RETINAL DISORDERS

Inverse relationship between macular pigment optical densityand axial length in Chinese subjects with myopia

Nianting Tong & Wei Zhang & Zhenzhen Zhang &

Yuanyuan Gong & Billy Wooten & Xingwei Wu

Received: 19 September 2012 /Revised: 3 November 2012 /Accepted: 20 November 2012# Springer-Verlag Berlin Heidelberg 2012

AbstractBackground Macular pigment (MP) has been the focus ofmuch attention in recent years, due to its protective effect againstmacular degenerations. In this study, we investigated the asso-ciation between macular pigment optical density (MPOD)and axial length (AL) in Chinese subjects with myopia.Methods In total, 173 myopes (mean spherical equivalent[MSE]≤-1.00D) were recruited for this prospective obser-vational study. MPOD was measured in both eyes of eachsubject using a macular metrics densitometer. AL was mea-sured in eyes using an IOL-Master. A raw coefficient ofcorrelation analysis and a partial correlation analysis wereused to investigate the relationship between MPOD and AL.Results The age of the subjects ranged from 18 to 67 years.The overall mean MPOD for the cohort was 0.412±0.119(range, 0.105–0.812). The mean AL was 25.18±1.08 mm(range, 23.14–28.19 mm). Using a raw coefficient of correla-tion, a significant inverse correlation was found betweenMPOD and AL (r0−0.134, p00.012). When using a partialcorrelation analysis to eliminate the impact of covariant, asignificant inverse correlation was also found betweenMPODand AL (r0−0.142, p00.008). Furthermore, when AL wasdivided into two groups: AL>26 mm and AL≤26 mm, asignificant inverse correlation was observed between MPODand AL in the former (r0−0.253, p00.029), but no significantrelationship was observed between these in the latter (r00.104, p00.067).

Conclusions MPOD correlated inversely with AL in thissample of Chinese subjects with myopia.

Keywords Macular pigment . Macular pigment opticaldensity . Customized heterochromatic flicker photometry .

Axial length . Myopia

Primate maculae have a distinctive yellow macular pigment(MP), which is a recognised specialisation. MP was originallyidentified by Wald as being composed of xanthophyllic car-otenoids and concentrated in the macula [1, 2]. These carote-noids are absorbed in the gut and ultimately deposited in theHenle fiber layer in primates [3]. Lutein (L), zeaxanthin (Z),and meso-zeaxanthin (meso-Z) are hydroxycarotenoids thatconstitute the MP in humans [4]. L and Z are of dietary originand are not synthesised de novo in humans, whereasmeso-Z isgenerally not found in the diet, but is primarily formed in theretina following biochemical isomerisation from L [5]. MP isfound at its highest concentration in the central macula, whereit functions as a powerful antioxidant [6], and acts as a filter ofactinic high-energy (short-wavelength) blue light before itreaches the photoreceptors or the retinal pigment epithelium,thus limiting photo-oxidative damage to retinal cells [3, 7].These properties of MP are believed to be the mechanism(s)through which it protects against the development and/orprogression of retinal degenerative diseases, such as age-related macular degeneration [8] and retinitis pigmentosa [9].

Myopia, which is much more prevalent in Asians than inCaucasians [10, 11], is a common refractive error seen world-wide, and complications related to severe myopia are a majorcause of blindness in many developed countries. As shown insome histopathological studies, pathological myopia involvesexcessive and progressive elongation of the globe, with con-sequential thinning of the retina at the posterior pole. In vivomeasurements of retinal thickness are possible with the

N. Tong :W. Zhang : Z. Zhang :Y. Gong :X. Wu (*)Department of Ophthalmology, Shanghai Jiaotong UniversityAffiliated Shanghai First People’s Hospital,No.85 Wujin Road,Hongkou District, Shanghai, Chinae-mail: eyewxw@gmail.com

B. WootenWalter S. Hunter Laboratory, Brown University,Box 1853, Providence, RI 02912, USA

Graefes Arch Clin Exp OphthalmolDOI 10.1007/s00417-012-2225-z

availability of modern imaging technologies, and the relation-ship between myopia and retinal thickness has been examined[12–18]. Although some earlier in vivo imaging studies[12–14] did not find an association between retinal thicknessand axial length (AL) of the eye, which contrasts with histo-pathological findings, the latest studies [15–18] have demon-strated an inverse relationship between AL and total averagemacular thickness, using relatively high scanning resolutionand large samples.

