myopia and feedback theory

 

MYOPIA RESEARCH MOVEs TO UNITED STATES

Treasures are often found when you do not look for them

As a scuba diver and young adventurous engineer with knowledge and access to salvage technology, I had looked for sunken treasure in expeditions that I carefully researched at the British Museum library and the Archivo de Indias, all without success. Science is like looking for treasure, you do not find what you are looking for, but whatever is there for you to discover. Here is just an example of something I found which I was not looking for. When I was at Cambridge England, I used to assist eye surgeons in the morning at Addrenbrooks hospital. Some surgeons entrusted me to do basic tasks during surgery. On one occasion I was assisting in routine cataract extraction. The patient, a machine shop operator, had complained in the clinic of a discomfort sensation in one of his eyes. After examination only an incipient cataract was found, that was the reason for the instant operation. Surgery went fine; I was holding the semicircular corneal flap done in those days while the chief surgeon extracted the frozen cataract when I noticed something shining on the back of the cornea through the Zeiss operating microscope. When the cataract was out and the fold in place I looked again carefully at the corresponding front side of the cornea. Barely noticeable was a foreign body. I pointed it to the chief surgeon, who increased the microscope magnification. Upon magnification, a foreign body was evident that perforated the cornea. He ordered a powerful ophthalmic magnet to the operating theater to attempt magnetic extraction in hope that the shiny reflexion indicated a ferrous metal body, consistent with the patient’s occupation. The magnet was approached slowly to the patient’s eye while we watched through the microscope. The foreign body suddenly disappeared, obviously removed by the magnet attraction. We had found during this operation what we did not expect and its discovery was far more important than the operation at hand. Not only the foreign body was the cause of the patient’s discomfort, but a perforating body like that could easily have resulted in infection and the patient losing his eye. We will see next how scientists found myopia when they were not looking for it and how this accidental discovery was much more important than many other experiments carefully designed to elucidate the cause of myopia. 

Harvard Research. A Nobel prize winner enters myopia research with a serendipitous discovery

The subject of Feedback Theory had been put to rest while I was occupied at Addenbrooke's hospital eye operating theater, with my Ph.D. work at the University of Cambridge and MIT. I followed the scientific literature however and exchanged information with others like Otis Brown, an engineer that also believed that lenses affected myopia in a way that could be modeled using engineering tools. I think I was still a graduate student at the time when I was honored with Otis' call to discuss the ideas that we shared. Then I knew that I was not alone. Otis, an experienced and brilliant engineer, had no doubt that feedback was behind myopia. At about that time I read a paper co-authored by Dr. Torsten Wiesel where they found by chance that they could produce myopia in monkeys but did not know why [5]. Brilliant minds know when some unexpected find is important and worth reporting. I knew that Feedback Theory predicted that myopia could be produced experimentally, so after I read the report I saw a connection and wanted to talk to him about the interpretation of his experiment. Our mutual friend, MIT professor Jerry Lettvin arranged the teleconference. We agreed that there was a connection, but we did not know what it was. I also paid a visit to coauthor Dr. Elio Raviola later in his Harvard laboratory. The reason why experimental myopia developed eluded him too. I offered him to join forces with him and Torsten Wiesel to find an answer to the puzzle but he declined. Many scientists replicated the experiment with monkeys and other animals, but the mystery remained. The puzzle was not solved until 2015 [6] at MIT. 

MIT Research. The connection between laboratory myopia and human myopia is made

MIT had given me a research job and two laboratories under the Research Laboratory of Electronics and the Man-Vehicle Laboratory of the Aeronautics and Astronautics department. Jerry Lettvin and others had entrusted substantial research grants funds to me. A lot of good work came out of those days that I am still trying to compile and publish. One day, a scientist visited my labs at MIT to see my work. He offered me a position at the Eye Research Institute, now part of Harvard Medical School. I accepted, declining a more prestigious and lucrative professorship offer from Madrid. The opportunity came to further look into the subject. This time I looked at Boston myopic patients. I searched hundreds of medical records of myopic and hyperopic patients; my Feedback Theory curves matched the refraction of real people. I could now match the curves not only to average development but to individuals. You only know something when you can describe it with numbers. Now I had the numbers. I found the average time constant k for emmetropization and for each patient that I examined. It was not easy in those days, my computer program run day and night nonstop crunching numbers to converge to a numerical solution for each patient’s unique parameters. Once I found their time constant (and a few more parameters explained below) then we knew it all. We knew what was going to happen to that patient, how his myopia would develop in the future and why. We compared predictions with the real numbers, they matched. In 1987 the time tested results were published in two ophthalmology journals [4, 7]. The Feedback Theory of emmetropization was more than a scientific curiosity. It could help real people and it predicted that myopia could be prevented with the appropriate action. It would take many more years until this prediction was tested successfully and myopia was prevented in individuals for the first time [8]. Many scientists replicated the experiments of Wiesel and Raviola and were producing laboratory myopia in monkeys and other animals, but the mystery remained. Finally, in 2015 I figured it out after more experimentation with Peter Greene and wrote a paper to explain it [6]. In essence, Wiesel and Raviola had unknowingly opened the emmetropization feedback loop, the monkeys developed progressive myopia for the same reason that humans do! I contacted Jerry Lettvin asking for his opinion on this paper. His wife Maggie called me telling me that she had read the paper to him; the reading glasses that he depended on for many years were no longer any use as he was now blind due to his myopic retinopathy. I was moved, my quest to remedy myopia and blindness continued stronger than ever.

When an “F” does not mean failure. NIH sponsors the first test of Feedback Theory

The toughest place where I have studied was the School of Electrical Engineering (Escuela de Ingenieros de Telecomunicacion) in Madrid. This engineering degree had a reputation as the hardest degree to get, with a student drop-out of 90% at the time and the students that succeded usually spent longer than the official 5 or 6 years required. In my first year, one day I went to see the results of my Algebra exam on the wallboard. Next to my name there was an F (failed). I was disillusioned as I had never received an F, but not for very long. I noticed that every single student in the class had received an F also. So the F was not a failure as I did no worse than the rest. My second F came from the NIH (National Institute of Health) in the USA, just like the first one It was not a failure at all. Feedback Theory predicted something that had never been observed, that placing positive or negative lenses in front of an eye would make it hyperopic or myopic respectively. Verifying this prediction in humans was not easy given the restrictions on medical experimentation. Because of this limitation, I prepared a plan of action with a long list of experiments to be conducted to demonstrate beyond doubt that emmetropization was a feedback process, the effect of lenses and that we could take control of the process. I emphasized and proposed to do a set of experiments where lenses of different sign and power were applied to monkeys’ eyes to confirm the Feedback Theory prediction that eyes would compensate and nullify the lens power. I sent it in the form of a detailed 50-page research grant application to the NIH [9]. The NIH had it reviewed by experts like Howard Howland and Josh Wallman. The NIH wrote to me saying that the experiments were of great interest and importance, but they felt that I was too young to direct them. The NIH broke the rules and took the unusual step to preserve my proposal, made it available to other investigators and paid them to do the experiments. The key experiments, involving the effect of lenses, were done to the letter and the results were resounding. The effect of lenses matched the predictions of my Feedback Theory. So, in the end, I was successful in the experiments that I designed showing that my Theory was correct. In one of these experiments, lenses of different sign and power were applied to chicks’ eyes and their refraction changed quickly to the values predicted by Feedback Theory with mathematical precision. Ironically it was done by Frank Schaeffel, a young graduate student under the direction of Howard Howland [10]. A set of experiments with twins was also proposed to the NIH, but the NIH did not fund them. It is also irony that an experiment that I did with twins in 2018 showed not only that myopia was the result of lens interference, but calculated interference made myopia prevention a reality [8].

