Comparison of the quantitative contrast sensitivity function between early keratoconus and normal eyes

Abstract

Purpose

To compare the characteristics of the quantitative contrast sensitivity function (qCSF) in eyes with early keratoconus (Early-KC) and normal control (NC) eyes and investigate the associated factors.

Design

A cross-sectional study.

Methods

This study included 43 eyes of 43 patients with Early-KC (including subclinical keratoconus [SKC] and forme fruste keratoconus [FFKC]) and 77 NC eyes of 77 participants with corrected distance visual acuity (CDVA) all ≥ 20/20. Contrast sensitivity (CS) was assessed using the qCSF tests. Subgroup analysis was performed according to keratoconus type(SKC and FFKC) and astigmatism(cylindrical refraction >-1.0D or ≤-1.0D).

Results

Sex ratio, spherical refraction, and spherical equivalent (SE) varied significantly between the two groups (all P < 0.01). The area under log CSF (AULCSF), CSF Acuity, and CS at low (1.0 and 1.5 cycles per degree [cpd]) and high (12.0 and 18.0 cpd) spatial frequencies decreased significantly in the Early-KC group than that in the NC group (all P < 0.05). The subgroup analysis revealed a similar decrease in the SKC group (all P < 0.05). AULCSF, CSF Acuity, and CS at high spatial frequencies of patients with cylindrical refraction ≤-1.0D in the Early-KC group decreased significantly (all P < 0.05) than those in the NC group. The index of vertical asymmetry and index of height decentration correlated negatively with CS at 1.5 cpd (r= -0.321 and -0.306; both P < 0.05).

Conclusions

CS decreased significantly at low and high spatial frequencies in Early-KC, though with normal CDVA. The qCSF test can sensitively reflect visual performance in early keratoconus.

Introduction

Keratoconus is a progressive ectatic corneal disease with a genetic, environmental, and biochemical pathogenesis that includes atopy and inflammation [1]. Patients with keratoconus experience irregular astigmatism, impaired vision, and corneal scarring due to the progressive decrease in the thickness and conic protrusion of the corneal stroma [2]. The global prevalence of keratoconus was estimated to be 138 cases per 100,000 individuals [3]. Keratoconus usually occurs in the second or third decade of life with an asymmetric onset of clinical manifestations between both eyes [4].

In patients with keratoconus, irregular changes in the corneal morphology combined with markedly increased ocular aberrations result in the formation of blurred images on the retina, thereby lowering the visual quality [5, 6]. In clinical settings, the visual acuity test is the most commonly used method to assess subjective visual performance; however, it can only evaluate the ability to distinguish between fine details at high contrast. A significant decrease in the vision-related quality of life (VR-QoL) is observed in some patients with keratoconus with normal corrected visual acuity [7], indicating the limitations of conventional visual acuity tests. In contrast, the contrast sensitivity (CS) test uses optotypes with different sizes and contrasts as visual stimuli and comprehensively assesses contrast thresholds at different spatial frequencies [8], which correlates more closely with daily visual performance [9, 10] and reflects physiological and pathological state more sensitively [11]. Previous studies have examined contrast sensitivity in patients with keratoconus using conventional methods, such as CSV-1000LV [12] and Pelli-Robinson charts; [13] however, the examined spatial frequencies were limited. Computerized tests, such as the Vistech CS chart and the Functional Acuity Contrast Test (FACT), have limited use in clinical practice due to the long testing times and poor repeatability [8].

