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Abstract
Purpose To investigate the characteristics, risk factors and visual impact of myopic traction maculopathy (MTM) among adults with myopia in Singapore.
Methods We analysed 3316 myopic eyes of adults aged over 40 years who participated in the Singapore Epidemiology of Eye Diseases-2 study. Detailed questionnaires and ophthalmic examinations were conducted. A total of 2913 myopic eyes of 1639 subjects were graded for MTM by spectral-domain optical coherence tomography. MTM is defined as the presence of retinoschisis, lamellar or full-thickness macula hole and foveal retinal detachment. Fundus photographs were graded for myopic macular degeneration (MMD).
Results Of these 2913 myopic eyes, the mean and SD of age was 60.1±8.0 years; the spherical equivalent (SE) was −2.5±2.3 D; and the axial length (AL) was 24.6±1.3 mm. MTM was found in 0.9% of myopic eyes and 7.3% of highly myopic eyes. In the multivariate analysis, myopic SE (p<0.001), longer AL (p<0.001), MMD (p=0.01) and epiretinal traction (p<0.001) were independent risk factors for MTM. MTM was not associated with age (p=0.38). MTM was significantly associated with poorer best-corrected visual acuity (BCVA) (p<0.01).
Conclusions Our population-based study revealed that MTM was present in 0.9% of myopic eyes and 7.3% of highly myopic eyes. While greater myopic SE, longer AL, MMD and epiretinal traction are risk factors of MTM, age was not related to MTM. MTM has a negative effect on BCVA.
- epidemiology
- imaging
- retina
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Introduction
Over the past few decades, the prevalence of high myopia (HM) has increased drastically in developed countries where myopia has reached epidemic levels.1–5 HM is associated with various sight-threatening ocular diseases with increasing age, such as pathological myopia (PM), and is predicted to be one of the main causes of visual impairment worldwide in the next few decades.6–8 The prevalence of blindness or visual impairment attributed to PM is 7% in Western populations and 12% to 27% in Asian populations.9–12 Considering the global public health burden of HM with its increasing prevalence, it is important to understand the factors that influence the development of these sight-threatening complications.
Myopic traction maculopathy (MTM) is a complication of HM that arises from tractional forces exerted on the macula and is characterised by retinoschisis (RS), lamellar or full-thickness macula hole (MH) and foveal retinal detachment (RD).13 14 A recent report from Japan revealed that the prevalence of MTM was 23.0% in 1487 highly myopic eyes of 884 hospital patients.15 Among the MTM lesions, RS was most frequently observed, with a reported prevalence ranging from 14.7% to 34.4% in hospital-based studies.14 16–18 Another population-based study in China reported the frequency of RS to be 0.8% in the population aged ≥50 years.19 MTM is usually accompanied by other HM-related changes, such as staphyloma, severe myopic macular degeneration (MMD) and vitreoretinal interface factors, such as epiretinal membrane (ERM) and vitreomacular traction (VMT).20 21 The presence of these comorbidities further complicates attempts to identify the cause of MTM.20 22–25 Despite the clinical significance of HM complications, there is limited information on the characteristics of MTM available from population-based studies.
The purpose of our study was to investigate the characteristics, risk factors and visual impact of MTM among adults with myopia in the Singapore Epidemiology of Eye Diseases-2 (SEED-2) study.
Method
Populations
The Singapore Epidemiology of Eye Diseases (SEED) study is a population-based study of common eye diseases in Singaporean residents 40 years of age and older and includes the three major ethnic groups: Malay, Indian and Chinese. Detailed methodology of the SEED study has been published elsewhere and identical methodology was used across the studies.26–28 Subsequently, a total of 6762 subjects participated in the follow-up SEED-2 study from 2011 through 2017. Subject numbers for each ethnic group were as follows: 1901 (72.1% of eligible) Malay participants, 2200 (75.5% of eligible) Indians and 2661 (87% of eligible) Chinese.
Among the 13 524 eyes from 6762 subjects in the SEED-2 study, there were 4577 myopic eyes (spherical equivalent (SE)≤−0.5 D). We excluded the following eyes from this study: those that had previous cataract surgery (1230 eyes) and those with self-reported refractive surgery (31 eyes). Previous cataract surgery was determined by slit-lamp biomicroscopic examination.29 Of the remaining 3316 myopic eyes after the aforementioned exclusions, 403 eyes had missing or ungradable optical coherence tomography (OCT). Because OCT examination was a key component of this study, these eyes were excluded as well.
