Abstract
PURPOSE:
The purpose of this study was to determine the prevalence of keratoconus (KC) and keratoconus suspect (KCS) among patients seeking refractive surgery in Syria.
METHODS:
This is a retrospective multicenter screening study. The study was conducted in Damascus University, Tishreen University, and Tartous Specialist Eye Center (a private center). Data were collected from refractive surgery candidates referred for preoperative evaluation before laser in situ keratomileusis, photorefractive keratectomy, intrastromal corneal rings, and phakic intraocular lens implantation. Corneal parameters were obtained by Scheimpflug–Placido tomography, Sirius (CSO, Italy).
RESULTS:
A total of 1479 patients were included in this analysis. The prevalence rates of KC and KCS were 18.19% (269/1479) and 13.52% (200/1479), respectively. In addition, patients with KC were found to have higher percentages of eye rubbing and astigmatism than suspect and normal (P < 0.0001).
CONCLUSION:
High prevalence rate of KC was found among patients seeking refractive surgery in Syria. Although this study was carried out on a highly selective population, it may reflect a high prevalence rate in a general population in Syria.
Keywords: Keratoconus suspect, prevalence of keratoconus, refractive surgery, retrospective, Syria
Introduction
Keratoconus (KC) is a chronic, progressive corneal disease characterized by progressive stromal thinning of the central and paracentral portion of the cornea resulting in irregular astigmatism and visual deterioration.[1,2] The prevalence of KC ranges from 0.3 per 100,000 in Russia to 2300 per 100,000 in Central India (0.0003%–2.3%).[3-5] Many factors influence the prevalence rate such as genetic, environmental, ethnic, and geographical, in addition to variations in the groups studied.[6-9] The prevalence also varies widely, depending upon the diagnostic criteria used and the cohort of patients examined. In Central India, the prevalence of KC was primarily based on keratometry, yielding a prevalence rate of 2.3% for subjects with a corneal refractive power of at least 48 D, 0.6% for a cutoff power of at least 49 D, and 0.1% using a cutoff power of at least 50 D.[5] Multiple studies have indicated that countries with warm climates such as Central India the Middle East and Northern Africa have a higher prevalence rate of KC[10-12] as compared to countries with cold climates such as Russia and the United Kingdom.[13] A recent population-based study from Denmark indicated that the annual incidence of KC had a threefold increase from 1.24 per 100,000 person-years in 2003 to 3.8 per 100,000 in 2011.[14] Screening for KC in keratorefractive surgery candidates is of particular importance, due to the risk of postoperative ectasia in subjects with abnormal corneal topography.[15-17] Randleman et al. proposed a risk score system to predict the risk of postlaser in situ keratomileusis (LASIK) ectasia consisting of different parameters and concluded that a diagnosis of early KC was the main risk factor for post-LASIK corneal ectasia.[18] Binder and Trattler reassessed this risk score system in 1702 eyes with myopic refractive errors and noted that only 3 eyes with preoperative topographic KC and no other risk factors developed ectasia.[19] Although advanced cases of KC do not pose challenges in diagnosis, many screening tests are required to detect the early form of this disease.
In the current study, we utilized the Scheimpflug/Placido-based corneal tomography, Sirius (CSO, Italy). The Sirius tomographer has shown good repeatability and accuracy in detecting KC.[20-23] Our objective was to establish the prevalence of KC and keratoconus suspect (KCS) among subjects screened for refractive surgery at three major cities in Syria. We also aimed to examine associations of KC with age, gender, eye rubbing, and astigmatism. To our knowledge, no studies have been reported to detect the prevalence rate of KC in candidates screened for refractive surgery in Syria.
Methods
All patients were referred for preoperative evaluation before LASIK, photorefractive keratectomy (PRK) intrastromal corneal ring segments, and phakic intraocular lens implantation between January 2018 and June 2018.
