a large change in the shape and thickness of this design as it approaches the limbus. The Onefit P&A lens is designed to be thinner near the limbus to promote oxygen transmission, but because they are fit much steeper than the cornea to vault the corneal surface, many of the Onefit P&A lenses required high minus power. The high minus power resulted in a thick lens near the edge of the optic zone, just inside the limbus. The quick transition from the thickened edge of the optic zone to the thinned section of lens overlying the limbus created optical distortion that made visualization through the lens with a slit-lamp biomicroscope difficult. To adequately assess these changes, the Onefit P&A needed to be removed and the cornea stained with sodium fluorescein.

These corneal changes included epithelial bullae, which were consistent with images and descriptions from a 1983 article describing cystic changes present in the epithelium of hydrogel contact lens wearers.6,55 Few descriptions of epithelial bullae and

contact lens wearers have been described before or since. Epithelial bullae in our study

population were commonly detected near the most anterior point of lens bearing and

limited to this location in an annular pattern in the corneal periphery. In contrast to more

common vacuoles and microcysts, bullae appear flat and oblong in shape and are larger

than the 5-30 microns that is typical of microcysts. Electron microscopy studies of

epithelial edema have shown that the swelling was primarily extracellular and greatest

near the base layer of the epithelium.65

It is thought that bullae develop when the tight junctions between epithelial cells are weakened from mechanical force, which allows fluid to enter the deeper epithelial layers.6 While the etiology of the bullae may be multifaceted, it has been demonstrated that hypoxia does not cause this specific type of epithelial edema.65 The epithelial bullae

found after six hours of wear in the Onefit lens may result from a similar underlying

etiology. The bullae associated with the Onefit lens wear were most frequently detected

near the anterior most edge of where the Onefit P&A contacted the cornea. This anterior

edge likely bears the greatest amount of pressure. Although the lens does not move with

each blink, the blink applies mechanical force to the lens, which is transferred to the

corneal epithelium and potentially weakens the tight junctions. Over time, the junctions

become sufficiently weak allow fluid to enter the extracellular space of the epithelium.

An alternate, or potentially additive, etiology for the development of the epithelial

compromise includes ocular surface desiccation in areas of prolonged contact lens and

corneal bearing. The tear film plays a significant role with respect to maintaining the

health of the eye and helps prevent infection, maintain hydration, provide nourishment

and promote good optical quality.66 In the Onefit P&A lens, peripheral corneal touch was

present and lens movement was minimal or completely absent. These qualities limit the

amount of tear exchange and may prevent access to fresh tears, resulting in dryness,

increasing osmolarity, and accumulating metabolic waste and other harmful particles on the ocular surface.

While corneal staining is commonly detected in rigid and soft contact lens

wearers, the location and severity of the epithelial compromise dictate its clinical

significance. In the population studied, the epithelial compromise following Onefit P&A

wear appeared more severe and was always located near the limbus, which led to concern

regarding long term contact lens wear. While corneal compromise was detected in nearly

all of the 14 subjects in this study, epithelial damage was not reported in the 40 subjects

enrolled and fit with the Onefit P&A lens during a separate, multi-location study.47 The

lack of similar findings may indicate that a difference in fitting process may play a

significant role in maintaining corneal health. Although the time of wear was unspecified,

the 2012 study reported that the average corneal clearance for the right eye was 116 ±

40.1 microns as measured with OCT. This reported value is in contrast to the amount of clearance estimated in this study with OCT following 6+ hours of lens wear, with the average clearance measuring 159 ± 64 microns. Inconsistencies in corneal clearance may be due to differences in lens diameter and base curve, which can be used to alter limbal clearance. In this study, an increase in lens diameter, from 14.6mm to 14.9mm, seemed to offer minimal additional limbal clearance. While steepening the base curve made a significant difference in the central corneal clearance, there was a much smaller change to the peripheral corneal clearance. These changes did not help clear the limbus, but moved the point of contact lens bearing more peripherally and closer to the limbus. Pressure, formally defined, is the amount of force divided by the area to which the force is applied.

Moving the point of contact outward reduces the amount of corneal tissue area supporting the lens and may increase the amount of pressure applied to the limbal area with each

blink. In contrast, lower levels of central corneal clearance would increase the total

corneal bearing, but would distribute the weight of the lens across a larger surface area

and reduce the amount of pressure. This could also lead to increased lens movement on

eye and could improve tear exchange beneath the lens.

