Peripheral Ocular Aberrations in Mild and Moderate Keratoconus

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Visual Psychophysics and Physiological Optics Peripheral Ocular Aberrations in Mild and Moderate Keratoconus

David A. Atchison, Ankit Mathur, Scott A. Read, Mitchell I. Walker, Alexander R. Newman, Photios P. Tanos, Roderick T. McLennan, and Andrew H. Tran

PURPOSE. To investigate the influence of keratoconus on pe- literature correlating their higher-order aberrations with visual ripheral ocular aberrations. performance.7,8 Some papers have addressed the diagnosis of ETHODS keratoconus before clinical signs and symptoms develop, by M . Aberrations in seven mild and five moderate kerato- 2,9 10 conics were determined over a 42° horizontal ϫ 32° vertical examining corneal or ocular higher-order aberrations. visual field, with a modified aberrometer. Control data were Thus, studies furthering our understanding of aberrations are obtained from an emmetropic group. fundamental to the future clinical management of keratoconic and other abnormal corneas. RESULTS. Most aberrations in the keratoconics showed field Studies have shown significantly greater magnitudes of on- dependence, predominately along the vertical meridian. Mean axis (along the line of sight), higher-order, and total eye aber- spherical equivalent M, oblique astigmatism J , and regular 45 rations—in particular, comalike aberrations—to be present in astigmatism J refraction components and total root mean 9–13 180 keratoconus patients compared with normal subjects. As square aberrations (excluding defocus) had high magnitudes in an example, Pantanelli et al.13 used a large-dynamic range the inferior visual field. The rates of change of aberrations were Hartmann-Shack wavefront sensor to characterize the on-axis higher in the moderate than in the mild keratoconics. Coma aberrations in 32 eyes with keratoconus. Analysis over a 6-mm was the dominant peripheral higher-order aberration in both pupil showed vertical coma to be the dominant higher-order the emmetropes and the keratoconics; for the latter, it had high aberration, followed by trefoil, and then by spherical aberra- magnitudes in the center and periphery of the visual field. tion. Every aberration coefficient up to the fifth order was CONCLUSIONS. Greater rates of change in aberrations across the between two and seven times greater in the keratoconus pop- visual field occurred in the keratoconus groups than in the ulation than in an emmetropia control group. emmetropic control group. The moderate keratoconics had Most research into ocular aberrations, both in normal eyes more rapid changes in, and higher magnitudes of, aberrations and in eyes with pathologic conditions such as keratoconus, across the visual field than did the mild keratoconics. The has been concentrated on axial aberrations. So far, studies of dominant higher-order aberration for the keratoconics across peripheral higher-order aberrations have been conducted by the visual field was vertical coma. (Invest Ophthalmol Vis Sci. only a few groups.14–18 Peripheral vision is used for tasks such 2010;51:6850–6857) DOI:10.1167/iovs.10-5188 as detection,19–21 peripheral motion perception,22 mobility and postural balance,23,24 and driving,25 which, compared eratoconus is a progressive and usually bilateral condition with visual acuity, have less demand for image quality. Periph- Kthat affects the cornea.1 Noninflammatory progressive eral vision is limited, not only by image quality, but also by the central thinning causes the cornea to assume a conical shape low-resolution capacity of the eccentric retina. There are sev- with significant reductions in visual performance.1,2 The “ir- eral reasons for investigating peripheral aberrations. Best cor- regular” astigmatism associated with keratoconus is difficult to recting eccentric fixation after central field loss,26 the possible correct with spectacles alone. Once visual acuity becomes adverse effects on peripheral tasks after LASIK,27 and the idea unsatisfactory with spectacles, rigid gas-permeable contact that peripheral defocus is a cause of myopia progression have lenses are typically prescribed that better neutralize the cor- all generated interest in peripheral refraction.28,29 From the neal aberrations by providing a spherical refractive surface.3 few studies measuring peripheral higher-order aberrations it is The concepts of wavefront-guided corneal refractive sur- well established that second-order aberrations dominate in gery4 and aberration-correcting contact lenses5,6 have sparked peripheral vision,14,26 but higher-order aberrations, in particu- interest in higher-order aberration studies. Keratoconus pa- lar coma, can also be substantial.14,27 Mathur et al.30–32 inves- tients are one population that has received attention, with the tigated the variations in aberration coefficients across the visual field of young emmetropic subjects. Although many terms varied across the visual field, only a selection showed obvious trends. Increases in the second-order astigmatic coefficients From the Visual and Ophthalmic Optics Laboratory, School of Ϫ2 2 Optometry and Institute of Health and Biomedical Innovation, Queens- C2 and C2 from the center to the periphery along 45° to 225° land University of Technology, Kelvin Grove, Queensland, Australia. and 0° to 180° meridians, respectively, were noted, as were Supported by Australian Research Council Discovery Grant decreases in these terms along the meridians perpendicular to DP0558209. the just-mentioned meridians. The vertical coma coefficient Ϫ1 Disclosure: D.A. Atchison, None; A. Mathur, None; S.A. Read , C3 increased linearly from the superior to the inferior field, None; M.I. Walker, None; A.R. Newman, None; P.P. Tanos, None; 1 whereas the horizontal coma coefficient C3 increased linearly R.T. McLennan, None; A.H. Tran, None Ϫ1 from the nasal to the temporal field. The rates of change in C3 Submitted for publication January 11, 2010; revised April 20 and 30 June 11, 2010; accepted June 19, 2010. across the visual field increased with myopia. The interven- tions of LASIK and orthokeratology changed the sign of the rate Corresponding author: David A. Atchison, Institute of Health and 33,34 Biomedical Innovation, Q-Block, Queensland University of Technol- of change of coma across the field. ogy, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia; We extended previous work by investigating peripheral [email protected]. aberrations in keratoconic eyes. We hypothesized that there is

