The utility of measures of anterior segment parameters of a Pentacam Scheimpflug tomographer in discriminating high myopic astigmatism from keratoconus.

The study aimed to evaluate and compare anterior segment parameters between keratoconic eyes and eyes with high myopic astigmatism using Pentacam Scheimpflug tomography. This was a retrospective cross-sectional study that included sixty keratoconic eyes (thirty-two persons) and seventy-three eyes (forty-six persons) with high myopic astigmatism with mean ages 24.72 ± 11.65years and 26.60 ± 10.69years, respectively. Twenty-three parameters from the topographic map and fifteen parameters from the Belin-Ambrosió enhanced ectasia display map of the printouts of a Scheimpflug principle-based Pentacam tomographer were evaluated for their diagnostic accuracy using Receiver Operating Characteristic (ROC) curve. All parameters except cornea volume, anterior chamber volume, and anterior chamber angle indicated a significant difference between high myopic astigmatism and keratoconic eyes. The area under the receiver operating characteristic (AUROC) of eighteen Pentacam parameters was excellent (0.9-1.0) in discriminating keratoconus from high myopic astigmatism, out of which four {anterior minimum sagittal curvature (ant. Rmin), posterior minimum sagittal curvature (post. Rmin), maximum Ambrosió relational thickness (ART max) and total deviation value (D)} indicated excellent (>90%) sensitivity and specificity in addition to the excellent AUROC values. Topographic and Belin-Ambrosió enhanced ectasia display (BAD) maps of a Scheimpflug principle-based Pentacam tomographer are useful in enhancing the diagnosis of keratoconus and may also provide valuable information in effectively screening for keratoconus cases among refractive surgery candidates with high myopic astigmatism.

Introduction

Keratoconus is a progressive, noninflammatory corneal thinning characterized by changes in the structure and organization of corneal collagen. It causes an uneven steepening of the central or paracentral zone of the cornea leading to irregular asymmetrical astigmatism, which cannot be fully corrected with glasses and therefore compromising the quality of life of the affected individuals [1-3]. The non-uniform steepening of the cornea that results from ectasia is the main cause of refractive error in eyes with keratoconus. However, oftentimes, increased axial length contributes to the myopic component of the refractive error [1-4]. Thus, it is not uncommon for keratoconus patients to develop high myopia with irregular astigmatism since most high myopias are axial [5].

Permanent correction of high myopia with refractive surgeries is increasing [6]. Laser-assisted in situ keratomileusis (LASIK) is the most common keratorefractive surgery [7]. This procedure reshapes the cornea by removing microscopic particles of tissue and may be associated with iatrogenic keratectasia (Post-LASIK ectasia) [8]. Keratoconic eyes are less resistant to deformation in post-LASIK ectasia due to focal weakening and significant reduction in corneal stiffness. This phenomenon results from variations in the expression of corneal epithelium and stroma-specific genes at the apex of the cone as well as changes in keratoconus-related proteome in non-cone regions of keratoconus corneas [9-11]. Accordingly, detecting keratoconus among refractive surgery candidates is crucial since removing tissue from an inherently weak cornea further weakens and threatens its integrity [12]. Besides, early diagnosis of keratoconus helps in prompt management of the condition to enhance the quality of life of patients.

Research has shown that high myopia irrespective of the degree of astigmatism can be considered as an alarming sign requiring further corneal examination to exclude any corneal abnormalities such as keratoconus [13]. A study on pediatric patients has also revealed cases of keratoconus that were misdiagnosed as meridional amblyopia secondary to myopic astigmatism due to the unavailability of corneal tomography measurements [14]. It is therefore important to always screen high myopic patients, particularly those considering refractive surgery, to identify high-risk corneas.

Despite these familiar clinical situations, the relationship between keratoconus and high myopia has not been extensively studied and investigated in the ophthalmic literature. There is a lag in the clinical uptake of corneal tomographic measurements for eyes with high myopic astigmatism. Besides, the majority of studies that attempted to explore the dynamics of anterior segment parameters in keratoconus were carried out among Asians and Caucasians [15-19], and to the best of our knowledge, this is the only study that has compared anterior segment parameters between eyes with keratoconus and eyes with high myopic astigmatism among black Africans.