 

Feedback Theory predictions confirmed in primates

In 1989 I had a visit from the secretary office of a pertinent Spanish Ministry and a follow-up meeting in their office in Madrid. The recent Socialist party had on their agenda to repatriate what they called the "brains" that had left Spain and I was on that list. They said the right words, they would sponsor my work. Soon thereafter I was at the University of Madrid with a visiting professorship. I organized a laboratory, researchers and projects on a global scale. One of them was with Dr. Fariza at Harvard to demonstrate that emmetropization applied beyond chickens to primates. In 1991, for the first time and as I proposed to the NIH 6 years before, we applied positive and negative lenses to monkeys' eyes. They developed myopia and hyperopia respectively, furthermore when the lenses were removed their refraction recovered [9]. The experiment was duplicated later by other investigators [15]. The results confirmed the effect of lenses predicted by Feedback Theory. It was then clear that emmetropization was indeed a feedback process active in primates.

What is “emmetropization” anyway?

It all started in Germany. Early definitions

Before we talk about a theory of emmetropization we should be clear about what we understand by it. The term emmetropization has been defined in several ways. The original definition, when the term was coined, referred to the observed shift from hyperopia at birth towards emmetropia in most individuals. The change towards emmetropia and its preservation was assumed to be accomplished by a mechanism first called “emmetropisierung” by Straub 1909 [16] and later “emmetropisation” [17-20]. At about the same time it was observed that the frequency distribution of refractive errors was normal (Gaussian) at birth but leptokurtic thereafter; that is, more eyes become emmetropic than it would be expected by chance [16]. Emmetropization has been alternatively defined this way [20, 21]. That refraction of babies shifts from hyperopia towards emmetropia has been reported many times [21, 22]. This trend was also observed in cross-sectional and longitudinal studies of humans [23-25]. The shift of the mean of the distribution of refractive errors is not necessarily related to the leptokurtic change. Emmetropization has been limited by many to the very first years of life and it does not make any connection to changes in the frequency distribution of refractive errors, and in particular to a myopic skew that develops much later.

The modern definition of emmetropization

Medina defined emmetropization broadly in 1987 as “the controlling process that regulates the refraction of the human eye to achieve optimal visual acuity over the years” [7]. This definition connects all observations, has no time limitation and it is free from the restriction that emmetropization seeks emmetropia. By this definition, emmetropization is a feedback process since it works by monitoring the quality of the retinal image. It also implies that if the retinal image is altered artificially, such as by the use of lenses, emmetropization will be misguided. In other words, emmetropization may direct an eye to become myopic or hyperopic instead of emmetropic because a corrective lens that provides “optimal visual acuity” has been placed in front of that eye. In contrast with the original definition, which was a mechanism that sought emmetropia, the newly defined mechanism does not; in fact, it does not even need to know when the eye is emmetropic. Emmetropization is active during the very early years of life, since the non-Gaussian leptokurtic distribution of refractive errors, as observed by Sorsby in the young adult [22], is established in 6 to 8-year-olds [26, 27]. But myopia progression and the effect of lenses affect older individuals, which implies that feedback, i.e. emmetropization, operates after the age of 8 years.

The proposal that there was feedback regulation explaining these observations, as well as this definition of emmetropization was generally accepted. This definition was implicitly adopted in animal experiments to explain the artificial ametropia produced with lenses and diffusers. Emmetropization would also make the distribution of refraction for adult eyes leptokurtic and would modify hyperopic errors towards emmetropia if there is no interference. The term “optimal visual acuity” has some intentional ambiguity as it may be that uncorrected optimal visual acuity is accomplished not with 0D, but e.g. with +1D for some individuals or group of individuals and -1D for others. The distribution of refractive errors supports such a range. By age 18 emmetropization has made 90% of the eyes to be in a narrow range around 0D [22]. See below and Fig. 3. Although emmetropization is now widely used to refer to the feedback mechanism, some still thought that passive (non-feedback) regulation is possible.

Passive control for emmetropization is ruled out

Passive emmetropization proposals are generally based on the fact that enlargement of the eye with growth reduces the power of the dioptric system in proportion to the increasing axial length [28]. The power of the cornea is reduced by lengthening the radius of curvature. The power of the lens is reduced by lengthening radii of curvature and the affectivity of the lens is reduced by deepening of the anterior chamber. This notion is flawed because it is simply a linear scaling property of an optical system [29], which only explains how the original (usually hyperopic) refractive error of the growing eye will be maintained, not reduced. It does not explain the leptokurtic change of the distribution of refractive errors or the effect of lenses. Any other conceivable passive mechanism is very unlikely because it could not explain the effect of lenses observed in animals and humans.

Physiological schemes for emmetropization and why coachmen do not care about them

Physiological hypotheses have been proposed to explain emmetropization, ranging from feedback mechanical schemes without nervous system intervention [8] to biochemical and neural control [85]. There are many more hypotheses that have been proposed to elucidate the physiology of myopia. They include genetics, accommodative lag, the wavelength of light, biochemical agents such as muscarinic receptors and dopamine and nitric oxide neurotransmitters. They are discussed here only in passing as they are hypotheses that do not explain emmetropization. They ignore the intimate relation between myopia and emmetropization and have little support or predictive power. Van Alphen [2] suggested a physiological scheme for the regulation of eye refraction based on a mix of passive and active control. He speculated that a particular feedback loop might be at work which was later discredited. He made the same mistake that many researchers investigating myopia and emmetropia do; he focused on finding a physiologically detailed mechanism instead of trying to learn its overall operation, that is, the defining feedback system. The underlying physiological intricacies of emmetropization remain unknown. When I was a kid horse carriages like in the photo were still used in my home town in Andalucia. They were soon replaced with automobiles and the coachmen had to learn to drive automobiles. Their mechanical intricacies were irrelevant to them, as well as most people, what mattered was the response of these new machines to their operating commands. In the same way, the system approach of Feedback Theory tells us the cause and the effect and gives us all we need to manage and control myopia. There are some people who put aside Feedback Theory because they do not understand it, or disregard it claiming it is “just a model” or a "mathematical construct." When Isaac Newton proposed his law of universal gravitation, it was discredited by some because it was just a cold equation that could not explain why masses were attracted to each other. Newton admitted his ignorance, which has been shared universally for three hundred years. Nevertheless, his equation is what we used when I worked at NASA to calculate orbits to deliver spacecraft to exact destinations in the solar system.

WE MEET THE ENEMY. MYOPIA IS NOT A DISEASE OR A DEFECT, IT IS JUST US FOOLING EMMETROPIZATION

The connection between myopia research and the Babel tower

Perhaps the greatest problem with myopia research is that the investigators do not communicate in the same language. By language I do not mean the spoken language, but their fields of expertise (ophthalmology, optometry, engineering, biology, physiology, mathematics, physics …) are so different that they do not fully understand each other, and as a result, there is disorganization, omission, contradiction, and many crucial mistakes. I will illustrate this point with a story where a communication mistake cost near a billion dollars. Part of my work at NASA involved innumerable meetings with representatives and engineers from many sections for defining future missions. In one of these missions, the Mars Surveyor '98 Orbiter (later renamed as the Mars Climate Orbiter) NASA-JPL had to decide who would be the contractor that would build the spacecraft. The finalist was Lockheed Martin. I had already advised against contracting Lockheed. My reason was simple, I noticed that Lockheed's proposals were not using the metric system, the system of unities that we used at NASA. I saw this discrepancy as a recipe for disaster. My objection was dismissed with the assertion that it would be easy to do the conversion to metric units. In December 1998 The spacecraft was launched from Cape Canaveral only to fail orbital insertion over Mars 9 months later. The failure was due to computer software supplied by Lockheed not using the metric units required by NASA. In short, the trajectory calculated with the wrong units brought the spacecraft too close to the planet and it was lost, as well as the mission and other missions that were to use it as a telecommunication relay. Just as the software output from Lockheed did not interface with NASA’s metric software, there is output from many investigators that can not be understood by many others.

