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Ocular axial length and prevalence of myopic macular degeneration among Chinese Americans
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Ocular axial length and prevalence of myopic macular degeneration among Chinese Americans
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Content
OCULAR AXIAL LENGTH AND PREVALENCE OF MYOPIC MACULAR
DEGENERATION AMONG CHINESE AMERICANS
by
Wenbo Jiang
A Thesis Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOSTATISTICS)
December 2022
Copyright 2022 Wenbo Jiang
ii
Acknowledgments
I would like to thank my professors, friends, and family who helped me with my master thesis.
I am profoundly grateful to the USC Keck School of Medicine, where my two years of study have
equipped me with the ability to do this research and analyze the data for my thesis.
I would like to express my utmost gratitude to my chair mentor, Dr. Choudhury, for providing me
with very valuable data and for her inspiration and guidance. I counted on her help and advice on every
part of my thesis. I am also very grateful to Dr. Piao and Dr. Siegmund for their guidance and support.
Finally, I would like to thank my family for giving me the opportunity to go abroad to study and
complete this thesis successfully. Also, I want to thank them for their constant encouragement during my
thesis writing process.
iii
TABLE OF CONTENTS
Acknowledgments ......................................................................................................................................... ii
List of Tables ............................................................................................................................................... iv
List of Figures ............................................................................................................................................... v
Abstract ........................................................................................................................................................ vi
Chapter 1: Introduction ................................................................................................................................. 1
Chapter 2: Materials and methods ................................................................................................................ 4
2-1 Source of data ..................................................................................................................................... 4
2-2 Objective of study ............................................................................................................................... 5
2-3 Definitions of outcome variables ........................................................................................................ 5
2-4 Variable categorizations in our analysis ............................................................................................. 6
2-5 Statistical analysis ............................................................................................................................... 6
Chapter 3: Result........................................................................................................................................... 8
3-1 Prevalence analysis ............................................................................................................................. 8
3-2 AL analysis ......................................................................................................................................... 9
3-3 Relationship between AL and prevalence of MMD ......................................................................... 11
3-3-a AL and the prevalence of MMD ................................................................................................ 11
3-3-b AL and the prevalence of diffuse atrophy ................................................................................. 12
3-3-c AL and the prevalence of lacquer cracks ................................................................................... 13
3-3-d AL and the prevalence of patchy atrophy .................................................................................. 14
3-3-e AL and the prevalence of staphyloma ....................................................................................... 15
3-3-f AL and the prevalence of disc tilt .............................................................................................. 16
3-3-g AL and the prevalence of peripapillary atrophy ........................................................................ 17
3-3-h AL and the prevalence of tessellation ....................................................................................... 18
3-3-i AL and the prevalence of intra-choroidal cavitation .................................................................. 19
3-4 Summary of Knot points analysis ..................................................................................................... 20
Chapter 4: Discussion ................................................................................................................................. 22
REFERENCES ........................................................................................................................................... 25
iv
List of Tables
Table 1: Fitted value prevalence of MMD and ocular lesions ...................................................................... 9
Table 2: Distribution of MMD by demographic factors ............................................................................... 9
Table 3: Distribution of AL by demographic factors .................................................................................. 10
Table 4: Odds ratio for MMD and its associated lesions ............................................................................ 20
Table 5: Knot point for MMD and its lesions ............................................................................................. 21
v
List of Figures
Figure 1: A scatter plot with a spline line depicting the association between the fitted value prevalence
of MMD and AL. ........................................................................................................................................ 12
Figure 2: A scatter plot with a spline line depicting the association between the fitted value prevalence
of diffuse atrophy and AL. .......................................................................................................................... 13
Figure 3: A scatter plot with a spline line depicting the association between the fitted value prevalence
of lacquer cracks and AL. ........................................................................................................................... 14
Figure 4: A scatter plot with a spline line depicting the association between the fitted value prevalence
of patchy atrophy and AL. .......................................................................................................................... 15
Figure 5: A scatter plot with a spline line depicting the association between the fitted value prevalence
of staphyloma and AL. ................................................................................................................................ 16
Figure 6: A scatter plot with a spline line depicting the association between the fitted value prevalence
of disc tilt and AL. ...................................................................................................................................... 17
Figure 7: A scatter plot with a spline line depicting the association between the prevalence of
peripapillary atrophy and AL. ..................................................................................................................... 18
Figure 8: A scatter plot with a spline line depicting the association between the fitted value prevalence
of tessellation and AL. ................................................................................................................................ 19
Figure 9: A scatter plot with a spline line depicting the association between the fitted value prevalence
of intra-choroidal cavitation and AL ........................................................................................................... 20
Figure 10: Fitted value prevalence of MMD and its lesions under specific AL ......................................... 21
vi
Abstract
Purpose:
To investigate the association between axial length (AL) and prevalence of myopic macular
degeneration (MMD) and MMD lesions, and to find out the inflection point in AL where the fitted value
prevalence of MMD and its associated lesions significantly increased among Chinese Americans.
Study Design:
A population-based cross-section study.
Method:
Data from a total of 1523 participants with myopia from the Chinese American Eye Study
(CHES), aged 50 years or older, were used for this analysis. Participants underwent an interview, clinical
exam, ophthalmic exam, and stereoscopic fundus photography. MMD was assessed in a masked manner
by an expert grader. A modified version of the Meta-Analysis for Pathologic Myopia (META-PM) was
used to define MMD that included presence of tessellation, diffuse and patchy chorio-retinal atrophy,
atrophic macula, lacquer cracks, choroidal neovascularization, and Fuchs’ spots. Multiple logistic
regression was used and odds ratios and 95% Confidence intervals [OR, (95% CI)] were calculated to
examine the association of MMD and AL. To assess the qualitative nature of the relationship between the
predictors and MMD, we performed locally estimated (Loess) regression. We also fitted linear spline
methods to determine the knots points of the fitted value prevalence of MMD and its lesions.
