Purpose
To examine the pattern of myopia-related macular and optic disc changes in Singapore adults with high myopia (spherical equivalent ≤−6.00 diopters).
Design
Asian adults with high myopia from 3 population-based surveys.
Methods
Adults 40 years and older (n = 359) with high myopia were pooled from 3 population-based surveys in Singapore Asians: (1) the Singapore Prospective Study Program (SP2, n = 184); (2) the Singapore Malay Eye Study (SiMES, n = 98); and (3) the Singapore Indian Eye Study (SINDI, n = 77). All study participants underwent standardized refraction and fundus photography, and SiMES and SINDI subjects also completed ocular biometry measurements. Myopia-related macular (posterior staphyloma, lacquer cracks, Fuchs spot, myopic chorioretinal atrophy, and myopic choroidal neovascularization) and optic disc (optic nerve head tilt, optic disc dimensions, and peripapillary atrophy) changes were evaluated.
Results
The most common myopia-related macular finding in adults with high myopia was staphyloma (23%), followed by chorioretinal atrophy (19.3%). There were few cases of lacquer crack (n = 6, 1.8%), T-sign (n = 6, 1.8%), retinal hemorrhage (n = 3, 0.9%), active myopic choroidal neovascularization (n = 3, 0.9%), and no case of Fuchs spot. The most common disc finding associated with high myopia was peripapillary atrophy (81.2%), followed by disc tilt (57.4%). Staphyloma and chorioretinal atrophy increased in prevalence with increasing age, increasing myopic refractive error, and increasing axial length (all P < .001). Ethnicity comparisons demonstrated the highest proportion of staphyloma ( P = .04) among Malays, the highest proportion of peripapillary atrophy ( P = .01) and disc tilt ( P < .001) among Chinese, and the largest cup-to-disc ratio ( P < .001) among Indians.
Conclusions
Staphyloma and chorioretinal atrophy lesions were the most common fundus findings among Asian adults with high myopia. In this population, tilted discs and peripapillary atrophy were also common, while choroidal neovascularization and Fuchs spot were rare. In contrast with Singapore teenagers, in whom tilted disc and peripapillary atrophy were common while staphyloma and chorioretinal atrophy were rare, pathologic myopia appears to be dependent on the duration of disease and, thus, age of the individual.
Pathologic myopia, defined as presence of a spectrum of myopia-related retinal and optic disc changes, is a leading cause of visual impairment and blindness in Asian countries. The socioeconomic impact of blindness and visual impairment from myopia and high myopia is considerable, as it typically affects individuals during their productive years.
In the Australian Blue Mountains Eye Study, the prevalence of myopia in excess of −5.00 diopters (D) was 2.49% in their cohort of 3654 white population 49 years or older, myopic retinopathy was 1.2%. The Beijing Eye Study found a higher prevalence of myopia in excess of −5.00 D, at 3.29% among 4439 adults 40 years or older, at 2.64% with myopia in excess of −6.00 D, with overall myopic retinopathy prevalence at 3.1%. In rural China, the Handan Eye Study conducted on 6830 individuals 30 years and older found myopic retinopathy prevalence to be 0.9%. More recently, the Hisayama Study, conducted on a Japanese cohort (n = 1892) older than 40 years, found the prevalence of myopic retinopathy to be 1.7%. In a clinic setting, a Japanese study of highly myopic individuals with greater than −8.00 D of spherical refractive myopia, several progressive patterns of pathologic myopia were seen—the initial finding of tessellated fundus, followed by staphyloma developing at approximately 40 years of age, and later with progression to diffuse atrophy and lacquer cracks. The number of cases from a single population-based survey is limited while clinic-based studies are not representative of the population. Although pathologic myopia typically progresses with increasing age and higher degrees of myopia, few studies have evaluated the pattern of pathologic myopia lesions and associations with axial length and refractive error.
Our aim is to examine the pattern of myopia-related macular and optic disc changes in Singapore adults with high myopia identified from population-based studies, and correlate these findings with refractive error and axial length.