Emmetropization flawless act

We know that there is a normal or Gaussian distribution of refractive errors after birth [16-22]. Fig. 3. Emmetropization changes the normal distribution to a leptokurtic distribution by age 6, that is, many children approach emmetropia. At age 12, 80% of them are within 1.5D of the mean near zero, which we can define as emmetropia [27, 31]. Emmetropization is capable of getting most eyes’ retinas in focus at age 12. About 15% of the population of that age is myopic. Only 4% of that population has myopia greater than 1D. Myopia of less than 1D is hardly a concern for that 11 %. Emmetropization has done a pretty good job at age 12. See also Fig. 3. Of course, these are general numbers, and variability has been reported depending on time and location. Because of the higher incidence of myopia in recent years, very recent data involving relatively small samples like [32] is intentionally omitted because of the artifact created by correction as it is discussed next.

Myopia kicks in

Unfortunately, after age 12, or earlier in Asian populations, the low myopes become mild and high myopes and new cases of myopia develop that progress fast to the 2 to 6 diopters range. The prevalence of myopia then doubles or triples and the distribution of refractive errors becomes skewed towards myopia. A skew is not yet visible at that age, but very noticeable for a population older than 40 [27, 31]. See Fig. 3. So, what happens after age 12 to cause those new cases of myopia to emerge? Feedback Theory explains the reason for the sudden myopia progression and resulting negative skewness simply and elegantly; it is the response of emmetropization to the negative lenses that low myopes are corrected with. Negative lenses include not only spectacle and contact lenses but their equivalent, near vision. Notice that the distributions are not skewed towards myopia until after correction of myopia becomes significant or around age 12 because the mean value of the frequency distributions shifts towards myopia and many new cases are detected and corrected. Before that age myopia and myopia correction are low.

No failure of emmetropization

Some people have a hard time understanding why emmetropization would be fooled when correcting a myope and why the patient’s myopia (e.g. 1D) developed in the first place. They assume that emmetropization should seek zero diopters and that if that is not achieved, emmetropization is not working. But emmetropization, as explained above, does not seek zero diopters. Myopia is not a dysfunction of emmetropization. Feedback Theory tells us that emmetropization is working perfectly when it is compensating for a minus lens. An individual may have myopia of 1D because that is what his emmetropization system seeks as correct, with near work being an alternative cause. It is only when we decide that the value is not correct and place a -1D “correction” lens in front of the eye that emmetropization will lengthen the eye to regain its 1D target myopia, only to prescribe yet another more powerful lens again and again. The emmetropization feedback loop is opened and the response is like that of a donkey trying to reach the carrots in front of him [33]. Fig.4. In essence, what we could call a natural “normal distribution myopia” advances uncontrolled like a runaway train, which becomes a myopia real concern. If we fight emmetropization, emmetropization will fight back, the result will be myopia. So now we know that the cause of myopia is negative lenses. We have finally met the enemy, it is ours and it is us. We can celebrate that it is ours, but not that it is us.

The cause of myopia: Is it done with mirrors? A magic story

During my work at NASA in California, I had some levitation experiences. One, based on the science of visual perception is illustrated in the picture in these pages. The other one came from a magic show at the Magic Castle in Hollywood. My friend and colleague Dr. Dan Diner, a vision scientist and engineer, was intrigued by the secrets that magicians used to perform their tricks and would invite me and our girlfriends Betina and Mary for night entertainment at the Magic Castle in his attempts to uncover the secret of the magical tricks by observation and discussions with me. We once watched an impressive levitation show where a young woman’s body was levitated in the air. Although we found the secret I asked one of the girls after the show if she knew how it was done. I got a depreciative response saying “it is done with mirrors.” Mirrors were not involved. Just like her, some people have preconceptions that cannot be changed even by what they see with their own eyes. Even if this girl had watched a body actually levitating, for her it was not believable, but “it was done with mirrors.” There are many professionals who ignore what their eyes and science tell them if it does not fit their preconceptions and when confronted with conflicting observations they simply disregard them saying “it is done with mirrors.” There is, fortunately, one way to dispel misconceptions as we will see below in another story involving a compass that happened not much later. The cause of myopia, lenses, has been in front of our eyes, but nevertheless, people thought that it was "done with mirrors."t

the Feedback Theory of emmetropization. is it just another "theory"?

Feedback Theory is not a theory but a scientific theory

A scientific theory is much more than a story, much more than an idea, a hypothesis or a "theory" as the word is ordinarily understood. It is for real. The theory of emmetropization is how emmetropization is. It is not just another hypothesis or “theory”; it is the scientific prevailing Theory. Someone may come with a better one, but until then that is emmetropization. The description of emmetropization requires mathematical rigor. It requires the use of terms of art belonging to several disciplines, to gain in-depth understanding requires some background knowledge of mathematics and engineering.

Definition

Feedback Theory only requires that there is an optically produced signal related to refractive state or error and that the signal is fed back to alter the eye to correct for the refractive error. The shift of the long-term focus of the human eye towards emmetropia is controlled by a mathematically defined second-order feedback system that produces quantitative predictions [7]. The feedback system was further simplified and a first-order was soon proposed when it was found from human data that one of the variables was zero [30]. A first-order feedback system is a particular case of the second-order system when the frequency is zero and it is fully defined by its transfer function F(s)=1/(1+ks). Fig. 2. Because of its mathematical formulation, it offers exact predictions [30]. This particular feedback control has been tested in eyes of subjects age 4 to 30 and is termed here and in many publications “Feedback Theory.” The Feedback Theory for emmetropization is based on and supported by data from children and young adults and as such, it is applicable to at least those ages [30].  Feedback Theory explains the long term refraction of the eye synthesizing large evidence and observations. Feedback Theory is a quantitative high-level theory: it does not aim at describing the mechanism at the level of neurophysiological implementation. On the contrary, it allows for different implementations while it does not require or depend on any. It does not need the involvement of accommodation, ciliary tone, intraocular pressure, choroidal or scleral stress, retinal blur, peripheral defocus or optical aberrations as other proposals do. Feedback Theory explains what happens, not how it happens. According to Feedback Theory, the monitored signal that is fed back is the refractive state, which is not necessarily sensed from blur or use of accommodation or other particular sources. There is a misconception that emmetropization is guided by retinal blur. There is no evidence of such, nor it is a requirement in Feedback Theory. The many references in the literature to “myopic defocus” or “hyperopic defocus” are implicitly assuming an unknown physiological model, where the refractive error is sensed from retinal blur and based on Straub’s definition of emmetropization. Although the accommodation system detects actual retinal defocus, the emmetropization system does not because there is no functional relation between defocus blur and refractive error. The refractive error must be sensed from some other source, such as the average accommodation state [3].

