Title page

Full title:Scleral Changes with Accommodation

Running head: Scleral changes with accommodation

Authors’ names: Alejandra Consejo1, Hema Radhakrishnan2 and D. Robert Iskander1

Institutional affiliation:1 Department of Biomedical Engineering, Wroclaw University of Science and Technology, Poland

`2 Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom

Corresponding author:

Alejandra Consejo

Department of Biomedical Engineering

Faculty of Fundamental Problems of Technology

Wroclaw University of Science and Technology

Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland

E-mail:

Phone: 48 71 320 4665

Keywords: accommodation, sclera, myopia, anterior eye surface.

DISCLOSURE

The authors report no conflicts of interest and have no proprietary interest in any of the materials mentioned in this article.

ACKNOWLEDGEMENTS

The authors thank Irene Sisó-Fuertes for help in preparation of the ethics approval and the measurement part of the study and Maciej M. Bartuzel for writing the simulation algorithms. This work was supported by the Marie Curie ITN grant, AGEYE, 608049.

ABSTRACT

Purpose: To assess whether the sclera changes its shape during accommodation, quantify those changes and ascertain whether they depend on age and refractive power.

Methods:Twenty-two subjects, aged between 19 and 84 years old were recruited for the study. Young subjects were grouped according to their refractive power as emmetropes (7 subjects) and myopes (7 subjects). Data were obtained with a heightcorneo-scleral topographer (Eye Surface Profiler) with coverage area far beyond the limbus. Lenses of different power were used to stimulate accommodative demand of 0.0 D, 2.5D and 4.0 D. Elevation differences between measurements acquired while focusing at the intermediate or close target and infinity where calculated for each participant for the horizontal meridian for a 16 mm chord.

Results:We found that sclera undergoes significant changes in its shape with accommodation in young subjects able to accommodate but not for those with limited accommodation. For a 4.0 D stimulus at the nasal side the scleral change amounted on average to 420±360 µm (mean ± SD) for the young group. This phenomenon was more pronounced in myopes (for a 4.0 D target; nasal part: 560±350 µm (mean ± SD)) than emmetropes (for a 4.0 D target; nasal part: 220±120 µm (mean ± SD)). Differences were also found between different meridians.

Conclusions: Scleral shape undergoes changes with accommodation and this phenomenon is more pronounced in myopes than emmetropes.

INTRODUCTION

For centuries,efforts have been made to fully explain the mechanism of accommodation in the human eye. The well-known bases of the accommodation process relate to the change in crystalline lens shape by the action of the ciliary muscles. However, gaining knowledge about the other processes that might occur in the eye during accommodation is still of scientific interest, to fully understand how the accommodation mechanism itself affects the human eye.

Some studies that related the accommodation process to changes in biometrical parameters of the eye, beyond those related to crystalline lens thickness,1,2 such as anterior chamber depth and anterior segment length, have been reported.3,4 Similarly, the assessment whether the cornea changes its shape with accommodation has been a debated issue. Some works limited to about 3mm5 or 6 mm6,7diameters of central corneal coverage suggested that the cornea modifies its shape with accommodation, while others ascertained that such changes are negligible and unlikely to occur if cyclotorsion correction is taken into account. Those works were conducted for 6 mm,8 8 mm9 and up to 10 mm10diameter of corneal coverage.In the past, the limitations of technology restricted the study of the anterior eye topography to the corneal region. Keratometers, keratoscopes, Scheimpflug-based topographers and optical coherence tomography (OCT) have been used to assess the shape of the human cornea11-13 and how it changes under certain conditions, such as during accommodation. However, today it is possible to overcome these technical limitationswith non-contact commercially available instruments, such as corneo-scleral profilometers, that cover the corneo-scleral area far beyond the limbus up to 20 mm in diameter, opening a new branch of possibilities. In particular, it has been proved that the Eye Surface profiler (ESP) provides excellent levels of accuracy for the central area of 8 mm diameter. This error increases with the radial distance.14Our preliminary experience with ESP showed changes in the scleral shape within measurements from a particular subject but not in thecorneal shape. Those changes could have been an artefact produced as a consequence of the increasing error variability in the peripheral area of the measurements or physiological changes that could happen as a consequence of the subject’s accommodation while focusing at the internal target of the instrument.

