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. 2023 Oct 19;38(4):745–751. doi: 10.1038/s41433-023-02767-7

Incidence and prevalence of keratoconus in Taiwan during 2000–2018 and their association with the use of corneal topography and tomography

Jack Min Ng 1, Ken-Kuo Lin 1,2, Jiahn-Shing Lee 1,2, Wei-Min Chen 3, Chiun-Ho Hou 1,2,4,5, Lai-Chu See 3,6,7,✉
PMCID: PMC10920627  PMID: 37857718

Abstract

Purpose

The aim of this study was to determine the age- and sex-specific incidence and prevalence of keratoconus (KC) in Taiwan and explore their association with the use of computerized corneal topography and tomography (TG).

Design

This nationwide retrospective study included the Taiwanese population (N = 27,540,859) from the National Health Insurance Research Database (NHIRD) between 2000 and 2018.

Method

We estimated the incidence of KC by identifying patients with newly diagnosed KC and estimated its prevalence by identifying patients who had the ICD9-CM code 371.6 or ICD-10-CM code H18.609 twice or more in NHIRD during 2000–2018.

Results

The incidence of KC in Taiwan during 2000–2018 was 7075, with the incidence rate being 1.56 (95% confidence interval [CI]: 1.53–1.60) per 100,000 person-years. The prevalence of KC was 4.29 (95% CI: 4.23–4.35) per 100,000 person-years. The KC incidence rate peaked in patients aged 21–25 (6.40 in males and 3.19 in females). The overall incidence rates in males and females were 2.01 and 1.35, respectively (incidence rate ratio: 1.46), indicating that KC had a significant male predisposition. Moreover, we noted a linear correlation (R2 = 0.7488) between the proportion of the use of TG and the incidence of KC.

Conclusion

Estimates of nationwide population-based incidence and prevalence can contribute to a better understanding of the risk of ethnic groups and geographic locations in KC, and the trend can help physicians improve the general vision health of the population.

Subject terms: Corneal diseases, Epidemiology

Introduction

Keratoconus (KC) is a bilateral and asymmetric condition of progressive thinning and ectasia of the cornea, leading to irregular astigmatism and decreased visual acuity. Traditionally, KC has been described as noninflammatory, but increasing evidence supports that KC is related to the degradation of an extracellular matrix involving inflammatory events [1]. Although the exact causes and underlying pathogenesis of KC are still unknown, environmental and genetic factors are generally recognized to contribute to the development of the disease [2]. Recognized environmental factors include chronic eye rubbing, allergic eye disease, UV ray exposure, and different geographical locations [3]. KC is typically manifested at puberty and progresses until the third or fourth decade of life [4]. Furthermore, KC can affect both sexes, but the difference in incidence and prevalence between the sexes is still highly inconsistent [5].

KC can be diagnosed based on clinical signs [6], slit lamp examination, pachymetry, and keratometry, but it can be challenging during its early stages. Corneal imaging, such as computerized corneal topography and tomography (TG), could identify corneal ectasia much earlier. While corneal topography characterizes the shape of the anterior surface of the cornea, tomography provides a detailed analysis of the shape of anterior and posterior corneal surfaces, as well as the thickness of the cornea [7]. TG indications include the diagnosis of corneal ectasia, management and observation of astigmatism, and assessment for refractive surgery. In Taiwan, corneal topography has been the primary diagnostic method for KC since the mid-1980s. Later on, corneal tomography became more popular among ophthalmologists partly because it is more readily available and with more metrics and partly because our understanding of tomography and its metrics has increased.

The KC incidence and prevalence reported in the literature are highly inconsistent [8].

This inconsistency may be due to differences in assessment methods, diagnostic criteria, sample sources, ethnicity, or genetic susceptibility. Socioeconomic considerations also affect patients receiving a consultation diagnosis or delaying the assessment, resulting in variations of KC incidence and prevalence among different countries. Differences in KC incidence and onset age among ethnic populations living in different locations strongly suggest that geographical distribution and genetic susceptibility in different ethnic groups play a major role in the pathogenesis of the disease [2, 3, 9].