Support

Feedback Theory is the governing theory for emmetropization in humans today because of its ability to explain a wide range of phenomena. It is concisely defined by a function, coherent, systematic, predictive, and broadly applicable, integrating many observations of eye refraction. It directed many studies, such as those applying lenses to primates and provided a basis for interpreting the results. It applies to refractive development in emmetropic, myopic and hyperopic eyes. It is a very powerful, quantitative and accurate predictor of refractive changes under multiple conditions, including wearing lenses of any power and near work. It explains myopia and why the distribution of refractive errors skews towards myopia. The refraction of newborn monkeys’ eyes placed in feedback open loop and followed for about a year progresses linearly towards myopia, just like juvenile humans when their emmetropization feedback loop was opened by continuous correction of their myopia even though their retinal images were completely different [6]. Feedback Theory predicts such linear progression in both cases. The suggestion is that Feedback Theory controls both observations and they are not different phenomena. Many predictions of Feedback Theory already observed will be described below. We finally describe a list of observations and experiments that support the Theory, but before we get technical, a story to show why it is so important. 

A compass can tell more than the North direction, and make the most feared lab the most popular

When I was invited as a professor at the University of Madrid I was honored being assigned one of the largest labs in the School of Electrical Engineering, or so I thought. I soon learned that many students feared that lab because it harbored a powerful gigantic magnet used for experiments of magnetic resonance of nuclei in human tissue. Some of the students were apprehensive because of the intensity of the magnetic field and were reluctant to work in the lab because it could be a health hazard. After all, the very nature of the experiments evidenced that it affected human tissue and the magnet had wiped out the data in the credit cards of those who approached it so, what could it do to them? Convictions and bias are very difficult to dispel even in intelligent people but there is a way, it is a test or experiment. One day I met with them outside the lab to test whether the magnetic field in the lab was innocuous. I had asked the students to bring a compass. We confirmed that the students’ compasses indicated the north correctly. Then we walked towards the lab while watching the needles in their compasses. They did not move. When we entered the lab they remained to point north correctly. Only when we were at a distance of less than 1 meter from the magnet the needles started to deviate from the north direction. It was then clear to them that the intensity of the magnetic field of the magnet was much less that the natural Earth magnetic field at distances greater than 1 meter, and therefore as innocuous as the Earth magnetic field. This simple experiment gave the students confidence and they lost their fear of the magnet. My lab became popular in the University and in the newspapers for its innovative research, including myopia research and development of non-invasive procedures to correct myopia and robotics 3D vision. We had visitors from all over the world. It went from being almost empty to full and busy at all times, even during summer months when other labs were empty. Many students came to the lab requesting to do their research under my supervision. In myopia research, as in any scientific research, simple experiments like the magnet experiment tell us much more than any impeccably reasoned hypothesis or belief and can change our convictions in an instant. The key experiments and observations that changed or will change established views about myopia and its cause will be described below.

How do we know that Feedback Theory is correct?
 

The Theory put to the test

A scientific theory is correct when the observed facts match the predictions of the theory. A theory that explains 10 observations is better than 10 theories that explain one. A further test is when the theory predicts a certain effect that has never been observed, but it is there when we examine it. An example of the latter is the prediction that placing positive or negative lenses in front of an eye would make it hyperopic or myopic respectively, tested in animals as explained above. Here follow 14 observations in humans involving myopia, hyperopia and emmetropia that are predicted by this Theory:

1. Near work

Feedback Theory establishes a causal link between near work and myopia, regardless of the physiological mechanism. Near work, meaning near vision of any kind, including viewing of electronic displays has been associated with myopia. There are books written about this old observation. For a recent report on myopia associated with computer use, see [34]. Near vision is equivalent to distant vision wearing a minus lens. The dioptric value of the lens is an added step input to the feedback system, which responds by myopizing. Many investigations and observations have evidenced that there is an association between near work and myopia. No study is needed to observe the tremendous amount of time that young people spend looking at handheld video screens, Fig. 8 and that such activity coincides with the myopia epidemic of recent years. However, nobody has been able to show that near work is the cause of myopia. Feedback theory is based on a feedback system that is causal. That is, the input of the system is the cause of the output. It shows that minus lenses, or near work, are the cause of myopia. The modern habit of frequent and prolonged looking at handheld electronics with high-resolution displays such as mobile phones is more myopigenic than the old-fashioned near work. The small size of the displays coupled with their high-resolution results in very high pixel density that requires a very close viewing distance to magnify and resolve fine detail. This reduced viewing distance is equivalent to around 3D negative lens placed in front of the eyes, which, as discussed here, causes myopia. See also observation 13 for the converse effect when handheld electronic devices are not used outdoors. Time spent in obtaining an education is a claimed causal risk factor for myopia [82, 83]. The longer the education, the longer the near work, so everything points to near work as the cause of myopia.

2. Correction for near

Correction for near vision (with reading lenses or plus lens add) has been known for a long time to have a beneficial effect to reduce a myopic progression [35]. According to Feedback Theory, this effect is small and hard to detect once myopia advances because it does not fully cancel the effect of the lenses used to correct myopia. This prediction was confirmed in a 30-month study evidencing a lower myopia progression rate of 0.25D in that time [36] and in a 3-year trial [37]. A more recent study shows a significant reduction in myopia progression when wearing bifocal contact lens correction [38]. Feedback Theory predicts the effect is modest, but substantial when the future myopic eye is so treated when still emmetropic or hyperopic. See below.

3. Under correction by a fixed amount

Under correction has a beneficial effect to reduce myopia progression. According to Feedback Theory, the effect of under correcting by a fraction of a diopter is small and variable during treatment of a few years. Studies attempting to measure the effect over a period of 2 or 3 years showed conflicting results because the induced change in that period was small and variable [39-41]. A paper reviewing these studies concluded that the effect of under correction for far or near vision in a short time span is close to noise level, this is, the effect is about the same as the customary error in clinical refractions [42]. A claim that under correction enhances rather than inhibits myopia reported in a paper was not really based on under correction, but instead fogging the treatment group to a given acuity. Additionally, the control group could be under corrected by up to 0.5D as their myopia increased [43]. Since visual acuity and actual under correction values were not provided for any group the results are meaningless. Feedback Theory predicts a significant reduction in myopia progression if the under correction is large enough or there is no correction at all (see below). It has been reported that uncorrected myopes of age 12 have a reduced progression of myopia as compared to those who are fully corrected and the authors of that study noted that Feedback Theory supports their findings [44]. A unilateral under correction of 2D reduces the rate of myopia progression by 50% compared to the fellow eye [45].

