Article Text

Download PDFPDF

Prevalence of myopic maculopathy in the German population: results from the Gutenberg health study
  1. Susanne Hopf1,
  2. Christina Korb1,
  3. Stefan Nickels1,
  4. Andreas Schulz2,
  5. Thomas Münzel2,
  6. Philipp S Wild2,3,
  7. Matthias Michal4,
  8. Irene Schmidtmann5,
  9. Karl J Lackner6,
  10. Norbert Pfeiffer1,
  11. Alexander K Schuster1
  1. 1Department of Ophthalmology, University Medical Center Mainz, Mainz University, Mainz, Germany
  2. 2Preventive Cardiology and Preventive Medicine/Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
  3. 3Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany
  4. 4Psychosomatic Medicine and Psychiatry, University Medical Center Mainz, Mainz, Germany
  5. 5Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
  6. 6Institute for Clinical Chemistry and Laboratory Medicine, Univeritätsmedizin, Mainz, Germany
  1. Correspondence to Dr Susanne Hopf, Department of Ophthalmology, University Medical Center Mainz, Mainz University, Mainz 55131, Germany; hopf101{at}gmail.com

Abstract

Aims To determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors.

Design The Gutenberg Health Study is a population-based study, including 15 010 participants aged 35–74 years.

Methods Myopic maculopathy was graded in phakic eyes with spherical equivalent ≤−6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associated factors with myopic maculopathy.

Results Myopic maculopathy was present in 10.3% (95% CI 7.9 to 13.3) study participants. The prevalence was 8.6% (95% CI 6.1% to 11.9%) in the 397 right eyes and 8.7% (95% CI 6.2% to 12.0%) in the 404 left eyes. The most common type of pathology was diffuse atrophy (8.1%), followed by patchy atrophy (1.3%) and macular atrophy (0.5%); plus lesions were present in 3% (right eyes). Age (OR 1.07 per year, 95% CI 1.03 to 1.11, p<0.001), higher myopic refractive error (p<0.001), and male gender (p=0.02) were associated with myopic maculopathy, while cardiovascular risk factors and socioeconomic factors were not.

Conclusions The prevalence of myopic maculopathy in the German population was 0.5%, and 10% in high myopic participants, aged 35–74 years. These population-based data are the first in Europe. Myopic maculopathy was related to severity of myopic refractive error and age.

  • myopia
  • tessellations
  • diffuse atrophy
  • patchy atrophy
  • myopic maculopathy
  • epidemiology
  • pathologic myopia
  • refractive error
  • myopic macular degeneration
  • Caucasian
  • Europe

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Introduction

Worldwide, myopia is an increasing health challenge requiring optical aids and leading to increased risk of severe secondary eye diseases such as myopic maculopathy, glaucoma, cataract and retinal detachment.1–3

Myopic maculopathy is an important cause of visual impairment and blindness worldwide.4 The principal alterations in pathologic myopia include excessive axial elongation of the globe and associated deformation of the posterior ocular segment including posterior staphyloma. Specific retinal and choroidal lesions may develop in the posterior pole (myopic maculopathy) leading to decreased vision and potentially loss of reading ability.5 These morphological changes are termed ‘myopic maculopathy’ or ‘myopic retinopathy’ or ‘myopic macular degeneration’. Recently, an international collaboration developed and evaluated a new simplified photographic grading system (META-PM) for myopic maculopathy to facilitate communication and comparison of findings from different populations clinical trials and epidemiological studies.6

The prevalence of myopic maculopathy in Asia and worldwide was estimated to be 0.9%–3.1% among middle-aged and elderly people.4 7 The prevalence of progressive high, degenerative myopia was estimated to be about 0.33% based on the National Health and Nutrition Examination Survey (NHANES), the US Population Census and the IRIS Registry.8

While myopic maculopathy is commonly reported to be associated with older age,4 9–12 there is conflicting evidence on associations with cardiovascular risk factors.9 13 Driven by hypotheses, we regard cardiovascular risk factors as potential risk factors for myopic maculopathy, because there is evidence from other retinal diseases that they have an impact.

Now, we aim to determine prevalence estimates for myopic maculopathy in a population-based sample for the first time in Europe, and we explore associated factors within this high myopic population.

