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Medical Forum / General / Vision / August 2004The O'Leary Bifocal Study -- and discussion, for Cathy
The Wildsoet Lab Controlling Myopia Progression - A Confusing Story The dilemma of managing young progressing myopes. The O'Leary study. The Comet Study Two recently published clinical trials involving under-correction and PALs as alternative myopia control strategies add more rather than less confusion. "Eye correction is seriously short-sighted" was the headline to an article by Andy Coghlan and Michel le Page in the New Scientist late last year (11-26-02) covering a randomized clinical trial of undercorrection as a treatment for myopia progression in children. The New Scientist article was referring to a paper published in the journal, Vision Research (2002, 42: 2555-9), describing a 2-year Malaysian-based study comparing the effects of undercorrecting myopia with full correction on myopia progression in children. The message from the principal investigator on this study, Dr O'Leary, to doctors, patients and parents, as reported in the New Scientist article is "No glasses is the worst option of all, But don't undercorrect. GO for full correction." The New Scientist article is likely to cause both alarm in patients and guilt in parents and clinicians alike with its headline statement: "Millions of people worldwide may have worse vision and even be more likely to go blind because of a long-held but misguided idea about how to correct short-sightedness." The article goes on to claim that: "A study intended to confirm the theory has instead been stopped because the children's eyesight was getting worse." A closer examination of the Vision Research paper covering the Chung et al study suggests that there are reasons to question under-correction as a management study for all progressing myopes but also a case of serious exaggeration by the New Scientist reporters. The Chung et al study is a small (n=94), 2 year randomized and masked prospective study comparing the effects of full-time undercorrection (UC, by approx 0.75 D) with full-time fully correction (FC) in young myopes (mean: -2.86 D). The study group comprised approximately 1.4 time the numbers of girls as boys with Chinese and Malay ethnic groups being approximately equally represented. Over the 2 years of the study, the full-correction group showed a progression of 0.77 D compared to the UC group that exhibited a progression of 1.00 D. [The -1/2 diopter per year appears to be normal for kids in a "reading" environment of this age -- as established by Dr. Francis Young. The difference between test/control group was -0.12 diopter/year of the O'Leary study. OSB] Rates of eye growth also differed between the two groups, as expected, being slower for the FC group. What message can we take home from the Chung et al study? Unfortunately this study is sparse on detail and thus difficult to interpret. We are told nothing about the refractive distribution of the subjects although we are told that analyses were based on 4 refractive error categories, including one covering >3 D myopia. We can not assume that all refractive groups would have behaved similarly for example, the more recently published COMET study observed significant refractive error differences (see below). We are not provided with any information about the binocular vision or accommodative status of the subjects yet these parameters are predicted to also influence outcomes based on other studies (see COMET study below). Finally, while full compliance was defined as wearing the glasses for at least 8 hr per day, we are not told when the children typically went to bed. Thus it seems impossible to rule out the possibility that compliant children from either or both treatment groups may have undertaken near activities without their glasses at night. It is interesting to compare progression rates for the two groups in the Chung et al study with values from the more recently published COMET study, converted in both cases to a D per year rate. The progression rate for the UC group (-0.5 D per year) corresponds closely to the mean rate reported for participants allocated single vision lenses in the COMET study (-0.49 D per year). A conclusion based on this comparison alone would be that undercorrection neither exacerbates or slows the progression of myopia, when applied unselectively. This outcome is predicted if we assume that the benefit of undercorrection is limited to those with poor accommodation. Animal model studies predict increased (myopic) eye growth with sustained poor accommodation in fully corrected eyes (see Wildsoet, 1997, for a more extensive discussion of animal-based emmetropization studies and their clinical implications). However undercorrection should improve the state of focus at near as less accommodation is required. A potential parallel with animal studies involves the imposition of binocular low powered positive lenses on young monkeys; their eye growth slows, presumably because their eyes now have