Lesmes et al. developed the quantitative contrast sensitivity function (qCSF) test by combining Bayesian adaptive algorithm with a 10-alternative forced choice (10-AFC) identification task [14–16]. The qCSF test has been validated; it possesses better test-retest reliability [17] and consistency compared with conventional methods [15]. The qCSF test has been used in several ocular diseases, such as amblyopia and diabetic retinopathy [18, 19]. In a previous study, we evaluated the characteristics of qCSF parameters in keratoconus of varying severity and its relationships with age, refraction, corrected distance visual acuity (CDVA), and corneal topographic parameters [20]. However, the characteristics of qCSF parameters in early keratoconus (including subclinical keratoconus [SKC] and forme fruste keratoconus [FFKC]) relative to those of normal eyes have not been fully evaluated and associated studies were still limited [21]. Therefore, the present study aimed to compare contrast sensitivity of early keratoconus with normal corrected distance visual acuity (CDVA ≥ 20/20) with that of healthy eyes and provide evidence for the use of the qCSF test in clinical practice for assessing visual abnormalities in early keratoconus.

Subjects and methods

Study design

This cross-sectional study was performed in accordance with the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University (ky2012-017). All patients provided written informed consent. Patients with normal CDVA (≥ 20/20) who were admitted to the Eye and ENT Hospital of Fudan University between 2021 and 2022 were enrolled in the study and divided into those with early keratoconus (Early-KC group) and those with normal control eyes (NC group). As there is no universal definition for early keratoconus [4, 22, 23], this study included SKC [24] and FFKC (also known as the fellow eyes of very asymmetric keratoconus with normal topography and tomography) [4, 25] in the Early-KC group based on findings from previous studies. SKC was defined as the contralateral eye of clinically manifest keratoconus with abnormal corneal tomography (paracentral inferior-superior dioptric asymmetry > 1.4 D or anterior/posterior elevations ≥ 8/13 µm on best-fit-sphere [BFS], respectively) without biomicroscopic signs (including Vogt´s striae, Fleischer´s ring, or corneal scarring). FFKC was defined as the contralateral eye of clinically manifest keratoconus without abnormal signs in the slit-lamp and corneal tomographic (paracentral inferior-superior dioptric asymmetry ≤ 1.4 D; or anterior/posterior elevations < 8/13 µm on BFS, respectively) examinations [4, 26–30]. Both eyes of patients in the normal control group were asymptomatic in the slit-lamp and corneal tomographic examinations, and they had no family history of corneal ectasia; only one eye from each patient was randomly enrolled. The exclusion criteria were: (1) history of other ophthalmic diseases, such as cataracts, age-related macular degeneration, or glaucoma; (2) history of systemic diseases, such as diabetes mellitus or connective tissue disease; and (3) a lack of cooperation during the examinations.

Examinations

(1) Subjective refraction: spherical refraction, cylindrical refraction, and CDVA were examined using the RT-5100 phoropter (Nidek Technologies, Japan). (2) Corneal tomography was performed using a Scheimpflug-based anterior segment analyzer (Pentacam HR, Oculus Optikgerate Wetzlar, Germany) and standard capturing procedures [31]. The mean keratometry (Km), maximum keratometry (Kmax) of the anterior surface, thinnest corneal thickness (TCT), front and back elevations at the thinnest point (AETh/BETh), the index of surface variance, index of vertical asymmetry (IVA), keratoconus index, central keratoconus index, index of height asymmetry, index of height decentration (IHD), and minimum sagittal curvature were measured and analyzed.

Quantitative contrast sensitivity function (qCSF) test

The qCSF test was performed as described in our previous studies [20, 32] using an NEC P403 monitor (Gension & Waltai Digital Video System Co., Ltd. China) with a display area of 116.84 × 77.89 cm, a resolution of 1920 × 1080 pixels, a typical background luminance of about 90 - 100 cd/m², and a contrast ratio of 4000:1 in a mesopic environment over a distance of 3 m. The NEC P403 monitor was the only light source in the test environment to ensure the same lighting condition among participants. All subjects underwent the qCSF test with optimum corrections determined by subjective refraction. One eye was tested at a time, while the other eye was covered. As reported by Zheng et al. [16, 33], the test used 10 digits in Sloan font as visual stimuli, with three digits of the same spatial frequency but different contrasts displayed in each trial. The computer depicted the contrast sensitivity function curves directly with estimation and analysis of four parameters: peak contrast sensitivity, peak spatial frequency, bandwidth, and low contrast intercept [16]. The technician entered the corresponding answer on a tablet computer as the patients reported the digits they could or could not see. Twenty-five trials lasting 3 to 5 min were performed for each eye. The qCSF results, including the area under log CSF (AULCSF), CSF Acuity (the cut-off spatial frequency), and CS (log units) at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd), were displayed automatically after the test.

