Myopic and 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 and was associated with older age (odds ratio of myopic maculopathy and specific optic disc and macu- [OR] 1.66; 95% CI: 1.22, 2.26), reduced choroidal lar changes in highly myopic eyes of young Asian adults thickness (OR 0.99; 95% CI: 0.98, 0.99), and increased and their impact on visual acuity. axial length (AL) (OR 1.52; 95% CI: 1.06, 2.19). DESIGN: Prospective cross-sectional study. The presence of disc tilt, posterior staphyloma, and METHODS: In total, 593 highly myopic (spherical chorioretinal atrophy were associated with reduced visual equivalent refraction [SER] less than L6.00 diopters acuity. [D]) and 156 emmetropic (SER between L1.00 CONCLUSIONS: Our study showed that -related and D1.00 D) male participants from a population- changes of the optic disc and macula were common in based survey were included. All participants underwent highly myopic eyes even at a young age. The risk factors standardized medical interviews, ophthalmic examina- for myopic maculopathy include increased age, longer tion, and color fundus photographs. These photographs AL, and reduced choroidal thickness. Some of these were graded systematically to determine the presence of changes were associated with reduced central visual optic disc and macular lesions. Myopic maculopathy was function. (Am J Ophthalmol 2016;164:69–79. classified based on the International Classification of Ó 2016 by Elsevier Inc. All rights reserved.) Myopic Maculopathy. RESULTS: The mean age was 21.1 ± 1.2 years. The mean SER for the highly myopic and emmetropic group YOPIA IS A MAJOR CAUSE OF was L8.87 ± 2.11 D and 0.40 ± 0.39 D, respectively in the world1,2 and the prevalence is especially (P < .001). Compared to emmetropic eyes, highly M high in East Asia.3 In Asia, the prevalence of myopic eyes were significantly more likely to have optic myopia (spherical equivalent refraction [SER] less disc tilt, peripapillary atrophy (PPA), posterior staphy- than 0.50 diopters [D]) and high myopia (SER less loma, chorioretinal atrophy, and myopic maculopathy than 6.00 D) in young adults (age range 18–24 years) (all P < .001). The main findings included PPA are 81.6%–96.5% and 6.8%–21.6%, respectively.4–7 In (98.3%), disc tilt (22.0%), posterior staphyloma addition, a study in Singapore comparing similar cohorts (32.0%), and chorioretinal atrophy (8.3%). Myopic of young Asian men (aged 16–25 years) between 1996– maculopathy was present in 8.3% of highly myopic eyes 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 prob- Supplemental Material available at AJO.com. lem in the future. Accepted for publication Jan 23, 2016. Complications associated with pathologic myopia can From the Vision Performance Centre, Military Medicine Institute, be irreversible and result in significant ocular morbidity. Singapore (V.K., M.T., G.N., P.Z.); Department of Ophthalmology, National University Health System, Singapore (V.K., M.T., V.B., This includes myopic choroidal neovascularization, C.C.-Y.); Department of Ophthalmology, Tan Tock Seng Hospital, chorioretinal atrophy, and foveoschisis. These sight- Singapore (C.T.); Biostatistics Unit (P.T.T.) and Department of threatening conditions result in reduced quality of life Ophthalmology (T.Y.W., S.S.-M.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Eye Research and increased socioeconomic burden, especially if they 8 Institute, Singapore National Eye Centre, Singapore (C.C.-Y., T.Y.W., occur early in life. In the Singapore Cohort Study of S.S.-M.); Department of Ophthalmology and Visual Science, Tokyo Risk Factors for Myopia (SCORM) study (age range Medical and Dental University Graduate School of Medicine, Tokyo, Japan (K.O.-M.); and Defence Medical & Environmental Research 12–16 years), the prevalence of optic disc tilt and peripa- Institute, DSO National Laboratories, Singapore (M.M.H.T., A.Y.). pillary atrophy for children with SER less than 6.00 D Inquiries to Prof Seang-Mei Saw, Department of Epidemiology and (n ¼ 89) was 67.5% and 92.2%, respectively. Interest- Public Health, Yong Loo Lin School of Medicine, National University of Singapore, MD 3, Level 16 Medical Dr, Singapore 117597; e-mail: ingly, compared to older myopic adults (aged more [email protected] than 40 years), the prevalence of these myopic