The criteria for the diagnosis and classification of keratoconus are based on anterior corneal curvature data derived with the Placido-based corneal topography [15, 16]. However, studies have suggested that early changes in eyes with keratoconus are also present on the posterior corneal surface [15-17]. Scheimpflug imaging measures the entire cornea thickness by determining the front and back surfaces of the cornea with a rotating Scheimpflug camera. Several studies have used Scheimpflug tomography to compare anterior segment parameters between normal eyes and eyes with keratoconus [15, 18, 19], but the use of Scheimpflug imaging to determine a difference between keratoconus and high myopic astigmatism is inadequately investigated. This study aimed at comparing Pentacam Scheimpflug corneal tomography findings between keratoconus eyes and high myopic astigmatic eyes and to determine the sensitivity and specificity of these parameters in discriminating keratoconus from high myopic astigmatism.

Materials and methods

The study employed a retrospective cross-sectional design and followed the tenets of the Declaration of Helsinki. The investigation covered a 7-year period from January 2014 to December 2020. Ethical approval for the current study protocol was obtained from the Institutional Review Board (IRB) of the University of Cape Coast, Ghana (UCCIRB/CHAS/2018/65). Since medical records were reviewed retrospectively and identifying particulars of patients’ details concealed, patients’ consents were not needed and were therefore waived by the IRB. All data and records generated throughout the study were handled with strict confidentiality in alignment with the University of Cape Coast institutional policies.

Clinical diagnosis of keratoconus was made if eyes had irregular corneas determined by distorted keratometric mires, distorted red reflex on retinoscopy or ophthalmoscopy or both, and at least one of the following slit-lamp biomicroscopic findings: Vogt striae, Fleischer ring of more than 2.0mm arc length, and corneal scarring consistent with keratoconus [20]. All diagnoses were made by an ophthalmologist with expertise in cornea and external eye disease. Records of patients diagnosed with ocular conditions other than keratoconus were excluded. Eyes were assigned to the control group of high myopic astigmatism if they had no history of ocular surgery, eye pathology, or irregular cornea patterns. Records of all eyes with a history of contact lens wear or any corneal intervention before Pentacam scans were excluded.

Records of patients examined with the Scheimpflug principle-based Pentacam corneal tomographer (Wavelight—Allegro Oculyzer, GmbH, Erlangen, Germany) were reviewed for topographic parameters and parameters of the BAD maps. Parameters studied included keratometry readings, topographic astigmatism, corneal eccentricity in the central 6mm, average radius of curvature between the 6mm and 9mm zone center (Rper), and minimum sagittal curvature (Rmin) for anterior and posterior cornea surfaces. Additionally, pachymetry, cornea volume, anterior chamber volume, anterior chamber angle, anterior chamber depth, keratometric power deviation (KPD), and Belin-Ambrosió enhanced ectasia display (BAD) readings were recorded.

Corneal thickness measurements were taken for multiple points (apex, thinnest location over anterior cornea surface, and pupil center). Cornea volume was reported for a diameter of 10mm centered on the anterior corneal apex. Anterior chamber depth was measured as the distance from the corneal endothelium to the anterior surface of the lens capsule. The anterior chamber volume was computed from the endothelium down to the iris and lens over a 12mm diameter centered on the anterior corneal apex. The anterior chamber angle recorded was the smallest in the horizontal position calculated from the Scheimpflug image. The float option of the best fit sphere served as a reference surface for front and back elevation data measurements, and the diameter of the reference surface was 8 mm. The front elevation was determined as the maximum difference in anterior corneal elevation between the best-fit sphere (BSF) and the enhanced best fit sphere obtained with the BAD display software. Back elevation was also determined as the maximum differential change in posterior corneal elevation between the best fit sphere (BFS) and the enhanced BFS obtained with the BAD display software. The progression index was computed as the average progression value at the different pachymetric rings.

Visual acuity was measured using a LogMAR chart. Spherical refractive error and total astigmatism were determined objectively using an auto refractometer and subjectively by the maximum plus to maximum visual acuity method at 6m. Patients who had sphero-cylindrical refractive errors with spherical components greater than -6.00D were considered high myopic astigmats.

Data were analyzed using the Statistical Package for Social Sciences (SPSS) for Windows, version 22.0 (Armonk, NY: IBM Corp.), and a p-value of less than 0.05 was considered statistically significant. Independent samples t-test was used to find the mean difference in parameters between the two groups. ROC curve was used to plot sensitivity (true positive rate) against 1-specificity (false positive rate) for the different thresholds of the diagnostic test, and the overall diagnostic accuracy of the test evaluated with the area under the ROC curve (AUROC). The AUROC curve ranges from 1 (100%) to 0.5 (50%). An AUROC curve of 1 (100%) indicates perfect discrimination, and an AUROC curve of 0.5 (50%) denotes a test that is only ever accurate by chance—a completely bad classification. Within this range, 0.9–1.0, 0.8–0.9, 0.7–0.8, 0.6–0.7 and 0.5–0.6 indicate excellent, good, fair, poor and very poor discrimination respectively [21].

