Anterior Segment Optical Coherence Tomography Indices and Their Value in Diagnosing Corneal Ectasia ()
1. Introduction
The keratoconus [1] [2] and the marginal pellucid degeneration [3] are the two most common corneal ectatic diseases. Both conditions are noninflammatory, bilateral and are characterized by corneal thinning, which leads to protrusion. The diagnostics of the corneal ectasias is based on several clinical features—patient’s refractive error, the presence or absence of Vogt striae, Fleisher ring, Munson sign as well as changes in the topographical [4] [5] and the biomechanical properties of the cornea [6] [7] [8] [9].
The main features of keratoconus according to the participants in the latest consensus [10] on the topic are posterior cornea ectasia, abnormal corneal thickness profile and noninflammatory thinning. In contrast to the corneal topography, which provides information about the changes in the anterior surface of the cornea, the corneal tomography and the anterior segment optical coherence tomography are excellent tools for observation of the changes in the corneal properties.
The anterior segment optical coherence tomography (AS-OCT) is already a widespread technology and has an important role in the diagnostic and the follow up of many ocular diseases—corneal dystrophies [11], glaucoma [12] [13] [14], ocular tumors [15] [16], keratitis [17] [18] [19] and others. When it comes to corneal ectasia, the anterior segment OCT gives us an excellent opportunity to evaluate corneal [20] [21] and epithelial [20] [21] thickness.
The purpose of the study is to determine the diagnostic capability of the anterior segment OCT indices in patients with keratoconus and pellucid marginal degeneration.
2. Patients and Methods
The current study includes two groups of patients—healthy controls and patients with corneal ectasia, that were age and sex-matched. Each group consists of 80 eyes of 43 caucasian individuals, 23 male and 20 female. Each participant underwent a standard ophthalmological examination followed by corneal topography with OCULUS Keratograph 5M (Oculus, Germany) and anterior-segment ОСТ with OptovueRTVue-100 (OptoVue, USA). Patients wearing contacts were instructed to discontinue them for at least 3 days before the examination.
Inclusion criteria for the ectatic group are:
· Kmax values above 47 diopters.
· Corneal astigmatism above 3 diopters.
· Asymmetrical topographical map consistent with corneal ectasia.
Inclusion criteria for the control group are:
· Kmax values under 47 diopters.
· Symmetrical topographical map consistent with corneal astigmatism.
Exclusion criteria for the ectatic group are:
· significant corneal scarring.
· corneal hydrops.
· previous crosslinking.
Exclusion criteria for the control group are:
· corneal astigmatism greater than 3 diopters.
· myopia or hyperopia greater than 5 diopters.
· history of keratitis.
· ocular surgery.
We took into consideration the following parameters generated by the anterior-segment OCT (Figure 1): Mean corneal thickness in 17 sectors, Min (minimal corneal thickness in the 6 mm zone), Min-Max index (the maximum corneal thickness subtracted from the minimal corneal thickness), Min-Median index (the mean corneal thickness subtracted from the minimal corneal thickness), SN-IT index (the mean corneal thickness of the interior temporal sector subtracted from the mean corneal thickness of the superior nasal sector), S-I index (the mean corneal thickness of the inferior corneal sector subtracted from the mean corneal thickness of the superior sector).
The statistical analysis was performed using SPSS version 15 and the following tests: Mann-Whitney U test, Independent-Samples T-test and ROC (Receiver
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Figure 1. AS-OCT printout with a pachymetric map with corneal thickness in 17 locations.
Operating Characteristic Analysis).
3. Results
The average age in the control group was 34,4 years and 34,6 years in the group with ectasia (Table 1).
After determining the distribution of the data, we used the independent-sample T-test to compare the following indices: central corneal thickness (CCT), superior nasal corneal thickness, inferior nasal corneal thickness, temporal corneal thickness, superior temporal corneal thickness, outer superior nasal corneal thickness, outer nasal corneal thickness, outer inferior nasal corneal thickness, outer inferior temporal corneal thickness, outer temporal corneal thickness, SN-IT and S-N (Table 2).
For the rest of the parameters (superior corneal thickness, nasal corneal thickness, inferior corneal thickness, inferior temporal corneal thickness, outer superior nasal corneal thickness, outer superior temporal corneal thickness, minimal corneal thickness (Min), Min-Max, Min-Med) we used the Mann-Whitney U test (Table 3). The null hypothesis was rejected for all of the examined indices
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Table 1. Age description for the control and ectatic groups
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Table 2. Independent-sample T-test.
using a confidence interval of 95% and p < 0.001, The ROC analysis determined that the mean corneal thickness in several sectors (outer inferior temporal, inferior temporal, central corneal thickness, outer inferior) alongside the indices of focal thinning (Min-Med and Min-Max) had excellent diagnostic capabilities to differentiate ectatic from normal corneas.