0002-9394/$36.00 Ó 2016 BY ELSEVIER INC.ALL RIGHTS RESERVED. 69 http://dx.doi.org/10.1016/j.ajo.2016.01.005 was much lower in these highly myopic ocular surgery that may alter the refractive status of the children (only 1 case each of posterior staphyloma and eye; and those who were unwilling or unable to take lacquer cracks).9–12 Electrophysiology studies have also part in the study or unable to return for scheduled visits. shown that the myopic of adolescents and Written informed consent were taken from the subjects young adults have diminished amplitudes and delayed and their parents/guardians (if they were below 21 years latency despite a normal-looking .13 This evidence of age). The study was conducted in accordance with suggested that myopia-related structural changes in the the tenets of the World Medical Association’s Declara- retina could be age- and time-dependent. On the other tion of Helsinki and had ethics approval from the Sing- hand, in population-based studies, among adults older health Centralized Institutional Review Board. than 40 years with high myopia (SER less than 5.00 D), only a relatively small proportion (0.9%–3.29%) INTERVIEW, VISUAL ACUITY MEASUREMENT, AND develop structural changes.10,14,15 It is possible that REFRACTION: All the participants who fulfill the inclu- apart from axial length (AL) and SER, there are other sion criteria and consented to the study underwent a contributing risk factors leading to pathologic myopic standardized interview regarding their refraction status, changes. To date, there is little literature on the visual including the age at which they started wearing glasses impact of pathologic myopia and when these myopia- and the age at which their spherical first related changes affect highly myopic young adults. This reached 6.00 D. Best-corrected visual acuity (BCVA) is important in the assessment of visual potential because measurement and subjective cycloplegic refraction were visual impairment at this young age group has significant conducted on the same day by a trained optometrist. impact on long-term visual prognosis and rehabilita- The subjects’ monocular VA was measured using the log- tion.14 arithm of the minimal angle of resolution (logMAR) We aim to describe the prevalence of myopic maculop- chart (Lighthouse International, New York, New York, athy and related structural abnormalities, including specific USA) at 4 meters. If the largest number could not be myopia-related optic disc and macular changes in a group identified at 4 meters, the chart was brought closer to of highly myopic (SER less than 6.00 D) young Asian the subject, then counting fingers, hand motion, or light men and compare them with emmetropic eyes of the perception vision was assessed. was induced same age group. We will also examine the risk factors for with 3 drops of cyclopentolate 1% 5 minutes apart. At these myopia-related changes and their impact on visual least 30 minutes after the last drop, subjective cyclople- acuity. gic refraction tests were performed by the same optome- trist for all the participants. SER was calculated as the sum of the spherical power and half of the cylindrical power. METHODS OCULAR EXAMINATION AND IMAGING: Ocular biom- STUDY POPULATION: The current study was conducted etry was performed using the IOL Master (Carl Zeiss between January 1, and December 31, 2012 and the meth- Meditec AG, Jena, Germany), which included AL odology for subject recruitment was detailed elsewhere.16 measurements. The mean of 3 AL measurements was taken Briefly, a total of 28 908 young male subjects aged 19–25 as the final AL. All the subjects underwent a standardized years underwent noncycloplegic autorefraction (Huvitz and detailed examination of the anterior segment at the MRK-3100P, Republic of Korea) as part of a compulsory Singapore Eye Research Institute by a trained ophthalmol- ophthalmic examination for pre-employment screening ogist. Slit-lamp examination included assessment of in Singapore. Out of 2584 persons identified to have and lenticular pathology and anterior chamber depth. high myopia (SER less than 6.00 D) based on noncyclo- Goldmann applanation tonometry was used to measure plegic autorefraction, 719 subjects were selected based on the intraocular pressure in mm Hg. Retinal photography refractive error–stratified random sampling strategy. They was performed by a trained ophthalmic technician using were invited to participate in the current study and under- the Canon CR-DGI (Canon Inc, Tokyo, Japan) nonmydri- went further examination and investigations at the atic retinal camera after dilation. Seven retinal pho- Singapore Eye Research Institute as described below. tographs were taken to obtain the view of the optic disc For the control group, 168 emmetropic male subjects (disc-centered and rotated at 30 degrees to the right and (SER between 1.00 and þ1.00 D) were recruited and 30 degrees to the left), macular view, and right and left up- underwent the same standardized examination and inves- per and lower arcade peripheral views from both eyes. tigations as the highly myopic group. We further excluded Spectral-domain optical coherence tomography (SD participants with any history of anterior segment ocular OCT; Spectralis OCT, Heidelberg Engineering, Heidel- diseases, trauma, or systemic condition that affects their berg, Germany) of the macula was also performed after pu- visual performance; any form of refractive surgery or pil dilation. The SD OCT scans were centered over the

