Acupuncture For Patients With Glaucoma

Acupuncture For Patients With Glaucoma

BRIEF REPORT ACUPUNCTURE FOR PATIENTS WITH GLAUCOMA Masayuki Kurusu MD, PhD,1,# Kei Watanabe, MD,2 Toru Nakazawa, MD, PhD,2 Takashi Seki, MD, PhD,3 H...

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BRIEF REPORT

ACUPUNCTURE FOR PATIENTS WITH GLAUCOMA Masayuki Kurusu MD, PhD,1,# Kei Watanabe, MD,2 Toru Nakazawa, MD, PhD,2 Takashi Seki, MD, PhD,3 Hiroyuki Arai, MD, PhD,3 Hidetada Sasaki, MD, PhD,1 Nobuo Fuse, MD, PhD,2 and Makoto Tamai, MD, PhD2

Context: Research of the effects of one acupuncture method for patients with glaucoma, focusing on intraocular pressure (IOP) and visual acuity. Objective: To explore the possibility of using acupuncture for patients with glaucoma. Design: Pilot study utilizing a one-group preintervention, postintervention design. Setting: Eleven patients with glaucoma were recruited through advertisement at the clinic for glaucoma. Intervention: Acupuncture was carried out twice a week over 5 weeks. Outcome Measures: IOP, visual acuity, and subjective symptoms were observed at 15 minutes before and after acupuncture once a week and in a four-week follow-up.

INTRODUCTION In most cases, glaucoma is a slowly progressive disease. Some patients may seek complementary or alternative medicine (CAM) to supplement their regular treatments.1 Acupuncture may be potentially useful in treating a variety of ocular conditions including dry eye, myopia, paralytic strabismus, retinitis pigmentosa, optic atrophy, iritis, conjunctivitis, and cataracts. In 1999, the American Academy of Ophthalmology task force acknowledged that acupuncture may be useful as an adjunctive therapy or as an acceptable alternative to conventional treatment for certain ocular conditions.2 However, at this time, there is no evidence to either encourage or discourage the use of acupuncture for the treatment of glaucoma.3 A case series with 50 acupuncture treatments for myopia, glaucoma, retinitis pigmentosa, and optic nerve atrophy showed some improvement in visual acuity subjectively, and three out of eight patients with glaucoma had a decrease in pressure in the

1 Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine; 2 Department of Ophthalmology, Tohoku University School of Medicine; 3 Department of Geriatric and Complementary Medicine, Center for Asian Traditional Medicine Research, Tohoku University Graduate School of Medicine, Sendai, Japan No proprietary interests or research funding for this study. # Corresponding author. Address: Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. e-mail [email protected]

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Results IOP was significantly improved at 15 minutes after acupuncture, at one week, two weeks, and five weeks and tended to be lower weekly. Uncorrected visual acuity was significantly improved at three weeks, four weeks, and five weeks, and best corrected visual acuity was significantly improved at five weeks. However at the four-week follow-up, significance remained only in uncorrected visual acuity. Conclusions: Although these results should be interpreted cautiously, acupuncture can be used to supplement the conventional therapy for glaucoma. Key words: Acupuncture, glaucoma, intraocular pressure, visual acuity (Explore 2005; 1:372-376. © Elsevier Inc. 2005)

eye, although the precise values were not cited.4 In another case series with over 500 acupuncture treatments for various kinds of ocular diseases, a subset of patients with glaucoma showed remarkable improvement in visual acuity.5 The authors, however, suggested that acupuncture did not affect intraocular pressure (IOP) obviously and could not regulate IOP alone. A clinical study of acupuncture on 18 patients with glaucoma and ocular hypertension indicated that IOP is significantly decreased at 15 minutes as well as at 24 hours after acupuncture.6 Generally, lowering IOP is, so far, the only means of treating glaucoma, and the primary goal of treatment is to prevent glaucomatous damage to the structures and function of the eye.7 No studies to date have assessed whether acupuncture can keep the IOP lower for more than a brief period of time following a treatment; to determine whether this is possible, a protocol involving a series of consecutive treatments is necessary. According to the principles of traditional Chinese medicine (TCM),8 selection of the acupoints and methods of acupuncture are generally based on the TCM diagnosis—rather than on the conventional diagnosis of “glaucoma”—and adjusted according to the patients’ condition and disease status at the moment of treatment. This individualized approach makes it difficult for medical practitioners who are unfamiliar with TCM to understand or apply acupuncture in the clinical setting. If an acupuncture method that does not need an exact TCM diagnosis is found to be effective, acupuncture could be used more easily as a treatment for glaucoma. The purpose of the present pilot study was to examine how manual acupuncture affects IOP and visual acuity in patients with glaucoma during five weeks of treatment and four weeks of

