Higher order aberrations and glare disability in Mild Keratoconus: A comparative study

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Method : Eighteen eyes with early keratoconus (grade 0–1, Belin ABCD) to age-matched controls. Visual acuity, wavefront aberrometry, and contrast sensitivity (CSV-1000HGT) were evaluated under baseline and glare conditions using best spectacle correction. Contrast thresholds were recorded across four spatial frequencies. Group differences were analyzed using non-parametric statistical tests. Results : Median age and visual acuity were similar between groups, though the Mild KC group had reduced acuity (0.13 log MAR). Higher-order aberrations (HOA) were significantly elevated in Mild KC (0.139 vs. 0.028; p < 0.05). Contrast sensitivity declined under glare in both groups, but significantly only in controls. Mild KC showed a 4% reduction vs. 3% in controls. A strong positive correlation was found between HOA and contrast sensitivity (R = 0.82, p < 0.05). Conclusion : Mild KCs are also associated with significantly elevated HOA and subtle but notable reduction in contrast sensitivity under glare, despite comparable median visual acuity between groups, the Mild KC cohort exhibited a greater reduction in AULCSF with glare exposure, although the effect of glare as defined by Glare disability doesn’t tend to differ significantly among the two groups. Figures Figure 1 Introduction Keratoconus (KC) is a progressive, bilateral corneal ectasia characterized by stromal thinning and biomechanical weakening, leading to irregular astigmatism, myopia, and significant visual distortion. 1 While the disease does not cause blindness, its impact on daily activities, such as reading, driving, and navigating low-light environments, can be profound, even in its mildest stages. 2 Globally, 0.2 to 4,790 per 100,000 persons and 1.5 and 25 per 100,000 individuals/year, a higher incidence is observed in younger populations. 3,4 Early detection and management are critical to preserving vision and quality of life, especially as advanced imaging techniques like Scheimpflug tomography have improved the diagnosis of subclinical and mild cases. 5 In keratoconus, structural changes in the cornea result in a marked increase in higher-order aberrations (HOAs), particularly vertical coma and spherical aberration. 6 These optical irregularities degrade visual quality by disrupting light focusing and reducing contrast sensitivity, a key functional vision metric that measures the ability to discern objects against varying luminance levels. 7 Studies have looked at the correlation between HOA and contrast sensitivity inpatients with keratoconus. Indeed, they found that increased HOA has been shown to correlate with a decrease in contrast sensitivity. 8,9,10 Studies have reported that elevated HOAs persist in milder forms of keratoconus and exhibit reduced contrast sensitivity and higher ocular HOAs compared to controls, suggesting that increased HOAs may partially explain the reduced vision quality in keratoconus and keratoconus suspects. 11 While keratoconus is well-recognized for its impact on visual quality, most existing research has focused on moderate to severe disease stages or relied heavily on high-contrast visual acuity, which fails to capture the nuances of real-world visual function. Even though some studies have explored contrast sensitivity in keratoconus, glare disability, a crucial component of functional vision remains largely uninvestigated in this population. Given the inherent heterogeneity of keratoconus, including variability in cone location and morphology, perfectly matching all disease parameters in a cross-sectional design is nearly impossible. Furthermore, visual performance may also be modulated by neural factors, such as age-related differences in visual processing, adding another layer of complexity. To minimize confounding variables, this study specifically targets mild keratoconus, by quantifying glare-induced contrast sensitivity deficits across spatial frequencies and examining their relationship with higher-order aberrations (HOAs), this study aims to shed light on subtle but impactful functional impairments in early keratoconus, offering a more sensitive approach to detecting visual disability than standard acuity metrics alone. Methods Study Design A prospective comparative cohort study was conducted in speciality contact lens clinic at Sankara Nethralaya between December 1, 2024, and April 1, 2025. The research adhered to the ethical principles outlined in the Declaration of Helsinki (1964). Patient anonymity was strictly maintained, and informed consent was obtained for all procedures. The study received approval from the Institutional Review Board and Ethics Committee of Medical Research Foundation. Participants Healthy, and mild keratoconus subjects (males and females) between the ages 17–40 years participated in this study. Subjects above 40 were not recruited to the study since contrast sensitivity has been shown to be reduced above this age. 12 Subjects were recruited from the clinics and student body of Sankara Nethralaya. The methods were orally explained to the participant and they signed a statement of informed consent prior to their participation. Subjects were classified into two groups, Keratoconus and control groups. The Keratoconus group included only included Grade 0 and 1 as per the ABCD classification developed by Belin MW. 5 All subjects had no previous history of any ocular surgery or trauma. Procedure Participants underwent a comprehensive eye examination which included a vision assessment, objective, subjective refraction, slit lamp and fundus examination. Total ocular wavefront aberrometry was performed following which the Contrast Sensitivity with and without Glare source was performed. Wavefront aberrations (3rd to 8th radial order Zernike polynomials) were using 785 nm wavelength aberrometer (Tracey Technologies, USA) under of light using the Itrace™ wavefront non-cycloplegic, unaided, mesopic conditions The Zernike coefficients were computed for a 4 mm pupil size using the rescaling algorithm within the Itrace software. Even though all wavefront aberration measurements were obtained under non-cycloplegic viewing conditions, a relatively stable accommodative state of the eye was ensured by the dynamic fogging method used by the Itrace™ aberrometer during its measurements 13 The ocular HOA were quantified using the root mean square as an index of the image quality. Root Mean Square values were obtained by calculating the square root of the sum of the squares of j6 to j20, using the standard nomenclature for describing Zernike terms found in Atchison et al. 14 From the 35 Zernike coefficients measured by the instrument, the following RMS groups were examined: total RMS HOA (all terms included in the third, fourth, fifth, and sixth order), total trefoil (including j6, j9, j16, and j19), total coma (including j7, j8, j17, and j18) and total tetrafoil (including j10, j14, j22, and j26) Auto-keratometry, corneal topography, and tomography were performed using the Pentacam (Oculus, Germany). Contrast sensitivity was assessed monocularly for all participants using their best spectacle correction across spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd) under mesopic lighting conditions, both with and without glare. Testing employed the CSV-100™ chart (Vector Vision), with a grating luminance