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Myopic Maculopathy and Optic Disc Changes in Highly Myopic Young Asian Eyes and Impact on Visual Acuity
Myopic Maculopathy and Optic Disc Changes in Highly Myopic Young Asian Eyes and Impact on Visual Acuity VICTOR KOH, COLIN TAN, PEI TING TAN, MARCUS TAN, VINAY BALLA, GERARD NAH, CHING-YU CHENG, KYOKO OHNO-MATSUI, MELLISA M.H. TAN, ADELINE YANG, PAUL ZHAO, TIEN YIN WONG, AND SEANG-MEI SAW PURPOSE:
To determine the prevalence and risk factors of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of young Asian adults and their impact on visual acuity. DESIGN: Prospective cross-sectional study. METHODS: In total, 593 highly myopic (spherical equivalent refraction [SER] less than L6.00 diopters [D]) and 156 emmetropic (SER between L1.00 and D1.00 D) male participants from a populationbased survey were included. All participants underwent standardized medical interviews, ophthalmic examination, and color fundus photographs. These photographs were graded systematically to determine the presence of optic disc and macular lesions. Myopic maculopathy was classified based on the International Classification of Myopic Maculopathy. RESULTS: The mean age was 21.1 ± 1.2 years. The mean SER for the highly myopic and emmetropic group was L8.87 ± 2.11 D and 0.40 ± 0.39 D, respectively (P < .001). Compared to emmetropic eyes, highly myopic eyes were significantly more likely to have optic disc tilt, peripapillary atrophy (PPA), posterior staphyloma, chorioretinal atrophy, and myopic maculopathy (all P < .001). The main findings included PPA (98.3%), disc tilt (22.0%), posterior staphyloma (32.0%), and chorioretinal atrophy (8.3%). Myopic maculopathy was present in 8.3% of highly myopic eyes
Supplemental Material available at AJO.com. Accepted for publication Jan 23, 2016. From the Vision Performance Centre, Military Medicine Institute, Singapore (V.K., M.T., G.N., P.Z.); Department of Ophthalmology, National University Health System, Singapore (V.K., M.T., V.B., C.C.-Y.); Department of Ophthalmology, Tan Tock Seng Hospital, Singapore (C.T.); Biostatistics Unit (P.T.T.) and Department of Ophthalmology (T.Y.W., S.S.-M.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore (C.C.-Y., T.Y.W., S.S.-M.); Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan (K.O.-M.); and Defence Medical & Environmental Research Institute, DSO National Laboratories, Singapore (M.M.H.T., A.Y.). Inquiries to Prof Seang-Mei Saw, Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, MD 3, Level 16 Medical Dr, Singapore 117597; e-mail: [email protected] 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2016.01.005
Ó
2016 BY
and was associated with older age (odds ratio [OR] 1.66; 95% CI: 1.22, 2.26), reduced choroidal thickness (OR 0.99; 95% CI: 0.98, 0.99), and increased axial length (AL) (OR 1.52; 95% CI: 1.06, 2.19). The presence of disc tilt, posterior staphyloma, and chorioretinal atrophy were associated with reduced visual acuity. CONCLUSIONS: Our study showed that myopia-related changes of the optic disc and macula were common in highly myopic eyes even at a young age. The risk factors for myopic maculopathy include increased age, longer AL, and reduced choroidal thickness. Some of these changes were associated with reduced central visual function. (Am J Ophthalmol 2016;164:69–79. Ó 2016 by Elsevier Inc. All rights reserved.)
M
YOPIA IS A MAJOR CAUSE OF VISUAL IMPAIRMENT
in the world1,2 and the prevalence is especially high in East Asia.3 In Asia, the prevalence of myopia (spherical equivalent refraction [SER] less than 0.50 diopters [D]) and high myopia (SER less than 6.00 D) in young adults (age range 18–24 years) are 81.6%–96.5% and 6.8%–21.6%, respectively.4–7 In addition, a study in Singapore comparing similar cohorts of young Asian men (aged 16–25 years) between 1996– 97 and 2009–10 showed that the prevalence of myopia and high myopia remained high in the latter group— 81.6% and 14.7%, respectively.4 This group of young myopic adults could pose a significant public health problem in the future. Complications associated with pathologic myopia can be irreversible and result in significant ocular morbidity. This includes myopic choroidal neovascularization, chorioretinal atrophy, and foveoschisis. These sightthreatening conditions result in reduced quality of life and increased socioeconomic burden, especially if they occur early in life.8 In the Singapore Cohort Study of Risk Factors for Myopia (SCORM) study (age range 12–16 years), the prevalence of optic disc tilt and peripapillary atrophy for children with SER less than 6.00 D (n ¼ 89) was 67.5% and 92.2%, respectively. Interestingly, compared to older myopic adults (aged more than 40 years), the prevalence of these myopic
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maculopathies was much lower in these highly myopic children (only 1 case each of posterior staphyloma and lacquer cracks).9–12 Electrophysiology studies have also shown that the myopic retinas of adolescents and young adults have diminished amplitudes and delayed latency despite a normal-looking retina.13 This evidence suggested that myopia-related structural changes in the retina could be age- and time-dependent. On the other hand, in population-based studies, among adults older than 40 years with high myopia (SER less than 5.00 D), only a relatively small proportion (0.9%–3.29%) develop structural changes.10,14,15 It is possible that apart from axial length (AL) and SER, there are other contributing risk factors leading to pathologic myopic changes. To date, there is little literature on the visual impact of pathologic myopia and when these myopiarelated changes affect highly myopic young adults. This is important in the assessment of visual potential because visual impairment at this young age group has significant impact on long-term visual prognosis and rehabilitation.14 We aim to describe the prevalence of myopic maculopathy and related structural abnormalities, including specific myopia-related optic disc and macular changes in a group of highly myopic (SER less than 6.00 D) young Asian men and compare them with emmetropic eyes of the same age group. We will also examine the risk factors for these myopia-related changes and their impact on visual acuity.
METHODS STUDY POPULATION:
INTERVIEW, VISUAL ACUITY MEASUREMENT, AND REFRACTION: All the participants who fulfill the inclu-
sion criteria and consented to the study underwent a standardized interview regarding their refraction status, including the age at which they started wearing glasses and the age at which their spherical refractive error first reached 6.00 D. Best-corrected visual acuity (BCVA) measurement and subjective cycloplegic refraction were conducted on the same day by a trained optometrist. The subjects’ monocular VA was measured using the logarithm of the minimal angle of resolution (logMAR) chart (Lighthouse International, New York, New York, USA) at 4 meters. If the largest number could not be identified at 4 meters, the chart was brought closer to the subject, then counting fingers, hand motion, or light perception vision was assessed. Cycloplegia was induced with 3 drops of cyclopentolate 1% 5 minutes apart. At least 30 minutes after the last drop, subjective cycloplegic refraction tests were performed by the same optometrist for all the participants. SER was calculated as the sum of the spherical power and half of the cylindrical power. OCULAR EXAMINATION AND IMAGING:
The current study was conducted between January 1, and December 31, 2012 and the methodology for subject recruitment was detailed elsewhere.16 Briefly, a total of 28 908 young male subjects aged 19–25 years underwent noncycloplegic autorefraction (Huvitz MRK-3100P, Republic of Korea) as part of a compulsory ophthalmic examination for pre-employment screening in Singapore. Out of 2584 persons identified to have high myopia (SER less than 6.00 D) based on noncycloplegic autorefraction, 719 subjects were selected based on refractive error–stratified random sampling strategy. They were invited to participate in the current study and underwent further examination and investigations at the Singapore Eye Research Institute as described below. For the control group, 168 emmetropic male subjects (SER between 1.00 and þ1.00 D) were recruited and underwent the same standardized examination and investigations as the highly myopic group. We further excluded participants with any history of anterior segment ocular diseases, trauma, or systemic condition that affects their visual performance; any form of refractive surgery or
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ocular surgery that may alter the refractive status of the eye; and those who were unwilling or unable to take part in the study or unable to return for scheduled visits. Written informed consent were taken from the subjects and their parents/guardians (if they were below 21 years of age). The study was conducted in accordance with the tenets of the World Medical Association’s Declaration of Helsinki and had ethics approval from the Singhealth Centralized Institutional Review Board.
Ocular biometry was performed using the IOL Master (Carl Zeiss Meditec AG, Jena, Germany), which included AL measurements. The mean of 3 AL measurements was taken as the final AL. All the subjects underwent a standardized and detailed examination of the anterior segment at the Singapore Eye Research Institute by a trained ophthalmologist. Slit-lamp examination included assessment of cornea and lenticular pathology and anterior chamber depth. Goldmann applanation tonometry was used to measure the intraocular pressure in mm Hg. Retinal photography was performed by a trained ophthalmic technician using the Canon CR-DGI (Canon Inc, Tokyo, Japan) nonmydriatic retinal camera after pupil dilation. Seven retinal photographs were taken to obtain the view of the optic disc (disc-centered and rotated at 30 degrees to the right and 30 degrees to the left), macular view, and right and left upper and lower arcade peripheral views from both eyes. Spectral-domain optical coherence tomography (SD OCT; Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) of the macula was also performed after pupil dilation. The SD OCT scans were centered over the
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FIGURE 1. Examples of various myopia-related optic disc and macular changes including optic disc tilt (Top left), peripapillary atrophy (Top center), posterior staphyloma (Top right), chorioretinal atrophy (Bottom left), lacquer cracks (Bottom center; black arrow), and Fuchs spot (Bottom right; black arrow).