While the Onefit P&A lenses demonstrated a trend of reduced HOAs compared to the Air Optix lenses, the difference was not statistically significant for the sample size tested. Compared to the baseline HOAs, the Onefit P&A lens offered similar values and did not appear to reduce HOAs in the population of normal eyes, consistent with previous

studies. 1,3 In addition, there was no detectable difference between the Onefit P&A and

Air Optix lenses in tests of visual performance including high contrast visual acuity, low

contrast visual acuity and contrast sensitivity. While rigid lenses may anecdotally offer

improved optical quality, this population of normal eyes with relatively low astigmatism

did not demonstrate a clinically significant difference.

While Onefit P&A lenses offer promising improvements in comfort and stability

compared to traditional rigid lenses, the unanticipated changes to the corneal surface

require further evaluation to ensure safety and to streamline the fitting process. Large

diameter rigid lenses are a promising option, but research investigating the influence of

scleral lenses on the ocular surface environment and the impact of scleral lens weight

distribution are critical if these lenses are to become a mainstream form of refractive

correction.

References

1. Choi J, Wee WR, Lee JH, Kim MK. Changes of ocular higher order aberration in on- and off-eye of rigid gas permeable contact lenses. Optom Vis Sci. 2007;84(1):42–51. doi:10.1097/01.opx.0000254036.45989.65.

2. Lu F, Mao X, Qu J, Xu D, He JC. Monochromatic wavefront aberrations in the human eye with contact lenses. Optom Vis Sci. 2003;80(2):135–41. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12597328. Accessed February 21, 2013.

3. Roberts B, Athappilly G, Tinio B, Naikoo H, Asbell P. Higher order aberrations induced by soft contact lenses in normal eyes with myopia. Eye Contact Lens. 2006;32(3):138–42. doi:10.1097/01.icl.0000195570.73454.a5.

4. Remington L. Clinical anatomy of the visual system. 2005.

5. HANNA C, BICKNELL DS, O’BRIEN JE. Cell turnover in the adult human eye. Arch Ophthalmol. 1961;65:695–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/13711260. Accessed March 16, 2014.

6. Efron N. Contact Lens Complications. Saunders; 3 edition; 2012:350.

7. Murphy PJ, Patel S, Marshall J. The effect of long-term, daily contact lens wear on corneal sensitivity. Cornea. 2001;20(3):264–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11322414. Accessed March 17, 2014.

8. Lakkis C, Brennan N. Bulbar conjunctival fluorescein staining in hydrogel contact lens wearers. Eye Contact Lens. 1996. Available at: http://journals.lww.com/claojournal/Abstract/1996/07000/Bulbar_Conjunctival_Fl uorescein_Staining_in.9.aspx. Accessed March 20, 2014.

9. McMonnies C, Chapman-Davies A. Assessment of conjunctival hyperemia in contact lens wearers. Part I. Am J …. 1987. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3591894. Accessed March 20, 2014.

10. McMonnies C, Chapman-Davies A. Assessment of conjunctival hyperemia in contact lens wearers. Part II. Am J …. 1987. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3591895. Accessed March 20, 2014.

11. Nichols, Jason, OD, MPH, PhD F. Contact Lenses 2013. Contact Lens Spectr. 2014;29(January):22–28. Available at: http://www.clspectrum.com/articleviewer.aspx?articleID=109320. Accessed March 17, 2014.

12. Fink B, HIll R, Carney L. Influence of rigid contact lens overall and optic zone diameters on tear pump efficiency. Optom Vis Sci. 1990. Available at: http://journals.lww.com/optvissci/Abstract/1990/08000/Influence_of_Rigid_Conta ct_Lens_Overall_and_Optic.16.aspx. Accessed March 20, 2014.

13. Bennett E. Clinical manual of contact lenses. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2009.

14. Williams-Lyn D, MacNeill K, Fonn D. The effect of rigid lens back optic zone radius and diameter changes on comfort. Int Contact Lens Clin. 1993;20(11- 12):223–229. doi:10.1016/0892-8967(93)90004-B.

15. Hazlett RD. Custom designing large-diameter rigid gas permeable contact lenses: A clinical approach intended to optimize lens comfort. Int Contact Lens Clin. 1997;24(1):5–9. doi:10.1016/S0892-8967(96)00126-5.

