Aberrations are unique features of a patient's eye that arise from refractive interfaces (eg, cornea and lens).1 Aberrations can affect the quality of vision1 and are known to increase in keratoconus and other ectatic disorders.2–4 Adaptive optics technology could play an important role in determining the best combination of aberrations to maximize the quality of vision. When corrected with adaptive optics, visual quality and contrast sensitivity can be improved beyond the limits of spectacles and contact lenses in normal eyes.5 A new prototype device that combined the Hartmann–Shack aberrometer and deformable mirror was demonstrated in 2002.6 The device was capable of measuring and modifying the ocular aberrations for functional vision testing of the patient.6,7 Subsequently, the device was modified to replace the deformable mirror with a liquid crystal on silicon light modulator to perform specific modulation of aberrations.8–10 The test–retest variability of the aberrometer in the commercial device was assessed in normal eyes.11 However, repeatability of this device on keratoconic eyes needs to be assessed. This is particularly important for surgical treatments such as wavefront-guided surgery, where ablation volume is computed based on reliable measurement of ocular aberrations. Therefore, the purpose of the current study was to analyze intrasession repeatability of the device for lower order aberrations and higher order aberrations (HOAs) in normal and keratoconic eyes.12
Patients and Methods
This was a prospective study, approved by the Narayana Nethralaya Eye Hospital Ethics Committee, Bengaluru, India. The research followed the tenets of the Declaration of Helsinki and all participants gave written informed consent. One hundred fifteen normal eyes of 115 patients and 92 keratoconic eyes (grade I and II severity on Amsler–Krumeich classification13,14) of 92 patients were recruited for the study. For the normal population, only normal eyes with a corrected distance visual acuity of 20/20 or better, spherical error less than −5.00 diopters (D), and astigmatism less than 4.00 D were included. Keratoconus was diagnosed on the basis of clinical signs such as scissoring of the red reflex or an abnormal retinoscopy reflex, Fleischer's ring, Vogt's striae, and topographic evidence.15 Exclusion criteria included the presence of progressive myopia, advanced keratoconus, active ocular disease, diabetic retinopathy, contact lens wear, or any other ocular diagnosis that may alter the optical quality. All participants underwent a complete ocular examination before the test.
Measurements of ocular aberrations were obtained using the Visual Adaptive Optics simulator (Voptica S.L., Murcia, Spain). The device measured the refraction in diopters and the root mean square of HOAs (HOARMS) in microns for a pupil size of 4.5 mm. The device software provided an output up to 8th order Zernike decomposition of the aberrations. However, the current study was limited up to 5th order to maintain clinical relevance because most Zernike coefficients of 5th order and higher were generally small in magnitude compared to 4th order and lower. After proper focus and alignment, three measurements were obtained by the same experienced operator (SK) using the same method for normal and keratoconic eyes. Defocus (sphere), astigmatism, trefoil (Z6 and Z9), coma (Z7 and Z8), spherical aberration (Z12), and the total HOAs (HOARMS) were assessed using the device.
Statistical analyses were performed using MedCalc statistical software (version 16.8; MedCalc Software, Inc., Mariakerke, Belgium) and included within-subject standard deviation. The standard deviation was calculated as the square root of the mean square error.16 An intraclass correlation coefficient (ICC), a measure of the repeatability of measurements, was also obtained.17 This correlation measured the relative homogeneity within groups (between the repeated measurements) in relation to the total variation. The ICC approached 1.0 when the variability within repeated measurements was zero. Low intra-observer repeatability is generally assumed when the ICC is below 0.75. The three measurements for each participant were considered to account for intra-session repeatability.
The sample size of normal and keratoconic eyes for this study was sufficient (within 10% confident limit).18
The mean age of the normal eyes was 27.3 ± 4.3 years (range: 16 to 40 years). Three measurements each for sphere (defocus), cylinder (astigmatism), HOARMS, and Zernike polynomials trefoil (Z6 and Z9), coma (Z7 and Z8), and spherical aberration (Z12) are summarized in Table 1. The mean value with 95% confidence interval and the mean ± SD across participants for a given measurement were assessed. Table 1 also shows ICCs for all of the parameters. An ICC above 0.8 was obtained for many parameters, suggesting good repeatability in normal eyes (sphere: 0.99, cylinder: 0.99, HOARMS: 0.80). Further, lower order aberrations (sphere and cylinder) were associated with better repeatability than HOAs in normal eyes. The ICC of axis of cylinder was low (0.71). Therefore, the ICC was calculated for the subgroup of eyes based on magnitude of cylinder. For eyes with cylinder less than 0.50 D, the ICC was only 0.49. For eyes with cylinder greater than 1.00 D, the ICC improved to 0.84. For eyes with cylinder greater than 2.00 D, ICC was 0.83. Thus, magnitude of cylinder was critical in obtaining repeatable measurements of axis.