The incidence estimated by hospital-based studies usually does not represent the incidence in the general population. Several studies [10–12] have used nationwide population-based data to investigate the association of KC incidence and prevalence with age, sex, and ethnicity. For example, a study in the Netherlands [11] included only individuals aged between 10 and 40 years, which could have affected the overall incidence and prevalence estimates. Another study in the United States [10] adopted a nationwide matched case–control design and discovered that Asian Americans had lower odds of KC than Caucasians, which contradicts the consensus of a Delphi panel [13]. Detailed longitudinal data demonstrating the trends of KC incidence and prevalence in a nationwide population are scant in the literature.

To fill the aforementioned research gap, this population-based study estimated the incidence and prevalence of KC and their trends from 2000 to 2018 in the entire population of Taiwan. The study also explored the association of KC incidence and prevalence with use of TG in diagnosis on a nationwide scale.

Materials and methods

Data source

Taiwan’s National Health Insurance (NHI) program was established in 1995 and is mandatory for all citizens. At the end of 2018, the NHI program covered more than 99% of the total population of Taiwan [14]. The National Health Insurance Research Database contains registration information and data on original claims for reimbursement, including comprehensive demographic information; clinical visit dates; medical diagnoses; medical expenditures; and prescription, examination, and procedure details. To ensure confidentiality, unique personal identification information is encrypted before the release of the data to researchers. Nevertheless, the identification remains unique for each beneficiary in the database to facilitate the internal cross-referencing of records. This study obtained approval from the Institutional Review Board of the Chang Gung Medical Foundation (protocol no. 20160177B0). The need for patient informed consent was waived because all data were anonymous and de-identified.

Ascertainment of KC

This nationwide retrospective study identified patients who received the International Classification of Diseases, Ninth Revision, Clinical Modification code 371.6 or International Classification of Diseases, Tenth Revision, Clinical Modification code H18.609 for KC twice or more from 2000 to 2018 to reduce false positives. We excluded patients who had never visited eye clinics or had received a corneal transplant before KC diagnosis (Fig. 1). The order code of corneal imaging for KC in Taiwan NHI was “23004B” and does not differentiate between corneal topography and tomography (TG).

Fig. 1. Subjects enrollment.

Fig. 1

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The flowchart illustrates the identification of patients with keratoconus (KC) from 2000 to 2018 in the National Health Insurance Research Database (NHIRD) for this study.

Statistical analysis of incidence rate and prevalence rate

The incidence of KC was computed as the number of new KC cases between 2000 and 2018 divided by the corresponding person-years. The prevalence of KC was calculated as the number of all new and pre-existing KC cases between 2000 and 2018 divided by population size. The 95% confidence intervals (CIs) corresponding to the calculated incidence and prevalence were derived under the assumption of a Poisson distribution. Direct age standardization was performed using the new World Health Organization Standard Population to study the KC incidence and prevalence time trends [15].

Results

Incidence of KC

From 2000 to 2018, 7075 new KC cases emerged, with the corresponding incidence rate being 1.56 per 100,000 person-years (95% CI = 1.53–1.60). The proportion of new KC cases was higher in male patients (4208, 59.5%) than in female patients (2867, 40.5%). Therefore, the KC incidence rate (per 100,000 person-years) was 2.01 for males and 1.35 for females. The overall male-to-female incidence rate ratio was 1.46. The age-specific pattern of the KC incidence rate was similar in both sexes. The incidence rate was minimal in young children (0–4 years old) but started to rise and peaked in ages 20–24, eventually declining. Among those aged 20–24, the KC incidence rate (per 100,000 person-years) was 6.40 for males and 3.19 for females (Fig. 2A).

Fig. 2. The age-specific rate of keratoconus (KC) from 2000–2018, Taiwan.

Fig. 2

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A The incidence rate. B The prevalence rate.