Statistical analysis

Continuous variables were presented as mean, standard deviations, and ranges, whereas categorical variables were presented as frequencies. The Levene’s test was used to assess variance homogeneity. The Shapiro-Wilk test and normal probability Q-Q plots were used to assess normality. As the parameters followed the normal distribution, parametric tests were applied. The participants were classified according to the keratoconus type (the Control, FFKC, and SKC group) and degree of astigmatism (cylindrical refraction > -1.0D and cylindrical refraction ≤ -1.0D) for the subgroup analysis. The Welch t-test, analysis of variance (ANOVA) were used to compare the differences between continuous variables among the groups, and the analysis of covariance (ANCOVA) was used to adjust for confounding factors. For parameters with significant variance heterogeneity, the generalized linear model was applied instead of ANCOVA. Bonferroni correction was used for post hoc tests. The chi-squared test was used to compare the differences between categorical variables (sex ratio) among the groups. Pearson analysis was used to investigate bivariate correlations. As other tomographic parameters were not significantly associated with qCSF parameters, only the correlation between qCSF parameters and IVA or IHD were presented. The simple linear regression models were used to quantify the correlations between these parameters. The Statistical Package For The Social Sciences (SPSS 26.0, IBM Corp., Armonk, NY, USA) was used for statistical analysis. All data were examined using a two-sided test, with P < 0.05 considered statistically significant.

The G*Power (version 3.1.9.7) was used to estimate the sample size required for the study, and the parameters were set as followed: (1) Statistical test: analysis of covariance; (2) Effect size f: 0.4; (3) probability of the α error: 0.05; (4) Power: 0.9; (5) Numerator df: 1; (6) Number of groups: 2; (7) Number of covariates:1. The results indicated a sample size of at least 34 eyes per group.

Results

Demographic and clinical characteristics

Table 1 presents the demographic profiles. The Early-KC group included 43 eyes from 43 patients (age: 23.0 ± 4.9 years, female/male: 12/31), and the NC group included 77 eyes from 77 participants (age: 24.1 ± 3.4 years, female/male: 42/35). The sex ratio, spherical refraction, and spherical equivalent differed significantly between the two groups (P = 0.005, < 0.001, < 0.001), whereas age, cylindrical refraction, and LogMAR CDVA were non-significant (all P > 0.05). Figure 1 depicts the distributions of age and spherical equivalent in the Early-KC and NC groups.

Table 1.

Demographic data of the normal control and early keratoconus groups

Parameters	NC group (n = 77)		Early-KC group (n = 43)		t	P
	Mean ± SD	Range	Mean ± SD	Range
Age (years)	24.1 ± 3.4	(18, 30)	23.0 ± 4.9	(16, 33)	1.370	0.175
Gender(F/M)	42/35	-	12/31	-	-	0.005
Sph (D)	-5.78 ± 2.10	(-13.00, -0.75)	-3.84 ± 2.24	(-9.25, 0.25)	-4.626	< 0.001
Cyl (D)	-1.16 ± 0.90	(-4.00, 0)	-0.88 ± 0.68	(-3.00, 0)	-1.959	0.053
SE (D)	-6.36 ± 2.26	(-13.75, -1.25)	-4.28 ± 2.32	(-10.25, 0)	-4.736	< 0.001
LogMAR BCVA	-0.01 ± 0.02	(-0.08, 0)	0 ± 0.01	(-0.08, 0)	-1.489	0.143

Notes: NC, normal control; Early-KC, early keratoconus; n, number of eyes; Sph, spherical refraction; Cyl, cylindrical refraction; SE, spherical equivalent; LogMAR BCVA, best corrected distance visual acuity (LogMAR); SD, standard deviation; D, diopter

Bold fonts: significant differences (P < 0.05) between the two groups

Fig. 1.

