A myopia boom1 has affected populations worldwide as the prevalence rates of myopia and high myopia in many countries continue to rise, especially among Asian countries.2 Most individuals develop myopia during childhood.3 An earlier onset of myopia is associated with higher degrees of myopia later in life.4,5 Myopia is the main cause of correctable visual impairment (VI) in both children and adults. The common methods used to correct myopic vision include spectacles, contact lenses, or surgical procedures. The prevalence of myopia among middle-aged and elderly adults ranges from 16.4% to 26.6% in Western populations6,7 and 19.4% to 48.1% in Asian populations.8–18 In contrast, the prevalence of high myopia among middle-aged and elderly adults is approximately 1.6% to 4.6% in Western populations6,7 and 0.8% to 9.1% in Asian populations.8–18 The definition of high myopia varies among studies and is mostly defined as spherical equivalent (SE) of less than −5.00 or −6.00 diopters (D). The prevalence rates of myopia and high myopia are generally higher in Asian countries. There is a myopia epidemic in Asia; thus, this review will have a particular focus on Asian populations.
High myopia is linked to pathologic myopia (PM). As the severity of myopia increases, excessive axial elongation of the globe exerts a biomechanical stretch on the posterior pole. This induces pathological changes of the eye, for instance, posterior staphyloma, optic disc changes, and myopic macular degeneration (MMD).19 Signs of MMD include chorioretinal atrophy (diffuse, patchy, or macular), lacquer cracks, choroidal neovascularization (CNV), Fuchs spot, and tessellated fundus.20 Studies have used varying definitions of PM lesions.21,22 There were 2 previous definitions by Avila et al23 and Curtin,24 followed by a recent META-PM classification by Ohno-Matsui et al25 in 2015. Myopic macular degeneration is graded according to severity: no myopic retinal degenerative lesion (category 0); tessellated fundus only (category 1); diffuse chorioretinal atrophy (category 2); patchy chorioretinal atrophy (category 3); and macular atrophy (category 4). Plus lesions supplement the META-PM categories, which comprise lacquer cracks, CNV, and Fuchs spot. Based on this classification, an eye is considered to have PM if category 2, 3, or 4 is observed.
In contrast to myopia, the VI caused by PM is not correctable and may lead to irreversible vision loss; thus, the assessment of the prevalence of blindness or VI attributable to PM is important. A meta-analysis22 on cross-sectional studies in Asian and Western populations reported the prevalence of PM and the associated VI. The prevalence of PM was reported to be 0.9% to 3.1%, and the prevalence rates of VI due to PM were 0.1% to 0.5% and 0.2% to 1.4% in European and Asian populations, respectively. The permanent loss of visual acuity due to PM is associated with poorer visual functioning26,27 and lower quality of life.26–28 In addition, PM tends to strike individuals in their productive years, resulting in a higher economic burden for PM than other eye diseases.2,29,30 Furthermore, treatment, eye care, and socioeconomic costs due to PM pose a large burden on individuals, caregivers, and societies.31,32
This review will highlight updates on the prevalence of PM and the associated VI from PM in Asia and around the world.
SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES
A comprehensive search was performed to identify all relevant epidemiological studies on PM. Databases (PubMed and Scopus) were searched (1980 to 2016) to identify English-language articles on studies reporting on PM. The search terms included pathologic myopia, pathological myopia, progressive myopia, malignant myopia, degenerative myopia, myopic degeneration, myopic retinal disorders, myopic retinopathy, myopic maculopathy, and myopic macular degeneration. Filters were used to identify articles that examined the epidemiology, prevalence, and associated VI due to PM. The reference lists of existing reviews and retrieved articles were also reviewed. The articles were identified and screened by a single researcher (W.Y.L.) and checked by a second researcher (S.S.M.).
The population-based studies reflect the true picture of the prevalence of PM in the population, whereas the findings from the clinic-based studies are subject to selection bias because the study sample consists of patients from clinics or hospitals. The cross-sectional studies report the prevalence of PM in each study population, whereas the longitudinal studies show the progression and development of new PM lesions over a period of several years.