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follow-up. The present study focuses on three points: (1) the short-term effect of the present acupuncture method (its potential and reproducibility), (2) the long-term effect of the present acupuncture method (its durability and accumulation), and (3) acceptability of the present acupuncture method (alleviated symptoms, feeling, adverse effects or risks, subjects’ willingness to continue acupuncture).

METHODS Eleven patients (age, 66.2 ⫾ 8.20 years; mean ⫾ SD; five males, six females) were recruited through advertisement at the clinic for glaucoma of the Department of Ophthalmology, Tohoku University School of Medicine. None of them had experienced acupuncture before. The inclusion criteria were as follows: (1) age 20 years or older and (2) unilateral or bilateral glaucoma treated for at least one year with ocular hypotensive medication. The exclusion criteria were as follows: (1) laser trabeculoplasty, any ocular surgery, or inflammation within one year; (2) other abnormal ocular conditions; and (3) starting or adjusting the use of any systemic medication affecting IOP within three months. Subjects were assessed for eligibility at a regular monthly visit, and written informed consent was obtained before enrollment. Ethical approval was given by the ethics committee of the Tohoku University School of Medicine. Of the 22 eyes in these 11 subjects, 20 showed glaucoma (11 primary open-angle glaucoma (POAG), two exfoliative glaucoma, two normal tension glaucoma, four primary angle-closure glaucoma, one secondary glaucoma because of trauma), one showed phthisis bulbi because of Eales disease, and one was normal. All the glaucomatous eyes were treated with topical medication consisting either of prostaglandin analogs, ␤-blockers, carbonic-anhydrase inhibitors, parasympathomimetics, ␣-1blockers alone, or a combination of the above. Two eyes of one subject with POAG were treated with systemic carbonic-anhydrase inhibitors, and 12 eyes had a past history of laser iridotomy or surgery. According to the Anderson criteria,9 five eyes were classified as mild, two as moderate and 13 as severe. The protocol of our study was as follows. Acupuncture was carried out twice a week during four weeks and once in the fifth week, totaling nine times. Objective and subjective examinations were performed at approximately 15 minutes before and 15 minutes after acupuncture once a week during the five-week sessions. The subjects were followed for four weeks following the completion of the therapy. Because there is a diurnal fluctuation in IOP, we consistently performed the treatments and the assessment procedures between one and four PM. One licensed acupuncturist and one physician-acupuncturist with over two years of acupuncture experience administered the acupuncture in the study. Acupuncture was performed by inserting disposable stainless steel needles (0.16 mm or 0.20 mm ⫻ 40 mm; Seirin Co. Ltd., Shizuoka, Japan) to a depth of approximately 20 mm at all acupoints or tender points, except points such as Cuanzhu (BL2), Sibai (ST2), Taiyang (EX-HN4), or Taichong (LR3) at which the subcutaneous tissue is very thin, and the needles were inserted close to the skull or bones, to a depth of approximately 3 to 10mm. Needles were simply inserted without any intention of eliciting specific responses such

Acupuncture for Glaucoma

Figure 1. (A) Acupoints used in the supine position. (B) Acupoints used in the prone position.

