Xie, Ruozhong*; Zhou, Xiang-Tian†; Lu, Fan‡; Chen, Min†; Xue, Anquan†; Chen, Shihao‡; Qu, Jia†
The onset of myopia is earlier and reaches a higher degree in the populations of China, Japan, and other East Asian countries compared with those in Western countries.1 Most of the myopes in Chinese ethnic groups are initially found at school age where intensive near reading is involved for a long period of time.2 Pathological changes may occur when the eye develops high myopia [higher than −6 Diopter (D)].3 These include glaucoma that is susceptible to optic disc atrophy,4 vitreous degeneration,5 retinal peripapillary atrophy, lattice degeneration, tilting of the optic disc, posterior staphyloma, breaks in Bruch membrane,3,6 and retinal detachment.3,7 It has been reported that 70% of high myopes could develop retinal changes causing deterioration in visual acuity.8 Therefore, an understanding of structural and dimensional changes in the refractive system and retina is important for myopic eyes.
Myopic development in children (11 to 12 years old) is correlated with a decrease in average macular volume and thickness.9,10 Young adults are among those with a high incidence of progressive myopia.1 Measurements using the first or third generation of optical coherence tomography (OCT)9,10 show an increased minimum foveal thickness but a decreased para-foveal thickness in young myopes. However, few reports correlate myopia with various axial components and retinal thickness of the eye for this age group. In a subsequent study,11 the macula was measured with the third generation OCT in more detail, including the fovea, inner macular region, outer macular region, and different quadrants within each region. This study showed that increasing myopia was correlated with an increased minimum foveal thickness and a decreased outer macular thickness. This indicates that changes in retinal thickness in myopic eyes vary with different regions of the posterior pole. Therefore, the retinal area susceptible to myopic development is clinically useful for a possible prediction of early myopia. This study investigated the relationship between myopia and changes in various axial components, corneal radius of curvature (CRC), and thickness of various macular regions for young adults.
MATERIALS AND METHODS
This study was approved by the Ethics Committee of Wenzhou Medical College in China and complied with the tenets of the Declaration of Helsinki. One hundred eight Chinese adults (216 eyes) with the age of 23.3 ± 6.3 years (mean ± SD) underwent retinoscopy, keratometry, and ultrasonography. One hundred eighteen eyes (from 59 subjects) underwent OCT.
Two drops of 0.5% phenylephrine and 0.5% tropicamide were topically administered to the eye to achieve mydriasis and cycloplegia, respectively. Retinoscopy was performed and recorded as spherical equivalence (SE) and then classified as emmetropia (+0.5 > SE > −0.50 D), low myopia (SE between −0.50 and >−3.00 D), moderate myopia (SE between −3.00 D and −6.00 D), or high myopia (SE<−6.00 D).
Optical Coherence Tomography
Stratus OCT3 (Carl Zeiss Meditec, Dublin, CA) was used to measure retinal thickness of the macula (6 mm diameter). The axial and transverse resolution of Stratus OCT3 is 10 and 20 μm, respectively. The OCT measurement was performed in a dark room immediately after the retinoscopy while the pupil was still dilated (>5 mm diameter). The subject’s head was fixed by a lower jaw sustainer and a forehead sustainer with the eye focusing on a target for few seconds without blinking during the OCT scanning. Every patient’s refractive power was compensated by focusing mechanism of the instrument. This procedure was accomplished by adjusting the focus knob to a value corresponding to the refractive power of the eye examined. The macular topographer was centered on the foveal pit and the macula was automatically divided to three concentric rings: center, inner, and outer rings (1, 3, and 6 mm diameter, respectively, Fig. 1A). Two reticules were used to divide each ring into four quadrants (temper, nasal, superior, and inferior). The fast macular scan was performed at six transverse scan directions with a 30-degree interval between any two scan directions. Each scan direction contained 128 scans and the average foveal thickness was determined by 128 data points within the 1-mm center ring (128/6 × 6 directions). Before accepting the topography of retinal thickness from the Stratus software, the six scanning lines were checked to ensure that the central wave trough of the retina was approximately at the 64th data point. Therefore, the center point of each scan direction reflected minimum foveal thickness12 (Fig. 1). All scanning results were automatically analyzed by the Version 4.1 software from the OCT system. Obscure images caused by a poor or de-centered fixation could be avoided by monitoring the dynamic scan screen.