4. Under correction by a percent

Feedback Theory predicts that under correction by a given percent of the refractive error will always result in eventual stabilization of myopia or ametropia, while a constant under correction will not. For patients who are under corrected by a given percent the Theory predicts stabilization of refraction when the amount of ametropia uncorrected equals the uncorrected myopia R, and the final stabilized refractive error is R plus the last correction. For example, if a myope of R = -0.5D is under corrected by 10%, the last and stable under correction will be -5D (-5.5D refractive error). To calculate the time or age of stabilization we calculate when R(∞) = -5.50D. For our example and practical purposes, stabilization will occurs when R= R(∞)-0.25D = -5.50D - 0.25D or -5.25D. The greater the percent of under correction, the lower the final myopia and the faster the stabilization. For example, if the same myope were under corrected by 50%, the final refractive error would be only -2.50D. The feedback system can also calculate the earlier age of stabilization. This explains why under correction by a fixed amount, which is how under correction is normally prescribed, will show little effect on myopia progression since the percent amount becomes less and less as myopia increases. The indication is to maintain myopes under corrected by a percent of their refractive error. Under correction by a given percent is equivalent to part-time correction. Thus the above calculations are not just of academic interest but have practical applications. Myopes who use their correction part-time should experience the same effect as wearing under correction by the same percent as their part-time duty cycle as explained below. The fact that myopia increases when corrected is by itself a good reason to suspect that it is its cause. The question that could be asked is why it stabilizes when it is still corrected. Feedback theory predicts eventual stabilization when lenses are used a percent of the time, which is a necessary event if only because lenses are not used during some time of the day, for example, showering, sports activities or bedtime. Independently, saturation of the feedback system will take place at some point since the eye cannot grow indefinitely in the axial direction because of anatomical constraints of the orbit. It would stabilize at different times or power simply because of individual differences in patients' habits or anatomy.

5. Part-time correction

Wearing glasses part-time will reduce myopia progression. Not wearing a full prescription full-time has the same effect as under correction. Under correction by a given percent of lens, power is equivalent to wearing the full power lens the same percentage of the time [46]. Investigators have found that the rate of progression of fully corrected myopes is about 3 times greater than those who do not wear their correction and part-time users having an in-between rate [47]. The significance of this result was however dismissed by its own authors after making an erroneous “correction” based on their calculation of the time of myopia onset. They did not have that data, so they calculated the onset using a single exponential to fit patients' refractions instead of the multiple exponentials required by Feedback Theory. The rate of myopia progression also triples after it is corrected [51]. It has also been observed that when one eye is not corrected, its myopia progression slows about 50% compared to the corrected fellow eye [45]. See below how Feedback theory predicts these numbers. The fact that myopia increases when corrected is by itself a good reason to suspect that it is its cause. The question that could be asked is why it stabilizes when it is still corrected. Feedback Theory predicts eventual stabilization when lenses are used a percent of the time, which is a necessary event if only because lenses are not used during some time of the day, for example, showering or bedtime. Independently, saturation of the feedback system will take place at some point since the eye cannot grow indefinitely in the axial direction because of anatomical constraints of the orbit. It would stabilize at different times or power simply because of individual differences in patients' habits or anatomy. Although statistics are lacking, many clinicians have observed that in some cases uncorrected myopia does not progress. There are some low myopes that, for cosmetic reasons or otherwise, choose not to wear their glasses. Feedback Theory predicts that myopia of R diopters will remain stable, which would explain the observation as further discussed next.

6. The linear progression of corrected myopia

Feedback theory offers a mathematical analytical solution or results in continuous correction of myopia. Corrected myopia progresses linearly at a rate of R/k, where R is the stable uncorrected refraction and k is the time constant [33]. Continuous correction of myopia results in what has been termed a “myopia depression” [33]. The linear progression of myopia has been reported by many investigators. See, for example, Goss, 1987 [50] and Fig. 5. A study of 605 children who transitioned from emmetropia to myopia shows the fall in the myopia depression as soon as they had their myopia corrected [51]. Fig. 6 is a modified figure from that study that includes regression lines for the corrected and uncorrected portions. It shows very clearly the increased slope of the corrected progression, which starts in year 5. The slope of the line triples from -0.18D/y to -0.54D/y after correction. Notice that their fellow emmetropes, subjected to the same environmental conditions maintain their refractive rate of change indicating that corrective lenses are the cause of myopia. The fall into the myopia depression at -0.54D/y starts after correction (thick line of a steep slope). Feedback theory predicts linear progression when myopia is corrected and exponential attenuation when it is not corrected [33]. See Fig. 2. We could calculate from their refractive data the individual k for the children in that trial and their end myopia R if they had not been corrected. These data were not provided in the paper but we can calculate the average k and R. Feedback Theory requires that the after/before progression ratio is R/(R-R1) where R1 is the average refraction when they were corrected or -0.75D. This is known by the definition of time constant k, which is equal to R-R1 divided by the myopia progression rate.  Solving R/(R+0.75) = 3 we obtain R = -1.12D, so these children would have ended up with average myopia of only -1.12D if they had not been corrected. See Fig. 6. The calculation of their average time constant is straight forward, k = 1.12/0.54 = 2 years, which is not far from the average time constant of 2.3 years of children of the same age from [33], Fig. 5. The interesting point is that, for any patient, we can calculate R and how much will the myopia progression rate increase after correction, the before and after rates being (R-R1)/k and R/k, all in agreement with the data.
Feedback Theory predicts that myopia progression will be faster once corrected, as it has been observed because R/(R-R1) is always greater than 1. Feedback Theory also shows that the progression rate of corrected myopia (R/k) is the same as the progression rate at the time when refraction is zero, so we can predict the future myopia progression rate of any patient if we know how fast they crossed from emmetropia to myopia.

7. The relation between age of myopia onset, initial correction and rate of progression

Feedback Theory predicts the following to happen. For subjects with the same natural myopia (equal R) the younger they are when their myopia R is diagnosed and corrected (lower k), the faster their corrected myopia progression (rate of progression = R/k). For subjects of the same age when myopia R is diagnosed and corrected (equal time constant k), the greater their initial myopia, the faster their corrected myopia progression [32]. These predictions have already been observed [52]. When R and k are not available or calculated, Feedback Theory can formulate a general rule for a group of patients that assumes that their R and k are similar and that their uncorrected myopia R is close to their myopia at the time of onset of spectacle wear. The earlier the child becomes myopic, the higher the rate of progression, but it is dependent on the individual values R and k and great variability will be observed [53]. Ong et al. [47] showed this general trend and the expected variability.

8. Partial correction of hyperopia

The amount of hyperopic under correction is significantly correlated to the reduction in hyperopic refractive errors [48] as predicted by Feedback Theory. Feedback Theory predicts which hyperopic children will become myopic and can determine which plus correction they should wear to slow emmetropization just enough to prevent myopia. Partial correction of hyperopia can prevent myopia in children at risk. This customized preventive measure has already been demonstrated in twins [8]. This treatment is successful because children easily comply with the use of plus lenses as they provide a larger retinal image and higher acuity. See Figs. 10 and 11 for contemporary illustrations of the twins’ compliance with the treatment. Fig. 7 shows the actual refractive development of a twin’s eye whose hyperopia was corrected by 50%. Fig. 8 depicts the prediction of Feedback Theory if his hyperopia had been fully corrected. Fig. 9 is the prediction if his hyperopia had not been corrected and his myopia had been fully corrected every time that it increased by 0.25D [8].

9. Stability of corrected hyperopia

Hyperopia will remain essentially unchanged if fully corrected [48, 49]. Studies on children prescribed spectacle lenses show that emmetropization occurs more rapidly and more completely in those children who do not wear their prescription full time. The amount of hyperopic under correction is significantly correlated to the reduction in hyperopic refractive errors. Full correction of hyperopia inhibits emmetropization during early and late childhood [48]. All these observations are precise predictions of Feedback Theory. See [4] and Fig 7 for real cases.

