Tomographic and aberrometric assessment of first-time diagnosed pediatric keratoconus based on age ranges: a multicentre study

Depósito de investigación de la Universidad de Sevilla https://idus.us.es/ “This is the peer reviewed version of the following article: Rocha-de-Lossada, C., Prieto-Godoy, M., Sánchez-González, J.-M., Romano, V., Borroni, D., Rachwani-Anil, R., Alba-Linero, C., Peraza-Nieves, J., Kaye, S.B. and Rodríguez-Calvo-de-Mora, M. (2021), Tomographic and aberrometric assessment of first-time diagnosed paediatric keratoconus based on age ranges: a multicentre study. Acta Ophthalmol, 99: e929-e936, which has been published in final form at https://doi.org/10.1111/aos.14715. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited." Title Tomographic and aberrometric assessment of first-time diagnosed pediatric keratoconus based on age ranges: a multicentre study. Authors 1. Rocha-de-Lossada, Carlos a b c 2. Prieto-Godoy, Mario d 3. Sánchez-González, José-María e f 4. Romano, Vito e 5. Borroni Davide e 6. Rachwani-Anil, Rahul a 7. Alba-Linero, Carmen a c 8. Peraza-Nieves, Jorge b 9. Kaye, Stephen B.e 10. Rodríguez-Calvo-de-Mora, Marina a a Department of Ophthalmology, Regional University Hospital of Malaga, Malaga, Spain. b Department of Ophthalmology, Hospital Costa del Sol, Malaga, Spain. c Department of Radiology and Physical Medicine, Ophthalmology and Otorhinolaryngology. Ophthalmology Area. University of Malaga, Malaga, Spain. d Centre for Plant Biotechnology and Genomics, Madrid, Spain. e Department of Physics of Condensed Matter. Optics Area. University of Seville, Seville, Spain. f Department of Ophthalmology (Tecnolaser Clinic Vision®). Refractive Surgery Centre, Seville, Spain e Department of Ophthalmology, Royal Liverpool University Hospital, Liverpool (UK) Corresponding Author Sánchez-González, José-María Reina Mercedes Street, University of Seville, Seville, Spain +34 618 20 41 10 / [email protected] Abstract Purpose To describe pediatric keratoconus (KC) patients by tomographic and aberrometric characteristics at first diagnosis, in a multicenter study. Methods We included 278 eyes from 139 pediatric patients, with a first tomographic diagnosis (Pentacam®) of KC prior to 18- years-old. KC classification was based on the KC Index (≥ 1.07) and Topographic Keratoconus Classification (TKC ≥ 1). Patients were divided based on age ranges (14 and under and over 14 years) and gender. Statistical analysis was performed with SPSS statistics 25.0. ANOVA factor was carried out comparing to compare groups. Results 278 eyes were screened, and 230 eyes were diagnosed with pediatric KC. Mean age was 15.48 ± 2.33 (6 to 18) years old. We found differences in terms of TKC (2.08 ± 0.89 and 2.38 ± 0.82, p < 0.05) and spherical aberration (-0.71 ± 0.97 and -1.07 ± 1.36, p < 0.05) among the 14 years old or under and above 14 years old groups, respectively. Overall, female pediatric KC patients presented a more severe TKC, Belin Ambrosio Display, maximum keratometry, asphericity and primary and secondary coma aberrations compared to male KC patients. We observed a correlation between CDVA and asphericity (r= 0.71, p < 0.01), as well as between CDVA and spherical aberration (r=0.69, p < 0.01). Conclusion Our findings revealed that the debut of KC is usually in a moderate to advanced stage in the pediatric population at first diagnosis, particularly in female patients. Corneal tomography should be systematically performed in children with recent onset of corneal astigmatism. Keywords: Pediatric keratoconus; anterior segment disorders; corneal disorders; keratoconus