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a greater rate of change in higher-order aberrations across the tion. The spherical equivalent for the mild and moderate keratoconics visual field within a keratoconic population than in an em- was 0.00 Ϯ 0.46 and ϩ1.30 Ϯ 1.44 D, respectively. The best spectacle- metropic one, and that the use of peripheral measures may corrected high (HCVA)- and low (LCVA)-contrast visual acuities of the amplify the differences in ocular aberrations between kerato- keratoconics are described in Table 1. In the emmetropes, only HCVA conic and normal subjects. was measured, which was Յ0.00 logMAR in all subjects. The cone location relative to the pupil center was determined with the videokeratoscope (E300; Medmont International, Pty., Ltd.). The ruler func- METHODS tion inbuilt in the software was used to measure the vertical and This research was approved by the Queensland University of Technol- horizontal displacements from the pupil center to the steepest anterior ogy’s Human Research Ethics Committee and conformed to the tenets corneal curvature location on the tangential power map (Table 1). of the Declaration of Helsinki. Information regarding the study was Each subject also had corneal thickness and topography measured given to the subjects and written consent obtained before testing. with a rotating Scheimpflug camera (Pentacam HR; Oculus). The in- Twelve subjects with keratoconus were recruited from the Univer- strument has been found to provide highly repeatable measures of sity’s optometry clinic, research department databases, and contact corneal thickness in patients with keratoconus.36,39 A Hartmann-Shack lens specialist private practices. Other ocular disease and severe kera- aberrometer (Complete Ophthalmic Analysis System–High Definition; toconus complications, including corneal scarring and acute hydrops, COAS-HD; AMO WaveFront Sciences LLC, Albuquerque, NM) was used were exclusion criteria. Rigid gas-permeable contact lens wearers were to determine peripheral aberrations of each subject’s right eye by using also excluded. If a patient wore soft contact lenses, a period of 1 day a procedure that has been described in detail previously.31 A 100 ϫ and 1 night without lens wear was enforced before testing, to ensure 75-cm rear projection screen was placed at a distance of 1.2 m, onto that the lenses’ effect on the corneas did not influence the results. which the fixation targets were projected and viewed via a glass slide Keratoconus was confirmed by a scissoring reflex on retinoscopy, beam splitter. Targets were arranged in a 6-row ϫ 7-column matrix to central or paracentral steepening on computerized topography with a give a visual field of 42° ϫ 32°. The center of the fixation target array videokeratoscope (model E300; Medmont International Pty. Limited, was aligned with the aberrometer’s internal fixation target. Two im- Sydney, Australia), and at least one of central or paracentral corneal ages only for each fixation target were taken to reduce the subject’s thinning, Vogt’s striae, or a Fleischer’s ring. All subjects exhibited total testing time to less than 2 hours. The dynamic range of the bilateral signs of keratoconus, with various degrees of between-eye Hartmann-Shack sensor limits the measurement of highly aberrated symmetry. The keratoconus program of the Pentacam (Oculus Inc., corneas,13 and therefore more severe cases were not investigated. The Wetzlar, Germany) offered further confirmation of the condition and quality of the images captured by the modified aberrometer was gen- was adopted to classify our subjects into seven mild (three men, four erally high. Only 10 of 916 images were unsuitable for analysis, which women) and five moderate (three men, two women) cases. The Pen- meant that only one image, rather than two images, was available for tacam software provides a keratoconus severity classification (from a particular subject and visual field position. For some images, the pre-keratoconus and mild keratoconus, KK-1, to advanced keratoco- software was unable to determine the centroids of some of the points. nus, KK-4) adapted from the Amsler grading system and based on eight In such cases, these were estimated by a manual procedure performed indices derived from the anterior surface topography and corneal by one of the authors. The number of points estimated manually was thickness progression.35 We used this classification to grade the sever- generally small (Յ30 points) relative to approximately 766 points ity of keratoconus for each subject and defined mild keratoconus as across a 5-mm pupil. With the use of an algorithm (MatLab; The being less than KK-2, and moderate keratoconus being KK-2 to -3. Most MathWorks, Inc., Natick, MA), the image magnification and contrast previous studies categorized keratoconus patients on their keratometry were increased, and the observer used a cursor to estimate the cen- values.36,37 Given the Pentacam’s recent popularity and demonstrated troid. Further analysis was performed with custom software that utility for detecting keratoconus,38 we felt the use of its indices were stretched elliptical pupils to circular pupils and converted from the justified, as it provided an objective assessment of the severity of instrument’s 840-nm wavelength to 555 nm.40,41 Aberration coeffi- keratoconus. cients up to the sixth order were estimated from the wavefront for a The mean ages were 28 Ϯ 5 years in the mild keratoconus group pupil diameter of 5 mm for all subjects. Aberration coefficients for the (range, 21–34) and 30 Ϯ 7 years in the moderate keratoconus group two images at each visual field position were averaged. (range, 22–37). Ocular aberration data from the keratoconus popula- Because of the large intersubject variations within the keratoconus tions were compared with a control population, described in detail groups, average group values for each aberration coefficient were elsewhere,30,32 consisting of 10 young adult emmetropic subjects with used. We determined refractive components’ mean spherical equiva- Ϯ a mean age of 25 3 years (age range, 20–30). Mean steep simulated lent M, oblique astigmatism J45, and with/against the rule astigmatism