Results and discussion

Sixty keratoconic eyes of thirty-two persons with a mean uncorrected visual acuity (UCVA) of 0.94 ± 0.45 were involved in the study. There were ten (31.25%) females and twenty-two (68.75%) males with a mean age of 24.72 ± 11.65 years (Range = 7–69 years).

The high myopic astigmatic group comprised 73 eyes of forty-six persons with a mean UCVA of 1.19 ± 0.40. The group consisted of 21(45.65%) females and 25(54.35%) males with a mean age of 26.60 ± 10.69 years (Range = 10–51 years).

There was no significant difference between the two groups regarding gender (χ2 = 2.39, p = 0.12) and age, t (121.29) = -0.96, p = 0.34. However, UCVA differed substantially between the two groups t (120.17) = -3.42, p = 0.001. The means and ranges of all Pentacam parameters obtained from the topographic and Belin-Ambrosió enhanced ectasia display maps are shown in Tables 1 and 2. All parameters except cornea volume, anterior chamber volume, and anterior chamber angle indicated a significant difference between keratoconic and myopic astigmatic eyes. Table 3 presents the mean refractive errors of both groups.

Table 1

Comparison of mean parameters of topographic maps between keratoconus and high myopic astigmatic eyes.

Pentacam parameter	Keratoconus Mean ± SD (Range)	High Myopic astigmatism Mean ± SD (Range)	P
Kflat (Front)	50.47 ± 7.9 (39.50–70)	42.82 ± 2.68 (38.7–57.8)	<0.001
Ksteep (Front)	57.09 ± 9.1 (42.7–76)	44.65 ± 2.97 (41.1–60.2)	<0.001
Kmean (Front)	53.31 ± 8.11 (42–72.9)	43.7 ± 2.73 (39.9–59)	<0.001
Kmax	62.54 ± 12.04 (44.6–89.5)	45.39 ± 4.21 (41.4–69.5)	<0.001
Astigmatism (Front)	-6.01 ± 4.17 {-0.6-(-25.7)}	-1.84 ± 1.43 {-0.2-(-7.1)}	<0.001
Eccentricity (Front)	-0.92 ± 0.49 {-0.07- (-2.04)}	-0.34 ± 0.22 {-0.01-(-0.96)}	<0.001
Rper (Front)	7.69 ± 0.55 (6.33–8.8)	8.15 ± 0.28 (7.46–8.82)	<0.001
Kflat (Back)	-7.18 ± 1.74 {-2.5-(-11.2)}	-6.03 ± 0.47 {-5.4-(-8.8)}	<0.001
Ksteep (Back)	-8.6 ± 1.9 {-5.9-(-14.4)}	-6.4 ± 0.56 {-5.8-(-9.4)}	<0.001
Kmean (Back)	-7.79 ± 1.74 {-4.0-(-11.9)}	-6.21 ± 0.5 {-5.6-(-9.1)}	<0.001
Astigmatism (Back)	-1.45 ± 1.3 {-0.3-(-6.7)}	-0.45 ± 0.73 {0.0- (-6.3)}	<0.001
Eccentricity (Back)	-0.97 ± 0.46 {-0.03- (-1.72)}	-0.56 ± 0.13 {-0.23- (-1.11)}	<0.001
Rper (Back)	6.47 ± 0.61 (4.72–8.81)	6.78 ± 0.27 (6.04–7.27)	0.001
Pupil center	455.45 ± 53.97 (246–536)	518.64 ± 35.36 (412–591)	<0.001
Pachy apex	446.98 ± 57.49 (267–556)	517.59 ± 36.91 (407–590)	<0.001
TCT	407.25 ± 81.67 (109–530)	513.52 ± 37.14 (403–589)	<0.001
Cornea vol	58.09 ± 5.06 (46.7–69.1)	57.43 ± 3.89 (49.5–65.5)	0.41
AC vol	184.35 ± 47.95 (68.4–349)	180.78 ± 36.51 (66–260)	0.64
ACD	4.11 ± 0.41 (3.26–4.89)	3.68 ± 0.33 (3.07–4.26)	<0.001
ACA	41.31 ± 11.99 (16.8–88.4)	40.75 ± 8.51 (25.9–82.9)	0.76
KPD	2.37 ± 1.29 (0.3–6.0)	1.13 ± 0.35 (0.7–3.4)	<0.001
Rmin (Front)	5.5 ± 1.32 (0.43–8.47)	7.49 ± 0.53 (4.86–8.15)	<0.001
Rmin (Back)	4.05 ± 1.09 (2.05–6.29)	6.1 ± 0.56 (3.33–6.75)	<0.001

K: keratometry reading, Rper: average radius of curvature between the 6mm and 9mm zone center, pachy apex: corneal thickness at the apex, TCT: thinnest corneal thickness; cornea vol.: corneal volume, AC vol.: anterior chamber volume, ACD: anterior chamber depth, ACA: anterior chamber angle, KPD: keratometric power deviation, Rmin: minimum sagittal curvature.