16. Scleral Lens Education Society. Scleral Lens Nomenclature. 2013. Available at: https://www.sclerallens.org/sites/default/files/files/SLS_Nomenclature_LtrHead06 _26_2013.pdf. Accessed March 21, 2014.

17. Pullum KW, Stapleton FJ. Scleral lens induced corneal swelling: what is the effect of varying Dk and lens thickness? CLAO J. 1997;23(4):259–63. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9348450. Accessed March 17, 2014.

18. Pullum KW, Whiting MA, Buckley RJ. Scleral contact lenses: the expanding role. Cornea. 2005;24(3):269–77. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15778597. Accessed September 5, 2013.

19. Kok JH, Visser R. Treatment of ocular surface disorders and dry eyes with high gas-permeable scleral lenses. Cornea. 1992;11(6):518–22. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1468214. Accessed September 5, 2013.

20. Rosenthal P, Croteau A. Fluid-ventilated, gas-permeable scleral contact lens is an effective option for managing severe ocular surface disease and many corneal disorders that would otherwise require penetrating keratoplasty. Eye Contact Lens. 2005;31(3):130–4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15894881. Accessed March 17, 2014.

21. Segal O, Barkana Y, Hourovitz D, et al. Scleral contact lenses may help where other modalities fail. Cornea. 2003;22(4):308–10. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12792472. Accessed August 9, 2013.

22. Romero-Rangel T, Stavrou P, Cotter J, Rosenthal P, Baltatzis S, Foster CS. Gas- permeable scleral contact lens therapy in ocular surface disease. Am J Ophthalmol. 2000;130(1):25–32. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11004256. Accessed March 17, 2014.

23. Bennett ES. GP Annual Report 2013. Contact Lens Spectr. 2013;28(October):20– 29. Available at: http://www.clspectrum.com/articleviewer.aspx?articleID=108953. Accessed March 9, 2014.

24. Prevent Blindness America. Vision Problems in the U.S. 2012. Available at: http://www.visionproblemsus.org/.

25. Johnson TJ, Schnider CM. Clinical performance and patient preferences for hydrogel versus RGP lenses: A crossover study. Int Contact Lens Clin. 1991;18(7):130–135. Available at: http://www.sciencedirect.com/science/article/pii/089289679190026V. Accessed January 2, 2014.

26. Thibos LN, Hong X. Clinical applications of the Shack-Hartmann aberrometer. Optom Vis Sci. 1999;76(12):817–25. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10612402. Accessed February 21, 2013.

27. Warwick R. Eugene Wolff’s anatomy of the eye and orbit. WB Saunders Co, Philadelphia. 1976. Available at: http://scholar.google.com/scholar?hl=en&q=wolff’s+anatomy+eye&btnG=&as_sd t=1,36&as_sdtp=#2. Accessed March 16, 2014.

28. Gemoules G. A novel method of fitting scleral lenses using high resolution optical coherence tomography. Eye Contact Lens. 2008;34(2):80–3. doi:10.1097/ICL.0b013e318166394d.

29. Pesudovs K, Marsack JD, Donnelly WJ, Thibos LN, Applegate RA. Measuring visual acuity--mesopic or photopic conditions, and high or low contrast letters? J Refract Surg. 2004;20(5):S508–14. Available at: http://europepmc.org/abstract/MED/15523967/reload=0. Accessed March 18, 2014.

30. Oshika T, Okamoto C, Samejima T, Tokunaga T, Miyata K. Contrast sensitivity function and ocular higher-order wavefront aberrations in normal human eyes. Ophthalmology. 2006;113(10):1807–12. doi:10.1016/j.ophtha.2006.03.061.

31. Cheng ACK, Rao SK, Lam DSC. Influence of wavefront aberration and corneal subepithelial haze on low-contrast visual acuity after photorefractive keratectomy. Am J Ophthalmol. 2005;140(5):955; author reply 955–6. doi:10.1016/j.ajo.2005.07.001.

32. Yamane N, Miyata K, Samejima T, et al. Ocular higher-order aberrations and contrast sensitivity after conventional laser in situ keratomileusis. Invest Ophthalmol Vis Sci. 2004;45(11):3986–90. doi:10.1167/iovs.04-0629.

33. Timberlake GT, Doane MG, Bertera JH. Short-term, low-contrast visual acuity reduction associated with in vivo contact lens drying. Optom Vis Sci. 1992;69(10):755–60. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1436995. Accessed January 2, 2014.