Distribution of age and spherical equivalent in the early keratoconus (Early-KC) and normal control (NC) groups

Group comparisons

Table 2 presents the intergroup differences in the qCSF parameters. All parameters differed significantly between the two groups in the independent t-test (P < 0.05), except for contrast sensitivity at 6.0 cpd. AULCSF and CSF Acuity in the Early-KC group were significantly lower than those in the NC group (0.92 ± 0.22 vs. 1.04 ± 0.19, P = 0.007; 17.08 ± 5.42 vs. 19.36 ± 5.34 cpd, P = 0.003) after adjusting for the sex ratio and spherical equivalent with ANCOVA (Fig. 2A, B). Contrast sensitivity in the Early-KC group was significantly lower than that in the NC group at low (1.0 and 1.5 cpd) and high (12.0 and 18.0 cpd) spatial frequencies (all P < 0.05) (Fig. 2C). There was no significant difference in contrast sensitivity between the two groups at medium spatial frequencies (3.0 and 6.0 cpd) (P = 0.234 and 0.252).

Table 2.

The differences of quantitative contrast sensitivity function between the two groups

Parameters	NC group (n = 77)		Early-KC group (n = 43)		t	P 1	F	P 2
	Mean ± SD	Range	Mean ± SD	Range
AULCSF	1.04 ± 0.19	(0.58, 1.4)	0.92 ± 0.22	(0.43, 1.42)	2.875	0.005	7.680	0.007
CSF Acuity (cpd)	19.36 ± 5.34	(7.0, 31.4)	17.08 ± 5.42	(7.2, 31.4)	1.895	0.061	9.274	0.003
CS (1.0 cpd)	1.27 ± 0.13	(0.97, 1.56)	1.19 ± 0.16	(0.86, 1.64)	2.547	0.013	5.017	0.027
CS (1.5 cpd)	1.31 ± 0.14	(0.69, 1.57)	1.22 ± 0.15	(0.90, 1.61)	3.131	0.002	4.773	0.031
CS (3.0 cpd)	1.26 ± 0.20	(0, 1.57)	1.17 ± 0.19	(0.71, 1.60)	2.432	0.017	1.430	0.234
CS (6.0 cpd)	1.00 ± 0.25	(0, 1.43)	0.92 ± 0.26	(0.30, 1.41)	1.663	0.100	1.325	0.252
CS (12.0 cpd)	0.49 ± 0.27	(0, 0.95)	0.37 ± 0.28	(0, 0.98)	2.139	0.035	5.898	0.017
CS (18.0 cpd)	0.15 ± 0.17	(0, 0.58)	0.09 ± 0.15	(0, 0.65)	2.075	0.041	5.611	0.020

Notes: NC, normal control; Early-KC, early keratoconus; n, number of eyes; SD, standard deviation; CS, contrast sensitivity; CSF, contrast sensitivity function; AULCSF, area under log CSF; cpd, cycle per degree.

P₁, Welch t-test; P₂, analysis of covariance with adjustment for gender and spherical equivalent

Bold fonts: significant differences (P < 0.05) between the two groups

Fig. 2.