almost perfect focus at near distances, the limit of the visual world of these young animals (Smith & Hung, 1999). It might also be argued based on animal studies, that because the undercorrection strategy imposes myopic defocus at distance, that eye growth should be slowed in all children. However as school children spend little time outdoors focussed on more distant tasks, they are likely to gain little benefit from this correction strategy in terms of reduced eye growth. Nonetheless, this interpretation leaves us with the dilemma of explaining why full correction slows myopia progression (rate: -0.39 D per year) in a population that is typically more susceptible to myopia compared to Western populations (and the COMET study subject base). However children from the FC group with poor accommodation and/or over-convergence problems had potentially the most to benefit from not wearing their glasses at night. Only another study will provide us with the answer as to whether such behavior is the explanation for the apparently slowed progression of FC myopes. The message that the Chung et al study should send to other would-be clinical myopia researchers is that randomization and masking are good but too little information about the participants can still render even the most well-controlled study useless in terms of clinical applicability. As a final aside, the New Scientist article quotes the principal investigator as saying: "The study was meant to run for three years but after two years, when we found out we were making the children's eyes worse, we had to stop it prematurely." This statement seems at odds with the statement in the methods section of the Vision Research paper that: "...results were only analyzed after the last reading of the last patient was collected." What really did happen? References Chung K, Mohidin N, O'Leary DJ. Undercorrection of myopia enhances rather than inhibits myopia progression. Vision Res. 2002, 42: 2555-9. Smith EL 3rd, Hung LF. The role of optical defocus in regulating refractive development in infant monkeys. Vision Res. 1999, 39: 1415-35. _______________________________________ Progressive addition lenses (PALs) should not be prescribed as a myopia-control treatment Evidence from The COMET (Correction of Myopia Evaluation Trial) study A randomized clinical trial of progressive addition lenses (PALs) for control of the myopia in children. The long awaited data from this multi-center US-based study, funded by the National Eye Institute (NEI), was published earlier this year in the prestigious journal, Investigative Ophthalmology and Visual Science (2003, 44: 1492-1500). The results of this study were disappointing, adding to an accumulating number of studies reporting only limited benefit from variable focus lenses. Indeed, around the same time as the paper appeared, NEI released a statement covering the study http://www.nei.nih.gov/news/statements/comet.htm indicating that progressive addition lenses should not be prescribed as a myopia-control treatment. What is the principle behind prescribing variable focus spectacle lenses for myopia control and why might the results of clinical trials not bear out the expected benefit of such lenses? Three key factors have driven the use of these lenses for myopia control: 1. accumulating data linking myopia with excessive near work; 2. observed association between high accommodative lags and progressing myopia; and 3. increased eye growth, as characteristic of myopia, in animals exposed to negative defocusing lenses. Both accommodative lags and negative lenses imposed on otherwise normal eyes, create conditions of hyperopic defocus where the true image plane lies behind the retina (the seeing layer of the eye). The ocular growth response to defocusing lenses reported in animal studies appears to be compensatory, reducing the amount of defocus experienced by the eye with the defocusing lens in place. It is conceivable that a similar growth response could be triggered in humans by accommodative errors during excessive near work. The resulting myopia, if left uncorrected, should lessen the demand on accommodation and thus accommodative lag. However, such changes are typically corrected with an updated prescription, thereby reintroducing the problem triggering the growth response. The main outcome of the COMET study was a small but significant slowing of myopia progression with PAL lenses that was limited to the first of the 3 years of the clinical trial. The 3-year difference in progression between participants wearing PALs compared to those wearing regular (single vision; SV) lenses was 0.20 +/-0.08 D. The study cannot be faulted in terms of its design it is a large (469 participants) randomized double-masked, multi-center (4 sites), ethnically diverse study with an excellent record of retention and masking throughout. None-the-less there are weaknesses. All children in the PAL group were prescribed the same +2 D lens addition based on an earlier report (Leung & Brown, 1999) that +2 D additions were more