70 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2016 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).

VOL. 164 MYOPIC MACULOPATHY,OPTIC DISC CHANGES IN HIGHLY MYOPIC EYES 71 TABLE 1. Myopia-related Optic Disc and Macular Changes in Myopic and Emmetropic Eyes and Their Relationship With Spherical Equivalent Refraction

Optic Disc Tilt Peripapillary Atrophy Posterior Staphyloma

All Subjects (n ¼ 749) N n (%) P Value N n (%) P Value N n (%) P Value

Emmetropic 151 2 (1.3) <.001 155 76 (49.0) <.001 136 1 (0.66) <.001 (0.75D to þ1.00 D) With high myopia 574 126 (22.0) 589 579 (98.3) 485 155 (32.0) (23.50 to 6.13 D)

Myopic Maculopathy Category (N ¼ 749) Presence of Myopic Maculopathya Chorioretinal Atrophy 0–1 2 3 4 (Yes vs No)

All Subjects (n ¼ 749) N n (%) P Value N n (%) n (%) n (%) n (%) P Value N n (%) P Value

Emmetropic 156 1 (0.6) .001 156 155 (99.4) 1 (0.6) 0 (0.0) 0 (0.0) .01 156 1 (0.6) <.001 (0.63 to þ1.50 D) With high myopia 590 49 (8.3) 593 544 (91.7) 31 (5.2) 11 (1.9) 7 (1.2) 593 49 (8.3) (23.50 to 6.13 D)

D ¼ diopters. aPresence of myopic maculopathy defined as findings in the fundus photograph consistent with category 2 and above based on the Inter- national Classification of Myopic Maculopathy.