Results:
Out of 1523 participants with myopia, a total of 684 (44.91%) had MMD. The prevalence of
MMD associated lesions among our observed participants were tessellation (31.73%), disc tilt (28.07%),
patchy atrophy (6.96%), diffuse atrophy (6.39%), staphyloma (5.73%), lacquer cracks (2.57%), intra-
choroidal cavitation (2.17%), peripapillary atrophy (0.92%). Sex, weight, height, and severity of myopia
were found to be significantly related to AL (P<0.001 for each association). For MMD and its lesions, the
vii
inflection points for increased prevalence were as follows: MMD (AL=23 mm), peripapillary atrophy
(AL=25 mm), staphyloma (AL=25 mm), diffuse atrophy (AL=26 mm), lacquer cracks (AL= 26 mm),
patchy atrophy (AL=28 mm).
Conclusion:
In this cohort of Chinese Americans, the prevalence of MMD and its associated lesions was
positively related to AL. From AL of 23 mm or longer, there was substantially higher prevalence of
MMD. For AL ≥ 25 mm, the fitted value prevalence of other lesions was much higher compared to AL <
25 mm.
Eye care providers should be aware of an increased risk of severe MMD lesions among Chinese
Americans with AL values above 23 mm. Therefore, they should consider performing regular detailed
retinal examination or refer the patient to a retina specialist for evaluation.
1
Chapter 1: Introduction
In recent decades, the burden of eye disease has increased rapidly throughout the world. More
and more younger people are suffering from eye disease. Visual impairment and blindness are the most
prevalent eye condition
1
. The previous study indicated that in 2020, an anticipated 43.3 million
individuals would be blind, and an estimated 295 million people would be diagnosed with moderate or
severe visual impairment
2
. Those numbers are expected to increase in the future.
Uncorrected refractive error is the most common cause of visual impairment and the second most
common cause of blindness
3
. Refractive errors include myopia, hyperopia, presbyopia, and astigmatism.
Myopia is the most common type of refractive error, and around 75% of refractive error-related problems
are caused by myopia, with negative impact on social and economic consequences
4
. The result from a
meta-analysis of 145 studies involving more than 2.1 million people suggested that the estimated number
of people with myopia would reach 1406 million in 2000, accounting for 22.9% of the world’s population,
and this number would reach 4758 million in 2050 which means 50% of the world’s human beings would
be myopic
5,6
.
Myopia can result in a plethora of degenerative structural changes in the chorio-retinal tissue in
the retina’s macular region. Myopic macular degeneration (MMD), or Pathological Myopia, can damage
the light-sensitive layer retina and result in irreversible vision loss. Approximately 2.1% of the world's
population suffered from MMD, and the prevalence of MMD for people with high myopia reached nearly
48%
7
. In the MMD lesions, the more common types were tessellation, tilted disc, and peripapillary, with
prevalence of 31.7%, 28.1%, and 7.0%, respectively, in people with myopia
8
.
MMD and myopia are more common in people of East Asian ancestry, especially Chinese
people
9
. The study done in Singapore indicated the prevalence of MMD was nearly 3.8% which was
much higher than the prevalence of MMD for the whole world (2.1%)
7,10
. Among Chinese, Malay, and
Indians, the prevalence of age-related MMD was 7.3%, 7.7%, and 5.7%, respectively, much higher than
2
in Western countries like the USA (1.47%)
11,12
. Worldwide, the estimated prevalence of myopia was 33.9%
(2.7% with high myopia), significantly lower than in East Asia (51.9%)
5
.
China is the largest and fastest-growing Asian country with a growing proportion of younger
people. The burden of myopia and associated complications has been a challenging issue in China.
According to the survey results, the prevalence of myopia among high school students in China was
higher than 80% in 2014 and was expected to keep increasing
13
.
Previous studies have identified several factors associated with MMD. The degree or severity of
myopia was a risk factor for MMD. The prevalence of MMD in participants with high myopia was 76.4%
which was much higher than participants with mild myopia (21.7%) or moderate myopia (49.1%)
8
. The
prevalence of MMD increased with age, with nearly 40% in people aged 50-60 and more than 80% in
people over 80
8,14
. Also, the prevalence of specific MMD lesions like diffuse atrophy, patchy atrophy,
choroidal neovascularization, and macular atrophy were more prevalent in people over 50 years old
15
.
Lacquer cracks were more common for people younger than 50 years old
15
. Moreover, smoking status
was associated with MMD, and people who smoked over 40 years were 2.39 times more likely to be
diagnosed with MMD than those who did not
16
. Studies have found certain drugs associated with MMD.
For instance, people who have ever taken angiotensin-converting enzyme inhibitors were three times
more likely to have MMD
16
.
Axial length (AL) is a parameter representing the distance from the cornea to the retina and
combines anterior chamber depth, length thickness, and vitreous chamber depth of the eye. When the light
comes through the cornea, it is transmitted to the retina by the lens through a certain angle of refraction.
For healthy eyes, the refracted light will focus on the retina, while for myopic eyes, the refracted light is
imaged in front of the retina because of the higher AL, which would cause our brain to receive the blurred
image
17
. AL is also known to be the primary determinant of MMD. Previous studies have explored the
relationship between AL and MMD. In the recent retrospective study conducted among 316 Japanese
people, there were two crucial findings: the AL increased more for people with myopia (0.041 ± 0.05 mm)
than for people with non-highly myopia (0.007 ± 0.02 mm)
18
. The other was that people with macular
3
complications such as choroidal neovascularization were detected to have significantly greater AL
changes than people with no complications
18
. Results from a population-based cross-sectional study
among 2790 Japanese over 40 years old indicated a positive linear association between AL and MMD in
both males and females
19
.