effective than +1.5 D additions in controlling progression of myopia in adolescents. It could be argued that lenses intended to correct near focusing errors should be designed on an individual basis. A second weakness of the study is the failure to verify that the children used the near addition during close work although the lenses were fitted in the spectacle frames in a way to encourage reading through the near addition. In general children have little incentive to use the near addition of their PALs; indeed, the distortions occurring in the lower periphery of theses lenses might act as a disincentive. In contrast, adults who are typically prescribed them to compensate for failing near focusing ability have the incentive of clear near vision to use the lower portion of their lenses. It is of potential significance that the study reporting the most promising outcome using PALs also involved adolescents who may have been better able to follow instructions in the use of their lenses. Although the overall trend of less than 0.50 D difference in progression in myopia between the PAL and SV groups after 3 years can not justify the wide-spread prescribing of PAL lenses for myopia control, a closer inspection of the COMET data provides some support for their more limited prescribing. Specifically, those with low myopia (<2.25 D initially) and low accommodation (<2.57 D in respond to a 3 D demand), showed greater benefit from PALs (0.55 D treatment effect for those showing both low myopia and low accommodation). It is of interest to know whether or not low accommodation was associated with a tendency to overconverge at near. There is suggestion from the COMET data that those exhibiting near esophoria and orthophoria showed more benefit from PALs compared to those with near exophoria although the differences were not statistically significant. Nonetheless this trend is consistent with other studies showing greater treatment effects in near esophoric participants (e.g. Grosvenor et al, 1987; Goss & Grosvenor, 1990; Fulk et al, 2000). That such participants would show greater accommodative lags through their normal SV corrections is also predictable. Where to now? The COMET study provides convincing evidence that PALs are not for everyone. It might also be argued that spectacles are not the optimum form of correction for proving near additions to young children because of their more limited understanding of the issues involved. Dr Tom Aller OD (San Bruno, California) has reported promising retrospective data involving variable focus soft contact lenses as a myopia control treatment. Look out for follow-up data from a randomized clinical trial of the same! As a final aside, the report on the COMET study makes the curious observation that the treatment effect was limited to the first year of the 3 years of the study. Overall, there were no differences in progression between the PAL and SV groups across the 2nd and 3rd years of the study. The authors of the report put forward a number of possible explanations for the short-term nature of the treatment effect, including the possibility that a single environmentally-based treatment intervention may have only a limited capacity to restrain progression that is influenced by additional visual and genetic factors as well. As studies involving drug intervention (Shih et al, 2001, Chua et al, 2002), and contact lenses (Khoo et al, 1999) for myopia control have reported similar time constraints related to treatment efficacy, this issue suggests a major reevaluation of the hypotheses underlying various treatment strategies. References Aller T, Grisham, D. Myopia control with bifocal contact lenses, Optom Vis Sci (Suppl), 2000, 77: 187. Aller T. Myopia progression with bifocal soft contact lenses A twin study Optom Vis Sci (Suppl), 2002, 79: 179. Chua W-H, Balakrishnan V, Tan D, Chan Y-H, ATOM Study Group. Efficacy results in the treatment of myopia (ATOM) study. ARVO 2003, Abstract#3119. Fulk GW, Cyert LA, Parker DE. A randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria. Optom Vis Sci. 2000, 77: 395-401. Goss DA, Grosvenor T. Rates of childhood myopia progression with bifocals as a function of nearpoint phoria: consistency of three studies. Optom Vis Sci. 1990. 67: 637-40. Grosvenor T, Perrigin DM, Perrigin J, Maslovitz B. Houston Myopia Control Study: a randomized clinical trial. Part II. Final report by the patient care team. Am J Optom Physiol Opt. 1987, 64: 482-98. Gwiazda J, Hyman L, Hussein M, Everett D, Norton TT, Kurtz D, Leske MC, Manny R, Marsh-Tootle W, Scheiman M. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci. 2003, 44: 1492-500. Khoo CY, Chong J, Rajan U. A 3-year study on the effect of RGP contact lenses on myopic children. Singapore Med J. 1999, 40: 230-7. Leung JT, Brown B. Progression of myopia in Hong Kong Chinese schoolchildren is slowed by wearing progressive lenses. Optom Vis Sci. 1999, 76: 346-54. Shih YF, Hsiao CK, Chen CJ, Chang CW, Hung PT, Lin LL. An intervention trial on efficacy of atropine and multi-focal glasses in controlling myopic progression. Acta Ophthalmol Scand. 