The hypothesis of this work is that accommodation might cause changes in the scleral shape. Beyond proving this hypothesis, this work aims to quantify those changes and ascertain whether they depend on age (accommodative ability) and refractive power.

METHODOLOGY

Subjects

Participants in this study included twenty two, healthy adult subjects (13 females, 9 males) aged between 19 and 84 (mean ± SD age: 39 ± 20 years). The study was approved by The University of Manchester Human Research Ethics Committee and adhered to the tenets of the Declaration of Helsinki. All subjects gave written informed consent to participate after the nature and possible consequences of the study were explained. All participants were free of ocular disease, had no anisometropia (i.e., had < 1.00 D difference in spherical equivalents between the eyes), had less than 1.00 D of astigmatism in both eyes and had best corrected visual acuity of 0.1logMAR or better.Subjects with hyperopia (>+1.00 D) were excluded.Young subjects whose accommodative response was inadequate (>1D difference between the stimulus and response) were also excluded. For statistical analysis, participants were grouped as young (14 subjects, aged between 19 and 37) and older (8 subjects, over 50 years old). One of the subjects from the older group had bifocal intraocular lenses in her eyes. Individual analysis of this subject isundertaken in the Results section. In addition,young subjects were also grouped in two different categories according to their refractive power. 7 subjects were categorised asemmetropes (refractive error between0.25 D and +0.75 D) and 7 subjects were categorised as myopes(refractive error between 1.50 D and 5.50 D).

Data acquisition

The study was performed in a single visit for each of the subjects. Firstly, the refractive state was measured monocularly (the non-tested eye was occluded with an eye patch) using a wide-view window autorefractometer (Shin Nippon SRW-500, Ajinomoto Trading Inc., Japan). Subjects were asked to focus on a 6-meter distant target (a Maltese cross). Five measurements were acquired from each eye. The autorefractometer provided the average value of those five measurements that we considered as the valid refractive power for the eye under analysis. Further, the right eye of the subject was corrected with the appropriate lens according to the reading of the autorefractometer and measured again to assess whether the correction lens was optimal. In addition, subjects were measured with negative lenses to estimate the accommodative response to the 2.5 D and 4.0 D stimuli.

Further, data was obtained using a non-contact corneo-scleral topographer (Eye Surface Profiler (ESP), Eaglet Eye BV, Netherlands), a height profilometer with the potential to measure the corneo-scleral topography far beyond the limbus. To determine surface heights, algorithms used in ESP achieve similar levels of accuracy to those reached in keratoscopy based instruments such as Placido disk videokeratoscopes.14Accurate measurements of anterior eye surface using ESP require instillation of fluorescein with a more viscous solution than saline.14 The BioGlo (HUB Pharmaceuticals) ophthalmic strips were used to gently touch the upper temporal ocular surface. They were impregnated with 1 mg of fluorescein sodium ophthalmic moisten with one drop of an eye lubricant (HYLO-Parin, 1mg/ml of sodium hyaluronate).Measurement setup is illustrated in Figure 1. Subjects were asked to put their chin on the headrest of the ESP device and look through a mirror focusing at a target located 6 meters away staying as steady as possible. Lenses of different power were used to stimulate accommodative demand of 0.0 D, 2.5D and 4.0 D. Non emmetropic subjects were corrected according to the spherical equivalent of the autorefractor reading. Three consecutive sets of measurements of the fellow eye (for 0.0 D, 2.5D and 4.0 D accommodative demand) were obtained for each subject with four measurements taken at each vergence.

Figure 1.Measurement setup. The lens power is adjusted depending on the subject’s refractive power and the fixation distance. Plano, 2.5 D and 4.0 D lenses were used for emmetropic subjects.