In the last decade, the Chinese American population grew by 48%, making them one of the
fastest-growing groups in the country
20
. However, there was limited data on their eye disease patterns
compared to other racial/ethnic groups. This gap was addressed by the Chinese American Eye Study
(CHES). Previous results from CHES suggested a greater prevalence of myopia and MMD among this
group
5,9,11
, but the specific factors that lead to MMD have not been thoroughly explored.
This analysis was based on the data provided by the Chinese American Eye Study. We aimed to
investigate and characterize the association of MMD and different MMD lesions with AL in elder Asian
people living in the Chinese community of Los Angeles.
4
Chapter 2: Materials and methods
2-1 Source of data
A total of 1523 people with myopia (954 female and 569 male) were recruited from Monterey
Park, a Los Angeles community with a large and stable Chinese American population. These data were
collected in a subgroup of people within the Chinese American Eye Study (CHES). CHES invited people
who meet the following conditions to participate in the development of the study: (1) People who visited
a doctor for eye health problems or basic eye examination from 2010 to 2013; (2) aged over 50 years old;
(3) voluntarily provided their health information and basic information for scientific research projects.
Also, the first generation of mainland immigrants was preferred
20
. Participants were interviewed when
they were potentially eligible. During the in-home computer-assisted interview, participants’ basic health
information including smoking, drinking, and medical histories was collected. They were then scheduled
to undergo a comprehensive eye examination at a local eye examination center.
Each eligible patient was tested for their AL, visual acuity (VA), intraocular pressure, and visual
fields in the comprehensive eye examination. CHES applied Early Treatment Diabetic Retinopathy Study
(ETDRS) charts and the Lea symbol charts to test the patient’s visual acuity
21
. Participants were
diagnosed with visual impairment if their VA for the better eye was less than 20/40; if it was less than
20/200, the patient was considered the blind. Spherical equivalent (SE), recorded during the examination,
was the measurement of myopia, and participants were considered myopic if their SE was lower than -
0.5D, highly myopic if SE was lower than -5.0D
20
.
In CHES, each patient’s AL, corneal curvature, and other ocular information was calculated and
reported by the laser interference device called ‘Zeiss IOL Master’
22
. This device used the patented
interference optical method and ultrasonic immersion measurement to help evaluate AL.
CHES adopted Blue Mountains Eye Study
23
, which pointed out the signs of MMD and other
ocular lesions. Meanwhile, CHES used fundus photographs and a modified Delphi process to help define
MMD based on features like Tessellated Fundus, Macular Atrophy, Patchy Atrophy, and Diffuse
5
Atrophy
24
. Also, CHES determined the prevalence of each age-related specific lesion and MMD using the
Wisconsin AMD Classification system
25
.
2-2 Objective of study
The main objective of this study was to look at the association between AL and MMD,
quantitatively and qualitatively. AL was used as the primary independent variable in this study. Criteria
used to evaluate the presence of MMD were participants diagnosed with all lesions present without
tessellation, disc title, and peripapillary atrophy. One particular focus was to detect the inflection point in
AL where the fitted value prevalence of MMD and associated lesions increased. So, we fitted spline terms
for all models and tested whether the knot point was significant. We also explored the risk factors related
to AL and demographic characteristics related to MMD or MMD lesions.
2-3 Definitions of outcome variables
MMD included staphyloma, lacquer cracks, Fuchs’ spot, and myopic chorio-retinal Atrophy
18
.
Also, for a more rigorous definition of MMD, diffuse atrophy and patchy atrophy was considered. Optic
Nerve Grading and Macula Grading defined eight associated ocular lesions.
(1) Disc Tilt was diagnosed if the participant’s optic disc appears to have tilted to the retinal plane
26
.
(2) Peripapillary Atrophy was diagnosed if participants had chorio-retinal thinning and disruption of the
retinal pigment epithelium (RPE) in the area around the optic disc
27
.
(3) Tessellation was diagnosed if well-defined choroidal vessels can be seen clearly both surrounding the
fovea and arcade. Questionably or partially, tessellated eyes will have well-defined choroidal vessels
evident in only one area (around the fovea or the arcade vessels)
28
.
(4) Lacquer Cracks: Fine, irregular, yellowish-white lines, indicative of linear breaks in the Bruch
membrane, were used to diagnose lacquer cracks
29
.
6
(5) Diffuse Atrophy: Diffuse atrophy manifests itself in the posterior pole as a yellowish-white “thinned
RPE” region. It might be patchy or present in a broad linear band, and it is mostly seen in the macula and
around the disc
14
.
(6) Patchy Atrophy: A greyish-white, well-defined lesion is observed in the inferotemporal part of the
fovea centralis
30
.
(7) Staphyloma: A noticeable change in retinal color, blood vessel deviation, and a clear-cut excavation of
the retina with hyper/hypo pigmented demarcation margins
31
.
(8) Intra-choroidal Cavitation (ICC): A yellow-orange lesion that is high, well confined, dome-shaped,
and commonly located along the periphery of the optic disc or close to an area of beta-peripapillary
atrophy
32
.
2-4 Variable categorizations in our analysis
For our analysis, Age was categorized into four groups: (1) 50-59 (2) 60-69 (3) 70-79 (4) 80+.
Data on Education level was categorized as: (1) 0-6 years (2) 6-12 years (3) college graduate (4)
postgraduate. We divided smoke status and drinking status into three subgroups in the same way: (1)
Never smoke/drink (2) Ex-smoker/drinker (3) Current smoker/drinker. We took the integer bits of AL as
subgroups. Every observation with AL greater than 31 mm was regarded as a whole group because of the
limited sample size in this range. There were 12 subgroups in total. Data on severity of myopia was
classified into three groups: Mild (-0.5D < SE < 2D), Moderate (-5D ≤ SE ≤ -0.5D) and Severe (SE < -
5D). Prevalence of MMD and MMD lesions as our independent variables were categorized as a binary
variable of whether the patient is diagnosed or not.
