|SYMPOSIUM - RETINOCHOROIDAL IMAGING
|Year : 2015 | Volume
| Issue : 5 | Page : 423-426
Axial length and cone density as assessed with adaptive optics in myopia
Supriya Dabir1, Shwetha Mangalesh1, Jan S A G Schouten2, Tos T J M Berendschot2, Mathew Kummelil Kurian3, Anupama Kiran Kumar1, Naresh K Yadav1, Rohit Shetty4
1 Department of Retina, Narayana Nethralaya, Bengaluru, Karnataka, India
2 Department of Ophthalmology, Maastricht University, Maastricht, The Netherlands
3 Department of Cataract and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India
4 Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India
|Date of Submission||04-Mar-2015|
|Date of Acceptance||25-May-2015|
|Date of Web Publication||2-Jul-2015|
Dr. Supriya Dabir
Plot No, 121/C, 1st R Block, Rajajinagar, Bengaluru - 560 010, Karnataka
Source of Support: None, Conflict of Interest: None
Aim: To assess the variations in cone mosaic in myopia and its correlation with axial length (AL). Subjects and Methods: Twenty-five healthy myopic volunteers underwent assessment of photoreceptors using adaptive optics retinal camera at 2° and 3° from the foveal center in four quadrants superior, inferior, temporal and nasal. Data was analyzed using SPSS version 17 (IBM). Multivariable regression analysis was conducted to study the relation between cone density and AL, quadrant around the fovea and eccentricity from the fovea. Results: The mean cone density was significantly lower as the eccentricity increased from 2° from the fovea to 3° (18,560 ± 5455-16,404 ± 4494/mm 2 respectively). There was also a statistically significant difference between four quadrants around the fovea. The correlation of cone density and spacing with AL showed that there was a significant inverse relation of AL with the cone density. Conclusion: In myopic patients with good visual acuity cone density around the fovea depends on the quadrant, distance from the fovea as well as the AL. The strength of the relation of AL with cone density depends on the quadrant and distance.
Keywords: Adaptive optics, axial length, cone density, myopia
|How to cite this article:|
Dabir S, Mangalesh S, Schouten JS, Berendschot TT, Kurian MK, Kumar AK, Yadav NK, Shetty R. Axial length and cone density as assessed with adaptive optics in myopia. Indian J Ophthalmol 2015;63:423-6
|How to cite this URL:|
Dabir S, Mangalesh S, Schouten JS, Berendschot TT, Kurian MK, Kumar AK, Yadav NK, Shetty R. Axial length and cone density as assessed with adaptive optics in myopia. Indian J Ophthalmol [serial online] 2015 [cited 2019 Nov 21];63:423-6. Available from: http://www.ijo.in/text.asp?2015/63/5/423/159876
Myopia is a common visual imperfection mostly due to an increase in the axial length (AL) of the eye. It can lead to severe visual loss when myopic degeneration develops. It may also cause both lower as well as higher order aberrations.  In a less severe stage, its vision loss can be corrected with glasses or contact lenses. Even with glasses the quality of vision with best-corrected visual acuity of 20/20 between myopes and emmetropes is not the same, and this may be due to multiple anatomical and physiological factors. ,,,, These could include the spatial distribution and orientation of the photoreceptors stretched along the posterior pole of the retina due to a larger AL in a myopic eye. It is to be expected that the cone density decreases with increasing myopia. ,, However, to what extend this occurs in relation to changes in the AL or extend of the refractive error is largely unknown. With the advent of adaptive optics (AO) technology in vision science, it is now feasible to determine the photoreceptor cone distribution. ,, In this study, we measured the variations in the cone mosaic in a population of young myopic adults in relation to the AL and extent of the refractive error. This may help to understand the missing link between increasing severity of myopia and changes in the visual acuity or quality of vision in patients with myopia and enhance the opportunity to monitor essential anatomic changes in myopia.
| Subjects and Methods|| |
Twenty-five consecutive patients who visited the comprehensive out-patient and the refractive out-patient departments with myopia within the age group of 20-40 years were included in the prospective study. An informed consent was obtained from all subjects, and the nature of the study was explained to them. The study adhered to the tenets of the declaration of Helsinki and was approved by the Ethics Committee and review board of the hospital. The patients in the study group were those who presented with myopia with the spherical equivalent between −1D and −12D and best corrected visual acuity of 20/20. Pathological myopia, and those with any ocular or systemic pathology were not included in the study and all patients enrolled had a clinically normal fundus. We grouped the myopes as low, moderate and high based on their spherical equivalent (mild being 1D-3D, moderate = 3D-6D and high >6D) for analysis.