keratometry (as measured by the Medmont corneal topographer) was J180 refraction components, based on second- to sixth-order aberration 44.2 Ϯ 1.5 D (range, 41.5–47.6) in the emmetropes, 46.8 Ϯ 1.1 D coefficients.40,41 Total root mean squared aberrations excluding defo- (range, 45.1–48.3) in the mild keratoconics, and 46.8 Ϯ 2.2 D (range, cus (TotalRMS), and higher-order root mean squared aberrations 44.8–50.0) in the moderate keratoconics. (HORMS) across the visual field were also determined. Each subject underwent an ophthalmic examination that included Contour plots were generated to represent refractive components, unaided vision, best corrected visual acuity using both high- and aberration coefficients, HORMS, and TotalRMS across the visual field. low-contrast Bailey-Lovie charts, retinoscopy, and subjective refrac- Further analysis was performed along the vertical visual field meridian

TABLE 1. Visual Acuities and Cone Locations in the Two Study Groups

Cone Location

Group HCVA (logMAR) LCVA (logMAR) x (mm) y (mm)

Mild keratoconus 0.02 Ϯ 0.10 0.45 Ϯ 0.17 0.5 Ϯ 0.2 Ϫ1.6 Ϯ 0.6 Moderate keratoconus 0.07 Ϯ 0.10 0.48 Ϯ 0.08 0.3 Ϯ 0.3 Ϫ2.0 Ϯ 0.2

Best spectacle-corrected HCVA and LCVA contrast visual acuity and cone locations along the horizontal (x) and vertical (y) corneal meridians in the keratoconus groups. Positive x and y values represent nasal and superior cornea, respectively.

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by using quadratic fits to the data. Quadratic fits were chosen because keratoconus groups than in the emmetropia control group for they most closely represented the change in most of the aberration all aberration terms considered. The moderate keratoconics coefficients. exhibited greater rates of change than did the mild keratocon- The refractive components, second-, third-, and fourth-order aber- ics for all aberrations. ration coefficients, HORMS, and TotalRMS were further analyzed with For spherical equivalent M (Fig. 1A), the emmetropes had repeated-measures analysis of variance (ANOVA) with field position little variation across the field, whereas the mild keratoconics (38 positions) as the within-subject factor and group as the between- had high negative (myopic) values in the inferior field, which subjects factor. Bonferroni post hoc analysis was also performed for became less negative in the superior field. The moderate kera- the three groups, and ANOVA was performed (SPSS; SPSS Inc., Chi- toconics had a similar pattern, but the magnitude in the inferior cago, IL). field and rate of change were higher.

Astigmatism J180 (Fig. 1B) in the emmetropes decreased RESULTS quadratically from the center to the periphery along the 0° to 180° meridian and increased quadratically along the 90° to

The average cone location relative to the pupil center with 270° meridian. The keratoconus groups had high negative J180 corneal topography was 1.60 Ϯ 0.6 mm inferiorly and 0.45 Ϯ in the superior field that became less negative and eventually 0.2 mm nasally in the mild keratoconics and 1.97 Ϯ 0.2 mm positive in the inferior field. The change was quadratic and inferiorly and 0.34 Ϯ 0.3 mm nasally in the moderate kerato- greater in the inferior field than in the superior field. The conics. The pupils during corneal topography were typically moderate keratoconics had greater rate of change than did the smaller than 5 mm, and in the larger pupil during aberrometry mild keratoconics.