10. The evolution of the frequency distribution of refractive errors

It is known that the distribution of refractive errors in newborns is normal (Gaussian) and has a mean of a few diopters of hyperopia. Feedback Theory predicts that 1- The distribution would become leptokurtic, 2- the mean would shift towards emmetropia, 3-the skewness would become slightly positive first, and 4- then strongly negative for distributions post-teenage years. All these phenomena have been observed. Fig.3. Feedback theory predicts a small skew towards hyperopia in young populations. Such positive skew is small because correcting hyperopia does not result in progression, but in the maintenance of hyperopia, as it has been observed and predicted by the Theory. Hyperopia, rather than myopia, is more likely the correction for children younger than 10 because it is much more common than myopia. The distribution of refractive errors in adults is not only leptokurtic, but it is skewed towards myopia. Fig.3. This observation is explained by Feedback Theory because it predicts that myopia, which is usually corrected, would progress quickly. That is not the case for hyperopia. Uncorrected or partially corrected hyperopia decreases [8]. Even corrected hyperopia does not increase significantly [49]. Fig. 8. Both observations are also predicted by Feedback Theory. The Theory predicts a small positive skewness for young populations that changes to a large negative skewness in the teenage years. The Theory further predicts increased negative skewness with age, as myopia cases will only increase, and also an eventual loss of leptokurtosis due to such increased skewness. This phenomenon has already been observed [31, 54, 55]. See Fig.3. This figure has a distribution of refractive errors for army recruits around age 18 from data from 1960 when the incidence of myopia was lower. For more recent distribution of refractive errors in teenage years showing the myopia skew, see Flitcroft 2014 [27] and French 2012 [31].

11. The connection between progressive myopia and experimental myopia

Experimental or laboratory myopia, including lid suture myopia, is myopia intentionally caused in the laboratory. Laboratory myopia was a mysterious phenomenon discovered by chance that changed the course of myopia research. It is a good example of how Feedback Theory is powerful enough to explain what appears to be a different way to cause myopia. Laboratory myopia, also known as form-deprivation myopia refers to myopia that is artificially caused by experimental manipulation such as lid suture, diffusers or lenses that create a retinal image blurred or deprived of form. Laboratory myopia was accidentally discovered in 1976 by Wiesel and Raviola [5]. Diffusers also produce myopia and have been widely used by experimenters as a simple replacement to lid suture since they are capable of removing form or high contrast in normal light conditions. Why lid suture and diffusers cause myopia remained a mystery and it was believed to be unrelated to lens myopia [56]. Feedback Theory predicts that negative lenses would cause myopia and positive lenses hyperopia. Experiments that applied lenses to animal eyes were designed to test this prediction and it was so demonstrated [9]. In 2015 Medina and Greene showed that Feedback Theory explained both lid suture myopia and lens myopia as the result of the opening of the feedback loop, they further showed why lid suture myopia progresses faster (rate of A/k) than lens myopia (rate R/k) using Feedback Theory [32]. The prediction that laboratory myopia progresses very fast had already been observed and reported many times.

12. Emmetropization is more active during the early years of life

The non-Gaussian leptokurtic distribution of refractive errors is established in 6 to 8-year-olds [27]. It also appears that the process of emmetropization in humans is more active during the early years of life (faster rate of refractive change). This could be explained simply because the slope of the feedback response is greater at an early age. It was found that the time constant k is greater in older patients or that k increases with age [32]. Any of these alternatives would explain why emmetropization is more active during the early years of life.

13. Benefits of outdoor activities, in contrast with indoor activities

It has been observed that outdoor activities, in contrast with indoor activities, reduce somewhat myopia development [57-65]. Feedback Theory predicts that indoor activities are myopigenic, which is the proper way to express the observation. This is so because the feedback system responds to the use of a minus lens myopizing as explained above, and near vision and use of a minus lens are optically the same. The view of scene outdoors while wearing a minus lens is equivalent to viewing a replica of the same indoors. For example, a monocular view of the picture of a mountain on a computer screen is visually indistinguishable from looking at the real mountain through a lens of about -2D. An eye seeing through a lens is optically equivalent to an eye whose power includes the additional vertex power of the lens. Lenses affect refractive development because their power is suddenly added to the eye power and therefore to the error detector output or equivalently to the input of the feedback system. Some experimenters mistakenly believe that the cause of the outdoor benefit is the high light level. Experiments were conducted where chickens wearing diffusers were reared under very bright artificial illumination to purportedly test the hypothesis. When the chickens did not develop myopia, the experimenters concluded that high illumination has a “protective effect” against myopia. But let us see what Feedback Theory has to say. Feedback Theory predicts that there will be no form-deprivation myopia under high Illumination because it produces high contrast in some features which will prevent the opening of the feedback loop as explained in the previous paragraph. In fact, it has been known for some time that diffusers do not cause myopia under high illumination [66]. Therefore if no myopia is induced in the first place, there is no myopia to “protect from” and light could not have any effect on something that does not exist. The correct reason why myopia is somewhat prevented outdoors has been explained above. It must also be noticed that the frequent use of high-resolution handheld devices with small displays is curtailed while outdoors. One reason is that these devices use backlighted Liquid Crystal Display (LCD) or Organic Light-Emitting Diode (OLED) screens, which are hard to see outdoors because their contrast drops when their illumination is competing with the sun. Outdoor activities are beneficial in part because they curtail modern myopigenic activities, not because they have any “protective effect” of their own as some call it. There is a possible related reason why high light level has the observed effect on myopia which involves the increased depth of focus with high illumination. The dioptric value of the distance-equivalent lens for near vision is not simply the inverse of the near distance, but it depends on the illumination level. This is so because the power of the equivalent lens is equal to the actual accommodative value of the crystalline lens, which in turn depends on illumination because the amplitude of accommodation is light-dependent [67]. In 1980 it was pointed out that a feedback model for emmetropization predicted that low light level would increase myopia caused by near work [3]. According to Feedback Theory, the cause of myopia is not related to accommodation or the light level, but the negative lenses or equivalent near vision. An observation related to outdoor activities that investigators found intriguing and unexplained is that its effect on myopia is preventive, but after myopia onset, it is insignificant [57]. Feedback theory predicts this observation. Those who confirmed this prediction were unaware of Feedback Theory, stating that “is unknown why this protective effect would not apply to both risk of onset and progression” and “one would have to propose a complex system for a different mechanism to control eye growth before compared with after the eye becomes myopic.” Feedback Theory is a simple system and a single mechanism that predicts both observations. The "protective effect" does not apply to both situations simply because after myopia onset, corrective lenses are used and therefore Feedback Theory predicts a fast progression for which the outdoor effect is comparatively insignificant.

14. Atropine effect

Numerous studies have demonstrated that atropine is effective in slowing myopia progression in children [68-80], as well as other cycloplegic agents. The basis of the atropine effectiveness may be the use of plus lenses. Although atropine treatment and myopia progression rate are associated, it has not been demonstrated that atropine itself is the ultimate cause of the reduction in the rate of progression rather than its effects. Feedback Theory offers an alternative cause. The Theory predicts a reduction in myopia progression rate when using atropine due to its effect on accommodation. Atropine reduces the accommodative amplitude, which requires that those so treated remove their glasses and/or use a plus addition to focus near objects [71, 77]. Atropine users are therefore uncorrected, under corrected, or plus corrected during near vision. In either case, Feedback Theory predicts a reduction in the progression rate of myopia, as several investigators have confirmed [34, 42, 45]. The results of Chia et al. 2012, 2014 [77, 78] also support the Feedback Theory explanation for the reduced progression rate. They used three different concentrations of atropine for three groups of patients and noted the percentage of patients in each group that requested plus addition. The rate of progression of myopia was proportionally less in the groups with a higher percent of plus lens users, as feedback theory predicts.