Comparison of the quantitative contrast sensitivity function (qCSF) parameters between the early keratoconus (Early-KC) and normal control (NC) groups, including [A] AULCSF, [B] CSF Acuity, and [C] contrast sensitivity (log units) at different spatial frequencies

Abbreviations: AULCSF, area under log contrast sensitivity function; cpd, cycle per degree; *, P < 0.05; **, P < 0.01

Subgroup comparisons

Table 3 presents the results of the subgroup analysis based on the keratoconus type and degree of cylindrical refraction. After adjusting for age, sex ratio, and spherical equivalent (SE), which were significantly different (P = 0.01, 0.003, and < 0.001, respectively) among the NC, FFKC, and SKC groups, the AULCSF, CSF Acuity, and contrast sensitivity at low and high spatial frequencies (1.0, 1.5, 12.0, and 18.0 cpd) differed significantly among the three groups (all P < 0.05). Post hoc tests revealed that these parameters were significantly lower in the SKC group compared with those in the NC group (all P < 0.05). The sex ratio and SE were significantly different between the two subgroups of patients with Cyl>-1.0D (P = 0.003 and 0.001, respectively), and were adjusted for the following analysis. The qCSF parameters did not differ significantly between the two subgroups of patients with Cyl >-1.0 D. AULCSF, CSF acuity, and contrast sensitivity at high spatial frequencies (12.0 and 18.0 cpd) in patients with Cyl ≤-1.0 D were significantly lower in the Early-KC group than those in the NC group (all P < 0.05), after adjusting for SE which were significantly different between the two groups (P = 0.002).

Table 3.

Subgroup comparisons of qCSF parameters

Parameters	AULCSF	CSF Acuity	CS (1.0 cpd)	CS (1.5 cpd)	CS (3.0 cpd)	CS (6.0 cpd)	CS (12.0 cpd)	CS (18.0 cpd)
Type
NC (n = 77)	1.04 ± 0.19 *	19.36 ± 5.34 *	1.27 ± 0.13 *	1.31 ± 0.14 *	1.26 ± 0.20	1.00 ± 0.25	0.49 ± 0.27 *	0.15 ± 0.17 *
FFKC (n = 22)	0.99 ± 0.23	18.47 ± 5.87	1.24 ± 0.14	1.27 ± 0.14	1.23 ± 0.20	0.98 ± 0.27	0.46 ± 0.29	0.13 ± 0.17
SKC (n = 21)	0.85 ± 0.20 *	15.62 ± 4.60 *	1.15 ± 0.18 *	1.16 ± 0.15 *	1.12 ± 0.18	0.86 ± 0.25	0.29 ± 0.25 *	0.05 ± 0.10 *
P1	0.006	0.004	0.028	0.014	0.166	0.262	0.016	0.024
Cyl > -1.0 D
NC (n = 34)	0.99 ± 0.19	18.81 ± 6.16	1.26 ± 0.13	1.30 ± 0.12	1.25 ± 0.13	0.96 ± 0.23	0.44 ± 0.26	0.14 ± 0.17
Early-KC (n = 21)	0.96 ± 0.24	17.97 ± 5.07	1.21 ± 0.13	1.24 ± 0.14	1.20 ± 0.20	0.96 ± 0.28	0.44 ± 0.29	0.12 ± 0.14
P2	0.608	0.326	0.567	0.477	0.536	0.834	0.659	0.540
Cyl ≤ -1.0 D
NC (n = 43)	1.07 ± 0.19	19.8 ± 4.61	1.28 ± 0.13	1.31 ± 0.15	1.27 ± 0.25	1.03 ± 0.27	0.52 ± 0.28	0.16 ± 0.16
Early-KC (n = 22)	0.88 ± 0.21	16.22 ± 5.71	1.18 ± 0.19	1.2 ± 0.17	1.15 ± 0.18	0.87 ± 0.25	0.31 ± 0.26	0.06 ± 0.15
P3	0.002	0.003	0.059	0.081	0.325	0.141	0.011	0.023

Notes: NC, normal control; Early-KC, early keratoconus; FFKC, forme fruste keratoconus; SKC, subclinical keratoconus; n, number of eyes; CS, contrast sensitivity; CSF, contrast sensitivity function; AULCSF, area under log CSF; cpd, cycle per degree