PREVALENCE OF HIGH MYOPIA IN YOUNG ADULTS
Many reviews have described the prevalence of high myopia in Asian and non-Asian populations.2,5,33,34 The definition of high myopia varies across countries, with SE levels of either less than −5.00 or −6.00 D in the right or worse eye. The reviews summarized data in middle-aged and elderly adults (40 years or older). The majority of the studies on high myopia in young adults were found to be conscript-based (Table 1). In Korea, 21.6%35 and 6.8%36 of male conscripts aged 19 years in urban (N = 23,616) and rural (N = 2805) populations, respectively, had high myopia, whereas 14.7%37 of Singaporean male conscripts aged 17 to 29 years (N = 28,908) had high myopia. The prevalence of high myopia among the conscript-based studies in Asia is significantly higher than in the non-Asian ones. In a conscript-based study conducted in Israel, the average prevalence of high myopia from 1990 to 2002 (N = 991,929) among conscripts aged 16 to 22 years was 2.0% in men and 2.3% in women.38 Considering participation rates of almost 100%, the prevalence rates of high myopia reported offer appropriate population-level estimates because the sampling is representative of these young adult populations. However, women were not investigated in the Asian conscript-based studies, thus limiting the generalizability of these findings to the young adult population. The use of noncycloplegic autorefraction in the conscript-based studies conducted in Singapore37 and Iran38 may have led to overestimations of the prevalence of high myopia. It must be noted that different refractive measurement methods, sampling frames, and response rates among epidemiological studies create inconsistency and difficulty in comparison of results.
There is an alarming prevalence of high myopia among young adults. As these young adults grow older and do not recover from myopia, there will be high prevalence rates of high myopia among the older adult population in the next few decades.21 The prevalence of high myopia is projected to increase from approximately 3% to 10% in 2050. This is a cause for concern because VI and blinding complications associated with high myopia may potentially develop in more than 1 billion individuals worldwide by 2050.34 Therefore, acquiring more data on PM in the younger populations is necessary, especially when the onset of PM may occur early30,39 in the individuals’ productive years.
PREVALENCE OF PATHOLOGIC MYOPIA IN POPULATION-BASED STUDIES
The only 2 population-based studies on PM among adolescents and children were found to be in Asian populations (Table 2). In these young populations, the definition of PM used by both studies in Western China40 and Singapore41 placed greater emphasis on optic disc abnormalities and peripapillary atrophy. Among young Chinese adolescents and children aged 6 to 15 years in Western China (N = 3079), the prevalence of PM was 0.19%, and the prevalence of high myopia was not reported.40 Potential selection bias may exist because children from orphanages and schools for the blind were not included. In contrast, the prevalence of PM among Singaporean adolescents aged 12 to 16 years (N = 1227) was comparable at 0.16%, and the prevalence of high myopia was 7.3%.41 The low prevalence of sight-threatening myopic complications observed in these young individuals suggests that the advanced pathological changes may occur when they are older. Therefore, the prolonged mechanical stress from excessive stretching of the globe and/or aging affects pathological progression.42 In addition, it has been postulated that the presence of peripapillary diffuse chorioretinal atrophy in highly myopic children may be a marker for the occurrence of myopic chorioretinal atrophy at an older age.43
Population-based studies conducted among adults in Australia,44 Handan,13 and Beijing45 defined myopic retinopathy as the degeneration of chorioretinal tissues, with at least 1 of the following lesions: staphyloma, lacquer cracks, Fuchs spot, or myopic chorioretinal atrophy. The classification of staphyloma type was adopted from Curtin’s definition.24 The Blue Mountains Eye Study in Australia reported 2.7% and 1.2% of individuals aged 49 years or older (N = 3583)44 to have high myopia and myopic retinopathy, respectively. Two other studies in China used the same definition of myopic retinopathy. Compared with the Australians, Chinese adults in the Handan Eye Study (30 years or older, N = 6603) had slightly lower prevalence rates of high myopia and myopic retinopathy at 2.1% and 0.9%, respectively.13 In contrast, the adults aged 40 years or older (N = 4319) in the Beijing Eye Study had the highest prevalence of myopic retinopathy of 3.1% among the 3 studies.45 It must be noted that the Chinese participants13,45 were younger than the Australian participants.44 Adoption of the same definition of PM by these 3 studies allows comparability of the findings from each study and reveals potential risk factors for PM. The common risk factors identified were greater myopic refractive error and longer axial length. Other risk factors of PM include age,13,45 larger optic disc,45 and family history of myopia.13
The Hisayama study46 adopted a slightly different definition from the previous 3 studies because staphyloma was not considered in the definition of PM. Among the Japanese population aged 40 years or older, 5.7% and 1.7% had high myopia and myopic maculopathy, respectively.46 In contrast, the Shihpai Eye Study47 used definitions by Avila et al,23 which did not consider staphyloma as well. In the Shihpai Eye Study,47 4.2% and 3.0% of Taiwanese elderly aged 65 years or older had high myopia and myopic retinopathy, respectively. Because these Taiwanese participants were significantly older, comparisons with other population-based studies may be limited. The reported prevalence rates may not be representative of the populations in Japan and Taiwan, owing to the low response rates of 44.4% and 66.6%, respectively.