All the subjects underwent a comprehensive ophthalmic examination including an assessment with the Tonoref RKT-7000 autorefractometer, Nidek, noncontact biometry (IOL master; Carl Zeiss Meditec, Germany) for AL and spectral-domain optical coherence tomography (Spectralis, Heidelberg) for central foveal thickness. A compact AO retinal camera prototype, the rtx 1 (Imagine Eyes, Orsay, France), was used to image the photoreceptor layer.
Adaptive optics imaging
As mentioned in our previous study on emmetropes,  the AO imaging sessions were conducted after dilating the pupils with 1 drop each of 0.5% tropicamide and 10% phenylephrine hydrochloride to achieve mid-dilated pupils. Aberrations induced by pupil dilation are negated by the AO system. Stable fixation was maintained by having the patient look at the system's inbuilt target and then as moved by the investigator to predetermined coordinates. The patient was instructed to fixate at 0°, 1°, 2° and 3° eccentricity along all the four quadrants, superior, inferior, nasal and temporal retina. A video (i.e., a series of 40 frames; 4° field size) was captured at each of the above retinal locations. After the acquisition, a program provided by the manufacturer correlated and averaged the captured image frames to produce a final image. Cone density (cones/mm 2 ) was measured at 1°, 2° and 3° eccentricity along all the four quadrants, superior, inferior, nasal and temporal retina. There has been no standardized protocol on which areas to image and size of the sampling window to choose the region of interest. The sampling window we choose was 100 μ and we placed it at specific coordinates calculated by a prefixed formula intentionally avoiding blood vessels. Eccentricity was computed as the distance between the center of each window and the foveal center reference point (identified as the point with fixation coordinates: x = 0°, y = 0°). The images were captured at temporal (−3°,0°) superior (0°,3°) nasal (3°,0°) and inferior (0°,−3°).  The cone counting software AO detect created on MATLAB by imagine eyes was used to process the images and calculate the data. The repeatability has been mentioned in our previous study.
The statistical analysis was performed using the IBM SPSS version 20 (SPSS Inc. Chicago, IL) and MedCalc version 11. The Shapiro-Wilk test was performed to determine whether the continuous data were parametric or nonparametric in distribution. We first described the values of cone density and spacing with AO per quadrant and per eccentricity, 2° and 3° from the fovea. Secondly, we tested by means of dependent t-test whether there was a difference in these parameters between the four quadrants per degree of eccentricity. Thirdly, we tested whether there was a difference between the degrees of eccentricity per quadrant. We finally studied the relation between either AL or degree of myopia expressed as spherical equivalents and AO parameters per quadrant and per degree of eccentricity. A linear regression analysis was conducted and a multivariable model was developed with the interaction of AL with the quadrant and degree of eccentricity. In both models the cone density was the dependent variable. The same analyses were conducted with refractive error instead of AL as the dependent variable.
| Results|| |
Fifty eyes of 25 myopic subjects (10 female, 15 male) between the ages of 20 and 40 years, refractive error of −1D to −12D and an AL of 22.68-28.20 mm were included in the study. The mean cone count and spacing the four quadrants (temporal, superior, nasal, inferior to the fovea) and at different eccentricities
(2° and 3° from the fovea) are represented in [Table 1]. The mean cone density was found to be significantly lower in the myopic group when compared to the age matched emmetropic group as reported in our previous study. 