2001, 79: 233-6. Wildsoet CF. Active emmetropization evidence for its existence and ramifications for clinical practice. Ophthalmic Physiol Opt 1997, 17: 279-290. > The O'Leary study. The Comet Study > Two recently published clinical trials involving > under-correction and PALs as alternative myopia control strategies > add more rather than less confusion. You're confused because you stubbornly believe in some predictable tendency for human eyes to change physical structure based on different spectacle corrections. Animal studies show a potential effect in very early life, but also an age where the adaptive response ceases. In humans of school age and after, most studies show no difference. Some show minor effects. Why is that confusing? It says we should not prescribe -10D lenses for +1.5D infants. -MT > It says we should not prescribe -10D lenses for +1.5D infants. Hello Mr. tyner. Yesterday the national television broadcasted that ophtalmology is looking to infants to prevent incept of refractive error. There was in show a doctor who was examining the eyes of a newborn. The contention was that if they could discover early refractive errors, they could correct them quickly and so save many people... I was a little bit shocked, because such test have been published by Dr. Bates in 1920, when he wrote that he had observed infants eyes every half an hour with the retinoscope and recorded that refraction changes very much and this is normal. What are doing these Italian doctors to check infants, for what? If there a more dreadful thing than to think of a newborn child with corrective glasses??? Isn't it not criminal? > I was a little bit shocked, because such test have been published by > Dr. Bates in 1920, when he wrote that he had observed infants eyes > every half an hour with the retinoscope and recorded that refraction > changes very much and this is normal. You're only shocked because you believe everything Dr. Bates wrote. > If there a more dreadful thing than to think of a newborn child with > corrective glasses??? > > Isn't it not criminal? Dreadful. Just dreadful. -MT > > Isn't it not criminal? > > Dreadful. Just dreadful. Definitely not criminal. I knew a woman here who's grandchild was going to get contacts, and was just a baby. The kid ended up not getting contacts, but had surgery instead. Of course maybe it would be better if the child grew up having vision only in one eye. Although, Rishi would talk to the baby and convince them to do Bates therapy.  SignatureDan Abel Sonoma State University AIS dabel@sonic.net snip > > If there a more dreadful thing than to think of a newborn child with > > corrective glasses??? I think it is more dreadful to think of a newborn child developing severe amblyopia and blindness due to not having corrective glasses. Dr Judy Subject: Mike is confused about the proven behavior of the natural eye -- and my statments about it. Re: The behavior of the adolescent primate eye. What I said was that the a population of primate eyes will change in a negative direction when you apply an "accommodation delta" of -0.80 diopters. When this is done, the refractive status of the control group follows the predictable time-constant equation of delta * e ^ (-t / TAU) where TAU = 100 days. This is predicted and expected behavior. You keep insisting that "this does not happen", when in fact it will happen every time your do this repeatable, scientific experiment. No, Mike, you do not understand. Best, Otis Engineer ***** > > The O'Leary study. The Comet Study > > Two recently published clinical trials involving [quoted text clipped - 4 lines] > for human eyes to change physical structure based on different spectacle > corrections. > Animal studies show a potential effect in very early life, but also an age > where the adaptive response ceases. Bull sh.t! The test that Francis Young ran concerned ADOLESCENT PRIMATES, since several were found to be pregnant while this test was in progress. No this issue is NOT "neonatal", and the control process does not stop as demonstrated objectively and scientifically hy Francis Youngs direct testing. "Neo-natal" has nothing to do with his test. You are confused -- by your own preferred misunderstandings of the dynamic nature of the primate eye. > In humans of school age and after, most studies show no difference. Again, you are confused. I will post the analysis of this test -- since you don't understand the nature of scientific proof. Some > show minor effects. > > Why is that confusing? > It says we should not prescribe -10D lenses for +1.5D infants. > -MT > Subject: Mike is confused about the proven behavior of the > natural eye -- and my statments about it. [quoted text clipped - 11 lines] > > This is predicted and expected behavior. Please provide or cite the experimental proof of your notion. DrG > You keep insisting that "this does not happen", > when in fact it will happen every time your [quoted text clipped - 47 lines] > >> -MT Dear