measurements, a mean absolute pupil shift of approximately Oblique astigmatism J45 (Fig. 1C) in the emmetropes de- 0.21 mm would be likely, but with mean changes in the creased from the central to the peripheral field along the 45° to horizontal and vertical locations of less than 0.03 mm,42 the 225° meridian and increased along the 135° to 315° meridian. estimated mean cone position relative to the larger pupil In the mild and moderate keratoconics, it decreased linearly would not be expected to change substantially. from the inferior nasal field to the superior temporal field along Refraction components and aberration coefficients across the 315° to 135° meridian. The moderate keratoconics exhib- the visual field were displayed as two-dimensional (2-D) con- ited a greater rate of change than did the mild keratoconics. tour maps, with a common scale for a refraction component/ Figure 2 shows the mean higher-order wavefront error aberration across all three groups. Negative (Ϫ) coordinates maps across the pupil at each of the 38 visual field positions. In represent temporal and inferior visual fields. Figure 1 shows the emmetropes, coma dominated the peripheral visual field. the refraction components across the visual field, Figure 2 Both keratoconus groups had larger aberrations than did the shows higher-order wavefront error maps across the eccentric emmetropes at any visual field position, with the moderate pupil for each location in the visual field, Figure 3 shows the keratoconics having the highest aberrations. Aberrations were third-order coefficients and spherical aberration coefficient across again dominated by the comas in the keratoconics, but with the visual field, and Figure 4 shows HORMS and TotalRMS across some influence of spherical aberration in the inferior visual the visual field. fields, as indicated by the increase in symmetry of the plots and The rates of change in the refraction components and higher- with some influence of trefoil in the inferior–nasal fields, as order coefficients across the visual field were greater in the indicated by the three-lobed nature of the plots. The mild keratoconics had their most aberrant wavefronts in the superior–temporal field, and the moderate keratoconics had their most aberrant wavefronts along the horizontal meridian. In the emmetropes, the axis of the combined horizontal and vertical comas approximately matched the visual field meridian. The axis of coma in the keratoconics was mainly vertical across the visual field, indicating the dominance of vertical coma, although with some rotation from this in the superior visual field, indicating the influence of horizontal coma. Ϫ1 The vertical coma coefficient C3 (Fig. 3A) in the emmetropes increased linearly from the superior to the inferior field. In the mild keratoconics, it increased quadratically from the superior to the inferior field. The moderate keratoconics Ϫ1 had a high negative C3 in the center of the visual field, which became less negative both superiorly and inferiorly. The hori- 1 zontal coma coefficient C3 (Fig. 3B) increased linearly from the nasal to the temporal fields in all three groups, with the variation in the moderate keratoconics rotated toward the 135° to 315° meridian. The rates of change were similar in the mild (Ϫ0.018 ␮m/deg) and moderate (Ϫ0.016 ␮m/deg) keratoconics, and these were approximately 2.5 times greater than those in the emmetropes (Ϫ0.007 ␮m/deg). Ϫ3 3 The vertical trefoil C3 and horizontal trefoil C3 coefficients (Figs. 3C, 3D) varied very little across the visual field in the emmetropes. In the keratoconics, however, there was consid- FIGURE 1. Mean refraction components across the visual field in di- erable variation in both coefficients, with high negative and opters (D; right axis)in(a) emmetropes, (b) mild keratoconics (Mild K’conus), and (c) moderate keratoconics (Mod K’conus). (A) Spherical high positive values evident in the peripheral fields, particu- equivalent M;(B) with/against-the-rule astigmatism, J , and (C) larly in the moderate keratoconus group. 