2-5 Statistical analysis
During exploratory data analysis, continuous variables were summarized by mean, standard
deviation, maximum value, minimum value, and quantiles, while categorical variables were summarized
7
by frequency and percentage. The association of AL with different demographic characteristics was
compared for our 1523 participants. To compare the distribution of AL among groups defined by multiple
categories of variables (sex, age, smoking status, drinking status, marriage status, income level, and
education level), the one-way analysis of variables (ANOVA) was used. Also, the Chi-square test was
applied to detect the distribution of MMD by demographic factors.
MMD and each component lesion were modeled separately for their association with AL.
Unconditional logistic regression was used to model the fitted value prevalence. Age, sex, and severity of
myopia were tested as possible confounders. Factors that resulted in more than a 15% change in the
regression coefficient were considered confounders of the relationship between AL and the fitted value
prevalence of MMD and its lesions. Wald’s tests were used to assess possible effect modification by these
covariates after incorporating proper interaction terms in the multivariable model.
Participants’ age, sex, and degree of myopia were found to be confounders and kept in the models
as adjustment variables. We set male participants aged between 50-59 with mild myopia as the reference
group in the model. None of the interaction tests were significant (P>0.10 for all interactions). Therefore,
the final model included independent variables: AL, age, sex, and degree of myopia. Then, we created a
table that contained only the mean estimated prevalence and each AL for MMD and other lesions.
To assess the qualitative nature of the relationship between the AL and estimated prevalence from
the covariate adjusted model, we performed locally estimated scatterplot smoothing (LOESS) regression
with slope calculations on the LOESS fitted curves for each consecutive unit of AL.
We further explored and assessed the inflection points associated with increased MMD
prevalence by looking at the knot points to characterize whether there is an increased risk of MMD
prevalence beyond that point. For these tests we corrected the significance level for multiple test (adjusted
P=0.0083). The MMD prevalence is the fitted value from the covariate adjusted logistic model.
All statistical analysis used SAS software 9.4 (SAS, Inc, Cary, North Carolina), and all
significance tests were conducted at a 2-sided 0.05 level, other than the knot point analysis.
8
Chapter 3: Result
3-1 Prevalence analysis
The prevalence of MMD among 1523 participants with myopia was 44.91% which was higher
than any other MMD lesions. Tessellation (31.37%), disc tilt (28.07%), and patchy atrophy (6.96%) were
the three lesions with a relatively high prevalence (Table-1). The prevalence for other lesions was:
Peripapillary Atrophy (0.92%), Lacquer Cracks (2.57%), Diffuse Atrophy (6.39%), Staphyloma (5.73%),
and Intra-choroidal Cavitation (2.17%).
We used stratified analysis to find out the demographic factors that related to the distribution of
MMD (Table-2). Age was statistically significantly related to the prevalence of MMD (P<0.001). The
prevalence of MMD in each stratum of age in ascending order was: 39.31% (50-59), 50.18% (60-69),
50.35% (70-79), 82.61% (80+). The prevalence of MMD was positively related to the severity of myopia.
The prevalence of MMD among participants with different severity of myopia was: 15.49% for mild
myopia, 41.89% for moderate myopia, and 80.92% for severe myopia. We also found that there was no
significant association between other categorical variables (sex, smoking status, and drinking status) and
the prevalence of MMD (P>0.1). The prevalence of MMD was only 0.97% difference between males
(45.52%) and females (44.55%). Interestingly, the prevalence of MMD was lower for participants who
were current smokers or ex-smokers. Compared to participants who did not drink, the prevalence of
MMD was lower for participants who were current or former drinkers.
The severity of myopia was associated with MMD and MMD lesions (P<0.05). As the severity of
myopia increased, the prevalence of lesions increased. However, age was only statistically significantly
related to the prevalence of disc tilt, diffuse atrophy, tessellation, and peripapillary atrophy. (P<0.05)
9
Table 1: Fitted value prevalence of MMD and ocular lesions
Total sample size Number of diagnosed Prevalence
Myopic Macular Degeneration 1523 684 44.91%
All Lesions:
Disc Tilt
Peripapillary Atrophy
Tessellation
Lacquer Cracks
Diffuse Atrophy
Patchy Atrophy
Staphyloma
Intra-choroidal Cavitation
1521
1523
1519
1517
1517
1517
1518
1520
427
14
482
39
97
106
87
33
28.07%
0.92%
31.73%
2.57%
6.39%
6.96%
5.73%
2.17%
Table 2: Distribution of MMD by demographic factors
Total sample size Number of diagnosed Prevalence of MMD P-value
Age level (in years):
50-59
60-69
70-79
80+
809
550
141
23
318
276
71
19
39.31%
50.18%
50.35%
82.61%
<0.001
The severity of
myopia:
Mild
Moderate
Severe
213
1048
262
33
439
212
15.49%
41.89%
80.92%
<0.001
Sex:
Male
Female
569
954
259
425
45.52%
44.55%
0.71
Smoking status:
Never
Ex-smoker
Current smoker
1337
107
78
609
47
28
45.55%
43.93%
35.90%
0.24
Drinking status:
Never
Ex-drinker
Current drinker
1287
105
86
584
45
34
45.38%
42.86%
39.53%
0.52
3-2 AL analysis
The association between AL and demographic variables was summarized in Table-3. As the
statistical test indicated, the mean AL for the female was statistically significantly lower than the mean
AL for the male (24.7 mm vs. 25.1 mm, P<0.001). Also, participants aged 50-59 had the mean AL of 24.8
mm; 60-69 had the mean AL of 25.0 mm; 70-79 had the mean AL of 24.5 mm; age above 80 had the
mean AL of 24.7 mm. The result from the ANOVA test indicated that AL was statistically significantly
different among different age groups (P<0.001).