Parameters in Normal Eyes (n = 115)
Relevant parameters for keratoconic patients (51 women and 41 men) with a mean age of 26.7 ± 10.8 years (range: 14 to 42 years) are summarized in Table 2. An ICC greater than 0.9 was obtained for all parameters (sphere: 0.94, cylinder: 0.96, HOARMS: 0.95), suggesting high repeatability in grade I and grade II keratoconus. In this cohort, the ICC was comparable for both lower order aberrations and HOAs. In patients with keratoconus, the ICC of the axis was greater than the ICC of the axis in normal eyes (0.95) due to greater magnitude of aberrations and abnormal curvature.
Parameters in Keratoconic Eyes (n = 92)
The Hartmann–Shack aberrometer (Irx3; Imagine Eyes, Orsay, France; Keratron, Optikon, Rome, Italy) can give excellent results for total ocular aberrations.19 A highly repeatable measurement of aberrations will help tremendously in designing optical corrections using wavefront-guided corneal surgery,20 aberration-correcting contact lenses,21 and wavefront-based custom intraocular lenses.22 In this study, overall the device achieved high and similar repeatability in both normal and keratoconic eyes.
Another study evaluated the inter-session and intra-session repeatability of aberrations in normal individuals using visual adaptive optics.11 They reported ICC values of 0.99 and 0.97 for sphere and cylinder, respectively. However, the ICC for HOARMS was 0.61, which implied that lower order aberrations had better repeatability than HOAs. Overall, better results were obtained with RMS values than with some of the individual Zernike coefficients (Tables 1–2). Other commercial instruments based on Hartmann–Shack sensors were comparable to our study. In a study using the Zywave (Bausch & Lomb, Rochester, NY), the ICC of total HOAs and second-order terms were greater than 0.94. The ICC for 3rd-order terms was high (ICCs > 0.87).23 Using the iDesign aberrometer (Abbot Medical Optics, Inc., Santa Ana, CA), the ICC for sphere and cylinder was 0.999 and 0.995 D, respectively.24 Another study evaluated the repeatability of Topcon KR-1W (Topcon, Inc., Tokyo, Japan).25 For intra-session repeatability, excellent ICC values were obtained (ICC > 0.87), except for internal primary coma (ICC = 0.75) and 3rd order (ICC = 0.72) HOA.25
Studies suggested that measurement errors may occur in keratoconic eyes with Hartmann–Shack devices.26 A study used the IRX3 (Imagine Eyes, Paris, France) to compare the aberrometry-derived refractive error in patients with keratoconus and normal eyes (n = 12, age: 33.6 ± 4.2 years). The lower order aberrations and HOAs measured in keratoconic eyes showed high variability compared to measurements in normal eyes.27 In the current study, most of the parameters had comparable repeatability in normal and keratoconic eyes, although keratoconic eyes had somewhat better repeatability. However, whether a similar trend will remain for higher grades of keratoconus is unknown at this point. Another study reported better repeatability (good to moderate) in keratoconic eyes than in normal eyes (moderate to poor).28 However, the current study established that visual adaptive optics demonstrated good performance in terms of single-session intra-user repeatability for refractive and wavefront parameters. A future study comparing this device with other Hartmann–Shack aberrometers could be worthwhile. The study conclusions may not apply to eyes with more advanced stages of the disease.
- Lombardo M, Lombardo G. Wave aberration of human eyes and new descriptors of image optical quality and visual performance. J Cataract Refract Surg. 2010;36:313–331. doi:10.1016/j.jcrs.2009.09.026 [CrossRef]
- Saad A, Gatinel D. Evaluation of total and corneal wavefront high order aberrations for the detection of forme fruste keratoconus. Invest Ophthalmol Vis Sci. 2012;53:2978–2992. doi:10.1167/iovs.11-8803 [CrossRef]
- Mahmoud AM, Nuñez MX, Blanco C, et al. Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus. Am J Ophthalmol. 2013;156:1102–1111. doi:10.1016/j.ajo.2013.07.018 [CrossRef]
- Hallahan KM, Sinha Roy A, Ambrósio R Jr, Salomão M, Dupps WJ Jr, . Discriminant value of custom ocular response analyzer waveform derivatives in keratoconus. Ophthalmology. 2014;121:459–468. doi:10.1016/j.ophtha.2013.09.013 [CrossRef]
- Liang J, Williams DR, Miller DT. Supernormal vision and high-resolution retinal imaging through adaptive optics. J Opt Soc Am A Opt Image Sci Vis. 1997;14:2884–2892. doi:10.1364/JOSAA.14.002884 [CrossRef]
- Fernandez EJ, Manzanera S, Piers P, Artal P. Adaptive optics visual simulator. J Refract Surg. 2002;18:S634–S638.