of 85 cd/m²; during glare assessments, a halogen light source providing an equivalent luminance of 2.5 cd/m² at eye level was introduced. Contrast sensitivity was graded on a 10-point scale at each frequency: participants who could not perceive the test strip or the highest contrast bar were scored − 1 and 0, respectively, while those detecting any of the eight progressively lower contrast levels were scored from 1 to 8. These raw scores were then converted into log contrast sensitivity values using Vector Vision’s standard definitions, as implemented by Chua et al. 15 Statistical analysis Statistical analysis was performed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Normality was checked on each parameter for each group separately by means of the Wilk-Shapiro test. Fisher’s exact test was used to test gender differences between groups. The Mann-Whitney test was performed to assess the differences between groups of subjects. Spearman correlation was performed to test the correlation between ocular HOA and contrast sensitivity. Friedman test and Post hoc analysis with Wilcoxon signed-rank tests were performed to compare contrast sensitivity in different frequencies (6, 9 and 12 cycles/deg) for each group of subjects. A p-value < 0.05 was considered significant. Results This study included 36 eyes of 22 patients. The median age was 22.0 years (IQR: 3.0; range: 16–38), and the median best-corrected visual acuity was 0.00 log MAR (IQR: 0.17; range: 0.00–0.39). The keratoconus group consisted of 18 eyes from 14 patients (9 males, 5 females) with mild keratoconus (Grades 0 and 1), aged 16–38 years (median: 23.0 years; IQR: 7.0). The median best-corrected visual acuity in this group was 0.17 log MAR (IQR: 0.12). The control group included 18 eyes from 9 healthy subjects (5 females), aged 20–34 years (median: 22.0 years; IQR: 1.0), with a median visual acuity of 0.00 log MAR (IQR: 0.00). There was no statistically significant difference in age between the groups (U = 116.0, p = 0.13) Fisher’s test was conducted to assess the association between gender and group membership, revealing no significant difference (p > 0.05). The odds ratio was 2.25 (95% C.I [0.9-5.0]). There was no statistically significant difference in age nor in gender distribution between the two groups. However, the keratoconus group had significantly poorer visual acuity (U = 45.0, p < 0.001) and greater spherical equivalent refractive error (U = 59.5, p < 0.001). Table 2 summarizes the corneal parameters and higher-order aberrations (HOAs) for both groups. Statistically significant group differences were observed for visual acuity, spherical equivalent, keratometric values, central corneal thickness, and the following HOAs: total RMS, trefoil, total coma, and tetrafoil. Given the established relationship between contrast sensitivity (CS) and visual acuity, CS was assessed under both glare and no-glare conditions. The area under the log contrast sensitivity function (AULCSF) was computed using Simpson’s rule via Python®. Figure 1 illustrates contrast sensitivity across spatial frequencies. In the no-glare condition, contrast sensitivity was significantly reduced in the keratoconus group at all frequencies: 1.49 (IQR: 0.18), 1.55 (0.32), 1.25 (0.36), and 0.56 (0.49) at 3, 6, 12, and 18 cycles per degree (cpd), respectively, compared to the control group which showed 1.78 (0.15), 2.14 (0.15), 1.84 (0.15), and 1.40 (0.30) at the same frequencies. Under glare conditions, the keratoconus group again showed reduced contrast sensitivity: 1.42 (0.33), 1.63 (0.32), 1.08 (0.49), and 0.64 (0.34) across 3, 6, 12, and 18 cpd, respectively, compared to the control group: 1.78 (0.15), 1.99 (0.15), 1.69 (0.15), and 1.40 (0.15). Individual Mann–Whitney U tests revealed statistically significant group differences at all spatial frequencies (3, 6, 12, and 18 cpd) under both glare and no-glare conditions, even after Bonferroni correction (adjusted α = 0.0125). The median AULCSF under no-glare conditions was significantly lower in the keratoconus group at 19.3 (IQR: 3.60) compared to 28.4 (IQR: 1.70) in controls (U = 0.00, p < 0.001). Under glare conditions, AULCSF was 18.2 (IQR: 5.20) in the keratoconus group versus 27.3 (IQR: 2.3) in controls (U = 0.00, p < 0.001). Glare disability, defined as the ratio of AULCSF under glare to no-glare, was 1.04 (IQR: 0.16) for keratoconus and 1.03 (IQR: 0.03) for controls, with no significant difference between the groups (U = 154.00, p = 0.80). The higher-order RMS aberrations were negatively correlated with contrast sensitivity at medium and high spatial frequencies. Although AULCSF was significantly reduced in mild keratoconus, the calculated glare disability scores were not significantly different from controls. Discussion This study revealed that individuals with mild keratoconus exhibit significantly elevated higher-order aberrations (HOAs) compared to normal controls, even when best-corrected visual acuity is similar, highlighting HOAs as a defining optical feature of keratoconus across all disease stages. Extensive research has consistently shown that keratoconic eyes have markedly higher root mean square (RMS) HOA values than normal eyes. 16 Both anterior and posterior corneal surfaces contribute to these elevated aberrations, with posterior surface HOAs alone showing mean total values of 1.09 µm in keratoconus compared to just 0.15 µm in normal eyes 17,18 and 0.02µm in this study. Vertical coma is the most dominant aberration type in keratoconus and shows the strongest correlation with corneal irregularity indices followed by spherical and horizontal coma as reported by a previous study. 18 This predominance of vertical coma is attributed to the typical inferior displacement of the cone, which leads to increased topographic asymmetry and explains the asymmetrical nature of HOA patterns observed in keratoconic eyes. Interestingly, posterior surface coma may partially compensate for the anterior surface aberrations, indicating a complex interplay between the two corneal surfaces in the generation of HOAs. Despite normal visual acuity, individuals with mild keratoconus frequently experience reduced contrast sensitivity, a finding that underscores the disconnect between standard acuity measurements and real-world visual quality. Quantitative contrast sensitivity function testing has demonstrated that even early keratoconus patients with 20/20 corrected vision show significantly impaired contrast sensitivity at both low (1.0 and 1.5 cycles per degree) and high (12.0 and 18.0 cycles per degree) spatial frequencies when compared to normal eyes. 19 This reduction in contrast sensitivity is particularly relevant, as it correlates more closely with refractive error, topographic indices, and HOA values than visual acuity alone. The inverse relationship between HOAs and contrast sensitivity has been well-documented, with studies employing psychophysical testing methods such as two-alternative forced-choice Gabor patches reporting strong negative correlations, for third-order aberrations. 20 Notably, these negative associations remain significant even in keratoconus patients who demonstrate perfect log MAR acuity (0.00), particularly at medium and high spatial frequencies, reinforcing the notion that HOAs are a key contributor to the functional visual limitations experienced by keratoconus patients. 