On the other hand, thickness asymmetry indices SN-IT and S-I had a lot worse performance (Figure 2).
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Figure 2. Area under the curve for SN-IT and S-I.
The minimal corneal thickness (MIN) has the highest area under the curve from all of the examined parameters—0.976 with a combination of sensitivity and specificity of 0.925, 0.911 and “cut-off”value оf 484.5 microns.
Min-Med and Min-Max have an area under the curve of 0.973 and 0.971 respectively (Figure 3). Min-Med index has a sensitivity of 0.938 and specificity of 0.962 with a “Cut off” value of −30, while the values for the Min-Max index were 0.938/0.937/−68 (sensitivity/specificity/“cut-off” value).
The mean corneal thickness in the outer inferior temporal sector (O INFT) has an area under the curve of 0.956 (Figure 4). The sensitivity, specificity and the “cut-off” values are 0.900, 0.886 and 510.5 respectively. The mean corneal thickness in the inferior temporal sector and the central corneal thickness (Figure 5) have almost identical areas under the curve 0.955 and 0.950.
The combination of sensitivity, specificity and the “cut-off” values are 0.900/ 0.900/499.5 for the former and 0.913/0.900/494.0 for the latter.
The rest of the sectors with still good performance are the outer inferior (OINF), the temporal (TEMP), the outer temporal (O Temp) and the inferior (INF) one. Their AUC are 0.950, 0.945, 0.939 and 0.927 respectively. The sensitivity, specificity and the “Cut off “values are shown in Table 4.
The area under the curve for the remainder of the indices is in the range from 0.914 to 0.814.
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Figure 3. Area under the curve for min-med and min-max.
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Figure 4. Area under the curve for Minimal corneal thickness and the following corneal sectors-Outer superior, Outer superior nasal, Outer nasal, Outer inferior nasal, Outer inferior, outer inferior temporal, outer temporal, outer superior temporal.
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Figure 5. Area under the curve for CCT and the following corneal sectors—superior, superior nasal, nasal, inferior nasal, inferior, temporal, superior temporal.
4. Discussion
In the current study, several indices show excellent diagnostic capabilities.
The central corneal thickness (ССТ) and the minimum corneal thickness (Min) are the two best performing parameters with an area under the curve of 0.950 and 0.976. Before the introduction of the Shleimflug devices and their new indices—ART (Ambrosio relational thickness), PPI (pachymetric progression index), PTI (percentage thickness increase) and others, the CCT [22] [23] [24] and the Min [22] [23] [24] [25] [26] were the most used commonly used pachymetric indices.
There is plenty of publications on the topic, but most of them are based on a tomographic [22] [23] [24] [25] examination and only a few are with ultrasound [27] or OCT devices [26] [27] [28]. Some of the authors haven’t taken into consideration the central corneal thickness and for those that have, it is performing worse than MIN [22] [23] [24]. There is a good reason for that—for most of the cases, the zone with the thinning is situated slightly inferior and temporal [27]
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Table 5. Values of indices of different authors.
and not centrally, so the Min and the CCT value don’t match.
Most of the authors also have lower AUC for both CCT and Min (Table 5).
The mean corneal thickness in several sectors also shows promising results. The area under the curve for the following zones: outer inferior, inferior temporal, outer inferior, and temporal, is in the range between 0.956 and 0.945.
Unfortunately, there are only a few publications with the OptoVueRTVue 100 device, and none of them examined the mean corneal thickness. As already stated, the thinnest zone in patients with ectasia is displaced inferiorly and temporally (in keratoconus) or inferiorly (in PMD), so it makes sense for those sectors to be with the best diagnostic value.
In the current study, the indices of focal thinning (Min-med and Min-max) outperform the thickness asymmetry ones (SN-IT and S-N). The area under the curve for Min-Med is 0.973 and for Min-Maх 0.971. In comparison, SN-IT and S-I have a lower area under the curve of 0.861 and 0.843 respectively. Most of the publications on the topic also confirm this finding.
Li et al. [26] were one of the first to use anterior segment OCT in the diagnostics of corneal ectasia. With the Zeiss OCT device, they found AUC for Min-Med of 0.929. The I-S and IT-SN indices, which are analogous to the ones we used, also have worse performance when compared to Min-Med with values of 0.868 and 0.894 respectively.
With the RTvue OCT, Qin et al. [28] have reported an AUC of 0.925 for Min-Med (they haven’t tested Min-Max). The results for SN-IT and S-I are like the ones we have reported—0.896 and 0.861.
5. Conclusion
The anterior segment OCT and its pachymetric indices and maps offer important information about the corneal thickness profile in patients with corneal ectasias. The focal thinning indices alongside the mean corneal thickness in the inferior and the temporal parts of the cornea can be used to distinguish normal from ectatic corneas.