THE EFFECT OF ATROPINE ON MYOPIA RoBERT H. BEDRossiAN, MD VANCOUVER, WASHINGTON low the plan of treatment, and (4) economic and geographic stability to allow regular follow-up.
Sixty-two children were treated with atropine in one eye for one year; the fellow eye was the control. The eyes were switched the second year. Twenty-eight patients were treated for four years on the same basis. Control eyes showed significant increases in myopia compared to treated eyes. Some treated eyes showed decreases in myopia; no decreases were seen in control eyes. Posttreatment data analysis indicates the effects are long-term.
MYOPIA is probably the most common condition seen by the general ophthalmologist in the more developed countries. Despite the dependency on glasses for carrying on life functions and the economic impact of changes in lenses for the growing child, many opthalmologists consider myopia an unimportant and untreatable condition. Suggestions to prevent the increase of myopia are usually met with skepticism. This study, evaluating atropine as a treatment vehicle,l- 4 was planned in consultation with persons knowledgeable in medical statistics and carried out in a private practice setting. Guidelines for selection of patients were (1) evidence of myopia increasing more than 0.50 diopter on an annualized basis, (2) ages of 8 to 13 years, (3) parents and children with sufficient intelligence and motivation to fol-
Submitted for publication Oct 22, 197R. From the University of Oregon Medical School, Portland. Presented at the 1978 Annual Meeting of the American Academy of Ophthalmology, Kansas City, Mo, Oct 22-26. Reprint requests to 3200 Main St, Vancouver, WA 98663.
Since both hereditary and environmental factors are the same in each pair of eyes, one eye was used as a control for one year while the fellow eye was treated. The following year, the eye initially used as a control became the test eye, and the original test eye was the control eye. Patients instilled 1o/o atropine in the test eye at bedtime every night. To assure that the initial and final refraction on each eye was standardized, the baseline refraction was performed one month after the test eye had begun receiving atropine. The test eye was examined under atropine and the control eye under tropicamide (Mydriacil) every three to four months for 12 months, when a final refraction was done. To determine whether using one eye as a control for its fellow eye is a valid method of control, pretreatment changes in refraction of right and left eye were compared in 45 of the patients. The differences in the rate of progress of the myopia between the two eyes were annualized. The results are shown in Fig 1. In 38 patients, the difference between the refractive change in the two eyes was less than 0.37 D. In seven patients, the difference was 0.38 D or greater. These differences were subjected to statistical analysis, and a predictability rate of greater than 76% was found. In biologic material, this is extremely good. Thus, one
713
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OPHTH
ROBERT H. BEDROSSIAN
714
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38 differences 0.37 or less 7 differences 0.38 or more Correlation coefficient = 0.8112 (Predictability 76%)
jt_
-0.50
-1.00
-1.50
-2.00
MYOPIA INCREASE LEFT EYE
Fig !.-Annualized pretreatment change in myopia in 45 patients, right eye compared to left eye.
whereas the control eyes showed an increase in myopia of 0.82 D. During the second year the treated eyes had a decrease in myopia of 0.17 D, and the control eyes, an increase of 0.99 D. The third year showed the myopia in the treated eyes decreased 0.28 D, and the control eyes increased 0.91 D. In the fourth year the atropinized eyes lost 0.29 D, whereas the controls increased 0.81 D. The of average initial and final refractions Table 1 shows the results these 236 comparisons. The treated of these eyes are also shown. eyes in the first year ~hawed a These data were statistically andecrease in myopia of 0.21 D, alyzed for each year. A significance
eye can be used as a control for its fellow eye in determining whether any form of treatment alters the changing refractive error in progressive myopia. This report is based on treatment of 90 children who used atropine in the manner previously described. Sixty-two (124 comparisons) were followed for two years, and 28 (112 comparisons) used the atropine for four years.