11 Findings on glare sensitivity in keratoconus have been somewhat inconsistent, with earlier research suggesting that glare testing may have limited clinical utility because visual loss in keratoconus is primarily driven by optical aberrations rather than intraocular light scatter. 21 However, more recent studies using alternative methods, such as the Brightness Acuity Tester (BAT) with lower intensity glare sources, have detected measurable glare-related visual losses in keratoconus patients. 22 This divergence in findings is likely due to differences in glare source intensity; higher-intensity glare tends to induce pupillary constriction, which reduces the influence of aberrated optics by limiting the entrance pupil. Consequently, studies using subtler glare stimuli may be better able to detect the functional visual disturbances caused by optical imperfections in keratoconus. In this study’s cohort, contrast sensitivity declined under glare conditions in both keratoconus and control eyes, but the reduction reached statistical significance only in the control group. Although the percentage drop in contrast sensitivity was slightly higher in the keratoconus group (4% vs. 3%), with no significant difference in glare-related contrast loss between the two groups. This suggests that while both groups are affected by glare, eyes with mild keratoconus may already function under compromised baseline conditions due to pre-existing optical aberrations, thereby reducing the relative impact of additional glare. A weak, non-significant positive correlation was observed between glare disability and total HOAs (RMS), in contrast to previous studies that reported stronger inverse relationships. Such discrepancies may stem from methodological variations, including the type of contrast sensitivity assessment (e.g., Gabor patches versus letter charts), the spatial frequencies tested, differences in aberrometric devices, or pupil size during measurement. Collectively, this study’s results, alongside existing literature, indicate that contrast sensitivity loss in keratoconus is multifactorial. While HOAs contribute significantly, other factors such as intraocular light scatter and neural adaptation to chronic optical blur also appear to influence visual performance. Indeed, even when HOAs are corrected with adaptive optics, keratoconic eyes often continue to underperform compared to normal eyes, possibly due to long-standing cortical adaptation or diminished retinal sensitivity. Declarations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution Madhumathi Subramanian - M.S - CONCEPTUALIZATION AND REVIEW OF THE MANUSCRIPTSayak Banerjee - S.B - Wrote the MANUSCRIPTAkshaya C Balakrishnan -A.B REVIEWED THE MANUSCRIPTDr.Rashima Asokan -R.A - CONCEPTUALIZATION AND REVIEW OF THE MANUSCRIPT Acknowledgement The authors would like to acknowledge the invaluable support provided by Sankara Nethralaya and the Elite School of Optometry. Special thanks to Dr. Girish Kumar for his assistance in developing the Python scripts used for data transformation in this study. References Rabinowitz YS. The genetic and environmental factors for keratoconus. Surv Ophthalmol. 1998;42(4):297–319. Gomes JA, Rapuano CJ, Belin MW, Ambrosio R Jr, Ambrósio R, et al. Global consensus on keratoconus diagnosis. Cornea. 2015;34(12):e38–e39. Gorskova EN, Sevost'ianov EN. Epidemiologiia keratokonusa na Urale [Epidemiology of keratoconus in the Urals]. Vestn Oftalmol. 1998;114(4):38–40. Torres Netto EA, Al-Otaibi WM, Hafezi NL, Kling S, Al-Farhan HM, Randleman JB, et al. Prevalence of keratoconus in pediatric patients in Riyadh, Saudi Arabia. Br J Ophthalmol. 2018;102(10):1436–41. Belin MW, Kundu G, Shetty N, Ambrósio R Jr, Gatinel D, Gomes JAP, et al. ABCD: A new classification for keratoconus. Indian J Ophthalmol. 2020;68(12):2831–4. Maeda N, Fujikado T, Kuroda T, Ninomiya S, Tano Y. Wavefront aberrations measured with Hartmann-Shack sensor in patients with keratoconus. Ophthalmology. 2002;109(11):1996–2003. Negishi K, Kumanomido T, Utsumi Y, Tsubota K. Effect of higher-order aberrations on visual function in keratoconus eyes with a rigid gas permeable contact lens. Am J Ophthalmol. 2007;144(6):924–9. Applegate RA, Hilmantel G, Howland HC, Tu EY, Starck T, Zayac EJ. Corneal first surface optical aberrations and visual performance. J Refract Surg. 2000;16(5):507–14. Maeda N, Fujikado T, Kuroda T, Ninomiya S, Tano Y. Wavefront aberrations measured with Hartmann-Shack sensor in patients with keratoconus. Ophthalmology. 2002;109(11):1996–2003. Barbero S, Marcos S, Merayo-Lloves J, Moreno-Barriuso E. Validation of the estimation of corneal aberrations from videokeratography in keratoconus. J Refract Surg. 2002;18(3):263–70. Shneor E, Piñero DP, Doron R. Contrast sensitivity and higher-order aberrations in keratoconus subjects. Sci Rep. 2021;11(1):12971. Tang Y, Zhou Y. Age-related decline of contrast sensitivity for second-order stimuli: earlier onset, but slower progression, than for first-order stimuli. J Vis. 2009;9(7):18. Berdahl JP, Yeu E. Clinical applications of ray tracing aberrometry in assessing accommodation and visual function. J Cataract Refract Surg. 2021;47(9):1179–85. Atchison DA. Recent advances in representation of monochromatic aberrations of human eyes. Clin Exp Optom. 2004;87(3):138–48. Chua BE, Mitchell P, Cumming RG. Effects of cataract type and location on visual function: the Blue Mountains Eye Study. Eye (Lond). 2004;18(8):765–72. Rocha KM, Vabre L, Chateau N, Krueger RR. Enhanced visual acuity and image perception in keratoconus eyes following correction of aberrations using an adaptive optics visual simulator. Invest Ophthalmol Vis Sci. 2009;50(13):3049. Nakagawa T, Maeda N, Kosaki R, Hori Y, Inoue T, Saika M, et al. Higher-order aberrations due to the posterior corneal surface in patients with keratoconus. Invest Ophthalmol Vis Sci. 2009;50(6):2660–5. Feizi S, Einollahi B, Raminkhoo A, Salehirad S. Correlation between corneal topographic indices and higher-order aberrations in keratoconus. J Ophthalmic Vis Res. 2013;8(2):113–8. Xian Y, Ye Y, Sun L, Shen Y, Zhang X, Lu ZL, et al. Comparison of the quantitative contrast sensitivity function between early keratoconus and normal eyes. BMC Ophthalmol. 2024;24(1):458. Okamoto C, Kitazawa K, Shimizu K. Higher-order wavefront aberration and letter-contrast sensitivity in keratoconus. Eye (Lond). 2008;22(12):1488–92. Pesudovs K, Schoneveld P, Seto RJ, Coster DJ. Contrast and glare testing in keratoconus and after penetrating keratoplasty. Br J Ophthalmol. 