Methods

Study population

The Gutenberg Health Study (GHS) is an ongoing population-based study, which started in 2007 at the University Medical Center of the Johannes Gutenberg-University Mainz. The sample was randomly selected from local residents’ registration offices (city of Mainz (n=196 425) and district of Mainz-Bingen (n=201 371)). Residents aged 35–74 years were eligible (n=210 867) and stratified by gender, decade of age and residence (rural vs urban); 35 008 selected residents were randomly selected and were contacted by invitation letters and phone calls.14

The recruitment efficacy proportion15 was 61.2% (n=15 010) and all study participants were eligible for this analysis to estimate the prevalence of myopic maculopathy.

All persons gave their written informed consent prior to inclusion in the study. The research adhered to the tenets of the Declaration of Helsinki.

Ophthalmic examination procedure

The ophthalmic evaluation performed on all 15 010 GHS participants included measurements of distant corrected visual acuity, and objective refractive error, measured without cycloplegia16 (Humphrey Automated Refractor/Keratometer (HARK) 599; Carl Zeiss Meditec, Jena, Germany). Spherical equivalent of the refractive correction of each eye was computed. Intraocular pressure was measured by non-contact tonometry (Nidek NT-2000, Nidek, Japan). A slit-lamp examination was carried out to determine lens status. Fundus images were taken with a non-mydriatic fundus camera (Visucam PRO NM, Carl Zeiss) from both eyes with physiological pupils in a darkened room.17 The photographs relevant for the grading were 30° centred on the macula. In case of insufficient picture detail, photographs 45° centred on the optic nerve head were used.

Inclusion and exclusion criteria

All study participants, who had phakic eyes with myopic refractive error (spherical equivalent) ≥−6D5 were included in the grading of fundus photographs for myopic maculopathy. In addition, a random sample of emmetropic (myopic refractive ≤−0.5 D, n=85) and low myopic eyes (myopic refractive error between −0.5 D and −6.0 D, n=153) were graded as controls. Only exclusion criterion was previous history of cataract surgery, as determined by the presence of pseudophakia or aphakia in slit-lamp examination.

Grading of myopic maculopathy

All available fundus images were graded at the Mainz Ophthalmic Reading Center, which provides standard operating procedures for its standardised working stations. The grading was performed by two masked graders (SH, AKS) following the international photographic grading system for myopic maculopathy (META-PM).6 In case of divergent findings, a retinal specialist (CK) decided in a consensus meeting.

Each photograph was assessed for the following items in the macular area: image quality, presence of tessellations in between the vessel arcades, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy and the plus lesions: lacquer cracks, choroidal neovascularisation and Fuchs’ spot. Kappa statistics based on photographs of controls and cases of myopic maculopathy revealed good intrarater agreement (fundus tessellations k=0.57, diffuse chorioretinal atrophy k=0.70, patchy chorioretinal atrophy k=0.68, macular atrophy k=0.54, plus lesions k=0.40). Examples are given in online supplementary eFigure 1.

Investigated factors and comorbidities

All GHS participants underwent general examinations including measurement of body weight and body height, measurement of systolic and diastolic blood pressure (Omron HEM-705CP II, Kyoto, Japan). Arterial blood pressure was defined as the mean of the second and third measurement after 8 and 11 min of rest. The mean of the systolic and diastolic arterial blood pressure was computed and taken for the analysis. Current smoking state was recorded as part of computer-assisted personal interview.

Venous blood was collected during fasting state. Blood concentration of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides and glycosylated haemoglobin A1c (HbA1c) was determined.

Each participant’s socioeconomic status (SES) was defined according to the SES index used for the German Health Update 2009 and ranged from 3 to 21 based on education, income and working position.18

Statistical analysis

Medians, IQRs, minimums and maximums were calculated for all primary and secondary continuous variables. For variables distributed normally, means and SD were computed. For dichotomous variables, absolute and relative frequencies were computed.

Stages of myopic maculopathy was categorised according to international photographic classification and grading system by Ohno-Matsui et al6 and grouped into categories: no myopic retinal degenerative lesion (stage 0), fundus tessellations only (stage 1), diffuse chorioretinal atrophy (stage 2), patchy chorioretinal atrophy (stage 3) or macular atrophy (stage 4).5 If several characteristic lesions were present, the highest stage was coded.

Prevalence estimates and 95% CIs were estimated for myopic maculopathy (at least stage 2, or stage 1 with a plus lesion) and for the stages of myopic maculopathy and for the individual macular myopic characteristics in relation to all high myopic eyes with available grading in the GHS. Prevalence was estimated separately for right eyes and left eyes. The overall prevalence of myopic maculopathy was estimated for all phakic participants in the GHS whose refractive error was measured objectively.