as de qi feelings, and neither needle manipulation techniques nor other auxiliary interventions were used. Based on our clinical experience of TCM, we predicted that most patients with glaucoma would suffer from “Liver” or “Kidney” patterns, so we selected the 20 acupoints that had been most frequently used in our practice (Figure 1). Taichong (LR3), Taixi (KI3), Sanyinjiao (SP6), Ganshu (BL18), Shenshu (BL23), and Fengchi (GB20) were chosen to treat a possible imbalance and pathology of “Liver” and “Kidney” meridians, and Zusanli (ST36) was chosen to tonify Qi (energy) for the eyes. Cuanzhu (BL2), Sibai (ST2), and Taiyang (EX-HN4) were the main local points around the eyes; all of these points are commonly used in ocular diseases. If the subjects suffered from any pain, and the acupuncturists found prominent tender points besides the predetermined 20 acupoints, we needled these tender points in the head, shoulder, back, or knees. The number of additional acupoints treated was 3.0 ⫾ 2.2 per treatment. For the acupuncture treatment, the subjects rested in a supine position at first for 15 minutes for the insertion of the needles in the 14 acupoints shown in Figure 1A. Following this, subjects moved to a prone position for 15 minutes for the 6 acupoints shown in Figure 1B. As an objective examination, IOP and visual acuity with or without glasses were measured by an ophthalmologist. IOP was measured with a Goldmann applanation tonometer. Visual acuity was examined with a 5-m visual acuity chart, and visual field was tested using a Humphrey Field Analyzer (Carl Zeiss Meditec AG, Jena, Germany). Subjective examination was carried out by a questionnaire, which consisted of 0-to-10 visual analog scales (VAS) of ocular pain, and other questions to be answered on a scale of zero to three (zero, none; one, slight; two, moderate; three, severe) in regard to blurred vision, asthenopia, dry eye, shoulder stiffness, irritated feeling, and general fatigue. To assess the IOP and visual acuity changes as a result of the acupuncture treatment, we expressed the data as a percentage

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change rate by setting the value at 15 minutes before acupuncture at week one as the baseline (100%) and dividing the values from the assessment 15 minutes following acupuncture by the baseline value. The glaucomatous eyes were used for analysis of IOP, as were eyes with better than 0.01 (decimal) visual acuity. For subjective symptoms, subjects whose symptoms presented at least once from week one to week nine were included. Scores of zero to 10 for VAS in ocular pain, and zero, one, two, and three in other symptoms for each week were used. We analyzed the data before and after acupuncture by means of the Friedman repeated measures analysis of variance on ranks. When a significant difference was found, we compared the baseline value (15 minutes before acupuncture at week one) to the other data by Wilcoxon’s signed-rank test, adjusted for multiple comparisons with Bonferroni correction. A value of P ⬍ .05 was taken as significant.

RESULTS The changes in IOP are shown in Figure 2A. At 15 minutes after acupuncture for each week, IOP decreased compared with the baseline (100%; 15.5 ⫾ 2.7 mm Hg, n ⫽ 20); this decrease was significant at week one, week two, and week five (81.4% ⫾ 15.7%, 81.1% ⫾ 18.3%, and 81.1% ⫾ 16.3%, respectively). This effect tended to decrease after three days; that is, IOP had risen again at 15 minutes before the next acupuncture treatment. On the whole, IOP was gradually lowered weekly when observed at 15 minutes before acupuncture for each week. This indicated that the effects of the previous acupuncture treatments remained to some extent for an interval of three days, and the effects accumulated with regular acupuncture treatments, suggesting that there was some carryover effect. Uncorrected and best corrected visual acuity had a tendency to improve at 15 minutes after acupuncture for each week compared with the baseline (100%; 0.432 ⫾ 0.337, 0.628 ⫾ 0.322 [decimal] respectively, n ⫽ 19) (Figure 2B and 2C). Uncorrected visual acuity increased steadily as the protocol proceeded, and, unlike IOP, the effect remained for more than three days with a significant improvement observed at week three (150.9% ⫾ 61.5%), week four (150.8% ⫾ 75.3%), and week five (159.4% ⫾ 59.0%) even before acupuncture. Although it became less, the significance still existed at the nine weeks follow-up (134.1% ⫾ 49.8%). On the other hand, best corrected visual acuity did not change remarkably, showing a significant improvement only at week five (128.9% ⫾ 43.9%) before acupuncture. For subjective symptoms, ocular pain, blurred vision, asthenopia, dry eye, shoulder stiffness, and irritated feeling tended to be improved at 15 minutes after acupuncture (Table 1). Only general fatigue did not show any obvious trends. Overall, the improvement of ocular pain, blurred vision, asthenopia, dry eye, shoulder stiffness, and irritated feeling at 15 minutes after acupuncture became less three days after acupuncture. Ocular pain, blurred vision, and asthenopia tended to improve over the entire five weeks of acupuncture treatment, although these improvements did not reach statistical significance.