Furthermore, Aleman et al. [19] observed a relative lackof MP in association with thinner retinas, and a recent studydemonstrated a positive correlation between MP opticaldensity (MPOD) and central foveal thickness [20]. There-fore, it is tempting to hypothesise that eyeballs with a longerAL may be deficient in MP, and that a relative lack of MPmay represent an antecedent common to the visually conse-quential sequelae of pathological myopia. We prospectivelyinvestigated the relationship between MPOD and AL in asample of Chinese adults with myopia.

Materials and methods

Subjects

Measurements were performed on both eyes of 173 myopes(mean spherical equivalent [MSE]≤−1.00D), recruited atthe Department of Ophthalmology, Affiliated First People’sHospital of Shanghai Jiaotong University, Shanghai, China.The mean age of the subjects was 35.01±12.59 years(range, 18–67 years; 82 men, 91 women).

This study was approved by the local ethics committee ofthe hospital, and adhered to the tenets of the Declaration ofHelsinki. All subjects gave their written informed consentbefore testing, after the purpose and possible consequencesof the study were explained.

All subjects underwent a full ophthalmic examination,including visual acuity, intraocular pressure measurementwith Goldmann tonometry, dilated fundus examination withstereoscopic biomicroscopy of the optic nerve head under slitlamp, indirect ophthalmoscopy, and refraction. Other than

refractive error, all included eyes had no concurrent diseaseand had a best corrected visual acuity of at least 20/20.

MPOD measurements

MPOD was measured psychophysically using a macular met-rics densitometer developed by Professor Billy Wooten(Brown University, USA), which was described previously[21–23]. This device utilises the principle of customized het-erochromatic flicker photometry (cHFP), a technique that hasbeen validated against the MP absorption spectrum in vitro[24] and by motion photometry in normal subjects [22]. HFPis a psychophysical method that is based on the fact that MPhas a peak absorption at a wavelength of 458 nm, and requiresthe subject to observe flickering stimuli that are composed oftwo alternating wavelengths of light. During the test, theluminance ratio of the two wavelengths is reduced until theflicker is eliminated, that is, when the iso-luminance matchesbetween green (560 nm, not absorbed by MP) and blue(460 nm, maximally absorbed by MP) flickering lights. Iso-luminance matches are made with the test field at 0.25°(foveal) eccentricity and at 7° (parafoveal) eccentricity. There-fore, the logarithm of the ratio of the blue luminance in thefovea (where MP is assumed to be maximal) to that in theparafovea (as the “reference point,” in which MP is assumed to

Table 1 Demographicfeatures (n0173) andaxial length (AL)(n0346) of the recruitedsubjects

Gender

Male 81 (46.82 %)

Female 92 (53.18 %)

Age(years old)

Mean±SD 35.01±12.59

Range 18–67

AL (mm)

≤ 26 269 (77.8 %)

> 26 77 (22.2 %)

Table 2 Statistical results for macular pigment optical density(MPOD) and axial length (AL)

MPOD AL (mm)

p-value p-value

Male 0.415±0.129 0.663 25.19±1.11 0.823

Female 0.410±0.109 25.16±1.06

Right eye 0.407±0.113 0.441 25.18±1.07 0.955

Left eye 0.417±0.125 25.17±1.09

Fig. 1 The scatter plot shows the association between macular pig-ment optical density (MPOD) and age in the study patients. Note thatthere is no significant association between MPOD and subject age(r0−0.096, p00.076)

Graefes Arch Clin Exp Ophthalmol

be zero) gives a measure of the MPOD. Two separate exam-iners conducted the same procedure in each subject, to mini-mise subjective errors.

