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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. THE CONTACT LENS AND MYOPIA PROGRESSION (CLAMP) STUDY

DISSERTATION

Presented in Partial Fulfillment of the Requirements for

the Degree Doctor of Philosophy in the Graduate

School of The Ohio State University

By

Jeffrey Jay Wallme, OD MS

*****

The Ohio State University 2002

Dissertation Committee: Approved by Professor Karla Zadnik, Advisor

Associate Professor Donald O. Mutti Advisor Professor Joseph T. Barr Vision Science Graduate Program

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ABSTRACT

The Contact Lens and Myopia Progression (CLAMP) Study is a single-masked,

randomized clinical trial designed to examine the effects of rigid gas permeable contact

lenses on myopia progression in children. Several studies have attempted to answer this

clinically important question, but limitations in study design have rendered then*

conclusions uncertain. A critical review of the previous literature allows the CLAMP

Study to avoid the pitfalls encountered by previous studies and to provide a more

definitive answer to the question. The three-year clinical trial is continuing, but this

dissertation will only report data from the first year of the study, and all data are strictly

confidential.

We screened 222 eight- to eleven-year-old children for eligibility. Out of the 222

children, 147 were eligible to participate in the CLAMP Study run-in period to ensure

that all subjects randomly assigned to a treatment group were able to adapt to rigid gas

permeable (RGP) contact lens wear. O f the 147 subjects, 116 (78.9%) were able to wear

their RGP contact lenses at least 40 hours per week and report that their contact lenses

were “always comfortable” or “usually comfortable”. We randomly assigned 59 subjects

to wear RGP contact lenses and 57 subjects to wear soft, two-week disposable contact

lenses. All outcomes were measured at the randomization visit and annually thereafter. ii

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The primary outcome measure was cycloplegic autorefraction; secondary outcome

measures included corneal topography, corneal thickness, axial dimensions, crystalline

lens curvatures, intraocular pressures, and peripheral refraction.

All data were dual-entered into Epi Info 6 or Microsoft Excel. Matching double

entries were required prior to output to the final data file. All data were analyzed using

SAS statistical software package (SAS Institute, Inc., Cary, NC) or Microsoft Excel

All analyses were repotted for the right eye only. Results that differed for the left eye

were discussed in the text. Descriptive statistics were presented as either means and

standard deviations or frequencies, depending on whether the data were continuous or

categorical in nature. Continuous variables were compared using a paired t-test or a

Student’s t-test, and categorical variables were analyzed using either Chi-square or the

Fisher’s exact test.

At randomization, all of the ocular parameters of the two treatment groups were equal

(Student’s t-test, p > 0.05). The mean ± standard deviation spherical equivalent

cycloplegic autorefraction of the right eye was -2.30 ± 0.90 D for the RGP contact lens

wearers and -2.48 ± 0.86 D for the soft contact lens wearers (Student’s t-test, p = 0.27).

From the randomization visit to the one-year visit, the spherical equivalent cycloplegic

autorefraction progressed -0.80 ± 0.65 D for the rigid gas permeable (RGP) contact lens

wearers and-1.19 ± 0.53 D for the soft contact lens wearers (Student’s t-test, p <

0.0005). None of the other ocular parameter changes between the randomization visit and

the one-year visit differed significantly between the two treatment groups except the flat

meridian of the soft contact lens wearers steepened significantly more than the RGP

contact lens wearers (paired t-test, p < 0.0001). iii

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. In summary, nearly 80% of myopic children were able to adapt to rigid gas permeable

contact lenses. The rigid gas permeable contact lenses slowed the progression of myopia

more than the soft contact lenses in young, myopic children over the first year of contact

lens wear, and the effect seems to be primarily due to corneal reshaping.

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. D e d ic a t e d t o t h e m e m o r y o f m y m o t h e r , C a r o l M a r ie W a l l in e

Learning is not attained by chance, it must be sought fo r with ardor and attended to with diligence. A bigail Adams, 1780

v

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGMENTS

In 1987,1 left rural Colorado to attend college in southern California. Since then I

have grown and changed, but my family has always been a strong resource of love,

support, and encouragement. The past 18 months have been very difficult for all of us,

but we have only grown closer and stronger. Dad, Quint, Jacque, Steve, and Ross: 1 love

you all very much.

So many people have helped with the CLAMP Study. Maijorie Rah, Kelly Nichols,

and Jason Nichols all served as masked examiners for the CLAMP Study, but far more

importantly, they are great friends and close colleagues. I still don’t know how and when

they do all the work, but Rachel Watson and Jeff Williams have been indispensable to the

conduct of the CLAMP Study while also being students. Lea Jones manages all of the

data for the CLAMP Study, but more importantly she is always there when I need

advice. ..thanks Lisa. Finally, none of the data analysis in this dissertation would have

been possible if it weren’t for Linda Barrett’s data entry.

My dissertation committee consisted of Joe Barr, Don Mutti, and Karla Zadnik. I am

most appreciative to them for their edits, their ideas, their thought-provoking questions,

but most of all for the uncompensated time and help they have provided over the past

several years.

vi

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Several friends and colleagues have provided more support than they can possibly

realize: Gil Pierce, Jodi Malone, Kurt Zadnik, Mark BuUimore, Lynn Mitchell, Melissa

Bailey, Mike Twa, Nora McFadden, Pam Wessel, Kathy Reuter, and Jessica Cullen.

Over the past year, another person has become very close to me and helped me to see

that there is more to the world than work. Philip Lortz, every day I still think how lucky I

was to meet you.

Don Mutti may not be my “Mentor”, but my education and the CLAMP Study would

not have been the same without him. Don, thank you so much for serving as a masked

examiner, for being an equipment guru, for your sage advice, for your hours upon hours

of time.. .and for taking a 1% pay cut to do all of this. I may be able to make up for the

1% pay cut some day, but I will never be able to repay you for the rest

Karla...thank you for your energy, enthusiasm, creativity, motivation, advocacy,

resources, ideas, and encouragement. I owe everything I have accomplished to you.

Neither optometry nor life would have been nearly as fulfilling without you there. Thank

y o u !

This research was supported by funds from the National Eye Institute (K23-

EY00383), Menicon Co., Ltd., CIBA Vision Care, SOLA Optical USA, and William C.

Ezell Fellowships from the American Optometric Association, sponsored by Essilor.

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. VITA

November 9,1968 Bora - Julesburg, Colorado

1996 OD Optometry, University of California, Berkeley.

1998 MS Physiological Optics, The Ohio State University

1996-1997 Graduate Teaching Associate, The Ohio State University

1997-present. Senior Research Associate, The Ohio State University

PUBLICATIONS

1. Walline JJ, Zadnik K, Mutti DO. The validity of surveys reporting myopia, astigmatism, and presbyopia. Optom Vis Sci 1996;73:376-81.

2. Walline JJ, Mutti DO, Zadnik K. Development of phoria in children. Optom Vis Sci 1998;8:605-10.

3. Walline JJ, Kinney KA, Mutti DO, Zadnik K. Repeatability and validity of astigmatism measurements. J Refract Surg 1999;15:23-31.

4. Walline JJ. Fitting kids with rigid gas permeable lenses. Cont Lens Spect 2000; 15:33- 9.

5. Walline JJ, Mutti DO, Jones LA, Rah MJ, Nichols KK, Watson R, Zadnik K. The Contact Lens and Myopia Progression (CLAMP) Study: design and baseline data. Optom Vis Sci 2001;78:223-233.

6 . Walline JJ. Rigid contact lenses and myopia progression. Cont Lens Spect 2001;16:20-4.

7. Walline JJ. Children: an untapped population of contact lens wearers. Cont Lens Spec 2002;17:25-32.

vm

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. FIELDS OF STUDY

Major Field: Vision Science

ix

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS

Page

Dedication ...... v

Acknowledgments ...... vi

V ita...... viii

List of Tables ...... xiv

List o f Figures ...... xviii

Chapters:

1. Introduction ...... 1

Public Health Significance ...... I Methods of Myopia Control ...... 3 Limitations of Previous Rigid Contact Lens Studies ...... 13 Avoiding Limitations of Previous Studies ...... 14

2. Methods ...... 19

Eligibility ...... 20 Informed Consent and Human Subjects ...... 22 V isits...... 22 Primary Outcome Measure...... 27 Secondary Outcome Measures ...... 28 Surveys...... 32 Masking ...... 33 Control Group ...... 34 Randomization ...... 35 Sample Size Considerations ...... 37 Contact Lens Fitting ...... 37 Data Safety Monitoring Committee ...... 39 Incentives for Participation ...... 39 x

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Intent-To-Treat Analysis ...... 40 Data Entry and Statistical Analyses...... 40

3. Run-In Period ...... 42

Introduction ...... 42 Results...... 44

4. Data at Randomization...... 52

Demographics...... 52 Refractive Error ...... 54 Ocular Components ...... 55

5. Subjects, Study Visits, and Surveys...... 57

Subjects...... 57 Study V isits...... 58 Surveys...... 60 Near Work Surveys ...... 60 Contact Lens Surveys ...... 63

6 . Refractive Error Changes ...... 71

Spherical Equivalent ...... 72 Astigmatism ...... 77

7. Ocular Component Changes ...... 79

Visual Acuity...... 80 Keratometry ...... 81 Intraocular Pressure ...... 82 Corneal Thickness ...... 82 Axial Dimensions ...... 84 Peripheral Autorefraction ...... 84

8 . Conclusions ...... 87

Significance ...... 87 Rationale for the Study ...... 88 Run-In Period ...... 88 Randomization Results ...... 91 Refractive Error Changes ...... 92 Ocular Component Changes ...... 93 Data Safety Monitoring Committee ...... 94 xi

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Summary...... 96

Bibliography ...... 97

Appendix A - Excerpts from the Operations Manual ...... 105

Study Organization and Policy Matters ...... 105 Stuffy Administration ...... 105 Subject Costs ...... 106 Publicity...... 106 Publication of Study Design, Methods, and Findings ...... 106 Presentations ...... 108 Ancillary Studies...... 109 Access to Study Information ...... I l l

Accommodation Measurement ...... 112 Accommodative Response ...... 112 Equipment Setup ...... 112 Calibration ...... 114 Uncorrected Measurement Procedure ...... 114 Soft Contact Lenses Measurement Procedure ...... 116 Rigid Contact Lenses Measurement Procedure ...... 117 Spectacles Measurement Procedure ...... 117

Visual Acuity, Pupillary Distance, Retinoscopy, Keratometry, and Tonometry Measurement of Visual Acuity ...... 119 Calibration ...... 119 Visual Acuity Technique ...... 119 Retinoscopy ...... 124 Cover-Uncover at Distance ...... 125 Alternate Cover Test at D istance ...... 125 Cover-Uncover at Near...... 126 Alternate Cover Test at N ear ...... 127 Interpupfllary Distance ...... 127 Keratometry ...... 128 Drop Installation ...... 131 Tonometry ...... 131

Videophakometry ...... 133

Cycloplegic Autorefraction and Peripheral Refraction ...... 141 Cycloplegic Autorefraction ...... 141 Peripheral Refraction ...... 142

Ultrasonography ...... 143 xii

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Videophakometry and AC/A Ratio Data Analysis ...... 145 Videophakometry ...... 145 Reading for AC/A Ratio ...... 152 AC/A Ratio Calculations ...... 157

Videokeratography and O rbscan ...... 161 Videokeratography ...... 161 Orbscan...... 163

Rigid Contact Lens Fitting and Assessment ...... 165

Certification Procedures ...... 169 Accommodative Testing ...... 171 Keratometry ...... 172 Tonometry ...... 173 Videophakometry ...... 173 Autorefraction ...... 174 Ultrasonography ...... 175

Appendix B - Forms ...... 177 Tracking Form ...... 178 Masked Exam Form ...... 180 Unmasked Exam F orm ...... 181 SCL Check Form ...... 186 1 and 2 Month Masked Form ...... 187 1 and 2 Month Unmasked Form ...... 190 6 Month RGP Form ...... 192 6 Month SCL Form ...... 194 Annual Masked Form ...... 195 Annual Unmasked Form ...... 198 Parents CL Form ...... 203 Subjects CL Form ...... 207 Parents NW Form ...... 212 Subjects NW Form ...... 213 V A Form ...... 214

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST O F TABLES

Table Page

1.1 Results from bifocal myopia control studies ...... 7

1.2 Results from cycloplegic agent myopia control studies ...... 9

1.3 Results from rigid contact lens myopia control studies ...... 13

1.4 Limitations of previous rigid contact lens myopia control studies ...... 14

1.5 CLAMP Study solutions to problems encountered by previous rigid

contact lens myopia control studies ...... 15

2.1 Inclusion and exclusion criteria ...... 20

2.2 Outcome measures performed at the baseline visit ...... 23

2.3 Outcome measures performed at the randomization visit ...... 24

2.4 Schedule of surveys completed ...... 32

2.5 Masked and unmasked outcome measures ...... 33

2.6 The CLAMP Study treatment group designation combinations ...... 36

2.7 Guide to determine the base curve from keratometry readings ...... 38

3.1 Demographic characteristics of subjects eligible to participate in the

CLAMP Study run-in period ...... 45

3.2 Median (range) days between the baseline visit and follow-up visits ...... 46

3.3 Mean ± SD ocular characteristics of subjects eligible to participate in the

run-in period...... 47

xiv

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 3.4 Patient-reported contact lens vision, comfort, and handling issues ...... 48

3.5 Variables in the final logistic regression model to predict children’s ability

to adapt to rigid gas permeable contact lens wear ...... 49

3.6 Wearing time and NEI-VFQ scores ...... 50

4.1 Demographic summary of participants in the CLAMP Study ...... 54

4.2 Mean ± SD refractive error components for the right eye of the two

treatment groups at the randomization visit ...... 55

4.3 Mean ± SD refractive ocular component dimensions for the right eye of

the two treatment groups at the randomization visit ...... 56

5.1 Number (percentage) of subjects not wearing the treatment they were

assigned at the one-year v isit ...... 58

5.2 Mean ± SD time (days) between randomization and study visits ...... 59

5.3 Proportion of subjects examine within ± I month of the anniversary date ...... 59

5.4 Mean ± SD difference in two reports of near work activities ...... 61

5.5 Mean ± SD difference in subjects’ report of near work activities at

baseline and one year ...... 62

5.6 Mean ± SD report of near work activities by subjects at the one-year visit ...... 63

5.7 Example of the calculation of the contact lens wearing time per week ...... 64

5.8 Mean ± SD wearing time per week reported by the subjects and the

parents at the randomization on one-year visits ...... 65

5.9 Mean ± standard deviation wearing time per week reported by the subjects

at the randomization and one-year visits ...... 65

xv

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. S. 10 Agreement between the subjects and the parents regarding the subjects’

contact lens comfort ...... 66

S. 11 Agreement between the subjects and the parents regarding the subjects’

preference for glasses or contact lenses ...... 67

S. 12 Agreement between the subjects and the parents regarding the subjects’

ability to handle contact lenses at the one-year visit ...... 68

S. 13 Comparison of the RGP contact lens wearers’ and the soft contact lens

wearers’ reports of contact lens comfort and handling ability, and the

subjects’ report of spectacle or contact lens preference at the one-year visit ...... 69

S. 14 Mean ± SD NEI-VFQ subscales reported by the subjects at the

randomization visit ...... 70

6.1 Maximum and minimum spherical equivalent refractive error for each

group at the randomization visit and the one-year visit ...... 77

6.2 Mean ± SD astigmatism components of the right eye ...... 77

7.1 Mean ± SD changes in the ocular component dimensions of the right eye

for the two treatment groups ...... 80

7.2 Steep and flat keratometry readings of the right eye at randomization and

one year ...... 81

7.3 Relative peripheral autorefraction of the right eye at the randomization

visit and the one-year visit for each treatment group ...... 86

8.1 Change in steep and flat meridians of the cornea from prior to contact lens

wear to randomization ...... 93

xvi

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 8.2 Change in steep and flat meridians of the cornea from baseline to the end

of year one ...... 94

xvii

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST O F FIGURES

Figure Page

2.1 Flow chart of CLAMP Study visits ...... 26

2.2 CLAMP Study block randomization treatment group allocation scheme ...... 36

3.1 Reasons subjects report they occasionally don’t like to wear contact lenses SI

4.1 Subjects eligible to participate in CLAMP Study ...... 53

6.1 Mean ± standard deviation one-year change m refractive error ...... 72

6.2 Progression of the spherical equivalent myopia for individual subjects ...... 74

6.3 Number of RGP contact lens wearers and soft contact lens wearers who

progressed in myopia a specified amount during the first year ...... 76

6.3 Change in refractive astigmatism of the right eye ...... 78

7.1 Mean ± SD change in the corneal thickness (pm) of the right eye of all

subjects from the randomization visit to the one-year visit ...... 83

7.2 Diagram of oblate and prolate shapes ...... 85

8.1 Refractive error changes in the rigid gas permeable contact lens study

conducted by Khoo, et al...... 96

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 1

INTRODUCTION

Public Health Significance

Approximately two percent of the United States population is myopic at school entry

(Blum, et al., 19S9), and about 15% of the people entering high school are myopic

(Sperduto, et al., 1983). Myopia development begins around age six years, and its

progression continues through fifteen to sixteen years (Goss, 1987). The majority of

myopia development therefore occurs during the school years.

Controlling myopia progression during childhood may potentially affect the cosmesis

and comfort of spectacle wear, the cost effectiveness of spectacles and contact lenses,

refractive surgery outcomes, and ocular health. Patients with less myopia have a wider

variety of spectacle and contact lens options available to them. Patients with high myopia

are encouraged to wear small, round spectacle lenses with plastic or metal frames in order

to minimize the thickness and weight of the lenses. Patients with less myopia may choose

from a wider variety of shapes and size s o f spectacle lenses that are cosmetically

appealing and comfortable for them, and rimless frames provide an additional option that

is typically not recommended for patients with high myopia. Contact lens options for 1

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. high myopes are also limited. The current primary mode of contact lens refractive error

correction is disposable contact lenses. O f the 30 brands available, only seven (23%)

have powers higher than -10.00 D, thereby limiting contact lens options for highly

myopic patients (Tyler Thompson, 2001).

Not only do people with less myopia have more options available, those options are

typically less expensive. For example, a pair of plastic lenses for a -2.00 D myope costs

$74. A pair of polycarbonate spectacle lenses of similar thickness and weight for a - 5.00

D myopic patient costs $104 (Ohio State University Eyewear Dispensary, 2002).

A recent increase in the popularity of refractive surgery also speaks to the potential

benefits of myopia control Refractive surgery results are more precise and side effects

are less prevalent for patients with less myopia than for patients with myopia greater than

-6.00 D(Halliday, 1995).

The ocular health benefits of myopia control are evident in that patients with high

myopia are at greater risk for retinal detachment and glaucoma (Curtin, 1985). One- to

three-diopter myopes have a four times greater risk of retinal detachment than

emmetropic and hyperopic eyes, and people with more than -3.00 D of myopia have a

ten times greater risk of retinal detachment (The Eye Disease Case-Control Study Group,

1993). The annual incidence of retinal detachment is 12.4 (Haimaim, et al, 1982) to 12.9

(Wilkes, et aL, 1982) per 100,000 patients, which means that approximately 35,000

people in the United States will suffer a retinal detachment over the next year.

Approximately half of the retinal detachments are non-traumatic (Haimann, et al., 1982),

and nearly 55% of these are attributable to myopia (The Eye Disease Case-Control Study

Group, 1993). 2

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Controversy exists regarding whether myopic individuals have higher intraocular

pressures than non-myopic individuals (Bengtsson, 1972; David, et aL, 1985), but myopic

individuals may be more susceptible to the glaucomatous changes associated with higher

intraocular pressures. Approximately 33% of myopes with ocular hypertension had

glaucomatous visual field defects, compared to only 5% of age-matched ocular

hypertensive emmetropic patients and 2.5% of the hyperopic patients (Perkins and

Phelps, 1982).

Controlling the progression of myopia in children may therefore provide a variety of

benefits to subjects, ranging from improved comfort to decreased risk of sight-threatening

problems.

Methods of Myopia Control

Several methods of myopia control have been investigated: bifocal spectacles,

cycloplegic eye drops, intraocular pressure-lowering agents, specific muscarinic

antagonists, and rigid gas permeable contact lenses.

For over half of a century, bifocal spectacles have been prescribed for children to

slow the progression of their myopia (Wick, 1947). Two theories for the potential

treatment effect ofbifocal spectacles exist:

1) Bifocals reduce accommodative demand, and/or

2) Bifocals reduce retinal blur due to insufficient accommodative response.

The first theory is based on the assumption that accommodation causes the

development or progression of myopia. Several studies have reported an association

between myopia and visual near work activity (Adams and McBrien, 1992; Saw, et al.,

3

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1999; Young, et aL, 1969). If the accommodative demand causes myopia, then the

accommodative relief provided by bifocal spectacles or the accommodative paralysis

caused by cycloplegic eye drops should slow the progression of myopia.

The second theory hypothesizes that myopia can be induced by retinal image blur

caused by lag of accommodation. Adolescent monkeys became more myopic when the

visual input to the eye was blurred (Smith, et al., 1994), and myopic children had greater

accommodative lag (Gwiazda, et al., 1993). The greater lag of accommodation exhibited

by myopic subjects may cause sufficient retinal blur to induce myopic eye growth in

children (Irving, et al., 1991; Wildsoet and Walhnan, 1995).

Myopic children with near point esophoria were found to have greater

accommodative lag than other myopic children (Gwiazda, et al., 1999). Assuming that

accommodative lag causes sufficient retinal blur to produce myopia, esophoric children

would be at greater risk for developing myopia. Bifocal spectacles reduce the

accommodative demand and reduce accommodative lag (Hung and Ciuffreda, 2000),

therefore they presumably slow the progression of myopia.

The accommodative lag exhibited by myopic subjects does not precede the onset of

myopia. Instead, accommodative lag may be a result of myopia development (Mutti, et

al., 2002). Furthermore, animal models show that animals with brief periods of clear

vision in a 12-hour day do not develop myopia (Napper, et aL, 1995; Smith, et al., 2002).

This indicates that the retinal blur necessary to cause myopia development may need to

be constant Further investigations into the mechanisms that lead to myopia progression

may be necessary.

4

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Spectacles are commonly prescribed for myopia, and bifocal spectacles minimally

increase the risks and discomfort over single vision spectacles, but the efficacy of bifocal

lenses in treating myopia progression is minimal (Fulk and Cyert, 1996; Fulk, et al.,

2000; Goss and Grosvenor, 1990; Grosvenor, et al., 1987; Jensen, 1991; Oakley and

Young, 1975; Roberts and Banford, 1967). Only three of these studies demonstrated

greater than a 25% treatment effect (Table 1.1). The greatest treatment effect for bifocal

spectacle contact lenses was demonstrated by Oakley and Young (Oakley and Young,

1975). The subjects were all six- to 21-year-old myopic patients reporting to a private

practice. Bifocal spectacles were recommended for all children, but the single vision

spectacle control group consisted of subjects who refused to wear bifocals. Although the

subjects were matched on age and initial refractive error, the potential for bias exists due

to a self-selected sample. Furthermore, a number of the control subjects were not

matched to bifocal wearers based on age or refractive error, and some control subjects

were used more than once for different age groups. These factors, combined with the

authors’ admitted potential for bias, make the results of the study less than conclusive.

Miles reported a nearly 50% treatment effect for bifocal spectacles (Miles, 1962). He

measured the rate of myopia progression in children who wore single vision spectacles

between the ages of six- and 14. All of these children were then fitted with flat-top

bifocal spectacles and followed for two additional years. He compared the progression

rates of the children before they wore bifocal spectacles to the progression rates after they

wore bifocal spectacles. The myopia progression may have slowed simply because the

subjects were older when they wore bifocal spectacles.

5

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Leung and Brown conducted a two-year clinical trial to examine the effects of

progressive addition bifocal spectacles on myopic children in Hong Kong (Leung and

Brown, 1999). Children were assigned to wear single vision spectacles or progressive

addition spectacles with a +1.50 D addition or a +2.00 D addition. The single vision

wearers progressed -1.23 D over two years, whereas the +1.50 D bifocal wearers

progressed -0.76 D and the +2.00 D bifocal wearers progressed -0.66 D over the same

period. The dose-dependent relationship of myopia control and bifocal power is

interesting, but the study has flaws that limit the conclusions that may be drawn.

Although subjects were assigned to treatment groups, the assignment was not random

Alternate subjects entering the study were assigned to wear either single vision or bifocal

spectacles until a sufficient number o f single vision wearers were assigned, then all

remaining subjects were assigned to wear bifocal spectacles. All subjects assigned to

wear bifocal spectacles were given a +1.50 D add until they ran out o f+1.50 D addition

spectacles, then the subjects were given a +2.00 D addition. The primary outcome of the

study was non-cycloplegic manifest refraction, and the examiners were not masked to the

treatment group assignment. The lack of random treatment group assignment, masking,

and objective outcome measures increase the potential for bias in the results.

The most recent clinical trial randomly assigned myopic children with esophoria to

wear bifocal or single vision spectacles. Over a 30-month period, the bifocal spectacle

wearers progressed -1.24 D, compared to -0.99 D for the single vision spectacle wearers

(Fulk, et al., 2000). While the difference is statistically significant, the 20% reduction in

myopia progression may not be clinically meaningful. The Correction ofMyopia

Evaluation Trial (COMET) Study is an ongoing three-year, single-masked, randomized 6

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. clinical trial to examine the effects of progressive addition spectacle lenses on myopia

progression in children (Gwiazda, et al., 2002; Hyman, et al., 2001). Results from this

multi-center study should provide further information on the efficacy of bifocal spectacle

myopia control.

Author Subjects SV BF % Study Design Addition (D) (year) enrolled Rate Rate reduction 6-12 year Fulk (2000) 30-month RCT old myopic +1.50 -0.50 -0.40 20.0 esophores Leung 9-12 year +1.50 PAL -0.62 -0.38 38.2 2-year trial (1999) old myopes +2.00 PAL -0.62 -0.33 46.3 Jensen 7-13 year 3-year RCT -0.65 -0.51 21.5 (1991) old myopes Goss 6-15 year Retrospective +1.00 or + 2.00 -0.46 -0.39 15.2 il.??0) old myopes Parssinen 9-11 year 3-year RCT +1.75 -0.49 -0.62 -26.5 (1989) old myopes Grosvenor 6-15 year +1.00 -0.34 -0.36 5.9 3-year RCT (1987) old myopes +2.00 -0.34 -0.34 5.9 6-17 year Age-, gendcr- Oakley old approximately and refractive -0.53 - 0.02 96.2 (1975) Caucasian +1.50 to +2.00 error-matched myopes Up to 17 Roberts (1967) Retrospective year old unknown -0.40 -0.36 10.0 myopes Miles 6-16 year Crossover trial -0.75 -0.40 46.7 (1962) old myopes RCT - randomized clinical trial PAL - progressive addition lens

Table l.l: Results from bifocal myopia control studies.

7

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Muscarinic antagonists, such as atropine and tropicandde, cause cycloplegia, and they

have been shown to slow the progression of myopia (Bedrossian, 1971; Bedrossian,

1979; Brodstein, et al, 1984; Ghnbel, 1973; Kennedy, et al, 2000; Romano and

Donovan, 2000; Yen, et al., 1989). The efficacy of theses agents is greater than bifocal

spectacles, but the risks may offset the benefits. Muscarinic antagonists bind to

muscarinic receptors and obstruct the effects of acetylcholine. This action results in

mydriasis as well as cycloplegia. Mydriasis may cause photophobia, and cycloplegia

necessitates the use of optical correction for reading. Other potential side effects of

muscarinic antagonists include blurred vision, ocular discomfort, headaches, dryness,

psychological problems, and dizziness (Kennedy, 1995). The discomfort involved with

muscarinic antagonists make them a rarely used treatment option.

8

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Author Subjects Treatment % Agent Control Rate (yew) Stady Design Enrolled Rate Redaction Age-, gender-, 6 -to 15- Kennedy and refractive year-old Atropine -0.35 -0.05 85.7 (2000) error matched myopes 12-year study ll-month comparison of “always 1% atropine -0.18 5 -to 15- +0.07 Romano compliant” nightly with (incompletely year-old (always 138.9 (2000) with +3.00 D or never myopes compliant) “incompletely bifocals compliant) or never compliant” 1% atropine every other -0.91 -0.22 75.8 10-year- night Yen (1989) 1-year RCT old 1% myopes cyclopentolate -0.91 -0.58 36.3 nightly younger than 8- 4-year Brodstein year-old 2dropsof 1% retrospective to older -0.34 -0.12 64.7 (1984) atropine daily control than 18- year-old myopes Two-year 8 -to 13- Bedrossian self-control 1% atropine year-old -0.91 +0.19 120.1 (1979) with daily myopes crossover 5-15 G urbel Self-selected 1% atropine year old -0.41 -0.14 65.9% (1973) 3-year trial nightly myopes Two-year 7 -to 13- Bedrossian self-control 1% atropine year-old -0.95 +0.19 120.0 (1971) with daily myopes crossover RCT - randomized clinical trial

Table 1.2: Results from cycloplegic agent myopia control studies.