OCT examinations
All myopic eyes were assessed with the spectral-domain optical coherence tomography (SD-OCT; Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, California, USA). After adequate pupil dilation, image acquisition of the macula was performed using the SD-OCT system. In each eye, a macular cube 512×128 scan protocol (A scans×B scans) was performed over a nominal 6×6 mm2 area centred at the fovea. All images were obtained by trained optometrists, and acquisitions were repeated multiple times to obtain high-quality images. The images with a signal strength of under 6 (ranging from 0 (poor) to 10 (excellent)) were excluded, and the image with the highest signal strength was selected for grading. All OCT images were reviewed and graded by an ophthalmologist (SM) masked to the identity of the participants, including their demographic and clinical information. Adjudication was conducted by a retinal specialist (QVH). The intergrader agreement was assessed using kappa statistics (κ coefficient of 0.90 (SM and QVH)). The intragrader agreement for the grader (SM) between gradings performed at baseline and at 1 month was 0.93.
Myopic macular lesions, including inner and outer RSs, lamellar or full-thickness MH and foveal RD, ERM and VMT, were examined. MTM was then defined as the presence of inner and/or outer RS, lamellar or full-thickness MH and foveal RD as previously reported.15 The outer RS was further graded for its location and extent according to the classification by Shimada et al: no RS (S0), extrafoveal region (S1), foveal region (S2), foveal but not the entire macular region (S3) and the entire macular region (S4).24
Other eye examinations
All participants underwent a comprehensive ocular examination, including slit-lamp examination (Haag-Streit model BQ-900; Haag-Streit, Koeniz, Switzerland). Details of the methodology have been reported previously.27 28 30 Autorefraction was performed using an autorefractometer (Canon RK-5 Auto Ref-Keratometer; Canon, Tokyo, Japan). Best-corrected visual acuity (BCVA) was measured using a logarithm of the minimum angle of resolution (logMAR) number chart (Lighthouse International, New York, New York, USA) at 4 m. Subjective refraction and measurements of BCVA were conducted by trained and certified study optometrists when the presenting visual acuity was worse than 0.3 logMAR. The SE of refractive error was calculated as spherical power plus half cylindrical power. HM was defined as SE≤−5.0 D. Axial length (AL) measurement was not available in the SEED-2 study, we used AL at the first visit for analysis. AL was measured using non-contact partial coherence interferometry (IOL Master V.3.01; Carl Zeiss Meditec AG, Jena, Germany).
Furthermore, fundus photographs were also graded for age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (DR), the results of which were previously reported.27 28
Other measurements
A detailed interviewer-administered questionnaire was used to collect information such as demographic information; socioeconomic characteristics; medical history, including systemic and ocular disease; and history of ocular surgery. Education level was classified as primary/below education and secondary/above education. Hypertension was defined as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg, physician-diagnosed hypertension or self-reported history of hypertension. Diabetes mellitus was defined as random blood glucose level of ≥11.1 mmol/L, diabetic medication use or a physician-diagnosed history of diabetes.
Grading of MMD on fundus colour photograph
Colour fundus photographs centred at the optic nerve and at the fovea, were obtained for each eye with fully dilated pupils using a non-mydriatic retinal camera (Canon CR-DGi with 10 DSLR back, Canon). Fundus photographs were graded according to the International Meta-Analysis for Pathologic Myopia classification, which were classified into five categories of ‘no myopic retinal lesions’ (category 0), ‘tessellated fundus only’ (category 1), ‘diffuse chorioretinal atrophy (CRA)’ (category 2), ‘patchy CRA’ (category 3) and ‘macular atrophy’ (category 4). Plus lesions including lacquer cracks, choroidal neovascularisation and Fuchs’ spot were also graded.30 Based on fundus photograph grading, an eye was considered to have MMD if META-PM category 2, 3, 4 or any ‘plus’ lesion was observed.
Statistical analysis
We examined the association between clinical parameters and MTM using manual stepwise multivariable generalised estimating equation (GEE) logistic regression models in both eyes of the participants. GEE was used to account for the correlation between the two eyes of the same individuals in all regression analyses. Collinearity between covariates was examined and found between AL and SE; ORs and their 95% CIs were presented. To investigate the impact of MTM on vision, the participants with ocular comorbidities, including glaucoma, AMD and DR, were excluded. We used GEE linear regression models to assess the association between MTM and BCVA (as the outcome variable), and reported the beta coefficients and their 95% CIs. P values of <0.05 were considered statistically significant. Statistical analysis was performed using a commercially available statistical software programme (SPSS V.20.0).