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Figure 2. (A) The results of intraocular pressure (mean ⫾ SD) during the acupuncture session from one week (1 w) to five weeks and at the nine-week follow-up (n ⫽ 20). *Significant difference from the point at 15 minutes before acupuncture at one week (100%, 15.5 ⫾ 2.7 mm Hg), P ⬍ .05. (B) The results of uncorrected visual acuity (mean ⫾ SD) (n ⫽ 19). *Significant difference from the point at 15 minutes before acupuncture at one week (100%, 0.432 ⫾ 0.337 [decimal]), P ⬍ .05. (C) The results of best corrected visual acuity (mean ⫾ SD) (n ⫽ 19). *Significant difference from the point at 15 minutes before acupuncture at one week (100%, 0.628 ⫾ 0.322 [decimal]), P ⬍ .05.

Acupuncture for Glaucoma

2.6 ⫾ 0.9 1.5 ⫾ 1.1 1.1 ⫾ 0.8 1.3 ⫾ 0.5 0.7 ⫾ 0.5 0.4 ⫾ 0.8 0.6 ⫾ 0.7 0.2 ⫾ 0.4 1.1 ⫾ 1.2 0.2 ⫾ 0.4 0.6 ⫾ 0.7 0.1 ⫾ 0.3 0.1 ⫾ 0.4 0.5 ⫾ 0.5 1.0 ⫾ 1.2 1.2 ⫾ 1.1 0.7 ⫾ 0.7 0.9 ⫾ 0.6 0.5 ⫾ 0.5 0.7 ⫾ 0.8 0.5 ⫾ 0.5 0.7 ⫾ 1.0 0.9 ⫾ 1.3 0.3 ⫾ 0.5 0.6 ⫾ 0.7 0.2 ⫾ 0.4 0.1 ⫾ 0.4 0.5 ⫾ 0.5 1.3 ⫾ 1.7 1.4 ⫾ 1.1 0.8 ⫾ 0.7 0.9 ⫾ 0.6 0.8 ⫾ 0.6 0.4 ⫾ 0.5 0.8 ⫾ 0.4 0.7 ⫾ 1.0 1.2 ⫾ 1.1 0.1 ⫾ 0.3* 0.8 ⫾ 0.7 0.3 ⫾ 0.5 0.3 ⫾ 0.5 0.3 ⫾ 0.5 Results are mean ⫾ standard deviation. B: before acupuncture; A: after acupuncture. a : Assessed by 0-to-10 visual analog scale. b : Assessed by 0/1/2/3 (0, none; 1, slight; 2, moderate; 3, severe). c : Significant difference from the point at 15 minutes before acupuncture at one week,P ⬍ .05.

1.5 ⫾ 1.5 1.4 ⫾ 1.1 0.8 ⫾ 0.4 1.0 ⫾ 0.8 0.5 ⫾ 0.5 0.7 ⫾ 1.1 0.5 ⫾ 0.7 1.4 ⫾ 2.2 1.3 ⫾ 1.2 0.3 ⫾ 0.5 0.5 ⫾ 0.8 0.2 ⫾ 0.4 0.4 ⫾ 0.8 0.7 ⫾ 0.8 2.3 ⫾ 2.6 1.6 ⫾ 1.0 1.2 ⫾ 0.7 1.3 ⫾ 0.9 0.4 ⫾ 0.5 0.7 ⫾ 0.8 0.7 ⫾ 0.7 2.3 ⫾ 2.8 1.8 ⫾ 1.0 0.8 ⫾ 0.8 0.6 ⫾ 0.7 0.2 ⫾ 0.4 0.4 ⫾ 1.1 0.8 ⫾ 0.8

B A B A B A B

2.3 ⫾ 2.8 2.0 ⫾ 0.8 1.3 ⫾ 0.7 0.6 ⫾ 0.7 0.7 ⫾ 0.5 1.1 ⫾ 0.9 0.7 ⫾ 0.7 9) 10) 9) 8) 10) 7) 10) ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ (n (n (n (n (n (n (n Ocular paina Blurred visionb Asthenopiab Dry eyeb Shoulder stiffnessb Irritated feelingb General fatigueb