In our sample, myopia severity was also significantly related to AL (P<0.001). There were 213
participants with mild myopia (-0.5D < SE < 2D), 1048 participants with moderate myopia (-5D ≤ SE ≤ -
10
0.5D), and 262 participants with severe myopia (SE < -5D). The AL for participants with mild, moderate,
and severe myopia was 23.7 mm, 24.6 mm, and 26.7 mm, respectively, which showed an increasing trend.
We also found that smoking and drinking status are not statistically significantly related to AL. (P=0.286
for smoking status vs. AL and P=0.216 for drinking status vs. AL).
The patient’s height and weight were associated with AL (P<0.001 for both). The parameter
estimated in simple linear regression indicated that as 1 cm increased in height, the mean estimated AL
would increase by 0.031mm (95% CI: [0.022,0.040]), and as 1 kg increased in weight, the mean estimated
axial length would increase 0.013mm (95% CI: [0.007,0.196]). Body Mass Index (BMI), Systolic blood
pressure (SBP), and Diastolic blood pressure (DBP) were not statistically significantly related to AL.
(P=0.52 for BMI vs. AL, P=0.062 for SBP vs. AL, and P=0.86 for DBP VS AL).
Table 3: Distribution of AL by demographic factors
AL (mm)
N(Frequency) Mean SD P value
Sex: <0.001
Male 566(37.4%) 25.1 1.4
Female 943(62.6%) 24.7 1.5
Smoking Status: 0.286
Never 1337(87.8%) 24.9 0.2
Ex-smoker 107(7.0%) 24.9 0.2
Current smoker 78(5.1%) 24.6 0.2
Age: <0.001
50-59 809(53.1%) 24.8 0.3
60-69 550(36.1%) 25.0 0.3
70-79 141(9.3%) 24.5 0.3
80+ 23(1.5%) 24.7 0.3
Alcohol status: 0.216
Never 1287(87.1%) 24.8 0.2
Ex-drinker 105(7.1%) 25.1 0.2
Current drinker 86(5.8%) 24.8 0.2
Severity of myopia: <0.001
Mild 213(14.0%) 23.7 0.1
Moderate 1048(68.8%) 24.6 0.1
Severe 262(17.2%) 26.7 0.1
11
3-3 Relationship between AL and prevalence of MMD
We found that as AL increased to a higher value, the fitted value prevalence of MMD and MMD
lesions showed an upward trend. We also identified knot points on the linear spline based on the
prevalence. The knots point in AL varied by eye conditions, with more severe lesions prevalent at longer
AL (Table-5).
3-3-a AL and the prevalence of MMD
Logistic regression revealed that, in this group of Chinese Americans, people with 1 mm higher
AL were 1.95 times as likely to have prevalent MMD, compared to people with 1 mm lower AL [95% CI:
1.74-2.19].
LOESS regression was suggestive of a higher fitted value prevalence of MMD in participants
with AL greater than 23 mm compared to AL not greater than 23 mm (Fig. 1). For participants with
specific AL ≤ 23 mm, the fitted value prevalence was all lower than 24%. However, the fitted value
prevalence for participant with AL greater than 23 mm were as follows: 38.28% (AL=24 mm), 57.72%
(AL=25 mm), 76.63% (AL=26 mm), 88.70% (AL=27 mm), 94.14% (AL=28 mm), and nearly 100% for
(AL≥29 mm).
We used spline regression with AL = 23 mm as the knot point to explore more on this association.
Although the model was more fitted to our data after using linear spline (r=0.95), the knot point was not
significant (P=0.40).
12
Figure 1: A scatter plot with a spline line depicting the association between the fitted value prevalence of
MMD and AL.
3-3-b AL and the prevalence of diffuse atrophy
The result obtained from logistic regression reflected that the odds of having diffuse atrophy were
2.19 times higher among people with 1 mm higher AL compared to people with 1mm lower AL [95% CI:
1.83, 2.61].
LOESS analysis indicated that there was an obvious difference in the fitted value prevalence of
diffuse atrophy before and after the AL reached 26 mm (Fig. 2). The fitted value prevalence was less than
13% in participants with specific AL not greater than 26 mm, but much higher in participants with AL
greater than 26 mm: 25.27% (AL=27 mm), 42.54% (AL=28 mm), 65.56% (AL=29 mm), 73.31% (AL=30
mm) and 91.20% (AL≥31 mm).
After applying the linear spline based on the knot point at AL = 26 mm, the relationship between
the prevalence of diffuse atrophy and AL for participants with AL no longer than 26 mm was
significantly different from the relationship for participants with AL over 26 mm (P<0.0001).
13
Figure 2: A scatter plot with a spline line depicting the association between the fitted value prevalence of
diffuse atrophy and AL.
3-3-c AL and the prevalence of lacquer cracks
Logistic regression showed that among our participants, those with 1 mm higher AL were 3.05
times more likely to have lacquer cracks compared with those with 1 mm lower AL [95% CI: 2.31-4.03].
As reflected in LOESS regression (Fig. 3), the fitted value prevalence of lacquer cracks for
participants with specific AL were as follows: nearly 0% (AL≤22 mm), 0.05% (AL=23 mm), 0.16%
(AL=24 mm), 0.70% (AL=25 mm), 3.22% (AL=26 mm), 10.88% (AL=27 mm), 24.08% (AL=28 mm),
64.14% (AL=29 mm), 68.39% (AL=30 mm), and 95.43% (AL≥31 mm). It was obvious to notice that the
fitted value prevalence of lacquer cracks was much higher for AL higher than 26 mm, compared to the
fitted value prevalence at AL ≤ 26 mm.