age; keratoconus Introduction Keratoconus (KC) is typically a bilateral and asymmetrical corneal non-inflammatory disease. However, recent publications have shown inflammatory response patterns in KC. (Galvis et al. 2015, Loh & Sherwin 2020). KC is characterized by a progressive corneal thinning resulting in a central or paracentral protrusion. This harmful disease causes a progressive decrease in visual acuity (VA) as a result of an increase in astigmatism and higher-order aberrations. (Alió & Shabayek 2006, Pahuja et al. 2017, Piñero et al. 2009) This irregularity implies changes that take place in the anterior and posterior corneal surfaces which can be evaluated using corneal tomography. (Alió & Shabayek 2006, Pahuja et al. 2017, Piñero et al. 2009) Anterior corneal aberration analysis has proven to be an effective tool in detecting and grading keratoconus. (Bühren, Kühne & Kohnen 2007) Higher amounts of vertical coma and increased values of coma-like root mean square (RMS) are often present in patients with KC or suspected KC. (Bühren, Kühne & Kohnen 2007) Coma-like aberrations are known to be dominant in KC, especially vertical coma Z-3 and Z-5. (Bühren, Kühne & Kohnen 2007) KC is easy to recognize in advanced stages, being difficult to detect in early stages. (Golan et al. 2019, Gomes et al. 2015, Saad & Gatinel 2010) The onset age is usually between the second and third decade of life, (Goebels et al. 2015, Mukhtar & Ambati 2018, Naderan et al. 2017, Naderan et al. 2015) approximately between the ages of 22 and 28, being the average diagnosis at 27 years old. (Kennedy, Bourne & Dyer 1986, Léoni-Mesplié et al. 2012, Pouliquen, Forman & Giraud 1981, Zadnik et al. 1996) It has a tendency to progress till the ages of 35-40 before stabilizing. (El-Khoury et al. 2016, Léoni-Mesplié et al. 2012) However, cases in patients under the age of 20 have been reported (Léoni-Mesplié et al. 2012), including a study describing the youngest reported case being four years old. (Mukhtar & Ambati 2018, Sabti, Tappeiner & Frueh 2015) In children, as in adults, KC is a rare disease and, so far, there are few detailed studies of characterization of this pathology at these ages compared to adults. (El-Khoury et al. 2016) In the pediatric population (age 0–17 years), the prevalence of KC is reported to be 0.16%. (Moshirfar et al. 2019) Early age appears to be associated with more severe forms of KC and a faster disease progression, with an inverse correlation between age and severity. (Al Suhaibani et al. 2007, Ertan & Muftuoglu 2008, Léoni-Mesplié et al. 2012, Li et al. 2004, Moshirfar et al. 2019, Mukhtar & Ambati 2018, Ozer et al. 2019) In addition, early age at diagnosis appears to be related to an increased risk of developing corneal opacity (Barr et al. 2006, El-Khoury et al. 2016, Léoni-Mesplié et al. 2012) and a higher rate of acute hydrops compared to the adult population. (Mukhtar & Ambati 2018) Younger patients diagnosed with KC are usually of Asian or Middle Eastern origin. (Assiri et al. 2005, Léoni-Mesplié et al. 2012, Saini et al. 2004) The purpose of this study is to characterize pediatric KC patients (under 18 years old) focusing on the tomographic and aberrometric analysis, and secondarily their correlation with visual acuity at the first tomographic diagnosis in a multicentre study. This study represents the largest pediatric sample, to the best of our knowledge, available in the scientific literature. Methods Setting This retrospective, cross-sectional, multicentre study evaluated 278 eyes from 139 pediatric keratoconus patients. All patients visited the following ophthalmology