9

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The evidence that non-selective muscarinic antagonists slow myopia progression used

to provide support for the role of accommodation in myopia development (Cottriall and

McBrien, 1996; Cottriall, et aL, 1999; Leech, et al, 1995; Rickers and Schaeffel, 1995;

Stone, et al., 1991; Tigges, et al., 1999). More recent studies have shown that the signals

that control eye growth are regulated by retinal signals, and they do not include higher

visual processing centers (McBrien, et al, 1995; Troilo, et al., 1987). Furthermore, the

mechanism of atropine may be non-accommodative (McBrien, et al., 1993; Stone, et al.,

1991). Muscarinic receptor subtypes Mi through M* exist in the retina, and subtypes M2

and M3 exist on the iris and ciliary body (Cottriall and McBrien, 1996; Stone, et al.,

1991). Agents that affect only receptor subtype Mt may have similar effects on myopia

progression as atropine without causing cycloplegia and mydriasis.

Topical preparations of pirenzepine affect only the Mi muscarinic antagonist

receptor, so they may reduce the cycloplegia and mydriasis experienced by children

taking non-selective muscarinic antagonists. Studies on animals have shown the efficacy

of a selective muscarinic antagonist at slowing myopia progression (Cottriall and

McBrien, 1996; Cottriall et al., 1999; Leech, et al, 1995; Rickers and Schaeffel, 1995;

Stone, et al., 1991; Tigges, et al., 1999), and studies on human subjects are underway to

examine the safety and efficacy of the treatment (Bartlett, et al., 2000; Kwon, et al.,

2000).

Other pharmaceutical agents have also been used to slow myopia progression in

children. Ku and Green found that the sclera o f rabbits can reversibly change within

normal intraocular pressure ranges, and higher pressures can result in irreversible axial

elongation (Ku and Greene, 1981). A few studies have also found an association between 10

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. myopia and elevated intraocular pressure or glaucoma (David, et aL, 1985; Quinn, et aL,

1995; Tomlinson and Phillips, 1970), although other studies reported contradictory

results (Bengtsson, 1972; Bonond, et al., 1982). hi theory, drugs that lower the

intraocular pressure decrease the scleral stress induced by higher pressure and reduce the

resultant axial growth. One study found that myopic children with intraocular pressures

greater than 16 mm Hg progressed in their myopia-1.32 Dover two years, and children

with intraocular pressures 16 mm Hg or less progressed only -0.84 D over two years

(Jensen, 1992).

A study of the effects of an intraocular pressure-lowering agent (timolol) on myopia

progression m chicks was recently reported (Schmid, et aL, 2000). Timolol significantly

lowered the intraocular pressure, but there was no difference in the mean (± SD)

refractive error for chickens fitted with diffusers if they received timolol (-26.9 ±3.3 D)

or if they received a control solution (-22.7 ± 9.1 D). The mean ± SD myopia in chickens

after they wore concave lenses was -14.9 ± 3.8 D if they received timolol and -14.9 ±3.6

D if they received a control solution. One study was also conducted on humans to

evaluate the effect of timolol maleate on myopia progression (Jensen, 1991). There was

no difference in the two-year myopia progression rates between subjects receiving

timolol (-1.18 D) and subjects receiving only single vision spectacles (-1.14 D).

The association between myopia and glaucoma that has been reported (David, et al.,

1985; Quinn, et aL, 1995; Tomlinson and Phillips, 1970) does not mean that glaucoma or

high intraocular pressures cause myopia. In feet, one study suggests the association

between myopia and glaucoma can be explained by the feet that myopic patients are

11

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. simply more susceptible to glaucomatous visual field changes (Perkins and Phelps,

1982), so glaucoma may be more readily diagnosed in myopic patients.

Rigid gas permeable contact lenses are a standard treatment option for myopic

patients, and they provide good vision with few side effects. They have also been

associated with slower progression of myopia in children (Baldwin, et al., 1969; Khoo, et

al., 1999; Levy, 2001; Perrigin, et al., 1990; Stone, 1976). Five studies have reported

seminal myopic progression rates, and three o f them show at least a 40% reduction in

myopia progression (Table 1.3). Baldwin conducted a study that found a higher rate of

myopia progression for polymethyl methacrylate (PMMA) contact lens wearers than

spectacle wearers (Baldwin, et al., 1969). This study may have failed to fold a treatment

effect for rigid contact lenses because the subjects in this study self-selected into two

treatment groups. The contact lens wearing group had more females, the subjects were

older, they had steeper comeal curvatures, and they had higher baseline refractive error.

All of these factors are associated with greater amounts of myopia and greater myopia

progression, which may have led to an erroneous conclusion.

The most recent RGP myopia control clinical trial was conducted in Singapore.

Results of the study have not been published, but data presented at the American

Academy o f Optometry meeting in December, 2001 did not show a significant reduction

in myopia progression (Levy, 2001). The rigid contact lens group progressed -1.34 D

over two years, and the spectacle group progressed-1.28 D over the same period (p =

0.55). The axial length of the eye increased 0.83 mm and 0.79 mm for the rigid contact

lens and spectacle wearers, respectively (p = 0.47).The other three studies show at least a

46% reduction in myopia progression. 12

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Rigid Contact Author (yr) Design Spectacles % Reduction Lenses Self-selected Baldwin (1969) -0.59 -0.43 -37.2 cohort Self-selected Stone(1976) - 0.10 -0.35 71.4 cohort Historical Perrigin (1990) -0.16 -0.51 68.6 control 3-year clinical K hoo(1999) -0.42 -0.78 46.2 trial Levy(2001) 2-year RCT -0.67 -0.64 -4.7 RCT - randomized clinical trial

Table 1.3: Results from rigid contact lens myopia control studies.

Rigid gas permeable contact lenses are a standard treatment option for myopia. They

are less noxious than cycloplegic agents, and previous studies suggest they may be more

effective than bifocal spectacles. However, discrepancies in the results of prior studies

and potential confounding factors not controlled for in previous studies warrant further

investigation of RGP contact lenses.

Limitations of Previous Rigid Contact Lens Studies

Previous studies have failed to provide proper attention to many important

confounding variables (Table 1.4). While earlier work produced intriguing results for

scientists and clinicians, previous studies contain many problems that challenge the

significance of their findings. These faults can be summarized in four categories: 1)

13

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. inadequate control group, 2) high losses to follow-up, 3) incomplete ocular component

measurements, and 4) inadequate or poorly selected entry criteria.

CL group Axial length Subjects older Author (year) Control group losses to measurement than 16 years follow-up Levy (2001) Randomized 40% Yes No Khoo (1999) Self-selected 47% Yes No Perrigin (1990) Historical 44% No“ No Stone(1976) Self-selected Unknown No Yes Morrison (1960) None Retrospective No Yes Kelly (1975) Self-selected Unknown No Yes Baldwin (1969) Self-selected 30% Yes No “No 3-year axial length data for the control group CL - contact lens

Table 1.4: Limitations of previous rigid contact lens myopia control studies.

Avoiding Limitations of Previous Studies

The Contact Lens and Myopia Progression (CLAMP) Study examines all of the

problems encountered by previous studies and addresses them in order to provide

meaningful answers to the questions regarding the effect of rigid contact lenses on

myopia progression that cannot currently be definitively answered (Table 1.5).

14

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Previous studies’ problems CLAMP Study solutions Poor retention of subjects Run-in period, soft contact lens control group, enroll subjects with -0.75 D or more myopia Outcome measures not masked to Measurement of the ocular components is treatment group completed by an examiner masked to the treatment group, soft contact lens instead of spectacle control group Inadequate control group After run-in period, patients random ized to experimental or control group Lack of ocular component measurements Measure all ocular components and other factors associated with myopia such as heterophoria, accommodative lag and response, and the gradient AC/A ratio Inadequate assessment of corneal Measure corneal curvature and comeal thickness curvature with videokeratography and keratometry Enrolled subjects after cessation of Restrict age at enrollment to 8-11 years old myopia progression Unwillingness of control group to wear Soft contact lens control group glasses

Table 1.5: CLAMP Study solutions to problems encountered by previous rigid contact lens myopia control studies.

Many studies suffered from differential loss to follow-up between treatment groups

(Baldwin, et aL, 1969; Bier and Lowther, 1988; Perrigin, et al., 1990). Adaptation to the

initial discomfort of rigid contact lenses is more difficult than adjusting to spectacle wear.

Many subjects drop out of the rigid contact lens group due to an inability to adapt to rigid

contact lenses (Grosvenor, et al., 1989), and the lack of data from these subjects

compromises the validity o f the results. For example, younger children are less able to

adapt to rigid gas permeable contact lens wear (Perrigin, et al., 1990; Walline, et al.,

15

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2001). These children are also more likely to progress in myopia at a fester rate (Goss

and Cox, 1985; Goss and Winkler, 1983). Eliminating subjects who were not able to

adapt to rigid contact lens wear would also eliminate subjects whose myopia progressed

faster. The result would be a false impression that rigid contact lenses slow the

progression of myopia, when in reality subjects wearing rigid contact lenses whose

myopia progresses fester were simply lost to follow-up. The CLAMP Study conducted a

run-in period to ensure that subjects were able to adapt to rigid contact lens wear prior to

being enrolled in the study.

The CLAMP Study is the first random ized clinical trial in the United States to

examine the effects of rigid contact lenses on myopia progression in young children. All

previous studies have used self-selected groups of contact lens wearers (Baldwin, et al.,

1969; Kelly, et al., 1975; Stone, 1976), historical control groups (Perrigin, et al., 1990),

or lacked a control group (Morrison, I960).

To decrease the potential for loss to follow-up, the CLAMP Study utilized a unique

control group of soft contact lens wearers. We chose soft contact lens wearers as the

control group without also involving a spectacle group because Homer et al. (1999)

showed that there was no difference in myopic progression for spectacle and soft contact

lens wearers aged 11 to 13 years over 30 months. Using soft contact lens correction for

the control group also helped increase retention, made the study more appealing to the

subjects and their parents, minimized differences in accommodative responses between

the experimental and control groups, and better masked the two groups to the examiners.

It would have been difficult to randomize subjects to a “spectacles only” group after they

determined that they were able to successfully wear contact lenses because subjects may 16

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. have wished to purchase contact lenses and not be compliant in wearing spectacles or

drop out of the study. Soft contact lens wear also minimized the differences in

accommodation and convergence that occur between contact lens wearers and spectacle

wearers. Spectacle wearers are more likely to remove their correction for reading than

contact lens wearers, which afters the accommodative demand at near. Spectacles often

leave marks where they contact the face, which may have identified which treatment

group the subject was in to the masked examiners. Providing the control group with soft

contact lenses instead of spectacles minimized the differences between the two groups.

Positive results in many studies failed to exclude alternate possibilities that may

explain the effect. For example, both the Houston Contact Lens Myopia Control Study

(Perrigin, et al., 1990) and Stone’s study (Stone, 1976) found that rigid contact lenses

slowed the progression of myopia and that comeal flattening accounted for some of the

treatment effect, but neither study was able to definitively answer other mechanisms that

may have retarded myopia progression.

The CLAMP Study measured all of the ocular components, including anterior

chamber and vitreous chamber depth, crystalline lens thickness and curvatures, comeal

curvature and thickness, and cycloplegic refractive error. Topographical analysis was

used to provide a more extensive examination of the changes in corneal curvature due to

rigid contact lens wear.

Thorough measurement of all o f the ocular components will provide greater insight

regarding the potential mechanism of treatment effect and the subjects most likely to

benefit from RGP contact lens myopia control. For example, we will be able to determine

whether rigid contact lenses slow the axial growth of the eye, whether they alter the 17

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. direction of growth of the eye (the eyes become more prolate or more oblate), whether a

sympathetic feedback loop caused by the sensation of rigid contact lenses on the eye may

alter eye growth, or whether accommodative differences between the two groups may

explain the potential difference in refractive error development

Previous studies included subjects older than 16 years of age (Kelly, et al., 1975;

Morrison, 1956). Myopia progression typically slows or ceases at age 15 years for boys

and at 16 years for girls (Goss and Winkler, 1983). Inclusion of subjects older than 15 or

16 years may have confounded the results because subjects could be more likely to

naturally slow myopia progression regardless of treatment which could lead to

misleading results.

A critical review of the limitations of rigid contact lens myopia treatment studies

enabled the CLAMP Study to avoid the pitfalls encountered by previous RGP contact

lens myopia control studies. Correcting the problems helped us to provide more definitive

answers to the following questions:

1) Do rigid gas permeable contact lenses slow the progression of myopia in children?

2) What is the mechanism of treatment effect, if one exists?

3) What subjects are most likely to benefit from the potential treatment effect?

18

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 2

METHODS

The Contact Lens and Myopia Progression (CLAMP) Study is a single masked,

randomized clinical trial to examine the effects of daily wear rigid gas permeable contact

lenses on myopia progression in children. Following a run-in period to exclude children

who were not able to adapt to rigid gas permeable contact lens wear, 116 subjects were

randomly assigned to wear rigid gas permeable contact lenses (Menicon Z, Menicon

USA, Clovis, CA; now available from Con-Cise, San Leandro, CA) or two-week

disposable, daily wear soft contact lenses (Focus, CIBA Vision Care, Atlanta, GA). The

refractive error and ocular components were measured annually for three years, but this

dissertation will only report results after one year of follow-up.

This chapter discusses the rationale for choosing the particular outcomes and provides

a brief description of the methods. For a detailed description of the outcome measure

methods, see Appendix A.

19

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Eligibility

The inclusion and exclusion criteria for enrollment in the CLAMP Study are listed in

Table 2.1.

Inclusion Criteria Age Eight to eleven years old at the randomization visit Myopia -0.75 D to -4.00D spherical component, inclusive, each eye by cycloplegic autorefraction Visual Acuity 20/20 or better in each eye Exclusion Criteria Astigmatism Greater than 1.50 DC in each eye by cycloplegic autorefraction or greater than 1.00 DC on manifest refraction Contact Lenses Previous or attempted history of contact lens wear Anisometropia Greater than 1.00 D difference (spherical component) between the eyes Ocular Health Eye disease and binocular vision problems (e.g., strabismus, amblyopia, oculomotor nerve palsies, corneal distortion, etc.) Systemic Health Systemic disease that may affect vision or vision development (e.g., diabetes, Down syndrome, etc.)

Table 2.1: Inclusion and exclusion criteria.

The rationale for the eligibility criteria are provided below:

Age: The minimum age was chosen because many younger children may not be able to

handle the responsibilities of contact lens care. The maximum age ensures that subjects 20

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. will be less than IS years old at the conclusion of the study. Children younger than IS

years are expected to still be progressing in myopia (Goss, 1987).

Myopia: The minimum amount of myopia (-0 .7 5 D) was used because children with less

myopia are not as motivated to wear contact lenses (Perrigin, et al., 1990). The upper

limit (-4.00 D) was used to reduce the potential for enrolling children with pathological

myopia and to protect against refractive error imbalance between the two treatment

groups due to extreme outliers in a relatively small sample.

Visual Acuity: The requirement o f20/20 vision or better in both eyes was used to

include only children free of amblyopia and other ocular anomalies that may affect

vision.

Astigmatism: Subjects could not have astigmatism greater than 1.50 DC by cycloplegic

autorefraction o r greater than 1.00 DC by manifest refraction. This level of astigmatism

was chosen so that subjects randomized to wear soft contact lenses would not have

unacceptable visual acuity due to uncorrected astigmatism.

Despite calibration, cycloplegic autorefraction occasionally yielded cylinder readings

that were far greater than those detected on manifest refraction. A potential subject

occasionally had excellent visual acuity with little or no cylinder, but cycloplegic

autorefraction yielded more than 1.00 D cylinder. In order to keep from unnecessarily

making these subjects ineligible, only subjects with astigmatism greater than either

criterion were excluded from the study.

Contact Lenses: Previous contact lens wear was an exclusion criterion in order to ensure

that subjects’ myopia progression was not previously affected and to reduce the potential

for enrolling unsuccessful contact lens wearers. 21

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Anisometropia: Subjects with a difference of greater than 1.00 D in the spherical

component between the two eyes were excluded because anisometropic individuals may

have had accommodative characteristics that differed from individuals without

anisometropia, which could have altered myopia progression.

Ocular and Systemic Health: Subjects affected by ocular or systemic health problems

were excluded from the study to ensure that vision or visual development were not

affected by factors unrelated to normal ocular growth.

Informed Consent and Human Subjects

Prior to determination of eligibility, parents provided informed consent for all

children. Children were also invited to provide informed assent. The Biomedical Sciences

Institutional Review Board at The Ohio State University approved the protocol.

Visits

Eight- to eleven-year-old children attended a baseline visit to determine eligibility for

the CLAMP Study. A comprehensive eye examination and rigid contact lens fitting were

performed at this visit, and subjects and their parents completed a survey regarding the

amount of time the subjects spent performing near work activities. The comprehensive

eye examination included the outcome measures listed m Table 2.2.

22

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Outcome measure Instrument Visual acuity Bailey-Lovie visual acuity chart, standardized protocol Comeal topography Humphrey ATLAS Comeal Topographer Comeal thickness* ORBSCAN Anterior Segment Analysis System Comeal curvature Bausch & Lomb Keratometer Accommodation Canon R-l Autoref Intraocular pressure Tonopen Cycloplegic refractive error Canon R-l Autoref •Not available at the beginning of the study

Table 2.2: Outcome measures performed at the baseline visit.

Eligible subjects were scheduled for a dispensing visit one to two weeks after the

baseline visit to teach insertion, removal, and care of rigid contact lenses and to assess the

vision with the contact lenses and fit of the contact lenses. Subjects and parents also

repeated the near work surveys at this visit

One week after the contact lens dispensing, patients were examined to assess the

vision, fit and comfort with rigid contact lens wear. Subjects and their parents also

completed surveys regarding rigid contact lens wearing time and comfort at that visit.

One month or more after the baseline visit subjects and their parents completed the

contact lens survey to determine wearing time and comfort of the rigid contact lenses.

Subjects who met the criteria for successful completion of the run-in period (Chapter 3)

were randomly assigned to wear rigid gas permeable contact lenses or soft disposable

23

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. contact lenses for the remainder of the three-year study. The outcome measures listed in

Table 2.3 were performed on all subjects at the randomization visit.

Outcome measure Instrument Visual acuity Bailey-Lovie visual acuity chart, standardized protocol Comeal topography Humphrey ATLAS Corneal Topographer Corneal thickness ORBSCAN Anterior Segment Analysis System Corneal curvature Bausch & Lomb Keratometer Accommodation Canon R-l Autoref Intraocular pressure Tonopen Cycloplegic refractive error Canon R-l Autoref Retinal contour Canon R-l Autoref Crystalline lens curvatures Video phakometer Axial dimensions Humphrey model 820 Ultrasound Biometer

Table 2.3: Outcome measures performed at the randomization visit.

Subjects who were randomly assigned to wear soft contact lenses at the

randomization visit were fitted with two-week disposable, daily wear contact lenses. An

8.8 base curve contact lens with the spherical equivalent manifest refraction was placed

on the right eye of the patient, and an 8.4 base curve contact lens with the spherical

equivalent manifest refraction was placed on the left eye. A slit lamp assessment of the

contact lens fitting was conducted. The flattest contact lens that exhibited a clinically

24

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. appropriate contact lens fit was chosen as the appropriate base curve, and that base curve

was dispensed to the patient in the appropriate powers.

The patients returned one week later for a soft contact lens fit evaluation, and the

subjects and their parents completed the contact lens form. The subjects were instructed

to wear their contact lenses for one more week, to dispose of their contact lenses, and to

wear a new pan* of contact lenses for approximately two weeks. The subjects were

examined approximately one month after the first day of soft contact lens wear.

Standardized visual acuity, slit lamp examination, and contact lens surveys were

completed during the one-month visit.

Comprehensive eye examinations were performed on the subjects annually, using the

date of the randomization visit to establish the subsequent anniversary dates. Subjects and

parents completed both the near work survey and the contact lens survey at each annual

visit. Outcome measures performed at annual visits were similar to the measures

performed at the randomization visit (Table 2.3).

At the six-month interval between annual visits, patients were examined to assess the

vision, fit, and comfort of the contact lenses. Subjects and parents also completed the

contact lens and near work surveys. A flow chart of the examination sequence is shown

in Figure 2.1.

25

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Initial Visit Screen for eligibility and fit rigid contact lenses

Dispense Visit Teach insertion and removal o f contact lenses

One Week Visit Check fit of contact lenses and health of eves

Randomization Visit Randomize and perform outcome measures

RGP 4 - SCL

One Week SCL Visit Check fit o f contact lenses and health of eyes

One Month SCL Visit Check fit o f contact lenses and health of eyes

Six Month RGP Visit Six Month SCL Visit Check fit of contact lenses Check fit of contact lenses and health of eves and health of eves Continue Continue for 3 years Annual RGP Visit Annual SCL Visit I Check fit of contact lenses Check fit o f contact lenses and health of eves and health o f eves

Figure 2.1: Flow chart of CLAMP Study visits.

26

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Primary Outcome Measure

The primary outcome measure for the CLAMP Study was the three-year change in

cycloplegic refractive error measured by autorefraction. Cycloplegia was achieved using

one drop of 0.5% proparacaine followed by two drops of 1.0% tropicamide, separated by

five minutes (Mutti, et al., 1994). Measurements were taken 25 minutes after the second

drop of tropicamide was instilled. Ten spherocylindrical refractions were taken while the

subject fixated 20/30 (6/9) size letters on a nearpoint test card viewed through a +4.00 D

Badal lens. The letters were presented at optical infinity, then moved to a slightly blurred

position to ensure relaxation of residual accommodation. The ten spherocylindrical

refractions were averaged using the power vector analysis described by Thibos (Thibos,

et al., 1997).

Cycloplegic measurement of refractive error has been shown to be more repeatable

than non-cycloplegic refractive error, and cycloplegic autorefraction has been shown to

be more repeatable than retinoscopy or subjective refraction (Walline, et al., 1999;

Zadnik, et al., 1992). The Canon R-l Autoref (Canon, Inc., Lake Success, NY; no longer

manufactured) autorefractor was used to measure refractive error because it has an open

field for fixation. The open field can be used to hold a Badal lens system to position a

trace at the subject’s far point in order to reduce potential accommodation, which may

affect the measurement of refractive error.

27

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Secondary Outcome Measures

Corneal curvature

Three methods were used to measure the corneal curvature of the subjects in the

CLAMP Study. Comeal curvature was measured with the Bausch & Lomb Keratometer

(Bausch & Lomb, Rochester, NY) and used to determine the appropriate contact lens

base curve. Two measures of each eye were performed. The power of the steep meridians

and flat meridians from each measure was averaged for each eye. Keratometry allows

comparison with results of previous studies, which all used this method to measure

corneal curvature (Khoo, et al., 1999; Perrigin, et al., 1990; Stone, 1976).

In order to measure the comeal curvature of a more complete area of the cornea,

including a more central curvature than keratometry, we used the Humphrey ATLAS

Comeal Topography System model 990 (Humphrey Instruments, San Leandro, CA). One

measurement with a “High Confidence” level was recorded for each eye. The Humphrey

topographer provides a map of the cornea out to approximately 4.0 mm from the corneal

apex in all directions.

The ORBSCAN Anterior Segment Analysis System (Bausch & Lomb, Rochester,

NY) also measured comeal curvature. The ORBSCAN instrument uses slit scan

technology to provide corneal curvature and elevation data. The repeatability of central

corneal curvature data of the ORBSCAN Anterior Segment Analysis System was

significantly worse than the repeatability o f the Humphrey ATLAS Corneal Topographer

(Walline, et al., 2000b), so this will not be used as the primary comeal topography data

28

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Corneal thickness

The slit scan technology of the ORBSCAN Anterior Segment Analysis System

(ORBTEK, Inc., Salt Lake City, UT) allowed us to obtain a topographical map of the

posterior corneal surface. Comparison of the anterior and posterior corneal surface

elevation maps allowed calculation o f comeal thickness across the entire cornea with one

reading. The repeatability of the ORBSCAN Anterior Segment Analysis System was

shown to be as good as optical or ultrasound pachometry measures (Marsich and

Bullimore, 2000). Furthermore, optical and ultrasound pachometry measures only allow

thickness readings of one area of the cornea per reading, but the Orbscan allows a

complete profile of comeal thickness.

Three attempts were made to obtain an image without receiving a warning from the

device for too much eye movement. If the warning was obtained on all three attempts, the

next image deemed “acceptable” by the operator was stored for analysis. “Acceptable”

was defined as a relatively complete map with a topography pattern that approximated a

normal cornea.

The ORBSCAN Anterior Segment Analysis System was not available at the

beginning of the study. Data on corneal thickness prior to wearing contact lenses were

available for only 60 subjects. When we began to use the ORBSCAN Anterior Segment

Analysis System, we accepted the first image with complete data even if we received the

warning for too much eye movement We did not make three attempts to obtain an image

without receiving a warning for too much eye movement until it was discovered that

images obtained without the warning yielded better repeatability (Walline, et al., 2000b).

29

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Retinal contour

Measurement of the retinal contour allows us to estimate the shape of the eye and

whether the growth was greater m the axial dimension or the equatorial dimension.

Myopic subjects tend to have eyes with axial lengths that are greater than equatorial

diameters (prolate) (Mutti, et al., 2000). Hyperopic subjects have eyes that have greater

equatorial diameters than axial lengths (oblate), and emmetropic subjects have more

balance between the two dimensions than the ametropic groups (Mutti, et al., 2000).

Measurement of the spherical equivalent refractive error in primary gaze compared to

the spherical equivalent refractive error, measured while the eye fixates 30 degrees

temporal, gives a good indication of the shape of the eye (Dunne, 1995). Myopic subjects

tend to have spherical equivalent refractive errors that are relatively more hyperopic in

temporal gaze, and hyperopic and emmetropic subjects typically have spherical

equivalent refractive errors that are more myopic in temporal gaze. The change in

spherical equivalent refractive error has been shown to be consistent in nasal and

temporal gazes (Millodot, 1981; Rempt, et al., 1971). While more eccentric gaze provides

a more accurate picture of the shape of the eye, a 30 degree gaze is the most feasible

angle measured by the Canon R-l because it is eccentric enough to discriminate

differences between the refractive error groups (Millodot, 1981).

Measurements were made while the subject was cyclopleged Subjects fixated a

reduced Snellen target through a +4.00 D Badal lens in primary gaze. Ten measurements

of each eye were made according to the standard protocol for cycloplegic autorefraction.

The track holding the Snellen target was rotated 30 degrees and the subject viewed the

target through a mirror by rotating the eyes while holding the head still. At least five 30

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. autorefraction measurements were made. The readings were hand-edited to eliminate

spurious readings (Appendix B). The spherical equivalent of the mean refraction in

primary gaze was subtracted from the spherical equivalent of the average refraction in

temporal gaze to yield the peripheral autorefraction (Mutti, et al., 2000).

Axial Dimensions

The Humphrey Ultrasonic Biometer model 820 was used to measure anterior

chamber depth, lens thickness, and axial length. Vitreous chamber depth was calculated

by subtracting the anterior chamber depth and the lens thickness from the axial length. A

hand-held probe was used to measure the length of the eye through a dilated pupil. Traces

were visually examined for equal lens peaks and properly marked retinal peaks. Poor

traces were replaced as they appeared or after five recordings were made. The dimensions

were calculated as the average of the five readings.

Crystalline Lens Parameters

The anterior and posterior curvatures of the crystalline lens were measured using

video ophthahnophakometry. Purkinje images I, m , and IV were produced using a

collimated, dual fiber optic fight source separated by a ten-degree angle at the eye and 20

degrees from the axis of the camera. Subjects fixated a red fight-emitting diode while the

Purkinje images were recorded on videotape. The video images were analyzed later using

Image Analyst version 8.1 (Acuity Imaging, Nashua, NH). The software determined the

center of each Purkinje image and measured the distance between the two centers. The

separation of the two Purkinje images was translated to an equivalent mirror radius using 31

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. calibration curves obtained from a series of steel ball bearings ranging in diameter from

11.91 to 5.96 mm. The curvatures in the eye were calculated by converting the equivalent

mirror radii to radii of curvature within the eye by paraxial ray tracing using ocular

dimensions from the axial dimensions, the refractive error, and the Purkinje images

(Mutti, et al., 1992).