Methods
We included Singapore adults 40 years and older with high myopia (spherical equivalent [SE] ≤−6.00 D) from 3 population-based surveys: (1) the Singapore Prospective Study Program (SP2), (2) the Singapore Malay Eye Study (SiMES), and (3) the Singapore Indian Eye Study (SINDI). The selection of adults 40 years and older with high myopia (SE ≤−6.00 D) was done in order to increase the yield of those with fundus changes and still allow for comparison with other published population-based studies. The study followed the principles of the Declaration of Helsinki, with ethics approval obtained from the Singapore Eye Research Institute Review Board. Written consent was obtained from each study participant.
The SP2 involved inviting participants of population-based surveys conducted in Singapore between 1982 and 1998 for repeat examinations between 2004 and 2007. The protocol has been described previously. All 3 major ethnic groups were represented, and there was a purposeful disproportionately larger representation of ethnic minorities (Malays and Asian Indians). A total of 5157 subjects underwent a clinical examination that included systemic and ocular assessment, and 4108 underwent fundus photography. SINDI and SiMES were complementary studies with identical methodology. A total of 3280 Malay adults and 3400 Indian adults between the ages of 40 and 80 years were recruited.
After informed consent, all subjects from the included projects underwent a detailed and standardized examination, which included measurements of height, weight, blood pressure, and heart rate, and a comprehensive ocular examination.
Visual Acuity Measurement and Refraction
The presenting visual acuity was measured using the logarithm of the minimal angle of resolution (logMAR) chart (Lighthouse International, New York, New York, USA) at 4 meters, with subjects wearing their current optical correction (glasses or contact lenses). 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.
Autorefraction and keratometry were obtained using the Canon RK-5 Autorefractor Keratometer (Canon Inc Ltd, Tokyo, Japan). Refraction was refined by certified study optometrists, and subjects’ best-corrected visual acuity in logMAR scores were recorded. SE was calculated as the sum of the spherical power and half of the cylindrical power. The IOL Master (Carl Zeiss Meditec AG, Jena, Germany) was used for ocular biometry that included axial length measurements.
Fundus Photography
For all studies, a 45-degree digital retinal camera was used. SP2 fundus photographs were obtained after pupillary dilation with tropicamide 1% and phenylephrine 2.5%, using Canon CR-DGi with Canon EOS 10D SLR backing (Canon Inc, Tokyo, Japan). For the SICC, SiMES, and SINDI studies fundus photographs were obtained without preceding pupillary dilation. Canon CR-DGi with the Canon EOS 10D or 20D SLR backing (Canon Inc) system was used for SICC and SiMES, while the Canon CR-DGi with Canon EOS 20D or 40D SLR backing (Canon Inc) was used in the SINDI study systems.
Two fields of each eye were photographed, with one centered at the optic disc and another centered at the fovea, following the Early Treatment for Diabetic Retinopathy Study standard photograph numbers 1 and 2. The high-resolution digital photographs were stored and retrieved digitally on the Singapore Eye Research Institute server.
Fundus photographs were viewed using Photoshop CS5 (Adobe Systems Inc, San Jose, California, USA). An ophthalmologist and trained grader (L.C.), masked to participant characteristics, performed detailed assessment of the fundus photographs using a standardized grading sheet (described in the next section). Because of disc tilt that is often observed in the myopic eye, the longest and shortest disc diameters (orthogonal to one another, irrespective of vertical or horizontal planes) were measured using the pixel ruler. Inter-grader reliability was accessed with additional grading of 50 randomly selected eyes by trained graders (H.H. and V.K.), and reliability was found to be excellent (intraclass correlation coefficient of 0.73). Any discrepancies were reviewed by 2 or more graders including ophthalmologists G.C. and K.O.M.