|Table 1: The mean and SD of the cone density and spacing at the 4 quadrants (temporal, superior, nasal, inferior) and at 2° and 3° retinal eccentricities |
Click here to view
There was a significant decrease in the mean cone density from 18560/mm 2 ± 5455 to 16404/mm 2 ± 4494 respectively and a significant increase in spacing from 8.40 μm ± 1.4 to 8.81 μm ± 1.7 with increase in eccentricity from 2° to 3° from the fovea respectively in the myopic group as seen in [Table 2], a mirror trend similar to that of the emmetropes (decrease in cone density and increase in cone spacing as the distance from fovea increases).
|Table 2: Mean and SD of cone density and cone spacing between 2° and 3°retinal eccentricity among myopic subjects |
Click here to view
The linear regression test performed to relate the cone density and spacing with AL showed that there was significant relation of AL with the cone density in all separate quadrants, at 2° as well as at 3° eccentric from the fovea [Figure 1] and [Figure 2] and is lower when AL is higher. The results for cone spacing showed an increase in the spacing between adjacent cones as eccentricity from the fovea increased. Moreover, there is interaction between AL on one hand and quadrant and degrees on the other implying that the strength of the relation between AL and cone density depends on the degree and quadrant as seen in [Table 3]. The relation strength was not different for the square of the radius (= half AL), a measure directly related to the surface area. [Figure 3] shows the variation in the cone density between the mild, moderate and high myopia groups. There was no statistically significant difference between these groups. When refractive error was used as the independent variable instead of AL the strength of the relation in all analyses was lower as seen in [Table 4]. The Pearson's coefficient, used to find the correlation between refractive errors versus AL s, was significant (r2 = 0.352, P = 0.012 [P < 0.05]).
|Figure 1: (a-d) scatter plots showing the variation in cone density with axial length in the 4 quadrants (temporal, superior, nasal, inferior) at 2° eccentricity|
Click here to view
|Figure 2: (a-d) scatter plots showing the variation in cone density with axial length in the 4 quadrants (temporal, superior, nasal, inferior) at 3° eccentricity|
Click here to view
|Figure 3: Box plot showing the difference in the cone density between the sub groups (mild, moderate, high) in the myopic subjects|
Click here to view
| Discussion|| |
There have been multiple studies that have looked at the axial elongation of the eye in myopia, rather than the equatorial elongation.  This is because it is easier to study changes in the photoreceptor mosaic at the posterior pole than at the equator. , It is well established that the cones do not get distributed evenly as the expansion occurs nonuniformly. The retinal vasculature is said to restrict the cone migration along the entire surface. , Curcio et al. in his histological analysis found the density at 1 mm in the parafoveal retina to be 16,000 cells/mm 2 , corresponding to a cone spacing of 7.4 mm.  In our previous study on emmetropes we found a statistically significant difference in the cone density was observed from 2° to 3°. At 2° eccentricity the mean was 25,350/mm 2 (5,300/mm 2 , 8,400-34,800/mm 2 ), at 3° eccentricity the mean was 20,750/mm 2 (6,000 mm 2 , 9,000-33,670/mm 2 ) P < 0.05. The spacing correspondingly was lower at 2° of eccentricity as compared to 3°. At 2° the mean was 6.9 mm (0.70 mm, 5.95-11.6 mm) and at 3° the mean was 7.80 mm (1.00 mm, 6.5-13.5 mm) P < 0.05.  In our current study, we found cone density was significantly less in myopes and also showed a similar difference in the count as the eccentricity increased from 2° from the fovea to 3° (18,560 ± 5,455-16,404 ± 4,494/mm 2 respectively).
When we used the variable as refractive error the relation with cone density was less strong as compared to AL as a variable.
Lombardo et al. studied 11 eyes and found cone density in moderately myopic eyes (up to −7.50 D) was significantly lower than in emmetropic eyes within (or at) 2.0 mm from the fovea, similar to our results. They reported the spatial vision and the Nyquist limit of resolution of the retinal cone mosaic to reduce with increasing AL from 22.60 to 26.60 mm. 