clinics between 2012 and 2019: Regional University Hospital of Malaga (Málaga, Spain), Royal Liverpool University Hospital (Liverpool, United Kingdom), Tecnolaser Clinic Vision (Seville, Spain), Virgen del Rocío University Hospital (Seville, Spain), Torrecárdenas University Hospital (Almería, Spain) and Monterrey University Hospital Dr. José Eleuterio González (Monterrey, Mexico). The study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Regional University Hospital of Málaga (promoter center). An identical protocol was approved by the ethics committee of each center. Patients and study population KC diagnosis had been confirmed by a licensed expert ophthalmologist through a clinical examination and corneal tomography with Pentacam® (Oculus Optikgerate GmbH, Wetzlar, Germany). All Pentacam® images of all pediatric patients were retrospectively reviewed to assess the quality of the tomographic maps. Those with good-quality scans were included and those with low-quality scans were excluded from the study. All eyes underwent an extensive ophthalmologic examination that included visual acuity (VA) measurements, manifest refraction, slit-lamp examination to detect any signs associated with keratoconus (i.e., Vogt striae, Fleischer ring, superficial and deep corneal scar, superficial punctate keratitis, or corneal ulceration at the top of the cone) and fundus examination in mydriasis. The inclusion criteria were (1) patients under 18-years-old, (2) first diagnosis of KC by tomographic maps carried out under 18-years-old, (3) unilateral or bilateral KC. The exclusion criteria included any previous ophthalmological surgeries (keratoplasty or intracorneal ring segments), previous crosslinking procedure, or presence of any ophthalmic or systemic disease different from KC. For KC diagnosis and classification, we selected the Keratoconus Index (KI, ≥ 1.07) and Topographic Keratoconus Classification (TKC ≥ 1). (Goebels et al. 2015). The preoperative cone location was determined by the location of the highest anterior elevation. If it was within the central 3-mm zone, it was defined as a central cone. If it was outside this zone, it was defined as a peripheral cone. Previous studies reported that studying only one eye may lead to a loss of statistical power, especially in diseases with asymmetric behaviour. (Bunce et al. 2014) Since KC is an asymmetric and bilateral disease and our intention is to study its behaviour at first tomographic diagnosis, we included the patient’s data of one or both eyes, depending on the involvement. A general classification of the entire sample was performed. Later, patients were divided into two groups. The first one was composed of 14-years-old or under and the second one was composed of those older to 14-years-old. This threshold point was established based on the cut-point proposed by El-Khoury et al. (El-Khoury et al. 2016). In addition, the sample was split by gender and both groups were individually divided by gender. Outcome Measures The clinical variables that were reported were: (1) objective cycloplegic spherical refraction, (2) objective cycloplegic cylinder refraction, both measured with autorefractometers (Topcon KR 8000, Topcon Corporation, Tokyo, Japan, Nidek ARK-510A, Nidek, Gamagori, Japan and Tonoref II, version 1.17; Nidek, Gamagori, Japan), (3) corrected distance VA (CDVA) measured by 20-feet Snellen chart in photopic conditions, (4) steep, flat, mean and maximum keratometry reading values, (5) central corneal thickness (CCT), (6) thinnest corneal thickness (TCT), (7) anterior corneal astigmatism, (8) corneal asphericity (Q) at 8 