Surveys

We surveyed the subjects and their parents regarding near work activities and contact

lens information. The subjects’ surveys can be read in Appendix B. Subjects and parents

completed the surveys according to the schedule in Table 2.4.

Near Work Contact Lens Baseline X Dispense X 1 week RGP check X Randomization X X 6 month X X 12 month X X 18 month X X 24 month X X 30 month X X 36 month X X

Table 2.4: Schedule of surveys completed.

32

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Masking

The Contact Lens and Myopia Progression (CLAMP) Study is a single-masked,

randomized clinical trial. In a clinical trial, masking is necessary to improve the

objectivity o f the data collection and to decrease the potential for treatment bias.

Treatment bias could obscure a treatment effect or it could create the impression that a

treatment effect exists when one truly does not.

Examiners masked to treatment group assignment measured the primary outcome and

most of the secondary outcome measures. One examiner (JJW) was not masked to

treatment group and performed all clinical measures while subjects wore contact lenses.

Masked and unmasked measures are listed in Table 2.5.

Masked Unmasked Corneal topography Visual acuity Corneal thickness Accommodation Keratometry Intraocular pressure Cycloplegic autorefraction Retinal contour Crystalline lens parameters Axial dimensions

Table 2.5: Masked and unmasked outcome measures.

33

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Control Group

We chose soft contact lens wear as the control without also involving a spectacle

group because Horner et al. (1995) showed that there was no difference in myopic

progression between spectacle and soft contact lens wearers aged 11 to 14 years over

three years (Horner, et al., 1999). The spectacle wearers progressed (mean ± standard

deviation) -0.91 ± 0.19 D, and the soft contact lens wearers progressed -1.07 ± 0.20 D

(no statistical test or p-value given).

Using soft contact lens correction for the control group also helped increase retention,

made the study more appealing to the subjects and their parents, minimized differences in

accommodative responses between the experimental and control groups, and better

masked the two groups to the examiner.

It would have been difficult to randomize subjects to a “spectacles only” group after

they determined that they were able to successfully wear rigid contact lenses during the

run-in period. Subjects might have purchased contact lenses and might not have been

compliant in wearing spectacles or dropped out of the study. Soft contact lens wear also

minimized differences in accommodation and convergence that occurred between contact

lens wearers and spectacle wearers. Spectacle wearers might have been more likely to

remove then correction for reading than contact lens wearers, which would alter the

accommodative demand at near. Spectacles often leave marks where they contact the

face, which may have identified which treatment group the subject was in to the masked

examiners. The differences between the two groups were minimized with a control group

wearing soft contact lenses.

34

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Randomization

We used block randomization to ensure treatment groups with equal gender

representation. The blocks were formed corresponding to the chronological order the

subjects entered the trial.

Two large envelopes were marked “male” or “female”. Twenty-five medium

envelopes were consecutively numbered 1 through 25 and placed in each large envelope.

Inside each medium envelope were three small envelopes with “A”, “B”, or “C” The

treatment group allocation for each subject was sealed in the small envelopes and was not

visible from the outside. The treatment groups were designated as follows:

R = Rigid contact lens group

S = Soft contact lens group

Treatment group designation blocks consisted of one of the eight combinations shown

in Table 2.1. Each of the 25 medium envelopes contained 3 treatment group designations.

Rachel Watson, Study Coordinator, recorded the envelope numbers and the treatment

group designation combination for data control.

When the subject reported for randomization, the medium envelope that had the

lowest number was opened, or the already open one was used. The small envelope in the

open medium envelope with the first remaining letter in the alphabet was used A paper

clip was placed on the medium envelope that was opened to signify the opened envelope.

The result of the randomization was recorded on the Randomization Form and in the 1

and 2 Month Unmasked Form.

35

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. A B C AB c RRR S s s RRS S s R R S R s R S R S S S R R

Table 2.6: The CLAMP Study treatment group designation combinations.

0 0 0 0 0 0 I I I

1-25 1-25

Male Female

Figure 2.2: CLAMP Study block randomization treatment group allocation scheme.

36

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Sample Size Considerations

The primary outcome for the CLAMP Study is the three-year change in refractive

error. Based on previous literature, we expect myopic children to progress by an average

of-l.SO D over a three-year period (Braun, et al, 1996; Goss and Winkler, 1983;

Parssinen, 1993; Perrigin, et al., 1990). The Houston Study showed that 4/50 (8%) of the

rigid contact lens wearers progressed more than -1.50 D over three years, compared to

8/20 (40%) for the spectacle-wearing control group. Using these values, we have 90%

power (a = 0.05) to detect this difference between the proportion of rigid and soft contact

lens groups progressing -1 .50 D over a three-year period with a sample size of 50

subjects per treatment group. That sample size also provides 90% power (a = 0.05) to

detect a difference of 0.50 D in the three-year progression between the treatment groups.

Estimating a 10% loss to follow-up, our goal was to recruit at least 55 subjects per

treatment group.

Contact Lens Fitting

The rigid gas permeable contact lenses were fitted to achieve central alignment. The

contact lenses were 9.2 mm in diameter with a 7.8 mm optic zone. The material of the

contact lenses was Menicon Z (Dk = 163-250), and the children were given Claris

solutions (Menicon USA Clovis, CA). Subjects randomly assigned to wear soft contact

lenses were fitted with Focus two-week disposable contact lenses, and they were given

SOLO Care multi-purpose solutions (CIBA Vision Care, Duluth, GA).

The initial prescription for the contact lenses was determined from the latest manifest

refraction. The spherical component of the manifest refraction was ordered as the power 37

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. for rigid contact lenses, and the spherical equivalent of the manifest refraction was used

for the power of the soft contact lenses. At each subsequent visit, the appropriate power

for the contact lens prescription was determined from a spherical over-refraction.

The initial base curve of the rigid gas permeable contact lens was chosen according to

the keratometry readings and Table 2.7.

Corneal Toricity Base Curve Spherical 0.50 D flatter than flat K Up to 0.75 D toricity 0.25 D flatter than flat K 0.87 D to 1.37 D Fit on flat K > 1.50 D toricity 0.33 times the toricity steeper than flat 1C

Table 2.7: Guide to determine the base curve from keratometry readings.

The unmasked examiner (JJW), determined the changes in prescriptions, using patient

complaints and improvement in visual acuity as the primary indicators. Adjustments in

the base curve of the rigid gas permeable contact lenses had to be approved by a clinician

not involved in routine patient care during the CLAMP Study. Children were examined

between study visits for specific problems and treated by the unmasked examiner (JJW).

38

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. No rules for discontinuation and resumption of contact lens wear were stated; each was

determined as clinically appropriate for the specific case.

Data Safety Monitoring Committee

The Data Safety Monitoring Committee (DSMC) consists of the Principal

Investigator (Jeffrey J. Walline, OD MS), the Mentor (Karla Zadnik, OD PhD), a

Consultant (Donald O. Mutti, OD PhD), and an independent member (David A. Goss,

OD PhD). The DSMC monitors the results of the study to ensure that one treatment group

does not benefit significantly more than the other, or that one group is not harmed more

than the other. The DSMC also approves all manuscript proposals, protocol amendments,

and issues related to conduct of the study.

Incentives for Participation

Children were encouraged to continue participation in the CLAMP Study by

receiving free contact lenses and solutions, a $125 credit toward spectacle frames, free

spectacle lenses, and free eye care throughout the study. Children who were able to

successfully complete the run-in period were allowed to choose a Beanie Baby (Ty,

Oakbrook, IL). Insulated lunch bags with the CLAMP logo were given to the children

who completed one year in the study, “Brutus Buckeye” key chains and “CLAMP Study”

mechanical pencils were given to children who completed two years in the study, and

“Happy CLAMPer” t-shirts were given to children who completed three years.

39

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Intent-To-T rest Analysis

Subjects may switch treatment mode, or they may refuse to wear a contact lens

correction during the trial. Statistical analyses could be performed according to the mode

of correction that the subject is wearing at the time of analyses, according to the mode of

correction that had been used most often prior to analyses, or according to the treatment

group the subject was originally assigned. The latter type of analysis is called intent-to-

treat analysis, and it is the basis o f the “gold standard” statistical analysis methods for

clinical trials.

Random treatment assignment is used to evenly distribute potential confounders

among the treatment groups, in order to reduce the chance of bias in the results.

Analyzing results with subjects in treatment groups other than the ones that they were

assigned to may increase the chance of confounding by unevenly distributing measured

or unmeasured variables among the groups. Intent-to-treat analysis analyzes data

according to the treatment groups that subjects were originally assigned to so it decreases

the potential for bias (Peduzzi, et aL, 1991).

Data Entry and Statistical Analyses

All data were dual-entered into Epi Info 6 (Center for Disease Control & Prevention,

Atlanta, GA) or Microsoft Excel (Microsoft Corporation, Seattle, WA). Matching double

entries were required prior to output to the final data file. All data were analyzed using

SAS statistical software package (SAS Institute, Inc., Cary, NC) or Microsoft Excel

All analyses are reported for the right eye only. Results that differed for the left eye

are discussed in the text Descriptive statistics are presented as either means and standard 40

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. deviations or frequencies, depending on whether the data were continuous or categorical

in nature. Continuous variables were compared using a paired t-test or a Student’s t-test,

and categorical variables were analyzed using either Chi-square or the Fisher’s exact test

Stepwise logistic regression was performed to determine the factors that predict

successful rigid gas permeable contact lens wear.

41

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 3

RUN-IN PERIOD

Introduction

A run-in period is a time of observation prior to randomization during which potential

subjects can be screened for compliance with a treatment regimen. A run-in period can

increase the proportion of compliant patients participating in a trial, decrease losses to

follow-up, improve the statistical power of a study, and allow investigators to assess the

outcome measures prior to randomization (Davis, et al., 1995; Lang, 1990; Lang, et al.,

1991). However, run-in periods may also limit generalizability, increase the length of the

stucfy, and reduce the sample of eligible subjects (Hudmon, et aL, 1997). The advantages

and disadvantages of a run-in period must be considered prior to implementation in a

clinical trial.

The CLAMP Stuffy utilized a run-in period to reduce the potential for unequal loss to

follow-up suffered by previous rigid gas permeable (RGP) contact lens myopia control

studies (Khoo, et al., 1999; Perrigin, et al., 1990).

Initially, rigid gas permeable contact lenses are less comfortable than soft contact

lenses, but the long-term comfort is comparable (Form, et al., 1995; Form and Holden, 42

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1988). Today’s patients often demand immediate satisfaction with products, so the initial

lid sensation with rigid gas permeable contact lenses often affects the ability of patients to

adapt to rigid contact lens wear. This may have an effect on the satisfaction of patients

and then* willingness to continue in a study o f rigid gas permeable contact lenses

compared to treatments with better initial comfort, such as soft contact lenses or glasses.

For example, a rigid gas permeable contact lens myopia control study reported that

100 myopic children eight to 13 years old were fitted with rigid gas permeable contact

lenses (Perrigin, et al, 1990). After three years, 44 subjects were not wearing their

contact lenses: 17 subjects were not able to adapt to rigid gas permeable contact lens

wear, 13 subjects initially adapted to rigid contact lens wear but later dropped out

because of discomfort or lack of motivation. Six subjects moved from the area, and eight

subjects failed to respond to telephone calls or letters.

A study conducted in Singapore reported that 10S ten- to twelve-year-old children

were fitted with RGP contact lenses. Out of the 105 children, 49 dropped out of the study.

Ten wore contact lenses only intermittently, and one moved from the area in a three-year

period. Out of the 49 who dropped out of the study, 20 said they dropped due to poor

comfort, and the rest said that they did not have time to care for their contact lenses.

Results of the two studies show that one-fifth to one-third of children were lost to follow-

up due to rigid gas permeable contact lens discomfort

The absence o f data from subjects who drop out of a study may compromise the

validity o f the results (Britton, et al., 1999). For example, age is related to myopia

progression and to contact lens tolerance. Young children are typically less motivated to

wear rigid gas permeable contact lenses than older children (Perrigin, et al., 1990; 43

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Walline, et al., 2001), and progression is more rapid at younger ages (Goss, 1987; Goss,

1990). Therefore, dropouts by young myopes could lead to the illusion that myopia

progression was slowed in RGP contact lens wearers when, in reality, the fast-

progressing RGP subjects were just lost to follow-up.

We enrolled 147 eligible subjects in the run-in period according to the inclusion and

exclusion criteria of the CLAMP Study (Chapter 2). Successful adaptation to rigid

contact lens wear was defined by the subjects’ report of at least 40 hours of wearing time

per week and contact lenses that were “always comfortable” or “usually comfortable.”

Subjects who reported good comfort but had not worn contact lenses for at least 40 hours

during the week prior to the randomization appointment were re-scheduled and told to

wear their contact lenses more regularly. Subjects were allowed one more visit

(approximately one month later) to build-up sufficient wearing time to be enrolled in the

clinical trial. Demographic and ocular characteristics information was collected at the

baseline visit, and subjects completed survey data at the contact lens check visit.

Results

Subjects who successfully completed the run-in period are referred to as “Adapters”,

and subjects who did not successfully complete the run-in period are referred to as “Non-

adapters.” Demographic information for the two groups is presented in Table 3.1. Boys

and girls were able to adapt to rigid gas permeable contact lens wear equally, and there

was no effect of ethnicity. However, adapters were, on average, 8.5 months oldet than

non-adapters. 44

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Adapters (n = 116) Non-adapters (n = 31) P value Age (years) 10.5 ±1.1 9.8 ± 1.5 0.005 Gender (% female) 59.5 58.1 0.88 Ethnicity (% Caucasian) 84.5 90.0 0.57

Table 3.1: Demographic characteristics of subjects eligible to participate in the CLAMP Study run-in period (mean ± SD unless stated otherwise).

Of the 147 subjects enrolled in the run-in period, 116 (78.9%) of the subjects were

able to adapt to rigid gas permeable contact lens wear. All non-adapters were unable to

wear the contact lenses for at least 40 hours per week except one subject who wore the

contact lenses for at least 40 hours per week, but reported that the contact lenses were

“always uncomfortable”. Approximately half of the non-adapters (16/31) did not report

for the contact lens check visit to complete surveys (Table 3.2).

45

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Visit Adapters n Non-Adapters n Contact Lens Dispense 11 (4-42) 116 12 (8-30) 31 Contact Lens Check 21 (12-140) 114 23 (14-90) 15 Randomization Visit 56(28-291) 116 N/A N/A N/A — not applicable

Table 3.2: Median (range) days between the baseline visit and follow-up visits.

The only ocular component that differed significantly between adapters and non­

adapters was astigmatism (Table 3-3). The adapters had an average Joo f 0.04 ± 0.2S D

with-the-rule astigmatism, whereas the non-adapters had an average Jo of 0.11 ± 0.22 D

against-the-rule astigmatism. The difference between adapters and non-adapters was not

significant for the left eye; the adapters had an average Joof 0.10 ± 0.21 D with-the-rule

astigmatism, and the non-adapters had an average Joof 0.01 ± 0.24 D with-the-rule

astigmatism (Student’s t-test, p=0.04).

46

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Adapters ______Non-adapters P vahic M(D)______-2.37 ±0.88 ______-2.11 ±0.80 ______0.13 Jo(D ) +0.04 ± 0.25 -0.11 ±0.22 0.002 *45 (D) +0.03 ±0.16 +0.01 ±0.17 0.60 Steep Keratometry (D) 44.49 ± 1.24 44.45 ±1.29 0.86 Flat Keratometry (D) 43.78 ± 1.24 43.76 ± 1.36 0.94 JoResidual Astigmatism (D) +0.38 ±0.42 +0.23 ±0.48 0.08 J45 Residual Astigmatism (D) +0.02 ±0.17 +0.01 ±0.17 0.70

Table 3.3: Mean ± SD ocular characteristics of subjects eligible to participate in the run- in period.

There was no significant difference between the two groups in terms of the subjects’

reports of contact lens handling, vision, or comfort The two groups reported that they did

not have problems handling their contact lenses 80 to 90 percent of the time (Table 3.4).

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Adapters Non­ Question/response(p value) (n=110- adapters 113) (UF14-15) How do the contact lenses feel in your eyes?(0.19) I never fed than when they are m my eyes 11.7 0.0 I fed them right when I put them in but I can’t fed them alter a while 49.6 42.9 I sometimes fed them in my eyes during the day 36.0 42.9 I always fed them until I take them out o f my eyes 2.7 14.3 How would you rate the comfort of your contact lenses?(0.S9) Always comfortable 27.6 13.3 Usually comfortable 67.0 80.0 Usually uncomfortable 5.4 6.7 Always uncomfortable 0.0 0.0 How is your vision when yon wear contact lenses?(0.18) I can’t read the board at school at all 0.0 0.0 I can’t read the board at school very well 0.1 0.0 I can see almost everything I want to see 8.0 20.0 I can see very well 71.4 80.0 I can see better than everybody dse 19.5 0.0 How often do yon Uke to wear contact lenses?(0.01) I never like to wear my contact lenses 1.0 0.0 1 don’t like to wear my contact lenses most of the time 1.7 13.3 I like to wear my contact lenses sometimes 9.8 26.7 I usually like to wear my contact lenses 40.2 26.7 I always like to wear my contact lenses 47.3 33.3 Do yon like contact lenses or glasses better? (0.12) I like glasses a lot better than contact lenses 1.8 0.0 I like glasses a little better than contact lenses 4.5 19.9 I like glasses and contact lenses the same 19.1 26.7 I like contact lenses a little better than glasses 17.3 26.7 I like contact lenses a little better than glasses 57.3 26.7 How do yon feel about handling your contact lenses?(0.22) I never have a problem 50.9 40.0 I usually do not have a problem 39.3 40.0 I sometimes have a problem 9.8 20.0 I usually have a problem 0.0 0.0 I never have a problem 0.0 0.0

Table 3.4: Patient-reported contact lens vision, comfort, and handling issues. Missing values or questions with more than one response were not included in the analyses. Only 15 of the 31 subjects who did not adapt to rigid contact lens wear reported for the contact lens visit and completed the survey. A p-value less than 0.008 indicates that the difference between the two means is significantly different (Chi-square or Fisher’s exact test with Bonferroni correction).

48

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. We performed logistic regression to determine the factors that predict RGP contact

lens adaptation. Controlling for age, the final model included astigmatism and amount of

contact lens wear (Table 3.5). Controlling for age and the amount of contact lens wear,

for every 0.25 DC change in J0 astigmatism toward with-the-rule, a child is 1.9 times

more likely to adapt to rigid gas permeable contact lens wear.

Variable O d d s R atio 95 % a Usually or always wears contact lenses (Yes/No) 4.6 1.4-15.3 Change in horizontal or vertical astigmatism (0.25 D) 1.9 1.1 -3 .6 t-~ © 00 Age (years) 1.1 1

Table 3.5. Variables in the final logistic regression model to predict children’s ability to adapt to rigid gas permeable contact lens wear.

We used three subscales from the National Eye Institute Visual Function

Questionnaire (NEI-VFQ) to compare the adapters’ subjective assessment of vision,

general health, and ocular pain to non-adapters’. There was not a significant difference

between the two groups on any o f the subscales, nor was the difference in wearing time

per week statistically significant (Table 3.6). 49

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Adapters Non-adapters p-value (n = 109 or 110) (n = 14 o r 15) Wearing Time (hours / week) 71.3 ±19.1 58.3 ±23.4 0.06 General Health 90.0 ±12.8 95.0 ± 10.4 0.15 General Vision 94.5 ±9.7 94.3 ± 12.2 0.93 Ocular Pain 82.6 ±14.3 80.0 ± 14.0 0.52

Table 3.6: Wearing time and National Eye Institute Visual Function Questionnaire (NEI- VFQ) scores. P-values are for Student’s t-tests.

Figure 3.1 shows the reasons subjects reported that they did not wear their contact

lenses; they were asked to mark all options that apply. Non-adapters reported that they

did not wear contact lenses due to difficulty with insertion (reasons 2 and 7) more often

than adapters. Adapters reported that they did not wear then* contact lenses because they

were afraid they would lose them more often than non-adapters. Only one subject

reported not wearing his or her contact lenses due to poor vision, and the rest of the

reasons for not wearing contact lenses were balanced between the adapters and non­

adapters.

50

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 35%

■ Non-adapters ■ Adapters

1 2 3 4 5 6 7 Reason

Reason 1 - 1 prefer to wear my glasses sometimes Reason 2 - It is too much trouble to put in my contact lenses Reason 3 - My contact lenses are uncomfortable Reason 4 - My vision is poor with contact lenses Reason 5 -1 want to give my eyes a break from contact lenses Reason 6 - 1 am afraid I will lose my contact lenses sometimes Reason 7 -1 don’t have time to put in my contact lenses sometimes

Figure 3.1: Reasons subjects report they occasionally didn’t like to wear contact lenses.

51

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 4

DATA AT RANDOMIZATION

Demographics

Between July 8,1998 and February 26,2000,222 children were examined for

eligibility in the CLAMP Study. O f the 222 children, 147 were eligible to participate in

the run-in period. Refractive error was the primary reason children were not eligible. Of

the 75 ineligible children, the spherical component of the cycioplegic autorefraction was

not myopic enough in 49 (65.3%) and too myopic in 14 (18.7%). Some children were not

eligible due to multiple reasons, so the percentage of subjects who were ineligible due to

various reasons does not add to 100%. Twenty-two subjects (29.3%) were ineligible due

to other reasons such as high astigmatism and strabismus. Of the 147 eligible subjects,

116 successfully completed the run-in period. They were randomly assigned to wear rigid

gas permeable contact lenses (n = 59) or soft contact lenses (n = 57).

52

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 222 Children 75 Children Examined for eligibility Not eligible to participate 14 -Sphere too high • 47 - Sphere too low 15 - Cylinder too high • 2-Strabismus 147 Children • 5 - O th e r Eligible to participate 31 Children I Did not complete run-in period 116 Children Enrolled in the study

57 Children 59 Children Soft contact lenses Rigid contact lenses

Figure 4.1: Subjects eligible to participate in CLAMP Study.

The eligibility criteria limited the children to eight- to eleven-year-olds, so the

average age of the children was 10.7 years. The participants are primarily ten- to eleven-

year-okl white females (Table 4.1).

53

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Median (range) age (years) 10.7 (8.1 to 12.0) Gender (% female) 59.5 Ethnicity (%) American Indian or Alaskan Native 0.0 Asian or Pacific Islander 8.6 Black, not of Hispanic origin 4.3 Hispanic 0.9 White, not of Hispanic origin 84.5 Other 1.7

Table 4.1: Demographic summary of participants in the CLAMP Study.

Refractive Error

At the randomization visit, the mean spherical equivalent refractive error of the two

treatment groups was not significantly different (Table 4.2). The two refractive

astigmatism components (Jo and J45 ) were also similar. Converting the power vector

representations back to spherocylindrical notation, the mean cycloplegic refractive error

for the rigid gas permeable contact lens wearers was -2.06 -0.48 x 083 at the

randomization visit, and the mean cycloplegic refractive error for the soft contact lens

wearers was -2.20 -0.56 x 087.

54

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RGP SCL P M(D) -2.30 ±0.90 -2.48 ±0.86 0.29 Jo(D) -0.23 ±0.24 -0.28 ± 0.20 0.22 J

Table 4.2: Mean ± standard deviation refractive error components for the right eye of the two treatment groups at the randomization visit. There are no significant differences between the two groups (Student’s t-test, p > 0.05).

Ocular Components

There is a not a statistically significant difference between the two treatment groups

for any of the ocular components measured at the randomization visit (Table 4.3). All of

the data shown are for the right eye, but there are no significant differences between the

two treatment groups for the left eye either. The mean logMAR visual acuity with

habitual correction at the randomization visit converts to a Snellen equivalent of 20/20

for the RGP contact lens wearers and the soft contact lens wearers. The mean relative

peripheral autorefraction of the right eye for both groups was +0.61 ± 1.14 D, indicating a

prolate eye shape.

55

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RGP (n = 59) SCL (n = 57) P Visual Acuity- High Contrast logMAR -0.01 ±0.10 -0.01 ± 0.08 0.68 Keratometry Steep Meridian (D) 43.88 ± 1.44 43.92 ±1.15 0.87 Flat Meridian (D) 43.29 ±1.34 43.36 ± 1.12 0.74 Intraocular Pressure Tonopen (mmHg) 17.0 ± 3.8 16.4 ± 3.5 0.42 Corneal Thickness Central Thickness (p) n=60 603 ±37.0 614.7 ±43.3 0.24 Axial Dimensions Anterior Chamber Depth (mm) 3.82 ±0.26 3.76 ±0.33 0.28 Lens Thickness (mm) 3.34 ±0.15 3.39 ±0.16 0.09 Vitreous Chamber Depth (mm) 17.00 ±0.70 16.94 ± 0.62 0.67 Axial Length (mm) 24.16 ±0.74 24.10 ±0.69 0.63 Peripheral Autorefraction Spherical Equivalent (D) +0.79 ±1.17 +0.43 ± 1.09 0.09

Table 4.3: Mean ± standard deviation ocular component dimensions of the right eye for the two treatment groups at the randomization visit (n = 116).

The randomization process was meant to distribute measured and unmeasured

parameters equally between the two treatment groups m order to reduce the potential for

bias, which may affect the results. The primary outcome, cycloplegic refractive error, and

the secondary outcome measures were evenly not significantly different between the two

groups, so conclusions from the CLAMP Study should not be affected by bias.

56

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 5

SUBJECTS, STUDY VISITS, AND SURVEYS

Subjects

A total of 116 subjects were randomly assigned to wear rigid gas permeable (RGP)

contact lenses (n = 59) or soft, deposable contact lenses (n = 57). Subjects returned

approximately six months after receiving their randomization assignment to have then-

contact lens fit checked; parents and subjects also completed surveys about near work

activities and contact lens wear. Approximately one year after being randomly assigned

to a treatment group, subjects reported for a comprehensive examination, including

outcome measures and completion of surveys. One subject randomly assigned to wear

RGP contact lenses did not report for the one year visit; she reported one day before her

two-year anniversary, so the one-year visit was not completed. One subject randomly

assigned to wear soft contact lenses moved out of the area and did not report for the one-

year visit, but he promised to attend the three-year visit

During the first year, a few subjects switched treatment groups or stopped wearing

contact lenses. Two subjects switched from soft to rigid gas permeable (RGP) contact

lenses because their parents thought myopia progression would be slowed by RGP 57

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. contact lenses but not by soft contact lenses. Two RGP contact lens wearers switched to

soft contact lenses because they felt the RGP contact lenses were uncomfortable, but they

still wanted to wear contact lenses. Four subjects (three RGP contact lens wearers and

one soft contact lens wearer) stopped wearing contact lenses (Table S. 1).

RGP SCL Switched treatment groups 2(3.4) 2(3.5) Stopped wearing contact lenses 3(5.1) 1 (1 8 ) Total not wearing assigned treatment 5(8.5) 3 (5.3)

Table S.l: Number (percentage) of subjects not wearing the treatment they were assigned at the one-year visit.

Although subjects switched treatment groups or stopped wearing contact lenses

during the course of the study, we analyzed their data according to the original

randomization assignment in order to decrease the potential for bias (Newell, 1992;

Peduzzi, et al., 1991).

Study Visits

Fifty-eight subjects assigned to the RGP group and 56 subjects assigned to the soft

contact lens group reported for the one-year visit. The average (± standard deviation) 58

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. number of days between the randomization visit and the six-month visit and the one-year

visit for each group is shown in Table 5.2.

RGP Soft P Six-month visit 190 ±15 185 ±44 0.45 One-year visit 397 ± 48 380 ±58 0.09

Table 5.2: Mean ± SD time (days) between randomization and study visits.

The subjects were to be examined at six months and one year within a window of one

month before or after the anniversary date. Table 5.3 shows the proportion of subjects

who were examined within the one-month window at six months and one year.

RGP Soft P Six-month visit 83.1 86.0 0.66 One-year visit 62.7 73.7 0.20

Table 5.3: Proportion (%) of subjects examined within ± 1 month of the anniversary date. There was no difference in the proportion of subjects examined within the window at the six-month visit or the one-year visit (Chi-square, p > 0.05).

59

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Surveys

Subjects and parents completed surveys regarding near work and contact lens-related

information. The Subjects Near Work Form and the Parents Near Work Form (Appendix

B) were completed at the baseline visit, die contact lens dispensing visit, the six-month

visit, and the one-year visit. The Subjects Contact Lens Form and the Parents Contact

Lens Forms (Appendix B) were completed at the one-week RGP visit, the randomization

visit, the six-month visit, and the one-year visit.

We report on the repeatability o f the Near Work Form by both subjects and parents.