Grading Sheet
The grading sheet was designed to capture all aspects of myopia-related fundus changes. First, the photograph quality was assessed. Staphyloma was determined by visualizing the border of the ectasia, then its location and type were documented based on the Curtin classification. Lacquer crack presence, location, and number were evaluated. With regard to peripapillary atrophy, Curtin and Karlin classification was used. Direction of disc tilt was determined, then the longest and shortest disc diameters were measured using a pixel ruler. The ratio between the longest and shortest disc diameters was calculated and used to compare degree of disc tilt. Direct pixel measurements were not used since there could be magnification differences with respect to refractive error. The horizontal cup-to-disc ratio was also assessed by the grader. The presence of a T-sign (bifurcation of the central retinal vessels beyond the lamina cribosa), Fuchs spot (small pigmented subretinal lesion in the posterior pole, representing the scar phase of myopic choroidal neovascularization), active myopic choroidal neovascularization (CNV), and hemorrhage were also evaluated. Chorioretinal atrophy was characterized based on location and size. Myopic macular chorioretinopathy was given a grade based on Avila classifications (M0-M5) : M0 representing normal fundus, M1 representing fundus pallor and tessellation, M2 representing M1 plus posterior pole staphyloma, M3 representing M2 plus lacquer cracks, M4 representing M3 plus focal deep chorioretinal atrophy, and M5 representing M3 plus large geographic area of deep chorioretinal atrophy.
Statistical Analysis
One eye per subject was chosen based on the highest myopic refractive error. We examined the association of pathologic myopia findings with age, sex, ethnicity, SE, and axial length (AL). The relationship was assessed using the χ 2 test (Fisher exact test if more than 20% of cells have expected count of less than 5) or analysis of variance. SE and AL were also analyzed as continuous variables. Multivariate linear regression and multivariate logistic regression were performed to determine the associations between pathologic myopia findings and SE or AL, with the former as a dependent variable and the latter as independent variables, adjusted for confounders. Two-tailed P values of <.05 were considered statistically significant. STATA version 11.0 (StataCorp LP, College Station, Texas, USA) was used for all statistical analyses.
Results
There were a total of 424 subjects older than 40 years and with ≤−6.00 D of myopia from the 3 population-surveys, of which 359 were identified to have fundus photographs. This represents 84.7% of all subjects older than 40 years and with ≤−6.00 D of myopia in the 3 population surveys. Of the subjects with fundus photographs, 332 subjects (92.5%) had gradable photographs. The eye with the highest magnitude of myopic refractive error was used for analyses. Table 1 shows subject distribution with respect to refractive error (−6 to −7.99 D, −8 to −9.99 D, and ≤−10 D), age (40-49 years, 50-59 years, and >60 years), sex, and ethnicity. There was a trend toward higher myopic refractive error with increasing age, though it was not statistically significant ( P = .06). Sex and ethnicity did not seem to differ with respect to degree of myopia.
| Number of Subjects | −6 to −7.99 D | −8 to −9.99 D | <−10.0 D | |
|---|---|---|---|---|
| n (%) | n (%) | n (%) | ||
| All | 332 | 191 (57.5) | 80 (24.1) | 61 (18.4) |
| Age (y) | ||||
| 40-49 | 177 | 112 (63.3) | 32 (18.1) | 33 (18.6) |
| 50-59 | 114 | 61 (53.5) | 33 (28.9) | 20 (17.5) |
| 60+ | 41 | 18 (43.9) | 15 (36.6) | 8 (19.5) |
| Sex | ||||
| Male | 147 | 89 (60.5) | 36 (24.5) | 22 (15.0) |
| Female | 185 | 102 (55.1) | 44 (23.8) | 39 (21.1) |
| Race | ||||
| Chinese | 135 | 80 (59.26) | 36 (26.67) | 19 (14.07) |
| Malay | 104 | 56 (53.85) | 25 (24.04) | 23 (22.12) |
| Indian | 89 | 54 (60.67) | 17 (19.10) | 18 (20.22) |
| Other | 4 | 1 (25.00) | 2 (50.0) | 1 (25.00) |
The most common myopic fundus finding was staphyloma (76/331; 23.0%), followed by chorioretinal atrophy (64/331; 19.3%) ( Table 2 ). The most common disc finding associated with high myopia is peripapillary atrophy (268/330; 81.2%), followed by disc tilt (190/331; 57.4%). Temporal peripapillary atrophy is the most common (51%; 137/268, data not shown). The most common Avila myopic macular chorioretinopathy grade among adults with high myopia is M1 (196/330; 59.4%), followed by M2 (75/330; 22.7%).