macula (scan diameter of 20 degrees) and used to evaluate above 0.75). However, more subtle posterior staphyloma the posterior pole for subtle posterior staphyloma and may be missed from fundus photographs. As such, after choroidal thickness. The details for choroidal thickness the initial screening for posterior staphyloma on fundus measurement were already described elsewhere and showed photographs, we further analyzed the remaining eyes using good reproducibility.17 cross-sectional images from SD OCT to detect shallower posterior staphyloma. All the SD OCT images were graded FUNDUS PHOTOGRAPH GRADING: The color fundus by a medical retinal specialist (C.T.). The presence of pos- photographs were graded similar to previously estab- terior staphyloma was defined as curvature of the retinal lished grading techniques by a single trained grader pigment epithelium layer, with a foveal depth of (V.Y.) masked to the participant characteristics.14 >_500 mm relative to the periphery of the OCT B-scan. Adjudication was performed by an experienced medical This allowed posterior staphyloma with more gentle and retina specialist (C.T.) from an accredited fundus subtle sloping edges to be detected. photograph grading center. The presence of myopic maculopathy was defined and The main findings that were graded included (1) optic classified based on the International Photographic Classifi- disc morphology (optic disc tilt and peripapillary atrophy) cation and Grading System for Myopic Maculopathy.20 and (2) myopia-related macular pathology, including Briefly, pathologic myopia was classified in order of staphyloma, lacquer crack, and peripapillary atrophy increasing severity (Figure 2): category 0, no macular le- (PPA) (Figure 1). Optic disc tilt was diagnosed when 1 sions; category 1, only tessellated fundus; category 2, diffuse margin of the optic disc was subjectively raised above the chorioretinal atrophy; category 3, patchy chorioretinal opposite margin and the direction of optic disc tilt was atrophy; and category 4, macular atrophy. In addition, determined. Presence of lacquer crack, its location, and ‘‘plus’’ lesions included lacquer cracks, choroidal neovascu- number were evaluated. The Curtin and Karlin classifica- larization, and Fuchs spot. Posterior staphyloma was classi- tion was used to determine the subtype and position of fied as supplemental information. For this study, the PPA.18 Staphyloma was determined by visualizing the presence of myopic maculopathy is defined as findings in border of the ectasia, then its location and type were docu- the fundus photograph consistent with category 2 and mented based on the Curtin classification.19 Intergrader above. reliability in grading for the aforementioned features was assessed with additional grading of 100 randomly selected STATISTICAL ANALYSIS: Statistical analysis was eyes by trained graders (V.Y. and V.K.), and reliability performed using IBM SPSS version 22 (IBM Corpora- was found to be good (all intraclass correlation coefficients tion, New York, USA). Only 1 eye per subject was

72 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2016 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 Peripapillary Atrophy Posterior Staphyloma

N n (%) P Value N n (%) P Value N n (%) P Value

Spherical equivalent <6.00 to 8.00 D 238 35 (14.7) <.001 246 239 (97.2) .06 210 52 (24.8) <.001 <8.00 to 10.00 D 197 46 (23.4) 202 202 (100.0) 169 49 (29.0) <10.00 D 139 45 (32.4) 141 138 (97.9) 106 54 (50.9) Axial length All 574 126 (22.0) 589 579 (98.3) 485 155 (32.0) 1st quartile 31 6 (19.4) .45 33 31 (93.9) .09 31 3 (9.7) <.001 (24.07–25.72 mm) 2nd quartile 147 26 (17.7) 152 148 (97.4) 129 29 (22.5) (25.74–26.85 mm) 3rd quartile (mm) 194 44 (22.7) 197 194 (98.5) 162 47 (29.0) (26.87–27.80 mm) 4th quartile 202 50 (24.8) 207 206 (99.5) 163 76 (46.6) (27.81–33.02 mm)

Myopic Maculopathy Category Presence of Myopic Chorioretinal Atrophy 0–1 2 3 4 Maculopathy (Yes vs No)

N n (%) P ValueN n (%) n (%) n (%) n (%) N n (%) P Value

Spherical equivalent <6.00 to 8.00 D 246 12 (4.9) <.001 248 236 (95.2) 12 (4.8) 0 (0.0) 0 (0.0) 248 12 (4.8) P < 0.001 <8.00 to 10.00 D 203 11 (5.4) 204 193 (94.6) 7 (3.4) 2 (1.0) 2 (1.0) 204 11 (5.4) <10.00 D 141 26 (18.4) 141 115 (81.6) 12 (8.5) 9 (6.4) 5 (3.5) 141 26 (18.4) P value for myopic Reference P ¼ .10 P < .001 P < .001 maculopathy category Axial length All 590 49 (8.3) 593 544 (91.7) 31 (5.2) 11 (1.9) 7 (1.2) 593 49 (8.3) 1st quartile 33 1 (3.0) <.001 34 33 (97.1) 1 (2.9) 0 (0.0) 0 (0.0) 34 1 (2.9) <.001 (24.07–25.72 mm) 2nd quartile 152 6 (3.9) 153 147 (96.1) 4 (2.6) 1 (0.7) 1 (0.7) 153 6 (3.9) (25.74–26.85 mm) 3rd quartile 197 9 (4.6) 198 189 (95.5) 6 (3.0) 2 (1.0) 1 (0.5) 198 9 (4.5) (26.87–27.80 mm) 4th quartile 208 33 (15.9) 208 175 (84.1) 20 (9.6) 8 (3.8) 5 (2.4) 208 33 (15.9) (27.81–33.02 mm) P value for myopic Reference P ¼ .003 P ¼ .02 P ¼ .09 maculopathy category