Results
The final study population consisted of 2913 myopic eyes of 1639 subjects (1393 eyes in the Chinese group, 705 eyes in the Malay group and 815 eyes in the Indian group). The mean and SD of age was 60.1±8.0 years; 45.9% were men; SE was −2.5±2.3 D; AL was 24.6±1.3 mm. Three hundred and fifty-five eyes (225 subjects) out of 2913 eyes (12.2%) had HM. Among highly myopic subjects, the mean and SD of age was 57.6±6.5 years; 39.4% were men; SE was −7.2±2.3 D; AL was 26.4±1.2 mm.
Frequency and type of MTM lesions among myopic and high myopic eyes
Among 2913 myopic eyes, 0.9% had MTM. Of the 27 myopic eyes with MTM, 70.4% had RS only, 14.8% had both RS and lamellar MH, and 14.8% had lamellar MH only. Among 23 eyes with RS, type S1 (extrafoveal) was most frequent (73.9%), followed by types S2 (foveal, 21.7%) and S4 (entire macular region, 4.4%). Representative fundus photographs and SD-OCT images of RS and combination of RS and lamellar MH are shown in figure 1. For epiretinal traction lesions, ERM and VMT were detected in 57 (2.0 %) and 8 (0.3%) myopic eyes, respectively.
Representative fundus photographs and SD-OCT images of MTM. (A) Fundus photograph of the left eye with a refractive error of −7.50 D and MMD category 2. The arrow indicates the direction of the OCT scan in the right figure. The horizontal OCT imaging shows lamellar macula hole and RS. (B) A fundus photograph of the right eye with a refractive error of −5.00 D and MMD category 3 with lacquer crack. The arrow indicates the direction of the OCT scan in the right figure. The horizontal OCT imaging shows RS (S1: extra foveal) and epiretinal membrane. (C) Fundus photograph of the right eye with a refractive error of −9.25 D and MMD category 2 with lacquer crack. The arrow indicates the direction of the OCT scan in the right figure. The horizontal OCT imaging shows RS (S3: both foveal and extra foveal). (D) Fundus photograph of the left eye with a refractive error of −10.40 D and MMD category 2+lacquer crack. The arrow indicates the direction of the OCT scan in the right figure. The horizontal OCT imaging shows RS (S4: entire macula) and inner limiting membrane detachment. MMD, myopic macular degeneration; MTM, myopic traction maculopathy; N, nasal; OCT, optical coherence tomography; RS, retinoschisis; T, temporal; SD-OCT, spectral-domain optical coherence tomography.
Among 355 high myopic eyes, 26 (7.3%) had MTM; 19 eyes (5.4%) had RS only; 4 eyes (1.1%) had both RS and lamellar MH; and 3 eyes (0.8%) had lamellar MH only. ERM and VMT were detected in 20 (5.6%) and 8 (2.3%) highly myopic eyes, respectively.
Association between MTM and other systemic and ocular factors
Figure 2A shows the relationship between SE and the percentage of MTM in myopic eyes. The frequency of MTM increased steeply with SE less than −10.0 D and plateaued at higher myopic SE levels. The frequency of MTM increased steeply with AL more than 28.0 mm (figure 2B). On the other hand, the frequency of MTM did not increase with age, as shown in figure 2C. In the univariate analysis, MTM was associated with more severe MMD categories (p<0.001). Category 2 and more severe MMD were uncommon in eyes without MTM (6.3%), whereas more than 70% of eyes with MTM had category 2 or above. Multivariate analysis showed that MTM was associated with longer AL (adjusted OR 3.6, 95% CI 2.3 to 5.6, p<0.001), the presence of MMD (adjusted OR 4.9, 95% CI 1.4 to 17.9, p=0.01) and more myopic SE (adjusted OR 0.6, 95% CI 0.5 to 0.6, p<0.001) (table 1). In the multivariate analysis including age, gender, ethnicity, AL and epiretinal traction, MTM was associated with the presence of epiretinal traction (adjusted OR 30.7, 95% CI 1.4 to 193.3, p<0.001).