Our model fitted to the data more (r=0.98) after adding a linear spline with a knot point at 26 mm
AL. The relationship between the prevalence of lacquer cracks and AL for participants with AL ≤ 26 mm
was significantly different from the relationship for participants with AL > 26 mm (P<0.0001).
14
Figure 3: A scatter plot with a spline line depicting the association between the fitted value prevalence of
lacquer cracks and AL.
3-3-d AL and the prevalence of patchy atrophy
The results derived from logistic regression model indicated that the odds of having patchy
atrophy were 2.89 times higher among participant with 1mm higher in AL compared to participants with
1 mm lower in AL [95% CI: 1.97-4.22].
LOESS analysis reflected that the fitted value prevalence of patchy atrophy was much different
before and after 28 mm AL (Fig. 4). The fitted value prevalence was below 6% for participants with
AL≤28 mm, but much higher for participant with AL >28 mm (27.64% for AL=29 mm, 28.06% for
AL=30 mm, 79.08% for AL≥31 mm).
15
We fitted linear spline with knot point at AL = 28 mm and found that the relation between the
prevalence of patchy atrophy and AL for participants with AL ≤ 28 mm was significantly different from
the relation for participants with AL over 28 mm (P < 0.001).
Figure 4: A scatter plot with a spline line depicting the association between the fitted value prevalence of
patchy atrophy and AL.
3-3-e AL and the prevalence of staphyloma
Logistic regression reflected that, among our participants, people with 1 mm higher AL were 1.86
times as likely to have staphyloma, compared to people with 1 mm lower AL [95% CI: 1.56-2.21].
LOESS regression provided the fitted value prevalence of staphyloma under different AL: 0
(AL=20 mm), 0.13% (AL=21 mm), 0.28% (AL=22 mm), 0.63% (AL= 23 mm), 1.37% (AL=24 mm),
4.23% (AL=25 mm), 12.79% (AL=26 mm), 26.37% (AL= 27 mm), 42.69% (AL=28 mm), 63.71%
(AL=29 mm), 64.39% (AL=30 mm), and 86.42% (AL ≥ 31 mm) which suggested that the fitted value
prevalence of staphyloma was significantly higher after 25 mm AL than before (Fig. 5).
16
The linear spline with knot point at AL = 25 mm showed that the relation between prevalence of
staphyloma and AL before it reached 25 mm was significantly different from the relation for participants
with AL exceeding 25 mm (P<0.001).
Figure 5: A scatter plot with a spline line depicting the association between the fitted value prevalence of
staphyloma and AL.
3-3-f AL and the prevalence of disc tilt
Logistic regression model indicated that participants with 1 mm higher AL were 1.42 times as
likely to have disc tilt compared to participants with 1 mm lower AL [95% CI:1.29-1.57].
As shown in figure 6, the disc tilt prevalence changed considerably before and after the AL
reached 23 mm according to a LOESS regression. In participants with AL not exceeding 23 mm, the
fitted value prevalence was as follows: 3.49% (AL=20 mm), 7.11% (AL=21 mm), 10.21% (AL=22 mm),
and 15.82% (AL=23 mm), whereas the prevalence was 22.74% for participants with AL=24 mm, 32.74%
for participants with AL=25 mm, and above 45% for participants with AL≥26 mm.
17
Applying linear spline with a knot point at AL = 23 mm, we found that the relation between
prevalence of disc tilt and AL for participants with AL less than 23 mm was not significantly different
from the relation for participants with AL over 23 mm (P=0.42).
Figure 6: A scatter plot with a spline line depicting the association between the fitted value prevalence of
disc tilt and AL.
3-3-g AL and the prevalence of peripapillary atrophy
The result obtained from logistic regression model indicated that the odds having peripapillary
atrophy was 2.13 times higher for our participants with 1 mm higher AL compared to participants with 1
mm lower AL [95% CI: 1.78-2.54].
The LOESS analysis (Fig. 7) suggested a higher fitted value prevalence of peripapillary atrophy
in participants with an axial length > 25 mm, compared to those with AL≤ 25 mm. Participants with AL
no greater than 25 mm had a fitted value prevalence less than 6%, while the fitted value prevalence for
participants with AL=26 mm was 14.63%, for participants with AL=27 mm was 31.40%, and above 50%
for participants with AL≥28 mm.
18
We fitted a linear spline with a knot point at 25 mm of AL and found that the relationship
between the prevalence of peripapillary atrophy and AL for participants with AL less than 25 mm was
significantly different from the relationship for participants with AL over 25 mm (P<0.0001).
Figure 7: A scatter plot with a spline line depicting the association between the prevalence of
peripapillary atrophy and AL.
3-3-h AL and the prevalence of tessellation
Logistic regression reflected that, in this group of Chinese Americans, people with 1 mm higher
AL were 2.02 times as likely to have tessellation, compared to people with 1 mm lower AL [95% CI:
1.79-2.27].
The LOESS analysis (Fig. 8) showed a huge difference in the fitted value prevalence of
tessellation before AL reached 23 mm and after AL reached 23 mm. The fitted value prevalence for
participants with AL≤23 mm was lower than 24%, but much higher for those with AL>23 mm: 40.00%
(AL=24 mm), 60.46% (AL=25 mm), and above 77% (AL≥26 mm).
19
We utilized splines with knot point at AL = 23 mm. The slope below the knot point was not
statistically significantly different from the slope above the knot (P=0.018).
Figure 8: A scatter plot with a spline line depicting the association between the fitted value prevalence of
tessellation and AL.