To investigate a relationship between myopic maculopathy (at least stage 2, or stage 1 with a plus lesion) and systemic and ocular parameters, we performed multivariable logistic regression analysis with generalised estimating equations including myopic maculopathy as the dependent variable and gender, age, intraocular pressure, spherical equivalent (categorical in 2D steps: ≤−6 D to −8 D, ≤−8 D to −10 D, ≤−10 D to −12 D, ≤−12 D to −14 D, ≤−14 D (equal or more myopic than −14 D)), SES, body mass index (BMI), HbA1c, mean arterial blood pressure, HDL, LDL and triglycerides as independent variables. A sensitivity analysis was carried out including systemic medication for arterial hypertension (ATC code: C02, C03, C07, C08, C09), for dyslipidemia (ATC code: C10) and for diabetes (ATC code: A10).

Statistical analysis was performed using R V.3.5.2.19 All p values should be regarded as continuous parameters that reflect the level of evidence from our explorative analysis and are therefore reported exactly.

Results

Study participants

In the GHS baseline examination of 15 010 participants, 28 140 eyes (14 122 participants) were phakic; 972 phakic eyes of 621 participants presented with a spherical equivalent ≤−6 D and were therefore candidates for this study. The other fellow eyes were either not phakic or not high myopic.

A total of 519 participants (801 eyes; 397 right eyes and 404 left eyes) had refractive error ≤−6 D and gradable fundus photographs. The characteristics of this analysis sample are given in table 1. The distribution of the refractive error (spherical equivalent) for right and left eyes of the study sample are described in online supplementary eFigure 2. Missing grading (photographs of insufficient quality or no photographs) accounted for 16.4% (102/621) of participants who had myopic refractive error of 6 D or worse. These eyes were slightly more myopic and had lower visual acuity (online supplementary eTable 1). Their BMI was higher, but the distribution gender, age and other cardiovascular risk factors was similar to the included participants.

Table 1

Study characteristics of the analysis sample of high myopic eyes (spherical equivalent more myopic or equal −6 D in at least one eye) with grading for myopic maculopathy in the German Gutenberg Health Study (2007–2012)

Prevalence

The prevalence of myopic maculopathy (at least stage 2, or stage 1 with a plus lesion) within the 519 high myopic participants of the GHS was 8.6% (34) (95% CI 6.1% to 11.9%) in the right eyes and 8.7% (35) (95% CI 6.2% to 12.0%) in the left eyes, while no eye in the control sample had myopic maculopathy. The per-person estimated prevalence of myopic maculopathy among high myopic participants was 10.3% (49) (95% CI 7.9 to 13.3), while the overall GHS population of 14 122 phakic persons revealed a prevalence of 0.5% (95% CI 0.4 to 0.6). The myopic maculopathy prevalence increased with the severity of high myopia (figure 1) and with age (figure 2). With respect to the four stages in the META-PM classification system, we found decrease in the prevalence with increase of severity (online supplementary eTable 2); 49.7% (258) of the high myopic participants had stage 1, 7.9% (41) had stage 2, 1.2% (6) had stage 3% and 0.4% (2) had stage 4 in at least one eye. Stratification of prevalence data revealed that stage 3 and 4 were not seen under the age of 45 (online supplementary eTable 3). Cross-tabulation of the stages of myopic maculopathy show high congruence between right and left eyes (online supplementary eTable 4). Visual acuity was remarkably reduced in stage 3 and 4 compared with stage 1 and 2 in right and left eyes (online supplementary eFigure 3).

Figure 1

Prevalence of myopic maculopathy in relation to myopia: data from the Gutenberg Health Study (2007–2012), including n=519 high myopic eyes (right eyes are reported).

Figure 2

Prevalence of myopic maculopathy in relation to age: data from the German Gutenberg Health Study (2007–2012), including n=519 highly myopic eyes (right eyes are reported).

The most common lesion observed as myopic maculopathy according to the international photographic META-PM classification was diffuse atrophy (right eyes: 8.1% (95% CI 5.7% to 11.3%); left eyes: 7.2% (95% CI 4.9% to 10.3%)), followed by lacquer cracks (right eyes: 2.5% (95% CI 1.3% to 4.7%); left eyes: 3.7% (95% CI 2.2% to 6.2%). Prevalence of myopic maculopathy in right and left eyes are summarised in table 2.