2004;88(5):653–7. Jinabhai A, O'Donnell C, Radhakrishnan H, Nourrit V. Forward light scatter and contrast sensitivity in keratoconic patients. Cont Lens Anterior Eye. 2012;35(1):22–7. Tables Table 1. Demography, median visual acuity, and refraction for the keratoconus group and control group. * Significant level of <0.05, **Significant level of <0.001. † Fisher’s exact test was used to test the gender differences between groups. VA, visual acuity; D, dioptre. P-values were calculated using the Mann–Whitney U test. KC group (n=14) Control group (n=9) KC versus controls No of eyes 18 18 - Age range(years) 16-38 20-34 - Median age(years)with IQR 23(7) 22(1) u=116, p=0.13 Gender (male: female) 9:5 4:5 χ 2 (1,36) = 0.45, p=0.52 † VA range 0.00 to 0.39 0.00 to 0.00 - VA (log MAR) with IQR 0.17(0.115) 0.00(0.00) u=45.0, p<0.05* Spherical Equivalent (D) with IQR -4.50(4.46) -0.75(2.31) u=59.5, p<0.001** Table 2 . Corneal parameters and ocular higher-order aberrations for the keratoconus group and the control group. *Significant at p < 0.05; *Significant at p < 0.001. VA, visual acuity; K, keratometry; CCT, central corneal thickness; TCT, thinnest corneal thickness; RMS, root mean square; HOA, higher-order aberrations; µm, micrometer. P-values were calculated using the Mann–Whitney U test. Keratoconus group (Median, IQR) Control group ( Median, IQR) KC versus controls Scheimpflug/Placido disc measurement K 1 (mm) 7.485 (0.458) 7.690 (0.185) u=88.500, p < 0.05* K 2 (mm) 6.945 (0.480) 7.550 (0.313) u=39.00, p<0.001** K av (mm) 7.185 (0.487) 7.585 (0.220) u= 55.500, p < 0.01** CCT (mm) 469.5 (38.75) 579.0 (23.25) u= 0.000, p < 0.001** Ray-Tracing ocular higher order aberrations Total RMS HOA (µm) 0.1397 (0.11) 0.0290 (0.01) u= 5.000, p < 0.001** Trefoil(µm) 0.3540 (0.30) 0.1000 (0.07) u= 16.000, p < 0.001** Total Coma(µm) 0.4845 (0.53) 0.0720 (0.05) u= 2.000, p < 0.001** Tetrafoil(µm) 0.1350 (0.07) 0.0355 (0.02) u= 24.000, p < 0.001** Table 3 Correlation between ocular higher-order aberrations and contrast sensitivity for keratoconus group and controls *Significant level of < 0.05, RMS, root mean square; HOA, higher-order aberrations; Spearman correlation results. RMS, root mean square; HOA, higher order aberrations; R Spearman correlation results. Mild KC Controls AULCSF AULCSF (Glare) Glare Disability AULCSF AULCSF (Glare) Glare Disability Total RMS HOA r -0.461 -0.38 -0.04 -0.48 -0.31 0.182 p 0.004* 0.12 0.12 0.04* 0.20 0.46 Trefoil r -0.27 -0.193 0.008 -0.45 -0.21 -0.23 p 0.26 0.40 0.70 0.05 0.38 0.30 Total Coma r -0.451 -0.364 -0.06 -0.50 -0.60 -0.175 p 0.04* 0.138 0.70 0.03* 0.008* 0.48 Tetrafoil r -0.22 -0.261 0.133 -0.13 -0.225 -0.121 p 0.38 0.29 0.59 0.58 0.37 0.637 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 25 Apr, 2026 Reviews received at journal 24 Apr, 2026 Reviews received at journal 13 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers agreed at journal 06 Apr, 2026 Reviewers agreed at journal 09 Dec, 2025 Reviewers invited by journal 04 Dec, 2025 Editor assigned by journal 04 Dec, 2025 Submission checks completed at journal 03 Dec, 2025 First submitted to journal 02 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":127010,"visible":true,"origin":"","legend":"\u003cp\u003eContrast Sensitivity in different spatial frequencies for the Keratoconus and the normal group (on the left) and Glare Contrast Sensitivities in different spatial frequencies for the Keratoconus and the normal group (on the right). Blue bars represent contrast sensitivity for control subjects while green bar represents contrast sensitivity for keratoconus subject. *Significant level of 0.005. The figure was generated using SPSS version 25 and the resolution adjusted using Microsoft 365 PowerPoint Version 2103.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-8257640/v1/68cc06a936952cf1343b0d1a.png"},{"id":98622520,"identity":"1e031dfa-c343-43df-9afa-d7145af46264","added_by":"auto","created_at":"2025-12-19 16:56:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1226830,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8257640/v1/a58e82cb-7820-4190-b311-77c7383c88f4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Higher order aberrations and glare disability in Mild Keratoconus: A comparative study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKeratoconus (KC) is a progressive, bilateral corneal ectasia characterized by stromal thinning and biomechanical weakening, leading to irregular astigmatism, myopia, and significant visual distortion.\u003csup\u003e1\u003c/sup\u003e While the disease does not cause blindness, its impact on daily activities, such as reading, driving, and navigating low-light environments, can be profound, even in its mildest stages. \u003csup\u003e2\u003c/sup\u003e Globally, 0.2 to 4,790 per 100,000 persons and 1.5 and 25 per 100,000 individuals/year, a higher incidence is observed in younger populations.\u003csup\u003e3,4\u003c/sup\u003e Early detection and management are critical to preserving vision and quality of life, especially as advanced imaging techniques like Scheimpflug tomography have improved the diagnosis of subclinical and mild cases. \u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn keratoconus, structural changes in the cornea result in a marked increase in higher-order aberrations (HOAs), particularly vertical coma and spherical aberration. \u003csup\u003e6\u003c/sup\u003e These optical irregularities degrade visual quality by disrupting light focusing and reducing contrast sensitivity, a key functional vision metric that measures the ability to discern objects against varying luminance levels. \u003csup\u003e7\u003c/sup\u003e Studies have looked at the correlation between HOA and contrast sensitivity inpatients with keratoconus. Indeed, they found that increased HOA has been shown to correlate with a decrease in contrast sensitivity. \u003csup\u003e8,9,10\u003c/sup\u003e Studies have reported that elevated HOAs persist in milder forms of keratoconus and exhibit reduced contrast sensitivity and higher ocular HOAs compared to controls, suggesting that increased HOAs may partially explain the reduced vision quality in keratoconus and keratoconus suspects.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhile keratoconus is well-recognized for its impact on visual quality, most existing research has focused on moderate to severe disease stages or relied heavily on high-contrast visual acuity, which fails to capture the nuances of real-world visual function. Even though some studies have explored contrast sensitivity in keratoconus, glare disability, a crucial component of functional vision remains largely uninvestigated in this population.\u003c/p\u003e\u003cp\u003eGiven the inherent heterogeneity of keratoconus, including variability in cone location and morphology, perfectly matching all disease parameters in a cross-sectional design is nearly impossible. Furthermore, visual performance may also be modulated by neural factors, such as age-related differences in visual processing, adding another layer of complexity.\u003c/p\u003e\u003cp\u003eTo minimize confounding variables, this study specifically targets mild keratoconus, by quantifying glare-induced contrast sensitivity deficits across spatial frequencies and examining their relationship with higher-order aberrations (HOAs), this study aims to shed light on subtle but impactful functional impairments in early keratoconus, offering a more sensitive approach to detecting visual disability than standard acuity metrics alone.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy Design\u003ch2\u003e\n\u003cp\u003eA prospective comparative cohort study was conducted in speciality contact lens clinic at Sankara Nethralaya between December 1, 2024, and April 1, 2025. The research adhered to the ethical principles outlined in the Declaration of Helsinki (1964). Patient anonymity was strictly maintained, and informed consent was obtained for all procedures. The study received approval from the Institutional Review Board and Ethics Committee of Medical Research Foundation.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eHealthy, and mild keratoconus subjects (males and females) between the ages 17\u0026ndash;40 years participated in this study. Subjects above 40 were not recruited to the study since contrast sensitivity has been shown to be reduced above this age.