A corneal topographer (Humphyrey Zeiss Atlas, Germany) was used to measure four points along the 3 mm radius from the center of the ring pattern. Axial map pattern from the Atlas software was used to provide the CRC based on the steepest and the flattest simulated keratometry readings.
A-scan ultrasonagraphy was used to measure the anterior chamber depth (ACD: distance between anterior surface of the cornea to anterior surface of the crystalline lens), the lens thickness (LT), and the vitreous length (VL). The ultrasound frequency was 8 MHz and the conducting velocity was 1532 m/sec for measurement of the ACD, 1641 m/sec for the LT, and 1532 m/sec for the VL. Topical anesthesia was administered with 0.5% proparacaine hydrochloride before the measurement. The ultrasound probe was placed at the center of the cornea perpendicularly. This perpendicular axis was confirmed by a series of consistent ultrasound traces when realigned the same eye for repeated measurements.13 Each of the axial components was the mean of the 10 repeated measurements (standard error <0.05 mm).
Results of all measurements were compared among different groups (one-way ANOVA with Post Hoc tests and Bonferroni correction). The inter-group difference in each parameter was defined as significant at p < 0.05 and highly significant at p < 0.01. Linear regression was performed between the refraction and each of the other biometric results in all groups (Pearson correlation).
There was a low but significant correlation between the two eyes of the same subjects (r = 0.35, p < 0.001) in absolute astigmatism. There was a high correlation between the 2 eyes of the same subjects (r = 0.72 to 0.99, p < 0.001) in all other parameters measured. Therefore, only results for the right eyes (a total of 108) were presented for analysis and comparison between different groups in the following sections.
The refractive status (mean ± SD in SE) was −0.09 ± 0.16 D in the emmetropia group (6.48% of total 108 eyes), −2.13 ± 0.71 D in the low myopia group (7.41% of total), −4.38 ± 0.77 D in the moderate myopia group (56.48% of total), and −7.70 ± 1.26 D in the high myopia group (29.63% of total). The absolute astigmatism was −0.38 ± 0.30 D (0 to −0.75) in low myopia, −0.55 ± 0.48 D (0 to −1.75) in moderate myopia, and −1.02 ± 0.93 D (0 to −3.50) in high myopia. There was a low but significant positive correlation between myopic spherical power and the absolute astigmatism (r = 0.37, p < 0.001).
Macular Thickness Measured by OCT
There were no significant inter-group differences in the minimum and average foveal thicknesses (Table 1). The inner ring macula in the emmetropia group was significantly thicker than in any of the myopia groups (p < 0.05) except the nasal quadrant (emmetropia vs. all myopia groups: p ≥ 0.247). The outer ring macula in the emmetropia group was significantly thicker than in any of the myopia groups (p ≤ 0.033) except the superior quadrant (emmetropia vs. all myopia groups: p ≥ 0.075). The average inner or outer ring macula in the emmetropic group was significantly thicker than in any of the myopia groups (p ≤ 0.021). There were no significant differences between any two myopia groups in all quadrants of the inner or outer ring macula. This lack of differences could result from the uneven distribution of subjects among the different groups.