Kitaguchi et al. reported the cone spacing in the moderate-to high-myopic group to be larger than that in the emmetropic and low-myopic group. They found the cone spacing in a −15 D myopic eye was 5.92 μm, which is 1.48 times the cone spacing in emmetropic eyes (4.00 μm), unlike a mathematical model where it would be 1.26-fold. We grouped the myopes as low, moderate and high based on their spherical equivalent (mild being 1D-3D, moderate = 3D-6D and high >6D) and evaluated the cone density at different eccentricities from the fovea to understand local anisotropia in correlation to increase in AL. The cone count and spacing between the mild and moderate group was not found to be significantly different but statistically significant variation was found between the mild and the moderate group with the high myopes [Figure 3]. This adds to the theory that the expansion is nonuniform. 
The limitations of our study was the cone mosaic at the fovea could not be assessed due to their dense arrangement  and absence of a correction factor due to the retinal magnification factor. 
| Conclusion|| |
The variables affecting vision in myopes is multifactorial. The higher order aberrations, size of the pupil, stretching of the photoreceptors, reduced retinal sampling and the contribution of postreceptor neural factors play a role. With AO we are now able to understand the placement of the photoreceptors with respect to the AL in myopes. In myopic patients with good visual acuity cone density around the fovea depends on the quadrant, distance from the fovea as well as the AL. The strength of the relation of AL with cone density depends on the quadrant and distance. Further research on the relation between cone density, visual acuity, psychophysical tests and micro-perimetry may help us understand the structural and functional vision of these patients. This may aid us better in counseling our patients, e.g., prior to any refractive or retinal surgical procedure.
| References|| |
Guirao A, Porter J, Williams DR, Cox IG. Calculated impact of higher-order monochromatic aberrations on retinal image quality in a population of human eyes. J Opt Soc Am A Opt Image Sci Vis 2002;19:620-8.
Atchison DA, Schmid KL, Pritchard N. Neural and optical limits to visual performance in myopia. Vision Res 2006;46:3707-22.
Chui TY, Yap MK, Chan HH, Thibos LN. Retinal stretching limits peripheral visual acuity in myopia. Vision Res 2005;45:593-605.
Coletta NJ, Watson T. Effect of myopia on visual acuity measured with laser interference fringes. Vision Res 2006;46:636-51.
Strang NC, Winn B, Bradley A. The role of neural and optical factors in limiting visual resolution in myopia. Vision Res 1998;38:1713-21.
Rossi EA, Weiser P, Tarrant J, Roorda A. Visual performance in emmetropia and low myopia after correction of high-order aberrations. J Vis 2007;7:14.
Kitaguchi Y, Bessho K, Yamaguchi T, Nakazawa N, Mihashi T, Fujikado T. In vivo
measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera. Jpn J Ophthalmol 2007;51:456-61.
Chui TY, Song H, Burns SA. Individual variations in human cone photoreceptor packing density: Variations with refractive error. Invest Ophthalmol Vis Sci 2008;49:4679-87.
Lombardo M, Serrao S, Ducoli P, Lombardo G. Variations in image optical quality of the eye and the sampling limit of resolution of the cone mosaic with axial length in young adults. J Cataract Refract Surg 2012;38:1147-55.
Dabir S, Mangalesh S, Kumar KA, Kummelil MK, Sinha Roy A, Shetty R. Variations in the cone packing density with eccentricity in emmetropes. Eye (Lond) 2014;28:1488-93.
Grossniklaus HE, Green WR. Pathologic findings in pathologic myopia. Retina 1992;12:127-33.
Atchison DA, Jones CE, Schmid KL, Pritchard N, Pope JM, Strugnell WE, et al.
Eye shape in emmetropia and myopia. Invest Ophthalmol Vis Sci 2004;45:3380-6.
Marcos S, Burns SA. Cone spacing and waveguide properties from cone directionality measurements. J Opt Soc Am A Opt Image Sci Vis 1999;16:995-1004.
Williams DR. Topography of the foveal cone mosaic in the living human eye. Vision Res 1988;28:433-54.
Curcio CA, Sloan KR, Kalina RE, Hendrickson AE. Human photoreceptor topography. J Comp Neurol 1990;292:497-523.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]