P₁, analysis of covariance (ANCOVA) or generalized linear model (for CS at 18.0 cpd) with adjustment for age, gender, and spherical equivalent (SE); P₂, ANCOVA with adjustment for gender and SE; P₃, ANCOVA with adjustment for SE

Bold fonts: significant differences (P < 0.05) between groups. ^*: significant differences (P < 0.05) in the multiple comparisons with Bonferroni adjustment

Correlation analysis

Pearson correlation analysis revealed that IVA and IHD in the Early-KC group were significantly negatively correlated with CS at 1.5 cpd (r = -0.321 and − 0.306, P = 0.036 and 0.046, respectively), while other variables were not. Figure 3 showed the linear regression models between CS at 1.5 cpd and IVA (Fig. 3A) and IHD (Fig. 3B).

Fig. 3.

Correlation of contrast sensitivity (CS) at 1.5 cycle per degree (cpd) with [A] index of vertical asymmetry (IVA) and [B] index of height decentration (IHD). (r, Pearson correlation coefficients)

Discussion

This study compared the qCSF characteristics of early keratoconus with normal CDVA with those of normal eyes. Our findings demonstrated that the overall contrast sensitivity in early keratoconus, especially in SKC with normal CDVA, was significantly lower than that in normal eyes and was correlated with corneal irregularity. The qCSF test can reflect subjective visual quality of early keratoconus and provide a basis for ideal optical correction.

The AULCSF in the Early-KC group was significantly lower than that in the NC group in the present study (Table 2), indicating that the overall visual performance was impaired in early keratoconus, although CDVA was normal. Previous studies have reported that compared with visual acuity, contrast sensitivity had better correlations with refraction, topographic indices, aberrometric data [34, 35], and quality of life [36], indicating the importance of evaluating subjective visual quality of early keratoconus using the qCSF test. A previous study used CSV-1000E chart to assess contrast sensitivity in patients with keratoconus wearing rigid gas permeable contact lens (RGP) and reported that although CDVA was normal (20/20 or better), contrast sensitivity of keratoconus was significantly lower than that of the normal control group [37]. A possible explanation for this finding might be the residual higher-order aberrations (HOA) after RGP correction [37]. These findings were consistent with those of the present study, suggesting the contrast sensitivity function is a more sensitive indicator of visual function in patients with keratoconus. The qCSF method used in this study assessed the overall contrast sensitivity in patients with keratoconus with high efficiency and convenience [16], and has potential for clinical application.

According to our findings, the decrease in contrast sensitivity in the Early-KC group occurred primarily at high and low spatial frequencies; correspondingly, CSF Acuity also decreased significantly (Table 2). Shneor et al. [38] reported that contrast sensitivity at 6.0, 9.0, and 12.0 cpd were decreased in patients with keratoconus with normal CDVA (0.00 LogMAR), which differed partially from the results of the current study. A possible explanation for this finding could be the inconsistent baseline characteristics of the two studies. In the study by Shneor et al. [34], the cylindrical refraction differed significantly between the keratoconus and control groups, which could be an confounding factor. The study by Maeda et al. [35] reported results similar to the present study for contrast sensitivity at 2.4 cpd. These findings consistently suggested a decrease in contrast sensitivity at high spatial frequencies in early keratoconus with normal CDVA.