Relation between SE, ageing, AL and the percentage of MTM in myopic eyes as calculated by univariate analysis (N=2913 eyes). (A) Relation between SE and the percentage of MTM in myopic eyes. (B) Relation between AL and the percentage of MTM in myopic eyes. (C) Relation between ageing and the percentage of MTM in myopic eyes. For all graphs (A–C), the size of the data points (represented by circles) is proportional to the sample size of the particular group. AL, axial length; MTM, myopic traction maculopathy; SE, spherical equivalent
Univariate and multivariate analyses of systemic and ocular factors associated with MTM in Singaporean myopic adults from the population-based Singapore Epidemiology of Eye Diseases-2 study (N=2913 eyes)
Impact of MTM on visual acuity in myopic eyes
After excluding 166 eyes with ocular comorbidities, we analysed the visual impact of MTM among the remaining 2747 eyes (table 2). In the second multivariate model (model 2) MTM was associated significantly with poorer BCVA (β 0.19, 95% CI 0.06 to 0.30, p<0.01), and MMD was also significantly associated with poorer BCVA (β 0.03, 95 % CI 0.001 to 0.06, p<0.05).
Association of MTM and MMD with visual acuity in myopic eyes in Singaporean myopic adults without ocular comorbidities from the population-based Singapore Epidemiology of Eye Diseases-2 study (N=2747 eyes)
Discussion
In our study, the frequency of MTM was 0.9% among myopic eyes and 7.3% in highly myopic eyes. Multivariate analysis revealed that more myopic refractive error, longer AL, MMD and epiretinal traction were independent risk factors of MTM. MTM was significantly associated with poorer BCVA.
Frequency and type of MTM
The frequency of MTM and RS, the most common lesion in MTM, among highly myopic eyes was reported in several previous studies, as summarised in table 3. The majority were hospital-based studies, and the reported frequencies ranged from 9% to 34%, higher than the rate reported in our present study. This difference could be attributed to the lower mean myopic refractive error in our population-based study compared with the previous hospital-based studies, all of which reported a mean SE worse than −10.0 D. To our knowledge, only one population-based study in China on the frequency of RS has been published previously,19 which showed a higher frequency of RS (32.9%) among less myopic eyes (mean SE −8.4±4.5 D) than most published hospital-based studies and our present study. There may be differences in imaging quality and the scan size obtained from different types of OCT from different studies that may have affected the sensitivity to detect MTM. In the 27 MTM cases in our study, RS occurred most frequently (70.4%), followed by the combination of RS and lamellar MH (14.8%), and lamellar MH alone (14.8%). This is in agreement with a previous study by Panozzo and Mercanti, which showed that the most frequent abnormality in MTM was RS (25 out of 43 eyes, 58.1%), followed by MH (14.0%) and RD (4.7%).14
Summary of the frequency of myopic-related lesions on OCT in a highly myopic population
MTM in low to moderate myopia
MTM is caused by traction force that makes it difficult for the retina to conform to the scleral curvature, and axial elongation is the most common factor that generates such traction force. Therefore, it is not surprising that subjects with severe myopia have a high risk of MTM development. In our study, one eye with low and moderate myopia (−0.50 D≥SE>−5.00 D) was found to have MTM. This case was suspected to have peripapillary staphyloma (type III), because the sclera on the edge of the staphyloma was elevated inward to the optic nerve. This was similar to another previous study that reported the presence of a peripapillary staphyloma as a gently sloping excavation around the optic disc in non-high myopic eye using swept source (SS)-OCT.31 While axial elongation generates posteriorly and tangentially directed traction force on the retina, a staphyloma can cause multidirectional tractional forces. Therefore, it is possible that the peripapillary staphyloma in this case led to MTM despite the absence of HM. Our finding suggests that clinicians should not exclude the possibility of the presence of MTM in low to moderately myopic eyes, though MTM is still rare.
Risk factors of MTM in myopic eyes
In the multivariate analysis, the presence of MTM was significantly associated with more myopic refractive error, longer AL, the presence of MMD and the presence of epiretinal traction. The relationship between RS and epiretinal traction, more myopic SE and longer AL is well-established in previous studies.14 19 22 Myopic maculoschisis was associated with longer AL and more myopic refractive error in the Beijing eye study.19 Also, Wu et al showed that longer AL and vitreoretinal interface factors were independent factors associated with foveoschisis and foveal detachment without MH.22 Myopic changes, longer AL and myopic SE are similar and partially overlapping concepts, all of which can cause mechanical stretching of the eyeball and subsequent retinal thinning. Our results suggest that the development of MTM is mainly related to epiretinal traction and retinal stretching caused by progressive myopic change.