VOLUME R6 MAY 1979
ATROPINE AND MYOPIA
715
1
TABLE
EFFECT OF ATROPINE ON MYOPIA
First yr (12.35 mo, 90 patients) Treated eye Control eye Second yr (12.53 mo, 90 patients) Treated eye Control eye Third yr (12.8 mo, 28 patients) Treated eye Control eye Fourth yr (12.4 mo, 28 patients) Treated eye Control eye
AVERAGE INITIAL REFRACTION
AVERAGE FINAL REFRACTION
CHANGE
ANNUALIZED CHANGE
-2.27 -2.30
-2.05 -3.14
+0.22 -0.84
+0.21 -0.82
-2.78 -2.39
-2.60 -3.42
+0.18 -1.03
+0.17 -0.99
-3.26 -3.01
-2.96 -3.98
+0.30 -0.97
+0.28 -0.91
-3.66 -3.18
-3.36 -4.01
+0.30 -0.83
+0.29 -0.81
level of less than 1% was found each time. (Latin squares used for analysis of variance). It is highly unlikely that these results were simply by chance. Table 2 compares the number of refractive changes that took place. In only 12 treated eyes was there an increase of myopia larger than 0.38 D. Control eyes numbered 201. No change (from +0.37 to -0.37) occurred in 152 treated eyes compared to only 35 control eyes. A decrease in myopia of greater than 0.38 D occurred in 72 atropinized eyes, whereas no control eyes showed this decrease. The largest changes in these eyes is also of interest. Table 3 shows
that the greatest increase in myopia in the atropinized eyes was 0.50 D, whereas in the control eyes it was 2.38 D. The largest decrease in the treated eyes was 1.62 D and in the control eyes was 0.25 D. It can be argued that each eye has a predestined degree of myopia and that the treatment simply postpones the inevitable refractive error. Thirty-four patients have been evaluated for a period of time after they have stopped treatment. These were patients who did not wear contact lenses at any time subsequent to their treatment, which was generally continued until the control eye showed little tendency for an increase in myopia.
TABLE
2
NuMBER OF REFRACTIVE CHANGES (236 COMPARISONS) MYOPIA INCREASE (0.38 OR MORE)
Treated eyes Control eyes
12 201
NO CHANGE TO +0.37)
(-0.37
152 35
MYOPIA DECREASE (0.38 OR MORE)
72 0
ROBERT H. BEDROSSIAN
716 TABLE 3
LARGEST REFRACTIVE CHANGES (236 COMPARISONS) LARGEST INCREASE IN MYOPIA
LARGEST DECREASE IN MYOPIA
Treated eye
-0.50
+1.62
Control eye
-2.38
+0.25
Thirty-three patients were examined between 12 and 36 months after treatment was stopped, and 24 patients, between 37 and 75 months (Table 4). In both groups, the average annualized increase in myopia was 0.06 D per year per eye. This strongly indicates that the effects of treatment are long-term. 3.00
0
OPHTH AAO
The changes during the treated and posttreatment period are summarized graphically in Fig 2. Prior to treatment, the increase in myopia was 0.91 D. Control eyes increased at about the same rate each year for the four years. Atropinized eyes had a decrease in their myopia. After treatment was concluded, the rate of myopia increased only minimally.
COMMENT No other statistically valid studies evaluating the treatment of myopia in growing children with atropine have been reported. In all areas of testing under the
,---------,---------,----------,---------,--------~.--------.
PRE-TREATMENT
1sT YEAR
2ND YEAR
3RD YEAR
4TH YEAR
POST-TREATMENT
Fig 2.-Annualized change in refraction for all study periods.
TABLE 4 PoSTTREATMENT REFRACTIVE CHANGES AVERAGE MONTHS
MAXIMUM INCREASE
MAXIMUM DECREASE
AVERAGE INCREASE
ANNUALIZED INCREASE
12 to 36 mo (33 patients)
21.1
-1.00/25 mo +0.63/24 mo
-0.10
-0.06/yr
37 to 75 mo (24 patients)
54.8
-1.62/57 mo +0.50/75 mo
-0.27
-0.06/yr
VOLUME R6 MAY 1979
ATROPINE AND MYOPIA
regimen of this study, atropine appears to be an effective form of controlling the increase in myopia. Data have been subjected to several different statistical approaches. The results show significant difference;; between the treated and control eyes. Furthermore, a long-term follow-up shows minimal changes after the treatment was discontinued. Further investigations into the mechanisms of how atropine controls the myopia are in order. The development of practical therapeutic measures would be of profound economic benefit and might enable some persons to be less dependent upon artificial means of seeing.
717
of Medical Psychology, University of Oregon Medical School, Portland assisted in develloping the plan of study. Statistical analyses were perlormed by Quentin D. Clarkson, PhD, associate professor, Regional Institute for Human Services, Portland State University, consultant, Medical Statistics, University of Oregon Health Science Center, Portland.
REFERENCES 1. Luedde WH: Monocular cycloplegia for the control of myopia. Am J Ophthalmol 15:603-610, 1932. 2. Lancaster WB: Refraction and Motility. Springfield, Ill, Charles C. Thomas Publisher, 1953, pp 114-154.
ACKNOWLEDGMENTS
3. Bedrossian RH: The effect of atropine on myopia. Read before the First International Conference on Myopia, New York, Sept 10-13, 1964.
Arthur N. Wiens, professor, and Joseph D. Matarasso, professor and head, Department
4. _ _ _ : The effect of atropine on myopia. Ann Ophthalmol 3:891-897, 1971.