Preoperative evaluation consisted of:
Complete history including age, sex, ophthalmic history such as eye rubbing and contact lens wear, and previous ocular surgery
Slit-lamp biomicroscopy examination
Manifest and cycloplegic refraction
Placido/Scheimpflug-based corneal imaging (Sirius, Costruzione, Strumenti, Oftalmici, Florence, Italy).
The exclusion criteria were patients under 18 years, ocular pathologies other than KC, previous ocular surgery, previous refractive surgery (e.g., LASIK and PRK), or corneal scarring not consistent with KC.
The diagnosis of KC was defined as a combination of clinical and topographic criteria consisting of: (a) corneal irregularity, determined by distorted keratometry mires and/or distortion of the dilated retinoscopic reflex, in addition to (b) at least two of the following topographic/tomographic findings: abnormal posterior ectasia, abnormal pachymetric distribution, or symmetry index front of 1.17 D or more; or one of the following slit-lamp findings: Vogt striae, 2-mm arc of Fleisher ring, or corneal scarring consistent with KC.[23] Diagnosis of KCS was confirmed if there were: (a) absence of clinical (keratometric, retinoscopic, or biomicroscopic) signs of KC, (b) best-corrected visual acuity of 20/20 or better, and (c) positive Sirius software indicator or symmetry index back of 0.12 D or more.[23] Sirius is provided with a network-based classification system to differentiate between KC, KC suspect, and normal eyes. The accuracy of the Sirius software has been described elsewhere.
Subjects were classified into: (a) KC: if one eye or both eyes had KC, (b) KC suspect: if both eyes were suspect, or one eye was KC suspect and the contralateral eye was normal, and (c) normal: if both eyes were normal.
Data analysis
Frequency and prevalence data are presented as n (%). All statistical analysis was presented using the Statistical Package for the Social Sciences (SPSS) software (Version 25, SPSS, Chicago, IL, USA). Categorical data were compared using the Chi-squared test, and statistical significance was defined as P < 0.05. This study was approved by the Research Committees of Damascus University, Tishreen University, and Tartous Specialist Eye Center. The entire study conduct adhered to the tenet of the Declaration of Helsinki.
Results
A total of 1479 (2958 eyes) subjects were included in this study, 500 (33.81%) from Tartous Specialist Eye Center (Tartous, Syria), 500 (33.81%) from Tishreen University (Latakia, Syria), and 479 (32.39%) from the University of Damascus (Damascus, Syria). The mean age was 31.72 ± 11.73 years. There was no statistically significant difference between males and females (P = 0.94) [Table 1]. The mean minimum corneal thickness values were 542.3 ± 33.9 um in normal subjects, 508.5 ± 33.8 um in KC suspect subjects, and 462.5 ± 35.5 um in KC subjects.
Table 1.
Characteristics of patients
| Variable | n (%) |
|---|---|
| City | |
| Damascus | 479 (32.39) |
| Latakia | 500 (33.81) |
| Tartous | 500 (33.81) |
| Sex | |
| Female | 741 (50.1) |
| Male | 738 (49.9) |
| Age | |
| 18–20 | 88 (5.95) |
| 20–30 | 729 (49.29) |
| 30–40 | 383 (25.9) |
| 40–50 | 139 (9.4) |
| 50–60 | 86 (5.81) |
| 60–83 | 54 (3.65) |
| Mean±SD | 31.72±11.73 |
SD: Standard deviation
The overall prevalence rate of KC and KC suspect was 18.19% and 13.52%, respectively. The prevalence rate of KC in Damascus, Latakia, and Tartous cities was 24.22%, 13.6%, and 17%, respectively (P < 0.0001). In addition, a significant difference was found between the coastal cities (Tartous and Latakia) and the city of Damascus, 15.3% versus 24.22%, respectively (P < 0.0001). While there was no significant difference in the prevalence rate of suspect KC between Damascus and Latakia (P = 0.59), the difference was statistically significant between Damascus and Tartous (P < 0.0001). We found that the higher percentage of KC (20.14%) and KC suspect (25.9%) was in the 40–49 age group. There was no significant difference in the prevalence rate of KC, nor in KC suspect across genders (P > 0.05, all). The mean Manifest refraction spherical equivalent (MRSE) values were significantly higher in eyes with KC than in KC suspect and normal patients (P < 0.0001) [Table 2].