Table 2

Comparison of mean parameters of Belin-Ambrosió enhanced ectasia display (BAD) maps between keratoconus and myopic astigmatic eyes.

Pentacam parameter	Keratoconus Mean ± SD (Range)	High Myopic astigmatism Mean ± SD (Range)	P
Front difference	21.68 ± 16.12 (1.0–68.0)	4.14 ± 2.29 (1.0–16.0)	<0.001
Back difference	45.75 ± 32.1 (2.0–140.0)	5.20 ± 4.29 (0.0–27)	<0.001
Dist.Apex.Th	1.02 ± 0.66 (0.22–4.12)	0.73 ± 0.29 (0.06–1.24)	0.002
Front elevation	49.57 ± 30.06 (8.0–143.0)	12.23 ± 9.57 (2.0–54.0)	<0.001
Back elevation	102.7 ± 66.12 (12.0–306.0)	21.52 ± 14.95 (6.0–100.0)	<0.001
ProgMin	2.69 ± 2.62 (0.56–13.71)	0.74 ± 0.37 (0.40–3.16	<0.001
ProgMax	6.46 ± 7.26 (1.29–30.19)	1.28 ± 0.51 (0.81–4.69)	<0.001
ProgAvg	2.9 ± 2.73 (0.00–15.27)	0.94 ± 0.27 (0.39–2.35)	<0.001
ARTmax	121.41 ± 82.95 (0.00–375)	430.43 ± 107.11 (86.0–724.0)	<0.001
Df	14.11 ± 11.13 (-0.55–44.34)	1.59 ± 3.76 (-1.3–25.76)	<0.001
Db	18.96 ± 36.25 (-0.91–265.52)	0.31 ± 2.81 (-1.4–19.79)	<0.001
Dp	15.15 ± 19.4 (-6.12–97.16)	0.52 ± 2.31 (-1.61–15.28)	<0.001
Dt	6.29 ± 8.61 (0.24–60.94)	0.8 ± 1.28 (-1.34–5.16)	<0.001
Da	3.04 ± 1.09 (0.17–4.46)	0.53 ± 1.42 (-7.0–3.67)	<0.001
D	14.64 ±15.41 (1.05–112.43)	1.46 ± 2.35 (-0.64–15.95)	<0.001

Dist.Apex.Th: distance from corneal apex to thinnest location, ProgMin/Max/Avg: progression index, ARTmax: maximum Ambrosió relational thickness, Df: deviation of front elevation difference map, Db: deviation of back elevation difference map, Dp: deviation of average pachymetric progression, Dt: deviation of minimum thickness, Da: deviation of ARTmax, D: total deviation value.

Table 3

Mean refractive errors of keratoconic and high myopic astigmatic eyes.

Component of error	Keratoconus Mean ± SD (Range)	High Myopic Astigmatism Mean ± SD (Range)	P
Sphere (myopic)	-7.82 ± 5.94 {-0.25 –(-)30.0}	-11.4 ± 3.37 {-6.25 –(-)18.5}	<0.001
Cylinder	-5.69 ± 2.84 {-0.25 –(-)14}	-2.17 ± 1.63 {-0.25 –(-)8.25}	<0.001

Results of the Receiver Operating Characteristic (ROC) curve analysis are shown in Tables 4 and 5.

Table 4

Receiver Operating Characteristic (ROC) curve analysis of topographic parameters of keratoconic and high myopic astigmatic eyes.