| Staphyloma | Peripapillary Atrophy | Disc Tilt | Chorioretinal Atrophy | Myopic Macular Chorioretinopathy | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | n (%) | N | n (%) | N | n (%) | N | n (%) | N | M0 | M1 | M2 | M3 | M4 | M5 | |
| All | 331 | 76 (23.0) | 330 | 268 (81.2) | 331 | 190 (57.4) | 331 | 64 (19.3) | 330 | 33 (10.0) | 196 (59.4) | 75 (22.7) | 3 (0.9) | 18 (5.5) | 5 (1.5) |
| Age (y) | |||||||||||||||
| 40-49 | 176 | 23 (13.1) | 176 | 152 (86.4) | 177 | 106 (59.9) | 177 | 20 (11.3) | 175 | 22 (12.6) | 123 (70.3) | 20 (11.4) | 2 (1.1) | 7 (4.0) | 1 (0.6) |
| 50-59 | 114 | 35 (30.7) | 113 | 83 (73.5) | 114 | 69 (60.5) | 113 | 28 (24.8) | 114 | 10 (8.8) | 59 (51.8) | 35 (30.7) | 1 (0.9) | 6 (5.3) | 3 (2.6) |
| 60+ | 41 | 18 (43.9) | 41 | 33 (80.5) | 40 | 15 (37.5) | 41 | 16 (39.0) | 41 | 1 (2.4) | 14 (34.1) | 20 (48.8) | 0 | 5 (12.2) | 1 (2.4) |
| P trend | <.001 | .02 | .03 | <.001 | <.001 a | ||||||||||
| Sex | |||||||||||||||
| Male | 146 | 33 (22.6) | 147 | 123 (83.7) | 147 | 86 (58.5) | 146 | 28 (19.2) | 146 | 12 (8.2) | 90 (61.6) | 35 (24.0) | 1 (0.7) | 6 (4.1) | 2 (1.4) |
| Female | 185 | 43 (23.2) | 183 | 145 (79.2) | 176 | 104 (56.5) | 185 | 36 (19.5) | 184 | 21 (11.4) | 106 (57.6) | 40 (21.7) | 2 (1.1) | 12 (6.5) | 3 (1.6) |
| P value a | .89 | .31 | .72 | .95 | .82 | ||||||||||
| Race | |||||||||||||||
| Chinese | 134 | 24 (17.91) | 133 | 117 (87.97) | 135 | 94 (69.63) | 134 | 27 (20.15) | 135 | 14 (10.4) | 84 (62.2) | 25 (18.5) | 1 (0.7) | 6 (4.4) | 5 (1.9) |
| Malay | 104 | 34 (32.69) | 104 | 84 (80.77) | 103 | 57 (55.34) | 104 | 27 (25.96) | 102 | 6 (5.9) | 58 (56.9) | 32 (31.4) | 1 (1.0) | 5 (4.9) | 0 |
| Indian | 89 | 17 (19.10) | 89 | 63 (70.79) | 89 | 38 (42.70) | 89 | 10 (11.24) | 89 | 13 (14.6) | 51 (57.3) | 17 (19.1) | 1 (1.1) | 7 (7.9) | 0 |
| Other | 4 | 1 (25.0) | 4 | 4 (100.0) | 4 | 1 (25.00) | 4 | 0 | 4 | 0 | 3 (75.0) | 1 (25.0) | 0 | 0 | 0 |
| P value a | .04 | .01 | <.001 | .06 | .19 | ||||||||||
Staphyloma ( P < .001), peripapillary atrophy ( P = .02), disc tilt ( P = .03), and chorioretinal atrophy ( P < .001) increased in prevalence with increasing age ( Table 2 ). Avila grading of myopic macular chorioretinopathy also advanced with age ( P < .001). Lacquer crack (6/333; 1.8%), T-sign (6/333; 1.8%), hemorrhage (3/333; 0.9%), CNV (3/333; 0.9%), and Fuchs spot (0/333) were observed in few subjects. There was a trend of decreasing cup-to-disc ratio with increasing age ( P = .09).