180 0 oblique astigmatism, J45. Pupil size, 5 mm. For any refraction compo- The spherical aberration coefficient C4 (Fig. 3E) in the nent, the scale is the same in all three groups. emmetropes varied little across the visual field. In the kerato-

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FIGURE 2. Wavefront error maps across the elliptical pupil at 38 visual ﬁeld locations for (a) emmetropes, (b) mild keratoconics (Mild K’conus), and (c) moderate keratoconics (Mod K’conus). Pupil size, 5 mm. The scale is the same for all three groups.

conics, it increased from the inferior to the superior field. Rates along the vertical meridian (0.72 and 0.60 ␮m, respectively) of change were greater in the moderate than in the mild were substantially larger than that in the emmetropes (0.11 keratoconics, with peak positive values in the moderate kera- ␮m), indicating the high variability between the individuals toconics in the midsuperior field. within each keratoconus group. HORMS (Fig. 4A) in all groups showed quadratic variation Table 2 shows the ANOVA results. Repeated-measures along the vertical meridian. The magnitudes and rates of ANOVA confirmed the differences in refractive components, change were more pronounced in the moderate keratoconics aberration coefficients, and HORMS and between the three than in the other groups. As an estimation of variability in groups. Refractive group had a significant effect on all refrac- aberrations along the vertical field meridian, the standard de- 0 tive components and most aberration coefficients, except C2, viations of HORMS and TotalRMS were calculated for each C2, C1, CϪ2, CϪ4 and C0. As expected, field position had a subject. The average standard deviations of HORMS in the mild 2 3 4 4 4 significant effect on all refractive components and aberration and moderate keratoconics (0.20 and 0.30 ␮m, respectively) coefficients. There were significant group-field interactions for were substantially larger than in the emmetropes (0.05 ␮m). all the terms, showing that group significantly affected the The similarities between the magnitudes and variations of HORMS and vertical coma (Fig. 3A) make it clear that vertical pattern of aberrations across the field. Bonferroni post hoc coma was the dominant higher-order aberration across the analysis showed that most of the terms were significantly field. different between the emmetropes and keratoconics. M, J180, Ϫ1 2 4 TotalRMS (Fig. 4B) in the emmetropes increased quadrati- C3 , C4, C4, and HORMS differed significantly between the mild cally from the center to the periphery. The keratoconics and moderate keratoconics. 43 showed increase in TotalRMS from the superior to the inferior Aberrations are affected by cone location. In our kerato- of the visual field. The vertical rates of change were similar in conus groups, the cone locations were usually more inferior the mild and moderate keratoconics (Ϫ0.041 ␮m/deg and than nasal, which resulted in higher aberrations for the inferior Ϫ0.052 ␮m/deg, respectively), but the magnitudes were than for the superior visual fields. We compared the anterior greater in the latter at any visual field position. The average surface power derived from the Medmont corneal topography standard deviations in the mild and moderate keratoconics data along the vertical corneal meridian (Fig. 5, passing