The KC annual incidence rate increased over time; specifically, it increased by 1.68-fold from 1.45 in 2000 to 2.44 in 2018 in males and 1.25-fold from 1.11 in 2000 to 1.39 in 2018 in females (Fig. 3A). In 2000, the age-standardized incidence rate of KC was 1.40 (95% CI = 1.19–1.61) in males and 1.06 (95% CI = 0.87–1.25) in females. The age-standardized incidence rate of KC was 3.08 (95% CI = 2.77–3.39) in males and 1.69 (95% CI = 1.46–1.92) in females in 2018 (Fig. 3B).

Fig. 3. The time trend of keratoconus (KC) incidence rate from 2000–2018, Taiwan.

Fig. 3

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A The unstandardized incidence rate. B age-standardized incidence rate using the World Health Organization’s (WHO) new World Standard Population as a standard population.

Prevalence of KC

A total of 19,431 patients were diagnosed as having KC during the 19-year study period, equivalent to 4.29 cases per 100,000 person-years (95% CI = 4.23–4.35). Of these patients, 11,737 (60.4%) were male, and 7694 (39.6%) were female. The prevalence rate (per 100,000 person-years) was 5.17 in males and 3.41 in females, and the overall male-to-female prevalence ratio was 1.52. The KC prevalence rate was very low in the young and peaked in those aged 20–24 years (16.81 for males) and 25–29 years (8.05 for females), eventually declining subsequently (Fig. 2B).

We observed a gradual increase in prevalence between 2000 and 2018 (Fig. 4A). The prevalence of KC in 2018 was 10.38 in males and 6.06 in females. In 2000, the age-standardized prevalence rate of KC was 1.40 (95% CI = 1.19–1.61) in males and 1.06 (95% CI = 0.87–1.25) in females. Prospectively, in 2018, the age-standardized prevalence rate of KC was 11.9 (95% CI = 11.3–12.5) in males and 6.93 (95% CI = 6.46–7.40) in females (Fig. 4B).

Fig. 4. The time trend of keratoconus (KC) prevalence rate from 2000–2018, Taiwan.

Fig. 4

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A The unstandardized prevalence rate. B age-standardized prevalence rate using the World Health Organization’s (WHO) new World Standard Population as a standard population.

Corneal topography and tomography use

Between 2000 and 2007, approximately 200 annual KC cases were diagnosed using TG. Specifically, 62.8–67.1% of KC cases were diagnosed after TG. From 2008, we noted a gradual increase in the proportion of annual KC cases (67.96–81.47%) diagnosed or managed using TG. The incidence rate of KC was highly linear with the proportion of TG use (R2 = 0.7488) (Fig. 5).

Fig. 5. Correlation between keratoconus (KC) rate and use of corneal topography and tomography (TG) from 2000–2018, Taiwan.

Fig. 5

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The scatter plot illustrates the high linear relationship between the KC incidence rate and the proportion of diagnostic use of TG, and the R-square is 74.8%.

Of the 7075 new KC cases between 2000 and 2018, 5539 (78.3%) were analyzed using TG at least once. Of these 5539 cases, 2163 (39.1%) were analyzed using TG only once, and the remaining (61.9%) were analyzed using TG twice or more, most possibly for follow-up that may contribute to the effective management of this disease. In terms of sequential distribution, of the 5539 cases, 682 (12.3%) had TG arranged before the confirmation of KC diagnosis, 2289 (52.2%) had TG performed during the time of diagnosis, and 1968 (35.5%) had TG performed 1 year or more after the confirmation of KC diagnosis. Of the 682 cases examined using TG before diagnosis, 311 (45.6%) were still analyzed through TG for disease follow-up.

Discussion

In Taiwan, the incidence rate of KC was approximately 1.6 per 100,000 person-years, and the prevalence was nearly 4.3 cases per 100,000 person-years. The peak incidence age was 16–30 years. We also observed that KC had a notable male predisposition. The incidence increased 0.5-fold from 2000 to 2018. We also noted a positive correlation between the incidence rate of KC and the proportion of TG used for KC diagnosis.