Parameters	AUC	SE	95%CI	P	Cutoff	Sensitivity	Specificity
Kflat (Front)	0.818	0.038	0.743–0.893	<0.001	45.10	0.65	0.92
Ksteep (Front)	0.927	0.024	0.880–0.975	<0.001	46.10	0.92	0.89
Kmean (Front)	0.900	0.028	0.846–0.954	<0.001	45.25	0.83	0.89
Kmax	0.953	0.018	0.919–0.988	<0.001	46.40	0.97	0.86
Astigmatism (Front)	0.861	0.033	0.796–0.925	<0.001	2.65	0.80	0.86
Eccentricity (Front)	0.827	0.037	0.754–0.900	<0.001	-0.39	0.77	0.60
Rper (Front)	0.761	0.041	0.680–0.842	<0.001	8.00	0.65	0.64
Kflat (Back)	0.760	0.048	0.666–0.854	<0.001	-6.05	0.77	0.56
Ksteep (Back)	0.901	0.030	0.843–0.960	<0.001	-6.75	0.87	0.89
Kmean (Back)	0.824	0.042	0.742–0.906	<0.001	-6.45	0.75	0.84
Astigmatism (Back)	0.911	0.026	0.861–0.961	<0.001	0.55	0.85	0.85
Eccentricity (Back)	0.774	0.049	0.678–870	<0.001	-0.59	0.77	0.64
Rper (Back)	0.690	0.047	0.598–0.783	<0.001	6.79	0.68	0.55
Pupil center	0.867	0.031	0.807–0.927	<0.001	505.50	0.80	0.75
Pachy apex	0.859	0.033	0.795–0.924	<0.001	497.00	0.80	0.75
TCT	0.919	0.023	0.874–0.963	<0.001	485.00	0.83	0.82
Cornea vol.	0.530	0.051	0.429–0.630	0.555	57.45	0.52	0.49
AC vol.	0.522	0.051	0.422–0.623	0.656	180	0.55	0.52
ACD	0.785	0.039	0.709–0.862	<0.001	3.99	0.63	0.81
ACA	0.517	0.051	0.416–0.618	0.740	40.25	0.57	0.51
KPD	0.833	0.041	0.752–0.914	<0.001	1.25	0.78	0.86
Rmin (Front)	0.939	0.023	0.894–0.985	<0.001	7.03	0.90	0.90
Rmin (Back)	0.950	0.019	0.913–0.986	<0.001	5.64	0.92	0.90

K: keratometry reading, Rper: average radius of curvature between the 6mm and 9mm zone center, pachy apex: corneal thickness at the apex, TCT: thinnest corneal thickness; cornea vol.: corneal volume, AC vol.: anterior chamber volume, ACD: anterior chamber depth, ACA: anterior chamber angle, KPD: keratometric power deviation, Rmin: minimum sagittal curvature.

Table 5

Receiver Operating Characteristic (ROC) curve analysis of parameters on Belin-Ambrosió enhanced ectasia display (BAD) maps of keratoconic and high myopic astigmatic eyes.

Parameters	AUC	SE	95%CI	P	Cutoff	Sensitivity	Specificity
Front difference	0.900	0.033	0.824–0.953	<0.001	5.50	0.83	0.86
Back difference	0.926	0.025	0.877–0.975	<0.001	8.50	0.87	0.85
Dist.Apex.Th	0.632	0.049	0.536–0.729	0.009	0.73	0.63	0.51
Front elevation	0.932	0.021	0.891–0.973	<0.001	17.5	0.92	0.86
Back elevation	0.952	0.019	0.915–0.988	<0.001	26.5	0.95	0.81
ProgMin	0.926	0.025	0.878–0.974	<0.001	0.88	0.88	0.85
ProgMax	0.963	0.014	0.935–0.991	<0.001	1.49	0.93	0.82
ProgAvg	0.900	0.038	0.803–0.950	<0.001	1.16	0.85	0.88
ARTmax	0.979	0.011	0.957–1.000	<0.001	300.50	0.93	0.90
Df	0.900	0.031	0.828–0.950	<0.001	2.46	0.83	0.88
Db	0.910	0.028	0.856–0.964	<0.001	2.01	0.83	0.93
Dp	0.891	0.035	0.821–0.960	<0.001	1.92	0.85	0.89
Dt	0.919	0.023	0.875–0.963	<0.001	1.65	0.83	0.81
Da	0.928	0.022	0.885–0.972	<0.001	1.85	0.85	0.88
D	0.957	0.017	0.923–0.991	<0.001	2.91	0.90	0.90

Dist.Apex.Th: distance from corneal apex to thinnest location, ProgMin/Max/Avg: progression index, ARTmax: maximum Ambrosió relational thickness, Df: deviation of front elevation difference map, Db: deviation of back elevation difference map, Dp: deviation of average pachymetric progression, Dt: deviation of minimum thickness, Da: deviation of ARTmax, D: total deviation value.

AUROC values of eighteen Pentacam parameters were excellent (0.9–1.0) in discriminating keratoconus from high myopic astigmatism, out of which four (Front Rmin, Back Rmin, ARTmax, and D) indicated excellent (>90%) sensitivity and specificity in addition.