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between the three groups. It changed linearly vertically in the emmetropes and quadratically in the mild and moderate keratoconics. The moderate keratoconics also had a high negative Ϫ1 vertical coma coefficient C3 across the vertical field meridian. 0 Spherical aberration coefficient C4 (Fig. 6f) changed little in the emmetropes, but changed linearly in the mild keratoconics and quadratically in the moderate keratoconics. HORMS (Fig. 6g) and TotalRMS (Fig. 6h) were highest across the field in the moderate keratoconics followed by those in the mild keratoconics. HORMS decreased as distance from the center of the field increased in the moderate keratoconics, increased toward the superior field in the mild keratoconics, Ϫ1 and was dominated by changes in vertical coma C3 in the two groups. TotalRMS increased toward the inferior field because of the increase in astigmatism in the inferior field. The mild and moderate keratoconus groups exhibited five and nine times greater axial TotalRMS, respectively, than the emmetropic subjects. In the inferior field, TotalRMS increased to 6 (mild keratoconus) and 11 (moderate keratoconus) times greater in the keratoconic than in the control subjects. In the keratoconic subjects, a significant correlation was found between the quadratic component of the rate of change in aberrations along the vertical meridian and the corneal power at the cone apex for both vertical coma coefficient (r2 ϭ 0.58, P Ͻ 0.001) and HORMS (r2 ϭ 0.41, P ϭ 0.03), indicative of a greater change in aberrations along the vertical meridian for greater corneal powers (Fig. 7).

DISCUSSION This study is the first conducted to investigate and quantify peripheral ocular aberrations in keratoconic subjects. The results support our hypothesis of a greater rate of change in aberrations across the visual field in keratoconic than in normal eyes. The magnitudes of aberrations and rates of their change across the visual field were greater for a moderate than for a mild keratoconus group, and with considerable variation within the keratoconus groups. Second-order terms were the FIGURE 3. Mean aberration components across the visual field in mi- dominant aberrations across the visual field for both em- crometers (␮m; right axis) for (a) emmetropes, (b) mild keratoconics metropes and keratoconics. Rapid changes in M and J180 were (Mild K’conus), and (c) moderate keratoconics (Mod K’conus). (A) Ϫ1 1 noted in the inferior field in keratoconics, with as much as Vertical coma coefficient C3 ;(B) horizontal coma coefficient C3;(C) Ϫ Ϫ3 3 8.00 D of spherical error occurring in the moderate kerato- vertical trefoil coefficient C3 ;(D) horizontal trefoil coefficient C3; 0 conus group. For 5-mm pupils, horizontal and vertical comas spherical aberration coefficient C4. Pupil size, 5 mm. For any coefficient, the scale is the same in all three groups. were the dominant higher-order aberrations for emmetropes across the visual field, but vertical coma alone was the domi- through the pupil center) with the ocular refraction and aberrations along the vertical visual field meridian (Fig. 6). The corneal power changed little in the emmetropes, but showed considerable changes in the keratoconus groups (Fig. 5). In the inferior field, the corneal power was, as expected, highest in the moderate keratoconus group. In the superior field, corneal power in the moderate keratoconics was considerably lower than in the other groups. Generally the refractive components and aberrations changed quadratically along the vertical meridian in the kera-

