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logical and clinical developments in ophthalmology. Conse- ..... JAMA. 1912;59:1010Y1013. 4. Hamasaki D, Ong J, Marg E. The amplitude of accommodation in.

ORIGINAL STUDY

New Compact Accommodometer to Measure Accommodation Amplitude as a Biomarker Takeshi Ide, MD,*Þ Kazuno Negishi, MD,Þ Takefumi Yamaguchi, MD,þ Shuya Hara, MD,§ Ikuko Toda, MD,*Þ and Kazuo Tsubota, MDÞ

Purpose: This study aimed to evaluate a newly designed compact accommodometer (CA) and compare this with a conventional accommodometer for measuring accommodation as a biomarker for aging and lifestyle. Design: This is an observational case series. Methods: Accommodative amplitude was measured using 2 different accommodometers in 114 patients. We obtained the data of the nearpoint accommodation amplitude. Subsequently, we used smoking habit as an example of lifestyle-related factor to evaluate its effect on the accommodative power. Results: The first part of the study included 60 eyes of 60 men and 54 eyes of 54 women, with a mean (SD) age of 43.8 (12.9) years (range, 18Y58 years). There was a consistency within each measuring method despite a significant difference between the 2 devices (P G 0.01). Measuring accommodation by CA was significantly faster than by conventional modality (190.9 T 58.1 seconds for CA and 371.8 T 123.6 seconds for D’ACOMO, P G 0.0001, paired t test). In the second part of the study, we found a significant correlation between age and accommodative amplitude both in smokers and in nonsmokers. The accommodative amplitude of the smoker group was significantly lower than that of the nonsmoker group (P G 0.001). Conclusions: Compact accommodometer may work as an alternative and convenient method in place of the conventional accommodometer for measuring accommodative amplitude as an aging biomarker. Lifestyle factors can affect the magnitude of accommodation, which can be measured by this newly developed CA. Key Words: accommodation, aging, biomarker, lifestyle, presbyopia (Asia Pac J Ophthalmol 2012;1: 24Y27)

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urrently, both medical professionals and the public pay more attention to antiaging medicine than ever. There are various biomarkers that can be used to measure aging clinically. However, investigating with most of these biomarkers requires invasive procedures, such as obtaining blood or tissue samples. In addition, none of these investigations can be used alone. For the past decade, we have witnessed extensive technological and clinical developments in ophthalmology. Conse-

From the *Minamiaoyama Eye Clinic Tokyo, Tokyo; †Department of Ophthalmology, Keio University School of Medicine, Tokyo; ‡Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba; and §Department of Ophthalmology, Social Insurance Chukyo Hospital, Aichi, Japan. Received August 17, 2011, and accepted October 7, 2011. Reprints: Kazuo Tsubota, MD, Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: [email protected] Supported by a grant from Singapore Eye Research Institute. Dr Tsubota has a pending Japanese patent on the compact. The other authors have no funding or conflicts of interest to declare. Copyright * 2012 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0b013e31823f1a69

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quently, we could reach a point where we can satisfactorily correct the refractive errors with laser refractive surgery, intraocular lens implantation, or other procedures. The baby boomer generation has reached their mid 40s, and as a result, presbyopia has become a major concern and practice focus for eye care professionals. The mechanisms of presbyopia have not been fully elucidated. However, several mechanisms are suggested.1,2 The degree of presbyopia is conventionally measured by the amplitude of residual accommodation power. Accommodation amplitude may work as an easy, sensitive, and noninvasive marker for aging. Several reports showed that the accommodation amplitude decreases with aging and reaches a plateau after the 60s.3,4 Therefore, it may be convenient to use this amplitude as one of the aging biomarkers. However, the conventional accommodometer requires trained ophthalmic staff and expensive modalities. To overcome this issue, we have recently developed a compact accommodometer (CA), which is simple and easy to use in patients for measuring accommodation amplitude. In this study, we aimed to evaluate if this CA can yield comparable and/or consistent results to the conventional accommodometer as a biomarker for aging. In addition to aging, lifestyle factors can also affect the magnitude of accommodation. We analyzed smoking habit as an example of a ‘‘lifestyle’’ factor. Smoking is directly linked to many adverse health effects, including high blood pressure, heart disease, and cancer. Smoking is also linked to specific eye diseases, like cataract, age-related macular degeneration, dry eye, and diabetic retinopathy.5Y8 Based on these reports, we evaluated the effect of smoking on the magnitude of subjective accommodation. In this study, we used 2 types of accommodometers: the conventional model (D’ACOMO; World Optical Corporation, Kyoto, Japan) and the newly designed CA.