There was a significant difference between keratoconic eyes and eyes with high myopic astigmatism concerning all parameters except corneal volume, anterior chamber volume, and anterior chamber angle. Of all the parameters evaluated on the topographic map, steepest front keratometry reading (Ksteep-front), mean front keratometry reading (Kmean-front), steepest back keratometry reading (Ksteep-back), maximum keratometry reading (Kmax), astigmatism (back), thinnest corneal thickness (TCT), minimum front sagittal curvature (Rmin-front) and minimum back sagittal curvature (Rmin-back) indicated excellent predictive accuracy.

In the present study, a cutoff value of 485μ for TCT yielded 83% sensitivity and 82% specificity in distinguishing between keratoconus and high myopic astigmatism, which further implicates corneal stromal thinning as the hallmark of keratoconus. Earlier studies reported cutoff points of TCT ranging from 489 μ to 506 μ [15, 20, 22, 23]. The outstanding diagnostic efficacy of TCT corroborates the results of similar studies that compared keratoconus eyes with normal emmetropic eyes [15, 24, 25].

The minimum sagittal curvature of the front and back corneal surfaces showed excellent predictive ability. A cutoff value of 7.03mm for the minimum front sagittal curvature had 90% sensitivity and 90% specificity in discriminating keratoconus from high myopic astigmatism. Also, a cutoff of 5.64mm for the minimum back sagittal curvature had 92% sensitivity and 90% specificity in differentiating keratoconus from high myopia. These results are consistent with those reported by Orucoglu and Toker, who also found minimum front and back sagittal curvatures as excellent in differentiating keratoconus from normal eyes [15].

Eccentricity coefficient is an index that describes how the corneal curvature changes from the central region to the peripheral region [26]. Consistent with an earlier investigation [15], front and back eccentricity coefficients did not indicate excellent predictive accuracy in differentiating keratoconus from high myopic astigmatism. A cornea with astigmatism has both oblate and prolate meridians [27]. The prolate axis has a more negative eccentricity value and the oblate axis, a less negative or positive eccentricity value. When the oblate meridian dominates, the mean eccentricity value becomes less negative or positive, and when the prolate meridian dominates, the mean eccentricity value becomes more negative [27]. Against this backdrop, the high total astigmatism values recorded in the two groups of the current study may not provide reliable information about corneal eccentricity. Therefore, the eccentricity coefficient is not specific for discriminating keratoconus from high myopic astigmatism and must be considered with the apex position of the cone and the magnitude of astigmatism.

Out of the fifteen parameters evaluated on the Belin-Ambrosió enhanced ectasia display map, fourteen demonstrated excellent discrimination. Consistent with the current study, Orucoglu and Toker [15] also reported fourteen BAD display map parameters as being outstanding in diagnostic ability. Fam and Lim [28] reported the clinical relevance of front and back elevation parameters for the detection of keratoconus and suspected or subclinical keratoconus eyes. Earlier investigations have indicated excellent diagnostic efficacies of front and back elevation measures in diagnosing keratoconus [15, 17, 29]. The results of these previous studies are consistent with the outcome of the current investigation. However, the cutoff values for detecting eyes with keratoconus in this study were higher compared to those of earlier studies. This could be due to variability in the control group as well as variability in the stages of keratoconus cases investigated.

The pachymetric progression index calculates the change in corneal thickness over 360 degrees of the cornea. The progression value at each meridian from the thinnest point is defined as progression index and the average of all meridians is illustrated by Prog-Avg [30-32]. Doctor and colleagues [33] reported the clinical significance of a rapid rate of pachymetric progression in distinguishing keratoconus from normal eyes. Other studies [20, 22, 30] have also reported excellent predictive accuracy in using pachymetric progression indices to discriminate keratoconus from normal eyes. In the current study, maximum pachymetric progression (Prog-Max) provided the best combination of sensitivity (93%) and specificity (82%) in predicting keratoconus. This corroborates outcomes reported in previous reviews [20, 22, 30]. Cutoffs for the progression indices also compare favorably to results of prior studies.

Ambrosió relational thickness (ART) is the ratio between the thinnest point and progression index. It includes ART max, ART min, and ART avg [33]. Several studies [15, 18, 22, 24, 25, 30] have reported ART max as a valid diagnostic index in discriminating keratoconic eyes from normal eyes. In the current study, the ART max produced the leading blend of sensitivity (93%) and specificity (90%) in discriminating keratoconus from high myopic astigmatism. The cutoff value of 300.50 was similar to those reported by earlier investigations [15, 22, 25].