toconus groups. Astigmatic components J45 and J180 became more positive (Figs. 6a, 6c), and the spherical equivalent M became more negative (Fig. 6b) in the inferior field compared with the respective results in the emmetropic group. The rates of change in the refractive components were highest in the moderate keratoconics followed by those in the mild kerato- Ϫ3 conics. Vertical trefoil coefficient C3 (Fig. 6d) changed little in the emmetropes and mild keratoconics, but was more positive FIGURE 4. Combined aberrations across the visual field in microme- overall across the field in the mild keratoconics than in the ters (␮m; right axis) in the (a) emmetropes, (b) mild keratoconics emmetropes. It increased linearly from the superior to the (Mild K’conus), and (c) moderate keratoconics (Mod K’conus). (A) inferior field in the moderate keratoconics. Vertical coma co- HORMS; (B) TotalRMS. Pupil size, 5 mm. For any combined aberra- Ϫ1 efficient C3 (Fig. 6e) showed the most prominent differences tions, the scale is the same in the three groups.

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TABLE 2. Probabilities of the Repeated-Measures ANOVA for Refraction Components and Aberration Coefﬁcients

Bonferroni Post Hoc Analysis of Groups

Refraction Component/ Group–Field Emm vs. Mild Emm vs. Mod Mild K’conus vs. Aberration Coefﬁcient Group Field Position Position Interaction* K’conus K’conus Mod K’conus

J45 0.00* 0.00* 0.00* 0.04* 0.00* 0.28 M 0.01* 0.00* 0.00* 1.00 0.03* 0.02*

J180 0.04* 0.00* 0.00* 0.16 1.00 0.05* Ϫ2 C2 0.00* 0.00* 0.00* 0.05* 0.00* 0.08 0 C2 0.40 0.00* 0.00* 2 C2 0.08 0.00* 0.00* Ϫ3 C3 0.00* 0.00* 0.00* 0.00* 0.00* 0.77 Ϫ1 C3 0.00* 0.00* 0.00* 0.00* 0.00* 0.00* 1 C3 0.10 0.00* 0.00* 3 C3 0.01* 0.00* 0.00* 0.03* 0.01* 1.00 Ϫ4 C4 0.06 0.00* 0.00* Ϫ2 C4 0.06 0.00* 0.00* 0 C4 0.08 0.00* 0.00* 2 C4 0.00* 0.00* 0.00* 1.00 0.00* 0.00* 4 C4 0.00* 0.00* 0.00* 0.05* 0.00* 0.00* HORMS 0.00* 0.00* 0.00* 0.00* 0.00* 0.00* TotalRMS 0.02* 0.00* 0.00* 0.07 0.03* 1.00

Refraction components, Zernike aberration coefficients and root-mean-square aberrations with within-subjects factor of field position and 0 between-subjects variable of group. The refraction component M and the defocus coefficient C 2 are relative to their central field values for each subject. Emm, emmetropia; Mild K’conus, mild keratoconus; Mod K’conus, moderate keratoconus. * Significant effects (P Յ 0.05). P Ͻ 0.005 is given as 0.00.

nant higher-order aberration for keratoconics across most of nus, even in a subclinical form, is considered a major risk factor the visual field. The latter is consistent with on-axis studies of in the development of iatrogenic keratoectasia after refractive keratoconus.10,13 surgery.44 Although videokeratoscopy is still the most com- The characteristics of the peripheral aberrations in our keratoconic population appeared to be related largely to the location and magnitude of the cone. Horizontal coma de- (a) (b) creased from the temporal to the nasal field in all three groups. In the keratoconus groups the horizontal coma change appeared to be rotated toward the 135° to 315° meridian. The Emmetropes rotation is explained by the cones being typically located in the Mild K’conus inferior–nasal quadrant. Furthermore, the cornea power at the Mod K’conus cone apex was associated with the change in certain aberrations (i.e., vertical coma and HORMS) along the vertical field. (c) (d) With the advent of laser refractive surgery, there has been considerable interest in identifying those patients with early or subclinical forms of keratoconus, as the presence of keratoco-