D ¼ diopters.

included for analysis. By default, the right eye is selected tilt, PPA, posterior staphyloma, chorioretinal atrophy, unless the SER of the right eye is more than 6.00 D for and myopic maculopathy on BCVA. Statistical signifi- the myopic group, then the left eye is selected for anal- cance was set at P < .05. ysis. 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 RESULTS was performed to determine the association with myopic maculopathy and its trend across SER and AL categories. OUT OF A TOTAL OF 887 PARTICIPANTS WHO WERE Linear regression models adjusted for age and ethnicity initially recruited for the study, we excluded 51 persons were performed to determine the effect of optic disc who did not meet the inclusion criteria and 87 persons

VOL. 164 MYOPIC MACULOPATHY,OPTIC DISC CHANGES IN HIGHLY MYOPIC EYES 73 Fuchs spots (2/593; 0.34%) were low in the myopic group. TABLE 3. Multivariate Regression Analysis for the Myopic maculopathy was present in 8.3% (49/593) of the Determinants of Myopic Maculopathy for the Group of Young eyes in the myopic group. Highly Myopic Eyes Table 2 shows that with decreasing SER, there is a signif- icantly increased frequency of myopia-related optic disc Presence of Myopic Maculopathy (N ¼ 593) and macular changes in the eyes with high myopia (all P a OR (95% CI) P Value < .001) except peripapillary atrophy (P ¼ .06). Increased History of parental myopia AL was also significantly associated with increased fre- No history Reference quency of chorioretinal atrophy and posterior staphyloma, 1 parent 1.24 (0.46, 3.37) .67 and similar trends for the other structural changes, Both parents 0.85 (0.29, 2.46) .76 although these did not reach statistical significance. The Age (y) 1.66 (1.22, 2.26) .001 proportions of the more severe categories of myopic macul- Age of onset of 1.05 (0.89, 1.24) .58 opathy (category 3 and 4) were significantly higher with myopia (y) Vertical choroidal 0.99 (0.98, 0.99) <.001 decreased SER. Overall, the proportion of eyes with myopic thickness (mm) maculopathy was significantly higher with decreased SER Axial length (mm) 1.52 (1.06, 2.19) .02 or increased AL. Table 3 shows multivariate logistic regression analysis for aAdjusted for family history of myopia, age, age of onset of the risk factors of myopic maculopathy. Our results showed myopia, axial length. 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 associ- whose final subjective cycloplegic refraction results did not ated with the development of myopic maculopathy (odds fulfill either the high myopia (SER less than 6.00 D) or ratio [OR] 0.99; 95% confidence interval [CI]: 0.98, 0.99; < emmetropia (SER between 1.00 and þ1.00 D) criteria. P .001). This is further illustrated in Figure 3, stratified For our final analyses, we included 593 and 156 participants by age, vertical fovea choroidal thickness, and AL, showing into the high myopia and emmetropic group, respectively. the relative proportions of eyes with