Sixty-two children were treated with atropine in one eye for one year; the fellow eye was the control. The eyes were switched the second year. Twenty-eight patients were treated for four years on the same basis. Control eyes showed significant increases in myopia compared to treated eyes. Some treated eyes showed decreases in myopia; no decreases were seen in control eyes. Posttreatment data analysis indicates the effects are long-term.
MYOPIA is probably the most common condition seen by the general ophthalmologist in the more developed countries. Despite the dependency on glasses for carrying on life functions and the economic impact of changes in lenses for the growing child, many opthalmologists consider myopia an unimportant and untreatable condition. Suggestions to prevent the increase of myopia are usually met with skepticism. This study, evaluating atropine as a treatment vehicle,l- 4 was planned in consultation with persons knowledgeable in medical statistics and carried out in a private practice setting. Guidelines for selection of patients were (1) evidence of myopia increasing more than 0.50 diopter on an annualized basis, (2) ages of 8 to 13 years, (3) parents and children with sufficient intelligence and motivation to fol-
Submitted for publication Oct 22, 197R. From the University of Oregon Medical School, Portland. Presented at the 1978 Annual Meeting of the American Academy of Ophthalmology, Kansas City, Mo, Oct 22-26. Reprint requests to 3200 Main St, Vancouver, WA 98663.
Since both hereditary and environmental factors are the same in each pair of eyes, one eye was used as a control for one year while the fellow eye was treated. The following year, the eye initially used as a control became the test eye, and the original test eye was the control eye. Patients instilled 1o/o atropine in the test eye at bedtime every night. To assure that the initial and final refraction on each eye was standardized, the baseline refraction was performed one month after the test eye had begun receiving atropine. The test eye was examined under atropine and the control eye under tropicamide (Mydriacil) every three to four months for 12 months, when a final refraction was done. To determine whether using one eye as a control for its fellow eye is a valid method of control, pretreatment changes in refraction of right and left eye were compared in 45 of the patients. The differences in the rate of progress of the myopia between the two eyes were annualized. The results are shown in Fig 1. In 38 patients, the difference between the refractive change in the two eyes was less than 0.37 D. In seven patients, the difference was 0.38 D or greater. These differences were subjected to statistical analysis, and a predictability rate of greater than 76% was found. In biologic material, this is extremely good. Thus, one
713
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/
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•
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•
•
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OPHTH
ROBERT H. BEDROSSIAN
714
•
/
•
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-
38 differences 0.37 or less 7 differences 0.38 or more Correlation coefficient = 0.8112 (Predictability 76%)
jt_
-0.50
-1.00
-1.50
-2.00
MYOPIA INCREASE LEFT EYE
Fig !.-Annualized pretreatment change in myopia in 45 patients, right eye compared to left eye.
whereas the control eyes showed an increase in myopia of 0.82 D. During the second year the treated eyes had a decrease in myopia of 0.17 D, and the control eyes, an increase of 0.99 D. The third year showed the myopia in the treated eyes decreased 0.28 D, and the control eyes increased 0.91 D. In the fourth year the atropinized eyes lost 0.29 D, whereas the controls increased 0.81 D. The of average initial and final refractions Table 1 shows the results these 236 comparisons. The treated of these eyes are also shown. eyes in the first year ~hawed a These data were statistically andecrease in myopia of 0.21 D, alyzed for each year. A significance
eye can be used as a control for its fellow eye in determining whether any form of treatment alters the changing refractive error in progressive myopia. This report is based on treatment of 90 children who used atropine in the manner previously described. Sixty-two (124 comparisons) were followed for two years, and 28 (112 comparisons) used the atropine for four years.