As for the relationship between MMD and MTM, the presence of MMD (category 2 or above) was associated with the presence of MTM in our study. Baba et al reported that RS was observed more frequently in high myopic eyes with advanced CRA compared with the group with less severe fundus change.25 The attachment between inner retina and sclera is considered to be weak in the area of advanced CRA. Our result suggested that traction force might facilitate the dissociation of the retinal tissue in the area of MMD.
Interestingly, we found that the presence of MTM was not associated with age in our study, which forms a contrast to the association between most myopic pathological lesions and older age.30 According to a previous study, RS was found in the absence of vitreoretinal pathology or severe MMD (categories 3 and 4) in highly myopic teenagers,18 which indicates that MTM can develop by traction forces related to severely myopic eyes and possible progressive eye elongation at any age. As such, the alterations from ageing of the retina and the sclera may not contribute much to the pathology of MTM.
Impact of MTM on visual acuity
Regarding the impact of MTM on vision, eyes with MTM were significantly associated with poorer BCVA in our study, and this finding is in agreement with previous reports.24 32 33 Shinohara et al reported that grade S4 MTM was present in 42.7% of eyes with RS, and the BCVA was significantly worse in eyes with grade S4 RS than in eyes with RS of other grades.33 Of note, the BCVA was significantly affected even though the majority of our RS cases had milder S1–S3 RS (96.3%). This might be due to the high frequency of ERM and MH in our cases with MTM (70.4%, 19 out of 27 cases) because Gaucher et al reported that the risk of MH formation and visual loss was much higher in the presence of ERM.34 In addition, our data suggest that the presence of both MTM and MMD contribute to poor BCVA. Further studies are recommended to reveal whether MTM and MMD affect BCVA.
Strengths and limitations
The strengths of our study include the large sample size, population-based study design, as well as the availability of ocular measurements and masked grading of fundus photographs and SD-OCT performed according to a standardised protocol. However, there are also several limitations in this study. First, the cross-sectional nature of our study limits inferences of causation. Second, the scan width of our OCT scans was not sufficient to detect posterior staphyloma conclusively from OCT alone. Third, the possibility of selection bias due to loss to follow-up cannot be excluded because not all participants returned for the second SEED follow-up visit (the rate of loss to follow-up was 24%).
Conclusions
In conclusion, our population-based study revealed that MTM was present in 0.9% in myopic eyes and 7.3% among highly myopic eyes. While more myopic refractive error, longer AL, MMD and epiretinal traction were risk factors for MTM, MTM was not related to age and was present even in low to moderate myopic eyes. Both MTM and MMD were associated with poorer BCVA. Our findings provide new insights on the pathophysiology of myopia and MTM and will contribute to identifying mechanisms and novel therapies capable of treating and/or preventing myopia-related complications in future.
Acknowledgments
The authors thank Shu-Ling Soo and Chye-Fong Peck from the Singapore Eye Research Institute for their contributions to the data collection.
References
Footnotes
Contributors SM: involved in all aspects of its design, conception, grading, analysis, manuscript creation and editing. CS: involved in manuscript creation and editing. CWW and AK: involved in conception and editing. C-ST: involved in analysis and editing. YLW: involved in fundus grading and editing. C-YC, KO-M and TYW: involved in conception and critical revision of the manuscript. QVH: involved in optical coherence tomography grading, conception and editing. SMS: involved in design, conception, analysis, manuscript creation and critical revision of the manuscript.
Funding This work was supported by the Singapore Ministry of Health’s National Medical Research Council (NMRC) (grant numbers NMRC/CIRG/1488/2018, NMRC/OFLCG/004a/2018 and NMRC/CIRG/1466/2017).
Competing interests None declared.
Patient consent for publication Written informed consent was obtained from all subjects.
Ethics approval All study procedures were performed in accordance with the tenets of the Declaration of Helsinki as revised in 1989. The study was approved by the centralised institutional review boards of the Singapore Health Services and the domain-specific review board of the National Healthcare Group.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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