We also compare the subjects’ reports to the parents’ reports at the randomization visit,

and we examine differences in near work reports by subjects between the baseline visit

and the one-year visit. We also look at the differences between RGP contact lens wearers

and soft contact lens wearers at the one-year visit.

We compare subjects’ and parents’ responses to parts of the contact lens surveys,

such as wearing tune, ability to handle contact lenses, and preference for glasses or

contact lenses. We also compare RGP contact lens wearers’ reports to soft contact lens

wearers’ reports for the same data and examine changes in these variables over time.

Near Work Surveys

We examined the repeatability of the Subjects Near Work Form and the Parents Near

Work Form by comparing the results of the surveys completed an average of 11.6 days

apart Table 5.4 shows the mean ± standard deviation difference between the two visits

for the five continuous variables. None of the differences were significantly different

from zero (Paired t-test, p > 0.05). 60

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. How many hours per week outside of school do you... Subjects Parents stuffy or read for school assignment? -0.3 ± 9.0 -0 .0 ±4.1 read for pleasure? -0 .8 ± 4.9 -0.1 ±3.1 watch television? -1.3 ±8.8 -0.3 ± 5.6 engage in outdoor/sports activities? 0.2 ±7.8 -0 .4 ± 4.7 play video/computer games? l.0± 5.2 -0 .2 ±2.2

Table S.4: Mean ± standard deviation (hours per week) difference (visit2 - visit 1) in two reports of near work activities separated by 11.6 days for subjects and parents. None of the differences were significantly different from zero with Bonferroni correction for multiple corrections (Paired t-test, p > 0.01). Positive values mean the duration in the second report was longer than in the first report

Subjects completed the Subjects Near Work Form at the baseline visit and at the one-

year visit We compared the reports to see if there were any changes in the subjects’

reported amount of near work from the beginning of the run-in period to the end of the

first year of the study (Table S.S). There were no significant changes in the subjects’

reports of near work activities over that period when the significance level was adjusted

with a Bonferroni correction factor for multiple corrections (Paved t-test, p > 0.01).

61

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. How many hours per week outside of school do Subjects y o n ... (y o r 1 - hwHwr) P study or read for school assignment? (n = 111) -1.6 ±11.9 0.17 read for pleasure? (n = 112) -1 .4 ±6.8 0.03 watch television? (n = 110) -2 .6 ±16.2 0.09 engage in outdoor/sports activities? (n = 111) -1 .4 ±12.6 0.25 play video/computer games? (n = 69) -0.2 ±4.9 0.77

Table S.S: Mean ± standard deviation (hours per week) difference (year 1 - baseline) in subjects’ report of near work activities at baseline and one year. None of the differences were significantly different from zero with Bonferroni correction for multiple comparisons (Paired t-test, p > 0.01). Negative values mean the duration in the baseline report was longer than in the one-year report

At the one-year visit the two treatment groups reported the amount of near work

activities that they performed outside of school (Table 5.6). There was not a significant

difference between the two treatment groups (Student’s t-te st P > 0.05).

62

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. How many hours per week outside of RGP SCL school do yon... P study or read for school assignment? 4.5 ± 3.8 3.8 ± 4 .7 0.38 read for pleasure? 5.1 ± 5.4 3.6 ±4.1 0.11 watch television? 6.7 ±6.8 6.5 ±6.5 0.84 engage in outdoor/sports activities? 7.2 ± 6.6 5.2 ± 4 .9 0.07 play video/computer games? 3.1 ±4.3 2.6 ±3.3 0.54

Table 5 .6 . Mean ± standard deviation (hours per week) report of near work activities by subjects at the one-year visit. None of the reports were significantly different between the RGP contact lens wearers and the soft contact lens wearers (Student’s t-test, p > 0.05).

Contact Lens Surveys

Subjects and parents were asked to report what time the subject usually inserted the

contact lenses and what time the subject removed the contact lenses during the week and

on weekends. Subjects and parents were also asked the number of days during the week

and the number of days during the weekend that subjects typically wore the contact

lenses. From this we calculated the number of hours during a week that contact lenses

were worn. For an example, see Table 5.7.

63

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Survey Question Answer Time insert contact lenses during the week 8:00 AM Time remove contact lenses during the week 9:00 pm Number of days contact lenses worn during the week 4 Time insert contact lenses during the weekend 9:30 AM Time remove contact lenses during the weekend 11:00 PM Number of days contact lenses worn during the week 1 Calculation Answer 13.0 hours per weekday times 4 weekdays 52.0 hours 13.5 hours per weekend day times 1 weekend day 13.5 hours Total 65.5 hours per week

Table 5.7: Example of the calculation of the contact lens wearing time per week (hours).

The subjects reported significantly greater wearing time per week (hours) than the

parents at the randomization visit, but the subjects and parents reported similar times at

the one-year visit. Although the difference is statistically significant at the randomization

visit, the mean difference at each of the visits is only two hours (approximately 2.5% of

the total reported wearing time per week). The mean difference is small enough that we

will report only the subjects’ responses for the remainder of the paper.

64

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Subjects Parents £ Randomization ______80.9 ± 15.9 ______78.8 ± 16.0 ______0.03 One-year______79.1 ±27.3 ______76.8 ± 27.6 ______0.08

Table S.8: Mean ± standard deviation wearing time per week (hours) reported by the subjects and the parents at the randomization and the one-year visits (paired t-test).

Table 5.9 shows that the wearing time per week was not different between the RGP

contact lens wearers and the soft contact lens wearers at the randomization visit

(Student’s t-test, p = 0.52). The RGP contact lens wearers reported less wearing time at

the one-year visit, and the soft contact lens wearers reported an increase in wearing time

per week. The soft contact lens wearers reported significantly greater wearing tune at the

one-year visit (Student’s t-test, p = 0.02).

RGP SCL P Randomization 81.9 ±13.8 80.0 ± 16.0 0.52 One-year 73.5 ±30.3 85.3 ±22.3 0.02

Table 5.9: Mean ± standard deviation wearing time per week (hours) reported by the subjects at the randomization and the one-year visits.

65

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. We compared the subjects’ reports to the parents’ reports of the subjects’ contact lens

comfort at the one-year visit (Table 5.10). The agreement between the subjects and the

parents regarding the subjects’ comfort was “fair” (Landis and Koch, 1977). The subjects

and parents agreed 55.5% of the time. When they didn’t agree, the parents generally

reported poorer comfort ratings than the subjects reported.

How would you rate Parents the comfort o f your Always Usually Usually Always lenses? k = 0.29 comfortable comfortable uncomfortable uncomfortable Always 2ft 19 4 3 comfortable Usually U 7 3ft 5 5 u comfortable T ' " f Usually V3 I 2 2 | i uncomfortable i Always 1 0 1 i uncomfortable

Table 5.10: Agreement between the subjects and the parents regarding the subjects’ contact lens comfort (weighted kappa, k = 0.29).

We asked the subjects and the parents whether they thought the subject preferred to

wear glasses or contact tenses. The subjects and the parents agreed 68.2% of the time,

and they both said that the subjects liked their contact lenses “a lot better than their

66

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. glasses” 54.5% of the time (Table S. 11). The agreement between the subjects and the

parents was “moderate” (Landis and Koch, 1977).

Do you like glasses or Parents contact lenses better? S p e c » CL » Spec > CL Spec = CL CL > Spec k = 0.60 CL Spec Spec » CL 5 1 0 0 1 § Spec > CL I ® 1 1 0 1* Spec = CL 3 2 5 4 I M CL > Spec 0 2 2 5 J 7 CL » Spec I 0 3 5 60

Table 5.11: Agreement between subjects and parents regarding the subjects’ preference for glasses or contact lenses (weighted kappa, k = 0.60).

We also asked the subjects and the parents about the subjects’ ability to handle the

contact lenses. The agreement between the subjects and the parents was “slight” (Landis

and Koch, 1977), as the subjects and parents only agreed 41.8% of the time. Parents were

more likely to report that the subjects “usually had no problems” than were the subjects

(Table 5.12).

67

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Parents UVff UU JUU ICVI flUUUI IHIIUUUg your contact lenses?tc = 0.09 Never have a Usually no Sometimes a problem problem problem Never have a problem 23 27 1 2g o ? Usually no problem 19 25 5 OA Sometimes a problem 1 3 1

Table 5.12: Agreement of the subjects’ and parents’ report of the subjects’ ability to handle contact lenses at the one-year visit (weighted kappa, k = 0.09).

We also compared the RGP contact lens wearers’ and the soft contact lens wearers’

reports of contact lens comfort and handling ability, and the subjects’ report of spectacle

or contact lens preference at the one-year visit (Table 5.13). There was no difference

between the RGP contact lens wearers and the soft contact lens wearers reports.

68

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RGP SCL How would yoo rate the comfort o f your contact Itnacs?n (%) Always comfortable 20 (33.9) 20 (35.7) Usually comfortable 36(61.2) 36(64.3) Usually uncomfortable 2(3.4) 0(0.0) 062 Always uncomfortable 1(1-7) 0 (0.0) Do yon Hke glasses or contact lenses better?n (%) Glasses » Contact Lenses 0 (0.0) 0 (0.0) Glasses > Contact Lenses 2(1.8) 2(3.6) Glasses = Contact Lenses 16 (28.6) 12 (21.4) 0.38 Contact Lenses > Glasses 13 (23.2) 8 (14.3) Contact Lenses » Glasses 25(44.6) 34 (60.7) How do you feel about handling your contact lenses? n (%) Never has a problem ______25 (43.9) ______25 (43.9) Usually no problem ______26 (45.6)______23 (40.4) Sometimes a problem 6(10.5) 8 (14.0) 0.81 Usually a problem 0 (0.0) 1 (18) Always a problem 0 (0.0) 0 (0.0) = — “the same as” » — “a lot better” > — “a little better”

Table 5.13: Comparison of the RGP contact lens wearers’ and the soft contact lens wearers’ reports of contact lens comfort and handling ability, and the subjects’ report of spectacle or contact lens preference at the one-year visit.

The subjects also completed three sub-scales from the National Eye Institute Visual

Function Questionnaire (NEI-VFQ): general health, general vision, and ocular pain. We

compared the three subscale scores at the randomization visit and the one-year visit

between the two treatment groups (Table 5.13). There were no significant differences

69

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. between the RGP contact lens wears and the soft contact lens wearers for any of the NEI-

VFQ subscales at the randomization visit or the one-year visit (Student’s t-test, p > 0.05).

RGP SCL P General health 94.7 ±10.4 90.5 ±10.3 0.44 Randomization General vision 91.1 ± 13.8 93.2 ±13.1 0.86 Ocular pain 83.8 ±17.2 81.3 ±13.3 0.39 General health 90.7 ±13.7 85.9 ±13.2 0.07 One-year General vision 88.4 ±14.3 88.9 ±15.1 0.86 Ocular pain 86.0 ± 18.6 88.0 ±15.2 0.54

Table 5.14: Mean ± standard deviation NEI-VFQ subscales reported by the subjects at the randomization visit.

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 6

REFRACTIVE ERROR CHANGES

The primary outcome of the CLAMP Study is the progression of cycloplegic

refractive error. For each measure of refractive error, ten readings were performed with a

Canon R-l Autorefractor while the subjects were under cycloplegia. Cycloplegia was

achieved by using one drop of 1% tropicamide applied twice to each eye, separated by

five minutes. All sphero-cylindrical readings were converted to three-dimensional vector

quantities using the method described by Thibos (Thibos, et al., 1997).

“M” represents the spherical equivalent o f the refractive error. “Jo” represents the

power of a Jackson crossed-cylinder lens with the axis at 180 degrees. “J45” represents

the power of a Jackson crossed-cylinder lens oriented at 45 degrees. A positive “Jo”

represents whh-the-rule astigmatism, and a negative “Jo” represents against-the-rule

astigmatism. A positive “J45”represents oblique astigmatism oriented with minus

cylinder axis near 45 degrees, and a negative “ J 4 5 ”represents oblique astigmatism

oriented with minus cylinder axis near 135 degrees.

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Spherical Equivalent

While the mean spherical equivalent refractive errors were balanced between the two

treatment groups at baseline (Chapter 4), the mean ± standard deviation progression of

the spherical equivalent refractive error of the right eye was -0.80 ± 0.6S D for the rigid

gas permeable (RGP) contact lens wearers and —1.19 ± 0.53 D for the soft contact lens

wearers (Student’s t-test, p < 0.0005). The data are shown in Figure 6.1.

-5.00 -4.50 - S -4 .0 0 ■ 2 -3.50 « -3.00 • •RGP > •SCL I9 - 2.50 ■ | -2.00 • AS -1.50 ■

- 1.00 Randomization One Year Visit

Figure 6.1: Mean ± standard deviation one-year change in refractive error.

72

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Although the rigid gas permeable contact lenses slowed the progression of myopia

approximately 33%, an inspection of Figure 6-2 shows that not all RGP contact lens

wearers’ myopia progresses slower than soft contact lens wearers’ myopia.

73

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 6.2: Progression o f the spherical equivalent myopia for individual subjects.

74

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Myopia typically progresses at a rate of 0.50 D per year in school age children who

wear spectacles (Goss, 1990; Perrigin, et al., 1990). In our study, 63.8% of the RGP

contact lens wearers progressed in myopia 0.50 D or more, compared to 92.9% of the soft

contact lens wearers (Chi-square, p < 0.0001). The myopia in our sample appears to

progress fester than previous studies of myopia progression performed in the United

States (Grosvenor, et aL, 1987; Perrigin, et aL, 1990).

Figure 6.3 shows that a greater proportion of soft contact lens wearers progressed in

myopia by more than 1.00 D than rigid gas permeable contact lens wearers. Although the

tails of the distributions are similar, a greater proportion o f RGP contact lens wearers

progressed in myopia less than 0.50, and a greater proportion of soft contact lens wearers

progressed in myopia between 1.00 and 1.50 D.

75

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 25

Myopia 0.00 to 0.50 to LOOto 1.50 lo 2.00 or decrease 0.49 0.99 1.49 1.99 more Change in Myopia (D)

Figure 6.3: Number of rigid gas permeable contact lens wearers and soft contact lens wearers who progressed in myopia a specified amount during the first year of the CLAMP Study.

Although RGP contact lens wearers progress more slowly than soft contact lens

wearers on average, a rigid gas permeable contact lens wearer exhibited the greatest

progression over the first year (Table 6.1). A rigid gas permeable contact lens wearer also

had the highest myopia at the end of the first year of the study.

76

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RGP SCL Minimum spherical equivalent myopia at randomization (D) -0.91 -0.72 Minimum spherical equivalent myopia at one year (D) -1.27 -1.44 Minimum change in spherical equivalent (D) +0.12 -0.08 Maximum spherical equivalent myopia at randomization (D) -4.13 -4.00 Maximum spherical equivalent myopia at one year (D) -6.31 -5.58 Maximum change in spherical equivalent (D) - 2.66 -2.39

Table 6.1: Maximum and minimum spherical equivalent refractive error for each group at the randomization visit and the one-year visit.

Astigmatism

The average astigmatism of subjects enrolled in the CLAMP Study was low because

the eligibility requirements were less than 1.00 D by manifest refraction. The mean ±

standard deviation astigmatic components of the subjects at the randomization visit and

the one-year visit are shown in Table 6.2, and there is no difference in J0 or J45 between

the two treatment groups at either the randomization visit or at the one-year visit.

RGP SCL P Randomization Jo (D) -0.23 ± 0.24 -0.28 ±0.20 0.22 One Year J0 (D) -0.19 ±0.25 -0.20 ±0.21 0.67 Randomization J45 (D) +0.06 ±0.17 +0.03 ±0.16 0.28 One Year J45 (D) +0.13 ± .1 7 +0.08 ±0.20 0.15

Table 6.2: Mean ± SD astigmatism components o f the right eye.

77

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. However, the Jo astigmatism component decreased in against-the-rule astigmatism

over the year (paired t-test, p = 0.019), and the J45 astigmatism component increased over

the year (paired t-test, p < 0.0001); these changes were consistent for both groups (Figure

0.5

S ' 0.25 • — ■— RGP JO — «— SCL JO RGPJ45 ■ SCLJ45 -0.25 ■

-0.5 One Year Visit

Figure 6.3: Change in refractive astigmatism of the right eye.

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 7

OCULAR COMPONENT CHANGES

The primary aim of the CLAMP Study is to determine whether there is a difference in

myopia progression between the RGP and soft contact lens wearers. A secondary aim is

to determine the potential mechanism of any treatment effect We measured the ocular

components to shed light on the means by which RGP contact lenses may slow the

progression of myopia.

79

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RGP (n = 59) SCL (n = 57) P Visual A cuity- High Contrast logMAR +0.04 ±0.13 +0.11 ± 0.12 0.0042 Keratometry Steep Meridian (D) +0.39 ± 0.54 +0.64 + 0.52 0.01 Flat Meridian (D) +0.15 + 0.35 +0.42 + 0.37 0.0001 Intraocular Pressure Tonopen (mmHg) -0.48 + 4.56 -0.76 + 3.92 0.03 Corneal Thickness Central Thickness (p) n=60 +5.3 + 82.7 -2.8 + 27.9 0.61 Axial Dimensions Anterior Chamber Depth (mm) +0.13+0.20 +0.13 + 0.20 0.20 Lens Thickness (mm) +0.00 + 0.05 -0.01 + 0.06 0.97 Vitreous Chamber Depth (mm) +0.26 + 0.23 +0.26 + 0.21 0.97 Axial Length (mm) +0.39 + 0.33 +0.37 + 0.29 0.78 Peripheral Autorefraction Spherical Equivalent (D) +0.04 + 0.93 +0.44+ 1.07 0.03

Table 7.1: Mean ± standard deviation changes (year one - randomization) in the ocular component dimensions of the right eye for the two treatment groups. A positive change means the visual acuity got worse, the keratometry steepened, the intraocular pressure rose, the cornea thickened, the axial dimensions, and the peripheral autorefraction became more prolate. A statistically significant difference with Bonferroni correction = 0.005.

Visual Acuity

Standardized visual acuity was performed on all o f the subjects while they wore their

habitual correction without any refractive error over-correction. At the randomization

visit, the visual acuities of the two groups were equal, but the soft contact lens wearers’

visual acuity decreased significantly more than the RGP contact lens wearers’ visual

80

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. acuity (Table 7.1). The mean visual acuity at the one-year visit was +0.03 ± 0.14

logMAR (Snellen 20/21) for the RGP contact lens wearers and +0.10 ± 0.13 logMAR

(Snellen 20/25) for the soft contact lens wearers (Student’s t-test, p < 0.006).

Keratometry

Corneal curvatures were measured by keratometry. Two readings of the steep

meridian and two readings of the flat meridian were averaged for each eye to yield

comeal curvature measures. The keratometry readings at the randomization visit and the

one-year visit can be seen in Table 7.2.

RGP SCL P Steep K. - Randomization 43.88 ± 1.44 43.92+1.15 0.87 Flat K - Randomization 43.29+ 1.34 43.36+1.12 0.74 Steep K-One Year 44.24+1.38 44.56+1.15 0.18 Flat K-One Year 43.43 ± 1.40 43.78 ± 1.07 0.13

Table 7.2: Steep and flat keratometry readings of the right eye at randomization and one year.

While the keratometry readings do not significantly differ between the RGP and soft

contact lens wearers at the randomization or one-year visits, Table 7.1 shows that the flat

81

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. meridian of the soft contact lens wearers steepened significantly more than the RGP

contact lens wearers between the randomization visit and the one-year visit (Student’s t-

test, p < 0.0001) The same holds true for the left eye (Student’s t-test, p = 0.001).

Intraocular Pressure

We measured the intraocular pressure of the subjects with a Tonopen and found that

there was no difference in the change in intraocular pressure between RGP contact lens

wearers (-0.5 ± 4.6 mm Hg) and soft contact lens wearers (-0.8 ±3.9 mm Hg) (Student’s

t-test, p = 0.66). The average ± standard deviation intraocular pressure for all of the

subjects at the one-year visit was 16.1 ±3.1 mmHg.

Corneal Thickness

The ORBSCAN Anterior Segment Analysis System was used to measure corneal

thickness. The ORBSCAN averages corneal thickness values over a 2-mm diameter

circular area at nine locations, as indicated in Figure 7.2. Each of the peripheral thickness

values are located 3 mm from the center of the cornea. The ORBSCAN unit was not

available at the beginning of the study, so data are incomplete for the randomization and

one-year visits. O f the 116 subjects, 42 were measured prior to contact lens wear and at

the randomization visit Seventy-two subjects were measured at the randomization visit

alone, and 62 were measured at the randomization visit and at the one-year visit

At randomization, all subjects had worn RGP contact lenses for an average of two

months. Over that two-month period, the thickness o f the cornea did not change

significantly at any of the locations (n = 42). The mean central corneal thickness of the 82

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. right eye for all subjects measured at randomization (n = 72) was 609 ± 40 nm. The mean

± SD change in corneal thickness at nine locations on the right eye over one year is

shown in Figure 7.1. None of the changes are statistically significant There was not a

significant difference in comeal thickness changes at any location over one year between

RGP (n = 32) and soft (n = 30) contact lens wearers.

-6 ± 8 9

-7 ± 8 6 0 ± 76

2 - ± 3 2 1 ± 6 2 -2 ± 7 4-3

- 7 ± 4 9

-3 ± 6 7 Temporal Nasal

Figure 7.1: Mean ± standard deviation change in the corneal thickness ((im) o f the right eye of all subjects from the randomization visit to the one-year visit

83

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Axial Dimensions

We used A-scan ultrasound to measure the axial dimensions of the eye. The anterior

and posterior lens peaks and the retinal peak were used to determine the axial length,

anterior chamber depth, and the lens thickness. The vitreous chamber depth was

calculated by subtracting the anterior chamber depth and the lens thickness from the axial

length. The one-year change in axial dimensions of the right eye can be seen in Table 7.1.

The average (± standard deviation) axial length at the one-year visit was 24.5 ± 0.7, and

ranged from 22.68 mm to 26.83 mm.

Peripheral Autorefraction

Myopic eyes are typically prolate (longer axial dimension than equatorial dimension),

and hyperopic eyes are typically oblate (longer equatorial diameter than axial diameter)

(Figure 7.2) (Mutti, et al., 2000).

84

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. t i 2 Prolate Oblate

4 ■ Axial ■ ■■■■»

Figure 7.2: Diagram of oblate and prolate shapes.

In order to determine the shape of the eye, autorefraction was performed while the

subject fixated a target straight ahead and while the subjects fixated a target that was

located 30 degrees temporal. The average spherical equivalent in primary gaze was

subtracted from the spherical equivalent in temporal gaze (Mutti, et al., 2000). A relative

hyperopic peripheral autorefraction indicated a prolate shape, and a relative myopic

peripheral autorefraction indicated an oblate shape.

As expected, the subjects had prolate eyes (Table 7.3). Although the change in ocular

shape was not significantly different between the two groups for the right eye, the

difference was significant for the left eye. The left eyes of the RGP contact lens wearers

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. became more oblate by 0.05 ± 1.40 D, and the soft contact lens wearers left eye became

more prolate by 0.98 ± 1.35 D (paired t-test, p = 0.0007).

Relative Peripheral Refraction (D) RGP SCL P Randomization +0.79 ± 1.17 +0.43 ± 1.09 0.09 One Year +0.80 ±1.18 +0.88 ± 1.30 0.74

Table 7.3: Relative peripheral autorefraction of the right eye at the randomization visit and the one-year visit for each treatment group.

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER 8

CONCLUSIONS

The Contact Lens and Myopia Progression (CLAMP) Study is a three-year, single-

masked, randomized clinical trial to examine the effects of rigid gas permeable contact

lenses on myopia progression in children. The CLAMP Study is due to be completed in

May, 2003. Because the trial is ongoing, all data and conclusions contained in this

dissertation are strictly confidential. This document discusses only the data resulting from

the first year of the study.

Significance

Myopia affects approximately 23% of the United States population (Sperduto, et aL,

1983) and it was estimated that myopia cost the nation $4.6 billion in 1990 (Javitt and

Chiang, 1990). Slowing the progression of myopia may impact the comfort and cosmesis,

economics, and ocular health of myopic patients.

87

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Rationale for the Study

Previous studies indicated that rigid contact lenses slow the progression of myopia in

children (Khoo, et aL, 1999; Pem'gin, et aL, 1990; Stone, 1976). All of these studies

suffered from flaws in study design that resulted in inconclusive outcomes. A critical

review may help us to avoid the pitfalls that the previous studies encountered, such as

unequal loss to follow-up, inadequate control groups, incomplete measurement of the

ocular components, and inclusion of inappropriate subjects.

All of these potential pitfalls were addressed by conducting a randomized clinical

trial, incorporating a run-in period, measuring all ocular components using the latest

technology, and carefully constructing entry criteria.

Run-In Period

A careful inspection of previous rigid contact lens myopia control studies helped

determine the beneficial effects of a run-in period. Because significant proportions of

subjects were lost to follow-up in previous RGP contact lens myopia control studies due

to poor initial comfort (Khoo, et al., 1999; Pem'gin, et al., 1990), a run-in period was used

to increase the number of compliant subjects, decrease losses to follow-up, and improve

the statistical power of the study. Without the run-in period, one of every five children

would not have adapted to RGP contact lens wear, and they would have been lost to

follow-up or non-compliant with the treatment.

On the other hand, a run-in period increased the time necessary to conduct a study.

The median length of the run-in period for the CLAMP Study was six weeks (Table 3-2),

which did not significantly impact the length of the three-year study. Some may also 88

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. argue that the CLAMP Study run-in period limits the generalizability of the study and

reduces the sample of eligible subjects. The results of the study only apply to children

who are able to wear RGP contact lenses. The effects of RGP contact lenses on myopia

progression are irrelevant for children who are not able to adapt to them.

A previous study of extended wear RGP contact lenses used a run-in period to include

only adult subjects who could adapt to daily wear RGP contact lenses (Poise, et aL,

1999). They fitted 411 subjects and found that 286 (69.6%) of them were able to wear

RGP contact lenses every day for at least 14 hours per day. Of the 411 patients, 67

(16.3%) were not able to adapt to RGP contact lens wear due to poor comfort. Just over

21% of the subjects in our study were not able to adapt to RGP contact lens wear, and all

but one of them could not achieve 40 hours per week wearing time. This may be slightly

higher than the adaptation rate of the Poise study because their subjects were required to

wear their contact lenses 91 hours per week to be considered a successful adapter.

We conducted a logistic regression analysis to determine the subjects most likely to

adapt to rigid gas permeable contact lens wear. We adjusted the model for age because

we found that older subjects were more likely to adapt than younger subjects, even

though the age range we examined was only eight to eleven years old. The only two

factors that were able to predict successful RGP contact lens adaptation were a self-report

of wearing contact lenses more often and refractive astigmatism that was more with-the-

rule. Neither of these predictors was particularly compelling because the self-report of

how often the subject liked to wear contact lenses was a circular argument for adaptation,

and the range of astigmatism was very narrow (0.50 DC with-the-rule to 0.50 DC agamst-

the-rule). 89

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The Adapters reported that they liked to wear their contact lenses more often, but the

wearing time was not significantly different between the two groups. Although the

difference in wearing time was not statistically different, there was a 13-hour per week

difference between the two groups, which is approximately one day’s wearing time. The

likely reason that the reported wearing time was not significantly different between the

two groups was the wide variation in reporting wearing time per week. The standard

deviations of the Adapters’ and Non-adapters’ reports were approximately 20 hours per

week.

We used three subscales from the National Eye Institute Visual Function

Questionnaire (NEI-VFQ) to compare the Adapters’ report of ocular comfort with RGP

contact lenses to the Non-adapters’ reports. The children in the CLAMP Study who

adapted to rigid gas permeable contact lens wear reported a mean ± standard deviation

Ocular Pain subscale score of 82.6 ± 14.3, which is very similar to the 8S.3 ± 17.9

reported by adults who wear RGP contact lenses (Wallme, et al., 2000a). Children in the

CLAMP Study also reported similar General Vision and General Health subscale scores

to the adult RGP contact lens wearers.

Figure 3.1 illustrates the reasons children chose not to wear their contact lenses.

Interestingly, the Non-adapters were more likely to choose reasons for not wearing their

contact lenses prior to contact lens wear (i.e., problems with insertion), whereas the

Adapters were more likely to not wear their contact lenses due to problems while wearing

then: contact lenses (i.e., afraid o f lens loss). The Non-adapters did not report more

difficulty handling their contact lenses than the contact lenses, so the problems were

90

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. likely due to not wanting to insert the contact lenses rather than not being able to insert

the contact lenses.