(e) (f)

(g) (h)

Emmetropes

Mild K’conus HORMS I S To t a l R M S Mod K’conus

FIGURE 6. Refraction and aberrations along the vertical visual ﬁeld

meridian. (a) Oblique astigmatism J45;(b) spherical equivalent M;(c) FIGURE 5. Axial anterior corneal power along the vertical meridian with/against-the-rule astigmatism J180;(d) vertical trefoil coefficient Ϫ3 Ϫ1 (passing through the pupil center, as estimated by corneal topogra- C3 ;(e) vertical coma coefficient C3 ;(f) spherical aberration coeffi- 0 phy), relative to the distance from the pupil center in the emmetropes, cient C4;(g) HORMS; and (h) TotalRMS. Lines: the quadratic fits to the mild keratoconics, and moderate keratoconics. Error bars, SD; I, infe- data; error bars: standard deviations. Different refractions and aberra- rior cornea; S, superior cornea. tions have different scales.

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0.004 Mild Keratoconus 2 Moderate Keratoconus 0.002 m/degree )

µ 0.000

-0.002 FIGURE 7. Second-order fitting coefficients along the vertical visual field, 2 coefficient along coefficient -0.004 y as a function of axial corneal power

3 2 2 (in diopters) at the cone apex in the (a) Vertical coma coefficient(C -1 ) R = 0.58, p = 0.00 (b) HORMS R = 0.41, p = 0.03 -0.006 mild and moderate keratoconics. (a) Ϫ vertical field meridian ( 46 48 50 52 54 56 46 48 50 52 54 56 1 Vertical coma coefﬁcient C3 ;(b) Corneal axial power at cone apex (D) Corneal axial power at cone apex (D) HORMS.

monly used clinical tool in the diagnosis of keratoconus, sev- refractive error development have demonstrated the human eral other novel methods may be useful in detecting early eye is capable of undergoing axial eye growth at this age,56–59 keratoconus, including those based on measures of corneal future studies using magnetic resonance imaging or peripheral thickness,38 posterior corneal topography,39 and on-axis cor- ocular length measures (e.g., partial coherence interferometry) neal2,9 and ocular1,45 aberrations. The aberrations are, of in keratoconic subjects may help to determine whether asym- course, an indirect measure of the corneal topography. This metric axial eye growth occurs in response to the substantially study shows that substantial differences exist in the magnitude asymmetric retinal defocus in these subjects. and rate of change of peripheral ocular aberrations between In conclusion, we have described in detail the magnitude emmetropes and subjects with mild keratoconus. The results and pattern of peripheral second- and higher-order ocular ab- suggest that metrics based on peripheral ocular higher-order errations in populations of mild and moderately advanced aberrations or the rate of change in these aberrations across the keratoconic subjects and have compared these aberrations to field would be of use in identifying patients with early or those from an emmetropic control group. Consistent with subclinical forms of keratoconus; a complicating factor is that previous studies of on-axis aberrations in keratoconus and with myopes tend to have greater rates of change of coma across the the measured corneal topographical changes, our keratoconic visual field than do emmetropes.30 Further research is needed subjects exhibited higher magnitudes and rates of change in in a larger sample of subjects to determine the optimum met- peripheral ocular aberrations compared with the emmetropic rics and the clinical utility and sensitivity of peripheral aberra- controls, with comatic terms being the dominant higher-order tion measurements in the diagnosis and screening of early peripheral aberrations. keratoconus. The lengthy time taken for data collection and analysis with currently available clinical instruments probably Acknowledgments precludes these measurements from being viable clinically at The authors thank optometrists Geoff Conwell and Kate Johnson for this stage. 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