mm, (9) topographic keratoconus classification (TKC), (10) keratoconus index (KI), (11) Belin Ambrosio display (BAD), (12) vertical primary coma Zernike coefficient (Z3-1), (13) vertical secondary coma Zernike coefficient (Z5-1) and (14) primary spherical aberration Zernike coefficient (Z40). All Zernike coefficients and RMS were calculated over a 6 mm-pupil diameter and measured from the anterior corneal surface. (Alió & Shabayek 2006, Bühren, Kühne & Kohnen 2007, Gobbe & Guillon 2005). If the cone was within the central 3-mm zone, it was termed a central cone. If it was outside this zone, it was termed peripheral (Padmanabhan et al. 2017). Statistical analysis Statistical analysis was performed with SPSS statistics 25.0 (IBM Corporation, Armonk, NY, USA). Student’s t-test was performed for parametric independent variables and Wilcoxon test was performed for non-parametric dependent variables. False Discovery Rate (FDR) was analyzed with the Benjamini-Hochberg method. All statistical tests were performed with a 95% confidence interval (p < 0.05). Results 230 eyes from 139 patients were diagnosed with pediatric KC and met the selection criteria. Out of 139 patients, 104 were male and 35 were female. Regarding origin, 86 were Caucasian, 23 were Hispanic, 15 Arab, 3 African and 12 with mixed origin. Patients’ mean age was 15.48 ± 2.33 (6 to 18) years old. The analysis of the total sample and distribution by gender are represented in Table 1. Correlation study between CDVA versus aberrations (Q value with Z40 and Z3-1 with Z5-1) are represented in Figure 1 and Figure 2, respectively. As for group comparisons, differences between children 14 years or under versus above 14 were carried out. Two variables (TKC and Z40) reported statistically significant differences (both p < 0.05). TKC in 14 years or under was 2.08 ± 0.89 (1.00 to 4.00), and 2.38 ± 0.82 (1.00 to 4.00) in over 14 years. In addition, Z40 was -0.71 ± 0.97 (-4.59 to +0.29) in 14 years or under and -1.07 ± 1.36 (-5.50 to +0.34) in over 14 years. There were no statistically significant differences amongst the other variables. Furthermore, gender analysis based on age range is represented in Table 2. Within male KC, non-significant differences were achieved between 14 years and under and over 14 years, however female KC patients presented significant differences in asphericity Q value, BAD and spherical aberration in over 14 years. Discussion Our results show differences in TKC and spherical aberration between pediatric KC when the cut-off point is set at 14 years of age (p < 0.05). Moreover, we observed a strong positive correlation between CDVA and Q (r = 0.71, p < 0.01), between CDVA and spherical aberration (r = 0.69, p < 0.01), as well as a moderate correlation between CDVA and coma aberration (r = 0.48, p < 0.01). This suggests that the more negative the value of Q, spherical aberration, and coma aberration (Z3-1 and Z5-1), the worse the CDVA. Furthermore, although males made up for the highest proportion of our sample, female patients, especially above 14 years, represented the most severe cases percentage wise regarding TKC, KI, Kmax, TCP, CCT; AST, BAD, Q, Z3-1 and Z5-1. KC seems to be more severe in children than in adults (Léoni-Mesplié et al. 2012) at first diagnosis. Moreover, it has been reported (Chatzis & Hafezi 2012) that a rapid advancement of the disease happens in pediatric KC patients, requiring a stricter monitoring. Yet, some literature argues against the hypothesis that younger age is linked to a more rapid progression of KC to stages III and IV requiring keratoplasty. (Dana et al. 1992, Mukhtar & Ambati 2018). Our study aims to characterize pediatric KC at the first tomographic diagnosis in a multicentre cross-sectional designed study. Pediatric and adult corneas are structurally different as a natural cross-linking of the corneal tissue may occur with aging, leading to a possible spontaneous stabilization of KC in later ages. (Mukhtar & Ambati 2018) Ertan et al. (Ertan & Muftuoglu 2008) studied 482 eyes with KC and found a clear inverse correlation between age and severity. An explanation for the advanced stages of KC at first diagnosis in children is the ‘‘explosive’’ progression of KC, meaning a short interval between noticeable symptoms and developing severe KC. (Léoni-Mesplié et al. 2012, Naderan et al. 2017) Nowadays, there is a variety of classifications and definitions used for KC (Papali’i-Curtin et al. 2019) and there is a consensus that tomography is the best and most comprehensive tool available to diagnose KC. (Gomes et al. 2015) (Gomes et al. 2015, Papali’i-Curtin et al. 2019) Currently, there is no threshold that determines the onset age (Hwang et al. 2018, Saad & Gatinel 2010, Schlegel, Hoang-Xuan & Gatinel 2008, Smadja et al. 2013, Uçakhan et al. 2011, Zadnik et al. 1996) and no isolated parameter is able to detect it. (de Sanctis et al. 2008, Saad & Gatinel 2010, Smadja et al. 2013) We retrospectively collected clinical data corresponding to all patients under 18-years-old with a diagnosis of KC at different ophthalmologic centres. Regarding the sample volume, to the best of our knowledge, our study represents the largest pediatric KC sample under 18-years-old. Naderan et al. (Naderan et al. 2015) studies almost 450 subjects but includes patients up to 20-years-old. In terms of age, reported pediatric KC ranges from 11.87 years by El-Khoury et al. (El-Khoury et al. 2016) up to 16.9 years by Naderan et al. (Naderan et al. 2015) Therefore, averagely, all the subjects included are pediatric. As for the CDVA, all studies report a mean VA of 0.40-0.60 in decimal scale, except for the subjects of Naderan et al. (Naderan et al. 2015) that reported a mean VA of 0.78 in decimal scale. Concerning maximum keratometry, our study provides one of the highest keratometry values along with the results reported by Naderan et al. (Naderan et al. 2017) being steeper among our female patients. Comparatively, other studies reported a lower mean maximum keratometry.(El-Khoury et al. 2016, Léoni-Mesplié et al. 2012, Naderan et al. 2015, Papali’i- Curtin et al. 2019) Regarding the classification of KC, only Papali´i-Curtin et al. (Papali’i-Curtin et al. 2019) studied the same variables as our study. We observed similar results in the KI, although our subjects had a greater TKC than their sample, once again, especially in our female patients. It is important to highlight that Papali´i-Curtin’s (Papali’i- Curtin et al. 2019) sample included only 10 pediatric KC. Changes in corneal Q and the corresponding increase in optical aberrations, mainly spherical aberration, have a significant negative impact in VA and in the quality of vision, such as contrast sensitivity, and visual functions, such as night vision or glare. Normal Q values range from -0.42 to 0.04 (Pahuja et al. 2017). Q value varies with the grade of KC, ranging from −0.35 in mild forms to −1.70 in severe KC, due to an exaggerated prolateness, leading to lower negative Q. (Pahuja et al. 2017) In our study, we observed a strong positive correlation between CDVA, Q value (r = 0.71, p < 0.01) and spherical aberration (r = 0.69, p < 0.01), as well as a moderate correlation between CDVA and coma aberration (r = 