The use of a run-in period in this particular case enhanced subject compliance,

improved statistical power considerations, and did not limit the generalizability of the

study. Careful inspection of limitations suffered by previous rigid contact lens myopia

control studies helped us to design a study that should provide results with less potential

for bias and more definitive answers for the clinical community. The run-in period also

showed us that approximately 78.9% of eight to eleven year old myopic children are able

to adapt to rigid gas permeable contact lens wear. Unfortunately, there were no strong

predictors of successful rigid gas permeable contact lens adaptation. Clinical anecdotal

information based on the experience of fitting children with rigid gas permeable contact

lenses would say that motivated, independent children with parents who are involved and

patient are the most likely to be successful RGP contact lens wearers.

Randomization Results

We measured all o f the outcome measures on the subjects at the randomization visit.

The two treatment groups were balanced with respect to all of the outcome measures in

both eyes, and the two eyes were similar when we compared them. The mean ± standard

deviation spherical equivalent refractive error of the right eye was -2.39 ± 0.89 D. The

mean ± standard deviation axial length was 24.1 ± 0.7 nun, and the mean ± standard

deviation steep keratometry reading was 43.90 ± 1.30 D. On average, the eyes were

prolate; the average ± standard deviation relative peripheral autorefraction was +0.61 ±

1.14 D. 91

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The refractive error and ocular components of the subjects in the CLAMP Study were

similar to those of children participating in studies of myopia control (Fulk, et al., 2000;

Grosvenor, et al., 1987; Khoo, et al., 1999; Perrigin, et aL, 1990; Stone, 1976), and the

peripheral autorefraction values were similar to a sample of myopic children (Mutti, et

al., 2000).

Refractive Error Changes

Over the first year of the CLAMP Study, the pooled subjects’ right eyes’ spherical

equivalent cycloplegic refractive error progressed -0.99 ± 0.61 D. The change in

refractive error change ranged from a decrease in myopia of +0.12 D to an increase of

-2.66 D. Rigid gas permeable contact lens wearers progressed -0.80 ± 0.65 D on

average, and soft contact lens wearers progressed-1 .19 ± 0.53 D on average (Student’s t-

test, p < 0.0005). The RGP contact lens treatment effect is approximately 33% after one

year.

The RGP contact lens wearers progressed slower than the soft contact lens wearers on

average, but not all RGP contact lens wearers benefited from slowed myopia progression.

A rigid contact lens wearer experienced the maximum progression over the first year of

the CLAMP Study.

An inspection of Figure 6.2 shows that it would be difficult to predict whether a

subject was a rigid gas permeable or a soft contact lens wearer based on myopia

progression.

Neither type of contact lens had much of an effect on refractive astigmatism

throughout the first year of the study, although we enrolled only low astigmats. 92

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Ocular Component Changes

Over the first year of the CLAMP Study, the only significant difference in ocular

component changes between the treatment groups was comeal curvature changes. The

flat meridian steepened significantly more for the soft contact lens wearers than for the

RGP contact lens wearers. One theory to explain the difference is that all comeas

flattened during the run-in period due to RGP contact lens wear. The corneas of subjects

that were randomly assigned to wear soft contact lenses may simply return to baseline

curvature, whereas the RGP contact lens wearers’ corneas maintain the flatter shape. The

corneas flattened approximately 0.50 D from the baseline visit to the randomization visit,

and there was no significant difference between the two groups (Table 8.1).

RGPSCL P Change in steep meridian -0.63 ±0.47 -0.58 ± 0.42 0.55 Change in flat meridian -0.41 ±0.39 -0.47 ± 0.40 0.41

Table 8.1: Change in steep and flat meridians o f the cornea from prior to contact lens wear to randomization. Negative numbers indicate flattening.

93

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. From the randomization visit to one year, the soft contact lens wearers’ corneas

returned to baseline corneal curvature, whereas the rigid gas permeable contact lens

wearers’ corneas were still significantly flatter at the end of the first year of the study

than they were at baseline (Table 8.2). Therefore, the difference in refractive error may

be partially due to a return to baseline corneal curvatures experienced only by the soft

contact lens group.

Treatment Group Change in Keratometry Change P Steep meridian -0.25 ±0.60 0.002 RGP Flat meridian -0.25 ±0.44 <0.0001 Steep meridian +0.05 ±0.47 0.42 SCL Flat meridian -0.06 ±0.35 0.15

Table 8.2: Change m steep and flat meridians of the comea from baseline to the end of year one. Negative numbers indicate flattening.

Data Safety and Monitoring Committee

The Data and Safety Monitoring Committee met after the conclusion o f the first year

of the study to determine whether further investigation was necessary or whether

continuing the study was harming one treatment group. The DSMC decided that the study

warranted continuation for another year and that continuing the study was not harming

94

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. one of the treatment groups. Although the rigid gas permeable contact lens wearers

benefited on average from slowed myopia progression during the first year of the

CLAMP Study, the results were not sufficiently different to believe that the soft contact

lens wearers were harmed by not wearing rigid gas permeable contact lenses. While the

rigid gas permeable contact lens wearers benefited from slowed myopia progression on

average, certainly not all of the rigid contact lens wearers benefited. In feet, a rigid gas

permeable contact lens wearer progressed faster than any o f the other subjects.

Previous contact lens myopia control studies have also shown that the treatment effect

may take place entirely in the first year of the study, and the myopia progression rate is

similar between the two treatment groups over the remainder of the study. Figure 8.1

shows the results of a rigid gas permeable myopia control study (Khoo, et al., 1999). At

the beginning of the study, the rigid gas permeable contact lens wearers had -1.31 D

more myopia than the spectacle wearers. At the end of the first year of the study, the

difference between the two treatment groups was approximately one-third of a diopter,

and it remained there throughout the remainder of the study. The DSMC decided that it

was important to see if the treatment effect of the rigid gas permeable contact lenses

continued beyond the first year o f the study.

95

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. -3.00 ■ ! -2 .50 . I - 2.0 0 - > m - 1.50 -5 ee -t.oo-

« -0 .5 0 - 75 ee 0.00 Baseline Year I Year 2 Year 3

Figure 8.1: Refractive error changes in the rigid gas permeable contact lens study conducted by Khoo, et al. (1999). The refractive error on the y-axis is relative refractive error because the mean refractive error for each group at the beginning of the study was not available (the mean refractive error o f the spectacle wearers was 1.31 D less myopic than the RGP contact lens wearers at the beginning of the study).

Summary

Approximately four out of every five myopic children are able to adapt to rigid gas

permeable contact lens wear. Those that are able to adapt to rigid contact lens wear may

experience 33% slower myopia progression on average, and the treatment effect may be

primarily due to a return to baseline corneal curvatures experienced by the soft contact

lens wearers.

96

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EXCERPTS FROM THE OPERATIONS MANUAL

Study Organization and Policy Matters

Study Administration

The Executive Committee provides the administration of the CLAMP Study. The

Executive Committee has overall responsibility for directing CLAMP Study activities

and formulating policy for the study. The Executive Committee meets in person at least

once each year and by telephone as necessary. The Principal Investigator, Mentor, and

Consultants are permanent voting members of the Executive Committee: The Principal

Investigator or Mentor may appoint other individuals to the committee for one-year terms

as necessary to assure the scientific quality of the deliberations. Any member who misses

two consecutive meetings of the Executive Committee is subject to replacement by the

Principal Investigator. All members are expected to file statements with the Principal

Investigator describing any personal or professional involvement with manufacturers or

others who might benefit financially from the findings o f the CLAMP Study.

105

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The Executive Committee deals with day-to-day operational matters which do not

involve changes in the study protocol or policy, assigns priorities for study activities,

performs administrative and logistic functions for the CLAMP Study, and coordinates

preparation of progress reports to the National Eye Institute Director and the Chair of the

Institutional Review Board of The Ohio State University.

Subject Costs

CLAMP Study subjects are not billed for study-related visits. Usual and customary

fees apply for non-study-related eye and vision care, even for conditions detected at a

CLAMP Examination Visit.

Publicity

All publicity and press releases for the CLAMP Study must have prior approval of the

Principal Investigator and Mentor. Study investigators who are approached by the press

for information concerning the study should refer these inquiries to the Principal

Investigator.

Publication of Study Design, Methods, and Findings

The Executive Committee will review all written reports prepared for publication. All

reports will list the primary author and co-authors as necessary for that particular

publication. There will not be a Contact Lens and Myopia Progression (CLAMP) Study

Group listed at the end of each publication.

106

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Conflicts regarding authorship are resolved by the Executive Committee. General

guidelines for authorship are: active participation in the production of the manuscript or

other important contribution. Authorship rights are not available for membership on the

writing committee only, use of data only, or signing the copyright form. If the timeline

for a paper has expired with no substantial evidence of progress, authorship rights are

assumed to have expired The Executive Committee will be informed of changes in lead

authorship. An individual may be given an acknowledgment for reading and providing

critical comments on the manuscript. An investigator will be added to the author list on

all papers that require his or her statistical input.

The Executive Committee may establish writing committees for papers from among

the CLAMP investigators as necessary. Investigators may volunteer for writing

assignments and suggest additional topics where appropriate. The investigator should

submit an abstract and a short description of the proposed paper including co-authors,

data to be repotted and timeline for drafts and submission. This information should be

sent to the Principal Investigator. The Executive Committee is responsible for reviewing

the proposal’s merit and deciding if it should be a CLAMP Study publication. This

review process is intended to insure the quality of study publications and to refine the

proposal. The Executive Committee is responsible for determining priorities (timeline

and order of preparation) of proposed papers/presentations.

The primary author is responsible for coordinating all activities related to the writing

and submission of papers and abstracts. This includes arranging conference calls,

discussing analytic plans, assigning writing responsibilities to co-authors, maintaining

timeliness, determining the order of authorship, circulating drafts to co-authors, and 107

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. circulating final drafts to the Executive Committee. Upon circulation o f the draft, there

will be a two-week period during which members can make comments about the paper. If

the focus of the paper changes as it moves from abstract to the manuscript stage, the

primary author will notify the Principal Investigator in writing. The Principal Investigator

will be responsible for insuring that the revised proposal receives appropriate review.

Each publication must acknowledge National Eye Institute support as follows: “This

study was supported by grants from the National Eye Institute, National Institutes of

Health, Bethesda, MD” and will list the number of the CLAMP Study grant (NEIK23

EY00383). Acknowledgment of study support must also be made to Menicon Co., Ltd.,

CIBA Vision Corporation, SOLA Optical USA, and a William C. Ezell Fellowship from

the American Optometric Foundation, sponsored by Essilor.

Presentations

The Executive Committee must approve oral presentations and abstracts to be printed.

Unpublished CLAMP Study results may not be used for oral presentations, local or

otherwise, unless the Executive Committee grants a specific exception. Study results

include all data collected for the CLAMP Study. The above restrictions do not apply to

local presentations of the design of the Study, provided these presentations contain no

unpublished study results. Such presentations are encouraged to stimulate subject

recruitment.

108

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Ancillary Studies

An ancillary study is a research project that requires supplemental data or procedures

to be performed on any CLAMP Study subjects according to a set protocol or additional

data analysis performed that would not otherwise be performed for the study.

Individual investigators who desire to cany out ancillary studies are encouraged to do

so. Ancillary studies may greatly enhance the value of the CLAMP Study and ensure the

continued interest of all investigators. However, to protect the integrity of the study,

ancillary studies must be reviewed and approved by the CLAMP Executive Committee

before then- inception, whether or not they require supplemental funds. The Executive

Committee can make no additional tests or measures on CLAMP Study subjects without

prior approval. Data analysis is the responsibility of the ancillary study investigators.

Everyone involved in the CLAMP Study is entitled to prior assurance that no

ancillary study will complicate the interpretation of CLAMP Study results, adversely

affect subject cooperation or recruitment, jeopardize the public image of the study, or

create a serious diversion of study resources.

The request for approval of an ancillary study involves two steps. The first requires a

brief description of the proposed ancillary study in narrative form stating the primary

hypothesis and a brief description of the study which addresses the issues above. This

brief description is sent to the Principal Investigator and reviewed by the Executive

Committee within one month of receipt. If approved for further consideration, a detailed

description should be submitted in narrative form and must provide information on the

additional subject burden imposed by the ancillary study informed consent procedure,

extra time, extra visits, etc. It should contain a description o f the objectives, methods, and 109

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. significance of the ancillary study. Full details should be given concerning any

procedures to be carried out on any CLAMP Study subjects, such as laboratory tests,

psychiatric interviews, psychological testing, etc. Mention should be made of any

substances to be injected or otherwise administered to the subjects. Any observations to

be made or procedures to be carried out on a subject outside of the clinic should be

described. Detailed information should be given concerning the extent to which the

ancillary study will require blood or other specimens. If specimens are to be obtained

from the subjects, mention should be made of all procedures to be carried out on these

specimens. If access to CLAMP Study data is required, the investigator must specify

what data are needed, on whom it is needed, and the timetable for access to such data All

ancillary studies must have IRB approval.

The investigator proposing an ancillary study should send a written request to the

Principal Investigator, who is responsible for distributing copies to all members of the

Executive Committee. Within a reasonable time the Principal Investigator summarizes

questions and/or objections raised by members of the Executive Committee and sends

this summary to the applicant for amplification, clarification, or withdrawal of the

request. The members of the Executive Committee have another opportunity to review

the request If the Executive Committee then approves the ancillary study proposal, the

Chairman prepares a statement of the Executive Committee consensus. The Chairman

then notifies the investigator proposing the ancillary study of the decision.

If no additional funds are required, the investigator may proceed with the ancillary

studty as soon as the Executive Committee has approved it. If additional funds are needed,

the investigator may prepare and submit a new research grant application to the potential 110

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. sponsor for review in the same manner as any other new research grant application.

Copies of the grant application are sent to the Principal Investigator, the investigator is

not to accept the grant or activate the ancillary study until approval has been received

from the CLAMP Executive Committee.

Manuscripts dealing with ancillary studies carried out in conjunction with the

CLAMP Study must be sent to the Executive Committee for review before submission

for publication. Investigators may not independently use study data collected. All

manuscripts of presentations for scientific meetings based on ancillary study data must be

reviewed and approved by the Executive Committee before publication or presentation.

Such review pertains only to the impact on CLAMP Study objectives, and not to the

ancillary study’s scientific merit.

The Principal Investigator of each ancillary study is expected to report to the

Principal Investigator at six-month intervals on the progress of the ancillary study. This

report may be prepared as a letter. The Principal Investigator reports on the status of all

ancillary studies to the Executive Committee at each meeting.

Access to Study Information

Access to CLAMP Study data on individual subjects is prohibited to unauthorized

persons. The identity of individual CLAMP Study subjects may not be revealed in any

public report or presentation.

I l l

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Accommodation Measurement

Accommodative Response

Measurement of accommodative response is done monocularly using the Canon R-l

autorefractor. Accommodative response is measured at three stimulus levels: 0.00 D, 2.00

D and 4.00 D. The response AC/A ratio is measured simultaneously through an accessory

camera mounted onto the Canon R-l. This camera photographs the positions of Purkinje

images I and IV as a measure of eye position at the three different levels of

accommodative response. Each subject is calibrated by measuring the change in the

positions of these images for a 10° eye movement prior to measurement.

Measurement of accommodative response and lag is taken on children wearing their

habitual correction. Their correction status is determined by what they wear to the testing

session. Children who have been prescribed lenses but do not wear them are presumed to

be uncorrected. Children are tested in four possible conditions: uncorrected, wearing rigid

contact lenses, wearing soft contact lenses, and wearing spectacles.

Equipment Setup

Cables should be arranged in the following manner

(1) A T-coimector should be placed on the monitor for the R -l.

(2) A video cable should go from the video-out port on the base of the R-l to the T-

connector on the R-l monitor.

(3) A video cable should go from the other side of the R-l T-connector to “VID I” on

the multiplexer.

112

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (4) A video cable should go from the video-out port on the accessory camera control

box to “VTD 2” on the multiplexer.

(5) A video cable should go from the VCR Out port on the multiplexer to the Video

In port on the VCR

(6) A video cable should go from the VCR In port on the multiplexer to the Video

Out port on the VCR

(7) A video cable should go from the Monitor A port on the multiplexer to the Video

In port on the TV Monitor, with the monitor set to Line Input.

(8) A camera control cable should go from the camera control box to the accessory

camera on the camera plate.

(9) The multiplexer should show inputs I and 2 as being on (LEDs lit), with the dial

set to Live, Quad, and Record.

(10) The VCR should be set to LI input.

(11) Confirm that the connections are correct by pressing and holding the dial of the

multiplexer m; the two channels should alternate at a rapid flicker.

The video camera plate is placed flat on the top of the R-l and infrared sources,

beneath the mirror, and forward to a position snug up against the base of the mirror. The

“hot mirror” is angled to reflect the image of the left eye into the camera with the coated

side o f the mirror facing the patient.

The microphone should be plugged into the left (Mono) port o f Audio In on the VCR

The recording level should be at maximum (10). Confirm that the connection is correct

by speaking into the microphone and noting that the recording level indicators move.

113

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Calibration

(1) The model eye is attached to the vertical supports for the R-l chin rest by means

of clamps and rods. The eye is sensitive to tilt, and therefore must be supported

by a piece of flat aluminum. The aluminum flat is held horizontally against the

two vertical chin rest supports by masking tape. The back of the model eye is

held flush against the aluminum flat by small pieces of masking tape on the top

and bottom of the barrel of the model eye.

(2) Allow the R-l to warm up for IS minutes.

(3) Obtain best focus of the “iris” of the model eye and place the Canon R-l

reference circle in the middle of the pupil of the model eye. Take 30 readings

with re-focusing between each reading. Calibration should be checked once per

month, or after the R-l is moved. Calibration data in the form of a Canon R-l

printout of at least 30 readings should be given to the Principal Investigator for

data entry.

Uncorrected Measurement Procedure

This protocol is used when the subject does not wear a correction at the testing

session.

(1) Slide the video camera plate on top of the Canon R-l lens and infrared sources

and beneath the mirror. The multiplexer should be set to “record” and “quad,” and

the VCR connected to record from line input.

114

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (2) Place the Badal track with the +6.00 D lens into the slots of the Canon R-l in

front of the patient’s left eye. Place the red and red dot 10° stimulus on the track

at the ID stimulus level. Turn on the accessory lighting to illuminate the target.

(3) Position the subject either sitting or standing comfortably behind the Canon R-l

autorefractor.

(4) Begin to record on the VCR, then say the subject’s ID aloud into the microphone

to mark the tape.

(5) Lower the paddle on the Canon R-l to occlude the subject’s right eye.

(6) Direct the patient to look at the red dot. Adjust the focus of Purkmje IV using the

joystick of the Canon R-l. Have the patient maintain fixation for a few seconds.

Re-direct the patient to fixate the green circles. Have the patient maintain fixation

for a few seconds. Re-direct the patient to fixate the red d o t Have the patient

maintain fixation for a few seconds. Re-direct the patient to fixate the green

circles. Have the patient maintain fixation for a few seconds.

(7) Raise the paddle to uncover the right eye. Place the Badal track into the slots in

front of the patient’s right eye. Replace the 10° target with the letter chart target

set at the 0.00 D mark. Place the infrared occlusion glasses on the patient. Adjust

the patient’s head in the chin rest so that the eyes are level and parallel to the front

of the Canon R-l. Adjust the accessory camera to place the patient’s left eye in

focus near the middle of the frame when the right eye is also focused and

centered.

(8) Have the patient fixate the letters in the center of the target and instruct them to

“keep the letters as clear as possible, without blur or fuzz.” Take five readings 115

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. with the target at 0 D. First and second grade children may only be able to

maintain attention for three readings. Adjust focus of the accessory camera as

necessary.

(9) Push the red button on the printer to advance the recording paper. Move the target

to the 2D mark and have the patient blink a few times. Repeat the instructions to

the patient. Take 5 readings. Adjust focus of the accessory camera as necessary.

(10) Push the red button on the printer to advance the recording paper. Move the

target to 4D and have the patient blink a few tones. Repeat the instructions to the

patient. Take 5 readings. Adjust focus of the accessory camera as necessary.

(11) Push the red button on the printer to advance the recording paper. Stop the VCR.

(12) Remove the readings, record the subject’s ID number on the top of the paper.

Tape the readings to the Unmasked Exam Form.

Soft Contact Lenses Measurement Procedure

This procedure should be used when the subject wears soft contact lenses to the

testing session.

(1) Follow steps (I) through (12) above.

(2) Push the red button on the printer to advance the recording paper. Remove the

readings and record the subject’s ID number. Tape the readings to the Unmasked

Exam Form.

116

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Rigid Contact Lenses Measurement Procedure

This procedure should be used when the subject wears contact lenses to the testing

session.

(1) Have the subject remove the left contact lens and follow steps (I) through (12)

above.

(2) Push the red button on the printer to advance the recording paper. Remove the

readings and record the subject’s ID number. Tape the readings to the Unmasked

Exam Form.

Spectacles Measurement Procedure

This procedure should be used when the subject wears spectacles to the testing

session.

(1) Slide the video camera plate on top of the Canon R-l lens and infrared sources

and beneath the mirror. The multiplexer should be set to “record” and “quad,” and

the VCR to record from line input.

(2) Place the Badal track with the +6D lens into the slots of the Canon R-l in front of

the right eye. Place the letter chart target on the track and have the patient remove

his or her spectacles. Turn on the accessory lighting to illuminate the target

Adjust the target on the Badal track to the point of maximum plus with maximum

clarity and take 5 readings.

117

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (3) Adjust the prescription from the Canon R-l for vertex distance according to the

chart provided and place this prescription into the infrared occlusion glasses using

the modified Janelli clip.

(4) Move the Badal track with the +6D lens into the slots of the Canon R-l in front of

the left eye. Place the red and red dot 10° stimulus on the track at the ID stimulus

level. Adjust its position as necessary to be visible to the patient.

(3) Follow steps (3) through (7) above.

(6) Take five readings with the target at 0.00 D. First and second grade children may

only be able to maintain attention for three readings. Adjust focus of the accessory

camera as necessary. Adjust the prescription in the Janelli clip as needed to obtain

an over-refraction of ±0.50=-1.00.

(7) Follow steps (9) through (12) above.

(8) Push the red button on the printer to advance the recording paper. Remove the

readings, record the subject’s ID number on the top of the paper, and the final

prescription in the Janelli clip on the bottom o f the paper. Tape the readings to

Unmasked Exam Form.

118

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Visual Acuity, Phoria, Pupillary Distance, Retinoscopy, Keratometry, and Tonometry

Measurement ofVisual Acuity

High contrast monocular visual acuity is measured by Dr. Walline or someone

certified to perform visual acuity according to the procedures developed for the

Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study using Bailey-Lovie

high contrast visual acuity charts.

Bailey-Lovie distance visual acuities are measured during the CLAMP Study

Baseline and Annual Examinations. Visual acuity is measured on the right eye, left eye,

and both eyes with habitual correction.

Calibration

Remove the light meter from the pouch. Press the M button, and the LCD display

illuminates. The only other buttons needed are the horizontal fu n c t io n arrows on the

right. These move the square cursor along the settings at the top o f the screen. Set the

cursor to the EV icon.

To calibrate, the investigator should be positioned as close as possible to the letter

charts without blocking the illumination falling on them. Press the M button, and inspect

the two numbers on the bottom left (“94” in Figure A. 1).

119

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. EV 94 ' 125 1.4 2 2.8 4 5.6 8 11 16 22 32 45 84 90

Figure A.1: Light meter display.

This EV scale is arbitrary (ie, not in candela/m2), but it has been calibrated such that the

target range is 96 to 102 EV; too low and more light is needed, too high and less light is

needed. This range applies to the whole useful area of the chart (the bottom comers are

unimportant). Calibration using the high contrast charts and testing in the four areas

shown in Figure A-2 is recommended. EV numbers should be logged in the Visual

Acuity Calibration Log Book.

120

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. THE

Figure A-2: Areas for visual acuity chart lighting calibration.

Important: The numbers 100 and 125 should always appear on the right o f the

display when in EV mode. If not, then the settings have been disturbed, most likely from

interference with the vertical arrows on the right. These should never be pressed, and

doing so will render your readings worthless. In this event, take the battery out of the

meter, wait 15 seconds and re-insert the battery. The horizontal arrows should be set to

move the square cursor to the EV setting. The light meter turns itself off after use.

121

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Visual Acuity Technique

(1) Visual acuity is measured with the patients’ eyes located 4 meters from the visual

acuity chart. The patient may stand or sit for the testing. The Clinician or

Technician should ensure that the patient’s head does not move forward or

backward during the test so that the patient's eyes remain at the set test distance.

(2) The testing begins in the right eye with the left eye occluded carefully.

(3) Instruct the patient to read each letter on the chart starting in the top left hand

corner with the first line, line by line, letter by letter, from left to right.

(4) Advise the patient to read slowly and to keep his or her head as still as possible.

The pace should not be foster than about one letter per second, so as to achieve

the best identification of each letter. Demonstrate the desired pace by reciting, “A,

B, C.” If the patient at any point reads too quickly, s/he should be asked stop, go

back to the beginning of the line, and read more slowly.

(5) S/he is not to go to the next letter until s/he has given a definite response. If the

patient reads a number, s/he should be reminded that the chart contains no

numbers and the Clinician or Technician should request a letter in lieu of a

number.

(6) When the patient says s/he cannot read a letter, s/he should be encouraged and

required to guess. A maximum effort should be made to identify each letter. If a

patient identifies a letter as one of two letters, s/he should be asked to choose one

letter and, if necessary, to guess. You can suggest that the patient fixate

eccentrically or turn or shake his or her head in any manner if this improves visual

122

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. acuity. If the patient employs these maneuvers, care must be taken to ensure that

the fellow eye remains covered and that the patient is not leaning forward.

(7) The Clinician or Technician uses the Quality of Life in Contact Lens Wearers

Study Visual Acuity Form to record the patient’s answers. Score each letter as

right or wrong. Letters read correctly are marked with a “slash” through them.

Letters read incorrectly are circled. If all the letters on a row are read correctly,

draw a horizontal line through all the letters on that line, or slash through each of

the 5 letters on that row. Record a perfectly read line by putting a check mark or

the number “5” in the right-hand column. The testing continues to the next line

with smaller letters. The patient continues reading down the chart to the last letter

of each line, until the patient has missed 3 letters on a given The incorrectline.

letters can occur at the beginning, middle or end of this line and do not have to be

consecutive. Visual acuity testing for an eye stops when the patient has read the

last letter of the line with 3 incorrect letters.

(8) The Clinician tallies the total number of letters read correctly for each visual

acuity measurement of each eye on the Visual Acuity Form and records this total

in the visual acuity section of the appropriate form.

123

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. logMAR Snellen denominator 0.80 126 0.70 100 0.60 80 0.50 63 0.40 50 0.30 40 0.20 32 0.10 25 0.00 20

Table A.1: Conversion of Snellen notation to logMAR. Add 0.02 for each letter missed on a given line, i.e. 20/20-2 corresponds to logMAR of 0.04

Retinoscopy

Conventional streak retinoscopy is performed primarily to serve as a beginning point

for manifest refraction and to assess the clarity of the ocular media. Retinoscopy is

always done uncorrected, not over glasses or contact lenses.

The child fixates a 20/400 letter on the distance visual acuity chart, with the

duochrome filter over the letters. Each meridian of each eye is neutralized separately,

using the phoropter. Begin by neutralizing the meridian with the most plus power, then

neutralize the meridian 90° away using the cylinder power and axis knob. Record the

prescription found on the Examination Form, with working distance subtracted

124

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Cover-Uncover at Distance

(1) Cover the child’s right eye and observe the left eye for any re-fixation movement.

Re-fixation movement indicates strabismus.

(2) Repeat if needed to rule out false positive movements due to poor fixation.

(3) Repeat but cover the left eye and observe the right eye for re-fixation movement.

If a re-fixation movement is seen this indicates strabismus.

Alternate Cover Test at Distance

(1) The examiner covers the child’s right eye. The examiner then moves the occluder

to the left eye while observing the right eye as it is uncovered. The occluder is

then moved back to the right eye while the examiner observes the left eye as it is

uncovered. The examiner notes the direction and the amount of movement of the

eye as it is uncovered. This alternate occlusion continues for at least 30 seconds.

The examiner is always watching the eye as it is uncovered.

(2) It is very important that fusion be completely disrupted so that the maximum

deviation is uncovered. The cover must be moved rapidly between eyes so that

one eye is always occluded and fusion is prevented. However, the occluder can

remain in front of each eye for several seconds to ensure complete dissociation.