3-3-i AL and the prevalence of intra-choroidal cavitation
Logistic regression reflected that, among our participants, people with 1 mm higher AL were 1.28
times as likely to have intra-choroidal cavitation, compared to people with 1 mm lower AL [95% CI:
1.03-1.59].
Based on LOESS analysis (Fig. 9), we noticed that the fitted value prevalence of intra-choroidal
cavitation before and after the AL reached 25 mm was much different (lower than 2.2% for AL≤25 mm
vs higher than 4.3% for AL>25 mm).
We fitted spline regression with a knot point at AL = 25 mm. The association between the fitted
value prevalence of intra-choroidal cavities and AL was not significantly different at AL ≤ 25 mm from
the association at AL ≥ 25 mm (P=0.042).
20
Figure 9: A scatter plot with a spline line depicting the association between the fitted value prevalence of
intra-choroidal cavitation and AL
Table 4: Odds ratio for MMD and its associated lesions
Odds Ratio 95% Confidence Interval
MMD 1.95 [1.74, 2.19]
Diffuse atrophy 2.19 [1.83, 2.61]
Lacquer crack 3.05 [2.31, 4.03]
Patchy Atrophy 2.89 [1.97, 4.22]
Staphyloma 1.86 [1.56, 2.21]
Disc Tilt 1.42 [1.29, 1.57]
Peripapillary Atrophy 2.13 [1.78, 2.54]
Tessellation 2.02 [1.80, 2.27]
Intra-choroidal Cavitation 1.28 [1.03, 1.59]
3-4 Summary of Knot points analysis
In the table-5, the knot points in the linear spline fitted by the relationship between fitted value
prevalence and AL were summarized. The fitted value prevalence of MMD inflected at AL = 23 mm. At
AL = 25 mm, the risk of having peripapillary atrophy and increased dramatically. As our data suggested,
the fitted value prevalence of diffuse atrophy, and lacquer cracks were much higher when AL >
21
26mm, compared to the fitted value prevalence of AL ≤ 26 mm. The knot point for the fitted value
prevalence of patchy atrophy was AL = 27 mm.
As shown in figure 10, the prevalence of MMD, disc tilt, and tessellation were lower than 25%
before their knot points, but higher than the fitted value prevalence of other lesions at AL ≤ 28 mm. At
AL ≥ 28 mm, the fitted value prevalence of peripheral atrophy, intra-choroidal cavitation, diffuse atrophy,
and lacquer cracks were over 50%, and the difference between their fitted value prevalence and that of
MMD, disc tilt, and tessellation was narrowing. Also, when the AL was at the extremely high values, the
prevalence was 100% for MMD and tessellation.
Table 5: Knot point for MMD and its lesions
Ocular disease: Knot point at axial length(mm)
Myopic macular degeneration 23
Diffuse Atrophy 26
Lacquer Cracks 26
Patchy Atrophy 28
Staphyloma 25
Peripapillary Atrophy 25
Figure 10: Fitted value prevalence of MMD and its lesions under specific AL
22
Chapter 4: Discussion
In this analysis, we investigated the relationship between the AL and the prevalence of MMD and
MMD lesions in a cohort of Chinese Americans living in Monterey Park. The overall prevalence MMD
was 44.91% and the three most common MMD lesions in our sample were tessellation (31.37%), disc tilt
(28.07%), and patchy atrophy (6.96%).
These data suggested that longer AL was an independent risk factor for prevalent MMD and its
associated lesions. Our analysis was suggestive of a minimal difference in the fitted value prevalence of
MMD between 20-23 mm of AL. From 23 mm onwards, there was a substantially higher MMD
prevalence for longer AL. All participants with an AL of 31 mm or more had evidence of MMD. Future
longitudinal studies with larger sample sizes and combined participants of different races could be done to
expand our analysis.
For other MMD lesions, the inflection points in AL associated with increased risk of prevalence
(in ascending order of AL) were as follows: MMD (23 mm), peripapillary (25 mm), staphyloma (25 mm),
diffuse atrophy (26 mm), lacquer cracks (26 mm), and patchy atrophy (28 mm). These might provide
clinically relevant information for eye care providers. At an AL of 23 mm, people could be checked more
vigorously and diligently for possible MMD since the prevalence of MMD increases to a high level when
AL exceeds 23 mm. Above the AL of 25 mm, the risk for other lesions listed above increased, so people
should be more careful to those lesions.
There were many studies done about the prevalence of MMD worldwide. The average worldwide
prevalence of MMD was 2.1%, while for a single country, the prevalence of MMD was 1.47% in the
United States, 7.3% in China, 7.7% in Malaysia, and 5.7% in India, 3.8% in Singapore, 1.3% in Russia
and 10.3% in German
7,10-12,33-36
. Another study which conducted in the Netherlands with 626 people of
European ancestry and our study investigated the prevalence of MMD among myopic participants. They
found the prevalence of MMD (25.9%)
37
was much lower than the Chinese American population
(44.91%).
23
While our data suggested sex, age, and level of myopia were statistically significant factors
related to the AL (P<0.001). The relationship between AL and sex has been different in studies of Asians.
AL was significantly higher for males than females in our study, but this relationship was not found in the
study of 428 Japanese participants with myopia
38
(P>0.05). The most significant difference in the AL was
because of the different severity of myopia. The AL length for participants with mild, moderate, and
severe myopia were 23.7 mm, 24.6 mm, and 26.7 mm, respectively. Similar results were found in the
Japanese study. It pointed out that AL for participants with high myopia increased much more than for
participants without high myopia (P<0.001)
18
.
To our knowledge, few published studies have investigated these knot points in the relationship
between AL and MMD. Therefore, it is a little challenging to compare these results. But we believe these
novel findings add to the literature and addresses the paucity of knowledge.