FIGURE 2. Examples of fundus photographs based on the International Classification of Myopic Maculopathy: (Top left) tessellated fundus only (category 1), (Top right) diffuse chorioretinal atrophy (category 2), (Bottom left) patchy chorioretinal atrophy (category 3), and (Bottom right) macular atrophy (category 4).
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TABLE 1. Myopia-related Optic Disc and Macular Changes in Myopic and Emmetropic Eyes and Their Relationship With Spherical Equivalent Refraction Optic Disc Tilt All Subjects (n ¼ 749)
N
Emmetropic (0.75D to þ1.00 D) With high myopia (23.50 to 6.13 D)
Peripapillary Atrophy
n (%)
P Value
N
151
2 (1.3)
<.001
155
76 (49.0)
574
126 (22.0)
589
579 (98.3)
n (%)
Posterior Staphyloma P Value
N
<.001
Myopic Maculopathy Category (N ¼ 749) Chorioretinal Atrophy All Subjects (n ¼ 749)
N
Emmetropic (0.63 to þ1.50 D) With high myopia (23.50 to 6.13 D)
156
1 (0.6)
590
49 (8.3)
n (%)
n (%)
P Value
136
1 (0.66)
<.001
485
155 (32.0)
Presence of Myopic Maculopathya (Yes vs No)
0–1
2
3
4
n (%)
n (%)
n (%)
P Value
N
.01
P Value
N
n (%)
.001
156
155 (99.4)
1 (0.6)
0 (0.0)
0 (0.0)
593
544 (91.7)
31 (5.2)
11 (1.9)
7 (1.2)
n (%)
P Value
156
1 (0.6)
<.001
593
49 (8.3)
D ¼ diopters. a Presence of myopic maculopathy defined as findings in the fundus photograph consistent with category 2 and above based on the International Classification of Myopic Maculopathy.
macula (scan diameter of 20 degrees) and used to evaluate the posterior pole for subtle posterior staphyloma and choroidal thickness. The details for choroidal thickness measurement were already described elsewhere and showed good reproducibility.17 FUNDUS PHOTOGRAPH GRADING:
The color fundus photographs were graded similar to previously established grading techniques by a single trained grader (V.Y.) masked to the participant characteristics.14 Adjudication was performed by an experienced medical retina specialist (C.T.) from an accredited fundus photograph grading center. The main findings that were graded included (1) optic disc morphology (optic disc tilt and peripapillary atrophy) and (2) myopia-related macular pathology, including staphyloma, lacquer crack, and peripapillary atrophy (PPA) (Figure 1). Optic disc tilt was diagnosed when 1 margin of the optic disc was subjectively raised above the opposite margin and the direction of optic disc tilt was determined. Presence of lacquer crack, its location, and number were evaluated. The Curtin and Karlin classification was used to determine the subtype and position of PPA.18 Staphyloma was determined by visualizing the border of the ectasia, then its location and type were documented based on the Curtin classification.19 Intergrader reliability in grading for the aforementioned features was assessed with additional grading of 100 randomly selected eyes by trained graders (V.Y. and V.K.), and reliability was found to be good (all intraclass correlation coefficients
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above 0.75). However, more subtle posterior staphyloma may be missed from fundus photographs. As such, after the initial screening for posterior staphyloma on fundus photographs, we further analyzed the remaining eyes using cross-sectional images from SD OCT to detect shallower posterior staphyloma. All the SD OCT images were graded by a medical retinal specialist (C.T.). The presence of posterior staphyloma was defined as curvature of the retinal pigment epithelium layer, with a foveal depth of > _500 mm relative to the periphery of the OCT B-scan. This allowed posterior staphyloma with more gentle and subtle sloping edges to be detected. The presence of myopic maculopathy was defined and classified based on the International Photographic Classification and Grading System for Myopic Maculopathy.20 Briefly, pathologic myopia was classified in order of increasing severity (Figure 2): category 0, no macular lesions; category 1, only tessellated fundus; category 2, diffuse chorioretinal atrophy; category 3, patchy chorioretinal atrophy; and category 4, macular atrophy. In addition, ‘‘plus’’ lesions included lacquer cracks, choroidal neovascularization, and Fuchs spot. Posterior staphyloma was classified as supplemental information. For this study, the presence of myopic maculopathy is defined as findings in the fundus photograph consistent with category 2 and above. STATISTICAL
analysis was ANALYSIS: Statistical performed using IBM SPSS version 22 (IBM Corporation, New York, USA). Only 1 eye per subject was
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TABLE 2. Relationship Between Optic Disc and Macular Changes With Spherical Equivalent Refraction and Axial Length for the Highly Myopic Group (N ¼ 593) Optic Disc Tilt N
Spherical equivalent <6.00 to 8.00 D <8.00 to 10.00 D <10.00 D Axial length All 1st quartile (24.07–25.72 mm) 2nd quartile (25.74–26.85 mm) 3rd quartile (mm) (26.87–27.80 mm) 4th quartile (27.81–33.02 mm)
n (%)
Peripapillary Atrophy
Posterior Staphyloma
P Value
N
n (%)
P Value
N
<.001
246 202 141
239 (97.2) 202 (100.0) 138 (97.9)
.06
210 169 106
52 (24.8) 49 (29.0) 54 (50.9)
589 33
579 (98.3) 31 (93.9)
485 31
155 (32.0) 3 (9.7)
n (%)
238 197 139
35 (14.7) 46 (23.4) 45 (32.4)
574 31
126 (22.0) 6 (19.4)
147
26 (17.7)
152
148 (97.4)
129
29 (22.5)
194
44 (22.7)
197
194 (98.5)
162
47 (29.0)
202
50 (24.8)
207
206 (99.5)
163
76 (46.6)
.45
.09
P Value
<.001
<.001
Myopic Maculopathy Category Chorioretinal Atrophy
Spherical equivalent <6.00 to 8.00 D <8.00 to 10.00 D <10.00 D P value for myopic maculopathy category Axial length All 1st quartile (24.07–25.72 mm) 2nd quartile (25.74–26.85 mm) 3rd quartile (26.87–27.80 mm) 4th quartile (27.81–33.02 mm) P value for myopic maculopathy category
0–1
2
3
4
Presence of Myopic Maculopathy (Yes vs No)
N
n (%)
P Value
N
n (%)
n (%)
n (%)
n (%)
N
n (%)
P Value
246 203 141
12 (4.9) 11 (5.4) 26 (18.4)
<.001
248 204 141
236 (95.2) 193 (94.6) 115 (81.6) Reference
12 (4.8) 7 (3.4) 12 (8.5) P ¼ .10
0 (0.0) 2 (1.0) 9 (6.4) P < .001
0 (0.0) 2 (1.0) 5 (3.5) P < .001
248 204 141
12 (4.8) 11 (5.4) 26 (18.4)
P < 0.001
590 33
49 (8.3) 1 (3.0)
593 34
544 (91.7) 33 (97.1)
31 (5.2) 1 (2.9)
11 (1.9) 0 (0.0)
7 (1.2) 0 (0.0)
593 34
49 (8.3) 1 (2.9)
152
6 (3.9)
153
147 (96.1)
4 (2.6)
1 (0.7)
1 (0.7)
153
6 (3.9)
197
9 (4.6)
198
189 (95.5)
6 (3.0)
2 (1.0)
1 (0.5)
198
9 (4.5)
208
33 (15.9)
208
175 (84.1)
20 (9.6)
8 (3.8)
5 (2.4)
208
33 (15.9)
Reference
P ¼ .003
P ¼ .02
P ¼ .09
<.001
<.001
D ¼ diopters.
included for analysis. By default, the right eye is selected unless the SER of the right eye is more than 6.00 D for the myopic group, then the left eye is selected for analysis. The x2 test or Fisher exact test was used for comparing categorical variables between highly myopic eyes and emmetropic eyes, and Student t test was performed for continuous variables. Logistic regression was performed to determine the association with myopic maculopathy and its trend across SER and AL categories. Linear regression models adjusted for age and ethnicity were performed to determine the effect of optic disc
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tilt, PPA, posterior staphyloma, chorioretinal atrophy, and myopic maculopathy on BCVA. Statistical significance was set at P < .05.