myopic maculopathy < ¼ All the subjects were male and the mean age was 21.1 6 1.2 among eyes with high myopia (SER 6.00, n 593). (standard deviation [SD]) years for the myopic group In addition, the area under the receiver operating curve and 21.5 6 1.1 years (SD) for the emmetropic group (AUROC) showed that vertical fovea choroidal thickness m (P ¼ .09). The mean SER for the myopic and emmetropic of less than 250 m showed the highest and fairly good ¼ ¼ group was 8.87 6 2.11 D and 0.40 6 0.39 D, respectively AUROC of 0.789 (sensitivity 95.3% and specificity (P < .001). The corresponding AL was 27.45 6 1.17 mm 62.4%). However, both AL (AL more than 27.8 mm; ¼ and 23.83 6 1.01 mm, respectively (P < .001). AUROC 0.722) and SER alone (SER less than 9.6 D; ¼ Table 1 shows the common myopia-related optic disc AUROC 0.705) showed modest accuracy in detecting and macular changes in highly myopic and emmetropic possible myopic maculopathy. eyes and their relationship with SER. Compared to emme- Table 4 showed the effect of optic disc, macular, and tropic eyes, the highly myopic eyes were significantly more myopic maculopathy changes on the visual acuity of this likely to be affected by optic disc tilt, PPA, posterior staph- group of young Asian men affected by high myopia. Our re- yloma, and chorioretinal atrophy (all P < .001). For optic sults showed that presence of optic disc tilt, posterior staph- disc tilt, the most common direction of tilt was temporal yloma, and chorioretinal atrophy were associated with (125/168; 74.4%) and for PPA, the most common location significantly poorer BCVA after adjusting for age and was temporal (434/655; 66.2%). Lacquer cracks were un- ethnicity. common (6/593; 1.0%) and there was no significant differ- ence in the presence of lacquer cracks between myopic eyes and emmetropic eyes (P ¼ .608). The lacquer cracks DISCUSSION detected in all 6 myopic eyes were located in the macular region without involvement of the fovea. The most com- OUR STUDY DOCUMENTS A RELATIVELY HIGH PREVALENCE mon type of staphyloma was peripapillary (103/155; of myopic maculopathy and specific myopia-related optic 66.5%). For myopic eyes with chorioretinal atrophy, disc and macular changes in young Asian adults (aged 19– 72.5% (37/51 eyes) were smaller than 1 disc diameter in 25 years) with high myopia. In our cohort, one-fifth had size. Most of the chorioretinal atrophy was also found in optic disc tilt, almost all had PPA, and one-third had pos- the peripapillary region (40/49; 81.6%). The prevalence terior staphyloma. It is interesting that among this group of more visually adverse myopia-related changes such as of highly myopic young men, a considerable proportion of macular hemorrhages, choroidal neovascularization, and eyes (8.3%) had myopic maculopathy. Most of the

74 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2016 FIGURE 3. Comparison of proportion of myopic maculopathy by age, vertical choroidal thickness, and axial length.