Mike, Subject: You are confused about NEONATAL. Neonatal does not mean ADOLESCENT. Get it? Are you confused about that point? Further, I stated that the natural eye would CHANGE ITS REFRACTIVE STATUS. I said absolutly NOTHING about CAUSE of anything. I just stated what would happen if you performed a very basic scientific operation concerning the behavior of the NATURAL primate eye. Best, Otis Engineer ***** Mike -- please read this -- this time: DR. YOUNG'S EXPERIMENT Dr. Young used Macaca Nemestrina (Pigtail) monkeys in his test. The monkeys were placed in a chair with their heads situated so their maximum visual distance was limited. The hoods were not more than 20 inches from the eyes of the monkeys at the furthest point, and averaged around 14 inches. Nine adolescent animals were selected and a control group was maintained. Their refractive status was measured at two week intervals. The experiment was continued for eleven months. The measured mean focal status for these monkeys is shown on the FORTRAN generated graph. Three monkeys were removed from the test after four months due to pregnancy and sickness. __________________________ Paper 26 By Otis Brown THE RESPONSE OF A DYNAMIC EYE TO A CONFINED VISUAL ENVIRONMENT "Part of the art and skill of the engineer and of the experimental physicist is to create conditions in which certain events are sure to occur." Eugene Wigner A CRITICAL EXPERIMENT THAT DEFINES THE EYE'S BEHAVIOR Critical experiments are those experiments that allow us to choose between two major versions of factual truth. Without this check of physical reality, we can never determine the behavioral characteristic of the normal eye. The concept that the normal eye is a rigid system is potentially a valid concept -- until we actually make measurements of the impact that a confined environment has focal state of the normal eye. When we make the measurements, we find that the Helmholtz-passive theory is not accurate in accounting for the experimental data. THE EXISTENCE OF A DYNAMIC CONTROL SYSTEM IS REQUIRED FOR ACCURATE FOCUS The normal human and primate eye maintain a high degree of focal accuracy while major optical components change in an unpredictable manner. (1) The equation, developed from a dynamic model that is capable of accounting for this degree of accuracy, also predicts that the eye's focal status will display a time-constant effect to a step change in its visual environment. (2) (3) The predictions of this theory are compared on a qualitative and semi-quantitative basis with a Helmholtz-passive theory of the normal eye's behavior. A THEORETICAL PREDICTION While such a test cannot be carried out on humans, monkeys can be subjected to a step-change in their visual environment. (4) The following equation predicts the eye's focal status as a function of time: Focus = Offset + Accommodation + Delta * [1 - EXP( -t/TAU ) ] The required values are the average value of accommodation before and after the start of the test. The time-constant, TAU, has an approximate value of 100 days for pigtail macaque monkeys. The physiological offset is a measurable characteristic of the human and primate eye. It has an approximate value of +1.5 diopters. Further experiment and measurement will be required to establish greater accuracy for these fundamental constants of the normal eye's behavior. The average value of accommodation is determined by the visual environment of the eye. For instance, if a monkey is kept in a hooded visual environment of 20 inches, his environment will have a minimum value of -2 diopters. If he spends 50 percent of his time looking at 20 inches (-2 diopters), and the other 50 percent of his time looking at 12 inches (-3.2 diopters), his average value of accommodation will be -2.6 diopters. Alternatively, if he spends 100 percent of his time looking at 15 inches (- 2.6 Diopters), his visual environment will be -2.6 Diopters. By this technique of quantitative estimation, and by actual observational measurements, we can establish the average value of accommodation for monkeys kept in various visual environments. The following values are preliminary estimates: ACCOMMODATION STATUS FOR POPULATIONS OF MONKEYS WILD CAGED HOODED - 0.8 Diopters -1.8 Diopters - 2.6 Diopters If monkeys in a caged visual environment are placed in a hooded environment, their eyes will experience a step-change of: 1.8 - 2.6 = - 0.8 Diopters Before the start of the test the focal status is: (At t = 0 ) Focus = 1.5 + (-1.8) + (0) * [ 1 - EXP ( - 0 / 100 ) ] Focus = -0.3 Diopters After 294 days their focal status will be: Focus = 1.5 + (-1.8) + (-0.8) * [1 - EXP ( - 294 / 100 ) ] Focus = - 1.1 Diopters DR. YOUNG'S EXPERIMENT Dr. Young used Macaca Nemestrina (Pigtail) monkeys in his test. The monkeys were placed in a chair with their heads situated so their maximum visual distance was limited. The hoods were not more than 20 inches from the eyes of the monkeys at the furthest point, and averaged around 14 inches. Nine adolescent animals were selected and a control group was maintained. Their