RESULTS OUT OF A TOTAL OF 887 PARTICIPANTS WHO WERE
initially recruited for the study, we excluded 51 persons who did not meet the inclusion criteria and 87 persons
MYOPIC MACULOPATHY, OPTIC DISC CHANGES IN HIGHLY MYOPIC EYES
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TABLE 3. Multivariate Regression Analysis for the Determinants of Myopic Maculopathy for the Group of Young Highly Myopic Eyes Presence of Myopic Maculopathy (N ¼ 593) OR (95% CI)a
History of parental myopia No history 1 parent Both parents Age (y) Age of onset of myopia (y) Vertical choroidal thickness (mm) Axial length (mm)
P Value
Reference 1.24 (0.46, 3.37) 0.85 (0.29, 2.46) 1.66 (1.22, 2.26) 1.05 (0.89, 1.24)
.67 .76 .001 .58
0.99 (0.98, 0.99)
<.001
1.52 (1.06, 2.19)
.02
a
Adjusted for family history of myopia, age, age of onset of myopia, axial length.
whose final subjective cycloplegic refraction results did not fulfill either the high myopia (SER less than 6.00 D) or emmetropia (SER between 1.00 and þ1.00 D) criteria. For our final analyses, we included 593 and 156 participants into the high myopia and emmetropic group, respectively. All the subjects were male and the mean age was 21.1 6 1.2 (standard deviation [SD]) years for the myopic group and 21.5 6 1.1 years (SD) for the emmetropic group (P ¼ .09). The mean SER for the myopic and emmetropic group was 8.87 6 2.11 D and 0.40 6 0.39 D, respectively (P < .001). The corresponding AL was 27.45 6 1.17 mm and 23.83 6 1.01 mm, respectively (P < .001). Table 1 shows the common myopia-related optic disc and macular changes in highly myopic and emmetropic eyes and their relationship with SER. Compared to emmetropic eyes, the highly myopic eyes were significantly more likely to be affected by optic disc tilt, PPA, posterior staphyloma, and chorioretinal atrophy (all P < .001). For optic disc tilt, the most common direction of tilt was temporal (125/168; 74.4%) and for PPA, the most common location was temporal (434/655; 66.2%). Lacquer cracks were uncommon (6/593; 1.0%) and there was no significant difference in the presence of lacquer cracks between myopic eyes and emmetropic eyes (P ¼ .608). The lacquer cracks detected in all 6 myopic eyes were located in the macular region without involvement of the fovea. The most common type of staphyloma was peripapillary (103/155; 66.5%). For myopic eyes with chorioretinal atrophy, 72.5% (37/51 eyes) were smaller than 1 disc diameter in size. Most of the chorioretinal atrophy was also found in the peripapillary region (40/49; 81.6%). The prevalence of more visually adverse myopia-related changes such as macular hemorrhages, choroidal neovascularization, and 74
Fuchs spots (2/593; 0.34%) were low in the myopic group. Myopic maculopathy was present in 8.3% (49/593) of the eyes in the myopic group. Table 2 shows that with decreasing SER, there is a significantly increased frequency of myopia-related optic disc and macular changes in the eyes with high myopia (all P < .001) except peripapillary atrophy (P ¼ .06). Increased AL was also significantly associated with increased frequency of chorioretinal atrophy and posterior staphyloma, and similar trends for the other structural changes, although these did not reach statistical significance. The proportions of the more severe categories of myopic maculopathy (category 3 and 4) were significantly higher with decreased SER. Overall, the proportion of eyes with myopic maculopathy was significantly higher with decreased SER or increased AL. Table 3 shows multivariate logistic regression analysis for the risk factors of myopic maculopathy. Our results showed that the risk of developing myopic maculopathy increased by 1.66 times for each year increase in age (P ¼ .001) and by 1.52 times for each 1 mm increase in AL (P ¼ .02). Reduced choroidal thickness was also significantly associated with the development of myopic maculopathy (odds ratio [OR] 0.99; 95% confidence interval [CI]: 0.98, 0.99; P < .001). This is further illustrated in Figure 3, stratified by age, vertical fovea choroidal thickness, and AL, showing the relative proportions of eyes with myopic maculopathy among eyes with high myopia (SER < 6.00, n ¼ 593). In addition, the area under the receiver operating curve (AUROC) showed that vertical fovea choroidal thickness of less than 250 mm showed the highest and fairly good AUROC of 0.789 (sensitivity ¼ 95.3% and specificity ¼ 62.4%). However, both AL (AL more than 27.8 mm; AUROC ¼ 0.722) and SER alone (SER less than 9.6 D; AUROC ¼ 0.705) showed modest accuracy in detecting possible myopic maculopathy. Table 4 showed the effect of optic disc, macular, and myopic maculopathy changes on the visual acuity of this group of young Asian men affected by high myopia. Our results showed that presence of optic disc tilt, posterior staphyloma, and chorioretinal atrophy were associated with significantly poorer BCVA after adjusting for age and ethnicity.
DISCUSSION OUR STUDY DOCUMENTS A RELATIVELY HIGH PREVALENCE
of myopic maculopathy and specific myopia-related optic disc and macular changes in young Asian adults (aged 19– 25 years) with high myopia. In our cohort, one-fifth had optic disc tilt, almost all had PPA, and one-third had posterior staphyloma. It is interesting that among this group of highly myopic young men, a considerable proportion of eyes (8.3%) had myopic maculopathy. Most of the
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FIGURE 3. Comparison of proportion of myopic maculopathy by age, vertical choroidal thickness, and axial length.
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TABLE 4. Effect of Optic Disc, Macular Changes, and Myopic Maculopathy on Best-Correctable Visual Acuity (N ¼ 593) Beta-correctable Visual Acuity (logMAR) Modela
Optic disc tilt No Yes Peripapillary atrophy No Yes Posterior staphyloma No Yes Chorioretinal atrophy No Yes Myopic maculopathy No Yes
Modelb
Mean
n
P Value
Mean
P Value
0.05 0.08
448 126
.001
0.07 0.11
<.001
0.07 0.05
10 579
.69
0.09 0.08
.84
0.05 0.06
330 155
.07
0.07 0.08
.05
0.05 0.10
541 49
.001
0.08 0.13
.001
0.05 0.10
544 49
.002
0.08 0.13
.001
a
Univariate. Adjusted for age and ethnicity.
b
changes were significantly more common with longer AL. This is clinically significant, as eyes with myopic maculopathy continue to elongate with age21 and may lead to higher prevalence of myopia-related changes in the retina. There is little information on the prevalence of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of the adolescents and young adults. Chang and associates reported the prevalence of myopiarelated retinal changes in a myopic Singapore population older than 40 years (SER < 6.00 D), while the SCORM study reported myopia changes in teenage children in Singapore.9,10 The most common findings of Chang and associates’ study were posterior staphyloma (23%), followed by chorioretinal atrophy (19.3%). The most common optic disc finding was PPA (81.2%), followed by disc tilt (57.4%). Of 1227 children in SCORM, in 89 highly myopic children (age range 12–16 years) with SER < 6.00 D, 67.4% (60/89 eyes) had tilted optic disc and 93.3% (83/89 eyes) had PPA. There was only 1 eye with posterior staphyloma (AL ¼ 26.72 mm and SER ¼ 6.7 D) and 1 eye with lacquer cracks (AL ¼ 25.53 mm and SER ¼ 5.2 D). The prevalence of disc tilt and PPA was also similarly high for children with moderate myopia (SER between 3.00 and 6.00 D): 63.5% (214/337 eyes) and 87.2% (294/337 eyes), respectively. The presence of myopic maculopathy was rare in highly
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myopic children. This leads to postulations that myopic macular changes are time-dependent changes as a result of mechanical stretching of the retina from axial elongation. Our results showed that there was a higher prevalence of macular changes such as posterior staphyloma and chorioretinal atrophy in these young myopic eyes which was more consistent with older adults.22 Interestingly, the age range of the current study (range 19–25 years) was not much older than the SCORM study (age range 12–16 years). Our results showed that myopic maculopathy is present in close to 10% of these young highly myopic eyes. However, the more vision-threatening complications, such as macular hemorrhages, choroidal neovascularization, and Fuchs spots, were rare in our study, suggesting that these changes appear much later in life. The majority of the young myopic eyes already had a tessellated fundus, which suggested that the overlying retina was thinner and allowed the deeper choroidal vessels to be seen more clearly. Fundal tessellation has clinically insignificant visual consequences but can be an early sign of choroidal thinning leading to myopic maculopathy.23 In particular, the risk of myopic maculopathy is negligible if choroidal thickness is thicker than 250 mm with a good sensitivity but poor specificity. Choroidal thickness could be an additional quantifiable prognostic parameter for young myopic eyes at risk of developing pathologic myopia, although longitudinal studies are required to determine the temporal relationships. Our most important finding is the clear documentation that myopic maculopathy changes, including chorioretinal atrophy and other lesions, are found in older teenagers and young adults. The significance of our study is 3-fold. First, our study demonstrated the negative effects of some features of myopia-related optic disc and macular changes on the BCVA. The presence of optic disc tilt, chorioretinal atrophy, and myopic maculopathy were significantly associated with poorer BCVA, even in young adults. Chen and associates reported that lower visual acuity was associated with lacquer cracks, chorioretinal atrophy, and choroidal neovascularization in an older (mean age 40.6 6 17.1 years) Chinese population.24 Histologic and OCT-based studies have shown that choroidal thickness decreases with increasing severity of myopia owing to axial elongation of the globe.25,26 In addition, choroidal circulation was also reduced in myopic eyes, with formation of fibrous tissue replacing the choroidal vasculature.27,28 As the choroidal vasculature supplies the retinal pigment epithelium and outer retina, it is conceivable that reduced choroidal thickness could have resulted in the myopia-related structural changes of the optic disc and macula. Reduced choroidal thickness has also been associated with reduced BCVA in myopic eyes even without obvious macular pathology.26,29 Chorioretinal atrophy represents the final endpoint of combined photoreceptor