Table 2.
Demographic data of study groups
| Keratoconus, n (%) | Keratoconus suspect, n (%) | Normal, n (%) | P | |
|---|---|---|---|---|
| Overall | 269 (18.19) | 200 (13.52) | 1010 (68.29) | |
| City | ||||
| Damascus | 116 (24.22) | 50 (10.44) | 313 (65.34) | <0.0001 |
| Latakia | 68 (13.6) | 54 (10.8) | 378 (75.6) | |
| Tartous | 85 (17) | 96 (19.2) | 319 (63.8) | |
| Region | ||||
| Damascus | 116 (24.22) | 50 (10.44) | 313 (65.34) | <0.0001 |
| Coast | 153 (15.3) | 150 (15) | 697 (69.7) | |
| Sex | ||||
| Female | 136 (50.56) | 102 (51) | 503 (49.8) | 0.94 |
| Male | 133 (49.44) | 98 (49) | 507 (50.2) | |
| Age | ||||
| 18–20 | 16 (18.18) | 5 (5.68) | 67 (76.14) | <0.0001 |
| 20–30 | 135 (18.52) | 71 (9.74) | 523 (71.74) | |
| 30–40 | 75 (19.58) | 59 (15.4) | 249 (65.01) | |
| 40–50 | 28 (20.14) | 36 (25.9) | 75 (53.96) | |
| 50–60 | 13 (15.12) | 16 (18.6) | 57 (66.28) | |
| 60–83 | 2 (3.7) | 13 (24.07) | 39 (72.22) | |
| MRSE (diopter), mean±SD | −4.6±3.99 | −2.27±2.82 | −2.31±1.98 | <0.0001 |
| Age, mean±SD | 30.58±9.47 | 35.91±12.34 | 31.21±11.99 | <0.0001 |
Statistically significant values (P<0.05). Values in bold are statistically significant. P: Chi-squared test, SD: Standard deviation, MRSE: Manifest refraction spherical equivalent
While an astigmatic error of ≥3 D was found in 237 (54.27%) eyes with KC, only 47 (12.05%) KC suspect eyes and 105 (4.93%) normal eyes had astigmatism of ≥3 D (P < 0.0001). KC subjects had a higher percentage of reported eye rubbing than KC suspect subjects and normal subjects (39.77%, 12%, and 14.95%, respectively, P < 0.0001) [Table 3].
Table 3.
Association of astigmatic error and reported history of eye rubbing with study cohorts
| Variables | Keratoconus, n (%) | Keratoconus suspect, n (%) | Normal, n (%) | P |
|---|---|---|---|---|
| Astigmatism (diopter) ≥3 (eyes) | 237 (54.23) | 47 (12.05) | 105 (4.93) | <0.0001 |
| Eye rubbing (patients) | 107 (39.77) | 24 (12) | 151 (14.95) | <0.0001 |
Statistically significant values (P<0.05). Values in bold are statistically significant. P: Chi-squared test
Discussion
The current study assessed the prevalence of KC among patients seeking refractive surgery in three major cities in Syria. In the study population, the overall prevalence of KC was 18.19%. Similar studies have been reported in the Middle East and other regions to assess the prevalence of KC among patients seeking refractive surgery [Table 4]. Our findings are comparable to the results of the two studies that have been reported in the Middle East region. The first study conducted in Asser, Saudi Arabia, by Al-Amri in 2017 reported a prevalence of 18.7%,[24] while the second study was carried out in Northern Egypt by Saro et al. who reported a KC prevalence of 17.5%.[27] Althomali et al. studied the prevalence of KC among patients seeking laser vision correction in Taif, Saudi Arabia, where a 8.59% prevalence rate was identified.[25] Wilson and Klyce investigated the prevalence of KC at Texas University, reporting a rate of 5.7% in a cohort of students seeking refractive surgery for correction of myopia.[26]
Table 4.
