EyeWorld Asia-Pacific December 2018 Issue

more challenging is differentiation between subclinical disease, such as with forme fruste keratoconus, and normal eyes. “Apart from the tomography, we would like to evaluate the biome- chanical properties of the cornea in order to have a complete picture of the cornea, especially since corneal biomechanical failure is the basis of keratoconus,” Dr. Chan said. The Cor- vis ST provides this information. An ultra high-speed Scheimp- flug device, the Corvis ST applies a non-contact tonometer symmetrically metered air pulse to the cornea and scans at 4,330 frames/sec, with 8-mm horizontal coverage. Dr. Chan discussed a number of parameters for evaluating cor- other hand, showed higher repeatabil- ity for ACD measurements. Tommy Chan, MD , shifted the discussion to the use of the Corvis ST (OCULUS), discussing “The use of combined tomographic and biome- chanical assessment in pre-refractive surgery screening.” Rotating Scheimpflug imaging, he said, provides useful information on the base of tomographic data for diagnosing early ectatic change, contextualizing the importance of this by calling corneal ectasia a “nightmare”—“one of the most dev- astating complications after corneal refractive surgery” that can occur any time. While current methods easily differentiate ectatic from normal eyes, neas and described the Vinciguerra Screening Report, which incorporates seven parameters, including DA ratio, integrated radius, Ambrosio relational thickness (ART), the new corneal stiffness parameter SP-A1, and Corvis biomechanical index (CBI). The Vinciguerra group used CBI to differentiate keratoconus from normal and found a very high AUC of 0.990 in differentiating kerato- conus from normal. Dr. Chan and his colleagues also found an AUC of 0.971 when using CBI to differentiate normal corneas from keratoconus. A comparable AUC was observed between CBI (AUC=0.785) and use of the Belin-Ambrosio Display (BAD, AUC=0.757) ( p =0.590) for detection of forme fruste keratoconus with sensi- tivities of 65% and 53%, respectively, specificity of 80%. Dr. Chan said that combin- ing tomography and evaluation of the biomechanical properties of the cornea would allow better detection of subclinical or forme fruste kerato- conus. OCULUS has thus introduced a new parameter with the Pentacam: the tomography biomechanical index (TBI). New software incorporates the Corvis parameters and the tomogra- phy values, generating a TBI at the end. Dr. Chan and his colleagues analyzed data from 41 keratoconus cases, with 37 controls and 23 sub- clinical keratoconus. They found a very high AUC of 0.925 with specific- ity of 82.4%, sensitivity of 84.4% for differentiating between normal and subclinical keratoconus using TBI (Figure 3). “The combination of corneal to- mography and biomechanical proper- ties is a very good tool to enhance the safety and efficiency of your surgery,” Dr. Chan concluded. Also speaking on her experience with the Corvis ST, Usanee Rein- prayoon, MD , discussed “Clinical applications of corneal biomechanics in corneal diseases.” Dr. Reinprayoon described her conceptual framework as follows: If you do refractive surgery on patients with subclinical keratoconus, the pa- tient may end up with corneal ectasia. Similarly, if you do cataract surgery on patients with Fuchs’ endothelial corneal dystrophy (FECD), the patient may end up with corneal decompen- sation. FECD, she said, is a progres- sive loss of corneal endothelial cells leading to corneal thickening and edema that may be focal or diffuse. It requires clinical assessment, with specular microscopy limited to a small central area and high variation in cell count and pachymetry providing an indirect measurement to evaluate endothelial cell function. In FECD, she said, tissue hydra- tion is increased. How does this affect corneal stiffness and biomechanics? Dr. Reinprayoon said that corneal biomechanics provides an understanding of the natural history, pathophysiology, and prognosis of FECD. She and her colleagues used the Corvis ST to analyze the corneal bio- mechanics in 80 FECD patients, look- ing at various parameters. During the inward motion (Applanation 1), they looked at A1-Time, the time taken for the cornea to reach first applanation; A1-Length, the length of the flat- tened portion at first applanation; and A1-Velocity, the velocity of inward motion at first applanation. At the point of highest concavity (HC), they looked at HC Time, the time taken for the cornea to reach HC; Peak Dis- tance, the distance between the peaks; HC Radius, the radius of curvature at HC; and Deformation Amplitude (DA), displacement from initial state. Finally, during outward motion (Ap- planation 2), they looked at A2-Time, the time taken for the cornea to reach second applanation; A2-Length, the length of flattened portion at second applanation; and A2-Velocity, the velocity of inward motion at second applanation. She said that nearly all corneal biomechanical parameters correlated with clinical staging; compared to the normal population, the FECD patient’s cornea is more easily com- pressed by pneumopressure, and the more advanced the disease, the flatter the cornea. A1-Time and A1-Length seem to be the sensitive parameters among those analyzed (Figure 4). This understanding will benefit the treatment plan of patients, she said. In the future, Dr. Reinprayoon said that corneal biomechanics is ap- plicable in the diagnosis of endotheli- al