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and retinal pigment epithelium cell death, with irreversible loss of central visual function. Although the absolute reduction in visual acuity associated with pathologic myopia may not be high in our study, this highly myopic young population requires good central visual acuity and has high visual demands. These pathologic changes are mostly irreversible and could have a negative impact to the quality of life and increase the socioeconomic burden of myopia.8,30 Our study is also one of the first to show the high prevalence of posterior staphyloma in this young age group. This is surprising, as the literature suggests that posterior staphyloma is a late sign of pathologic myopia, which is much more prevalent in older adults (age >50 years) in population-based studies. This may have significant impact on visual prognosis, as posterior staphyloma was associated with a higher incidence of visually threatening complications such as macular hole retinal detachment,31 myopic foveoschisis, and choroidal neovascularization.32 This was attributed to the increased internal vector force from the posterior protrusion of the sclera wall coupled with early vitreous shrinkage.33,34 In addition, Hayashi and associates showed that up to 40% of highly myopic eyes with myopic maculopathy showed progression over a mean duration of 12.7 years and eyes with posterior staphyloma are at a higher risk of progression compared to eyes without posterior staphyloma.35 We recognized the limitation of color fundus photographs, which could underestimate the frequency of posterior staphyloma. As such, we used SD OCT imaging to provide crosssectional images of the posterior pole to detect more subtle and early posterior bowing of the retina. Owing to the potential vision-threatening complications that could be detected and treated effectively, eyes with posterior staphyloma require increased surveillance and detailed examination. Finally, the high prevalence of optic disc tilt and betaperipapillary atrophy in these myopic eyes makes it hard to assess the optic nerve head (ONH) characteristics. Multiple studies have shown a significant association between high myopia (SE less than 6.00 D) and primary openangle glaucoma.36,37 Optic disc tilt has been shown to affect ONH measurements measured by Heidelberg retinal tomography (Heidelberg Engineering, Heidelberg, Germany), and this may affect the diagnostic accuracy of its classification algorithm based on a normative database.38 Studies also showed that optic disc tilt was
associated with static visual field defects.39,40 These unique changes to the myopic optic disc make the diagnosis and monitoring of glaucoma in myopic eyes more challenging. Our study showed that the risk factors for developing myopic maculopathy included older age, reduced central choroidal thickness, and increased AL. Our results support the hypothesis that myopic maculopathy is timedependent and increases in prevalence with age owing to prolonged axial elongation of the globe.10,15 This highlights the importance of long-term and regular screening of young myopic eyes, especially if choroidal thickness is thinner than 250 mm on macular SD OCT. Our results also support early introduction of preventive strategies at a young age to retard ocular axial elongation and reduce the risk of developing pathologic myopiarelated structural changes earlier in life. The strength of this study includes a large sample size of highly myopic young Asian adults who prospectively underwent standardized examinations and detailed color fundus photograph grading. These young subjects are less likely to have media opacities that may affect visualization of structural changes in the retina or glaucoma. The limitations of our study should be mentioned. First, the subjects were predominantly Chinese (92.0%) and all were male. As such, the generalization of our results needs to be more cautious, although Cheng and associates reported that sex did not alter the prevalence of pathologic myopia findings in a population-based study involving subjects more than 40 years old.12 Second, the cross-sectional nature of our study cannot confirm the temporal relationships of these myopia-related changes with its risk factors. In conclusion, our study showed that myopic maculopathy and other structural changes in the optic disc and macula were common, even in young highly myopic adults in an urban Asian population. Most of the lesions were significantly associated with reduced SER, increased AL, and reduced central choroidal thickness. The risk factors for myopic maculopathy were older age, increased AL, and reduced central choroidal thickness. Myopic maculopathy and specific changes including chorioretinal atrophy, posterior staphyloma, and optic disc tilt were associated with reduced visual acuity. These visually disabling myopiarelated changes could worsen with age and significantly increase the disease burden of an increasingly common ocular condition in the world.
FUNDING/SUPPORT: MINISTRY OF DEFENCE GRANT DSO 20101136. FINANCIAL DISCLOSURES: THE FOLLOWING AUTHORS have no financial disclosures: Victor Koh, Colin Tan, Pei Ting Tan, Marcus Tan, Vinay Balla, Gerard Nah, Cheng Ching-Yu, Kyoko OhnoMatsui, Mellisa M.H. Tan, Adeline Yang, Paul Zhao, Tien Yin Wong, and Saw Seang-Mei. All authors attest that they meet the current ICMJE criteria for authorship. The authors acknowledge Chan Yiong Huak from the Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore for providing statistical support.
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REFERENCES 1. Liu JH, Cheng CY, Chen SJ, Lee FL. Visual impairment in a Taiwanese population: prevalence, causes, and socioeconomic factors. Ophthalmic Epidemiol 2001;8(5): 339–350. 2. Klaver CC, Wolfs RC, Vingerling JR, Hofman A, de Jong PT. Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. Arch Ophthalmol 1998;116(5):653–658. 3. Wong TY, Foster PJ, Hee J, et al. Prevalence and risk factors for refractive errors in adult Chinese in Singapore. Invest Ophthalmol Vis Sci 2000;41(9):2486–2494. 4. Koh V, Yang A, Saw SM, et al. Differences in prevalence of refractive errors in young Asian males in Singapore between 1996-1997 and 2009-2010. Ophthalmic Epidemiol 2014;21(4): 247–255. 5. Lee JH, Jee D, Kwon JW, Lee WK. Prevalence and risk factors for myopia in a rural Korean population. Invest Ophthalmol Vis Sci 2013;54(8):5466–5471. 6. Lee YY, Lo CT, Sheu SJ, Lin JL. What factors are associated with myopia in young adults? A survey study in Taiwan Military Conscripts. Invest Ophthalmol Vis Sci 2013;54(2): 1026–1033. 7. Lee SJ, Urm SH, Yu BC, et al. [The prevalence of high myopia in 19 year-old men in Busan, Ulsan and Gyeongsangnam-do]. J Prev Med Public Health 2011;44(1):56–64. 8. Wong TY, Ferreira A, Hughes R, Carter G, Mitchell P. Epidemiology and disease burden of pathologic myopia and myopic choroidal neovascularization: an evidencebased systematic review. Am J Ophthalmol 2014;157(1): 9–25.e12. 9. Samarawickrama C, Mitchell P, Tong L, et al. Myopiarelated optic disc and retinal changes in adolescent children from Singapore. Ophthalmology 2011;118(10): 2050–2057. 10. Chang L, Pan CW, Ohno-Matsui K, et al. Myopia-related fundus changes in Singapore adults with high myopia. Am J Ophthalmol 2013;155(6):991–999.e1. 11. Koh VT, Nah GK, Chang L, et al. Pathologic changes in highly myopic eyes of young males in Singapore. Ann Acad Med Singapore 2013;42(5):216–224. 12. Cheng SC, Lam CS, Yap MK. Prevalence of myopiarelated retinal changes among 12-18 year old Hong Kong Chinese high myopes. Ophthalmic Physiol Opt 2013;33(6): 652–660. 13. Koh V, Tan C, Nah G, et al. Correlation of structural and electrophysiological changes in the retina of young high myopes. Ophthalmic Physiol Opt 2014;34(6):658–666. 14. Vongphanit J, Mitchell P, Wang JJ. Prevalence and progression of myopic retinopathy in an older population. Ophthalmology 2002;109(4):704–711. 15. Asakuma T, Yasuda M, Ninomiya T, et al. Prevalence and risk factors for myopic retinopathy in a Japanese population: the Hisayama Study. Ophthalmology 2012;119(9): 1760–1765. 16. Gupta P, Saw SM, Cheung CY, et al. Choroidal thickness and high myopia: a case-control study of young Chinese men in Singapore. Acta Ophthalmol 2015;93(7):e585–e592.