Our study has strong strengths. First, our data came from the Chinese American Eye Study
(CHES), a population-based assessment of the prevalence of ocular disease and the largest ophthalmic
study among Chinese Americans, which contained more than 4500 eligible participants. A large sample
size of 1523 participants over 50 years old with myopia participated in our study. Secondly, by repeating
the measurement multiple times and taking the average of them, the measurement errors were minimized.
Sufficient and reliable data supported the accuracy and validity of our research and allowed us to obtain a
more convincing conclusion. Also, our study helped ophthalmic professionals inform people with myopia
at an early stage about the potential risk of MMD or its lesions.
Our research still has some limitations. The results from our study might not be generalizable to
the entire Chinese diaspora or other ethnic populations. Also, the logistic regression model with adjusted
confounding variables had R-square higher than 0.9 for each association between AL and fitted value
prevalence, so we cannot rule out the concerns of the models being overfitted. Furthermore, our study was
not longitudinal, so we could not explore the pattern of change in prevalence among our participants. We
used the same dataset for knot point selection and model performance evaluation rather than splitting the
dataset into training and testing dataset, which is another limitation of our study.
24
In the conclusion, we found axial length of the eye to be an independent risk factor for prevalence
of myopic macular degeneration and associated lesions in this cohort of Chinese Americans. There was
evidence of a substantial increase in risk of MMD and MMD lesion prevalence when AL was above 23
mm. Future longitudinal studies might help to confirm these associations. It might be beneficial for the
eye care providers to be aware of these associations in this demographic group, so that they are extra-
cautious in conducting regular retinal exams in the myopes with >23 mm of AL and referring them to
retina specialists for evaluation.
25
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Abstract (if available)
Abstract
Purpose:
To investigate the association between axial length (AL) and prevalence of myopic macular degeneration (MMD) and MMD lesions, and to find out the inflection point in AL where the fitted value prevalence of MMD and its associated lesions significantly increased among Chinese Americans.
Study Design:
A population-based cross-section study.
Method:
Data from a total of 1523 participants with myopia from the Chinese American Eye Study (CHES), aged 50 years or older, were used for this analysis. Participants underwent an interview, clinical exam, ophthalmic exam, and stereoscopic fundus photography. MMD was assessed in a masked manner by an expert grader. A modified version of the Meta-Analysis for Pathologic Myopia (META-PM) was used to define MMD that included presence of tessellation, diffuse and patchy chorio-retinal atrophy, atrophic macula, lacquer cracks, choroidal neovascularization, and Fuchs’ spots. Multiple logistic regression was used and odds ratios and 95% Confidence intervals [OR, (95% CI)] were calculated to examine the association of MMD and AL. To assess the qualitative nature of the relationship between the predictors and MMD, we performed locally estimated (Loess) regression. We also fitted linear spline methods to determine the knots points of the fitted value prevalence of MMD and its lesions.
Results:
Out of 1523 participants with myopia, a total of 684 (44.91%) had MMD. The prevalence of MMD associated lesions among our observed participants were tessellation (31.73%), disc tilt (28.07%), patchy atrophy (6.96%), diffuse atrophy (6.39%), staphyloma (5.73%), lacquer cracks (2.57%), intra-choroidal cavitation (2.17%), peripapillary atrophy (0.92%). Sex, weight, height, and severity of myopia were found to be significantly related to AL (P<0.001 for each association). For MMD and its lesions, the inflection points for increased prevalence were as follows: MMD (AL=23 mm), peripapillary atrophy (AL=25 mm), staphyloma (AL=25 mm), diffuse atrophy (AL=26 mm), lacquer cracks (AL= 26 mm), patchy atrophy (AL=28 mm).
Conclusion:
In this cohort of Chinese Americans, the prevalence of MMD and its associated lesions was positively related to AL. From AL of 23 mm or longer, there was substantially higher prevalence of MMD. For AL ≥ 25 mm, the fitted value prevalence of other lesions was much higher compared to AL < 25 mm.
Eye care providers should be aware of an increased risk of severe MMD lesions among Chinese Americans with AL values above 23 mm. Therefore, they should consider performing regular detailed retinal examination or refer the patient to a retina specialist for evaluation.
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Asset Metadata
Creator
Jiang, Wenbo
(author)
Core Title
Ocular axial length and prevalence of myopic macular degeneration among Chinese Americans
School
Keck School of Medicine
Degree
Master of Science
Degree Program
Biostatistics
Degree Conferral Date
2022-12
Publication Date
08/31/2022
Defense Date
08/30/2022
Publisher
University of Southern California
(original),
University of Southern California. Libraries
(digital)
Tag
axial length,Chinese American eye health study,myopic macular degeneration,OAI-PMH Harvest
Format
application/pdf
(imt)
Language
English
Contributor
Electronically uploaded by the author
(provenance)
Advisor
Choudhury, Farzana (
committee chair
), Piao, Jin (
committee member
), Siegmund, Kim (
committee member
)
Creator Email
websterjwb@gmail.com,wenbojia@usc.edu
Permanent Link (DOI)
https://doi.org/10.25549/usctheses-oUC111384902
Unique identifier
UC111384902
Legacy Identifier
etd-JiangWenbo-11164
Document Type
Thesis
Format
application/pdf (imt)
Rights
Jiang, Wenbo
Type
texts
Source
20220901-usctheses-batch-976
(batch),
University of Southern California
(contributing entity),
University of Southern California Dissertations and Theses
(collection)
Access Conditions
The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given.
Repository Name
University of Southern California Digital Library
Repository Location
USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA
Repository Email
cisadmin@lib.usc.edu
Tags
axial length
Chinese American eye health study
myopic macular degeneration