The illumination conditions were always the same: dark room, with the target illuminated with a commercial lamp permanently fixed in the same position and intensity.

Preliminary data analysis

Following data acquisition, the raw anterior eye height data (three columns with X, Y, and Z coordinates) was exported from ESP for further analysis. To ensure that the data is not tilted, data alignment is needed. The instrument has an internal procedure for 3D (three-dimensional) data alignment which ensures that the output anterior eye elevation is not tilted or rotated. To ensure that the data is not tilted, the realignment was performed using 3D data. The basic steps of this realignment are as follow. First, a preliminary apex was selected and corrected, if necessary, by an internal algorithm. Second, after the apex was properly found from 3D data, a geodesic (a straight line that joins two points on a given surface) of specific distance from the apex was calculated. Third, a 3D plane was fit in least square sense to the geodesic points. Fourth, the normal vector of the estimated plane was forced to coincide with the optical axis and in this manner the tilt in the data is finally corrected. Figure 2 graphically represents the procedure described above. This correction is necessary to further compare within different measurements, especially eye surface maps acquired at different vergences.

Figure 2. Four basic steps for internal correction of the tilt in the measuring instrument (ESP). Step 1: A preliminary apex point (red point) is sought. Given the preliminary axis, a certain range around it is stablished (points a and b). In the area enclosed by this region a change in the sign of the derivative is sought. The correct apex corresponds to that point where there is a change in the sign of the derivative (green point). Step 2: Calculation of a geodesic (straight line that joins two points on a given surface) of specific distance from the apex (green point). Step 3: Fitting, in a least square sense, a 3-dimensional plane to the geodesic points (blue plane). The normal to this plane is marked in orange while the optical axis is marked in dark red. Step 4: Correct the anterior eye data with the estimated tilt, tilting the data in such manner that both vectors coincide.

The rotation and tilt of the measured anterior eye surfaces were internally corrected by the instrument. Additionally, we performed simulation, presented in thediscussion section, to ensure that this requirement was met. With this procedure we proved that the potential change of scleral shape with accommodation was not a displacement of the eye due to the rotation caused by the accommodative convergence.

Cyclotorsion

The effect of accommodative cyclotorsion was studied on a subgroup of five randomly chosen subjects. Anterior eye surface mapsfor 0.0D condition were correlated with those corresponding to 2.5D and 4.0 D and were appropriately repositioned using an appropriatealgorithm.15In the discussion section are shown the results for the worst case (in a sense of the largest absolute differencebetween the original and repositioned surfaces) found among those five randomly chosen subjects. The effect of cyclotorsion was negligible in comparison with the changes found in the scleral shape.

Data analysis

Elevation differences between measurements acquired while focusing at the intermediate target and infinity were calculated for each participant for the horizontal meridian for a 16 mm chord (in a radial distance range from 8.0 mm to +8.0 mm in steps of 0.5 m). The same calculations were performed between measurements acquired while focusing at the close target and infinity. Figure3 illustrates the process for a single subject. A sampling (or grid) of 0.5 mm was selected for subsequent statistical analysis. The methodology shown in Figure 3 was performed for each subject.

Figure 3.Data analysis procedure in the horizontal meridian.An example for a particular subject (female, 28 years-old, myopic (2.5 D)) is given. Elevation corresponds to the horizontal meridian. Four measurements were acquired in each vergence (blue, infinity target; red, intermediate target and green, close target) (A). Median of the four measurements acquired at each vergence with a 0.5 mm grid (B).Absolute value of the elevation differences between medians of measurements acquired while focusing at the intermediate target and infinity (red) and between medians of measurements acquired while focusing at the close target and infinity (green) for the grid points (C).