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17. Gupta P, Sidhartha E, Girard MJ, Mari JM, Wong TY, Cheng CY. A simplified method to measure choroidal thickness using adaptive compensation in enhanced depth imaging optical coherence tomography. PLoS One 2014;9(5):e96661. 18. Curtin BJ, Karlin DB. Axial length measurements and fundus changes of the myopic eye. I. The posterior fundus. Trans Am Ophthalmol Soc 1970;68:312–334. 19. Curtin BJ. The posterior staphyloma of pathologic myopia. Trans Am Ophthalmol Soc 1977;75:67–86. 20. Ohno-Matsui K, Kawasaki R, Jonas JB, et al. International photographic classification and grading system for myopic maculopathy. Am J Ophthalmol 2015;159(5): 877–883.e7. 21. Saka N, Ohno-Matsui K, Shimada N, et al. Long-term changes in axial length in adult eyes with pathologic myopia. Am J Ophthalmol 2010;150(4):562–568.e1. 22. Gao LQ, Liu W, Liang YB, et al. Prevalence and characteristics of myopic retinopathy in a rural Chinese adult population: the Handan Eye Study. Arch Ophthalmol 2011;129(9): 1199–1204. 23. Yan YN, Wang YX, Xu L, Xu J, Wei WB, Jonas JB. Fundus tessellation: prevalence and associated factors: The Beijing Eye Study 2011. Ophthalmology 2015;122(9):1873–1880. 24. Chen H, Wen F, Li H, et al. The types and severity of high myopic maculopathy in Chinese patients. Ophthalmic Physiol Opt 2012;32(1):60–67. 25. Grossniklaus HE, Green WR. Pathologic findings in pathologic myopia. Retina 1992;12(2):127–133. 26. Ho M, Liu DT, Chan VC, Lam DS. Choroidal thickness measurement in myopic eyes by enhanced depth optical coherence tomography. Ophthalmology 2013;120(9):1909–1914. 27. Akyol N, Kukner AS, Ozdemir T, Esmerligil S. Choroidal and retinal blood flow changes in degenerative myopia. Can J Ophthalmol 1996;31(3):113–119. 28. Moriyama M, Ohno-Matsui K, Futagami S, et al. Morphology and long-term changes of choroidal vascular structure in highly myopic eyes with and without posterior staphyloma. Ophthalmology 2007;114(9):1755–1762. 29. Flores-Moreno I, Ruiz-Medrano J, Duker JS, RuizMoreno JM. The relationship between retinal and choroidal thickness and visual acuity in highly myopic eyes. Br J Ophthalmol 2014;98(1):143–144. 30. Zheng YF, Pan CW, Chay J, Wong TY, Finkelstein E, Saw SM. The economic cost of myopia in adults aged over 40 years in Singapore. Invest Ophthalmol Vis Sci 2013; 54(12):7532–7537. 31. Lam DS, Tam BS, Chan W, Leung AT. Retinal breaks. Ophthalmology 1999;106(5):859–860. 32. Steidl SM, Pruett RC. Macular complications associated with posterior staphyloma. Am J Ophthalmol 1997;123(2): 181–187. 33. Takano M, Kishi S. Foveal retinoschisis and retinal detachment in severely myopic eyes with posterior staphyloma. Am J Ophthalmol 1999;128(4):472–476. 34. Morita H, Funata M, Tokoro T. A clinical study of the development of posterior vitreous detachment in high myopia. Retina 1995;15(2):117–124. 35. Hayashi K, Ohno-Matsui K, Shimada N, et al. Longterm pattern of progression of myopic maculopathy: a
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natural history study. Ophthalmology 2010;117(8):1595–1611. 1611.e1-4. 36. Xu L, Wang Y, Wang S, Jonas JB. High myopia and glaucoma susceptibility the Beijing Eye Study. Ophthalmology 2007; 114(2):216–220. 37. Pan CW, Cheung CY, Aung T, et al. Differential associations of myopia with major age-related eye diseases: the Singapore Indian Eye Study. Ophthalmology 2013;120(2):284–291. 38. Tong L, Chan YH, Gazzard G, et al. Heidelberg retinal tomography of optic disc and nerve fiber layer in Singapore
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children: variations with disc tilt and refractive error. Invest Ophthalmol Vis Sci 2007;48(11):4939–4944. 39. Lee KS, Lee JR, Kook MS. Optic disc torsion presenting as unilateral glaucomatous-appearing visual field defect in young myopic Korean eyes. Ophthalmology 2014;121(5): 1013–1019. 40. Kumar RS, Baskaran M, Singh K, Aung T. Clinical characterization of young Chinese myopes with optic nerve and visual field changes resembling glaucoma. J Glaucoma 2012;21(5): 281–286.
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To determine the prevalence and risk factors of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of young Asian adults and their impact on visual acuity. DESIGN: Prospective cross-sectional study. METHODS: In total, 593 highly myopic (spherical equivalent refraction [SER] less than L6.00 diopters [D]) and 156 emmetropic (SER between L1.00 and D1.00 D) male participants from a populationbased survey were included. All participants underwent standardized medical interviews, ophthalmic examination, and color fundus photographs. These photographs were graded systematically to determine the presence of optic disc and macular lesions. Myopic maculopathy was classified based on the International Classification of Myopic Maculopathy. RESULTS: The mean age was 21.1 ± 1.2 years. The mean SER for the highly myopic and emmetropic group was L8.87 ± 2.11 D and 0.40 ± 0.39 D, respectively (P < .001). Compared to emmetropic eyes, highly myopic eyes were significantly more likely to have optic disc tilt, peripapillary atrophy (PPA), posterior staphyloma, chorioretinal atrophy, and myopic maculopathy (all P < .001). The main findings included PPA (98.3%), disc tilt (22.0%), posterior staphyloma (32.0%), and chorioretinal atrophy (8.3%). Myopic maculopathy was present in 8.3% of highly myopic eyes
Supplemental Material available at AJO.com. Accepted for publication Jan 23, 2016. From the Vision Performance Centre, Military Medicine Institute, Singapore (V.K., M.T., G.N., P.Z.); Department of Ophthalmology, National University Health System, Singapore (V.K., M.T., V.B., C.C.-Y.); Department of Ophthalmology, Tan Tock Seng Hospital, Singapore (C.T.); Biostatistics Unit (P.T.T.) and Department of Ophthalmology (T.Y.W., S.S.-M.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore (C.C.-Y., T.Y.W., S.S.-M.); Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan (K.O.-M.); and Defence Medical & Environmental Research Institute, DSO National Laboratories, Singapore (M.M.H.T., A.Y.). Inquiries to Prof Seang-Mei Saw, Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, MD 3, Level 16 Medical Dr, Singapore 117597; e-mail: [email protected] 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2016.01.005
Ó
2016 BY
and was associated with older age (odds ratio [OR] 1.66; 95% CI: 1.22, 2.26), reduced choroidal thickness (OR 0.99; 95% CI: 0.98, 0.99), and increased axial length (AL) (OR 1.52; 95% CI: 1.06, 2.19). The presence of disc tilt, posterior staphyloma, and chorioretinal atrophy were associated with reduced visual acuity. CONCLUSIONS: Our study showed that myopia-related changes of the optic disc and macula were common in highly myopic eyes even at a young age. The risk factors for myopic maculopathy include increased age, longer AL, and reduced choroidal thickness. Some of these changes were associated with reduced central visual function. (Am J Ophthalmol 2016;164:69–79. Ó 2016 by Elsevier Inc. All rights reserved.)
M
YOPIA IS A MAJOR CAUSE OF VISUAL IMPAIRMENT
in the world1,2 and the prevalence is especially high in East Asia.3 In Asia, the prevalence of myopia (spherical equivalent refraction [SER] less than 0.50 diopters [D]) and high myopia (SER less than 6.00 D) in young adults (age range 18–24 years) are 81.6%–96.5% and 6.8%–21.6%, respectively.4–7 In addition, a study in Singapore comparing similar cohorts of young Asian men (aged 16–25 years) between 1996– 97 and 2009–10 showed that the prevalence of myopia and high myopia remained high in the latter group— 81.6% and 14.7%, respectively.4 This group of young myopic adults could pose a significant public health problem in the future. Complications associated with pathologic myopia can be irreversible and result in significant ocular morbidity. This includes myopic choroidal neovascularization, chorioretinal atrophy, and foveoschisis. These sightthreatening conditions result in reduced quality of life and increased socioeconomic burden, especially if they occur early in life.8 In the Singapore Cohort Study of Risk Factors for Myopia (SCORM) study (age range 12–16 years), the prevalence of optic disc tilt and peripapillary atrophy for children with SER less than 6.00 D (n ¼ 89) was 67.5% and 92.2%, respectively. Interestingly, compared to older myopic adults (aged more than 40 years), the prevalence of these myopic
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RIGHTS RESERVED.