0.48, p < 0.01). It is known that higher values of vertical coma and increased values of comalike RMS are often present in patients with KC or suspected KC (Alió & Shabayek 2006, Piñero et al. 2009), being coma-like aberrations, especially vertical coma Z-3 and Z-5 ,dominant in KC (Bühren, Kühne & Kohnen 2007). According to our results, an increase in the values of these aberrations (spherical aberration, Q value and coma patterns) have a negative impact on the CDVA. Moreover, we observed that a central cone, where Q value and spherical aberration are more negative, had a worse visual acuity than a paracentral cone, where the coma pattern predominates. These results are consistent with those reported by Alió et al. (Alió et al. 2011) in adult KC patients, describing how mean keratometry value was significantly correlated with CDVA, corneal astigmatism, corneal aberrations and internal astigmatism. The higher the mean keratometry, the worse the CDVA. The more severe the internal astigmatism, corneal astigmatism in the 3.0 mm central zone, and corneal aberrations, the worse the CDVA. Corneal Q values, spherical aberration and coma aberration could be a useful parameter in pediatric KC analysis as Figure Legends Figure 1. Spearman correlation graph between corrected distance visual acuity (CDVA) versus asphericity Q value (up) and spherical aberration (down). Both points have been integrated in the same graph due to the relationship between both variables. Figure 2. Spearman correlation graph between corrected distance visual acuity (CDVA) versus primary (Z3) (up) and secondary (Z5) (down) vertical coma. Both points have been integrated in the same graph due to the relationship between both variables. Table 1.Topographic and tomographic differences between the two age-based ranges group in paediatric keratoconus. Group 1 (≥ 6 and ≤14) n = 70 Group 2 (> 14 and ≤ 18) n = 160 P value Age (years) 12.67 ± 1.83 (6 to 14) 16.71 ± 1.15 (15 to 18) < .01 Sphere (D) -1.12 ± 3.52 (-11.50 to +6.00) -2.25 ± 2.67 (-10.00 to +2.25) .106 Cylinder (D) -3.58 ± 2.13 (-9.00 to 0.00) -3.09 ± 1.76 (-8.50 to -0.50) .239 CDVA (Decimal) 0.64 ± 0.25 (0.05 to 1.00) 0.58 ± 0.29 (0.05 to 1.00) .339 K steep (D) 50.45 ± 6.78 (41.60 to 75.60) 50.75 ± 6.72 (40.20 to 77.70) .754 K flat (D) 46.13 ± 5.88 (39.30 to 70.90) 46.71 ± 5.72 (40.20 to 68.70) .483 K mean (D) 48.25 ± 6.20 (42.10 to 72.50) 48.64 ± 6.06 (41.00 to 72.60) .655 K maximum (D) 56.12 ± 9.32 (44.50 to 85.20) 57.80 ± 9.65 (43.20 to 89.80) .219 CCT (µm) 476.47 ± 63.84 (231.00 to 626.00) 476.05 ± 50.10 (328.00 to 603.00) .957 TCT (µm) 466.17 ± 64.80 (204.00 to 613.00) 466.53 ± 50.67 (323.00 to 593.00) .963 AST (D) 4.25 ± 2.52 (0.30 to 11.20) 4.02 ± 2.40 (0.00 to 14.50) .511 Q value -0.84 ± 0.46 (-2.33 to -0.22) -0.96 ± 0.56 (-2.76 to -0.16) .128 TKC 2.08 ± 0.89 (1.00 to 4.00) 2.38 ± 0.82 (1.00 to 4.00) < .05 KI 1.20 ± 0.12 (1.07 to 1.61) 1.23 ± 0.14 (1.07 to 2.20) .06 BAD 8.30 ± 7.57 (0.53 to 42.88) 9.23 ± 5.79 (0.49 to 33.41) .308 Z3-1 -1.88 ± 1.39 (-7.48 to +0.27) -2.22 ± 1.17 (-5.55 to -0.23) .059 Z5-1 -0.24 ± 0.40 (-1.24 to +0.48) -0.34 ± 0.40 (-1.47 to +0.87) .09 Z40 -0.71 ± 0.97 (-4.59 to +0.29) -1.07 ± 1.36 (-5.50 to +0.34) < .05 Data were reported as mean ± standard deviation (minimum to maximum range). D: dioptres; CDVA: corrected distance visual acuity; K: keratometry; CCT: central corneal thickness; TCT: thinnest corneal thickness; AST: anterior corneal astigmatism; Q value: corneal asphericity at 8 mm; TKC: topographic keratoconus classification; KI: keratoconus index; BAD: Belin Ambrosio display; Z3-1: vertical primary comma Zernike