MATERIALS AND METHODS The Compact Accommodometer The CA measures 200 mm wide, 100 mm high, and 24 mm deep. It is battery-powered and weighs 320 g. There is a starburst symbol on the center of the device, which is equivalent in size to 0.6 of decimal near visual acuity charts at 33 cm (Fig. 1A). This device uses an ultrasound transmitter and sensor. The ultrasound sensor in this CA detects the round-trip time from the forehead of the subject to the device (Fig. 1B), and the time is automatically converted to the distance when the button is pushed. The measurable range of the CA is 20 to 50 cm, and the minimum scale step is 1 cm. The luminance of the examination room should be within 500 (100) lux. The measurement is performed with corrective lenses for distance; however, additional power lens (j2.0 D) is added if the near-point accommodation is outside the measurable range. In that case, the accommodation range is calculated, taking the power of the additional lens into consideration. The actual measurement is performed as follows: first, the subject holds the CA with both hands and positions it in front of his or her

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Volume 1, Number 1, January/February 2012 A New Compact Accommodometer as a Biomarker

face with arms extended. The subject brings the CA closer to his or her face until the he or she notices the margins of the symbol begin to blur. Then, the subject stops moving and pushes the button to record the distance (Fig. 1C). We measured the near point 3 times for each eye with distant correction or an additional j2.0 D lens correction. We also measured subjective accommodative amplitude using the existing subjective accommodometer (D’ACOMO; World Optical Corporation; Fig. 1D). The patient is required to read a cross-shaped target that corresponds in size to a visual acuity of 1.0 at a distance of 30 cm. The chart is brought closer mechanically until the patient reported blurring of the image. The measurable range of the D’ACOMO is 5 to 55 cm, and the minimum scale step is 1 mm. We carried out the measurement 3 times with both modalities, and the average accommodation power was recorded for analysis.

Participants Subjects were normal healthy volunteers who had best corrected visual acuity (BCVA) of 1.0 or better and refractive errors (spherical equivalent) between +2.0 D and j5.0 D. Exclusion criteria included any ocular or systemic disease. All subjects signed an informed consent form, and the study

adhered to the Declaration of Helsinki. This study protocol was approved by the Institutional review board of Keio University. In the first part of the study, subjects in the age-related study (60 eyes of 60 men and 54 eyes of 54 women) had a mean (SD) age of 43.8 (T12.9) years (range, 18Y58 years). In the second part of the study, subjects in the smoker study group (48 eyes of 24 nonsmoking subjects and 46 eyes of 23 smoking subjects) had a mean (SD) age of 39.2 (5.9) years (range, 30Y49 years) and 38.9 (5.9) years (range, 31Y49 years), respectively. There was no statistically significant difference in the age of the subjects in the 2 groups (P = 0.634).

Statistical Analysis For each modality, the average of 3 measurements using both machines was recorded. The interval of each measurement was 5 minutes. We performed Mann-Whitney U test because the samples showed nonnormal distributions. In addition, BlandAltman assessment for agreement was used to compare the 2 accommodation measuring methods. Statistical analyses were performed using SPSS software (SPSS, Inc, Chicago, Ill) and Analyse-it software (Analyse-it Software, Ltd, Leeds, United Kingdom).

FIGURE 1. A, Compact accommodometer. B, The principle of measurement of the CA. The distance from the device to the subject’s forehead is measured using ultrasound, and it adjusts automatically to the distance from the device to the eye. The accuracy of the adjustment is T1 cm in our data (data not shown). C, The method of measurement using the CA. The subject holds the CA at the height of the eye and brings it nearer to the eye. D, D’ACOMO subjective accommodometer being used in clinical practice. * 2012 Asia Pacific Academy of Ophthalmology

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RESULTS CA Evaluation Study There was a consistency within each measuring method (R2 value for each approximation line: 0.92 for CA and 0.87 for D’ACOMO, respectively). However, from the Mann-Whitney U test, significant differences were found between 2 groups (P G 0.01), and the Bland-Altman assessment suggests that these 2 methods did not consistently provide similar accommodative amplitudes. Data from both devices had inverse correlations with age (Fig. 2), as reported previously.1,2 The CA tended to underestimate the accommodation amplitude in younger subjects, and overestimate it in older subjects, compared with D’ACOMO. The mean required times for measurements were 190.9 (58.1) seconds for CA and 371.8 (123.6) seconds for D’ACOMO (P G 0.0001, paired t test).