Nine Week A A

B

Five Week Four Week Three Week Two Week One Week

Table 1. Results of Subjective Symptoms (mean ⫾ SD)

Acupuncture for Glaucoma

DISCUSSION In this study, acupuncture treatment resulted in a significant decrease in IOP 15 minutes following treatment in week 1 of the protocol. Uncorrected and best corrected visual acuity also improved at 15 minutes after acupuncture, although these improvements were not statistically significant. The same trend of short-term effects was observed from weeks two to five; however, these results should be interpreted cautiously because the influence of the former acupuncture treatments could remain at these later measurement points. This finding regarding IOP is consistent with previous reports of acupuncture-induced ocular hypotension lasting up to 24 hours.6 Subjective symptoms examined in the present study were also alleviated, except for general fatigue. This finding again is consistent with previous reports including that of Nepp et al,10 suggesting that acupuncture could reduce pain when used with patients with therapy-refractory pain in ophthalmology. Nepp et al also showed in a doubleblind study that both laser and needle acupuncture had a beneficial effect for dry eye.11 In our study, the effects of acupuncture on IOP and uncorrected visual acuity tended to weaken as time passed following each treatment, with subjects returning nearly to baseline levels by three or fours days following a treatment. Nevertheless, during the four-week treatment period (consisting of eight acupuncture treatments), the IOP as measured before each treatment showed a downward trend from the prior week, and the uncorrected visual acuity showed a gradual improvement (see Figure 2). These results suggest that ongoing acupuncture treatment may be desirable to maintain the beneficial effects demonstrated in this study. Wong and Ching,12 who reported that visual acuity of a subset of patients with glaucoma was improved by acupuncture, suggested similarly that ongoing treatment was probably necessary to maintain the improvement in vision. These authors, however, did not find a change in IOP with acupuncture, although they did find an improvement in vision. Based on animal studies, Chu and Potter13 hypothesized that the mechanism of acupuncture in treatment of glaucoma may be a reduction in the aqueous humor flow rate, possibly mediated through suppressed activity of the sympathetic nervous system and elevated levels of ␤-endorphin. In our study, we observed that the subjects did feel relaxed and less irritated after acupuncture while IOP decreased; this improvement in mood could be explained by the same increase in ␤-endorphin levels, although this was not measured in our study. Another possible mechanism for the improvement in visual acuity may be related to the effect of acupuncture on local blood flow. A reduction of the retinal and optic disk blood flow is thought to play a role in glaucoma.14 In 12 healthy volunteers, Naruse et al15 observed that stimulation of the acupoint Hegu for 30 minutes resulted in increased chorioretinal blood flow, as measured using a Heidelberg retina flowmeter (Heidelberg Engineering, Inc., Dossenheim, Germany). This improvement in circulation was thought to be mediated by a parasympathetic reaction to the acupuncture stimulation. Litscher et al16 reported that needling certain “visionrelated” acupoints around the orbits and on the limbs increased the blood flow velocity in the supratrochlear artery. Acupuncture to the vision-related acupoints also appears to activate the visual processing areas of the occipital lobes as measured by fMRI,17,18 thus the