AL measurement

AL was measured using an optical biometry instrument(IOL-Master, Carl Zeiss Meditec, Jena, Germany), basedon partial coherence interferometry (PCI), which has beendescribed previously [25, 26]. Measurements were per-formed by the same examiner in the same place, accordingto the manufacturer’s recommendations. Five consecutivemeasurements were performed with IOLMaster softwareversion 5.01. Sixteen scans were performed within secondsto complete one measurement, and the mean was calculated.

Statistical analysis

The experimental data were expressed as the mean±standarddeviation. Significant differences between two groups were

calculated by the Student t test using the statistical softwareprogram SPSS for Windows version 17.0 (SPSS, Inc, Chi-cago, Illinois, USA). Pearson correlation tests were performedfor raw coefficient of correlation, and partial correlation anal-yses were performed for eliminating influences from cova-riants. P values<.05 were considered significant in all cases.

Results

The general characteristics of the subjects are shown inTable 1.

The mean AL was 25.18±1.08 mm (range, 23.14–28.19 mm), and the mean MPOD was 0.412±0.119 (range,0.105–0.812). The mean MPOD in males and females was0.415±0.129 and 0.410±0.109, respectively. ThemeanMPODin the right and left eyes was 0.407±0.113 and 0.417±0.125,respectively (Table 2). The mean AL in males and females was25.19±1.11 mm and 25.16±1.06 mm, respectively. The meanAL in the right and left eyes was 25.18±1.07 mm and 25.17±1.09 mm, respectively (Table 2). No differences were found forgender or asymmetry between fellow eyes.

We found no correlation between MPOD and subject age(r0−0.096, p00.076), but found an inverse relationshipbetween MPOD and AL (r0−0.134, p00.012). Figure 1shows a scatter plot of age and MPOD, and Fig. 2 shows ascatter plot of AL and MPOD.

In order to investigate the correlation between MPOD andAL in high myopia and in mild and moderate myopia respec-tively, we divided the AL into two groups, AL>26 mm andAL≤26 mm. As shown in Fig. 3, we found that the inverserelationship between MPOD and AL disappeared in AL≤26 mm (r00.117, p00.056), while the inverse relationshipbetween MPOD and AL was much more significant in AL>26 mm(r0−0.348, p00.002).

When using a partial correlation analysis to eliminate theimpact of covariance, a significant inverse correlation was

Fig. 2 The scatter plot shows the association between macular pig-ment optical density (MPOD) and axial length (AL) in the studypatients. Note that there is a inverse relationship between MPOD andAL (r0−0.134, p00.012)

Fig. 3 In this scatter plot, axial length (AL) is divided into two groups:AL>26 mm and AL≤26 mm, and the association between macularpigment optical density (MPOD) and axial length (AL) in two groupsis shown in one scatter plot. Note that there is a inverse relationship

between MPOD and AL in the former group (r0−0.348, p00.002),while there is no significant association between MPOD and AL in thelatter group (r00.117, p00.056)

Graefes Arch Clin Exp Ophthalmol

also found between MPOD and AL (r0−0.142, p00.008).Furthermore, when AL was divided into two groups: AL>26 mm and AL≤26 mm, a significant inverse correlationbetween MPOD and AL was also observed in the former(r0−0.253, p00.029), but no significant relationship wasobserved in the latter (r00.104, p00.067).