34. Oshika T, Okamoto C, Samejima T, Tokunaga T, Miyata K. Contrast Sensitivity Function and Ocular Higher-Order Wavefront Aberrations in Normal Human Eyes. Ophthalmology. 2006;113(10):1807–12. doi:10.1016/j.ophtha.2006.03.061.

35. Liang J, Williams DR. Aberrations and retinal image quality of the normal human eye. J Opt Soc Am A. 1997;14(11):2873. doi:10.1364/JOSAA.14.002873.

36. Cheng X, Himebaugh NL, Kollbaum PS, Thibos LN, Bradley A. Validation of a clinical Shack-Hartmann aberrometer. Optom Vis Sci. 2003;80(8):587–95. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12917578. Accessed January 2, 2014.

37. Porter J, Guirao A, Cox IG, Williams DR. Monochromatic aberrations of the human eye in a large population. J Opt Soc Am A. 2001;18(8):1793. doi:10.1364/JOSAA.18.001793.

38. Wang L, Koch DD. Ocular higher-order aberrations in individuals screened for refractive surgery. J Cataract Refract Surg. 2003;29(10):1896–1903. doi:10.1016/S0886-3350(03)00643-6.

39. Salmon TO, van de Pol C. Normal-eye Zernike coefficients and root-mean-square wavefront errors. J Cataract Refract Surg. 2006;32(12):2064–2074. doi:10.1016/j.jcrs.2006.07.022.

40. Oshika T, Klyce S, Applegate R, Howland H. Changes in corneal wavefront aberrations with aging. Invest Ophthalmol Vis Sci. 1999;40(7):1351–1355. 76

Available at: http://www.iovs.org/content/40/7/1351.short. Accessed April 4, 2013.

41. Glenn Fry Award Lecture 2002: Wavefront Sensing, Ideal Correction and Visual Performance. Available at: http://voi.opt.uh.edu/2004-OVS- wavefrontsensingidealcorrectionandvisualperformance.pdf.

42. Applegate RA, Marsack JD, Ramos R, Sarver EJ. Interaction between aberrations to improve or reduce visual performance. J Cataract Refract Surg. 2003;29(8):1487–1495. doi:10.1016/S0886-3350(03)00334-1.

43. Fonn D, Gauthier CA, Pritchard N. Patient preferences and comparative ocular responses to rigid and soft contact lenses. Optom Vis Sci. 1995;72(12):857–63. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8749332. Accessed January 2, 2014.

44. Hong X, Himebaugh N, Thibos LN. On-eye evaluation of optical performance of rigid and soft contact lenses. Optom Vis Sci. 2001;78(12):872–80. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11780664. Accessed February 21, 2013.

45. Dorronsoro C, Barbero S, Llorente L, Marcos S. On-eye measurement of optical performance of rigid gas permeable contact lenses based on ocular and corneal aberrometry. Optom Vis Sci. 2003;80(2):115–25. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12597326. Accessed April 4, 2013.

46. Ho A, Manns F, Pham T, Farrar S. The Effect of RGP Lens Decentration on Aberration: the Influence of the Tear Lens. ARVO Meet Abstr. 2002;43(12):3105. Available at: http://abstracts.iovs.org.proxy.lib.ohio- state.edu/cgi/content/abstract/43/12/3105. Accessed January 2, 2014.

47. Michaud L, Woo S, Dinardo-Lotoczky A, et al. Clinical Evaluation of a Large Diameter Rigid Gas Permeable Lens for the Correction of Refractive Astigmatism. 2012. Available at: http://www.blanchardlab.com/pdf/AAO2012LRGPvsBiofitnityV2 morgandinardo edit.pdf.

48. Michaud L, van der Worp E, Brazeau D, Warde R, Giasson CJ. Predicting estimates of oxygen transmissibility for scleral lenses. Cont Lens Anterior Eye. 2012;35(6):266–71. doi:10.1016/j.clae.2012.07.004.

49. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992. Available at: http://www.med.upenn.edu/timm/documents/DunaiefTIMMShweikietal-1.pdf. Accessed March 19, 2014. 77

50. COGAN D. Vascularization of the cornea: its experimental induction by small lesions and a new theory of its pathogenesis. Arch Ophthalmol. 1949. Available at: http://archopht.ama-assn.org/cgi/content/summary/41/4/406. Accessed March 23, 2014.