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beneficial effects of acupuncture on visual acuity in glaucoma may be mediated by a number of different mechanisms. The present study has several significant limitations. Most significant is the lack of a control group to distinguish the nonspecific benefits of acupuncture treatment from the specific benefits of this treatment approach. Furthermore, because we sought to develop a protocol that could be easily reproduced by practitioners with limited TCM experience, we used 20 predetermined acupoints and a small number of tender points without any manipulation of needles and electrostimulation. Although this protocol did appear to reduce IOP, improve visual acuity, and alleviate subjective symptoms, it is possible that this selection of points and omission of needle stimulation resulted in less than optimal results. The selection of acupoints in this study represented only one possible protocol; there are numerous other acupoints commonly used in treating eye problems, such as He Gu (LI4) and Guang Ming (GB37), and the inclusion of these points and/or needle stimulation techniques may have improved the outcomes. A longer duration of the treatment protocol beyond four weeks might also have led to better outcomes. We chose to include the needling of the additional tender points to examine the possible impact of acupuncture on the subjective symptoms that often accompany glaucoma including fatigue, ocular pain, and shoulder stiffness. However, including these points, which led to some individualization of the treatment protocol for different patients, compromises the replicability of the outcomes in this study. Although we should view these results cautiously because this was a pilot study with a small sample size and no control interventions, the present study suggests that acupuncture can be used to supplement conventional therapy for glaucoma and other ocular diseases and symptoms without any major adverse effects. To the best of our knowledge, although several research groups have shown short-term effects of acupuncture on IOP, there is no study that describes the effects of consecutive acupuncture treatments over a longer period of time. The present study does suggest that, to maintain the beneficial effects on IOP and visual acuity, continuing acupuncture treatment is probably necessary. To clarify further the role of acupuncture in controlling IOP and preventing the progression of glaucoma, larger, placebo-controlled and blinded studies will be needed in the future. Acknowledgments The authors thank T. Sagara for inputting data and assisting with examinations, the staff and acupuncturists at Tohoku University Hospital for their administrative assistance, and the participating patients.

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REFERENCES 1. Rhee DJ, Spaeth GL, Myers JS, et al. Prevalence of the use of complementary and alternative medicine for glaucoma. Ophthalmology. 2002;109:438-443. 2. Taylor D. Alternative eye care. Br J Ophthalmol. 2001;85:767-768. 3. Rhee DJ, Katz LJ, Spaeth GL, Myers JS. Complementary and alternative medicine for glaucoma. Surv Ophthalmol. 2001;46:43-55. 4. Dabov S, Goutoranov G, Ivanova R, Petkova N. Clinical application of acupuncture in ophthalmology. Acupunct Electrother Res. 1985;10:79-93. 5. Wong S, Ching R. The use of acupuncture in ophthalmology. Am J Chin Med. 1980;8:104-153. 6. Uhrig S, Hummelsberger J, Brinkhaus B. Standardized acupuncture therapy in patients with ocular hypertension or glaucoma - results of a prospective observation study [Article in German]. Forsch Komplementarmed Klass Naturheilkd. 2003;10:256-261. 7. Tuulonen A, Airaksinen PJ, Erola E, et al. The Finnish evidencebased guideline for open-angle glaucoma. Acta Ophthalmol Scand. 2003;81:3-18. 8. Maciocia G. The Foundations of Chinese Medicine. 1st ed. Edinburgh: Churchill Livingstone; 1989. 9. Anderson DR, Patella VM. Automated Static Perimetry. 2nd ed. St. Louis: Mosby; 1999:164. 10. Nepp J, Jandrasits K, Schauersberger J, et al. Is acupuncture an useful tool for pain treatment in ophthalmology? Acupunct Electrother Res. 2002;27:171-182. 11. Nepp J, Wedrich A, Akramian J, et al. Dry eye treatment with acupuncture. A prospective, randomized, double-masked study. Adv Exp Med Biol. 1998;438:1011-1016. 12. Wong S, Ching R. The use of acupuncture in ophthalmology. Am J Chin Med. 1980;8:104-153. 13. Chu TC, Potter DE. Ocular hypotension induced by electroacupuncture. J Ocul Pharmacol Ther. 2002;18:293-305. 14. Nicolela MT, Hnik P, Drance SM. Scanning laser Doppler flowmeter study of retinal and optic disk blood flow in glaucomatous patients. Am J Ophthalmol. 1996;122:775-783. 15. Naruse S, Mori K, Kurihara M, et al. Chorioretinal blood flow changes following acupuncture between thumb and forefinger [Article in Japanese]. Nippon Ganka Gakkai Zasshi. 2000;104:717-723. 16. Litscher G, Wang L, Yang NH, Schwarz G. Computer-controlled acupuncture. Quantification and separation of specific effects. Neurol Res. 1999;21:530-534. 17. Cho ZH, Chung SC, Jones JP, et al. New findings of the correlation between acupoints and corresponding brain cortices using functional MRI. Proc Natl Acad Sci U S A. 1998;95:2670-2673. 18. Siedentopf CM, Golaszewski SM, Mottaghy FM, Ruff CC, Felber S, Schlager A. Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans. Neurosci Lett. 2002;327:53-56.

Acupuncture for Glaucoma