69
maculopathies was much lower in these highly myopic children (only 1 case each of posterior staphyloma and lacquer cracks).9–12 Electrophysiology studies have also shown that the myopic retinas of adolescents and young adults have diminished amplitudes and delayed latency despite a normal-looking retina.13 This evidence suggested that myopia-related structural changes in the retina could be age- and time-dependent. On the other hand, in population-based studies, among adults older than 40 years with high myopia (SER less than 5.00 D), only a relatively small proportion (0.9%–3.29%) develop structural changes.10,14,15 It is possible that apart from axial length (AL) and SER, there are other contributing risk factors leading to pathologic myopic changes. To date, there is little literature on the visual impact of pathologic myopia and when these myopiarelated changes affect highly myopic young adults. This is important in the assessment of visual potential because visual impairment at this young age group has significant impact on long-term visual prognosis and rehabilitation.14 We aim to describe the prevalence of myopic maculopathy and related structural abnormalities, including specific myopia-related optic disc and macular changes in a group of highly myopic (SER less than 6.00 D) young Asian men and compare them with emmetropic eyes of the same age group. We will also examine the risk factors for these myopia-related changes and their impact on visual acuity.
METHODS STUDY POPULATION:
INTERVIEW, VISUAL ACUITY MEASUREMENT, AND REFRACTION: All the participants who fulfill the inclu-
sion criteria and consented to the study underwent a standardized interview regarding their refraction status, including the age at which they started wearing glasses and the age at which their spherical refractive error first reached 6.00 D. Best-corrected visual acuity (BCVA) measurement and subjective cycloplegic refraction were conducted on the same day by a trained optometrist. The subjects’ monocular VA was measured using the logarithm of the minimal angle of resolution (logMAR) chart (Lighthouse International, New York, New York, USA) at 4 meters. If the largest number could not be identified at 4 meters, the chart was brought closer to the subject, then counting fingers, hand motion, or light perception vision was assessed. Cycloplegia was induced with 3 drops of cyclopentolate 1% 5 minutes apart. At least 30 minutes after the last drop, subjective cycloplegic refraction tests were performed by the same optometrist for all the participants. SER was calculated as the sum of the spherical power and half of the cylindrical power. OCULAR EXAMINATION AND IMAGING:
The current study was conducted between January 1, and December 31, 2012 and the methodology for subject recruitment was detailed elsewhere.16 Briefly, a total of 28 908 young male subjects aged 19–25 years underwent noncycloplegic autorefraction (Huvitz MRK-3100P, Republic of Korea) as part of a compulsory ophthalmic examination for pre-employment screening in Singapore. Out of 2584 persons identified to have high myopia (SER less than 6.00 D) based on noncycloplegic autorefraction, 719 subjects were selected based on refractive error–stratified random sampling strategy. They were invited to participate in the current study and underwent further examination and investigations at the Singapore Eye Research Institute as described below. For the control group, 168 emmetropic male subjects (SER between 1.00 and þ1.00 D) were recruited and underwent the same standardized examination and investigations as the highly myopic group. We further excluded participants with any history of anterior segment ocular diseases, trauma, or systemic condition that affects their visual performance; any form of refractive surgery or
70
ocular surgery that may alter the refractive status of the eye; and those who were unwilling or unable to take part in the study or unable to return for scheduled visits. Written informed consent were taken from the subjects and their parents/guardians (if they were below 21 years of age). The study was conducted in accordance with the tenets of the World Medical Association’s Declaration of Helsinki and had ethics approval from the Singhealth Centralized Institutional Review Board.
Ocular biometry was performed using the IOL Master (Carl Zeiss Meditec AG, Jena, Germany), which included AL measurements. The mean of 3 AL measurements was taken as the final AL. All the subjects underwent a standardized and detailed examination of the anterior segment at the Singapore Eye Research Institute by a trained ophthalmologist. Slit-lamp examination included assessment of cornea and lenticular pathology and anterior chamber depth. Goldmann applanation tonometry was used to measure the intraocular pressure in mm Hg. Retinal photography was performed by a trained ophthalmic technician using the Canon CR-DGI (Canon Inc, Tokyo, Japan) nonmydriatic retinal camera after pupil dilation. Seven retinal photographs were taken to obtain the view of the optic disc (disc-centered and rotated at 30 degrees to the right and 30 degrees to the left), macular view, and right and left upper and lower arcade peripheral views from both eyes. Spectral-domain optical coherence tomography (SD OCT; Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) of the macula was also performed after pupil dilation. The SD OCT scans were centered over the
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FIGURE 1. Examples of various myopia-related optic disc and macular changes including optic disc tilt (Top left), peripapillary atrophy (Top center), posterior staphyloma (Top right), chorioretinal atrophy (Bottom left), lacquer cracks (Bottom center; black arrow), and Fuchs spot (Bottom right; black arrow).
FIGURE 2. Examples of fundus photographs based on the International Classification of Myopic Maculopathy: (Top left) tessellated fundus only (category 1), (Top right) diffuse chorioretinal atrophy (category 2), (Bottom left) patchy chorioretinal atrophy (category 3), and (Bottom right) macular atrophy (category 4).
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TABLE 1. Myopia-related Optic Disc and Macular Changes in Myopic and Emmetropic Eyes and Their Relationship With Spherical Equivalent Refraction Optic Disc Tilt All Subjects (n ¼ 749)
N
Emmetropic (0.75D to þ1.00 D) With high myopia (23.50 to 6.13 D)
Peripapillary Atrophy
n (%)
P Value
N
151
2 (1.3)
<.001
155
76 (49.0)
574
126 (22.0)
589
579 (98.3)
n (%)
Posterior Staphyloma P Value
N
<.001
Myopic Maculopathy Category (N ¼ 749) Chorioretinal Atrophy All Subjects (n ¼ 749)
N
Emmetropic (0.63 to þ1.50 D) With high myopia (23.50 to 6.13 D)
156
1 (0.6)
590
49 (8.3)
n (%)
n (%)
P Value
136
1 (0.66)
<.001
485
155 (32.0)
Presence of Myopic Maculopathya (Yes vs No)
0–1
2
3
4
n (%)
n (%)
n (%)
P Value
N
.01
P Value
N
n (%)
.001
156
155 (99.4)
1 (0.6)
0 (0.0)
0 (0.0)
593
544 (91.7)
31 (5.2)
11 (1.9)
7 (1.2)
n (%)
P Value
156
1 (0.6)
<.001
593
49 (8.3)
D ¼ diopters. a Presence of myopic maculopathy defined as findings in the fundus photograph consistent with category 2 and above based on the International Classification of Myopic Maculopathy.
macula (scan diameter of 20 degrees) and used to evaluate the posterior pole for subtle posterior staphyloma and choroidal thickness. The details for choroidal thickness measurement were already described elsewhere and showed good reproducibility.17 FUNDUS PHOTOGRAPH GRADING:
The color fundus photographs were graded similar to previously established grading techniques by a single trained grader (V.Y.) masked to the participant characteristics.14 Adjudication was performed by an experienced medical retina specialist (C.T.) from an accredited fundus photograph grading center. The main findings that were graded included (1) optic disc morphology (optic disc tilt and peripapillary atrophy) and (2) myopia-related macular pathology, including staphyloma, lacquer crack, and peripapillary atrophy (PPA) (Figure 1). Optic disc tilt was diagnosed when 1 margin of the optic disc was subjectively raised above the opposite margin and the direction of optic disc tilt was determined. Presence of lacquer crack, its location, and number were evaluated. The Curtin and Karlin classification was used to determine the subtype and position of PPA.18 Staphyloma was determined by visualizing the border of the ectasia, then its location and type were documented based on the Curtin classification.19 Intergrader reliability in grading for the aforementioned features was assessed with additional grading of 100 randomly selected eyes by trained graders (V.Y. and V.K.), and reliability was found to be good (all intraclass correlation coefficients
72