The D parameters denote the standard deviation from the mean of the normative database. They are changes in anterior elevation from standard to enhanced reference surface, changes in posterior elevation, corneal thickness at the thinnest point, thinnest point displacement, and pachymetric progression {Df(front), Db (back), Dp (pachymetry progression), Dt (thinnest value), and Da (thinnest displacement)}. The total deviation (D) is computed by considering all 5 parameters and running a linear regression analysis against a standard database of normal and keratoconus corneas [33]. In common with what is reported in a previous study, it was found that all D parameters showed excellent precision in the diagnosis of keratoconus [11].

A limitation of the study is that eyes with early-stage keratoconus were not separated from eyes with later-stage keratoconus. Besides, the study is retrospective and non-randomized therefore further longitudinal and randomized studies are needed to affirm the finding of the study. Of all the Pentacam parameters evaluated, ARTmax, D, front Rmin, and back Rmin were the most sensitive and specific in discriminating keratoconus from high myopic astigmatism since they had excellent sensitivity and specificity in addition to excellent AUROC. Topographic and Belin-Ambrosió enhanced ectasia display maps of a Scheimpflug principle-based Pentacam corneal topographer can be useful in the diagnosis of keratoconus; they may also provide valuable information in screening for keratoconus cases among refractive surgery candidates with high myopic astigmatism.

(SAV)

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3 Aug 2021

PONE-D-21-20839

The utility of measures of anterior segment parameters of pentacam scheimpflug tomographer in discriminating high myopic astigmatism from keratoconus

PLOS ONE

Dear Dr. Kyei,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Kind regards,

Michael Mimouni

Academic Editor

PLOS ONE

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2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

3. In the Methods section of the manuscript please additional information regarding how the participants were recruited for the study included any eligibility criteria applied.

4. You indicated that you had ethical approval for your study. In your Methods section, please ensure you have also stated whether you obtained consent from parents or guardians of the minors included in the study or whether the research ethics committee or IRB specifically waived the need for their consent.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a well written article comparing keratoconus with high myopic astigmatism based on tomography data. This is of relevance in daily practice especially in the refractive sphere. Whilst well written, I query the originality of the paper and if it adds anything new to our understanding. I would recommend a further literature search to show what is known so far to give the reader context. Furthermore, whilst the data is comprehensive, it is presented in a laboroius manner and I would consider revising the manuscript by providing a summary.

Reviewer #2: dear Author most of my inquiries are from Materials and methods

1.“Patients were examined with a Scheimpflug principle-based Pentacam corneal topographer” suold be tomographer.

2.The Pentacam posses some very distinct parameters that are very specific for keratoconus and where not included in the paper: Anterior Radius of Curvature (ARC) Posterior Radius of Curvature (PRC) and on the BAD display Df,Db,Dp,Dt,De, BAD-D which were validated by Beilin and Ambrosio’s work and makes them the “go to” parameters to distinguish normal from keratoconus cornea when using the Pentacam

3.Way the particular parameters where chosen?

4.How was high myopic astigmatic patient were defined in diopters? And was the astigmatism matched to KC patients?

5.No details on inclusion and exclusion criteria like corneal interventions, use of contact lens and proper contact lens discontinuation before Pentacam scans etc.

6.Was there any randomization in choosing the patients in both groups ?

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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28 Aug 2021

COMMENTS OF ACADEMIC EDITOR

COMMENT

“Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.”

RESPONSE

Thank you. The suggested corrections are valid. The manuscript has been edited in the reference section to meet PLOS ONE’s style requirements and files have been named as requested. See red highlights on lines 287-373 of pages 16-20.

COMMENT

“Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.”

RESPONSE

We are very grateful for the academic editor’s constructive comment. We are sorry for the unfortunate mix up and the oversight of stating that the study employed a prospective design. The study rather used a retrospective design and covered a 7-year period from January 2014 to December, 2020. We are actually working on multiple articles that are based on similar datasets collected from the same facilities. Thus, the articles have got practically the same methods except that some are retrospective whereas others are prospective. We are sorry to say that there was a mix up of the methods of the current study protocol with that of another, and we assume responsibility for that and extend our apology. However, it is readily evident and can be confirmed from the discussion of our first submission that the current study is really retrospective as we stated the retrospective and non-randomized design of the study as a limitation. This statement has been highlighted in blue for ease of reference. Since medical records were reviewed retrospectively and identifying particulars of patients’ details concealed, patients’ consents were not needed for the study and were therefore waived by the IRB. Thank you so much for critical review which brought to bear this mix up.

See red highlights on lines 92-99 of page 5 and on lines 271-272 of page 15.

COMMENT

“In the Methods section of the manuscript please additional information regarding how the participants were recruited for the study included any eligibility criteria applied.”