\u003csup\u003e12\u003c/sup\u003e Subjects were recruited from the clinics and student body of Sankara Nethralaya. The methods were orally explained to the participant and they signed a statement of informed consent prior to their participation.\u003c/p\u003e\u003cp\u003eSubjects were classified into two groups, Keratoconus and control groups. The Keratoconus group included only included Grade 0 and 1 as per the ABCD classification developed by Belin MW.\u003csup\u003e5\u003c/sup\u003e All subjects had no previous history of any ocular surgery or trauma.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProcedure\u003c/h3\u003e\n\u003cp\u003eParticipants underwent a comprehensive eye examination which included a vision assessment, objective, subjective refraction, slit lamp and fundus examination. Total ocular wavefront aberrometry was performed following which the Contrast Sensitivity with and without Glare source was performed. Wavefront aberrations (3rd to 8th radial order Zernike polynomials) were using 785 nm wavelength aberrometer (Tracey Technologies, USA) under of light using the Itrace\u0026trade; wavefront non-cycloplegic, unaided, mesopic conditions The Zernike coefficients were computed for a 4 mm pupil size using the rescaling algorithm within the Itrace software. Even though all wavefront aberration measurements were obtained under non-cycloplegic viewing conditions, a relatively stable accommodative state of the eye was ensured by the dynamic fogging method used by the Itrace\u0026trade; aberrometer during its measurements \u003csup\u003e13\u003c/sup\u003e The ocular HOA were quantified using the root mean square as an index of the image quality. Root Mean Square values were obtained by calculating the square root of the sum of the squares of j6 to j20, using the standard nomenclature for describing Zernike terms found in Atchison et al. \u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eFrom the 35 Zernike coefficients measured by the instrument, the following RMS groups were examined: total RMS HOA (all terms included in the third, fourth, fifth, and sixth order), total trefoil (including j6, j9, j16, and j19), total coma (including j7, j8, j17, and j18) and total tetrafoil (including j10, j14, j22, and j26) Auto-keratometry, corneal topography, and tomography were performed using the Pentacam (Oculus, Germany).\u003c/p\u003e\u003cp\u003eContrast sensitivity was assessed monocularly for all participants using their best spectacle correction across spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd) under mesopic lighting conditions, both with and without glare. Testing employed the CSV-100\u0026trade; chart (Vector Vision), with a grating luminance of 85 cd/m\u0026sup2;; during glare assessments, a halogen light source providing an equivalent luminance of 2.5 cd/m\u0026sup2; at eye level was introduced. Contrast sensitivity was graded on a 10-point scale at each frequency: participants who could not perceive the test strip or the highest contrast bar were scored \u0026minus;\u0026thinsp;1 and 0, respectively, while those detecting any of the eight progressively lower contrast levels were scored from 1 to 8. These raw scores were then converted into log contrast sensitivity values using Vector Vision\u0026rsquo;s standard definitions, as implemented by Chua et al.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Normality was checked on each parameter for each group separately by means of the Wilk-Shapiro test. Fisher\u0026rsquo;s exact test was used to test gender differences between groups. The Mann-Whitney test was performed to assess the differences between groups of subjects. Spearman correlation was performed to test the correlation between ocular HOA and contrast sensitivity. Friedman test and Post hoc analysis with Wilcoxon signed-rank tests were performed to compare contrast sensitivity in different frequencies (6, 9 and 12 cycles/deg) for each group of subjects. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included 36 eyes of 22 patients. The median age was 22.0 years (IQR: 3.0; range: 16\u0026ndash;38), and the median best-corrected visual acuity was 0.00 log MAR (IQR: 0.17; range: 0.00\u0026ndash;0.39).\u003c/p\u003e\n\u003cp\u003eThe keratoconus group consisted of 18 eyes from 14 patients (9 males, 5 females) with mild keratoconus (Grades 0 and 1), aged 16\u0026ndash;38 years (median: 23.0 years; IQR: 7.0). The median best-corrected visual acuity in this group was 0.17 log MAR (IQR: 0.12). The control group included 18 eyes from 9 healthy subjects (5 females), aged 20\u0026ndash;34 years (median: 22.0 years; IQR: 1.0), with a median visual acuity of 0.00 log MAR (IQR: 0.00).\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference in age between the groups (U\u0026thinsp;=\u0026thinsp;116.0, p\u0026thinsp;=\u0026thinsp;0.13) Fisher\u0026rsquo;s test was conducted to assess the association between gender and group membership, revealing no significant difference (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The odds ratio was 2.25 (95% C.I [0.9-5.0]). There was no statistically significant difference in age nor in gender distribution between the two groups. However, the keratoconus group had significantly poorer visual acuity (U\u0026thinsp;=\u0026thinsp;45.0, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and greater spherical equivalent refractive error (U\u0026thinsp;=\u0026thinsp;59.5, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the corneal parameters and higher-order aberrations (HOAs) for both groups. Statistically significant group differences were observed for visual acuity, spherical equivalent, keratometric values, central corneal thickness, and the following HOAs: total RMS, trefoil, total coma, and tetrafoil. Given the established relationship between contrast sensitivity (CS) and visual acuity, CS was assessed under both glare and no-glare conditions. The area under the log contrast sensitivity function (AULCSF) was computed using Simpson\u0026rsquo;s rule via Python\u0026reg;.\u003c/p\u003e\n\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates contrast sensitivity across spatial frequencies. In the no-glare condition, contrast sensitivity was significantly reduced in the keratoconus group at all frequencies: 1.49 (IQR: 0.18), 1.55 (0.32), 1.25 (0.36), and 0.56 (0.49) at 3, 6, 12, and 18 cycles per degree (cpd), respectively, compared to the control group which showed 1.78 (0.15), 2.14 (0.15), 1.84 (0.15), and 1.40 (0.30) at the same frequencies. Under glare conditions, the keratoconus group again showed reduced contrast sensitivity: 1.42 (0.33), 1.63 (0.32), 1.08 (0.49), and 0.64 (0.34) across 3, 6, 12, and 18 cpd, respectively, compared to the control group: 1.78 (0.15), 1.99 (0.15), 1.69 (0.15), and 1.40 (0.15).\u003c/p\u003e\n\u003cp\u003eIndividual Mann\u0026ndash;Whitney U tests revealed statistically significant group differences at all spatial frequencies (3, 6, 12, and 18 cpd) under both glare and no-glare conditions, even after Bonferroni correction (adjusted \u0026alpha;\u0026thinsp;=\u0026thinsp;0.0125).\u003c/p\u003e\n\u003cp\u003eThe median AULCSF under no-glare conditions was significantly lower in the keratoconus group at 19.3 (IQR: 3.60) compared to 28.4 (IQR: 1.70) in controls (U\u0026thinsp;=\u0026thinsp;0.00, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Under glare conditions, AULCSF was 18.2 (IQR: 5.20) in the keratoconus group versus 27.3 (IQR: 2.3) in controls (U\u0026thinsp;=\u0026thinsp;0.00, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Glare disability, defined as the ratio of AULCSF under glare to no-glare, was 1.04 (IQR: 0.16) for keratoconus and 1.03 (IQR: 0.03) for controls, with no significant difference between the groups (U\u0026thinsp;=\u0026thinsp;154.00, p\u0026thinsp;=\u0026thinsp;0.80).