above 0.75). However, more subtle posterior staphyloma may be missed from fundus photographs. As such, after the initial screening for posterior staphyloma on fundus photographs, we further analyzed the remaining eyes using cross-sectional images from SD OCT to detect shallower posterior staphyloma. All the SD OCT images were graded by a medical retinal specialist (C.T.). The presence of posterior staphyloma was defined as curvature of the retinal pigment epithelium layer, with a foveal depth of > _500 mm relative to the periphery of the OCT B-scan. This allowed posterior staphyloma with more gentle and subtle sloping edges to be detected. The presence of myopic maculopathy was defined and classified based on the International Photographic Classification and Grading System for Myopic Maculopathy.20 Briefly, pathologic myopia was classified in order of increasing severity (Figure 2): category 0, no macular lesions; category 1, only tessellated fundus; category 2, diffuse chorioretinal atrophy; category 3, patchy chorioretinal atrophy; and category 4, macular atrophy. In addition, ‘‘plus’’ lesions included lacquer cracks, choroidal neovascularization, and Fuchs spot. Posterior staphyloma was classified as supplemental information. For this study, the presence of myopic maculopathy is defined as findings in the fundus photograph consistent with category 2 and above. STATISTICAL
analysis was ANALYSIS: Statistical performed using IBM SPSS version 22 (IBM Corporation, New York, USA). Only 1 eye per subject was
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TABLE 2. Relationship Between Optic Disc and Macular Changes With Spherical Equivalent Refraction and Axial Length for the Highly Myopic Group (N ¼ 593) Optic Disc Tilt N
Spherical equivalent <6.00 to 8.00 D <8.00 to 10.00 D <10.00 D Axial length All 1st quartile (24.07–25.72 mm) 2nd quartile (25.74–26.85 mm) 3rd quartile (mm) (26.87–27.80 mm) 4th quartile (27.81–33.02 mm)
n (%)
Peripapillary Atrophy
Posterior Staphyloma
P Value
N
n (%)
P Value
N
<.001
246 202 141
239 (97.2) 202 (100.0) 138 (97.9)
.06
210 169 106
52 (24.8) 49 (29.0) 54 (50.9)
589 33
579 (98.3) 31 (93.9)
485 31
155 (32.0) 3 (9.7)
n (%)
238 197 139
35 (14.7) 46 (23.4) 45 (32.4)
574 31
126 (22.0) 6 (19.4)
147
26 (17.7)
152
148 (97.4)
129
29 (22.5)
194
44 (22.7)
197
194 (98.5)
162
47 (29.0)
202
50 (24.8)
207
206 (99.5)
163
76 (46.6)
.45
.09
P Value
<.001
<.001
Myopic Maculopathy Category Chorioretinal Atrophy
Spherical equivalent <6.00 to 8.00 D <8.00 to 10.00 D <10.00 D P value for myopic maculopathy category Axial length All 1st quartile (24.07–25.72 mm) 2nd quartile (25.74–26.85 mm) 3rd quartile (26.87–27.80 mm) 4th quartile (27.81–33.02 mm) P value for myopic maculopathy category
0–1
2
3
4
Presence of Myopic Maculopathy (Yes vs No)
N
n (%)
P Value
N
n (%)
n (%)
n (%)
n (%)
N
n (%)
P Value
246 203 141
12 (4.9) 11 (5.4) 26 (18.4)
<.001
248 204 141
236 (95.2) 193 (94.6) 115 (81.6) Reference
12 (4.8) 7 (3.4) 12 (8.5) P ¼ .10
0 (0.0) 2 (1.0) 9 (6.4) P < .001
0 (0.0) 2 (1.0) 5 (3.5) P < .001
248 204 141
12 (4.8) 11 (5.4) 26 (18.4)
P < 0.001
590 33
49 (8.3) 1 (3.0)
593 34
544 (91.7) 33 (97.1)
31 (5.2) 1 (2.9)
11 (1.9) 0 (0.0)
7 (1.2) 0 (0.0)
593 34
49 (8.3) 1 (2.9)
152
6 (3.9)
153
147 (96.1)
4 (2.6)
1 (0.7)
1 (0.7)
153
6 (3.9)
197
9 (4.6)
198
189 (95.5)
6 (3.0)
2 (1.0)
1 (0.5)
198
9 (4.5)
208
33 (15.9)
208
175 (84.1)
20 (9.6)
8 (3.8)
5 (2.4)
208
33 (15.9)
Reference
P ¼ .003
P ¼ .02
P ¼ .09
<.001
<.001
D ¼ diopters.
included for analysis. By default, the right eye is selected unless the SER of the right eye is more than 6.00 D for the myopic group, then the left eye is selected for analysis. The x2 test or Fisher exact test was used for comparing categorical variables between highly myopic eyes and emmetropic eyes, and Student t test was performed for continuous variables. Logistic regression was performed to determine the association with myopic maculopathy and its trend across SER and AL categories. Linear regression models adjusted for age and ethnicity were performed to determine the effect of optic disc
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tilt, PPA, posterior staphyloma, chorioretinal atrophy, and myopic maculopathy on BCVA. Statistical significance was set at P < .05.
RESULTS OUT OF A TOTAL OF 887 PARTICIPANTS WHO WERE
initially recruited for the study, we excluded 51 persons who did not meet the inclusion criteria and 87 persons
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TABLE 3. Multivariate Regression Analysis for the Determinants of Myopic Maculopathy for the Group of Young Highly Myopic Eyes Presence of Myopic Maculopathy (N ¼ 593) OR (95% CI)a
History of parental myopia No history 1 parent Both parents Age (y) Age of onset of myopia (y) Vertical choroidal thickness (mm) Axial length (mm)
P Value
Reference 1.24 (0.46, 3.37) 0.85 (0.29, 2.46) 1.66 (1.22, 2.26) 1.05 (0.89, 1.24)
.67 .76 .001 .58
0.99 (0.98, 0.99)
<.001
1.52 (1.06, 2.19)
.02
a
Adjusted for family history of myopia, age, age of onset of myopia, axial length.
whose final subjective cycloplegic refraction results did not fulfill either the high myopia (SER less than 6.00 D) or emmetropia (SER between 1.00 and þ1.00 D) criteria. For our final analyses, we included 593 and 156 participants into the high myopia and emmetropic group, respectively. All the subjects were male and the mean age was 21.1 6 1.2 (standard deviation [SD]) years for the myopic group and 21.5 6 1.1 years (SD) for the emmetropic group (P ¼ .09). The mean SER for the myopic and emmetropic group was 8.87 6 2.11 D and 0.40 6 0.39 D, respectively (P < .001). The corresponding AL was 27.45 6 1.17 mm and 23.83 6 1.01 mm, respectively (P < .001). Table 1 shows the common myopia-related optic disc and macular changes in highly myopic and emmetropic eyes and their relationship with SER. Compared to emmetropic eyes, the highly myopic eyes were significantly more likely to be affected by optic disc tilt, PPA, posterior staphyloma, and chorioretinal atrophy (all P < .001). For optic disc tilt, the most common direction of tilt was temporal (125/168; 74.4%) and for PPA, the most common location was temporal (434/655; 66.2%). Lacquer cracks were uncommon (6/593; 1.0%) and there was no significant difference in the presence of lacquer cracks between myopic eyes and emmetropic eyes (P ¼ .608). The lacquer cracks detected in all 6 myopic eyes were located in the macular region without involvement of the fovea. The most common type of staphyloma was peripapillary (103/155; 66.5%). For myopic eyes with chorioretinal atrophy, 72.5% (37/51 eyes) were smaller than 1 disc diameter in size. Most of the chorioretinal atrophy was also found in the peripapillary region (40/49; 81.6%). The prevalence of more visually adverse myopia-related changes such as macular hemorrhages, choroidal neovascularization, and 74
Fuchs spots (2/593; 0.34%) were low in the myopic group. Myopic maculopathy was present in 8.3% (49/593) of the eyes in the myopic group. Table 2 shows that with decreasing SER, there is a significantly increased frequency of myopia-related optic disc and macular changes in the eyes with high myopia (all P < .001) except peripapillary atrophy (P ¼ .06). Increased AL was also significantly associated with increased frequency of chorioretinal atrophy and posterior staphyloma, and similar trends for the other structural changes, although these did not reach statistical significance. The proportions of the more severe categories of myopic maculopathy (category 3 and 4) were significantly higher with decreased SER. Overall, the proportion of eyes with myopic maculopathy was significantly higher with decreased SER or increased AL. Table 3 shows multivariate logistic regression analysis for the risk factors of myopic maculopathy. Our results showed that the risk of developing myopic maculopathy increased by 1.66 times for each year increase in age (P ¼ .001) and by 1.52 times for each 1 mm increase in AL (P ¼ .02). Reduced choroidal thickness was also significantly associated with the development of myopic maculopathy (odds ratio [OR] 0.99; 95% confidence interval [CI]: 0.98, 0.99; P < .001). This is further illustrated in Figure 3, stratified by age, vertical fovea choroidal thickness, and AL, showing the relative proportions of eyes with myopic maculopathy among eyes with high myopia (SER < 6.00, n ¼ 593). In addition, the area under the receiver operating curve (AUROC) showed that vertical fovea choroidal thickness of less than 250 mm showed the highest and fairly good AUROC of 0.789 (sensitivity ¼ 95.3% and specificity ¼ 62.4%). However, both AL (AL more than 27.8 mm; AUROC ¼ 0.722) and SER alone (SER less than 9.6 D; AUROC ¼ 0.705) showed modest accuracy in detecting possible myopic maculopathy. Table 4 showed the effect of optic disc, macular, and myopic maculopathy changes on the visual acuity of this group of young Asian men affected by high myopia. Our results showed that presence of optic disc tilt, posterior staphyloma, and chorioretinal atrophy were associated with significantly poorer BCVA after adjusting for age and ethnicity.
DISCUSSION OUR STUDY DOCUMENTS A RELATIVELY HIGH PREVALENCE
of myopic maculopathy and specific myopia-related optic disc and macular changes in young Asian adults (aged 19– 25 years) with high myopia. In our cohort, one-fifth had optic disc tilt, almost all had PPA, and one-third had posterior staphyloma. It is interesting that among this group of highly myopic young men, a considerable proportion of eyes (8.3%) had myopic maculopathy. Most of the
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FIGURE 3. Comparison of proportion of myopic maculopathy by age, vertical choroidal thickness, and axial length.