(3) The direction of the deviation is determined by the direction the eye moves as the

cover is removed. If the eye was turned in behind the occluder (esophoria or

esotropia), the examiner will see the eye move out to pick up fixation when the

occluder is moved to the other eye. If the right eye was down (right hypophoria,

or right hypotropia) when it was occluded the right eye must move up to pick up 125

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. fixation when the occluder is moved to the left eye. Some patients may show a

diagonal eye movement as the occluder is moved to the other eye. These patients

have both a horizontal and vertical component to the deviation and both

components must be specified and measured.

(4) The magnitude of the deviation must now be determined Place a prism in front of

the right eye in the same direction as the eye movement observed during the

alternate cover test If the eye moves out as the occluder is moved to the other eye

the patient is esophoric and the deviation is neutralized with base out prism. The

prism is placed in front of the eye in the proper orientation and the occluder is

then placed in front of the prism. The eye is observed through the prism as the

occluder is moved to the other eye. The power of the prism is adjusted until no

movement of the eye behind the prism is seen as the occluded is removed from

this eye and placed over the fellow eye. It is important to keep the patient

dissociated during the measurement Therefore, the examiner should continue to

occlude an eye between measurements while the prism power is adjusted.

Cover-Uncover at Near

Near phoria measurement is performed while the child fixates a small letter taped to

the end of the PD rule, held 40 cm from the child’s eyes. Repeat the procedures in used

for the distance cover tests with the same distance prescription in place. Any re-fixation

movement that is seen and verified with repeat observation indicates strabismus.

126

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Alternate Cover Test at Near

The same procedures used to determine the direction and magnitude of the deviation

at distance must be repeated with the patient fixating the near target at 40 cm.

Interpupillary Distance

The distance interpupillary distance is needed for the response AC/A ratio calculation

described in Chapter 6. It is measured with a conventional PD rule as follows.

(1)The examiner is positioned directly in front of the patient at a distance of 40 cm.

The patient and examiner should be on the same vertical plane.

(2) The millimeter rule is placed on the bridge of the patient’s nose (in the spectacle

plane) with the millimeter scale positioned under both the right and left eyes.

(3) The examiner closes his right eye and positions his left eye directly in from of the

patient’s right eye. The “zero” on the millimeter rule is then aligned with the

temporal limbus of the patient’s right eye. Once the zero has been aligned with

the patient’s right eye, the ruler is not moved until the PD measurement is

complete.

(4) The examiner measures from the temporal limbus of the patient's right eye to the

nasal limbus of the patient’s left eye while the patient views the examiner’s left

eye

(5) The examiner then closes his left eye, opens his right eye, and instructs the patient

to look at his right eye.

127

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (6) The distance PD is measured to the nearest millimeter from the temporal limbus

of the patient’s right eye to the nasal limbus of the patient’s left eye while the

patient views the examiner’s right eye.

(7) Record the PD in the Unmasked Examination Form as follows:

distance PD / near PD

Keratometry

Comeal curvature is measured primarily by central keratometry according to the

protocol that follows. Keratometry is a long accepted method of measuring central

comeal curvature. Keratometry was chosen as a comeal curvature measurement due to

the ease with which it can be performed and because it provides useful information in the

fitting of contact lenses.

The keratometer eyepiece is focused prior to each use as follows:

(1) Hold a white card at the front of the instrument housing of the keratometer or use

the white occluder if present on the instrument The purpose of using the white

background is to allow greater ease in viewing the black eyepiece reticule (black

cross).

(2) The eyepiece is turned all the way counterclockwise into most plus power.

(3) Both eyes are kept open as the clinician looks into the eyepiece to decrease

accommodation. The eyepiece is then slowly rotated clockwise until the black

cross first clears.

128

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Someone certified to perform keratometry uses the following protocol for calibrating

the keratometer on a monthly basis. Calibration results should be logged in the

Keratometry Calibration Log.

(1) Attach the steel ball holder (Lensco-meter) to the upright support of the forehead

rest, at approximately the canthus mark, if present. Angle the steel ball holder

toward the barrel of the instrument so that the steel calibration ball is

approximately at the plane that the eye would be during routine keratometry.

(2) Take a reading from each steel ball (40.50 D, 42.50 D, and 44.75 D) in both the

vertical and horizontal meridians.

(3) If the keratometer is more than 0.25 D out of calibration, recalibrate the

keratometer by adjusting the measuring wheels. This is accomplished by

loosening the two set screws and rotating the wheels into the appropriate

positions.

Keratometry is performed as follows:

(1) Ask the patient to place his/her chin in the chin rest and forehead against the

headrest.

(2) With the keratometer in the straight ahead position, sight down the outside of the

instrument and adjust the instrument vertically until the leveling sight is aligned

with the patient’s temporal canthus.

(3) Release the knob for locking the instrument and rotate the instrument until it

points directly at the eye to be tested. Instruct the patient to look into the

instrument where he/she may see a reflection o f his/her own eye.

(4) Adjust the focus o f the instrument until the image of the mires is clear. 129

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (5) Make fine vertical and horizontal adjustments necessary to place the reticule cross

near the center of the lower right mire image.

(6) Rotate the instrument (to locate the horizontal or near horizontal principal

meridian) until the horizontal bars of the two crosses to the left of the focusing

mire are aligned. Maintain clarity of the image during this step by continual

refinement of the focus.

(7) Turn the horizontal measuring knob (on the left of the instrument) until these two

crosses are superimposed.

(8) The orientation of the keratometer drum may have to be changed to align the

mires for the vertical meridian. This represents irregular astigmatism, ie, the two

principal meridians are not oriented exactly 90° apart, and they should be

recorded as they appear on the keratometer.

(9) Direct your attention to the two horizontal lines above the focusing mire and turn

the vertical measuring knob (on the right of the instrument) until these lines are

superimposed.

(10) Record the dioptric value of the flatter and steeper curvatures to the nearest 0.12

D, and the meridians of each curvature as indicated on the instrument scale.

(11) Move the vertical and horizontal measuring knobs away from the final

measurement, and repeat procedure steps 1 through 10 for the left eye.

(12) Move the vertical and horizontal measuring knobs away from the final

measurement, and repeat steps 1-11 and record a second set of keratometric

readings.

130

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Drop Instillation

Each drop is instilled individually. The easiest way is to hand the child a tissue,

instruct him or her that the drop will be put in, open the lids manually, and instill the

drop. The child should be instructed to “dab the eye with the tissue” immediately

following each drop.

One drop of 0.5% proparacaine is instilled prior to Tonopen. This is typically the only

drop where the child will feel any sting, but the stinging should not be over-emphasized

in telling the child about the eye drops. Cycioplegia and dilation are accomplished with

one drop o f 1% mydriacyl in each eye followed by a second drop o f 1% mydriacyl 5

minutes later.

Tonometry

The intraocular pressure is measured using a Tonopen applanation tonometer. The

tonometer calibration should be checked every day.

(1) Depress the switch quickly and release.

(2) If the previous calibration was “Good” the LCD will briefly display “------”

followed by “= = = =“, accompanied by a beep. A calibration check can only be

performed when “ ------” is displayed. If ‘ - = = =“ is displayed, depress the

activation switch once to change the display to “ ------

(3) If the previous calibration was “bAd” or the memory of that calibration has been

lost due to battery change or depressing the RESET button, then a long beep

sounds. Following this, “CAL” appears and a short beep will sound. The display

will then change to “ ------” and another short beep will sound. 131

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (4) If the activation switch is not depressed for a long enough period, “ ------” will be

displayed momentarily, followed by a blank LCD. Repeat step 2 and hold the

activation switch in the depressed position for a longer period of time.

(5) Hold the tonometer vertically with the probe tip pointing straight down.

(6) Press and release the activation switch twice in rapid succession. Two beeps will

sound and “CAL” will appear on the LCD.

(7) Wait (up to 20 seconds) until a beep sounds and “-UP-” appears on the LCD.

(8) Quickly turn the unit so that the probe tip is pointing straight up.

(9) Wait a few seconds. A second beep will sound indicating the end of the

calibration check.

(10) If the LCD reads “Good”, the calibration was successful. If the LCD reads

“bAd”, the calibration needs to be repeated.

(11) Instill a drop of 0.5% proparacame into each eye.

(12) The Tonopen must always be covered by a Tonocover. These are used for one

person only.

(13) Activate the Tonopen by depressing the activation switch momentarily, then

release.

(14) The LCD will change to “= = = =“ and a beep will sound.

(15) When “= = = =“ is displayed, touch the unit to the cornea lightly and briefly,

then withdraw. Repeat several times.

(16) A click will sound and a digital IOP measurement will be displayed each tune a

valid reading is obtained.

132

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (17) After four valid readings are obtained, a final beep will sound and the average

measurement will be displayed.

(18) If “ ------” appears, an insufficient number of readings were obtained. If this

occurs, repeat the examination beginning with step 13.

(19) Repeat steps (13) through (18) for the left eye.

(20) Record the readings on the examination form.

Videophakometry

Measurement of lens radii of curvature is analogous to measurement of corneal

curvature. The size of a reflected image is proportional to the radius of curvature of the

reflecting surface. Comparison of the separations of pans of Purkinje images I (cornea),

in (anterior lens surface), and IV (posterior lens surface) to values from calibration on

steel balls of known radius yields radii of curvature in air fin each of these surfaces. Later

calculations transform these raw values in air to radii of curvature in the eye.

Additionally, the calculations yield an individual equivalent index of refraction for the

crystalline lens.

Cables should be arranged in the following manner

(1) A video cable should go from the VID 1 output port on the camera control box to

the Video In port on the VCR.

(2) A video cable should go from the Video Out port on the VCR to the Video In port

on the TV Monitor, with the monitor set to Line Input.

(3) The camera control cable should go between the camera and the camera control

box. 133

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The light source should be to the left of the slit lamp base with the lights arranged

vertically. The camera control box should be set to the following:

•Enhance - Minimum

•Bandwidth - Maximum

•Gamma - 9.45

•Stretch - On

•Polarity - Positive

•Black Level - Preset and Auto (both toggle switches down)

•Gain - Auto (toggle switch down)

•Gain Switch at back of control box - LO (down)

•Camera Aperture - F2.8

The phakometer is calibrated by finding the size of reflections from steel ball

bearings of radii 11.91,9.53,8.735,8.345,7.94,7.55, 7.135,6.35, and 5.955 mm. The

balls are held in place by a magnetic attachment to the chmrest of the phakometer.

Calibration should be performed every 6 months.

(1) Change the aperture to F4 (remember to change back to F2.8 at the end of

calibration). The aperture is changed because of the high reflectivity of steel.

(2) Record a tag for the calibration with school or location, date, and the radius of the

ball.

(3) Place the largest ball (longest radius) into the magnetic holder (it may need to be

held in place by hand).

(4) Turn the light source to the lowest setting. Obtain best focus for the two light

sources and record for 5 seconds. 134

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (5) Move the slit-lamp base to blur the images, re-focus and record again for 5

seconds.

(6) Move the slit-lamp base to blur the images one more time, re-focus for a third

tune and record again for 5 seconds.

(7) Stop the VCR and repeat this process for each successively steeper steel

calibration ball. (Remember to record the radius for each ball before recording the

images.)

(8) Procedures for digitization and measurement are described in the following

section. Two measurements are taken for each 5 second recording period (total six

readings per ball). Copy and paste the average for each ball radius and the ball

radius itself into a statistical/graphing program such as Cricket. Perform a linear

regression with the radii of the balls as the dependent variable and the average

number of pixels per ball as the independent variable. Record the slope and

intercept for each calibration occasion, as well as which patients are measured at

that site.

Measurement of videophakometry is as follows:

(1) Write the ID numbers of the subjects to be measured on a chronological log sheet

Record the ID# of the subject to be tested on the videotape prior to measurement

Retain the log sheet for later use by the reading center.

(2) Position the patient either sitting or standing comfortably at the chinrest. Turn on

the fixation light and the fiber optic light source. Adjust the height of the chinrest,

not the slit lamp, in order to bring the reflected images to the middle of the

monitor screen. This keeps the light sources and the camera at the same level. 135

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (3) With the illumination of the light sources low, move the fixation fight so that it

appears between the two Purldnje I images. Find the best focus of Purkinje image

I. They should be small, nearly round, and equal in size. Avoid clipping of the

images by the eyelids. Record for about 10 seconds.

*

Figure A. 3: Appearance of Purkinje image I in the phakometer.

136

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (4) Turn up the intensity of the Ught sources. Purkinje image IV is in nearly the same

focal plane as Purkinje image I and should come into view. Adjust the fixation

light to bring the midpoint of the two Purkinje image IVs to the same level as the

Purkinje image Is. They should be placed to the right of the Purkinje image Is on

the monitor screen in order to keep them distinct. Purkinje image IV will move in

the same direction as the fixation light Often the fixation light obscures Purkinje

image IV and must be switched off and on during measurement Find the best

focus for Purkinje image IV and record for about 6 seconds or switch the light off

and on six times.

137

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure A.4: Appearance of Purkinje image IV in the phakometer.

(5) Move the slit-lamp toward the patient by about I cm to find the focal plane for

Purkinje image m . Adjust the fixation light to bring the midpoint of the two

Purkinje image IDs to the same level as the Purkinje image Is. Adjust the intensity

of the illumination to produce visible Purkinje image IDs. They should be placed

138

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. to the right of the Purkinje image Is on the monitor screen in order to keep them

distinct. Purkmje image HI will move in the opposite direction of the fixation

light. If the fixation light obscures Purkmje image ID, it must be switched on and

off during measurement. Find the best focus for Purkmje image HI and record for

about 3 seconds or switch the light off and on once.

(6) Turn off the illumination of the right eye and turn on the illumination of the left

eye.

(7) Record an image of the nose to indicate switching eyes.

(8) Repeat steps (2) through (3).

(9) Stop the VCR and turn off the illumination.

139

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure A.5: Appearance of Purkmje image ID in the phakometer.

After the video is analyzed and the data are input, die Videophakometry log sheet is

marked. The video should be analyzed as soon as possible following each Examination.

140

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Cydoplegic Autorefraction and Peripheral Refraction

Cydoplegic Autorefraction

Cycloplegic autorefraction is the primary outcome measure of the CLAMP Study.

Ten repeated measurements are performed on each eye, followed by peripheral

refraction.

(1) Place the +4 Badal lens rod in straight ahead position.

(2) Place the letter card initially at 25 cm mark. Ask the child if the letters on bottom

line (largest letters) are clear. If yes, instruct child to pick a letter on the bottom

line and report when letter becomes fuzzy. Slide the card slowly away from the

lens until the child first reports blur.

(3) If the bottom line is not clear at 25 cm and the child is myopic based on the

noncycloplegic autorefraction, move the card forward, instructing the child to tell

you when it first becomes clear. Stop and back card off slightly (1 cm or so). If

bottom line still blurred with card at closest position (IS cm mark, corresponding

to for point for about -1.50D), switch to the large asterisk target. If child has 4D of

myopia or more, attach the card (with tape) to the front of the Badal lens,

otherwise insert large the target in the card clip and move it to IS cm mark.

Instruct the myopic child to look at the center of the target and proceed.

(4) If the child is hyperopic, move the card away until child reports that the card is

clear, keep going until child reports blur again. Proceed.

141

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (S) Instruct the child to pick one letter and stare at it. Take at least 10 “good”

readings, meaning the eyes are aligned and the sphere and cylinder readings are

reasonably close to the mode.

Peripheral Refraction

(1) With the child still in the chin rest, position the removable mirror and align the +4

Badal lens rod with angled markings on instrument, being careful to line up front

of rod with appropriate mark. Leave the letter card or target in same position as

for wet AR.

(2) Instruct the child to keep his/her head straight and turn the eyes o n ly to look in the

side mirror. Ask if the child can see the letters (backward, now) in the m h T o r. If

not, rotate the rod slig h tly in either direction until child reports seeing the letters.

Again instruct child to pick a letter on the bottom line. Monitor child’s head and

eye position while performing at least 5 “good” readings. A few children find it

hard to turn just their eyes, and manual straightening of the head (while

instructing child to keep looking at letters in the mirror) may be necessary.

142

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Ultrasonography

A-scan ultrasonography is performed to measure the axial dimensions of the eye. It

requires corneal anesthesia, mydriacyl, and cycloplegia for accurate measurement

The ultrasonography unit (Humphrey 820) is calibrated every six months. Calibration

of the ultrasound is accomplished with a plastic disc of known thickness (4.33mm). Place

this disc in the special round holder on the side of the ultrasound. From the main menu,

choose “Instrument Set-Up” then ‘Test Piece Menu.” The gain is at 40%. Place a small

drop of water on the test piece disc and hold the probe perpendicular to its surface. The

ultrasound will begin to take readings. These readings should equal the printed value on

the disc to the second decimal place.

The ultrasonography procedure is as follows:

(1) The ultrasonography unit (Humphrey 820) is set on these settings:

• Gain = 60%

• Semi-automatic measurement mode

• Phakic

(2) The device is turned on to generate the device menu on the viewing screen.

(3) Choose the “Patient’s Name” option from the menu, and enter the child’s

identification number, followed by touching “Enter” with the light pen.

(4) Choose “Biometry” from the menu with the light pen.

(5) Instill one drop o f 0.5% proparacame in both eyes.

(6) Perform five readings on the each eye:

143

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (a) Instruct the child to look at a distant target during the procedure. He or she is

told that the little light in the end of the probe will come close to his or her

eye.

(b) Introduced the probe very near the right cornea, bringing it in from the side.

(c) Contact the tear film, and shift the probe slightly until an ultrasound trace is

frozen on the screen by the device. As soon as the image is frozen, tap the foot

pedal, once, to maintain the image for inspection.

(d) Visually inspect the frozen trace. If the two lens peaks are approximately

equal in height and the retinal peak is sharp at its anterior most location, save

the image by tapping the foot pedal again. If the image is unacceptable,

depress the foot pedal for a longer period of time until the image disappears

from the screen.

(e) Save five acceptable images.

(f) Choose the “Print” option with the light pen and print out five rows of data,

with anterior chamber depth, lens thickness, and axial length on each row.

(g) Trim the printout to fit the Examination Form and attach it with scotch tape.

Repeat steps (a) through (g) for the left eye. Care must be taken not to affix

tape over the printed data.

144

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Videophakometry Data Analysis

Videophakomctry

Recordings of Purkinje images I, m , and IV will yield anterior and posterior lens

radius of curvatures, Gullstrand posterior lens radius of curvature, and the equivalent

refractive index of the crystalline lens. These raw data are used to calculate the power of

the lens. Recordings of Purkinje images I and IV during measurement of accommodative

response yield the position of the eye during that accommodative response. These data

are used to calculate the response AC/A ratio.

Data is extracted from the videotapes according to the following protocol:

(1) Start the program “Image Analyst.” Select the sequence for PI. Open the tools and

select the intensity tool. Check to see that the intensity threshold of each ROI is

set at 100, and the pathway directs data to the appropriate file for data storage.

(2) Select the sequence for PIV. Check to see that the intensity threshold of each ROI

is set at 85, and the pathway directs data to the appropriate file for data storage.

(3) Select the sequence for PHI. Check to see that the pathway directs data to the

appropriate file for data storage. The intensity threshold can be set at any level.

(4) The VCR output should be connected by cable to the input line of the frame

grabber. Set Image Analyst to live video feed (Command-L). Push play on the

VCR. The video output should appear on the computer monitor. Verify that the

patient name appearing on the screen prior to the Purkinje images is the same as

the chronological log sheet

145

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (5) Click on the screen to freeze the image and stop the VCR. Select Measurement

Modify (Command-E). Type in the last name, then first name o f the subject.

Highlight the name and press Command-C to copy it. Close the dialog box.

(6) Select the sequence for PI. Go back to live video and push play on the VCR Look

for Purkinje image Is that are in focus, round, and equal in size. When suitable

images are found, click on the screen to freeze the image and push pause on the

VCR to hold the place on the videotape.

(7) Place one ROI over each image. Adjust the size and position of the ROI such that

no other reflections are contained within the ROI. Make the measurement by

pressing Command-minus.

(8) Go back to live video and push play on the VCR Find another suitable Purkinje

image I, click on the screen and push pause on the VCR Repeat for a total of six

measurements. If the recording of Purkinje image Is ends before six

measurements were obtained, rewind the tape and review the recordings until six

images are measured.

(7) Select the sequence for PIV. Select Measurement Modify (Command-E) and paste

the subject’s name in place (Command-V). Press “OK.” Go back to live video

(Command-L) and push play on the VCR Look for Purkinje image IVs that are in

focus, distinct, bright, and not covered by either the fixation light or Purkmje

image I. When suitable images are found, click on the screen to freeze the image

and push pause on the VCR to hold the place on the videotape.

(8) Place one ROI over each image. Adjust the size and position of the ROI such that

no other reflections are contained within the ROI. Confirm that each ROI contains

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the outline of an image, ie., that the intensity threshold level in “Tools” is not set

too high. If an ROI does not outline an image, the measurement will fail. Adjust

the intensity threshold to the maximum level that will outline the image. Make the

measurement by pressing Command-minus.

(9) Go back to live video (Command-L) and push play on the VCR. Find another

suitable Purkinje image IV, click on the screen and push pause on the VCR.

Repeat Step 8 for a total o f four measurements. If the recording of Purkinje image

IVs ends before four measurements were obtained, rewind the tape and review the

recordings until four images are measured.

(10) Select the sequence for Pin. Select Measurement Modify (Command-E) and

paste the subject’s name in place (Command-V). Press “OK.” Go back to live

video (Command-L) and push play on the VCR. Look for Purkinje image Ills

that are in best focus, close to but not covered by either the fixation lights or

Purkinje image I, and the brightest. When suitable images are found, click on the

screen to freeze the image and push pause on the VCR to hold the place on the

videotape.

(11) Place one ROI over each image. Adjust the size of the ROI to be larger than the

image. The distribution of brightness within the ROI appears as a “hill” in the

intensity toolbox. Adjust the intensity threshold of the ROI to approximately half

the distance from the peak to the right-hand base of the “hill.” The outline of the

Purkinje image m should appear to be continuous and smooth. Repeat for the

second ROI. Make the measurement by pressing Command-minus.

147

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (12) Go back to live video (Command-L) and push play on the VCR. Find another

suitable Purkinje image m , click on the screen and push pause on the VCR.

Repeat Step 11 for a total of two measurements. If the recording of Purkinje

image Ills ends before two measurements were obtained, rewind the tape and

review the recordings until two images are measured.

(13) Repeat for the left eye.

The files are stored according to the following procedure:

(1) Data are transferred to Excel text files within the folder “Image Analyst.” These

files are named by the year and site of data collection, e.g., “1998 CLAMP

Phakometry Data.” These files become large and cumbersome after about 100

children have been measured (1,000 rows). At every 100 children, the file is re­

named and saved in “Normal” format using a sequential number, e.g., “1998

CLAMP Phakometry Data #1.” Make a backup copy of this file. After the new

numbered data file has been created and backed-up, the file “1998 CLAMP

Phakometry Data” can be deleted. Image Analyst will automatically make a new

“1998 CLAMP Phakometry Data” in the folder “Image Analyst” when the next

child is measured.

(2) Image Analyst will not write to file formats other than text, nor if the text file is

open.

(3) After five or she children have been measured, the number of readings per image

type per child should be checked. Open “1998 CLAMP Phakometry Data” in

Excel. Confirm that there are six Pis, four PIVs, and two PHIs for each subject. If

there are fewer, go back to the tapes and measure images to make the correct 148

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. number of measurements. If there are more readings, do not delete them. They

can be included in the averages.

(4) Excel often puts the next line of text written to it by Image Analyst on the same

line of the last line of the file during saving. When the text file is opened, check to

see if text has failed to be inserted on a new row. If so, insert a row where this text

should appear. Cut and paste the text into the appropriate row.

Lens data are calculated according to the following protocol:

(1) Open the file “1998 CLAMP Phakometry Data #1.” Erase columns A (blank), H,

and I (two columns o f zeroes). Erase the excess wording in the new column A by

selecting that column and replacing “CLAMP:IMAGE 8.1 :PI_8.1” with “PF\

“CLAMP:IMAGE 8.1 :PIV_8.1” with “PIV”, and “CLAMP:IMAGE 8.1 :PHI_8 I”

w ith“P Iir.

(2) For the first subject, write statements to average the six readings for PI, the four

readings for PIV, and the two readings for Pm. Highlight and copy these

statements, then paste them into the rows for the next subject. Adjust the range for

the statements if the number of readings differs from the standard amount.

(3) After all averages have been calculated, save the file in Normal format Copy the

column of averages and paste special the values back into the column. Select the

entire spreadsheet and sort on the column of averages. Confirm that the sort has

effectively separated all Pis, PIVs, and PDIs. If there is any overlap, cut and paste

to keep the same categories together, but separate from each other without

overlap. Erase column F (non-averaged values).

149

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (4) Create a new file called “1998 CLAMP Phakometry Averages.” Cut and paste the

rows containing PIV data from the file “1998 CLAMP Phakometry Data #1” to

the file “1998 CLAMP Averages.” Erase the columns containing PIV, date, time,

and zeroes leaving only the subject names and the average data. Select these two

remaining columns and sort by the subject name. Create the headings “Subject

Name” and “PIV” at the top of the columns. Repeat for PI and P in data. Confirm

that the names are the same across the rows of values. Erase the two extra

columns of names. Save the file “1998 CLAMP Phakometry Averages.”

(5) Repeat for the other numbered data files.

(6) Insert a column for SIDs in column A in the file “1998 CLAMP Phakometry

Averages.” Obtain SIDs from the Filemaker Pro Database and insert the

appropriate SID for each subject.

(7) Open the Excel file “Data Calc.” Open the Excel file for the appropriate year, for

example “1998 CLAMP Phakometry Averages.” Copy and paste the SIDs,

names, and values for Purkinje image I, IH, and IV into the appropriate columns.

Cut and paste the PHI data to the appropriate column, then the PIV data, then the

PI data.

(8) Sort all data by SID. Obtain the school for each SID that year from the data base.

Re-sort the data by school. Write the appropriate calibration formula from that

school into the three columns “Eq Mirror Rad” and fill down for that school. Re­

sort the data by SID.

150

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (9) Obtain biometric data for the appropriate study year, containing, SID,

VREFWET, ACD, LT, and VCD. Copy and paste these values into the

appropriate columns in the spreadsheet “Data Calc.”

(10) Paste SID from the biometry file into one of the columns in “Data Calc .” Check

that the SIDs for the Purkinje images match the SIDs for the biometric variables,

then erase the extra column of SIDs.

(11) Perform a fill down on all remaining columns.

(12) Open the macro “Index Calc.” Check that the range of the macro equals or

exceeds the range of rows in the “Data Calc” spreadsheet. Run the macro.

(13) Conform that the value for VREF WET equal the calculated refractive error to

four decimal places. If not, re-run the macro and re-check the agreement between

VREF WET and the calculated refractive error. Re-run the macro as necessary

to create agreement to four decimal places.

(14) Save the file with appropriate site and year, (e.g., “1998 CLAMP Data Calc.”)

(15) Create an Excel file with the appropriate site and year, for example “1998

CLAMP Lens Data Transmission.” Copy and paste special the values for SID,

ALC, PLC, and IND from “1998 CLAMP Data Calc” into “1998 CLAMP Lens

Data Transmission.”

(16) Change the values of IND in “1998 CLAMP Data Calc” from those calculated to

1.416. Fill down the column of IND with the value of 1.416.

(17) Copy the values and paste special the values of PLC from “1998 CLAMP Data

Calc” into a column titled “GPLC” in “1998 CLAMP Lens Data Transmission.”

(18) Save the file “1998 CLAMP Lens Data Transmission.” 151

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reading for AC/A Ratio

AC/A ratio data are extracted from videotapes according to the following protocol;

(1) Assemble Xerox copies of the edited raw data sheets that were sent to the

Coordinating Center in chronological order with respect to the date of testing.

Organize the days of testing in the order of children tested according to the log

from corneal topography or phakometry. This is the order in which children will

appear on the tapes.

(2) Cables should be arranged m the following manner

A) a video cable should go from the VCR Out port on the multiplexer to the

Video In port on the VCR

B) a video cable should go from the VCR In port on the multiplexer to the Video

Out port on the VCR

C) a video cable should go from the Monitor A port on the multiplexer to the

input cable to the frame grabber

D) a video cable should go from the left Audio Out port on the VCR to the EX

/ MIC input on the Sony CD Player/Amplifier—earphones plug into the

earphone jack on the front of the Sony CD Player/Amplifier

E) The multiplexer should be set to “Quad” and “Play.”

F) The VCR should be set to LI input.

(3) Start the program “Image Analyst.” Select the sequence for Calibration. Open the

tools and select the intensity threshold tool. Check to see that the intensity

threshold of the upper ROI is set at 100, and the pathway directs data to the 152

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. appropriate file for data storage. Repeat for the sequences OD, 2D, and 4D. Re­

select the sequence for Calibration.