KC incidence and prevalence

Our results reveal lower KC incidence and prevalence rates in Taiwan than those reported by other nationwide cohort studies conducted in South Korea [12] in 2018 and the Netherlands [11] in 2017. Our results demonstrate that the incidence ranged from 1.5 to 5.5 per 100,000 person-years in all age groups and from 4 to 13 per 100,000 person-years in the age group 21–25 years old was associated with a high incidence. Epidemiological studies, including those based on hospitals or small populations, have indicated a significant global variation in KC incidence and prevalence, the rates of which have been estimated to be 1.5–25 and 0.2–4790 per 100,000 person-years, respectively [3]. In addition to sampling designs, the different criteria and modalities used to calculate the incidence and prevalence of KC in various studies could hinder fair comparisons between studies on KC [16]. Different studies have used various methods to diagnose KC, including keratometry with retinoscopy [9, 17], without retinoscopy [18], [19–21], which could cause wide variations in KC incidence and prevalence rates [22].

Age

KC is typically manifested at puberty and progresses until the third or fourth decade of life [4]. Our study and the study conducted in South Korea [12] revealed that the highest KC incidence was in aged 20–30. In the study conducted in the Netherlands [11], the mean age at diagnosis was 28 years in the population between 10 and 40 years old. This could be why studies [23] focusing on young populations tended to yield higher KC incidence rates. However, we should keep in mind that many eye-related disorders increase with age [24], such as cataracts, open-angle glaucoma, and early AMD, and two-thirds of persons with late AMD. TG is not a mandatory clinical examination. Hence, without the corresponding use of TG to diagnose KC in the presence of other ocularocular diseases, KC in older patients may not be accurately detected and thus remain undiagnosed.

Sex

Similar to other studies [9, 18, 23, 25, 26], our study revealed that KC had a male predominance; however, the study conducted in South Korea [12] did not suggest a sex predisposition. Because eye rubbing is a known risk factor for KC, a study conducted in the United Kingdom [26] reported that male patients with an earlier KC diagnosis tended to rub their eyes more frequently than female patients, thus leading to a male KC predominance. However, a regional study conducted in central rural India [27] has reported a higher KC incidence and prevalence in females. Hormonal regulation has been proposed as a risk factor for KC because it was correlated with puberty [28] and pregnancy [29]. Accordingly, additional nationwide population-based studies should be conducted to elucidate the sex predisposition for KC.

Ethnic and geographical variation

Previous studies have extensively suggested that the prevalence and incidence of KC were higher in Asians than in Caucasians [9, 18, 21]. By contrast, the nationwide study conducted in the United States [10] reported that Asians have a lower chance of developing KC than Caucasians. Similarly, the KC incidence and prevalence reported in the Netherlands [11] considerably exceed those observed in our study and the South Korean study [12], including populations within similar age groups. Not all Asians are ethnically similar and are predisposed to a similar risk for KC. A Singaporean study [30] revealed that steep corneas, related to an increased risk of KC, were more commonly associated with Indians than with Malays or Chinese. Apart from ethnic differences, differences in geographical locations, latitudinal range, and ultraviolet exposure [2] may explain why the KC incidence and prevalence rates are higher in populations in the Middle East and Indian subcontinents than in Caucasian and East Asian populations [22]. In our study, most Taiwanese are of Han descent, which makes understanding different ethnic groups challenging.

Time trend

Our study indicated a significant increase in the KC incidence rate between 2000 and 2018, even after age standardization. The longitudinal increase in KC incidence could be related to increased risk factors for KC, such as eye rubbing, among young people [3]. The increase in atopy and immunologic diseases in recent years [31] has engendered an increase in chronic eye inflammation and ocular allergy in Taiwan [32], possibly leading to higher rates of KC. TG in Taiwan, especially tomography, may partially explain the increasing KC incidence and prevalence trends. However, we did not know whether most cases of KC were clinically diagnosed using TG or whether the use of TG in ophthalmic/optometric clinics was increasing.

Corneal Topography and Tomography use

In Taiwan, corneal topography has been the primary diagnostic method for KC since the mid-1980s and corneal tomography began to grow in popularity among ophthalmologists as time progressed. This study revealed that the increased KC incidence in Taiwan was associated with increased use of TG, particularly since 2008. A review of KC published in 2022 [4] reported that with the current widespread use of TG and built-in state-of-the-art software, eye care practitioners could identify corneal ectasia at a much earlier stage than previously possible, which additionally explains the higher incidence rates of KC reported in recent studies.