\u003c/p\u003e\n\u003cp\u003eThe higher-order RMS aberrations were negatively correlated with contrast sensitivity at medium and high spatial frequencies. Although AULCSF was significantly reduced in mild keratoconus, the calculated glare disability scores were not significantly different from controls.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study revealed that individuals with mild keratoconus exhibit significantly elevated higher-order aberrations (HOAs) compared to normal controls, even when best-corrected visual acuity is similar, highlighting HOAs as a defining optical feature of keratoconus across all disease stages. Extensive research has consistently shown that keratoconic eyes have markedly higher root mean square (RMS) HOA values than normal eyes.\u003csup\u003e16\u003c/sup\u003e Both anterior and posterior corneal surfaces contribute to these elevated aberrations, with posterior surface HOAs alone showing mean total values of 1.09 \u0026micro;m in keratoconus compared to just 0.15 \u0026micro;m in normal eyes \u003csup\u003e17,18\u003c/sup\u003e and 0.02\u0026micro;m in this study. Vertical coma is the most dominant aberration type in keratoconus and shows the strongest correlation with corneal irregularity indices followed by spherical and horizontal coma as reported by a previous study.\u003csup\u003e18\u003c/sup\u003e This predominance of vertical coma is attributed to the typical inferior displacement of the cone, which leads to increased topographic asymmetry and explains the asymmetrical nature of HOA patterns observed in keratoconic eyes. Interestingly, posterior surface coma may partially compensate for the anterior surface aberrations, indicating a complex interplay between the two corneal surfaces in the generation of HOAs.\u003c/p\u003e\u003cp\u003eDespite normal visual acuity, individuals with mild keratoconus frequently experience reduced contrast sensitivity, a finding that underscores the disconnect between standard acuity measurements and real-world visual quality. Quantitative contrast sensitivity function testing has demonstrated that even early keratoconus patients with 20/20 corrected vision show significantly impaired contrast sensitivity at both low (1.0 and 1.5 cycles per degree) and high (12.0 and 18.0 cycles per degree) spatial frequencies when compared to normal eyes.\u003csup\u003e19\u003c/sup\u003e This reduction in contrast sensitivity is particularly relevant, as it correlates more closely with refractive error, topographic indices, and HOA values than visual acuity alone. The inverse relationship between HOAs and contrast sensitivity has been well-documented, with studies employing psychophysical testing methods such as two-alternative forced-choice Gabor patches reporting strong negative correlations, for third-order aberrations. \u003csup\u003e20\u003c/sup\u003e Notably, these negative associations remain significant even in keratoconus patients who demonstrate perfect log MAR acuity (0.00), particularly at medium and high spatial frequencies, reinforcing the notion that HOAs are a key contributor to the functional visual limitations experienced by keratoconus patients.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eFindings on glare sensitivity in keratoconus have been somewhat inconsistent, with earlier research suggesting that glare testing may have limited clinical utility because visual loss in keratoconus is primarily driven by optical aberrations rather than intraocular light scatter. \u003csup\u003e21\u003c/sup\u003e However, more recent studies using alternative methods, such as the Brightness Acuity Tester (BAT) with lower intensity glare sources, have detected measurable glare-related visual losses in keratoconus patients. \u003csup\u003e22\u003c/sup\u003e This divergence in findings is likely due to differences in glare source intensity; higher-intensity glare tends to induce pupillary constriction, which reduces the influence of aberrated optics by limiting the entrance pupil. Consequently, studies using subtler glare stimuli may be better able to detect the functional visual disturbances caused by optical imperfections in keratoconus.\u003c/p\u003e\u003cp\u003eIn this study\u0026rsquo;s cohort, contrast sensitivity declined under glare conditions in both keratoconus and control eyes, but the reduction reached statistical significance only in the control group. Although the percentage drop in contrast sensitivity was slightly higher in the keratoconus group (4% vs. 3%), with no significant difference in glare-related contrast loss between the two groups. This suggests that while both groups are affected by glare, eyes with mild keratoconus may already function under compromised baseline conditions due to pre-existing optical aberrations, thereby reducing the relative impact of additional glare. A weak, non-significant positive correlation was observed between glare disability and total HOAs (RMS), in contrast to previous studies that reported stronger inverse relationships. Such discrepancies may stem from methodological variations, including the type of contrast sensitivity assessment (e.g., Gabor patches versus letter charts), the spatial frequencies tested, differences in aberrometric devices, or pupil size during measurement. Collectively, this study\u0026rsquo;s results, alongside existing literature, indicate that contrast sensitivity loss in keratoconus is multifactorial. While HOAs contribute significantly, other factors such as intraocular light scatter and neural adaptation to chronic optical blur also appear to influence visual performance. Indeed, even when HOAs are corrected with adaptive optics, keratoconic eyes often continue to underperform compared to normal eyes, possibly due to long-standing cortical adaptation or diminished retinal sensitivity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMadhumathi Subramanian - M.S - CONCEPTUALIZATION AND REVIEW OF THE MANUSCRIPTSayak Banerjee - S.B - Wrote the MANUSCRIPTAkshaya C Balakrishnan -A.B REVIEWED THE MANUSCRIPTDr.Rashima Asokan -R.A - CONCEPTUALIZATION AND REVIEW OF THE MANUSCRIPT\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e The authors would like to acknowledge the invaluable support provided by Sankara Nethralaya and the Elite School of Optometry. Special thanks to Dr. Girish Kumar for his assistance in developing the Python scripts used for data transformation in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRabinowitz YS. The genetic and environmental factors for keratoconus. Surv Ophthalmol. 1998;42(4):297\u0026ndash;319.\u003c/li\u003e\n\u003cli\u003eGomes JA, Rapuano CJ, Belin MW, Ambrosio R Jr, Ambr\u0026oacute;sio R, et al. Global consensus on keratoconus diagnosis. Cornea. 2015;34(12):e38\u0026ndash;e39.\u003c/li\u003e\n\u003cli\u003eGorskova EN, Sevost\u0026apos;ianov EN. Epidemiologiia keratokonusa na Urale [Epidemiology of keratoconus in the Urals]. Vestn Oftalmol. 1998;114(4):38\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eTorres Netto EA, Al-Otaibi WM, Hafezi NL, Kling S, Al-Farhan HM, Randleman JB, et al. Prevalence of keratoconus in pediatric patients in Riyadh, Saudi Arabia. Br J Ophthalmol. 