The contrast sensitivity at medium spatial frequencies (3.0 and 6.0 cpd) was reportedly significantly correlated with visual performance for daily tasks, such as reading and driving [39]. This study found that contrast sensitivity at 3.0 and 6.0 cpd in the Early-KC group did not differ significantly from that in the NC group (Table 2), possibly due to sensory plasticity in keratoconus. Barbot et al. [40] reported that the contrast sensitivity at low and medium frequencies in keratoconus was higher than those in control groups after adaptive optics correction. It would appear that as higher order aberrations increase, the attenuation of contrast sensitivity at high spatial frequencies and the compensatory effect of contrast sensitivity at low and medium spatial frequencies become more pronounced. The contrast sensitivity at medium spatial frequency increased slightly in the relatively milder keratoconus group, which was consistent with the findings of this study. Long-term exposure to degraded retinal images (especially reduction of high-frequency signals) may result in the reallocation of the limited cerebral sensory resources in patients with keratoconus. The processing ability of visual signals might improve at low and medium spatial frequencies in a compensatory manner [40] through perceptual learning with adaptive optics [41]. Therefore, it is hypothesized that the contrast sensitivity at medium spatial frequency (most closely related to daily life) [39] may undergo a greater degree of neural compensation, resulting in statistically insignificant differences between the two groups, despite spectacle correction.

The qCSF parameters differed significantly between the SKC and NC groups in the subgroup analysis; however, similar phenomenon was not observed between the FFKC and control groups or between the FFKC and SKC groups (Table 3). Keratoconus is a degenerative corneal disease that affects both eyes [42], and corneal tomography and in vivo corneal biomechanical examinations can accurately identify clinical keratoconus and some subclinical forms of keratoconus [43]. FFKC is difficult to distinguish due to its unremarkable tomographic and biomechanical properties; thus, its diagnosis is primarily dependent on the fellow eye with clinical keratoconus [4, 44]. No statistically significant difference was observed in contrast sensitivity between the FFKC and NC groups, which was consistent with the findings of previous studies. However, in terms of SKC, some morphological abnormalities, such as inferior-superior asymmetry of the cornea or elevations of the anterior and posterior surfaces, can result in a significant increase in higher order aberrations [5, 45] and a significant decrease in subjective visual quality. Furthermore, in patients with a high degree of astigmatism (cylindrical refraction ≤-1.0 D), a significant decrease in contrast sensitivity (especially at high spatial frequencies) was observed in the Early-KC group compared with that in the NC group (Table 3), possibly due to the irregular astigmatism induced by keratoconus [2]. It would be difficult to make ideal correction for irregular astigmatism with spectacles alone [46]. Patients with SKC in this study had significantly lower visual quality in terms of contrast sensitivity, indicating the importance of ideal optical correction using RGP or scleral lens, especially for uncorrected irregular astigmatism in early keratoconus [46]. Despite the distinctions in corneal tomography between FFKC and SKC, the contrast sensitivity parameters did not show a statistically significance difference. This indicates that in early keratoconus patients with normal visual acuity, the impact of corneal irregularities and HOAs on visual function has not yet induced notable differences. Therefore, further research should explore the specific roles of HOAs and other visual parameters in different types of keratoconus, to obtain a more comprehensive understanding of the subtle differences in visual function among these patients with early-stage keratoconus.

A difference of 0.15 log units is considered one contrast sensitivity “step”, that is to say, a significant difference for contrast sensitivity [47]. In the subgroup analysis, the difference of contrast sensitivity at 1.5 and 12.0 cpd between the control and SKC groups were greater than or equal to 0.15 log units (Table 3), indicating a significant decrease in contrast sensitivity in patients with SKC despite having normal visual acuity. Moreover, the significant changes of contrast sensitivity were correlated with changes in corneal irregularity. However, the difference of contrast sensitivity at 1.0 and 18.0 cpd between the control and SKC groups were less than 0.15 log units, which indicated that the changes of contrast sensitivity at these spatial frequencies were subtle. But it suggested that the qCSF method were sensitive enough to detect subtle changes in contrast sensitivity that may not be apparent using conventional methods, which has been pointed out in a previous study [48].