VOLUME R6 MAY 1979
ATROPINE AND MYOPIA
715
1
TABLE
EFFECT OF ATROPINE ON MYOPIA
First yr (12.35 mo, 90 patients) Treated eye Control eye Second yr (12.53 mo, 90 patients) Treated eye Control eye Third yr (12.8 mo, 28 patients) Treated eye Control eye Fourth yr (12.4 mo, 28 patients) Treated eye Control eye
AVERAGE INITIAL REFRACTION
AVERAGE FINAL REFRACTION
CHANGE
ANNUALIZED CHANGE
-2.27 -2.30
-2.05 -3.14
+0.22 -0.84
+0.21 -0.82
-2.78 -2.39
-2.60 -3.42
+0.18 -1.03
+0.17 -0.99
-3.26 -3.01
-2.96 -3.98
+0.30 -0.97
+0.28 -0.91
-3.66 -3.18
-3.36 -4.01
+0.30 -0.83
+0.29 -0.81
level of less than 1% was found each time. (Latin squares used for analysis of variance). It is highly unlikely that these results were simply by chance. Table 2 compares the number of refractive changes that took place. In only 12 treated eyes was there an increase of myopia larger than 0.38 D. Control eyes numbered 201. No change (from +0.37 to -0.37) occurred in 152 treated eyes compared to only 35 control eyes. A decrease in myopia of greater than 0.38 D occurred in 72 atropinized eyes, whereas no control eyes showed this decrease. The largest changes in these eyes is also of interest. Table 3 shows
that the greatest increase in myopia in the atropinized eyes was 0.50 D, whereas in the control eyes it was 2.38 D. The largest decrease in the treated eyes was 1.62 D and in the control eyes was 0.25 D. It can be argued that each eye has a predestined degree of myopia and that the treatment simply postpones the inevitable refractive error. Thirty-four patients have been evaluated for a period of time after they have stopped treatment. These were patients who did not wear contact lenses at any time subsequent to their treatment, which was generally continued until the control eye showed little tendency for an increase in myopia.
TABLE
2
NuMBER OF REFRACTIVE CHANGES (236 COMPARISONS) MYOPIA INCREASE (0.38 OR MORE)
Treated eyes Control eyes
12 201
NO CHANGE TO +0.37)
(-0.37
152 35
MYOPIA DECREASE (0.38 OR MORE)
72 0
ROBERT H. BEDROSSIAN
716 TABLE 3
LARGEST REFRACTIVE CHANGES (236 COMPARISONS) LARGEST INCREASE IN MYOPIA
LARGEST DECREASE IN MYOPIA
Treated eye
-0.50
+1.62
Control eye
-2.38
+0.25
Thirty-three patients were examined between 12 and 36 months after treatment was stopped, and 24 patients, between 37 and 75 months (Table 4). In both groups, the average annualized increase in myopia was 0.06 D per year per eye. This strongly indicates that the effects of treatment are long-term. 3.00
0
OPHTH AAO
The changes during the treated and posttreatment period are summarized graphically in Fig 2. Prior to treatment, the increase in myopia was 0.91 D. Control eyes increased at about the same rate each year for the four years. Atropinized eyes had a decrease in their myopia. After treatment was concluded, the rate of myopia increased only minimally.
COMMENT No other statistically valid studies evaluating the treatment of myopia in growing children with atropine have been reported. In all areas of testing under the
,---------,---------,----------,---------,--------~.--------.
PRE-TREATMENT
1sT YEAR
2ND YEAR
3RD YEAR
4TH YEAR
POST-TREATMENT
Fig 2.-Annualized change in refraction for all study periods.
TABLE 4 PoSTTREATMENT REFRACTIVE CHANGES AVERAGE MONTHS
MAXIMUM INCREASE
MAXIMUM DECREASE
AVERAGE INCREASE
ANNUALIZED INCREASE
12 to 36 mo (33 patients)
21.1
-1.00/25 mo +0.63/24 mo
-0.10
-0.06/yr
37 to 75 mo (24 patients)
54.8
-1.62/57 mo +0.50/75 mo
-0.27
-0.06/yr
VOLUME R6 MAY 1979
ATROPINE AND MYOPIA
regimen of this study, atropine appears to be an effective form of controlling the increase in myopia. Data have been subjected to several different statistical approaches. The results show significant difference;; between the treated and control eyes. Furthermore, a long-term follow-up shows minimal changes after the treatment was discontinued. Further investigations into the mechanisms of how atropine controls the myopia are in order. The development of practical therapeutic measures would be of profound economic benefit and might enable some persons to be less dependent upon artificial means of seeing.
717
of Medical Psychology, University of Oregon Medical School, Portland assisted in develloping the plan of study. Statistical analyses were perlormed by Quentin D. Clarkson, PhD, associate professor, Regional Institute for Human Services, Portland State University, consultant, Medical Statistics, University of Oregon Health Science Center, Portland.
REFERENCES 1. Luedde WH: Monocular cycloplegia for the control of myopia. Am J Ophthalmol 15:603-610, 1932. 2. Lancaster WB: Refraction and Motility. Springfield, Ill, Charles C. Thomas Publisher, 1953, pp 114-154.
ACKNOWLEDGMENTS
3. Bedrossian RH: The effect of atropine on myopia. Read before the First International Conference on Myopia, New York, Sept 10-13, 1964.
Arthur N. Wiens, professor, and Joseph D. Matarasso, professor and head, Department
4. _ _ _ : The effect of atropine on myopia. Ann Ophthalmol 3:891-897, 1971.