- Roorda A. Adaptive optics for studying visual function: a comprehensive review. J Vision. 2011;11:pii:6 doi:10.1167/11.5.6 [CrossRef]
- Manzanera S, Prieto PM, Ayala DB, Lindacher JM, Artal P. Liquid crystal Adaptive Optics Visual Simulator: application to testing and design of ophthalmic optical elements. Opt Express. 2007;15:16177–16188. doi:10.1364/OE.15.016177 [CrossRef]
- Fernández EJ, Prieto PM, Artal P. Binocular adaptive optics visual simulator. Opt Lett. 2009;34:2628–2630. doi:10.1364/OL.34.002628 [CrossRef]
- Prieto PM, Vargas-Martín F, Goelz S, Artal P. Analysis of the performance of the Hartmann-Shack sensor in the human eye. J Opt Soc Am A Opt Image Sci Vis. 2000;17:1388–1398. doi:10.1364/JOSAA.17.001388 [CrossRef]
- Otero C, Vilaseca M, Arjona M, Martínez-Roda JA, Pujol J. Repeatability of aberrometric measurements with a new instrument for vision analysis based on adaptive optics. J Refract Surg. 2015;31:188–194. doi:10.3928/1081597X-20150224-03 [CrossRef]
- Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–310. doi:10.1016/S0140-6736(86)90837-8 [CrossRef]
- Colak HN, Kantarci FA, Yildirim A, et al. Comparison of corneal topographic measurements and high order aberrations in keratoconus and normal eyes. Cont Lens Anterior Eye. 2016;39:380–384. doi:10.1016/j.clae.2016.06.005 [CrossRef]
- Alio JL, Shabayek MH. Corneal higher order aberrations: a method to grade keratoconus. J Refract Surg. 2006;22:539–545.
- Wygledowska-Promienska D, Zawojska I. Procedure for keratoconus detection according to the Rabinowitz-Rasheed method--personal experience [article in Polish]. Klinika Oczna. 2000;102:241–244.
- Bland JM, Altman DG. Measurement error. BMJ. 1996;313:744. doi:10.1136/bmj.313.7059.744 [CrossRef]
- Weir JP. Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res. 2005;19:231–240.
- McAlinden C, Khadka J, Pesudovs K. Precision (repeatability and reproducibility) studies and sample-size calculation. J Cataract Refract Surg. 2015;41:2598–2604. doi:10.1016/j.jcrs.2015.06.029 [CrossRef]
- Visser N, Berendschot TT, Verbakel F, Tan AN, de Brabander J, Nuijts RM. Evaluation of the comparability and repeatability of four wavefront aberrometers. Invest Ophthalmol Vis Sci. 2011;52:1302–1311. doi:10.1167/iovs.10-5841 [CrossRef]
- Kim A, Chuck RS. Wavefront-guided customized corneal ablation. Curr Opin Ophthalmol. 2008;19:314–320. doi:10.1097/ICU.0b013e328302ccae [CrossRef]
- Marsack JD, Parker KE, Applegate RA. Performance of wavefront-guided soft lenses in three keratoconus subjects. Optom Vis Sci. 2008;85:E1172–E1178. doi:10.1097/OPX.0b013e31818e8eaa [CrossRef]
- Nochez Y, Favard A, Majzoub S, Pisella PJ. Measurement of corneal aberrations for customisation of intraocular lens asphericity: impact on quality of vision after micro-incision cataract surgery. Br J Ophthalmol. 2010;94:440–444. doi:10.1136/bjo.2009.167775 [CrossRef]
- Lopez-Miguel A, Maldonado MJ, Belzunce A, Barrio-Barrio J, Coco-Martin MB, Nieto JC. Precision of a commercial Hartmann-Shack aberrometer: limits of total wavefront laser vision correction. Am J Ophthalmol. 2012;154:799–807. doi:10.1016/j.ajo.2012.04.024 [CrossRef]