Weak and negative correlations were found between IVA and IHD and contrast sensitivity at 1.5 cpd (Fig. 3). IVA represents the symmetry in anterior keratometry between the superior and inferior halves of the cornea, while IHD represents the vertical eccentricity of the anterior elevations of the cornea; [49] both indices have been demonstrated to possess good discriminative ability for the diagnosis of early keratoconus [50–52]. Previous studies reported relatively good correlations (r<-0.5) between the ocular aberrations and contrast sensitivity at 9.0 and 12.0 cpd [38], and between the videokeratoscopic indices and contrast sensitivity at 2.4 cpd in keratoconus with normal CDVA [35]. A possible explanation for these findings could be the inclusion of SKC and FFKC in the present study, whose contrast sensitivity was less affected by corneal irregularity compared with that of clinical keratoconus. The negative correlation between the parameters in patients with normal CDVA suggested the negative impact of corneal irregularity on visual function. Thus, the qCSF parameters could reflect the corneal morphological characteristics of early keratoconus to a certain extent.

This study has some limitations. First, the sample size of the present study was limited. Given the relatively small sample size of subclinical and forme fruste keratoconus, they were combined into one group to achieve a sufficient statistical power. While in the subgroup analysis (Table 3), post hoc analysis with the G*Power (version 3.1.9.7) software showed that the power of the three ANCOVA tests was 0.88, 0.71, and 0.73, respectively. Second, the characteristics of the two groups, such as sex ratio, spherical refraction, and spherical equivalent, differed at baseline. Although statistical methods were used to adjust for these differences, larger samples are required in future studies to provide better control of confounding factors. Third, higher-order aberrations (HOAs) were not assessed in the study. Increased HOAs were recognized as a significant factor for the decline in visual quality in patients with keratoconus [37, 53]. We believe that evaluating HOAs could provide deeper insights into the underlying reasons for the reduction of contrast sensitivity in these patients, which needs further research in the future. Fourth, the axis of astigmatism was not analyzed in the study, and it may affect retinal image quality due to its interaction with ocular wavefront aberrations. Future studies are necessary to interpret the associations among the axis of astigmatism, ocular wavefront aberrations, and contrast sensitivity in patients with keratoconus.

In conclusion, early keratoconus with normal CDVA (≥ 20/20) showed a significant decrease in contrast sensitivity, especially at low and high spatial frequencies. The qCSF test can assess visual function in patients with early keratoconus with greater sensitivity.

Author contributions

Study concept and design (YX, LS, JZ); provide materials (ZLL); data collection (YX, YY, LS, XYZ, JZ); data analysis and interpretation (YX, YY, JZ); drafting of the manuscript (YX, YY, JZ); critical revision of the manuscript (YX, YY, LS, YS, XTZ, JZ); supervision (XTZ, JZ). All authors read and approved the final manuscript.

Funding

National Natural Science Foundation of China (Grant No. 82271119); Shanghai Rising-Star Program (23QA1401000); Healthy Young Talents Project of Shanghai Municipal Health Commission (2022YQ015); Project of Shanghai Science and Technology (Grant No.20410710100) (Grant No. 21Y11909800); Clinical Research Plan of SHDC (SHDC2020CR1043B); Project of Shanghai Xuhui District Science and Technology (XHLHGG202104).

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to funding requirement but are available from the corresponding author on reasonable request.

Declarations

Competing interests

The sponsor or funding organization had no role in the design or conduct of this research. ZLL holds intellectual property interests in visual function measurement and rehabilitation technologies and equity interests in Adaptive Sensory Technology, Inc. (San Diego, CA) and Juehua Medical Technology, Ltd (Beijing, China). The other authors (YX, YY, LS, YS, Xiaoyu Zhang, Xingtao Zhou, and JZ) declared no competing interests.

Ethics approval and consent to participate

This study followed the tenets of the Declaration of Helsinki and was approved by by the Ethics Committee of Fudan University Eye and ENT Hospital Review Board (Shanghai, China) (ky2012-017). Informed consent was obtained from all participants.

Consent for Publish

Written informed consent was obtained from the patients for the publication of this paper. Patient names and the eyes/facial region of study participants is not applicable.