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TABLE 4. Effect of Optic Disc, Macular Changes, and Myopic Maculopathy on Best-Correctable Visual Acuity (N ¼ 593) Beta-correctable Visual Acuity (logMAR) Modela
Optic disc tilt No Yes Peripapillary atrophy No Yes Posterior staphyloma No Yes Chorioretinal atrophy No Yes Myopic maculopathy No Yes
Modelb
Mean
n
P Value
Mean
P Value
0.05 0.08
448 126
.001
0.07 0.11
<.001
0.07 0.05
10 579
.69
0.09 0.08
.84
0.05 0.06
330 155
.07
0.07 0.08
.05
0.05 0.10
541 49
.001
0.08 0.13
.001
0.05 0.10
544 49
.002
0.08 0.13
.001
a
Univariate. Adjusted for age and ethnicity.
b
changes were significantly more common with longer AL. This is clinically significant, as eyes with myopic maculopathy continue to elongate with age21 and may lead to higher prevalence of myopia-related changes in the retina. There is little information on the prevalence of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of the adolescents and young adults. Chang and associates reported the prevalence of myopiarelated retinal changes in a myopic Singapore population older than 40 years (SER < 6.00 D), while the SCORM study reported myopia changes in teenage children in Singapore.9,10 The most common findings of Chang and associates’ study were posterior staphyloma (23%), followed by chorioretinal atrophy (19.3%). The most common optic disc finding was PPA (81.2%), followed by disc tilt (57.4%). Of 1227 children in SCORM, in 89 highly myopic children (age range 12–16 years) with SER < 6.00 D, 67.4% (60/89 eyes) had tilted optic disc and 93.3% (83/89 eyes) had PPA. There was only 1 eye with posterior staphyloma (AL ¼ 26.72 mm and SER ¼ 6.7 D) and 1 eye with lacquer cracks (AL ¼ 25.53 mm and SER ¼ 5.2 D). The prevalence of disc tilt and PPA was also similarly high for children with moderate myopia (SER between 3.00 and 6.00 D): 63.5% (214/337 eyes) and 87.2% (294/337 eyes), respectively. The presence of myopic maculopathy was rare in highly
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myopic children. This leads to postulations that myopic macular changes are time-dependent changes as a result of mechanical stretching of the retina from axial elongation. Our results showed that there was a higher prevalence of macular changes such as posterior staphyloma and chorioretinal atrophy in these young myopic eyes which was more consistent with older adults.22 Interestingly, the age range of the current study (range 19–25 years) was not much older than the SCORM study (age range 12–16 years). Our results showed that myopic maculopathy is present in close to 10% of these young highly myopic eyes. However, the more vision-threatening complications, such as macular hemorrhages, choroidal neovascularization, and Fuchs spots, were rare in our study, suggesting that these changes appear much later in life. The majority of the young myopic eyes already had a tessellated fundus, which suggested that the overlying retina was thinner and allowed the deeper choroidal vessels to be seen more clearly. Fundal tessellation has clinically insignificant visual consequences but can be an early sign of choroidal thinning leading to myopic maculopathy.23 In particular, the risk of myopic maculopathy is negligible if choroidal thickness is thicker than 250 mm with a good sensitivity but poor specificity. Choroidal thickness could be an additional quantifiable prognostic parameter for young myopic eyes at risk of developing pathologic myopia, although longitudinal studies are required to determine the temporal relationships. Our most important finding is the clear documentation that myopic maculopathy changes, including chorioretinal atrophy and other lesions, are found in older teenagers and young adults. The significance of our study is 3-fold. First, our study demonstrated the negative effects of some features of myopia-related optic disc and macular changes on the BCVA. The presence of optic disc tilt, chorioretinal atrophy, and myopic maculopathy were significantly associated with poorer BCVA, even in young adults. Chen and associates reported that lower visual acuity was associated with lacquer cracks, chorioretinal atrophy, and choroidal neovascularization in an older (mean age 40.6 6 17.1 years) Chinese population.24 Histologic and OCT-based studies have shown that choroidal thickness decreases with increasing severity of myopia owing to axial elongation of the globe.25,26 In addition, choroidal circulation was also reduced in myopic eyes, with formation of fibrous tissue replacing the choroidal vasculature.27,28 As the choroidal vasculature supplies the retinal pigment epithelium and outer retina, it is conceivable that reduced choroidal thickness could have resulted in the myopia-related structural changes of the optic disc and macula. Reduced choroidal thickness has also been associated with reduced BCVA in myopic eyes even without obvious macular pathology.26,29 Chorioretinal atrophy represents the final endpoint of combined photoreceptor
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and retinal pigment epithelium cell death, with irreversible loss of central visual function. Although the absolute reduction in visual acuity associated with pathologic myopia may not be high in our study, this highly myopic young population requires good central visual acuity and has high visual demands. These pathologic changes are mostly irreversible and could have a negative impact to the quality of life and increase the socioeconomic burden of myopia.8,30 Our study is also one of the first to show the high prevalence of posterior staphyloma in this young age group. This is surprising, as the literature suggests that posterior staphyloma is a late sign of pathologic myopia, which is much more prevalent in older adults (age >50 years) in population-based studies. This may have significant impact on visual prognosis, as posterior staphyloma was associated with a higher incidence of visually threatening complications such as macular hole retinal detachment,31 myopic foveoschisis, and choroidal neovascularization.32 This was attributed to the increased internal vector force from the posterior protrusion of the sclera wall coupled with early vitreous shrinkage.33,34 In addition, Hayashi and associates showed that up to 40% of highly myopic eyes with myopic maculopathy showed progression over a mean duration of 12.7 years and eyes with posterior staphyloma are at a higher risk of progression compared to eyes without posterior staphyloma.35 We recognized the limitation of color fundus photographs, which could underestimate the frequency of posterior staphyloma. As such, we used SD OCT imaging to provide crosssectional images of the posterior pole to detect more subtle and early posterior bowing of the retina. Owing to the potential vision-threatening complications that could be detected and treated effectively, eyes with posterior staphyloma require increased surveillance and detailed examination. Finally, the high prevalence of optic disc tilt and betaperipapillary atrophy in these myopic eyes makes it hard to assess the optic nerve head (ONH) characteristics. Multiple studies have shown a significant association between high myopia (SE less than 6.00 D) and primary openangle glaucoma.36,37 Optic disc tilt has been shown to affect ONH measurements measured by Heidelberg retinal tomography (Heidelberg Engineering, Heidelberg, Germany), and this may affect the diagnostic accuracy of its classification algorithm based on a normative database.38 Studies also showed that optic disc tilt was
associated with static visual field defects.39,40 These unique changes to the myopic optic disc make the diagnosis and monitoring of glaucoma in myopic eyes more challenging. Our study showed that the risk factors for developing myopic maculopathy included older age, reduced central choroidal thickness, and increased AL. Our results support the hypothesis that myopic maculopathy is timedependent and increases in prevalence with age owing to prolonged axial elongation of the globe.10,15 This highlights the importance of long-term and regular screening of young myopic eyes, especially if choroidal thickness is thinner than 250 mm on macular SD OCT. Our results also support early introduction of preventive strategies at a young age to retard ocular axial elongation and reduce the risk of developing pathologic myopiarelated structural changes earlier in life. The strength of this study includes a large sample size of highly myopic young Asian adults who prospectively underwent standardized examinations and detailed color fundus photograph grading. These young subjects are less likely to have media opacities that may affect visualization of structural changes in the retina or glaucoma. The limitations of our study should be mentioned. First, the subjects were predominantly Chinese (92.0%) and all were male. As such, the generalization of our results needs to be more cautious, although Cheng and associates reported that sex did not alter the prevalence of pathologic myopia findings in a population-based study involving subjects more than 40 years old.12 Second, the cross-sectional nature of our study cannot confirm the temporal relationships of these myopia-related changes with its risk factors. In conclusion, our study showed that myopic maculopathy and other structural changes in the optic disc and macula were common, even in young highly myopic adults in an urban Asian population. Most of the lesions were significantly associated with reduced SER, increased AL, and reduced central choroidal thickness. The risk factors for myopic maculopathy were older age, increased AL, and reduced central choroidal thickness. Myopic maculopathy and specific changes including chorioretinal atrophy, posterior staphyloma, and optic disc tilt were associated with reduced visual acuity. These visually disabling myopiarelated changes could worsen with age and significantly increase the disease burden of an increasingly common ocular condition in the world.
FUNDING/SUPPORT: MINISTRY OF DEFENCE GRANT DSO 20101136. FINANCIAL DISCLOSURES: THE FOLLOWING AUTHORS have no financial disclosures: Victor Koh, Colin Tan, Pei Ting Tan, Marcus Tan, Vinay Balla, Gerard Nah, Cheng Ching-Yu, Kyoko OhnoMatsui, Mellisa M.H. Tan, Adeline Yang, Paul Zhao, Tien Yin Wong, and Saw Seang-Mei. All authors attest that they meet the current ICMJE criteria for authorship. The authors acknowledge Chan Yiong Huak from the Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore for providing statistical support.
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