Two population-based studies were conducted among high myopes in Singapore. A cross-sectional study conducted among Singaporean adults aged 40 years or older (N = 332) used definitions by Avila et al.23 It was found that 19.3% and 23.0% of them had chorioretinal atrophy and posterior staphyloma, respectively.48 The presence of media opacities in this group of middle-aged and elderly participants is likely to hinder the detection of both chorioretinal atrophy and posterior staphyloma. Another cross-sectional study conducted among highly myopic young conscripts aged 19 to 25 years (N = 593) in Singapore adopted the recent META-PM MMD classification.25 The results showed that 8.3% and 32.0% of them had chorioretinal atrophy and posterior staphyloma, respectively.30 In addition to fundus photography, the detection of posterior staphyloma was supplemented with spectral domain optical coherence tomography, thus preventing the underestimation of posterior staphylomas with identification of subtle cases.
In brief, the prevalence of PM among adolescents and children is less than 0.2%, whereas the prevalence of PM among the middle-aged and elderly adult population is approximately 0.9% to 3.1% in Asian populations and 1.2% in non-Asian populations. Although the current prevalence of PM worldwide seems to be low, increased rates of PM in the near future will be no surprising matter, given the projected rise in rates of myopia and high myopia.34 In addition, the outcome of the generational effect is becoming evident because the prevalence of PM is 8.3% among young adults with high myopia in Singapore.30
PREVALENCE OF PM IN CLINIC-BASED STUDIES
Because current literature on PM in population-based studies is limited, clinic-based studies are summarized in Table 2. A prospective case series study in a high myopia clinic in Japan recruited patients aged 12 to 89 years with high myopia (N = 272).49 Among 488 myopic eyes, 31.6% had myopic chorioretinal atrophy, indicating a strong association between high myopia and PM. However, subanalysis on the young adults group was not performed. Another cross-sectional study among children aged 1 to 8 years (N = 46) visiting a high myopia clinic in Japan was conducted. Eighty eyes with high myopia were reported, of which 16.3% had mild chorioretinal atrophy.42 This is of clinical significance, especially in the younger generation, because continuously increasing axial length with age50 is likely to lead to the development of more advanced myopia-related lesions in the eyes of patients with PM.
LONGITUDINAL CHANGES IN PM
Longitudinal changes in PM were reported in 2 studies44,45 (Table 3). The progression of PM in participants in the Beijing Eye Study45 included the development and expansion of chorioretinal atrophy, enlargement of beta peripapillary atrophy, and growth of lacquer cracks, similar to the Blue Mountains Eye Study.44 For the urban Australian population, 67 eyes had PM at baseline, of which 17.4% (8 eyes) were detected to have progression of myopic retinopathic lesions because enlargement of the beta peripapillary atrophy and development of new chorioretinal atrophy were observed. During the long follow-up period of 5 years in both studies, there was a loss to follow-up of more than 30%. In addition, the development and expansion of advanced myopic lesions are associated with decreased best-corrected visual acuity (BCVA),44,45 thus resulting in deteriorating vision health for individuals with PM.
A retrospective case series study (N = 29) in a Japanese high myopia clinic included children and adolescents aged 15 years or younger with a follow-up period of 20 years or more.43 At the last visit, 35 eyes had PM, of which 55%, 5%, and 2% had diffuse, patchy, or macular chorioretinal atrophy, respectively. Of these 35 eyes, 29 eyes already had diffuse chorioretinal atrophy during childhood or adolescence. This suggests that high myopia and early grades of PM among young individuals can worsen and progress to advanced myopic lesions at a later age. It can be postulated that the longitudinal changes in PM depend on the age of onset of PM because the axial length of eyes with PM continue to increase with age.50 Eyes with an earlier age of onset of PM are likely to develop more advanced PM lesions.43 Although the presence of tessellated fundus has little clinical significance on visual outcomes, it can be an early marker of choroidal thinning leading to PM.51 Another risk factor for the progression of PM includes having higher myopic refractive errors.43
PREVALENCE OF BLINDNESS OR LOW VISION ATTRIBUTED TO PM
Several population-based studies have reported the prevalence of blindness or low vision attributed to PM (Table 4). A majority of the studies have adopted the World Health Organization definition of blindness (BCVA of <20/400 in the better eye) and low vision (BCVA between 20/60 and 20/400 in the better eye), whereas only 1 study used the less stringent US definition of blindness (BCVA of <20/200 in the better eye) and low vision (BCVA between 20/40 and 20/200 in the better eye).
The Beijing Eye Study consisted of Chinese residents aged 40 years or older, of which PM was the cause of blindness in 7.7% (1 of 13 individuals) and of low vision in 32.7% of individuals (16 of 49 individuals).52 Pathologic myopia was ranked as the third and second causes of blindness and low vision, respectively. In the Tajimi Study, 22.4% (11 of 49 eyes) and 9.2% (7 of 76 eyes) of Japanese residents aged 40 years or older had blindness and low vision due to PM, respectively.53 In this Japanese population, PM was the leading cause of blindness and the third leading cause of low vision.