CRC and Axial Components of the Eye
The CRC was 7.76 ± 0.28 mm in the emmetropia group, 7.59 ± 0.29 mm in the low myopia group, 7.70 ± 0.26 mm in the moderate myopia group, and 7.64 ± 0.23 mm in the high myopia group (CRC between any two groups: p ≥ 0.50, Fig. 2). The ACD was 3.42 ± 0.17 mm in the emmetropia group, 3.67 ± 0.25 mm in the low myopia group, 3.85 ± 0.25 mm in the moderate myopia group, and 3.75 ± 0.29 mm in the high myopia group. The ACD in the emmetropia group was significantly shorter than in any of the myopia groups (p ≤ 0.024). However, this value was statistically the same for the three myopia groups (p ≥ 0.347). The LT was 3.81 ± 0.15 mm in the emmetropia group, 3.63 ± 0.21 mm in the low myopia group, 3.72 ± 0.29 mm in the moderate myopia group, and 3.86 ± 0.36 mm in the high myopia group. There was no significant difference in LT between any two groups (p ≥ 0.213). The VL was 16.39 ± 0.55 mm in the emmetropia group, 16.58 ± 0.85 mm in the low myopia group, 16.65 ± 0.83 mm in the moderate myopia group, and 18.66 ± 0.79 mm in the high myopia group. There was a highly significant difference between any two groups in VL (p ≤ 0.004, Fig. 2).
Correlation Between Refraction and Each of the Other Biometric Results
The refraction SE was not correlated to the minimum and average foveal thickness (r < 0.02, p ≥ 0.709, Table 2). However, this value was positively correlated to the thickness of each quadrant of the inner and outer ring macula (r = 0.29 − 0.53, p ≤ 0.026) except the nasal quadrant of the inner ring (r = 0.22, p = 0.093). The inferior quadrant of the outer ring macula was more correlated to the refraction compared with the other quadrants (r = 0.53, p < 0.001). The refraction was positively correlated to the average thickness of the inner and outer ring macula (r = 0.33 and 0.45, respectively, p ≤ 0.011) but negatively correlated to the VL (r = −0.67, p < 0.001) and LT (r = −0.20, p = 0.034). There was no correlation between the refraction (SE) and the CRC or ACD (r ≤ 0.17, p ≥ 0.119).
In this study, the absolute astigmatism increases when the eyes become more myopic, suggesting that corneal surface irregularity or asymmetry of the optical system increases with myopic progression.14,15 The VL increases significantly with the increased degree of myopia (Fig. 2). This result is consistent with those found in previous human trials.9,16,17 The ACD in the myopic eyes is significantly greater than in the emmetropic eyes, but similar among the three myopia groups. A longitudinal study shows that the ACD increases slightly with increasing myopia.18 It should be noted that the linear regression used in this study mainly reflects the biometric changes of the myopic eyes that progress from moderate to high myopia (over 80% of the eyes are at least moderate myopia). Therefore, an increasing ACD may occur only at the beginning of the myopia as indicated by no significant correlation between the ACD and refraction. An absence of obvious correlation between CRC or LT and refraction in the present study suggests that these two components do not play a significant role in the myopic development (Table 2). Results in CRC in relation to refraction from previous reports are controversial in human trials.19–24 Studies from McBrien and Adams19 and Goss and Erickson20 do not show changes of CRC with myopic development. Other studies demonstrate an increasing steepness of the anterior corneal surface in myopic development.21
In the emmetropic eyes, the macular thickness increases in such an order: minimum foveal thickness, average fovea, outer ring macula, and inner ring macula (Table 1). These results are similar to those found in previous studies.9,25 The minimum and average foveal thickness is similar for the emmetropia and the myopia groups. One study on humans (38 to 48 years of age) shows that the minimum and average foveal thickness is similar for emmetropia and moderate myopia but increases from moderate to high myopia.11 Another study on school children (11 to 12 years of age) showed that minimum foveal thickness is similar for emmetropia and low myopia but increases from low to moderate myopia.9 All these results indicate that foveal thickness increases only when the eye progresses to moderate myopia.
It is noted that the foveal minimum thickness and central 1-mm average thickness in the present study are smaller than in Chan et al. study.26 This discrepancy may be associated with a different scanning protocol (radial scanning in Chan and fast macular scanning in the present study). It appears that the fast macular scanning is more accurate than the radial scanning as suggested by Ishikawa et al.27
The present study demonstrates more detail in regional changes of the retina among different degrees of myopia than previous studies.9,22 Three quarters of the inner ring or outer ring macular quadrants were thinner when eyes were myopic (Table 1). The linear regression shows that average thickness in the outer ring macula is more consistently correlated to the refraction than in the inner ring macula (Table 2). Furthermore, the thinness in the inferior quadrant of the outer ring macula appears to be more related to myopia than any of the other macular regions. These results suggest that the retinal thickness in the outer ring macula is more related to myopia than the inner ring macula.