Limitations

This study has several limitations that should be addressed in future research. First, young people may show higher rates of KC, but this may be biased because there are likely fewer conditions to assess and/or a lower likelihood of confusion with other causes of vision loss. Older patients with stable disease may not prompt a TG assessment because of other degenerative ocular disorders and therefore may be undiagnosed, thus contributing to lower incidence and prevalence rates. Second, the NHI data could be miscoded. Nevertheless, the Taiwan National Health Insurance Administration frequently reviews the consistency between claims data and medical charts, and the accuracy of diagnostic coding was reported to range from moderate to high [33]. Third, the diagnostic criteria of TG for KC vary based on the individual clinician or examiner. Although several criteria of TG in diagnosing KC [34] are available, ophthalmologists often face cases that cannot be categorized entirely as KC or normal corneal conditions. Therefore, intrinsic and extrinsic errors during acquisition and data handling could cause misdiagnosis [35]. Subclinical and forme fruste KC cases that require sensitive methods for proper diagnosis might also be unintentionally excluded from our study, resulting in underestimation. Finally, we did not know which specific corneal imaging method (topography or tomography) was used in this study because both diagnostic methods fall under the same examination code in NHI.

Conclusion

Our nationwide population-based study revealed that the incidence of KC in Taiwan was lower than those reported by studies conducted in South Korea and the Netherlands. Our findings are consistent with those of the US study that reported that the incidence of KC is lower in Asians than in Caucasians. The incidence of KC was noted to peak in the early to mid-20s for both sexes, but the overall incidence and prevalence of KC exhibited a male predisposition. Moreover, we noted a significant increase in the incidence of KC annually during this study period, and this is associated with the increase in the rate of TG application for KC diagnosis.

Further and deeper investigation can lead to more clarifying evidence about the epidemiology of KC. We hope that the findings of this study can help elucidate the incidence and prevalence rates of KC among different populations and serve as a reference for the estimation of disease burden for formulating policies targeting KC.

Summary

What was known before

  • Keratoconus (KC) is a multi-factorial corneal degenerative condition with varying incidence and prevalence across different reports.

  • Detailed longitudinal data demonstrating the trends of KC incidence and prevalence in a nationwide population are scant in the literature; thus, more nationwide, population-based studies are needed to provide better insight.

What this study adds

  • Our study revealed that between 2000 and 2018, the incidence and prevalence of the Taiwanese population is lower in comparison with other studies showing that Asians have higher KC rates than Caucasians.

  • Our study showed a longitudinal trend of increased KC incidence rate associated with increased frequency of the use of corneal topography and tomography (TG) during 2000–2018 in Taiwan.

  • Our study can provide an important reference for comparing incidence and prevalence rates across different ethnic populations while contributing to estimating disease burden for policies targeting KC.

Author contributions

L-CS, CHH and JMN designed the study. L-CS and W-MC performed statistical analyses. CHH, K-KL and J-SL interpreted the findings. JMN, CHH and L-CS, and all co-authors, wrote the manuscript. All authors edited and approved the manuscript.

Data availability

Our data availability is legally restricted. The data we used in this study were owned by a third-party organization, the Health and Welfare Data Science Center (HWDC), an official data center belonging to the Ministry of Health and Welfare. According to government regulation, the data were only available upon request by researchers, not open to the general public. Fellow researchers can apply for the use of the whole database with an ethical permit issued by the institutional review board. The Application Management Review Committee in HWDC will issue access to the national database.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Our data availability is legally restricted. The data we used in this study were owned by a third-party organization, the Health and Welfare Data Science Center (HWDC), an official data center belonging to the Ministry of Health and Welfare. According to government regulation, the data were only available upon request by researchers, not open to the general public. Fellow researchers can apply for the use of the whole database with an ethical permit issued by the institutional review board. The Application Management Review Committee in HWDC will issue access to the national database.

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