Studies evaluated the prevalence of keratoconus in refractive surgery population
| Author | City/Country | Method of screening | Prevalence of keratoconus (%) |
|---|---|---|---|
| Al-Amri 2018[24] | Aseer, Saudi Arabia | Scheimpflug Tomographer | 18.7 |
| Althomali et al., 2017[25] | Taif, Saudi Arabia | Scheimpflug Tomographer | 8.59 |
| Saro et al., 2018[24] | Sohag, Northern Egypt | Scheimpflug Placido Tomographer | 17.5 |
| Wilson and Klyce, 1994[26] | Texas, USA | Computed Topographic analysis | 5.7 |
| Present study | Damascus, Latakia, Tarotus/Syria | Scheimpflug Placido Tomographer | 18.19 |
While Sharma et al. found that suboptimal central corneal thickness was the most common reason for rejecting LASIK,[28] Gyldenkerne et al. found that change of mind was the most common reason.[29]
In this study, we found that the prevalence of KC was higher in Damascus (24.22%) compared to the coastal cities (Latakia and Tartous; 15.3%). This difference could be attributed to ethnic, geographic, and environmental differences, as Latakia and Tartous are Mediterranean coastal cities, while Damascus is located in the South West of Syria, 80 km from the Mediterranean Sea coastline with a hot, dry, and sunny climate. A positive correlation between altitude and KC has been reported and has been attributed to the increased level of ultraviolet (UV) radiation at higher altitudes.[30] Damascus sits at an altitude of 700 m above sea level and typically has a dry and sunny climate, which is likely to be associated with increased UV radiation in this city. Excessive exposure to UV light causes exudative damage to the cornea, in which there is a reduced amount of enzymes such as aldehyde dehydrogenase and superoxide dismutase necessary to remove the reactive oxygen species.[31,32] KC is influenced by ethnicity[8,9] and ethnic differences between the coastal cities (Latakia, Tartous) and Damascus could be yet another contributing factor, as coastal cities are ethnically phoenicians while Damascus is ethnically Aramean. Ethnicity was determined by the location of patients’ cities, as a direct evaluation of ethnicity and descent was not performed.
We found no significant difference in the prevalence rate of KC between males and females (P = 0.94). Although it is not clear whether significant difference exists, some studies have reported a higher incidence in males,[33,34] while others have found a higher rate in females.[35]
We further evaluated the association of KC with astigmatism and self-reported eye rubbing. Serdarogullari et al. recommended that all patients with 2 D or more astigmatism should undergo corneal topography screening for early diagnosis of KC.[36] This is to an extent, consistent with our results, as we found that 54.23% of patients with KC had ≥3 D astigmatism. Several studies have reported an association of KC with eye rubbing. Mcmonnies and Boneham reported higher levels of allergy, itch, and rubbing in KC eyes than in nonkeratoconic eyes.[37] Their finding added weight to the circumstantial evidence that eye rubbing contributes to the pathogenesis of KC. Eye rubbing may alter corneal biomechanics and trigger KC onset or exacerbate its clinical presentation.[38] In our recently published study, which evaluated the prevalence rate of KC in a population-based study in Syria, eye rubbing was the strongest predictor to be associated with KC where 50% of subjects with KC reported a positive eye rubbing.[39] In the current study, eye rubbing was present in 39.77% of patients with KC. The retrospective nature of the study has its limitations. Moreover, the findings in this study may be population specific. Results should be interpreted and extrapolated to other cohorts with caution, particularly with the small sample size. Prospective studies with larger number of patients are needed.
Conclusion
Both KC (18.19%) and KCS (13.52%) were commonly found among patients undergoing screening for refractive surgery. KC was frequently coexistent with eye rubbing and astigmatism. This highlights the need for rigorous and thorough preassessment for patients seeking keratorefractive surgery in the Middle Eastern population, where there may be an increased risk of ectatic disease in the background population.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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