In general, sex did not alter the prevalence of pathologic myopia findings; however, several differences with respect to ethnicity were seen. Malays were noted to have higher prevalence of staphyloma ( P = .04, with borderline significance); Chinese were noted to have higher prevalence of peripapillary atrophy ( P = .01), disc tilt ( P < .001), and largest ratio between the longest to shortest disc diameters ( P = .006); and Indians had the largest cup-to-disc ratio ( P < .001).
Table 3 illustrates the relationship between pathologic findings and SE. The risk of staphyloma increased by 1.56 times for each diopter of increasing myopic refractive error ( P < .001), adjusting for all other confounders in multivariate logistic regression analysis. Similarly, chorioretinal atrophy increased 1.68 times for each diopter of increasing myopic refractive error ( P < .001). Multivariate logistic regression analyses for comparing peripapillary atrophy and disc tilt to SE were not as revealing. Lacquer crack increased 1.37 times for each diopter of increasing myopic refractive error ( P = .002, data not shown) and retinal hemorrhage increased 1.57 times for each diopter of increasing myopic refractive error ( P = .03, data not shown). The ratio between the longest to shortest disc diameter (a marker for disc tilt) increased by 0.02 for each diopter of increasing myopic refractive error ( P < .001, data not shown). This shows that the nerve tends to tilt more with increasing myopic refractive error. Logistic regression also showed a trend of decreasing optic nerve head cup-to-disc ratio ( P = .06) with increasing myopic refractive error (data not shown).
| SE group | Staphyloma | Peripapillary Atrophy | Disc Tilt | Chorioretinal Atrophy | Myopic Macular Chorioretinopathy | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | M0 | M1 | M2 and more | |||||||||
| N | n (%) | N | n (%) | N | n (%) | N | n (%) | n (%) | n (%) | n (%) | ||
| All | 331 | 76 (23.0) | 330 | 268 (81.2) | 331 | 190 (57.4) | 331 | 64 (19.3) | 330 | 33 (10.0) | 196 (59.4) | 110 (30.6) |
| −6 to −7.99D | 190 | 21 (11.1) | 191 | 163 (85.3) | 191 | 100 (52.4) | 191 | 10 (5.2) | 191 | 29 (15.2) | 131 (68.6) | 31 (16.2) |
| −8 to −9.99D | 80 | 19 (23.8) | 78 | 61 (78.2) | 79 | 50 (63.3) | 80 | 20 (25.0) | 80 | 4 (5.0) | 47 (58.8) | 29 (36.3) |
| <−10.0D | 61 | 36 (59.0) | 61 | 44 (72.1) | 61 | 40 (65.6) | 60 | 34 (56.7) | 59 | 0 | 18 (30.5) | 41 (69.5) |
| P trend | <.001 | .05 | .09 | <.001 | <.001 d | |||||||
| SE (D) a , OR (95% CI), P | ||||||||||||
| Unadjusted b | 1.51 (1.34, 1.71) | <0.001 | 0.91 (0.83, 1.00) | 0.06 | 1.03 (0.95, 1.15) | 0.47 | 1.54 (1.36, 1.75) | <0.001 | ||||
| Multivariate adjusted c | 1.56 (1.37, 1.77) | <0.001 | 0.92 (0.84, 1.02) | 0.1 | 1.05 (0.96, 1.15) | 0.26 | 1.68 (1.46, 1.95) | <0.001 | ||||
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