(4) The multiplexer should be set to “Quad” and “Play.” Channel I on the multiplexer

controls the playback from the Canon R-l autorefractor, Channel 2 the playback

from the accessory camera monitoring eye position. Have both channels active.

Set Image Analyst to live video feed (Command-L). Push play on the VCR. The

output from both channels should appear on the computer monitor.

(5) Listen for the name of the patient as recorded on the audio track of the tape and

verify that the patient name agrees with the data form and the chronological log

sheet. Confirm that the sequence is for Calibration. Select Measurement Modify

(Command-E). Type in the last name then first name of the subject. Highlight the

name and press Command-C to copy it. Close the dialog box.

(6) Push pause on the VCR. Push the button on the multiplexer for Channel 2. Push

play on the VCR. Listen for the examiner instructing the patient to look at the

green dot. When the patient’s fixation appears to be stable, push pause on the

VCR.

(7) Click on the screen to freeze the image. Often the screen will appear to have

interference on it Without changing the VCR, push Command-L to go back to

live video and then re-click on the screen to freeze it again. Often this clears up

the interference. If this is unsuccessful after several attempts, go back to live

video (Command-L) and advance the VCR by one or two frames with the

jog/shuttle wheel, then re-freeze the screen by clicking on it Repeating these

153

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. procedures will produce a “clean” freeze, one that is clear and without

interference.

(8) Confirm that the sequence is for Calibration. Place the upper ROI over Purkmje

image I and the lower ROI over Purkinje image IV. Adjust the brightness

threshold for the lower ROI to the maximum level that detects the presence of

the Purkinje image IV. Make the measurement by pressing Command-minus.

(9) Return to live video (Command-L). Push play on the VCR and listen for the

examiner instructing the patient to fixate the red circles. When the patient moves

his eyes from the green dot to the red circles, push pause on the VCR. Repeat

steps (7) and (8).

(10) Repeat step (9) once more after the patient looks for a second time at the green

dot and once more after the patient looks for a second time at the red circles.

(11) Select the sequence for OD. Select Measurement Modify (Command-E) and

paste the subject’s name in place (Command-V).

(12) Return to live video (Command-L) with the VCR on pause. Push the button on

the multiplexer for Channel 1. Advance the tape either by play or by the

jog/shuttle wheel to the frame corresponding to the first autorefractor reading for

OD, then pause the VCR. The location of OD readings on the form differs

depending on whether the subject wears a correction or not (see Figures I and 2).

Do not include readings that are crossed out during editing.

(13) Push the button on the multiplexer for Channel 2. If an image of the eye appears,

freeze the image by clicking on the screen. Follow the protocol in step (7) until a

clear frozen image is obtained. If the screen is black, advance the VCR with 154

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. jog/shuttle wheel by one or two frames until an image of the eye appears, then

freeze the image by clicking on the screen. Follow the protocol in step (7) until a

clear frozen image is obtained.

(14) Confirm that the sequence is for OD. Place the upper ROI over Puikinje image I

and the lower ROI over Purkmje image IV. Adjust the brightness threshold for

the lower ROI to the maximum level that detects the presence of the Puikinje

image IV. Make the measurement by pressing Command-minus.

(15) Repeat steps (12)-(14) for the next autorefractor reading in OD. Make

measurements for up to five readings for OD.

(16) Select the sequence for 2D. Select Measurement Modify (Command-E) and

paste the subject’s name in place (Command-V).

(17) Repeat steps (12)-(14) for the five autorefractor readings for 2D.

(18) Select the sequence for 4D. Select Measurement Modify (Command-E) and

paste the subject’s name in place (Command-V).

(19) Repeat steps (12)-(14) for the five autorefractor readings for 4D.

AC/A files are stored according to the following procedures:

(1) Data are transferred to Excel text files within the folder “Image Analyst.” These

files are named by the year and site of data collection, e.g., “1995 CLAMP AC/A

Data.” These files become large and cumbersome after about 50 children have

been measured (1,000 rows). At every 50 children, the file is re-named and saved

in “Normal” format using a sequential number, e.g., “1995 CLAMP AC/A Data

#1.” Make a backup copy of this file. After the new numbered data file has been

created and backed-up, the file “1995 CLAMP AC/A Data” can be deleted. Image 155

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Analyst will automatically make a new “1995 CLAMP AC/A Data” in the folder

“Image Analyst” when the next child is measured.

(2) Image Analyst will not write to file formats other than text, nor if the text file is

open.

(3) After five or six children have been measured, the number of readings per child

and sequence selection should be checked. Open “1995 CLAMP AC/A Data” in

Excel. Confirm that there are four calibrations and up to five readings each in the

sequences for OD, 2D, and 4D. If there are fewer by error, go back to the tapes

and measure images to make the correct number of measurements. If the

sequences are mislabeled, re-label them according to the number of readings

taken (e.g., the last five readings belong to 4D), or according to the values of the

measurement (e.g., an abrupt jump to higher values indicates a change in

sequence). If there is any ambiguity as to which sequence readings belong, repeat

the measurements for the subject.

(4) If a subject has any missing or unreadable data, keep a log of these events for later

reconciliation with the Excel data files.

(5) Excel often puts the next line of text written to it by Image Analyst on the same

line of the last line of the file during saving. When the text file is opened, check to

see if text has failed to be inserted on a new row. If so, insert a row where this text

should appear. Cut and paste the text into the appropriate row.

156

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. AC/A Ratio Calculations

(1) Open the file “1995 CLAMP AC/A Data #1.” Erase columns A (blank), H, and I

(two columns of zeroes). Erase the excess wording m the new column A by

selecting that column and replacing “08893 :IMAGE 8. l :Calibration_8.1” with

Calibration, “08893:IMAGE 8.1:0D_8 1” with OD, “08893:IMAGE 8.1:2D_8.1”

with 2D, and “08893:IMAGE 8.1:4D_8.1” with 4D.

(2) Sort the Calibrations subject by subject by selecting rows containing the four

Calibration readings per subject, then sorting by the column containing

Calibration data.

(3) Sorting will produce two pans of Calibration data, one pah: for the green dot and

one pair for the red circles. For the first subject, write a statement to average one

of the pairs of Calibration, then another statement to average the other pair.

Highlight and copy these statements, then paste them in for each subject.

(4) Take a difference between the two averages for each subject. The difference

should be positive. After all averages have been calculated, copy the column of

averages and paste special the values back into the column.

(5) Insert a column for SIDs. Obtain SIDs from the Filemaker Pro Database and insert

the appropriate SID for each subject Fill down so that the SID appears on every

line containing that subject’s name.

(6) Review the data for OD, 2D, and 4D for each subject. Confirm that there is at least

one data point for each o f these sequences. If a subject has missing data (no data)

for one of these sequences that is not in the log of missing data created during

measurement, go back to the original tapes and re-measure. Copy the data from 157

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the Excel text spreadsheet Image Analyst is writing to into the spreadsheet with

the missing data. If the data are truly absent, enter the sequence that has no data

and place a period (.) to mark the place for the missing data.

(7) Repeat steps (I) through (6 ) for the other numbered data files.

(8) Open the Excel file “1995 CLAMP AC/A Data #1.” Select the entire spreadsheet

except for the headings and sort on column of averages. Create a new Excel file

named for the year and site, for example “1995 CLAMP ACCAL.” Cut and paste

the SIDs and the column containing the Calibration difference data from the file

“1995 CLAMP AC/A Data #1” into the file “1995 CLAMP ACCAL” under the

headings “SID” and “ACCAL,” respectively. Close the file “1995 CLAMP

AC/A Data #1.” Do not save any changes.

(9) Repeat step (8) for the other numbered data files. Do not create a new Excel file.

Cut and paste data into the existing file “1995 CLAMP ACCAL.” Select the

entire spreadsheet in the file “1995 CLAMP ACCAL” except for the headings

and sort by the column for the SID. Save the file “1995 CLAMP ACCAL” in

Normal format.

(10) Re-open the file “1995 CLAMP AC/A Data #1.” Select the entire spreadsheet

except for the headings. Sort by column A, the sequence name. Confirm that the

sort has separated the sequences OD, 2D, and 4D from each other.

(11) Create a new Excel file named for the year and site, for example “1995 CLAMP

ACOD.” Cut and paste the SIDs and the column o f data containing the sequence

OD data from the file “1995 CLAMP AC/A Data #1” into the file “1995 CLAMP

ACOD” under the headings “SID” and “ACOD,” respectively. 158

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (12) Create a new Excel file named for the year and site, for example “1995 CLAMP

AC2DCut and paste the SIDs and the column o f data containing the sequence

2D data from the file “1995 CLAMP AC/A Data #1” into the file “1995 CLAMP

AC2D” under the headings “SID” and “AC2Drespectively.

(13) Create anew Excel file named for the year and site, for example “1995 CLAMP

AC4D.” Cut and paste the SIDs and the column of data containing the sequence

4D data from the file “1995 CLAMP AC/A Data #1” into the file “1995 CLAMP

AC4D” under the headings “SID” and “AC4D,” respectively.

(14) Close the file “1995 CLAMP AC/A Data #1.” Do not save any changes.

(15) Repeat steps (10) through (15) for the other numbered data files. Do not create

new Excel files. Cut and paste data from numbered data files into the existing

files “1995 CLAMP ACOD,” “1995 CLAMP AC2D,” and “1995 CLAMP

AC4D.”

(16) To facilitate data transmission, each of the sequences OD, 2D, and 4D must have

five values each. If the number of values is less than that amount, enter the SID

and a period (.) for the missing data the number of times needed to bring the

number of entries to five. Save the file in Normal format with the appropriate

year and site as in the examples “1995 CLAMP ACOD,” “1995 CLAMP AC2D,”

and “1995 CLAMP AC4D.”

(17) Open the Excel file “1995 CLAMP ACOD.” Pull down the Tools menu and

select the macro “ACOD 1995.2! ACTranspose” Confirm that the range of rows

named in the macro equals or exceeds the number of rows in the spreadsheet.

159

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Run the macro. This will transpose the data from rows to columns. Label the five

transposed columns “ACODOl” through “AC0DO5.”

(18) Select the entire spreadsheet in the file “1995 CLAMP ACOD” except for the

headings and sort by the column for AC0D01. Some rows will now contain SID

numbers rather than data. Select rows above the last row containing only SIDs.

Sort by SID. Erase rows which contain the duplicate SID, leaving rows

containing data. Erase the column o f ACOD which has bee transposed. Save the

file “1995 CLAMP ACOD” in Normal format

(19) Repeat steps (17) and (18) for the files “1995 CLAMP AC2D” and “1995

CLAMP AC4D”

(20) Confirm that the number and order of SIDs is the same for each file “1995

CLAMP ACCAL,” “ 1995 CLAMP ACOD,” “ 1995 CLAMP AC2D,” and “ 1995

CLAMP AC4D.” Discrepancies must be resolved before transmission of data to

the Coordinating Center.

160

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Videokeratography and Orbscan

The purpose of the videokeratography is to provide a topographic map of the corneal

curvature in order to provide information about how the contact lens may affect the shape

of approximately the central 8 mm of the cornea. Orbscan provides similar information to

the videokeratography along with topography o f the posterior cornea and comeal

thickness.

Videokeratography

Following is the complete instructions on how to conduct the videokeratography

portion of the examination:

(1) Click the pointer on the Full Exam button in the Main Menu.

(2) Enter patient’s name or select patient in the Patient Information screen.

• New patient

• Enter the patient’s name in the format:

ID Jnitials (eg, 066, SC)

•H it return

• Existing patient

• Search for patient’s name by clicking in the name box to activate the blinking

cursor.

• Begin typing the patient’s last name.

• When name appears in the Name field, hit return

• Add Patient Information screen appears

161

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. • Click Yes on Unknown Patient Name screen

• Enter ID# in Patient # if the patient has ID#; if not skip this step

• Confirm First name

• Confirm Last name

• Enter gender

• Click OK under Operator

(3) The Exam Information screen appears

• Select OU

• Select CLAMP under Group

• Select your name under Operator

• Hit return

(4) Align patient in chin rest with chin positioned in the side marked “R” and head at a

45° angle.

(5) Make sure the patient’s forehead is pressed against the forehead rest.

(6) Tell the patient to look at the red light.

(7) Position the projection head of the instrument until a clear image of the eye appears

on the screen.

(8) Adjust the height of the instrument by rotating the joystick handle.

(9) Center the crosshairs inside the smallest ring o f the live image.

(10) Move the joystick forward and back to get the clearest image of the smallest ring.

(11) Ask patient to blink eyes then open their eyes wide.

(12) Make minor corrections to focus.

(13) Press the button on top of the joystick to capture the image. 162

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (14) Capture another image? Hit no if the image is of good quality.

(15) If the image on the next screen says high confidence, click the cursor on it. If there

is message other than high confidence on the screen, hit the redo button and capture

one high confidenceimage.

(16) If the image is acceptable, click OK.

(17) Click OK to perform videokeratography on the other eye.

(18) Repeat steps (4) using the side marked “L” through (16).

(19) Hit options.

(20) Hit print.

Orbscan

Following is the complete instructions on how to conduct the videokeratography

portion of the examination:

(1) Click the pointer on the New Exam button in the File Menu.

(2) Enter patient’s name or select patient in the Unsaved Exam screen.

• New patient

• Enter information in Patient: Last, First in the format:

ID Jnititds (eg, 066,SC)

• Enter information in ID in the format:

CLAMPID (eg, CLAMP066)

(3) Position the patient in the chin rest and tell them to place then hands on then knees

(4) Instruct the patient to not move the hands or the feet when s/he is told to open wide.

(5) Instruct the patient to look at the red, flashing light while holding the eyes wide open. 163

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (6) Align the red circle on the reflection of the flashing light both horizontally and

vertically. Push in or out on the joystick to focus the camera and bring the two

arches together in the circle, as in Figure A.6.

Figure A.6: Proper position of arches to take Orbscan reading.

(7) Press the button on the side of the camera to take the picture and tell the subjects to

remain very still for a few seconds.

(8) Repeat steps (5) through (7) for the left eye.

(9) When an image of the eye appears, hit Done. Repeat this four times.

Note: If a message appears that states “Too much eye movement. Do you wish to

continue processing?” Hit Yes.

Note: If a message appears that states “Not enough data is available to continue with

this analysis. Please reacquire this exam.” Hit OK then continue.

(10) When the map appears on the screen, hit X on the top, right of the screen. Hit Return

twice to save the information.

(II) Repeat steps (9) through (10) for the left eye. 164

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (12) Place the printouts in the patients file.

Rigid Contact Lens Fitting and Assessment

The goal of the contact lens fitting is to fit the subjects on alignment. The contact lens

fitting will be assessed by evaluation of the fluorescein pattern by the clinician.

Photographs of the fluorescein pattern will be taken. Throughout the study, another eye

care practitioner must approve any changes of the contact lens parameters, other than

power.

The trial lens set consists of 31 lenses. The steepest base curve is 7.00 mm (48.25 D);

the flattest base curve is 8.50 mm (39.75 D). The following parameters will be constant

throughout the lenses:

• Diameter 9.2 mm

• Optic Zone Diameter 7.8 mm

• Power -2.00 D

• Material Z thin

(1) Choose the initial base curve based on keratometry according to Table A.2.

165

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Difference between Ks Initial BC Spherical 0.50 D flatter than flat K 0.12 D - 0.75 D 0.25 D flatter than flat K 0.87 D- 1.37 D equal to flat K > 1.50 D (0.33 D X difference b/t Ks) steeper than flat K

Table A.2: Table to determine initial base curve from keratometry readings.

(2) Place the appropriate contact lens on each eye with one drop of 0.5% proparacaine

in the contact lens.

(3) Instill sodium fluorescein as follows:

• Wet the fluorescein strip with a sterile saline or multi-purpose solution.

• Apply a small amount of fluorescein by just touching the tip of the wetted

fluorescein strip to the superior bulbar conjunctiva.

(4) Evaluate the fluorescein pattern for each eye and record the findings on the

Unmasked Examination Form

(5) Photograph both fluorescein patterns according to the protocol in section 13.4.

(6) Remove both contact lenses.

(7) Repeat steps (2) through (6) with a 0.1 mm steeper base curve contact lens.

(8) Repeat steps (2) through (6) with a 0.1 mm flatter base curve contact lens.

166

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (9) Order the contact lens with a power equal to the spherical component from the

manifest refraction that provides the best alignment fit by clinical assessment and

the fluorescein photographs.

Photography of the fluorescent patterns should take place on all rigid contact lens

wearing-subjects at the 6-month visits.

(1) Clean the slit lamp biomicroscope chin and head rest.

(2) Verify that the following parameters are correct:

• Flash intensity = 5

• Beam splitter = in

• Magnification = 16X

• Background illuminator = off

• Aperture = wide open

• Cobalt filter = in

(2) Place the Wratten 12 filter in front of the slit lamp’s objective lenses.

(3) Assure the patient’s comfort and position in the slit lamp camera.

(4) Set the light tower angle at 30* temporal, moving the illumination angle slightly to

eliminate light reflexes.

(5) Set the light intensity to a tolerable level for the patient. Lowering light intensity

may be particularly helpful with extremely photophobic patients.

(6) Instill sodium fluorescein as follows:

• Wet the fluorescein strip with a sterile saline or multi-purpose solution.

• Apply a small amount of fluorescein by just touching the tip of the wetted

fluorescein strip to the superior bulbar conjunctiva. 167

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. • Wait 30 to 60 seconds after fluorescein application to take the photograph.

(7) Photograph the fluorescein pattern twice on each eye, counting to three slowly

between each photograph.

(8) When the film is finished, place the film in the envelope and write the subject

number on the outside.

The rigid contact lenses should be assessed every six months according to the following protocol: (1) Complete a spherical over refraction with trial lenses on each eye separately.

(2) Instill sodium fluorescein as follows:

• Wet the fluorescein strip with a sterile saline or multi-purpose solution.

• Apply a small amount of fluorescein by just touching the tip of the wetted

fluorescent strip to the superior bulbar conjunctiva.

(3) Evaluate the fluorescein pattern for each eye and record the findings on the

Unmasked Examination Form

(4) Photograph both fluorescein patterns according to the protocol in section 13.4.

Another licensed eye care practitioner must approve a change of any parameter of

the contact lens except power.

168

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Certification Procedures

The purpose of certification requirements in the CLAMP Study is to assure that

procedures are being performed in accordance with the CLAMP Study protocol. The

Principal Investigator and Mentor supervise certification. The Principal Investigator

oversees certification, issues certification documents and reports any deviation from

protocol to the Mentor.

Prior to enrolling any CLAMP Study subjects or collecting any CLAMP Study data,

each Optometrist must be certified to perform each of the tasks listed below. The

CLAMP Principal Investigator encourages all Optometrists to participate actively in

examining CLAMP Study subjects, and in order to be re-certified each year, each

individual must process at least 10 CLAMP Study patients in a calendar year.

The key CLAMP Study tasks requiring certification are:

• Accommodative testing (accommodative response, and response AC/A ratio)

• Keratometry

• Tonometry

• Cycloplegic autorefraction

• Peripheral refraction

• Videophakometry

• Ultrasonography

Each CLAMP Study certified task has two levels of certification (granted by the

Principal Investigator or Mentor):

169

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. • Full certification for a given task is granted upon satisfactory completion of a

written examination on that task and demonstration o f the specific procedures

associated with that task as detailed below. Full certification is usually granted

following the initial training meeting but will sometimes be accomplished by mail

and telephone. Throughout the Study, full certification is maintained by performing

the specific task on at least 10 CLEK Study patients in a calendar year.

• Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination

from the Study should be considered.

All CLAMP Study personnel are required to:

(1) read the CLAMP Operations Manual and

(2) demonstrate their ability to perform their appointed tasks by completion of a

written examination and demonstration of proper Study procedures.

A centralized training and certification meeting will be held at The Ohio State

University College o f Optometry prior to patient enrollment. Two participating

Optometrists will be certified in each of the key CLAMP Study tasks.

In the event someone joins the CLAMP Study after the training meeting, he or she

will be certified for the appropriate key tasks as follows:

(1) Complete a written test

(2) Complete a telephone interview with the examiner who certifies that task.

Each person certified in at least one of the key tasks listed above is assigned his or her

certification initials (eg, KSZ) by the Principal Investigator. These certification initials

are entered on all CLAMP Forms as indicated. 170

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Accommodative Testing

The CLAMP Study must have at least two people certified for accommodative testing

in order to enroll and follow CLAMP Study subjects. This person can be either an

Optometrist or the Mentor. The certification requirements for accommodative testing are:

• To attend a CLAMP Study training session concerning CLAMP Study design and

methods, accommodative testing, and forms completion and data inspection;

• To read the CLAMP Operations Manual, particularly Chapter 6, “Accommodation

Measurement;”

• To review CLAMP Study data collection forms, particularly the CLAMP Masked

Examination Form;

• To complete a written examination on accommodative testing; and

• To complete an in-person or telephone accommodative testing training session.

After satisfactory completion of all requirements, the Principal Investigator issues

verification of certification. To keep certification current, the certified task must be

performed satisfactorily on at least 10 Study patients in a calendar year.

Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Study should be considered.

171

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Keratometry

The CLAMP Study must have at least two people certified for keratometry in order to

enroll and follow CLAMP Study subjects. This person can be either an Optometrist or the

Mentor. The certification requirements for keratometry are:

• To attend the CLAMP Study training session concerning the design of the CLAMP

Study and the methods for keratometry,

• To read the CLAMP Operations Manual, especially Chapter 6, “Visual Acuity,

Phoria, Pupillary Distance, Retinoscopy, Keratometry, and Tonometry” and to learn

the documentation of keratometry using the CLAMP Examination Form;

• To review CLAMP Study data collection forms, especially the CLAMP Masked

Examination Form;

• To complete a written examination on keratometry; and

• To complete an in-person or telephone keratometry training session.

After satisfactory completion of all requirements, verification of certification is issued

by the Principal Investigator. To keep certification current, this certified task must be

performed on at least 10 Study patients in a calendar year.

Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Study should be considered.

172

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Tonometry

The CLAMP Study must have at least two people certified for Tonometry in order to

enroll and follow CLAMP Study subjects. This person can be either an Optometrist or the

Mentor. The certification requirements for tonometry are:

• To attend a CLAMP Study training session concerning CLAMP Study design and

methods, tonometry, and forms completion and data inspection;

• To read the CLAMP Operations Manual, particularly Chapter 7, “Visual Acuity,

Phoria, Pupillary Distance, Retinoscopy, Keratometry, and Tonometry;”

• To review CLAMP Study data collection forms, particularly the CLAMP Masked

Examination Form;

• To complete a written examination on tonometry; and

• To complete an in-person or telephone tonometry training session.

After satisfactory completion of all requirements, the Principal Investigator issues

verification of certification. To keep certification current, the certified task must be

performed satisfactorily on at least 10 Study patients in a calendar year.

Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Study should be considered.

Videophakometry

The CLAMP Study must have at least two people certified for videophakometry

measurement. Certification requirements for videophakometry are:

173

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. • To attend a CLAMP Study training session concerning the design of the CLAMP

Study and the methods for videophakometry and documentation;

• To read the CLAMP Operations Manual, especially Chapter 8, “Videophakometry”,

and to learn videophakometry measurement and disk storage techniques;

• To complete a written examination on videophakometry; and

• To complete an in-person or telephone videophakometry training session.

After satisfactory completion of all requirements, the Principal Investigator issues

verification of certification. To keep certification current, the certified task must be

performed satisfactorily on at least 10 Study patients in a calendar year.

Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Study should be considered.

Autorefraction

The CLAMP Study must have at least two people certified for cycloplegic

autorefraction and peripheral refraction. Certification requirements for autorefraction are:

• To attend the CLAMP Study training session concerning the design of the CLAMP

Study and the methods for refractive error measurement by autorefraction;

• To read the CLEK Operations Manual, especially Chapter 9, “Cycloplegic

Autorefraction and Peripheral Refraction”, and to learn the documentation of

refractive error via autorefraction using the CLAMP Examination Form;

• To review CLAMP Study data collection forms, especially the CLAMP

Examination Form; 174

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. • To complete a written examination on autorefraction; and

• To complete an in-person or telephone autorefraction training session.

After satisfactory completion o f all requirements, the Principal Investigator issues

verification of certification. To keep certification current, this certified task must be

performed on at least 10 Study patients in a calendar year.

Probationary certification is granted in the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Stucfy should be considered.

Ultrasonography

The CLAMP Study must have two certified people for ultrasonography. Certification

requirements for the ultrasonography protocol are:

• To attend a CLAMP Study training session concerning the design of the CLAMP

Stuffy and the methods for ultrasonography;

• To read the CLAMP Operations Manual, especially Chapter 10, “Ultrasonography”;

• To review CLAMP Study data collection forms, especially the CLAMP

Examination Form;

• To complete a written examination on ultrasonography; and

• To complete an in-person or telephone training session.

After satisfactory completion of all requirements, verification of certification is issued

by the Principal Investigator To keep certification current, the certified task must be

performed satisfactorily on at least 10 Study patients in a calendar year.

175

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Probationary certification is granted m the event of unsatisfactory performance. Full

certification must be restored within a reasonable period of time, or termination from the

Study should be considered.

176

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Appendix B

Forms

This appendix contains the following forms:

Tracking Form Masked Exam Form Unmasked Exam Form SCL Check Form 1 and 2 Month Masked Form 1 and 2 Unmasked Form 6 Month RGP Form 6 Month SCL Form Annual Masked Form Annual Unmasked Form Parents CL Form Subjects CL Form Parents NW Form Subjects NW Form VAForm

177

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Tracking Form

•Complete this form at enrollment for every subject ■Update each year as necessary. •Keep hard copy only (no data entry necessary) 1. Patient's Name:

Last First Middle 2. School:

3. Mother's Name (even if last name same as subject’s):

Last First Middle

4. Father's Name (even if last name same as subject’s):

Last First Middle 5. Subject’s Home Address:

Number and street

City State Zip code

6. ( ) Home phone Best time to call

7. ( ) Work phone o f parent Which parent Best tune to call

8. Date o f birth: c o c o m mm dd yy 9. Place of birth: City, state

10. Gender Di Male 0 2 Female

11. Social Security Number I — 1“ —

178

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 12. Closest friend or relative n o living t with subject

Last First

Number and street

City State Zip code

( ) Phone

13. Which of the following categories best describes your child? (optional) □ i American Indian or Alaskan Native □2 Asian or Pacific Islander □ 3 Black, not of Hispanic origin □4 Hispanic □s White, not of Hispanic origin □s Other or unknown

14. Name of present eye doctor:

Last First

Number and street

City State Zip code ( ) Phone

The Contact Lett a and Myopia Progression (CLAMP) Study has my permission to forward information pertaining to my visual health to the eye cate practitioner listed in question #14.

