Study Population

The current study was conducted between January 1, and December 31, 2012 and the methodology for subject recruitment was detailed elsewhere. 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 +1.00 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 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.

Interview, Visual Acuity Measurement, and Refraction

All the participants who fulfill the inclusion 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

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 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.

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. 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. Staphyloma was determined by visualizing the border of the ectasia, then its location and type were documented based on the Curtin classification. 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 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 μm relative to the periphery of the OCT B-scan. This allowed posterior staphyloma with more gentle and subtle sloping edges to be detected.

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).

The presence of myopic maculopathy was defined and classified based on the International Photographic Classification and Grading System for Myopic Maculopathy. 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.

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).

Statistical Analysis

Statistical analysis was performed using IBM SPSS version 22 (IBM Corporation, New York, USA). Only 1 eye per subject was 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 χ ² 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 tilt, PPA, posterior staphyloma, chorioretinal atrophy, and myopic maculopathy on BCVA. Statistical significance was set at P < .05.