2018;102(10):1436\u0026ndash;41.\u003c/li\u003e\n\u003cli\u003eBelin MW, Kundu G, Shetty N, Ambr\u0026oacute;sio R Jr, Gatinel D, Gomes JAP, et al. ABCD: A new classification for keratoconus. Indian J Ophthalmol. 2020;68(12):2831\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eMaeda N, Fujikado T, Kuroda T, Ninomiya S, Tano Y. Wavefront aberrations measured with Hartmann-Shack sensor in patients with keratoconus. Ophthalmology. 2002;109(11):1996\u0026ndash;2003.\u003c/li\u003e\n\u003cli\u003eNegishi K, Kumanomido T, Utsumi Y, Tsubota K. Effect of higher-order aberrations on visual function in keratoconus eyes with a rigid gas permeable contact lens. Am J Ophthalmol. 2007;144(6):924\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eApplegate RA, Hilmantel G, Howland HC, Tu EY, Starck T, Zayac EJ. Corneal first surface optical aberrations and visual performance. J Refract Surg. 2000;16(5):507\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eMaeda N, Fujikado T, Kuroda T, Ninomiya S, Tano Y. Wavefront aberrations measured with Hartmann-Shack sensor in patients with keratoconus. Ophthalmology. 2002;109(11):1996\u0026ndash;2003.\u003c/li\u003e\n\u003cli\u003eBarbero S, Marcos S, Merayo-Lloves J, Moreno-Barriuso E. Validation of the estimation of corneal aberrations from videokeratography in keratoconus. J Refract Surg. 2002;18(3):263\u0026ndash;70.\u003c/li\u003e\n\u003cli\u003eShneor E, Pi\u0026ntilde;ero DP, Doron R. Contrast sensitivity and higher-order aberrations in keratoconus subjects. Sci Rep. 2021;11(1):12971.\u003c/li\u003e\n\u003cli\u003eTang Y, Zhou Y. Age-related decline of contrast sensitivity for second-order stimuli: earlier onset, but slower progression, than for first-order stimuli. J Vis. 2009;9(7):18.\u003c/li\u003e\n\u003cli\u003eBerdahl JP, Yeu E. Clinical applications of ray tracing aberrometry in assessing accommodation and visual function. J Cataract Refract Surg. 2021;47(9):1179\u0026ndash;85.\u003c/li\u003e\n\u003cli\u003eAtchison DA. Recent advances in representation of monochromatic aberrations of human eyes. Clin Exp Optom. 2004;87(3):138\u0026ndash;48.\u003c/li\u003e\n\u003cli\u003eChua BE, Mitchell P, Cumming RG. Effects of cataract type and location on visual function: the Blue Mountains Eye Study. Eye (Lond). 2004;18(8):765\u0026ndash;72.\u003c/li\u003e\n\u003cli\u003eRocha KM, Vabre L, Chateau N, Krueger RR. Enhanced visual acuity and image perception in keratoconus eyes following correction of aberrations using an adaptive optics visual simulator. Invest Ophthalmol Vis Sci. 2009;50(13):3049.\u003c/li\u003e\n\u003cli\u003eNakagawa T, Maeda N, Kosaki R, Hori Y, Inoue T, Saika M, et al. Higher-order aberrations due to the posterior corneal surface in patients with keratoconus. Invest Ophthalmol Vis Sci. 2009;50(6):2660\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eFeizi S, Einollahi B, Raminkhoo A, Salehirad S. Correlation between corneal topographic indices and higher-order aberrations in keratoconus. J Ophthalmic Vis Res. 2013;8(2):113\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eXian Y, Ye Y, Sun L, Shen Y, Zhang X, Lu ZL, et al. Comparison of the quantitative contrast sensitivity function between early keratoconus and normal eyes. BMC Ophthalmol. 2024;24(1):458.\u003c/li\u003e\n\u003cli\u003eOkamoto C, Kitazawa K, Shimizu K. Higher-order wavefront aberration and letter-contrast sensitivity in keratoconus. Eye (Lond). 2008;22(12):1488\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003ePesudovs K, Schoneveld P, Seto RJ, Coster DJ. Contrast and glare testing in keratoconus and after penetrating keratoplasty. Br J Ophthalmol. 2004;88(5):653\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eJinabhai A, O\u0026apos;Donnell C, Radhakrishnan H, Nourrit V. Forward light scatter and contrast sensitivity in keratoconic patients. Cont Lens Anterior Eye. 2012;35(1):22\u0026ndash;7.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Demography, median visual acuity, and refraction for the keratoconus group and control group. * Significant level of \u0026lt;0.05, **Significant level of \u0026lt;0.001. \u0026dagger; Fisher\u0026rsquo;s exact test was used to test the gender differences between groups. VA, visual acuity; D, dioptre. P-values were calculated using the Mann\u0026ndash;Whitney U test.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"681\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKC group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKC versus controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eNo of eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eAge range(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e16-38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e20-34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eMedian age(years)with IQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e23(7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e22(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eu=116, p=0.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eGender (male: female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e9:5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4:5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e (1,36) = 0.45, p=0.52 \u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eVA range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 to 0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.00 to 0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eVA (log MAR) with IQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.17(0.115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eu=45.0, p\u0026lt;0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 248px;\"\u003e\n \u003cp\u003eSpherical Equivalent (D) with IQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e-4.50(4.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e-0.75(2.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eu=59.5, p\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Corneal parameters and ocular higher-order aberrations for the keratoconus group and the control group. *Significant at p \u0026lt; 0.05; *Significant at p \u0026lt; 0.001. VA, visual acuity; K, keratometry; CCT, central corneal thickness; TCT, thinnest corneal thickness; RMS, root mean square; HOA, higher-order aberrations; \u0026micro;m, micrometer. P-values were calculated using the Mann\u0026ndash;Whitney U test.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"681\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKeratoconus group (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003e\u003cstrong\u003eMedian, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKC versus controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 681px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScheimpflug/Placido disc measurement\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eK\u003csub\u003e1\u003c/sub\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e7.485 (0.458)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e7.690 (0.185)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=88.500, p \u0026lt; 0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eK\u003csub\u003e2\u003c/sub\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e6.945 (0.480)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e7.550 (0.313)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=39.00, p\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eK\u003csub\u003eav\u003c/sub\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e7.185 (0.487)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e7.585 (0.220)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=\u0026nbsp;55.500, p \u0026lt; 0.01**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eCCT (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e469.5 (38.