coefficient; Z5-1: vertical secondary comma Zernike coefficient; Z40: primary spherical aberration Zernike coefficient. Table 2.Topographic and tomographic differences between the three age-based ranges group in paediatric keratoconus. Group 1 (≥ 6 and ≤14) n = 70 Group 2 (> 14 and < 17) n = 71 Group 3 (≥ 17 and ≤ 18) n = 89 P value (1 vs. 3) Age (years) 12.67 ± 1.83 (6 to 14) 15.48 ± 0.50 (15 to 16) 17.60 ± 0.49 (17 to 18) < .01 Sphere (D) -1.12 ± 3.52 (-11.50 to +6.00) -2.25 ± 2.81 (-10.00 to +1.50) -2.25 ± 2.58 (-9.00 to +2.25) .21 Cylinder (D) -3.58 ± 2.13 (-9.00 to 0.00) -3.40 ± 1.85 (-8.50 to -0.50) -2,74 ± 1.62 (-6.00 to -0.50) .11 CDVA (Decimal) 0.64 ± 0.25 (0.05 to 1.00) 0.52 ± 0.26 (0.10 to 1.00) 0.64 ± 0.31 (0.05 to 1.00) .93 K steep (D) 50.45 ± 6.78 (41.60 to 75.60) 51.01 ± 6.89 (41.80 to 77.70) 50.55 ± 6.61 (40.20 to 73.00) .92 K flat (D) 46.13 ± 5.88 (39.30 to 70.90) 46.46 ± 5.63 (41.30 to 68.10) 46.89 ± 5.81 (40.20 to 68.70) .40 K mean (D) 48.25 ± 6.20 (42.10 to 72.50) 48.63 ± 6.11 (41.60 to 72.60) 48.65 ± 6.05 (41.00 to 70.80) .67 K maximum (D) 56.12 ± 9.32 (44.50 to 85.20) 57.82 ± 9.65 (43.20 ± 89.90) 57.78 ± 9.71 (43.40 to 89.70) .26 CCT (µm) 476.47 ± 63.84 (231.00 to 626.00) 468.52 ± 43.63 (328.00 to 570.00) 481.57 ± 53.91 (356.00 to 603.00) .57 TCT (µm) 466.17 ± 64.80 (204.00 to 613.00) 458.91 ± 44.03 (323.00 to 567.00) 472.35 ± 54.73 (355.00 to 593.00) .51 AST (D) 4.25 ± 2.52 (0.30 to 11.20) 4.68 ± 2.62 (0.40 to 14.50) 3.55 ± 2.12 (0.00 to 12.60) .06 Q value -0.84 ± 0.46 (-2.33 to -0.22) -1.00 ± 0.54 (-2.46 to -0.16) -0.93 ± 0.57 (-2.76 to -0.20) .32 TKC 2.08 ± 0.89 (1.00 to 4.00) 2.41 ± 0.78 (1.00 to 4.00) 2.35 ± 0.85 (1.00 to 4.00) < .05 KI 1.20 ± 0.12 (1.07 to 1.61) 1.21 ± 0.10 (1.07 to 1.62) 1.25 ± 0.16 (1.07 to 2.20) < .05 BAD 8.30 ± 7.57 (0.53 to 42.88) 9.46 ± 5.81 (1.39 to 33.41) 9.06 ± 5.79 (0.49 to 29.73) .46 Z3-1 -1.88 ± 1.39 (-7.48 to 0.27) -1.98 ± 0.99 (-4.57 to -0.23) -2.40 ± 1.26 (-5.55 to -0.25) < .05 Z5-1 -0.24 ± 0.40 (-1.24 to +0.48) -0.29 ± 0.39 (-1.18 to +0.87) -0.37 ± 0.41 (-1.47 to +0.48) < .05 Z40 -0.71 ± 0.97 (-4.59 to +0.29) -1.14 ± 1.38 (-5.32 to +0.28) -1.03 ± 1.35 (-5.50 to +0.34) .12 Data were reported as mean ± standard deviation (minimum to maximum range). D: dioptres; CDVA: corrected distance visual acuity; K: keratometry; CCT: central corneal thickness; TCT: thinnest corneal thickness; AST: anterior corneal astigmatism; Q value: corneal asphericity at 8 mm; TKC: topographic keratoconus classification; KI: keratoconus index; BAD: Belin Ambrosio display; Z3-1: vertical primary comma Zernike coefficient; Z5-1: vertical secondary comma Zernike coefficient; Z40: primary spherical aberration Zernike coefficient. Table 3. Comparison chart in paediatric keratoconus available in scientific literature N Age CDVA K Max CCT TCT TKC KI Léoni-Mesplié et al. 1 (2012) 98 13.1 ± 2.1 0.50 51.32 ± 0.66 481.70 ± 7.03 454.94 ± 7.50 - - Naderan et al. 2 (2015) a 443 16.9 ± 2.2 0.78 55.8 ± 7.10 463.00 ± 48 447 ± 51 - - El-Khoury et al.3 (2016) 16 11.87 ± 2.0 0.40 53.66 ± 11.12 487.00 ± 54.9 - - - Naderan et al.4 (2017) 158 15 ± 1.9 0.51 60.5 ± 8.6 440.00 ± 41.0 420.00 ± 46.00 - - Papaliʼi-Curtin et al.7 (2019) 10 14.9 ± 0.7 0.63 48.7 ± 6.1 - 493.6 ± 35.1 1.4 1.1 ± 0.1 Rocha-De-Lossada et al. (2019) 278 15.48 0.61 57.29 ± 9.69 477.63 ± 55.71 467.56 ± 56.64 2.27 ± 0.85 1.22 ± 0.14 a Subjects were under 20 years old. N: number of subjects in the study; CDVA: corrected distance visual acuity; K Max: mean maximum keratometry; CCT: central corneal thickness; TCT: thinnest corneal thickness; TKC: topographic keratoconus classification; KI: keratoconus index.