So what? Can you reverse myopia? Can you prevent CHILDREN from becoming myopic?

And finally, for those who ask these questions and look for medicine or treatment, we have some for them. Several important conclusions can be reached with our current knowledge of myopia and its cause. The last story is about one such treatment.

You are a lucky kid

This is what an ophthalmologist told my son Nicolas when I took him for a routine yearly eye exam at age 9. I took him because he was on a prevention treatment wearing plus lenses. The lens prescription was calculated using Feedback Theory to avoid Nicolas ever becoming nearsighted. His refraction and other eye particulars had to be recorded regularly to document and test the treatment efficacy. The ophthalmologist had no idea about that. In fact the purpose of him doing the eye examination instead of me or anyone who knew about the treatment was to avoid bias. I was intrigued by the comment, as was my son, who asked him “why”. He responded, “you couldn’t be in better hands than your father’s to take care of your eyes”. I do not know why he said that, but he was correct in that he was “a lucky kid.” The result of the prevention treatment was that Nicolas, as well as his brother treated the same way, avoided myopia after the treatment ended several years later, just as Feedback Theory predicted. As of this date he is not nearsighted and does not wear any glasses. See [8] for the details of the treatment. So in these days when almost half of the students his age are myopic, he is indeed a lucky kid.

There is no need to have mathematical skills to apply Feedback Theory to real-life cases; it is enough to know its predictions. It predicts that a myope who starts wearing minus lenses full time with the full prescription will fall in a myopia depression of no return [33]. Myopia will also be the result of using the eyes massively for near work because that is equivalent to wearing a minus lens. So, as long as all that happens, there is little hope to stop myopia. Refractive surgery will not stop the fall in the myopia depression because it is also equivalent to placing a minus lens and for that reason, it is not indicated in progressive myopia. However, the indiscriminate use of lenses can be changed, although not easily or comfortably. Creative treatments for myopia are suggested here, including substantial under correction of myopia. If myopia is not corrected it would quickly stabilize. The prediction that half of the world population will be myopic by 2050 [81] does not have to happen. This is what we can do: arrest and slow its progression and prevent it in the first place. Fig. 11 is a summarizing picture showing myopia developing, progressing and being prevented. Myopia can be prevented quite easily by partial correction of hyperopia. A bright future without glasses is now an option for a child destined to be myopic. He can be "a lucky kid."

REFERENCES AND FIGURES ARE LOCATED IN PAPERS TAB,  FEEDBACK THEORY

 

The birthplace of Feedback Theory

THE HISTORY OF EMMETROPIZATION AND FEEDBACK THEORY

THIS IS A REAL STORY WITH REAL PEOPLE OF THE REAL PROBLEM OF MYOPIA

IT IS MORE THAN A STORY, IT IS HISTORY, IT IS THE THEORY OF MYOPIA

 

Nearsightedness: A thing called myopia

You can see a complex phenomenon as simple or see a simple one as complex. It all depends on the model or theory that you have to explain it. When you have a good theory the phenomenon looks simple and understandable. Many other things that appeared different and disconnected become one and the same; the good theory becomes the Theory. We have the Theory that explains myopia.

Many people want to know why myopia develops, why it is reaching epidemic proportions, they want to know its cause to meet and fight the enemy. Keep reading and you will meet it. The Theory of emmetropization is the feedback mechanism that connects myopia with its cause, negative lenses.

Understanding myopia is simple if we understand emmetropization and in particular Feedback Theory of emmetropization. We will start from the beginning and end with current knowledge and practical conclusions, traveling through the key findings in 40 exciting years of myopia research. What follows is science, it has been written so that non-scientist will also read to the end.

Myopia feedback loop, from Medina 1980

Feedback Theory test and recapitulation

Left:

These two boys in green gowns were at risk of developing myopia, but are free of myopia and glasses at graduation (upper photo) after 9 years of preventive positive lens wear (lower photos). Their fellow student (middle) who had a similar visual experience but no preventive treatment developed several diopters of myopia in those years.

 

Bottom:

A candid photo  illustrates Feedback Theory explanation of myopia, its progression (1: negative lenses), its cause (2-5: near work negative lens equivalent) and its prevention (6-7: positive lenses).

 

 

THE HISTORY OF THE BIRTH OF FEEDBACK THEORY FOR THE REFRACTION OF THE EYE, A HUMAN PERSPECTIVE AND REAL STORIES

Born in a car

It was a spring day in Madrid, I was 22 years old and was driving my Seat 600 from engineering school to my ophthalmology class. I was an engineering student in the morning and a medical student in the afternoon in the two main universities in Madrid. I had fresh in my mind from the last ophthalmology class the time course of eye refraction for people who develop myopia, hyperopia or those who to become emmetropic. I had also learned about some other time course, the response of engineering feedback systems to a step input. All four kept flashing in my head as if trying to tell me something. We did not have graphing calculators in those days, we did engineering calculations with slide rules. But my brain was able to graph those data in my mind. Then, the four graphs superimposed and fused for a second. They all had something in common; in fact, they were the same when comparing their shape!
In an instant, I realized that myopia, hyperopia and emmetropia were all just the response of a feedback system. Not an engineering system, but a biological one. Myopia and hyperopia were no disease as we were taught, but a different healthy expression of the same feedback system. But this was just an idea, a hunch, a guess, or in scientific terms, a hypothesis. The idea was put aside for a while having a busy full schedule in two university campuses, finals approaching and other demanding questions occupying my mind. The idea was too intriguing, however, to be put aside too long. I spent the summer vacation researching whether it was new and whether there was any evidence to support it. I read about the term “emmetropization” in the German papers, which noted that the Gaussian distribution of ametropia at birth mysteriously became leptokurtic with age and the apparently unrelated phenomenon of birth hyperopia reducing to zero diopters with age. It all made sense now. A feedback system control would explain it all at once for the first time. I found only one paper that speculated that active regulation for eye refraction could be a factor, but there was no data or engineering or math support. I found the data from thousands of eyes compiled by ophthalmologists who dedicated their lives to collecting it. Their graphs matched again the engineering feedback curves. This was no speculative idea anymore; the “Feedback Theory” of emmetropia an ametropia was born. In the fall I wrote a paper with my observations and my conclusions for publication in the main ophthalmology journal in Spain in 1979. It was soon accepted and published in 1980 [3]. There were many pieces of the puzzle still waiting to be put together.

What the experts knew: “The eye is an accordion”

There was something very relevant that I did not learn at the university classes, but from my clinical training at the clinic of Optica Medica. When inquiring about the effect of patients not having their correct prescription on their glasses a senior practitioner told me with a smile: “Do not worry, the eye is an accordion”. He was telling me that the eye would adapt to whatever prescription was put on their glasses. He was absolutely correct although he did not know the depth of his statement. He knew from experience that the eye will eventually accept whatever lens power was in the glasses, but he did not know that the refraction of the eye would actually change in response to that lens, by enlarging like an accordion, so that it would end being the “correct” lens. There are some who believe that a lens in front of the eye could not change its refraction. We will see below how mistaken that view is.