The parafoveal regions (particularly the outer ring) covered by OCT in the myopic eyes may be more peripheral than in the emmetropic eyes due to the higher retinal magnification of the myopic eyes.28 The retinal image in a −6.00 D myope could undergo a minification of 8% when corrected with spectacle lenses. Based on this estimation, there is approximately 10% (2.86 mm2), 5.8% (1.64 mm2), and 2.8% (0.79 mm2) more peripheral area being covered by the OCT in the high myopia, moderate myopia and low myopia, respectively, when compared with the emmetropia in the present study. The difference in parafoveal thickness could be partly explained by the magnification effect. However, this effect has been found to be small among different refractive errors in the OCT measurement (with the same protocol as the present study).11 Furthermore, the magnification effect may be decreased because the magnification effect in greater axial lengths (myopia) can be reduced by the focusing mechanism. The para-foveal thinning of the myopic eyes is consistent with findings on monkeys where form deprivation myopia is functionally related to changes in the paracentral retina.25
Compared with other macular regions, the fovea has the highest density of cells (cone photoreceptors) with no overriding vessels. Therefore, the parafoveal regions are supposed to be more elastic. During myopic development, an axial elongation of the eye can cause mechanical stretching of the posterior pole, which is more likely to occur in the parafoveal regions. Furthermore, the peripheral thinning may act to preserve the function of the central retina during the axial elongation of the eye.29 This speculation is supported by findings in animal myopia where photoreceptors move towards the central retina from the periphery.30 These anatomical and physiological factors may determine that the parafoveal regions (inner and outer rings) are more susceptible to myopic changes than the fovea.
In summary, the degree of myopia in young adults is positively correlated to the VL but negatively correlated to the para-foveal thickness. The thickness of the retina inferior to the fovea appears more related to myopia when compared with the other regions.
This study was supported by the Chinese National Key Technologies R&D Program (2004BA720A16) and Zhejiang Provincial Natural Science Foundation of China (R205739).
School of Optometry and Ophthalmology
Wenzhou Medical College
270 Xueyuan Road
Wenzhou, Zhejiang 325003, People’s Republic of China
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1. Morgan I, Rose K. How genetic is school myopia? Prog Retin Eye Res 2005;24:1–38.
2. Paritsis N, Sarafidou E, Koliopoulos J, Trichopoulos D. Epidemiologic research on the role of studying and urban environment in the development of myopia during school-age years. Ann Ophthalmol 1983;15:1061–5.
3. Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and associated pathological complications. Ophthalmic Physiol Opt 2005;25:381–91.
4. Fong DS, Epstein DL, Allingham RR. Glaucoma and myopia: are they related? Int Ophthalmol Clin 1990;30:215–8.
5. Stirpe M, Heimann K. Vitreous changes and retinal detachment in highly myopic eyes. Eur J Ophthalmol 1996;6:50–8.
6. Saw SM, Katz J, Schein OD, Chew SJ, Chan TK. Epidemiology of myopia. Epidemiol Rev 1996;18:175–87.
7. Ishida S, Yamazaki K, Shinoda K, Kawashima S, Oguchi Y. Macular hole retinal detachment in highly myopic eyes: ultrastructure of surgically removed epiretinal membrane and clinicopathologic correlation. Retina 2000;20:176–83.
8. Grossniklaus HE, Green WR. Pathologic findings in pathologic myopia. Retina 1992;12:127–33.
9. Luo HD, Gazzard G, Fong A, Aung T, Hoh ST, Loon SC, Healey P, Tan DT, Wong TY, Saw SM. Myopia, axial length, and OCT characteristics of the macula in Singaporean children. Invest Ophthalmol Vis Sci 2006;47:2773–81.