RESPONSE

Thank you. Since the study was retrospective and involved reviewing of medical records of already existing cases, there was no recruitment of subjects. See highlights on lines 92-99 of page 5.

COMMENT

“You indicated that you had ethical approval for your study. In your Methods section, please ensure you have also stated whether you obtained consent from parents or guardians of the minors included in the study or whether the research ethics committee or IRB specifically waived the need for their consent.”

RESPONSE

Thank you. Since medical records were reviewed retrospectively and identifying particulars of patients’ details concealed, patients’ consents were not needed for the study and were therefore waived by the IRB.

See red highlight on page 5, lines 92-99.

COMMENT OF REVIEWER 1

“This is a well written article comparing keratoconus with high myopic astigmatism based on tomography data. This is of relevance in daily practice especially in the refractive sphere. Whilst well written, I query the originality of the paper and if it adds anything new to our understanding. I would recommend a further literature search to show what is known so far to give the reader context. Furthermore, whilst the data is comprehensive, it is presented in a laboroius manner and I would consider revising the manuscript by providing a summary.”

RESPONSE

Thank you. A further literature search has been conducted to show what is known so far to provide the reader with context. Also, even though the data appear too elaborate, it was presented in a manner that would enable easy comparison with similar studies, many of which presented their data in an equal fashion. (reference numbers 15, 18, 20, 22, 32). Besides, the tables have been split to form five tables with independent table headings. See highlighted changes on pages 3-4. Lines 53-78. Also see red highlights on lines 321, 329, 335, 340 and 368 of pages 18 and 20.

COMMENT OF REVIEWER 2

dear Author most of my inquiries are from Materials and methods

“Patients were examined with a Scheimpflug principle-based Pentacam corneal topographer” suold be tomographer.

RESPONSE

Thank you. “topographer” has been replaced with “tomographer” in the Materials and methods section. Kindly see highlighted changes on lines 109-110 of page 5.

COMMENT

‘The Pentacam posses some very distinct parameters that are very specific for keratoconus and where not included in the paper: Anterior Radius of Curvature (ARC) Posterior Radius of Curvature (PRC) and on the BAD display Df,Db,Dp,Dt,De, BAD-D which were validated by Beilin and Ambrosio’s work and makes them the “go to” parameters to distinguish normal from keratoconus cornea when using the Pentacam’

RESPONSE

Thank you. All the parameters you have drawn our attention to were actually included in the results section and written about in the discussion section of the main manuscript as well as in the abstract.

Kindly see red highlights on tables 1, 2, 4 and 5 of pages 8, 9, 10, 11 and 12. Also see red highlights on lines 264-271 of page 15.

COMMENT

“Way the particular parameters where chosen?”

RESPONSE

Thank you very much.

All chosen parameters were informed by literature and related studies.

COMMENT

“How was high myopic astigmatic patient were defined in diopters? And was the astigmatism matched to KC patients?”

RESPONSE

Thank you. This is a valid question. Patients who had sphero-cylindrical refractive errors with spherical components greater than -6.00D were considered high myopic astigmats. Besides, because keratoconus induces high and irregular astigmatism, it was difficult getting high myopic astigmats with matched cylinder components. However, cases in both groups were age matched.

See highlighted changes on lines 135-137 of page 7.

COMMENT

“No details on inclusion and exclusion criteria like corneal interventions, use of contact lens and proper contact lens discontinuation before Pentacam scans etc.”

RESPONSE

Thank you. Inclusion and exclusion criteria have been expanded to include details on contact lens wear and corneal interventions prior to Pentacam scans. See highlighted changes on lines 104-108 of page 5.

COMMENT

“Was there any randomization in choosing the patients in both groups?”

RESPONSE

Thank you. The study employed a retrospective cross-sectional design and did not require random assignment of participants. See red highlights on lines 92-99 of page 5.

Submitted filename: Response to Reviewers 2.docx

Click here for additional data file.

15 Nov 2021

The utility of measures of anterior segment parameters of pentacam scheimpflug tomographer in discriminating high myopic astigmatism from keratoconus

PONE-D-21-20839R1

Dear Dr. Kyei,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Michael Mimouni

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have adequately responded to the issues raised in the previous review. This is a relevant paper which the readership will find useful.

Reviewer #2: Dear Author, I appreciate your dedicated and thorough response.

you addressed all of my questions and modified the the paper accordingly.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

17 Nov 2021

PONE-D-21-20839R1

The utility of measures of anterior segment parameters of a Pentacam Scheimpflug tomographer in discriminating high myopic astigmatism from keratoconus

Dear Dr. Kyei:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Michael Mimouni

Academic Editor

PLOS ONE