refractive status was measured at two week intervals. The experiment was continued for eleven months. The measured mean focal status for these monkeys is shown on the FORTRAN generated graph. Three monkeys were removed from the test after four months due to pregnancy and sickness. The refractive characteristics of the control group did not exhibit the time- constant effect demonstrated by the monkeys subjected to a step change in their visual environment. (Figure 1) TWO THEORIES OF FOCAL GROWTH There are two fundamental theories of how the normal eye sets its focus while growing. One theory can be described as a Helmholtz-heredity theory of the eye's focal growth. This theory states that the cause of nearsightedness is purely genetic in origin, and asserts that the visual environment has no effect on the focal state of the normal eye. This is a passive theory of the normal eye's behavior. For this experiment the prediction of this theory is that there should be no change in the focal status of monkeys who experience a delta in their visual environment, since their genetic characteristic is not altered by the experimental situation. Alternatively, the prediction of this theory is that no difference in focal status should develop between the normal eyes of the test group relative to the control group. A dynamic (feedback control) theory states that the eye continuously servos, or sets its focus based on the eye's average value of accommodation. This theory predicts that there will be a time-constant response to a delta in the eye's value of accommodation. (FIGURE 1) THIS GRAPH SHOWS THE PREDICTIONS OF TWO THEORIES DAYS FEED- MEAS- DIOPTERS NEARSIGHTED INTO BACK URED -1.1 -1.0 -.9 -.8 -.7 -.6 -.5 -.4 -.3 -.2 -.1 TEST ................................................... 0 -.33 -.33 <-----------------------------------<< M 7 -.38 Accommodation Delta F H 14 -.43 -.40 - 0.8 Diopters F M H 21 -.48 F H 28 -.53 -.48 F M H 35 -.57 F H 42 -.60 -.60 M H 49 -.64 F H 56 -.67 -.71 MF H 63 -.70 Measured (M) F H 70 -.73 -.78 Status >>---> M F H 77 -.76 F H 84 -.78 -.83 M F H 91 -.81 F H 98 -.83 -.87 M F H 105 -.85 F H 112 -.87 -.90 M F H 119 -.89 F H 126 -.90 -.95 M F H 133 -.92 F H 140 -.93 -1.00 M F H 147 -.95 F Test Group (F) H 154 -.96 -1.05 M F <-----<< Prediction H 161 -.97 F H 168 -.98 -1.10 M F H 175 -.99 F H 182 -1.00 -1.08 M F H 189 -1.01 F H 196 -1.02 -1.06 M F Control Group (H) H 203 -1.02 F Prediction >>--------> H 210 -1.03 -1.07 M F H 217 -1.04 F H 224 -1.04 -1.08 M F H 231 -1.05 F H 238 -1.06 -1.09 M F H 245 -1.06 F H 252 -1.07 -1.10 M F H 259 -1.07 F H 266 -1.07 -1.10 MF H 273 -1.08 F H 280 -1.08 -1.10 MF H 287 -1.08 F H 294 -1.09 -1.10 MF H ................................................... -1.1 -1.0 -.9 -.8 -.7 -.6 -.5 -.4 -.3 -.2 -.1 The best way to choose between these two competing theories is to compare their predictions on a qualitative and semi-quantitative basis. On a qualitative basis the dynamic theory predicts a net change in focal state of the test group relative to the control group. The passive theory predicts no change. The passive theory can not be put in a form which will yield quantitative predictions for the eye's focal status as a function of time, and for that reason cannot be compared on a quantitative basis. THE FOCAL GROWTH TRANSFER FUNCTION The Laplace transfer function for the long-term focal control behavior of the normal eye is: (2) 1/ (TAU s + 1 ) The impulse (perturbation) time response of this function is: (5) Focus = Offset + Accommodation - Impulse * EXP (-t/TAU ) This time-domain equation represents the basic underlying dynamic behavior characteristic of the normal eye when it is subjected to a sudden change in its accommodation status. FOCAL STATUS MEASUREMENT If the estimated value of accommodation ( - .8 Diopters) for a population of wild monkeys is used in the impulse equation, the result is: Focus = 1.5 + ( -.8 ) - ( 0 ) * EXP ( - t / TAU ) Focus = + 0.7 Diopters The plus indicates that the normal eyes of these monkeys have a normal (positive) focal state. The focal status of the normal eye (hyperopia) is measured with a plus lens. The measurement for the normal eye's focal status is made with the individual reading the eye chart at 20/20. Increasingly stronger positive lenses are placed in front of the eye until a lens strong enough to blur the 20/20 line is obtained. This lens strength is the specific value for the focal state of the normal eye. A positive focal state (sometimes called hyperopia) is the condition of the normal eye. If the eye is placed in a confined visual environment, the eye will gradually change its focal status in a negative direction. When the normal eye changes its focal state to a minus value the eye is said to be nearsighted. This result is observed in populations of Naval students. (6) FOCAL STATE CORRELATION TO THE SNELLEN EYE CHART Initially, the monkeys in this experiment were, on the average, slightly nearsighted. Their eyes were 20/25 at the start of the test and became more myopic (20/80) at the end