10. Lim MC, Hoh ST, Foster PJ, Lim TH, Chew SJ, Seah SK, Aung T. Use of optical coherence tomography to assess variations in macular retinal thickness in myopia. Invest Ophthalmol Vis Sci 2005;46:974–8.
11. Lam DS, Leung KS, Mohamed S, Chan WM, Palanivelu MS, Cheung CY, Li EY, Lai RY, Leung CK. Regional variations in the relationship between macular thickness measurements and myopia. Invest Ophthalmol Vis Sci 2007;48:376–82.
12. Chan A, Duker JS. A standardized method for reporting changes in macular thickening using optical coherence tomography. Arch Ophthalmol 2005;123:939–43.
13. Zhou X, Qu J, Xie R, Wang R, Jiang L, Zhao H, Wen J, Lu F. Normal development of refractive state and ocular dimensions in guinea pigs. Vision Res 2006;46:2815–23.
14. Goss DA, Criswell MH. Bilateral monocular polyopia following television viewing. Clin Eye Vis Care 1992;4:28–32.
15. Wilson G, Bell C, Chotai S. The effect of lifting the lids on corneal astigmatism. Am J Optom Physiol Opt 1982;59:670–4.
16. Grosvenor T, Scott R. Comparison of refractive components in youth-onset and early adult-onset myopia. Optom Vis Sci 1991;68:204–9.
17. Grosvenor T, Scott R. Three-year changes in refraction and its components in youth-onset and early adult-onset myopia. Optom Vis Sci 1993;70:677–83.
18. Horner DG, Soni PS, Vyas N, Himebaugh NL. Longitudinal changes in corneal asphericity in myopia. Optom Vis Sci 2000;77:198–203.
19. McBrien NA, Adams DW. A longitudinal investigation of adult-onset and adult-progression of myopia in an occupational group. Refractive and biometric findings. Invest Ophthalmol Vis Sci 1997;38:321–33.
20. Goss DA, Erickson P. Meridional corneal components of myopia progression in young adults and children. Am J Optom Physiol Opt 1987;64:475–81.
21. Goss DA, Jackson TW. Clinical findings before the onset of myopia in youth. I. Ocular optical components. Optom Vis Sci 1995;72:870–8.
22. Grosvenor T. High axial length/corneal radius ratio as a risk factor in the development of myopia. Am J Optom Physiol Opt 1988;65:689–96.
23. Goss DA. Refractive status and premature birth. Optom Monthly 1985;76:109–11.
24. Sorsby A, Leary GA. A longitudinal study of refraction and its components during growth. Spec Rep Ser Med Res Counc 1969;309:1–41.
25. Smith EL, III, Kee CS, Ramamirtham R, Qiao-Grider Y, Hung LF. Peripheral vision can influence eye growth and refractive development in infant monkeys. Invest Ophthalmol Vis Sci 2005;46:3965–72.
26. Chan A, Duker JS, Ko TH, Fujimoto JG, Schuman JS. Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography. Arch Ophthalmol 2006;124:193–8.
27. Ishikawa H, Stein DM, Wollstein G, Beaton S, Fujimoto JG, Schuman JS. Macular segmentation with optical coherence tomography. Invest Ophthalmol Vis Sci 2005;46:2012–7.
28. Sanchez-Cano A, Baraibar B, Pablo LE, Honrubia FM. Magnification characteristics of the Optical Coherence Tomograph STRATUS OCT 3000. Ophthalmic Physiol Opt 2008;28:21–8.
29. Wakitani Y, Sasoh M, Sugimoto M, Ito Y, Ido M, Uji Y. Macular thickness measurements in healthy subjects with different axial lengths using optical coherence tomography. Retina 2003;23:177–82.
30. Liang H, Crewther DP, Crewther SG, Barila AM. A role for photoreceptor outer segments in the induction of deprivation myopia. Vision Res 1995;35:1217–25.