In contrast, in the Rotterdam Study, PM was the cause of blindness in 6.3% (4 of 64 eyes) and of low vision in 5.7% of eyes (11 of 192 eyes) and was ranked third for both causes among Europeans aged 55 years or older.54 This European population consisted of a greater proportion of older adults compared with the other studies52,53 comprising younger individuals aged 40 years or older. In the Copenhagen City Eye Study, 14.2% (4 of 28 individuals) and 7.7% (8 of 103 individuals) of adults aged 20 to 84 years had blindness and low vision attributed to PM, respectively.55 Pathologic myopia was ranked third as a cause of blindness and fourth as a cause of low vision. However, this study did not report the World Health Organization definition and used the US definition only. The Los Angeles Latino Eye Study conducted among Latin American residents aged 40 years older reported PM as the cause of blindness in 11.6% (5 of 43 eyes) and of low vision in 1.1% of eyes (1 of 91 eyes) and was ranked third and ninth, respectively.56 However, the observed number of cases having blindness and low vision attributed to PM was small. For all reports on the prevalence of VI attributed to PM, the methods and definitions of PM are not identical among the studies; thus, direct comparisons are cautioned. Nevertheless, the vision-threatening impact of PM is demonstrated in epidemiological studies worldwide.
Pathologic myopia is an important cause of blindness in most of the population-based studies, and the prevalence of blindness or low vision attributed to PM is higher among Asian countries compared with Western and European countries. In addition, PM is ranked as a more important cause of low vision in Asian populations (second to third) compared with Western and European populations (third to ninth). The detrimental effect on vision due to PM seems to be worse in Asian populations and is often underestimated because fundus photographs may not have been graded for PM. Therefore, further investigations are required.
There is a myopic epidemic, especially in Asia, because 8 of 10 young adults in Asian populations have myopia.35–37 In addition, the prevalence of high myopia in young adults is higher among Asian populations (6.7% to 21.6%) compared with non-Asian ones (2.0% to 2.3%). As these young adults grow older, the prevalence of high myopia among older adults in the next few decades will be high. The high prevalence rates of high myopia will consequently lead to elevated prevalence rates of PM in the future.
Recently, a relatively high prevalence of PM of 8% among highly myopic young Singaporean adults aged 19 to 25 years was reported.30 In addition, early grades of PM lesions among young individuals can worsen and progress to advanced PM lesions as they grow older.43 However, more data on the prevalence and progression of PM in young adults are needed. Studies on PM among middle-aged and elderly adults demonstrated a relatively low prevalence of PM among populations worldwide13,44–47 because the prevalence of PM is approximately 0.9% to 3.1% in Asian populations and 1.2% in non-Asian populations. The PM lesions detected among older adults include the more advanced lesions, such as chorioretinal atrophy, lacquer cracks, Fuchs spot, and posterior staphyloma. Diffuse chorioretinal atrophy and posterior staphyloma are the more common PM lesions among adults with PM. In contrast, the prevalence of PM is low at less than 0.2% among children and adolescents. Advanced PM lesions are not seen in young individuals. Instead, both beta peripapillary atrophy and optic disc abnormalities, which are not included in the definition of PM, are the more common lesions found among young individuals.
Two studies44,45 examined the longitudinal changes in PM lesions. The enlargement of beta peripapillary atrophy occurred most frequently, followed by the development and expansion of chorioretinal atrophy, and the growth of lacquer cracks occurred less frequently. The longitudinal changes in PM are still lacking; thus, causal inferences of PM and potential risk factors cannot be established.
Pathologic myopia is one of the leading causes of blindness among populations, implying a potential global health issue, especially in Asian populations. The prevalence of VI attributed to PM seems to be higher among Asian populations compared with Western and European populations. Pathologic myopia is ranked as a more important cause of low vision (second to third) in Asian populations compared with Western and European populations (third to ninth). There are no data on the prevalence of VI attributed to PM among younger individuals because studies have focused on older adults.
Because the onset of PM is earlier than other ocular diseases, it is crucial to determine the detrimental impact due to PM on vision and quality of life among individuals with PM. As individuals experiencing PM do not recover, vision loss is irreversible. With the lack of effective treatments strategies against PM,22 there is an urgent need to push for the prevention of myopia onset and myopia progression to mitigate this future blinding epidemic. Constant monitoring and reporting of the changing myopia prevalence rates are necessary to complement and support existing myopia control programs.29
The authors thank Ms Serene Ong from Duke-NUS Medical School for her contributions in checking the manuscript.
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