- Prakash G, Jhanji V, Srivastava D, et al. Single session, intra-observer repeatability of an advanced new generation Hartmann-Shack aberrometer in refractive surgery candidates. J Ophthalmic Vis Res. 2015;10:498–501. doi:10.4103/2008-322X.176893 [CrossRef]
- López-Miguel A, Martínez-Almeida L, González-García MJ, Coco-Martin MB, Sobrado-Calvo P, Maldonado MJ. Precision of higher-order aberration measurements with a new Placido-disk topographer and Hartmann-Shack wavefront sensor. J Cataract Refract Surg. 2013;39:242–249. doi:10.1016/j.jcrs.2012.08.061 [CrossRef]
- Katsoulos C, Karageorgiadis L, Vasileiou N, Mousafeiropoulos T, Asimellis G. Customized hydrogel contact lenses for keratoconus incorporating correction for vertical coma aberration. Ophthalmic Physiol Opt. 2009;29:321–329. doi:10.1111/j.1475-1313.2009.00645.x [CrossRef]
- Jinabhai A, Radhakrishnan H, O'Donnell C. Repeatability of ocular aberration measurements in patients with keratoconus. Ophthalmic Physiol Opt. 2011;31:588–594. doi:10.1111/j.1475-1313.2011.00868.x [CrossRef]
- Ortiz-Toquero S, Rodriguez G, de Juan V, Martin R. Repeatability of wavefront aberration measurements with a Placido-based topographer in normal and keratoconic eyes. J Refract Surg. 2016;32:338–344. doi:10.3928/1081597X-20160121-04 [CrossRef]
Parameters in Normal Eyes (n = 115)a
|Parameter||Exam 1||Exam 2||Exam 3||ICC|
|Sphere (D)||−1.82 ± 2.05 (−2.20, −1.44)||−1.81 ± 2.07 (−2.20, −1.43)||−1.82 ± 2.09 (−2.21, −1.44)||0.99|
|Cylinder (D)||−0.72 ± 0.94 (−0.90, −0.55)||−0.76 ± 0.99 (−0.94, −0.57)||−0.73 ± 0.98 (−0.92, −0.55)||0.99|
|Axis (degrees)||92.94 ± 61.29 (81.62, 104.26)||92.23 ± 59.75 (81.20, 103.27)||90.16 ± 60.85 (78.92, 101.40)||0.71|
|HOARMS||0.18 ± 0.09 (0.17, 0.20)||0.17 ± 0.08 (0.15, 0.18)||0.18 ± 0.10 (0.17, 0.20)||0.80|
|Z6||−0.05 ± 0.06 (−0.06, −0.04)||−0.05 ± 0.06 (−0.06, −0.04)||−0.05 ± 0.07 (−0.06, −0.04)||0.85|
|Z7||−0.02 ± 0.10 (−0.04, 0.0)||−0.02 ± 0.10 (−0.03, 0.0)||−0.02 ± 0.10 (−0.04, 0.0)||0.95|
|Z8||0.0 ± 0.065 (−0.02, 0.0)||0.0 ± 0.063 (−0.01, 0.01)||0.0 ± 0.065 (−0.017, 0.01)||0.81|
|Z9||0.0 ± 0.07 (−0.01, 0.01)||0.02 ± 0.06 (0.0, 0.03)||0.0 ± 0.07 (−0.01, 0.02)||0.86|
|Z12||0.02 ± 0.05 (0.01, 0.025)||0.01 ± 0.05 (0.0, 0.02)||0.02 ± 0.06 (0.0, 0.03)||0.91|
Parameters in Keratoconic Eyes (n = 92)a
|Parameter||Exam 1||Exam 2||Exam 3||ICC|
|Sphere (D)||−1.77 ± 2.53 (−2.32, −1.22)||−1.88 ± 2.48 (−2.42, −1.34)||−1.82 ± 2.48 (−2.36, −1.28)||0.94|
|Cylinder (D)||−3.51 ± 2.79 (−4.11, −2.90)||−3.42 ± 2.76 (−4.02, −2.83)||−3.43 ± 2.51 (−3.98, −2.88)||0.96|
|Axis (degrees)||93.02 ± 53.7 (81.36, 104.68)||90.70 ± 54.0 (78.99, 102.42)||90.62 ± 53.8 (78.96, 102.28)||0.95|
|HOARMS||0.72 ± 0.51 (0.61, 0.83)||0.72 ± 0.51 (0.61, 0.83)||0.72 ± 0.50 (0.62, 0.83)||0.98|
|Z6||−0.01 ± 0.39 (−0.10, 0.07)||−0.03 ± 0.41 (−0.12, 0.06)||−0.02 ± 0.35 (−0.10, 0.06)||0.89|
|Z7||−0.37 ± 0.33 (−0.45, −0.30)||−0.35 ± 0.40 (−0.44, −0.26)||−0.40 ± 0.40 (−0.48, −0.31)||0.88|
|Z8||0.01 ± 0.33 (−0.04, 0.06)||0.03 ± 0.40(−0.02, 0.07)||0.03 ± 0.40 (−0.02, 0.08)||0.90|
|Z9||0.07 ± 0.34 (0.0, 0.14)||0.03 ± 0.32 (−0.04, 0.10)||0.02 ± 0.26 (−0.04, 0.08)||0.95|
|Z12||−0.08 ± 0.16 (−0.12, −0.05)||−0.09 ± 0.18 (−0.12, −0.05)||−0.07 ± 0.18 (−0.11, −0.03)||0.87|