Statistical analysis

The statistical analysis was performed using SPSS software for Windows version 23.0 (SPSS Inc., Chicago, Illinois, United States). Wilcoxon sign-rank test was performed to determine whether there were statistically significant differences between focus at different targets, between age groups and between different refractive groups. Bonferroni correction was used to overcome the problem of multiple comparisons. We considered cornea from 6.0 to +6.0 mm diameter and sclera from 8.0 to 6.5 mm and from +6.5 mm to +8.0 mm (see Figure 3C). For a 0.05 significance level the alfa error per comparison is 0.0020 and 0.0062 for the corneal and scleral area, respectively.

RESULTS

All data reported in this section are given for older subjects with limited accommodation and young subjects who did not have limited accommodation. The average accommodative response for the group of young subjects was 1.98± 0.25 D (mean ± SD), range [1.80, 2.25] D, and 3.45 ± 0.10 (mean ± SD), range [3.30, 3.75] D, for the 2.5 D and 4.0 D stimulus, respectively. For the older (over 50 years old)the accommodative response amounted on average to 0.06 ± 0.29D (mean ± SD) and 0.06 ± 0.18 (mean ± SD) for the 2.5 D and 4.0 D stimulus, respectively.

We found that sclera undergoes changes in its shape with accommodation in young subjects able to accommodate. The following results are given in absolute values. For a 4.0 D stimulus at the nasal side (at 8.0 mm) the scleral change amounted on average to 420±360 µm(mean ± SD). Similarly, at the temporal side (at +8.0 mm) it amounted to 380±280 µm (mean ± SD). This phenomenon was more pronounced in myopes (for a 4.0 D target; nasal part: 620±360 µm (mean ± SD); temporal part: 500±320 µm (mean ± SD)) than emmetropes (for a 4.0 D target; nasal part: 220±120 µm (mean ± SD); temporal part: 250±170 µm (mean ± SD)).

It has been observed that the change in scleral shape for young subjects while accommodating is not uniform, it depends on the meridian under analysis. Figure 4 shows an example of the horizontal, vertical and oblique (±45˚) elevation changes for a 28 years-old female myopic subject.

Figure 4. An example of horizontal meridian (A), vertical meridian (B), 45˚ away from horizontal meridian (C) and 45˚ away from horizontal meridian (D) analysis for different (0.0D, 2.5D and 4.0D) accommodative demand. ‘N’ denotes nasal part and ‘T’ denotes temporal part while in (C) ‘S’ denotes superior part and ‘I’ denotes inferior part. These data corresponds to a randomly chosen subject (female, 28 years-old, myopic (-2.5 D)).

The scleral shape change with accommodation for the group of older subjects with limited accommodation was much less pronounced. Figure 5 shows and example of scleral changes for two randomly chosen subjects from each age group.

Figure 5.Comparison of the elevation in the horizontal meridian for different (0.0D, 2.5D and 4.0D) accommodative demandsfor a young subject (female, 20 years-old) (left) and an older subject (female, 68 years-old) (right).

It is known that when a young observer attempts to accommodate steadily on a fixed stimulus, usually the steady-state response shows small fluctuations. This phenomenon was noticeable among some of the young subjects who participated in our study. Figure 6 shows and example of a young myopic subject where all measurements acquired (four at each vergence) are plot for the horizontal meridian. More variability of accommodation in the scleral shape was observed for higher level of accommodation stimulus, suggesting that the small fluctuations of accommodation may influence the scleral shape.

Figure 6. Example of variations in scleral topography while accommodating for a young subject (female, 20 years old).

We found that scleral shape changes with accommodation are only significant (please refer to Table 1) for young subjects focusing at a close target and not for those with limited accommodation. Age-dependent results corresponding to the whole group of subjects are shown in Figure 7.

Figure 7. Boxplots showing the group mean elevation change in absolute value with respect to infinite target (in µm) for different age groups and different accommodative demands.

An outlier is present among the old subjects for a close target of 4.0 D (denoted by red crosses in Figure 7). These data correspond to an 84 years old female subject who was implanted with bifocal intraocular lenses. Data of this subject was excluded from further statistical analysis. It is worth noticing that the results for this subject closely correspond to those achieved for the group of young subjects.