Signature: Date:

179

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Masked Exam Form

1. Vldeokeratography 'Attach vkfeokeratowiiphy printouts to Unmasked Exam Fonnl

2. Keratometry 2m. OD /I II 1•1 II 1 @ 2b. Irregular Mires OD: □ i No ChYes 2c. OS /111 •1 II 1 2d. Irregular Mires OS: □ i No ChYes 2e. OD 1 111 . 1 II 1/Mil .1 II 1

2f. Irregular Mires OD: □ l N o □2 Yes 2*.os n n . n n /I II 1•1 II 1 @ 2h. Irregular Mires OS: □ i No □2 Yes

3 .1 drop 0.5% proparacaine OU 3a. J am / pm

4. Tonopen: 4a. OD | || | mmHp 4b. O mmHg

5.1 drop 1.0% tropicamide OU 5a. am /pm LAntorefractkn 30 minntes after first droe 5b. : | || 1 am / pm

6. Cydoplegic Autorefraction: jattachAmoceftactorFonn below

7. Certification:______

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Unmasked Exam Form

I. Chief complaint:

2. Personal Ocular Hx: 2a. Eye turns? □iNo D2 Yes. 2b. Last eye exam? 2c. Last Rx? ___ 3. Family Ocular Hx: 3a. Glaucoma? □ 1 No Yes 4. Personal Health Hx: 4a. DM? □ 1 No Yes 4b. HTN? □ t No □ 9 Yes 4c. Thyroid? □ 1 No □ 9 Yes 4d. Heart probs? □ 1 No □ 9 Yes 5. Family Health Hx: 5a. DM? Di No □ 9 Yes

5b. HTN? □ 1 No □ 9 Yes 5c. Thyroid? □ 1 No □ 9 Yes 5d. Heart probs? □1 No □ 9 Yes 6. Medications: □ 1 No □ 9 Yes 7. Allergies: □ 1 No □ 9 Yes

8. VA with habitual correction: □ i SCL □2rgp □ 3 Glasses □* None 8a. OD 8b. OS 8c. OU 9. Accommodative Assessment: lAdacfa amarefractor printout here

Trial lens: I— ll— I* I__ 11__I

181

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 10. Versions: □ i Full and smooth Oz Other______11. Pupillary distance: 11a. Distance: ______lib . N ea r _____ 12. Near Point of Convergence:______cm 13. Accommodative amplitudes: 13a. OD ______D 13b. OS______D 13c. OU______D 14. Randot stereo:______seconds o f arc 15. Confrontation visual field: □ Full to finger count OU 0 Other:_____ 16. Pupils are equal, round and reactive to light: □ Yes □ No: _ 17. Retinoscopy: _ _ ^ 17..OD ( ) I I 1.1 I ~1(—) I I X

17b.OS ( ) I I l.| I | (~) I I X 18. Manifest refraction: ^ ^ 18.-OD ( ) | | | . l I ~[ (—) I I 20/

18b.OS ( ) I I I-I |~~|(-) I I 20/ 19. Final Rx (if different from manifest refraction): WfcOD ( ) I I I-I I ~| (-) I I X

19b. OS ( ) I I I ■ I I | ( - ) I I X

20. Von Graefe phoria: distance (+ = eso; - = exo) 20a. Horiz:______20b. Vert: 20. Von Graefe phoria: near (+ - eso; - = exo) 21a. Horiz:______21b. Gradient AC/A: (+1.00) 22. Cover Test with manifest refraction: (+ = eso; - = exo) 22a. Distance: ______22b. Near ______

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 23. SUt Lamp Examination: OD OS Lids and Lashes Cornea Conjunctiva Anterior Chamber bis Lens Vitreous

24. Contact lens fitting — OP: O D -C nhil BC Definite Clearance Clearance Alignment Touch Definite Touch 24a. Initial 1 2 3 4 5 24b. 0.2 steeper I 2 3 4 5 24c. 0.2 flatter 1 2 3 4 5

OD-Peripheral Minimal Unacceptable Minimal Acceptable Avenge High Acceptable High Unacceptable 24d Initial I 2 3 4 5 24c. 0.2 steeper 1 2 3 4 5 24C 0.2 flatter 1 2 3 4 5

OD-Mevameat Minimal Unacceptable Minimal Acceptable Avenge High Acceptable High Unacceptable 24ft In itia l 1 2 3 4 5 24b. 0 2 steeper 1 2 3 4 5 24i. 0 .2 flatter I 2 3 4 5

OD-Centratieu Ccntnl Temporal Nasal Superior Inferior 24j. Initial 1 2 3 4 5 24k. 0.2 deeper 1 2 3 4 5 24L 0.2 flatter 1 2 3 4 5

OD-Cantratian Acceptable Unacceptable 24m. initial I 2 24n. 0.2 steeper 1 2 24o. 0.2 flatter 1 2

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 25. Contact lens fitting — OS: OS-C«ntr*l BC Definite Clcatance Cleamnce Alignment Touch Definite Touch 25a. Initial 1 2 3 4 5 25b. 0.2 steeper 1 2 3 4 5 25c. 0.2 flatter 1 2 3 4 5

OS-Peripheral Minimal Unacceptable Minimal Acceptable Average High Acceptable High Unacceptable 254 Initial 1 2 3 4 5 25e. 0.2 steeper I 2 3 4 5 25C 0.2 flatter 1 2 3 4 5

OS-Mevement Minimal Unacceptable Minimal Acceptable Avenge High Acceptable High Unacceptable 25ft initial 1 2 3 4 5 25b. 0.2 steeper I 2 3 4 5 25L 0.2 flatter 1 2 3 4 5

OS-Cantratien Central Temporal Nani Superior Inferior 25j. Initial 1 2 3 4 5 25k. 0.2 steeper 1 2 3 4 5 251 0.2 flatter I 2 3 4 5

OS-Cantratien Acceptable Unacceptable 25m. Initial 1 2 25n. 0.2 steeper I 2 25o. 0.2 flatter I 2 26. Funduscopy (BIO and 78D): OD OS C/D Rim Color Macula Vessels Periphery

Other findings

28. Assessment: 29. Plan:

184

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 30. Included: OtYes ID#

□ 2 No Reason:

Signature.______Jeffrey J. Walline, ODMS

185

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. SCX Check Form

1. Entrance visual acuity: la . OD 20 / lb . OS 20 / 2. Spherical overrefraction: 2a.OD ( 20/

2b. OS ( 2 0 / 3. Contact lens fitting-OD:

Minimal Minimal High High OD-Movemcnt Unacceptable Acceptable Average Acceptable Unacceptable 3k. I Initial I 2 3 4 5

OD-Centratioo Central Temporal Nasal Superior Inferior 3j. | Initial 1 2 3 4 5

OD-Centration Acceptable Unacceptable 3 m. | Initial 1 2 4. Contact lens fitting-OS: Minimal Minimal High High OS-Movement Unacceptable Acceptable Average Acceptable Unacceptable 4k. 1 Initial 1 2 3 4 5

OS-Centratioa Central Temporal Nasal Superior Inferior 4j. | Initial 1 2 3 4 5

OS-Centratioa Acceptable Unacceptable 4m. I Initial I 2 6. Other tests

7. Assessment 8. Plan

Signature: ______Jeffrey J. Walline, OD MS

186

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. I and 2 Month Masked Form

1. Entrance visual acuity: la.OD20/ lb . OS 20/ 2. Spherical overrefraction: 2a.OD ( 20/ 2b. OS ( 20/

S. Rigid Contact lens fitting-OD: Definite Clearance Definite Touch OD-Ceatral Cleennce Alignment Touch 1 5a. I 2 1 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Peripheral Avetaite 1 5b. 1 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Movemeat Avenge 1 5c. 1 2 3 4 5

OD-Centratioo Ccntial Temporal Nasal Superior Inferior 1 54 I 2 3 4 5

OD-Centratien Acceptable Unacceptable 1 5e. 1 2 5. Rigid Zontact lens fittine-OS: Definite Clearance Definite Touch OS-Central Clearance Alignment Touch 1 5a. I 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OS-Peripheral Avenge | 5b. 1 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OS-Mevemeat Avenge I 5c. 1 2 3 4 5

OS-Centratian Central Tcmpoml Nasal Superior Inferior 1 54 1 2 3 4 5

OS-CnatraMon Acceptable Unacceptable 1 5 t 1 2 6. Adapted to RGP: □[ No (go to 15) CI 2 Yes (go to 7)

7. Randomization: Di Rigid contact lenses (go to 15) D2 Soft Contact lenses (go to 8)

187

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 8. Keratometry 8a.OD / □□ @ □□□ 8b. Irregular M ins OD: Dt No D^Yes 8c.OS □□ / □□ @ □□□ 8d. Irregular Mires OS: DiNo ChYes

9. Initial contact lens: 9a. Base curve: 9b. Power:

10. Visual acuity: 10a. OD 20 / 10b. OS 20 / 11. Spherical overrefraction: Ila-OD ( 2 0 /

lib.OS ( 201

3. Contact lens fitting-OD:

Minimal Minimal High High OD-Movement Unacceptable Acceptable Average Acceptable Unacceptable 3k. | Initial 1 2 3 4 5

OD-Centration Central Temporal Nasal Superior Inferior 3j. | Initial 1 2 3 4 5

OD-CentratioB Acceptable Unacceptable 3m. | Initial 1 2 4. Contact lens fitting-OS:

Minimal Minimal High High OS-Moveraent Unacceptable Acceptable Average Acceptable Unacceptable 4r. I Initial 1 2 3 4 5

OS-Centratioa Central Temporal Nasal Superior Inferior 4j. | Initial 1 2 3 4 5

OS-Ceatration Acceptable Unacceptable 4m. | Initial 1 2 14. Other tests:

188

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 15. Assessment 16. Plan

Signature: ______Jeffrey J. Walline

189

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1 and 2 Month Unmasked Form

1. Vidcokeratography |Awari| videokcratogaohy printouts to Unmasked Exam Fermi

2. Keratometry la. OD /111 .1 II ] @ LII II 1 lb . Irregular Mires OD: □ iN o □2 Yes lc. OS /111 .1 II 1 @1 II II 1 Id. Irregular Mires OS: □ iN o □^Yes

i» .n n 1 II 1.1 II 1 /111 .1 II ] @cV-/ II II 1 If. Irregular Mires OD: □ 1 No □iYes

lg.O S • 1 @1 II II 1 lh. Irregular Mires OS: □ i No □iYes

3.1 drop 0.5% proparacaine OU 3a. 1 II 1 :| II 1am/pm

4. Tonopen: 4a. OD | |f | m m H g 4b. OS | || | m m H g

5.1 drop 1.0% tropicamide OU 5a. 1 II 1:1 II 1(am/ pm lAutardraction 30 mmntes after first droc 5b. 1 II hi II_1[am/pm

6 . Cydoplegk Autorefraction:|macliaiitoKfiactar printouts hen OD o s

190

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 7. Peripheral A ntorefnetkm : jaOacfaagtorefractorprintoutslK OD ------.OS

8. Videophakometry: perform vkteophakometry now

9. A-scan ultrasonography: jattadmhrasound printouts hert OD ------OS

10. Certification: | || || [

191

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 6 Month RGP Form

1. Current contact lens parameters: Base Curve Diameter Power. la. OD U U ( ) lb. OS □ □ ( ) 2. VA with habitual correction: Di SCL Ch RGP CI3 Glasses □« None 2a. OD □ □ 2b. OS □ □ 2c. OU 3. Spherical overrefraction: 3a. OD ( ) 2 0 / 3b. OS ( ) 2 0 /

Di finite Clearance I 1 Definite Touch OD-CdrtnU Clearance Alignment Touch 14* 1 1 2 1 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Pertoheral Avenge 1 4b. I 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Mevement Avenge 1 4c. 1 2 3 4 5

OD-Centratian Central Temporal Nasal Superior In (inior 1 4A I 2 3 4 5

OD-Centratian Acceptable Unacceptable 1 4c. 1 2

Definite Cleanncc Definite Touch OS-Central Clearance Alignment Touch 5a. I 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OS-Peripheral Avenge 1 5b. 1 2 3 4 5

Minimal Unacceptable Minima] Acceptable High Acceptable High Unacceptable OS-Muvement Avenge rs c . 1 2 3 4 5

OS-Centratian Central Temporal Nani Superior Inferior 1 5A 1 2 3 4 5

OS-Centratian Acceptable Unacceptable F Se. 1 2 6. Photography Take three fluorescein photographs o f each eye

192

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 7. Other tests

8. Assessment 9. Plan

Signature: ______• Jeffrey J. Walline

193

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 6 Month SCL Form

1. Current contact lens parameters: Base Curve Piaijict : la. OD lb. OS □a 2. VA with habitnalcorrection: Oi SCL IH2 RGP CI3 Glasses □*None 2a. OD 2b. OS L 2c. OU 3. Spherical overrefraction: 3a. OD ( ) 2 0 / 3b. OS ( ) 2 0 / 4. Contact lens fitting-OD:

Minimal Minimal High High OD-Movcment Unacceptable Acceptable Avenge Acceptable Unacceptable 4k. | Initial 1 2 3 4 5

OD-Ccntratioa Central Temporal Masai Superior Inferior 4j. | Initial 1 2 3 4 5

OD-Centratioo Acceptable Unacceptable 4m. 1 Initial 1 2 5. Contact lens fitting-OS:

Minimal Minimal High High OS-Movemcnt Unacceptable Acceptable Avenge Acceptable Unacceptable Sr. | Initial 1 2 3 4 5

OS-Centratioa Central Temporal Nasal Superior Inferior 3i. 1 Initial 1 2 3 4 5

OS-Centratioa Acceptable Unacceptable 5 m. | Initial 1 2 6. Other tests

7. Assessment 8. Plan

Signature: ______Jeffrey J. Walline 194

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Annual Masked Form

1. Videokeratography ______Attach vidcokcratograohy printouts to Masked Exam Fonii

2. Orbscan ______Attach Orbscan printouts to Masked Exam Fotml

3. Keratomctry 3a. OD I/I II l.l II 1@ . n n n 3b. Irregular Mires OD: □ iN o ChYes 3c. OS □ □ . □ r I/I II l.l II 1 @ . n n n 3d. Irregular Mires OS: □ i No □2Yes 3e.OD 1 II l.l T I/I II l.l II 1 @ n n n 3f. Irregular Mires OD: □ iN o ChYes 3g. OS □ □ • □ C l/lll l.l II I a r m 3h. Irregular Mires OS: □ iN o □2Yes

4.1 drop 0.5% proparacaine OU ______|__ || | :|__ ||__ 1 am / pm

5. Tonopen: 5a. OD |__ ||__ | mmHg 5b. OS | __ ||__ | mmHg

6.1 drop 1.0% tropicamide OU 6a. I __ II I: I II lam / pm lAntorefraction 30 minutes after first drop! 6b.__ |__ ||__ | : |__ || | am / pm

195

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 7. C ydoplegk Autorefraction: jutachaatorefractor printouts hcrtl

8. P eripheral A utorefraction: i«tachautordhKior printouts hart

196

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 9. Videophakometry: perfcra vidcochakoinctTvno^

10. A-scan ultrasonography: lattachaltrasonndprmtontshcd

II. Certification: | [[ |[

197

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Annual Unmasked Form

1. Current contact lens parameters: Curve Diameter Power la . OD ( ) lb . OS ( ) 2. Chief complaint: a 3. Changes in Personal or Family Health Hx: □ iNo 02 Yes ______4. VA with habitual correction: Di SCL □2 RGP 03 Glasses □.» None 4a. OD 4b. OS ] 4c. OU □□ 5. Spherical overrefraction: 5a. OD ( ) 2 0 / 5b. OS ( ) 2 0 / 6. Does the subject wear rigid contact lenses? □ 1 Yes — G oto #7 □2 No — Go to #10

Definite Clearance 1 1 Definite Touch OD-Central Clearance 1 Alignment Touch 1 7a. 1 1 2 1 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Pertoharnl Avenge 1 7b. I 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OD-Mevement Average 1 7c. t 2 3 4 5 O i Central Temporal Naal Superior Inferior 1 74 I 2 3 4 5

OD-Cantratten Acceptable Unacceptable 1 7c. 1 2

198

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 8. Rigid IContact lens fitting-OS: Definite Clearance Definite Touch OS-Central Clearance Alignment Touch 1 8*. 1 2 3 4 5

Mhnnal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OS-Pnribhnnl Average 1 8b. 1 2 3 4 5

Minimal Unacceptable Minimal Acceptable High Acceptable High Unacceptable OS-Mevement Average 1 8a 1 2 3 4 5

OS-Centratien Central Temporal Naxal Superior Inferior 1 84 1 2 3 4 5

OS-Centratisn Acceptable Unacceptable 1 8a 1 2 9. Photography Take three fluorescein photographs o f each eye 10. Contact lens fitting-OD:

Minimal Minimal High High OD-Movernent Unacceptable Acceptable Average Acceptable Unacceptable IOr. | Initial 1 2 3 4 5

OD-CentraUoo Central Temporal Nasal Superior Inferior lOj. | Initial 1 ? 3 4 5

OD-Centrntioa Acceptable Unacceptable lOta | Initial 1 2 11. Contact lens fitting-OS:

Minimal Minimal High High OS-Movemeat Unacceptable Acceptable Average Acceptable Unacceptable llg. | Initial I 2 3 4 5

OS-Centratioa Central Temporal Nasal Superior Inferior III. I Initial 1 2 3 4 5

OS-Ceatratioa Acceptable Unacceptable Urn. | initial 1 2 12. Cover Test with habitual correction: (+ =eso; - = exo) 12a. Distance:______12b. N e a r______13. Versions: Dt Full and smooth 0 2 O ther______14. Pupillary distance: 14a. Distance: 14b. Near: 15. Near Point of Convergence:______cm

199

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 16. Accommodative amplitudes: 16a. O D ______D 16b. OS 16c. OU 17. Randot stereo: seconds of arc 18. Confrontation visual field: □ Full to finger count OU □ O ther 19. Pupils are equal, round and reactive to fight: □ Yes □ No: 20. Accommodative Assessment: lAdach antoreftactor printoat hen

21. Retinoscopy: 21a. OD ( ) (-) x 21b. OS ( ) m ( - > [ x 22. Manifest refraction: 22a. OD ( ) (->

22b. OS ( ) (-) X 23. Final Rx (if different from manifest refraction) 23a. OD ( ) (-) X

23b. OS ( )

24. Von Graefe phoria: distance (+ - eso; - = exo) 24a. Horiz:______24b. Vert: 25. Von Graefe phoria: near (+ = e s o ;- - e x o ) 25a. Horiz: 25b. Gradient AC/A: (+1.00).

26. Cover Test with manifest refraction: (+ = eso; - = exo) 26a. D istance:______26b. _ N e a r______

27. Visual Acuity with spectacles: 27a. OD: 20/ 27b. OS: 20/ 27c. OU: 20/

200

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 28. SHt Lamp Examination: OD OS Lids and Lashes Cornea Conjunctiva Anterior Chamber Iris Lens Vitreous

29. To Masked Examiner

30. Funduscopy (BIO and 78D): OD OS C/D Rim Color Macula Vessels Periphery

31. Contact lens to order: Base Curve Diameter Power. 31a. OD ( ) 31b. OS dB: ( ) 32. Other findings:

201

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 33. Assessment: 34. Plan:

Signature:______Jeffrey J. Wallinc. OD MS

202

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Parents CL Form

1. How many days last week (Monday through Friday) did your child have his/her contact lenses in more than ontof his/her eyes while awake? □0 DI 02 D3 D4 D5

2. How many days last weekend (Saturday and Sunday) did your child have contact lenses in more than ontof his/her eyes while awake? □0 DI D2

3. How many days last week (Monday through Friday) did your child have glasses on more than offwhile awake? □0 DI 02 IH3 D4 D5

4. How many days last weekend (Saturday and Sunday) did your child have glasses on more than offwhile awake? □0 01 02

5. What time did your child usually put his/her contact lenses in last week (Monday - Friday)? I I I J II I am / pm (circle one)

6. What time did your child usually take his/her contact lenses ontlast week (Monday - Friday)? I I I d II I am/pm (circleone)

7. What time did your child usually put his/her contact lenses in last Saturday and Sunday? I I I j III am / pm (circle one)

8 . What time did your child usually take his/her contact lenses ontlast Saturday and Sunday? □ □ □ □ am / pm (circle one)

9. How often does your child mention discomfort o f the eyes due to contact lenses? □^Always □2Often □jSometimes CURarely □sNever

203

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 10. When your child wears contact lenses how often does s/he mention itching eyes? □ i Always □aOften □3 Sometimes CURarely □jNever

11. When your child wears contact lenses how often does s/he mention red eyes? □.1 Always □2Often □jSometimes □4Rarely □jNever

12. When your child wears contact lenses how often does s/he mention burning eyes? □.1 Always □2Often

□ 3 Sometimes □jRarely □sNever

13. When your child wears contact lenses how often does s/he mention tearing? □.1 Always CUOften

□ 3 Sometimes □^Rarely □.sNever

14. When your child wears contact lenses how often does s/he mention lig h t sen sitiv ity? □ 1 Always □2Often

□ 3 Sometimes □^Rarely □jNever

15. How often does your child mention poor vision when s/he wears contact lenses? □3 Always □2Often

□ 3 Sometimes □4Rarely □5Never

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 16. How do you feel your child would rate the comfort o f his/her contact lenses? □ i Always comfortable □2 Usually comfortable □3 Usually uncomfortable □4 Always uncomfortable

17. How do you feel your child’s vision is when s/he wears contact lenses? □jMy child sees extremely poorly with contact lenses □2My child doesn’t see very well with contact lenses □3My child sees OK with contact lenses □jMy child sees fairly well with contact lenses □^My child sees very well with contact lenses

18. How often does your child like to wear contact lenses? □.iMy child never likes to wear contact lenses □2My child doesn’t like to wear contact lenses most of the time □3My child likes to wear contact lenses sometimes □jMy child usually likes to wear contact lenses □jMy child always likes to wear contact lenses

19. Does your child like contact lenses or glasses better? □ jMy child likes glasses a lot better than contact lenses □2My child likes glasses a little better than contact lenses □jMy child likes glasses and contact lenses equally □jMy child likes contact lenses a little better than glasses □jMy child likes contact lenses a lot better than glasses

20. When your child doesn’t wear his/her contact lenses, why doesn’t s/he wear them? (check all that apply) □jMy child wears contact lenses almost all of the time □2My child prefers to wear glasses sometimes □jit is too much trouble for my child to put in contact lenses sometimes □jMy child’s contact lenses are uncomfortable □jMy child’s vision is poor with contact lenses □jMy child wants to give his/her eyes a break from contact lenses □jMy child is afraid s/he may lose the contact lenses in some situations □jMy child doesn’t have time to put in contact lenses sometimes □oO ther______

205

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 21. How do you feel about your child’s ability to insert his/her contact lenses? □ t My child never has a problem □2 My child usually does not have a problem □3 My child sometimes has a problem

□ 4 My child usually has a problem □5 My child always has a problem

22. How do you feel about your child’s ability to remove his/her contact lenses? □ 1 My child never has a problem □2 My child usually does not have a problem □3 My child sometimes has a problem

□ 4 My child usually has a problem □5 My child always has a problem

23. How does your child feel about cleaning his/her contact lenses? □ 1 My child loves to clean his/her contact lenses □2 My child likes to clean his/her contact lenses □ 3 My child does not mind cleaning his/her contact lenses □4 My child does not like to clean his/her contact lenses □ s My child hates to clean his/her contact lenses

24. How do you feel about your child’s ability to handle his/her contact lenses? □1 My child never has a problem □2 My child usually does not have a problem □3 My child sometimes has a problem

□ 4 My child usually has a problem □ s My child always has a problem

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Subjects CL Form

1. How many days last week (Monday through Friday) did you have your contact lenses in your eyes more than outof your eyes while you were awake? □0 ml 02 D3 D4 D5

2. How many days last weekend (Saturday and Sunday) did you have your contact lenses in your eyes more than outof your eyes while you were awake? □o mi m2

3. How many days last week (Monday through Friday) did you have your glasses on more than offwhile you were awake? □0 D1 D2 D3 D4 D5

4. How many days last weekend (Saturday and Sunday) did you have your glasses on more than offwhile you were awake? □0 Ql 02

5. What time did you usually put your contact lenses in last week (Monday through Friday)? FI! 1*1 11 I morning / afternoon (circle one) 6. What time did you usually take your contact lenses outlast week (Monday through Friday)? morning / afternoon (circle one) 7. What time did you usually put your contact lenses in last Saturday and Sunday? ~Z1 morning / afternoon (circle one)

8. What time did you usually take your contact lenses outlast Saturday and Sunday? morning / afternoon (circle one)

9. How do the contact lenses feel in your eyes? □ i I never feel them when they are in my eyes □ 2 I feel them right when I put them in but I can’t feel them after a while

□ 3 I sometimes feel them in my eyes during the day □4 I always feel them until I take them out of my eyes

207

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 10. When you wear your contact lenses how often do your eyes itch? □ i Always □2 Often □3 Sometimes □4 Rarely □ 5 Never

11. When you wear your contact lenses how often do your eyes g e t red ! □1 Always □2 Often □ 3 Sometimes □4 Rarely □ 5 Never

12. When you wear your contact lenses how often do your eyes b u m l □ 1 Always □2 Often □ 3 Sometimes □4 Rarely □ 5 Never 13. When you wear your contact lenses how often do your eyes tear? □ 1 Always □2 Often □ 3 Sometimes □4 Rarely □s Never 14. When you wear your contact lenses how often do your eyes feel light sensitive? □ 1 Always □2 Often □ 3 Sometimes □4 Rarely □5 Never 13. How would you rate the comfort of your contact lenses? □ t Always comfortable □2 Usually comfortable

□ 3 Usually uncomfortable □4 Always uncomfortable

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 16. How is your vision when you wear contact lenses? □ i My vision is terrible □2 My vision is not very good □ 3 My vision is OK □4 My vision is pretty good □s My vision is perfect

17. How is your vision when you wear contact lenses? □ 1 I can’t read the board at school at all □2 I can’t read the board at school very well □ 3 I can see almost everything I want to see □« I can see very well □5 I can see better than everybody else

18. How often do you like to wear contact lenses? □ 1 I never like to wear my contact lenses □2 I don’t like to wear my contact lenses most of the time □ 3 I like to wear my contact lenses sometimes □4 I usually like to wear my contact lenses □s I always like to wear my contact lenses

19. Do you like contact lenses or glasses better? □ 1 I like glasses a lot better than contact lenses □2 I like glasses a little better than contact lenses □ 3 1 like glasses and contact lenses the same □4 I like contact lenses a little better than contact lenses □s I like contact lenses a lot better than contact lenses

20. When you don’t wear your contact lenses, why don’t you wear them? (check all that apply) □ 1 I wear contact lenses almost all of the time □2 I prefer to wear my glasses sometimes □ 3 It is too much trouble to put in my contact lenses □4 My contact lenses are uncomfortable □s My vision is poor with contact lenses □6 I want to give my eyes a break from contact lenses □ 7 I am afraid I will lose my contact lenses sometimes □s I don’t have time to put in my contact lenses sometimes □9 O th e r______

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 21. How much pain or discomfort have you had in and around your eyes (for example, burning, itching, or aching)? Would you say it is: □ 1 None □2 Mild

□ 3 Moderate □4 Severe, or □5 Very severe?

22. How much does pain or discomfort in or around your eyes, for example, burning, itching, or aching, keep you from doing what you’d like to be doing? Would you say: □ 1 All of the time □2 Most o f the time □ 3 Some of the time □4 A little o f the time □s None o f the time

23. At the present time, would you say your eyesight using both eyes (with your contact lenses) is excellent, good, fair, poor, or very poor or are you completely blind? □ 1 Excellent □2 Good

□ 3 Fair □4 Poor □5 Very Poor □6 Completely Blind

24. In general, would you say your overall health is: □ 1 Excellent □2 Good

□ 3 Fair □4 Poor □5 Very Poor

25. How do you feel about putting your contact lenses in your eyes? □ t I never have a problem □ 2 I usually do not have a problem □ 3 I sometimes have a problem □4 I usually have a problem □ s I always have a problem

26. How do you feel about taking your contact lenses out of your eyes? □ 1 I never have a problem □2 I usually do not have a problem

□ 3 I sometimes have a problem □4 I usually have a problem □5 I always have a problem 210

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 27. How do you feel about cleaning your contact lenses? □i I love to clean my contact lenses □2 I like to clean my contact lenses □4 I do not like to clean my contact lenses □ 51 hate to clean my contact lenses

28. How do you feel about handling your contact lenses? □ 1 I never have a problem □ 2 I usually do not have a problem □ 3 I sometimes have a problem □ 4 I usually have a problem □s I always have a problem

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Parents NW Form

1. How often does your child read for pleasure (outside of school)? (check one) □ t Never □2 Rarely □ 3 Sometimes □4 Often

2. How many hours per week (outside of regular school hours) would you estimate your child: (Please fill in every blank; use a zero to indicate no hours.) Studies or reads for school assignments: hours Reads for pleasure: hours Watches television: hours Engages in outdoor/sports activities: hours Plays video/computer games: hours

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Subjects NW Form

1. How often do you read for pleasure (outside of school)? (check one) □ 1 Never □2 Rarely

□ 3 Sometimes □ 4 Often

2. How many hours per week (outside of regular school hours) do you: (Please fill in every blank; use a zero to indicate no hours.) Study or read for school assignments: hours Read for pleasure: hours Watch television: hours Engage in outdoor/sports activities: hours Play video/computer games: hours

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. VAForm

•Slash through letters read correctly •Circle missed letters •Test to last letter of a line until patient missed 3 or more letters on a line

Visual acuity with habitual correction OD Chart 4 Score OS Charts Score OU Chart 4 Score 5 DVNZR 5 HEFPU 5 DVNZR 10 HNFDV 10 EPURZ 10 HNFDV 15 FUPVE 15 HNRZD 15 FUPVE 20 PERZU 20 FNHVD 20 PERZU 25 FHPVE 25 NDZRU 25 FHPVE 30 ZRFNU 30 VDEHP 30 ZRFNU 35 PRZEU 35 NFVHD 35 PRZEU 40 FVPZD 40 NREHU 40 FVPZD 45 UPNFH 45 RZVDE 45 UPNFH 50 RZUFN 50 D HE VP 50 RZUFN 55 FHUVD 55 EPNRZ 55 FHUVD 60 NEFZR 60 HPVDU 60 NEFZR 65 ZDRVE 65 NUPFH 65 ZDRVE 70 UDFVN 70 ZPEHR 70 UDFVN Total Total Total

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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.