of the test. Wild monkeys have 20/20 vision with an average focal state of +0.7 diopters. THE CORRELATION COEFFICIENT DATA AND CALCULATION (See Fortran graph for data.) Unexplained Variation = 0.07227 Explained Variation = 1.23809 Total Variation = 1.31037 Correlation Coefficient = 0.97203 This data, which represents the fundamental behavior characteristic of the normal eye, correlates with the equation: Focus = Offset + Accommodation + Delta * [1 - EXP(-t/TAU ) ] STUDENTS "T" CALCULATION FOR THE CORRELATION COEFFICIENT Was the correlation coefficient from this experiment accidental? Did Dr. Young randomly obtain 0.972 for the monkeys in the test when the actual population correlation coefficient was zero? This assertion can be checked by use of the students "t" distribution: r t = ------------------------ ___________________ / 2 / 1 - r \ / --------- \/ n - 2 Where: n = 23 (Number of measurements made) r = 0.97 (Correlation coefficient from the experiment) for v = 21 (Degrees of freedom = 23 - 2) t = 3.819 (Value for 99.9 percent confidence limit) .001 2 t = 0.97 / SQRT [ ( 1 - 0.97 ) / ( 23 - 2 ) ] t = 18.28 Since 18.28 exceeds 3.819 (the 99.9 percent confidence limit) we can reject the idea that the Helmholtz-passive concept is correct. There is a very high correlation between the average value of accommodation and the focal state of the normal eye. THE REPEATABILITY OF THIS EXPERIMENT TO OBTAIN THE SAME CORRELATION COEFFICIENT The Range of Possible Values for the Correlation Coefficient If the experiment is repeated 100 times, will we get the same correlation coefficient? What is the range of correlation coefficients that we can expect from the large population of normal eyed individuals? If from a bivariate population with a correlation coefficient, RHO, all samples of size n are taken, then: Z - m (r) (RHO) z = ----------------- Sigma Where: Z(r) = 0.5 * ln ( (1 + r) / (1 - r) ) m(RHO) = 0.5 * ln ( (1 + RHO) / (1 - RHO) ) Sigma = 1 / Square Root (n - 3) z = Abscissa for area under probability curve Values: r = 0.97 Z(r) = 2.092 n = 23 Sigma = 0.2236 Z = +/- 2.58 for 99 percent confidence Area = 1.0 - 2 * ( 0.495 ) = .01 By rearranging the equation: m(RHO) = Z(r) +/- (Sigma * z) using values: r = 0.97, n = 23, z = +/- 2.58 m(RHO) = 2.092 +/- 0.57688 Using look-up tables: m(RHO) = 2.6688 and therefore the upper limit for RHO is 0.99 m(RHO) = 1.5151 and therefore the lower limit for RHO is 0.90 In other words, given the results of this experiment, we can conclude that it is virtually certain that the large-scale population coefficient will lie between 0.90 and 0.99 for all primate eyes. There is a very high correlation between the normal eye's accommodation system and the focal state of the normal eye. The concept that the normal eye behaves as a (dynamic) neurological control system is strongly supported by direct factual data. The concept that the normal eye is passive in its behavioral characteristic is rejected by direct factual data. These statistical tests are standard and conclusively demonstrate the truth that the normal eye DOES NOT obey the Helmholtz-passive model for the normal eye's behavior. It is very unlikely that future experiments will support the Helmholtz-passive model of the normal eye's behavior. CONCLUSIONS There are two powerful conceptual tools available for dealing with difficult servo problems -- analysis and synthesis. Since it is almost impossible to gain access to the accommodation system (that controls the eye's long-term focus), an indirect approach is required to establish the fundamental behavior characteristic of the normal human eye. An indirect approach results in the development of mathematical models. By constructing two reasonable physiological models for the normal eye's behavior, we can develop two sets of theoretical predictions. We can then decide, on the basis of direct experimentation, which model is more fully confirmed by the available experimental evidence. An analysis of the focal design requirements of the normal eye demonstrates that each eye must maintain a dynamic accuracy of better than 1.5 percent while growing to maintain normal vision. (5) In synthesis, we develop a dynamic design which will account for the maximum number of facts known about the normal eye's focal setting action. Since the human body relies on feedback control principles in its design -- accommodation, temperature, and pH levels -- we find it appropriate to apply this concept to the eye's focal behavior. The opposite suggestion, that the normal eye ignores the accommodation signal while growing, leads to a theory that is incapable of accurate quantitative predictions. This analysis/synthesis approach points to an equation that accurately predicts the dynamic behavior of the human and primate eye. The equation can support a procedure that will be effective in preventing nearsightedness, if the eye's dynamic behavior is understood, and the preventative procedure is assiduously carried out. Accuracy and stability of the normal eye's behavior can be