Lifestyle (Smoking)-Related Study The mean accommodative amplitude was 4.9 (2.7) diopters (D) in the smoker group and 6.9 (3.1) D in the nonsmoker group. The accommodative amplitude of the smoker group was significantly lower than that of the nonsmoker group (P G 0.001). There was a significant positive correlation between age and accommodative amplitude both in smokers and in nonsmokers (Pearson correlation: P = 0.001 and P = 0.002, respectively).

DISCUSSION The data obtained in the current study suggest that the CA and conventional accommodometer yield statistically different results for measuring age-related accommodation power but that each method shows highly dependable results within its method. The R2 value for each approximation line is strong enough (0.92 for CA and 0.87 for D’ACOMO, respectively). The CA has advantages over the existing subjective accommodometer. It gives quick measurements and requires less space. It is easy to use and the subjects can measure their accommodation amplitude even by themselves. In addition to the aging trend, we could observe a statistical difference in accommodation power between smokers and nonsmokers.

FIGURE 2. Changes in accommodative amplitude with age. Circles and solid line indicate the data and approximate curve of the CA. Triangles and the dotted line indicate the data and approximate curve of the D’ACOMO. Both data were highly correlated with age. The compact accommodometer tends to underestimate the accommodation amplitude in younger subjects and to overestimate it in older subjects compared to the D’ACOMO. CA indicates compact accommodometer; D’ACOMO, subjective accommodometer; D, diopters.

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FIGURE 3. There were significant correlations between age and accommodative amplitude in smokers and nonsmokers. There was a significant difference in accommodative amplitude between smokers and nonsmokers (analysis of variance, P G 0.05).

The accommodative amplitude is a very good marker for aging because all people lose accommodation as they age. Presbyopia is currently among the hot topics in ophthalmology, but in actual clinical and research situations, we do not have any widely accepted definition and criteria. We recently published the article, ‘‘Definition and diagnostic criteria of presbyopia 2010.’’9 To avoid discrepancies between patients’ complaints and these criteria, we developed 2 separate definitions: clinical and medical presbyopia. Clinical presbyopia is defined as bilateral decimal near vision of less than 0.4 at 40 cm, along with the patient’s complaints. Medical presbyopia is defined as unilateral accommodation of less than 2.5 D, regardless of the subject’s complaints.9 This accommodation amplitude test has not been used widely in epidemiological or other clinical studies. However, the CA is small and portable and can easily be used by specialists as well as nonspecialists. There are a variety of supplements available for ocular health such as lutein, astaxanthin, or other vitamins. Although there is a general belief about improvement in sight after taking these supplements, this has not been categorically confirmed. Furthermore, we cannot confirm whether the accommodative amplitude can be improved with these health supplements. Cataract is another aging disease, and some data have shown that the level of vitamin C is related to cataract formation.10 Dherani et al11 have shown that insufficient nutrients accelerate cataract formation. It would be interesting to observe if there are any changes in the accommodative power with long-term health supplements. The CA would be a handy device for such population-based studies. In the present study, we showed the possibility of tobacco smoking as a risk factor for presbyopia, although there has been no report of this phenomenon. Therefore, it could be applied to a large-scale cohort study in the future for the detection of risk factors for presbyopia. This study is not without limitations. First, this is not available in the market yet. We used and compared 2 modalities, but they have different specifications. For instance, the target size and shape are different in both instruments. D’ACOMO target movement is controlled mechanically, whereas subjects can change the CA’s target moving speed at their own will. The CA has an inherent measurement error. This error is within 1 cm. We believe this specification is accurate enough for this kind of device. But at the same time, in theory, there are variations in measured distance even within a single subject, depending on the holding direction. When the subject has the * 2012 Asia Pacific Academy of Ophthalmology