decompensation from other causes and in the follow-up of patients post- corneal transplantation, for the novel prediction of corneal diseases, and to evaluate the effect of corneal trans- plantation and donor parameters. Copyright 2019 ASCRS Ophthalmic Corporation. All rights reserved. The views expressed here do not necessarily reflect those of the editor, editorial board, or publisher, and in no way imply endorsement by EyeWorld, ASCRS, or APACRS. Figure 3. TBI had a high AUC for differentiating between normal and subclinical keratoconus. Source: Tommy Chan, MD Figure 4. Applanation 1 parameters Source: Usanee Reinprayoon, MD Applanation 1 Inward motion 1.79 1.84 1.92 1.6 1.65 1.7 1.75 1.8 1.85 1.9 1.95 2 2.05 Stage1 Stage2 Stage3 A1- Length (mm) 6.89 6.83 6.66 5.8 6 6.2 6.4 6.6 6.8 7 7.2 7.4 Stage1 Stage2 Stage3 A1- Time (ms) 0.14 0.14 0.16 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2 Stage1 Stage2 Stage3 A1- Velocity (m/s) General linear model l n ti 1 I r ti 1.79 1.84 1.92 1.6 1.65 1.7 1.75 1.8 1.85 1.9 1.95 2 2.05 Stage1 Stage2 Stage3 A1- Length (mm) 6.89 6.83 6.66 5.8 6 6.2 6.4 6.6 6.8 7 7.2 7.4 Stage1 Stage2 Stage3 A1- Time (ms) 0.14 0.14 0.16 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2 Stage1 Stage2 Stage3 A1- Velocity (m/s) General linear model Applanation 1 Inward motion 618 Copyright © SLACK Incorporated Corneal Tomography vs New Biomechanical Index/Chan et al combined parameter based on Scheimpflug-based cor- neal tomography and biomechanical assessments. S TATISTICAL A NALYSIS Only one eye with the lower average keratometry was selected for analysis for normal participants. As for pa- tients with subclinical keratoconus, the less severe eye with lower average keratometry value was selected. Statistical analysis w s performed using R 3.2.5 soft- ware (R Foundation, Vienna, Austria). Classification analyses between normal a d subclinical keratoconus were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) and partial AUC (pAUC) with specificity of 80% or greater for each classifying parameter was compared based on bootstrap resampling with 200 replicates, one eye from each participant was sampled with re- placement in each bootstrap replicate. AUCs provide an overall comparison of the whole ROC curves with an AUC of 1 representing a perfect classification at any level of specificity. A common classifying system in which AUC 0.5 to 0.6 = fail; 0.6 to 0.7 = poor; 0.7 to 0.8 = fair; 0.8 to 0.9 = good; and 0.9 to 1.0 = excellent is adopted. Although pAUCs focus on the comparison of ROC curves at the sector with specificity of 80% or greater, a pAUC of 0.2 represents a perfect classifica- tion at any level of specificity of 80% or greater. Be- cause a low level of specificity is usually irrelevant to practical use, it is believed that the pAUC is more rele- vant to cli ical practice. The mean nd median values for each parameter measured for all eyes were estimat- ed. Comparison of median values in each parameter between groups was performed using Mann–Whitney U tests. A P value of less than .05 was considered sta- tistically significant. RESULTS The study included 23 eyes with subclinical kera- toconus and 37 normal eyes. The mean age was 32.4 ± 8.4 years (range: 16 to 53 years) with no difference be- tween groups ( P = .779). Parameters obtained from the Pentacam are shown in Table A (available in the online version of this article). There was no difference in Km, astigmatism, BFS from the anterior and posterior cor- nea, and CKI and KI between normal and SCKC eyes ( P ≥ .097). Significant differences were found in ISV, IVA, CTmin, CTapex, ARTmax, and final D value of BAD between normal and SCKC eyes ( P ≤ .007). Parameters measured with the Corvis ST and the combined TBI are shown in Table A . Significant differences were found in A1T, A1V, DA ratio 1, DA ratio 2, ARTh, RC, IR, Max Inv Rad, SPA1, TBI, and CBI between normal and SCKC eyes ( P ≤ .011). Parameters from the Corvis ST and Pentacam were analyzed for differentiating normal and SCKC eyes. The TBI and BAD final D value demonstrated the high- est AUC (0.925 and 0.786, respectively) and pAUC (0.150 and 0.088, respectively) from the two devices TABLE 1 AUC and pAUC With Specificity ≥ 80% for Classification Between Normal and Subclinical Keratoconus Parameter a AUC pAUC Cut-off Specificity Sensitivity TBI 0.925 0.150 0.16 82.4% 84.4% Corvis ST ARTh 0.836 0.129 444.0 82.4% 81.3% Max inv rad 0.754 0.079 0.19 82.4% 59.4% A1T 0.750 0.052 7.18 82.4% 46.9% RC 0.736 0.094 6.78 82.4% 62.5% Pentacam BAD final D 0.786 0.088 1.38 85.3% 53.1% IVA 0.781 0.125 0.15 88.2% 68.8% ARTmax 0.759 0.095 386.5 82.4% 65.6% CTapex 0.722 0.058 534.5 82.4% 37.5% CTmin 0.710 0.059 529.5 82.4% 43.8% AUC = area under the receiver operating curve; pAUC = partial area under the receiver operating curve; TBI = tomographic biomechanical index; ARTh = hori- zontal Ambrósio’s relational thickness; Max Inv Rad = maximum inverse radius; A1T = time from the initiation of air-puff until the first applanation; RC = radius of curvature at highest concavity; BAD final D = Belin/Ambrósio Enhanced Ectasia Display final D value; IVA = index of vertical asymmetry; ARTmax = maximum Ambrósio’s relational thickness; CTapex = corneal thickness at apex, CTmin = minimum corneal thickness a Only the highest 5 parameters from each device were selected. The Pentacam and the Corvis ST are manufactured by Oculus Optikgeräte, Wetzlar, Germany. Sponsored by OCULUS Optikgeräte GmbH