VOL. 164 MYOPIC MACULOPATHY,OPTIC DISC CHANGES IN HIGHLY MYOPIC EYES 75 myopic children. This leads to postulations that myopic TABLE 4. Effect of Optic Disc, Macular Changes, and macular changes are time-dependent changes as a result Myopic Maculopathy on Best-Correctable Visual Acuity of mechanical stretching of the retina from axial ¼ (N 593) elongation. Our results showed that there was a higher prevalence of Beta-correctable Visual Acuity (logMAR) macular changes such as posterior staphyloma and chorior- a b Model Model etinal atrophy in these young myopic eyes which was more Mean n P Value Mean P Value consistent with older adults.22 Interestingly, the age Optic disc tilt range of the current study (range 19–25 years) was not No 0.05 448 .001 0.07 <.001 much older than the SCORM study (age range 12–16 Yes 0.08 126 0.11 years). Our results showed that myopic maculopathy is Peripapillary atrophy present in close to 10% of these young highly myopic No 0.07 10 .69 0.09 .84 eyes. However, the more vision-threatening complications, Yes 0.05 579 0.08 such as macular hemorrhages, choroidal neovasculariza- Posterior staphyloma tion, and Fuchs spots, were rare in our study, suggesting No 0.05 330 .07 0.07 .05 that these changes appear much later in life. The majority Yes 0.06 155 0.08 of the young myopic eyes already had a tessellated fundus, Chorioretinal atrophy No 0.05 541 .001 0.08 .001 which suggested that the overlying retina was thinner and Yes 0.10 49 0.13 allowed the deeper choroidal vessels to be seen more Myopic maculopathy clearly. Fundal tessellation has clinically insignificant No 0.05 544 .002 0.08 .001 visual consequences but can be an early sign of choroidal 23 Yes 0.10 49 0.13 thinning leading to myopic maculopathy. In particular, the risk of myopic maculopathy is negligible if choroidal aUnivariate. m b thickness is thicker than 250 m with a good sensitivity Adjusted for age and ethnicity. but poor specificity. Choroidal thickness could be an addi- tional quantifiable prognostic parameter for young myopic eyes at risk of developing pathologic myopia, although lon- gitudinal studies are required to determine the temporal changes were significantly more common with longer AL. relationships. This is clinically significant, as eyes with myopic maculop- Our most important finding is the clear documentation athy continue to elongate with age21 and may lead to that myopic maculopathy changes, including chorioretinal higher prevalence of myopia-related changes in the atrophy and other lesions, are found in older teenagers and retina. young adults. The significance of our study is 3-fold. First, There is little information on the prevalence of myopic our study demonstrated the negative effects of some fea- maculopathy and specific optic disc and macular changes in tures of myopia-related optic disc and macular changes highly myopic eyes of the adolescents and young adults. on the BCVA. The presence of optic disc tilt, chorioretinal Chang and associates reported the prevalence of myopia- atrophy, and myopic maculopathy were significantly associ- related retinal changes in a myopic Singapore population ated with poorer BCVA, even in young adults. Chen and older than 40 years (SER < 6.00 D), while the SCORM associates reported that lower visual acuity was associated study reported myopia changes in teenage children in with lacquer cracks, chorioretinal atrophy, and choroidal Singapore.9,10 The most common findings of Chang and neovascularization in an older (mean age 40.6 6 17.1 associates’ study were posterior staphyloma (23%), years) Chinese population.24 Histologic and OCT-based followed by chorioretinal atrophy (19.3%). The most studies have shown that choroidal thickness decreases common optic disc finding was PPA (81.2%), followed by with increasing severity of myopia owing to axial elonga- disc tilt (57.4%). Of 1227 children in SCORM, in 89 tion of the .25,26 In addition, choroidal circulation highly myopic children (age range 12–16 years) with SER was also reduced in myopic eyes, with formation of < 6.00 D, 67.4% (60/89 eyes) had tilted optic disc and fibrous tissue replacing the choroidal vasculature.27,28 As 93.3% (83/89 eyes) had PPA. There was only 1 eye with the choroidal vasculature supplies the retinal pigment posterior staphyloma (AL ¼ 26.72 mm and SER ¼6.7 epithelium and outer retina, it is conceivable that D) and 1 eye with lacquer cracks (AL ¼ 25.53 mm and reduced choroidal thickness could have resulted in the SER ¼5.2 D). The prevalence of disc tilt and PPA was myopia-related structural changes of the optic disc and also similarly high for children with moderate myopia macula. Reduced choroidal thickness has also been associ- (SER between 3.00 and 6.00 D): 63.5% (214/337 ated with reduced BCVA in myopic eyes even without eyes) and 87.2% (294/337 eyes), respectively. The obvious macular pathology.26,29 Chorioretinal atrophy presence of myopic maculopathy was rare in highly represents the final endpoint of combined photoreceptor