Table 2

Prevalence of myopic maculopathy lesions in high myopic eyes (spherical equivalent more myopic or equal −6 D) in the German Gutenberg Health Study (2007–2012)

Association analysis

Multivariable logistic regression analysis revealed that the severity of myopic refractive error and age were associated with myopic maculopathy: per year of age, the OR 1.07 (95% CI 1.03 to 1.11). On the other hand, increased myopic refractive error was associated with myopic maculopathy. The ORs for the different categories of myopic refractive error were 71.9 (≤−14 D), 9.29 (≤−12 D to −14 D), 4.60 (≤−10 D to −12 D) and 0.92 (≤−8 D to −10 D) compared with a myopic error of −6 D to −8 D (table 3). Other systemic factors such as cardiovascular parameters were not associated with myopic maculopathy (table 3). Sensitivity analysis showed that systemic medication for arterial hypertension, dyslipidemia and diabetes was neither associated with myopic maculopathy nor did alter the before reported associations (online supplementary eTable 5).

Table 3

Association analysis of ocular and systemic parameters with myopic maculopathy in high myopic participants (spherical equivalent more myopic or equal −6 D) in the Gutenberg Health Study (2007–2012)

Discussion

This population-based study reports on the prevalence of myopic maculopathy in Germany. Previous reports mostly originated from South East Asia and the USA.8 10 To the best of our knowledge, these are the first population-based data on myopic maculopathy in Europe. Beyond that, we analysed the association between the myopic maculopathy and spherical equivalent, age, gender and cardiovascular parameters.

Based on this population-based study, myopic maculopathy prevalence is about 0.5% (1 in 200 persons) in the German population aged 35–74 years, according to the international photographic META-PM classification. This is similar to data from NHANES reporting a 0.33% prevalence of progressive high (degenerative) myopia among adults aged 18 years and older.8 Within only high myopic participants, which accounted for 4.5% of the GHS study population, the myopic maculopathy prevalence is 10.3%. Our prevalence data are in line with studies from South East Asia and the USA: the frequency of myopic maculopathy in high myopic eyes was estimated 8.3% in young Asian adults (male only), however they were younger (mean age 21 years)10 compared with our cohort being aged 35–74 years.

In contrast, another recent study on high myopic Chinese aged 7–70 years reported clinically significant myopic maculopathy (category 2 or worse) to occur in 23% of their cohort of 890 subjects being recruited from a refraction clinic, a provider of refraction services to a large population. This high proportion is remarkable high as the median age was only 19 years, while the median refractive error was −8.9 D.12 Another large high myopic Asian cohort from Zhongshan Ophthalmic Center including 1841 eyes even reported higher prevalence estimates. The authors describe a distribution of no myopic maculopathy (category 0) in only 3.2%, while they found tessellated fundus (category 1) in 42.3%, diffuse chorioretinal atrophy (category 2) in 28.5%, patchy atrophy (category 3) in 19.1% and macular atrophy (category 4) in 7.0%.20 Nevertheless, both studies do not represent a population-based sample. An even higher rate of myopic maculopathy (72.7%) was found in a small cohort of high myopic elderly Chinese (Shihpai eye study),9 while in an adult myopic cohort of Chinese Americans, 32.2% had myopic maculopathy.21

In China, myopic maculopathy is the second main reason for impaired vision and blindness.22 With increasing category of myopic maculopathy, visual acuity decreased in our study sample. This finding is in accordance with Wong et al reporting visual impairment in category 3 and 4 of myopic maculopathy.23 Equally, diffuse atrophy and tessellated fundus were associated with better visual acuity while lacquer cracks, macular atrophy and choroidal neovascularisation were associated with worse visual in a study with 443 eyes from Chen et al.11 To conclude, in the stage of diffuse atrophy (category 2) visual acuity remains mostly preserved.