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device parallel to the face, the device yields accurate measurements. But when the subject tilts the CA device, the obtained distance should not be accurate. In addition, because of the limitation of the measuring range, some patients have to wear glasses just for measurements, whereas others do not. We are not sure of the reflecting surface exactly, but we think there should be some errors between glass wearers and nonYglass wearers. Although it is evident from Figure 3 that the smokers had lower accommodative amplitudes than the nonsmokers did, the control data shown in this figure seem to be larger than the normative data shown in Figure 2. One of the supposed reasons is that the different subjects were included in 2 studies in different measuring situations (light, room, time, etc). This is a weak aspect of this device, which yields different data depending on the test conditions. But in each of the 2 test conditions, the measured data were relatively tightly packed around the approximation line (0.92 for CA and 0.87 for D’ACOMO, respectively, in Fig. 2 and 0.68 for smokers and for nonsmokers 0.69 in Fig. 3). Therefore, we can say that this device cannot be used universally but can be used at a certain place or conditions. Also, the definition of blurriness differs from person to person. This study would have been strengthened if we had combined subjective and objective modalities. In addition, we did not specify the smoking period and the number of cigarettes smoked per day. One study has also shown that there is no correlation between presbyopia and smoking.12 The mean and SD of the measurement times have a significant difference in the present study (P G 0.0001, paired t test), suggesting that the CA is time saving and easy to operate. But we have to remember that the measurable range of CA is smaller and needs additional lens correction for those who have a wide accommodation range. Therefore, the overall time required may be more than what is reported. Researchers have also pointed out that subjective measurements may be inaccurate when compared with objective methods.13Y18 In summary, despite several limitations and a lack of a large sample size, our results showed that the CA could be a useful piece of equipment for screening and studying accommodation amplitude as a biomarker for aging. We are now using this device in our clinics to collect large-scale data. Future large case series study with different age groups should add strength to this device reliability. REFERENCES 1. von Helmholtz H. Uber die akkommodation des auges. Albrecht von Graefef Arch Klin Ophthalmol. 1855;1:1Y89. 2. Schachar RA. Cause and treatment of presbyopia with a method for

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increasing the amplitude of accommodation. Ann Ophthalmol. 1992;24:445Y447, 452. 3. Duane A. Normal values of the accommodation at all ages. JAMA. 1912;59:1010Y1013. 4. Hamasaki D, Ong J, Marg E. The amplitude of accommodation in presbyopia. Am J Optom Arch Am Acad Optom. 1956;33:3Y14. 5. Klein R, Klein BE, Linton KL, et al. The Beaver Dam Eye Study: the relation of age-related maculopathy to smoking. Am J Epidemiol. 1993;137:190Y200. 6. Christen WG, Manson JE, Seddon JM, et al. A prospective study of cigarette smoking and risk of cataract in men. JAMA. 1992;268:989Y993. 7. Moss SE, Klein R, Klein BE, et al. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000;118:1264Y1268. 8. Paetkau ME, Boyd TA, Winship B, et al. Cigarette smoking and diabetic retinopathy. Diabetes. 1977;26:46Y49. 9. Ide T. Definition and diagnostic criteria of presbyopia 2010. J Eye. 2011;28:985Y988. 10. Shirai K, Iso H, Ohira T, et al. Perceived level of life enjoyment and risks of cardiovascular disease incidence and mortality: the Japan public health center-based study. Circulation. 2009;120:956Y963. 11. Dherani M, Murthy GV, Gupta SK, et al. Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population. Invest Ophthalmol Vis Sci. 2008;49: 3328Y3335. 12. Nirmalan PK, Krishnaiah S, Shamanna BR, et al. A population-based assessment of presbyopia in the state of Andhra Pradesh, south India: the Andhra Pradesh Eye Disease Study. Invest Ophthalmol Vis Sci. 2006;47:2324Y2328. 13. Atchison DA, Charman WN, Woods RL. Subjective depth-of-focus of the eye. Optom Vis Sci. 1997;74:511Y520. 14. Hung GK, Ciuffreda KJ, Rosenfield M. Proximal contribution to a linear static model of accommodation and vergence. Ophthalmic Physiol Opt. 1996;16:31Y41. 15. Ostrin LA, Glasser A. Accommodation measurements in a prepresbyopic and presbyopic population. J Cataract Refract Surg. 2004;30:1435Y1444. 16. Rosenfield M, Cohen AS. Repeatability of clinical measurements of the amplitude of accommodation. Ophthalmic Physiol Opt. 1966;16:247Y249. 17. Wold JE, Hu A, Chen S, et al. Subjective and objective measurement of human accommodative amplitude. J Cataract Refract Surg. 2003;29:1878Y1888. 18. Atchison DA, Capper EJ, McCabe KL. Clinical subjective measurement of amplitude of accommodation. Optom Vis Sci. 1994;71:699Y706.

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