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e579.0 (23.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=\u0026nbsp;0.000, p \u0026lt; 0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 681px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRay-Tracing ocular higher order aberrations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eTotal RMS HOA (\u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.1397 (0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e0.0290 (0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=\u0026nbsp;5.000, p \u0026lt; 0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eTrefoil(\u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.3540 (0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e0.1000 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=\u0026nbsp;16.000, p \u0026lt; 0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eTotal Coma(\u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.4845 (0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e0.0720 (0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu=\u0026nbsp;2.000, p \u0026lt; 0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eTetrafoil(\u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.1350 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e0.0355 (0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eu= 24.000, p \u0026lt; 0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Correlation between ocular higher-order aberrations and contrast sensitivity for keratoconus group and controls *Significant level of \u0026lt; 0.05, RMS, root mean square; HOA, higher-order aberrations; Spearman correlation results. RMS, root mean square; HOA, higher order aberrations; R Spearman correlation results.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"674\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 116px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 271px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild KC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAULCSF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAULCSF\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Glare)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlare Disability\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAULCSF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAULCSF (Glare)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlare Disability\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal RMS HOA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e-0.461\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e-0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e-0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e-0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrefoil\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e-0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e-0.193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e-0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e-0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Coma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e-0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e-0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e-0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e-0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.008*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTetrafoil\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e-0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e-0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e-0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e-0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e-0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.637\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8257640/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8257640/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e:\u0026nbsp; To quantify glare-induced contrast sensitivity deficits across spatial frequencies in mild keratoconus and compare these functional impairments to age-matched controls.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: Eighteen eyes with early keratoconus (grade 0–1, Belin ABCD) to age-matched controls. Visual acuity, wavefront aberrometry, and contrast sensitivity (CSV-1000HGT) were evaluated under baseline and glare conditions using best spectacle correction. Contrast thresholds were recorded across four spatial frequencies. Group differences were analyzed using non-parametric statistical tests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Median age and visual acuity were similar between groups, though the Mild KC group had reduced acuity (0.13 log MAR). Higher-order aberrations (HOA) were significantly elevated in Mild KC (0.139 vs. 0.028; p \u0026lt; 0.05). Contrast sensitivity declined under glare in both groups, but significantly only in controls. Mild KC showed a 4% reduction vs. 3% in controls. A strong positive correlation was found between HOA and contrast sensitivity (R = 0.82, p \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Mild KCs are also associated with significantly elevated HOA and subtle but notable reduction in contrast sensitivity under glare, despite comparable median visual acuity between groups, the Mild KC cohort exhibited a greater reduction in AULCSF with glare exposure, although the effect of glare as defined by Glare disability doesn’t tend to differ significantly among the two groups.\u003c/p\u003e","manuscriptTitle":"Higher order aberrations and glare disability in Mild Keratoconus: A comparative study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 16:39:31","doi":"10.21203/rs.3.rs-8257640/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-25T12:35:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-24T20:51:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-13T20:34:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176967134401220193868006773756902858202","date":"2026-04-07T19:23:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333808781419609110519627067158490345265","date":"2026-04-06T18:10:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227980893444315846930294670395094542460","date":"2025-12-09T20:10:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-04T18:51:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-04T18:50:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-04T00:28:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Ophthalmic and Physiological Optics","date":"2025-12-02T07:57:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fe2318f3-cf15-411c-90d7-955e185c8d59","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-25T12:39:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 16:39:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8257640","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8257640","identity":"rs-8257640","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}