We found myopic maculopathy prevalence to be associated with male gender in multivariable analysis, but not in univariate analysis. Recent studies reported that female gender was a component of the risk factors for myopic maculopathy progression in Asian people.24–26

Associations

Increasing myopic refractive error was associated with a higher prevalence of myopic maculopathy in our study, with an OR of 71.9 comparing eyes with a myopic refractive error of −14 D or more compared with −6 D to −8 D. Our results are in line with other studies reporting an increase of myopic maculopathy with higher myopic refractive error in Chinese people (OR 1.57 per diopter) and Chinese Americans.12 20 21 Axial myopia is consistently held responsible for the development of myopic maculopathy.12

However, myopic maculopathy is related to myopic refactive error and an ‘age-related eye disease’ with prevalence rates ranging from 1% in adults (40–50 years) to 3% in older adults (≥70 years).7 This is congruent with our findings, reporting an increase of prevalence with higher age (OR=1.06 per year). Accordingly, Wong et al reported in a Singaporean cohort study that higher age and myopic refractive error was related to myopic maculopathy.23 Although myopic maculopathy occurs more often at older age, even younger age may be affected, however less frequently, as reported by Koh et al in 593 high myopic eyes with a mean age of 21 years.10

On the other hand, Xiao et al reported that children aged 7–11 years showed a significant higher rate (21%) of myopic maculopathy compared with older children aged 12–18 years (11%).12 The greater prevalence of pathology at an early age might reflect the genetic-driven early manifestations and the later cases might be environmentally driven, too. Under East Asian conditions, progression to high myopia of subjects with early onset myopia is high and may pose an additional risk factor for myopic maculopathy. Congruently, the pattern of myopic lesions is reported to be age-specific: younger age was noticed to be associated with lacquer cracks (OR 0.96, 95% CI 0.95 to 0.98, p<0.001) by Chen et al, while diffuse and patchy chorioretinal atrophy, macular atrophy and choroidal neovascularisation were more prevalent in older age (mean age in this study was 40.6±17.1 years and study participants were recruited from patient presenting to the Zhongshan Ophthalmic Center with visual symptoms due to high myopia).11

With respect to the impact of cardiovascular factors on myopic maculopathy, the Shihpai eye study reported an association with high blood pressure.9 Nevertheless, this study only considered 32 elderly Chinese people being affected with myopic maculopathy. In contrast, we could not find an association of arterial blood pressure with myopic maculopathy in the present study, nor with other cardiovascular parameters such as BMI, serum lipids or HbA1c serum level. These findings are in accordance with results from You et al in the Beijing Eye Study.27

Limitations and perspective

The international META-PM consortium has published a photographic classification system of myopic maculopathy in 20156 that is widely used in epidemiological studies10 12 20 23 26 and in genetic evaluation.28 Reliability measures showed sufficient quality with lower values for plus signs in our study, thus we decided to carry out two independent grading of all images. The META-PM was recently under discussion,5 29 as Ruiz-Medrano et al proposed a new classification and grading system for pathologic myopia. Beside the atrophic (A) and neovascular (N) components of pathological myopia, they introduce the aspect of traction (T), which is mainly detectable by advanced imaging modalities such as optical coherence tomography (OCT).29 As we did not perform OCT imaging, we cannot state on this classification system, nor on choroidal thickness which correlates negatively with myopic maculopathy.10 Furthermore, axial length was not measured, we therefore relied on refractive error instead and excluded eyes with prior cataract surgery. We did not perform a weighting procedure for age and sex to achieve strictly population-representative estimates due to low numbers in some strata. Overestimation of high myopia without cycloplegia is unlikely because effects of pharmacological cycloplegia on refractive error in myopic adults are minor.16 The non-responder analysis revealed that only visual acuity was relevantly lower in the non-responder participants indicating that our results represent rather conservative estimates of myopic maculopathy. Several studies reported contrary results on the impact of dietary factors or biochemical blood measurements on axial length25 30 and occurrence of myopic maculopathy,27 respectively. Unfortunately, our data do not allow to further discuss this aspect.

In summary, the prevalence of myopic maculopathy was 0.5% in the total phakic German population at age 35–74 years and 10.3% in high myopic people. Myopic maculopathy was associated with higher myopic refractive error, with older age, and with male gender, but not with cardiovascular parameters. To the best of our knowledge, these are the first population-based data on myopic maculopathy in Europe.

References

Footnotes

  • Contributors SH, SN, NP and AKS conceived and designed the study. SH, SN, CK, AS, IS and AKS analysed and interpreted the data. SH, SN and AKS wrote the paper. TM, PSW, MM and KJL made substantial contributions to the study design. All authors revised the manuscript critically and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The Gutenberg Health Study was approved by the Medical Ethical Committee of the State Chamber of Medicine of Rhineland Palatinate in Mainz, Germany.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.