51. Fromer CH, Klintworth GK. An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization. III. Studies related to the vasoproliferative capability of polymorphonuclear leukocytes and lymphocytes. Am J Pathol. 1976;82(1):157–70. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2032283&tool=pmcen trez&rendertype=abstract. Accessed March 23, 2014.

52. Holden B, Sweeney D, Vannas A. Effects of long-term extended contact lens wear on the human cornea. … Ophthalmol Vis …. 1985. Available at: http://www.iovs.org/content/26/11/1489.short. Accessed March 20, 2014.

53. Madigan M. Cat and Monkey Cornea as Models for Extended Hydrogel Contact Lens Wear in Humans. 1989. Available at: http://scholar.google.com/scholar?q=Cat+and+monkey+as+models+for+extended +hydrogel+contact+lens+wear+in+humans&btnG=&hl=en&as_sdt=1,36#5. Accessed March 23, 2014.

54. Keay L, Sweeney D. Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis …. 2000. Available at: http://journals.lww.com/optvissci/Abstract/2000/11000/Microcyst_Response_to_H igh_Dk_t_Silicone_Hydrogel.7.aspx. Accessed March 23, 2014.

55. Zantos S. Cystic formations in the corneal epithelium during extended wear of contact lenses. Int Contact Lens Clin. 1983. Available at: http://scholar.google.com/scholar?q=Cystic+formations+in+the+corneal+epitheliu m+during+extended+wear&btnG=&hl=en&as_sdt=1,36#0. Accessed March 23, 2014.

56. Brautaset RL, Nilsson M, Leach N, et al. Corneal and conjunctival epithelial staining in hydrogel contact lens wearers. Eye Contact Lens. 2008;34(6):312–6. doi:10.1097/ICL.0b013e3181891439.

57. Cheng KH, Leung SL, Hoekman HW, et al. Incidence of contact-lens-associated microbial keratitis and its related morbidity. Lancet. 1999;354(9174):181–5. doi:10.1016/S0140-6736(98)09385-4.

58. Kuroda T, Fujikado T, Maeda N, Oshika T, Hirohara Y, Mihashi T. Wavefront analysis in eyes with nuclear or cortical cataract. Am J Ophthalmol. 2002;134(1):1–9. Available at: 78

http://www.sciencedirect.com/science/article/pii/S0002939402014022. Accessed January 1, 2014.

59. Rocha KM, Nosé W, Bottós K, Bottós J, Morimoto L, Soriano E. Higher-order aberrations of age-related cataract. J Cataract Refract Surg. 2007;33(8):1442– 1446. Available at: http://www.sciencedirect.com/science/article/pii/S0886335007007353. Accessed January 1, 2014.

60. Sharma S, Rekha W, Sharma T, Downey G. Refractive issues in pregnancy. Aust N Z J Obstet Gynaecol. 2006;46(3):186–8. doi:10.1111/j.1479-828X.2006.00569.x.

61. Dougherty BE, Flom RE, Bullimore MA. An evaluation of the Mars Letter Contrast Sensitivity Test. Optom Vis Sci. 2005;82(11):970–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16317373. Accessed March 18, 2014.

62. Andre M, Caroline P. Scleral Lens Settling. Contact Lens Spectr. 2012;27:56. Available at: http://www.clspectrum.com/articleviewer.aspx?articleID=106982.

63. Michaud L, Woo S, Dinardo-Lotoczky A, et al. Clinical Evaluation of a Large Diameter Rigid Gas Permeable Lens for the Correction of Refractive Astigmatism. 2012.

64. Cox I, Holden B. Can vision loss be used as a quantitative assessment of corneal edema? Int Contact Lens Clin. 1990. Available at: http://www.sciencedirect.com/science/article/pii/089289679090004Y. Accessed March 19, 2014.

65. Wang J, Fonn D, Simpson TL, Jones L. The measurement of corneal epithelial thickness in response to hypoxia using optical coherence tomography. Am J Ophthalmol. 2002;133(3):315–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11860966. Accessed March 27, 2014.

66. Adler’s Physiology of the Eye: Expert Consult - Online and Print, 11e [Hardcover]. Saunders; 11 edition; 2011:820. Available at: http://www.amazon.com/Adlers-Physiology-Eye-Expert-Consult/dp/0323057144. Accessed April 14, 2014.