Discussion

We enrolled 173 subjects with myopia for the purpose ofinvestigating the relationship between MPOD and AL.MPOD was measured using cHFP, which is a subjectivepsychophysical method that requires subjects to make iso-luminance matches between green and blue flickering lights.ALwasmeasuredwith an IOL-Master, which is based on PCI.Our data showed a significant inverse relationship betweenAL and MPOD. This finding could be explained by recentstudies that focused on the relationship among AL, centralretinal thickness, and MPOD. Liew et al. [15] and van derVeen et al. [20] reported a significant and positive relationshipbetween central retinal thickness and MPOD, whereas in-creasing evidence [15–18] has shown a significant inverserelationship between AL and central retinal thickness. In otherwords, eyes with longer AL, particularly in those with patho-logical myopia, have thinner central retinas and less MPOD.MP is mainly located in the Henle fiber layer in primates [3].Central retinal thickness, including the Henle fiber layer,decreases with AL elongation, so the fovea seems much moreapplanated. That is to say, the foveal volume is invariable;once thickness decreases, the area of the fovea, or the fovealwidth, increases [20]; thus, an inverse correlation between thefoveal width and foveal thickness was discovered. Thischange to the central retina makes the measured data of0.25° (foveal) eccentricity decrease, and causes a decreasedMPOD reading on the macular metrics densitometer. Further-more, longer axial length is perhaps correlated with largerretinal images. Since the flicker method measures at the edgeof a stimulus and the MP distribution falls as perimetric angleincreases, one might expect a decreased MPOD in patientswith longer axial lengths.

There are various ways to measure MPOD, including ob-jective examinations, such as autofluorescence spectrometry[27], spectral fundus reflectometry [28], scanning laser oph-thalmoscopy [29], and resonance raman spectroscopy [30], aswell as subjective examinations such as HFP [31] or motionphotometry [32]. We used HFP in this study, which is apsychophysical method used extensively in the clinic. Despitethe many advantages of HFP, such as its convenience of useand rapid and high retest reliability, it is not without its prob-lems. As a psychophysical examination, the reliability andaccuracy of HFP results depend on subject cognition andcooperation. Therefore, two examiners conducted the same

procedure in each subject to minimise subjective errors, andvariance of > 10 % between individual measurements wasdiscarded. As to the measurement for AL, considering the dailyaxial length fluctuations [33], not a conventional A-scan ultra-sonography, but an optical biometry instrument, IOL-Master,which based on partial coherence interferometry, was used inorder to resolve this small magnitude of such fluctuations.

The level of MP is determined by ethnic differences. In thisstudy, the mean MPOD was 0.412±0.119 (range, 0.105–0.812), slightly lower than that of other studies in China [34,35]. This discrepancy is due to differences in the subjectpopulation between the present study and the other two stud-ies. In the present study, the mean AL in subjects with myopiawas 25.18±1.08 mm (range, 23.14–28.19 mm), obviouslylonger than that in healthy subjects in the previous studies.This difference inMPOD also supports the inverse correlationbetween MPOD and AL. Compared to studies on other sub-ject populations, we found a slightly higherMPOD in Chinesethan in Caucasians [20, 23, 36, 37], and a moderately lowerMPOD than that in South Indians and Africans [38, 39].Manystudies have demonstrated a decreasing MPOD during aging[40, 41], so we also investigated the relationship betweenMPOD and age. Similar to some studies [42, 43], MPODtended to decrease with age, but was not significantly corre-lated with subject age.

AsMPOD is influenced bymany other various factors, suchas food habits (lutein supplementation) [44], smoking [41],obesity [45], serum concentrations of lutein and zeaxanthin[2], and macular diseases [9, 46–49], a well-designed follow-up study with a larger sample size and the elimination of otherMPOD influential factors is needed to determine the correlationbetween MPOD and age and between MPOD and AL.

In conclusion, we found that MPOD was inversely cor-related with AL in Chinese subjects with myopia.

Acknowledgments This study was supported by the Opening Projectof Shanghai Key Laboratory of Fundus Diseases (07Z22911)

Competing Interests None declared.

Conflict of Interest We declare that we have no financial and personalrelationships with other people or organizations that can inappropriatelyinfluence our work.

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