understood by modeling the eye as a servomechanism. An eye with this type of control system will exhibit a time-constant effect if subjected to a step-change in the eye's visual environment. In this experiment a "brute force" change was induced in the average visual environment. A time-constant response was measured in the eye's focal status. The theory which is compared to this concept is a Helmholtz-passive theory of the eye's focal behavior. The dynamic analysis leads to a general equation for the long-term behavior of the normal eye. On the basis of this experiment we suggest that the dynamic (cybernetic) model is strengthened. As with most mathematical models, certain effects (e.g., noise and perturbations in the system) have not been included. These effects will be assessed and represented in later chapters. Our experience, however, indicates that this model is very accurate with respect to other dynamic tests that have established the normal eye's behavioral characteristic. In the absence of any other experimentally confirmed equation we can tentatively conclude that this test confirms the accuracy of this equation -- within the limits imposed by the expeerimental data that is available to us. REFERENCES 1. Young, F., Leary, G. VISUAL CHARACTERISTICS OF APES AND PERSONS, (207-225) Progress in Ape Research (1977) 2. Brown, O., Berger, R. A NEARSIGHTEDNESS COMPUTER, (343-346), The 7th Annual New England Bioengineering Conference (1979) 3. Brown, O., Young, F. PHYSIOLOGICAL MODELING: THE LONG-TERM GROWTH OF THE EYE, (133-136) The 8th Annual New England Bioengineering Conference (1980) 4. Young, F. THE EFFECT OF RESTRICTED VISUAL SPACE ON THE PRIMATE EYE, American Journal of Ophthalmology, Vol. 52, No. 5, Part II, November 1961 5. Brown, O., Young, F. THE RESPONSE OF A SERVO CONTROLLED EYE TO FOCAL PERTURBATIONS, The 2nd Annual conference of the IEEE Engineering in Medicine and Biology Society (1980) 6. Hayden, R. DEVELOPMENT AND PREVENTION OF MYOPIA AT THE UNITED STATES NAVAL ACADEMY, Archives of Ophthalmology Volume 25, #4 (April 1941) ___________________________ > > The O'Leary study. The Comet Study > > Two recently published clinical trials involving [quoted text clipped - 16 lines] > > -MT Look at Otis bob and weave and pirhouette. DrG > The Wildsoet Lab > [quoted text clipped - 333 lines] > and ramifications for clinical practice. Ophthalmic > Physiol Opt 1997, 17: 279-290. Dear DrG, Re: > Look at Otis bob and weave and pirhouette. DrG Interesting comment -- since I posted it to clarify Cathy's question. But if you wish some sharper remarks I will be pleased to supply them. My remarks simply reflect "things as they are", and almost all of the remarks concerned the poor quality of to O'Leary study -- and I certainly agree on that point. Your remaraks more reflect the fact that the foxes are in charge of the chicken coop -- more than anything else. Best, Otis > The Wildsoet Lab > [quoted text clipped - 26 lines] > group showed a progression of 0.77 D compared to the UC > group that exhibited a progression of 1.00 D. minor snip > It is interesting to compare progression rates for the two > groups in the Chung et al study with values from the more recently [quoted text clipped - 21 lines] > distances, the limit of the visual world of these young animals > (Smith & Hung, 1999). More recemt animal studies suggest that accommodation in not a factor in eye growth stimulated by minus lenses. There is no confusion here for me; neonatal animal eyes do not provide a model for non neonatal human eyes. Animal eyes that are not naturally myopic and do not naturally develop myopia may provide a model for human eyes that naturally do not become myopic, but do not provide a model for human eye that do become myopic. Any hypothesis for prevention of myopia that is based on the evidence from animal studies is based on evidence that is irrelevant to humans. Dr Judy snip rest of message > > The Wildsoet Lab > > [quoted text clipped - 54 lines] > > distances, the limit of the visual world of these young animals > > (Smith & Hung, 1999). Dear Dr. Judy, Thanks for your commentary on your decision to exclude all DIRECT experimental data proving the dynamic behavior of both the monkey-primate adolescent, as well as the human-primate eye. With this total exclusion of ALL SCIENTIFIC data it is hardly surprising that you have no clue about the behavior of the natural eye -- let alone any concept of preventing the development of a negative refractive state for the fundamental eye. But I am certain you are sincere in you office mind-set. An actual solution can only occur when the person concerned with the issue actually pays attention to objective-scientific data, and realizes how you totally ignore this critical scientific data. But that is the issue. Best, Otis Engineer ****** > More recemt animal studies suggest that accommodation in not a factor in eye > growth stimulated by minus lenses. [quoted text clipped - 11 lines] > > snip rest of message |
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