76 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2016 and retinal pigment epithelium cell death, with irreversible associated with static visual field defects.39,40 These loss of central visual function. Although the absolute unique changes to the myopic optic disc make the reduction in visual acuity associated with pathologic diagnosis and monitoring of in myopic eyes myopia may not be high in our study, this highly myopic more challenging. young population requires good central visual acuity and Our study showed that the risk factors for developing has high visual demands. These pathologic changes are myopic maculopathy included older age, reduced central mostly irreversible and could have a negative impact to choroidal thickness, and increased AL. Our results support the quality of life and increase the socioeconomic burden the hypothesis that myopic maculopathy is time- of myopia.8,30 dependent and increases in prevalence with age owing to Our study is also one of the first to show the high preva- prolonged axial elongation of the globe.10,15 This lence of posterior staphyloma in this young age group. This highlights the importance of long-term and regular is surprising, as the literature suggests that posterior staph- screening of young myopic eyes, especially if choroidal yloma is a late sign of pathologic myopia, which is much thickness is thinner than 250 mm on macular SD OCT. more prevalent in older adults (age >50 years) in Our results also support early introduction of preventive population-based studies. This may have significant impact strategies at a young age to retard ocular axial elongation on visual prognosis, as posterior staphyloma was associated and reduce the risk of developing pathologic myopia- with a higher incidence of visually threatening complica- related structural changes earlier in life. tions such as macular hole ,31 myopic The strength of this study includes a large sample size of foveoschisis, and choroidal neovascularization.32 This was highly myopic young Asian adults who prospectively un- attributed to the increased internal vector force from the derwent standardized examinations and detailed color posterior protrusion of the wall coupled with early fundus photograph grading. These young subjects are vitreous shrinkage.33,34 In addition, Hayashi and less likely to have media opacities that may affect visual- associates showed that up to 40% of highly myopic eyes ization of structural changes in the retina or glaucoma. with myopic maculopathy showed progression over a The limitations of our study should be mentioned. First, mean duration of 12.7 years and eyes with posterior the subjects were predominantly Chinese (92.0%) and staphyloma are at a higher risk of progression compared all were male. As such, the generalization of our results to eyes without posterior staphyloma.35 We recognized needs to be more cautious, although Cheng and associates the limitation of color fundus photographs, which could reported that sex did not alter the prevalence of patho- underestimate the frequency of posterior staphyloma. As logic myopia findings in a population-based study such, we used SD OCT imaging to provide cross- involving subjects more than 40 years old.12 Second, the sectional images of the posterior pole to detect more subtle cross-sectional nature of our study cannot confirm the and early posterior bowing of the retina. Owing to the po- temporal relationships of these myopia-related changes tential vision-threatening complications that could be with its risk factors. detected and treated effectively, eyes with posterior staph- In conclusion, our study showed that myopic maculop- yloma require increased surveillance and detailed examina- athy and other structural changes in the optic disc and mac- tion. ula were common, even in young highly myopic adults in Finally, the high prevalence of optic disc tilt and beta- an urban Asian population. Most of the lesions were signif- peripapillary atrophy in these myopic eyes makes it hard icantly associated with reduced SER, increased AL, and to assess the head (ONH) characteristics. Mul- reduced central choroidal thickness. The risk factors for tiple studies have shown a significant association between myopic maculopathy were older age, increased AL, and high myopia (SE less than 6.00 D) and primary open- reduced central choroidal thickness. Myopic maculopathy angle glaucoma.36,37 Optic disc tilt has been shown to and specific changes including chorioretinal atrophy, pos- affect ONH measurements measured by Heidelberg terior staphyloma, and optic disc tilt were associated with retinal tomography (Heidelberg Engineering, Heidelberg, reduced visual acuity. These visually disabling myopia- Germany), and this may affect the diagnostic accuracy of related changes could worsen with age and significantly in- its classification algorithm based on a normative crease the disease burden of an increasingly common ocular database.38 Studies also showed that optic disc tilt was 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 Ohno- Matsui, 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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