A crucial experiment made in my mind

I will mention a summer parenthesis because it was then when I discovered that near work causes myopia and why. Simply because I realized that near vision and negative lenses are optically the same for the visual system and therefore also undistinguishable for Feedback Theory. The implications are profound as we will see later. In the summer before I went to Cambridge University a friend and I volunteered at a center for severely disabled individuals. I think it was called Leonard Cheshire. I had helped before people with disabilities, but this was a little more than what I and my friend were prepared for.  I remember he introduced me to the most severely handicapped individuals. One in particular named Peter, being tetraplegic, had no motion control of his body, other than his head, and he was also unable to speak, so someone, before I came, had fitted him with a metal horn on his forehead so he could use it to hit a touch screen keyboard on his wheelchair, like the one used by my colleague Steve Hawking in Cambridge University. Their keyboard controlled a synthesizer that would display on a screen or speak their typing. He was not happy with his horn but frustrated because it would not work reliably. I saw the problem immediately as the horn he used did not make good electrical contact with his forehead, as needed for the capacitive touch screen. While trying to find a solution to Peter's problem he informed me that his distance eyesight had deteriorated in the years that he used the device. I confirmed that he had developed myopia after he used the device. I made a metal contact for his horn with foil, placed the screen further from his eyes and ordered glasses. He was delighted with the results but I was puzzled why he developed myopia so fast. The paper that I published in 1980 explained that myopia would develop if a negative lens was placed in front of the eye, but he had used no lenses... or had he? I made a thought experiment while lying on my bed in the hospital. I placed Peter's screen far away an infinite distance and made it big so the retinal image would be the same size as if near, then I examined his eye while he was looking at the actual near screen and while he was looking at the far screen with a negative lens. I found that there was no difference. Looking at the screen placed near his eye was like looking through a minus lens at a further distance. If I could not detect any difference by any means, his eye's feedback system could not detect it either. That fact had far-reaching implications. This is the principle of equivalency of near work and concave lenses, that I postulated in a paper in 1987 [4]. The view of a distant scene seen through a minus lens is equivalent to viewing a replica of the same at close distance. Feedback Theory told me that was the reason he developed myopia. It was the result of those invisible minus lenses.  When I announced him and the others that I was leaving to start the academic year at Cambridge University I noticed that his paralysis did not stop the tears in his eyes. I was moved, I learned from him and the others and I missed them, their image and legacy stayed with me. I had two interests grown stronger that summer. I was determined to help those who were impaired and to continue my ophthalmic studies. I spent a great deal of time during the academic year at Cambridge England observing and assisting ophthalmological surgical procedures at Addenbrooke's hospital with head surgeon Mr. Watson while continuing my Ph.D. in Engineering under the direction of Professor Frank Fallside. It was only interrupted when the Massachusetts Institute of Technology (MIT) offered me to continue with my Ph.D. in Cambridge, USA. I and my myopia research moved to Cambridge USA with new ammunition from Cambridge England.

THE HISTORY OF THE BIRTH OF FEEDBACK THEORY FOR THE REFRACTION OF THE EYE, A HUMAN PERSPECTIVE AND REAL STORIES

Born in a car

It was a spring day in Madrid, I was 22 years old and was driving my Seat 600 from engineering school to my ophthalmology class. I was an engineering student in the morning and a medical student in the afternoon in the two main universities in Madrid. I had fresh in my mind from the last ophthalmology class the time course of eye refraction for people who develop myopia, hyperopia or those who are lucky enough to become emmetropic. Today I had learnt about some other time course, the output of engineering feedback systems. All four kept flashing in my head as if trying to tell me something. They all graphed in my mind and the four graphs superimposed and fused for a second. They all had something in common; in fact they were the same when comparing their shape!
In an instant I realized that myopia, hyperopia and emmetropia were all just the response of a feedback system. Not an engineering system, but a biological one. Myopia and hyperopia were no disease as we were taught, but a different healthy expression of the same feedback system. But this was just an idea, a hunch, a guess, or in scientific terms, a hypothesis. The idea was put aside for a while having a busy full schedule in two university campuses, finals approaching and other demanding questions occupying my mind. The idea was too intriguing, however, to be put aside too long. I spent the summer vacation researching whether it was new and whether there was any evidence to support it. I read about the term “emmetropization” in the German papers, which noted that the Gaussian distribution of ametropia at birth mysteriously became leptokurtic with age and the apparently unrelated phenomenon of birth hyperopia reducing to zero diopters with age. It all made sense now. A feedback system control would explain it all at once for the first time. I found only one paper that speculated that active regulation for eye refraction could be a factor, but there was no data or engineering or math support. I found the data from thousands of eyes compiled by ophthalmologists who dedicated their lives to collecting it. Their curves matched again the engineering feedback curves. This was no speculative idea anymore; the “Feedback Theory” of emmetropia an ametropia was born. In the fall I wrote a paper with my observations and my conclusions for publication in the main ophthalmology journal in Spain in 1979. It was soon accepted and published in 1980 [3]. There were many pieces of the puzzle still waiting to be put together.

What the experts knew: “The eye is an accordion”

There was something very relevant that I did not learn at the university classes, but from my clinical training at the clinic of Optica Medica. When inquiring about the effect of patients not having their correct prescription on their glasses a senior practitioner told me with a smile: “Do not worry, the eye is an accordion”. He was telling me that the eye would adapt to whatever prescription was put on their glasses. He was absolutely correct although he did not know the depth of his statement. He knew from experience that the eye will eventually accept whatever lens power was in the glasses, but he did not know that the refraction of the eye would actually change in response to that lens so that it would end being the “correct” lens. There are some who believe that a lens in front of the eye could not change its refraction. We will see below how mistaken that view is.

A crucial experiment made in my mind

I will mention a summer parenthesis because it was then when I discovered that near work causes myopia and why. Simply because I realized that near vision and negative lenses are optically the same for the visual system and therefore also undistinguishable for Feedback Theory. The implications are profound as we will see later. In the summer before I went to Cambridge University a friend and I volunteered at a center for severely disabled individuals. I think it was called Leonard Cheshire. I always liked to help people with disabilities, but this was a little more than what I and my friend were prepared for.  I remember he introduced me the most severely handicapped individuals. One in particular named Peter, being tetraplegic, had no motion control of his body, other than his head, and he was also unable to speak, so someone before I came had fitted him with a metal horn on his forehead so he could use it to hit a touch screen keyboard on his wheelchair, like the one used by my colleague Steve Hawking in Cambridge University. Their keyboard controlled a synthesizer that would display on a screen or speak their typing. He was not happy with his horn, but frustrated because it would not work reliably. I saw the problem immediately as the horn he used did not make a good electrical contact with his forehead, as needed for the capacitive touch screen. While trying to find a solution to Peter's problem he informed me that his distance eyesight had deteriorated in the years that he used the device. I confirmed that he had developed myopia after he used the device. I made a metal contact for his horn with foil, placed the screen further from his eyes and ordered glasses. He was delighted with the results but I was puzzled why he developed myopia so fast. The paper that I published in 1980 explained that myopia would develop if a negative lens was placed in front of the eye, but he had used no lenses... or had he? I made a thought experiment while lying on my bed in the hospital. I placed Peter's screen far away and made it big so the retinal image would be the same size as if near, then I examined his eye  while he was looking at the actual near screen and while he was looking at the far screen with a negative lens. I found that there was no difference. Looking at the screen placed near his eye was like looking through a minus lens at a further distance. If I could not detect any difference, his eye's feedback system could not detect it either. That fact had far reaching implications. This is the principle of equivalency of near work and concave lenses, that I postulated in a paper in 1987 [4]. The view of a distant scene seen through a minus lens is equivalent to viewing a replica of the same at close distance. Feedback Theory told me that was the reason he developed myopia. It was the result of those invisible minus lenses.  When I announced him and the others that I was leaving to start the academic year in Cambridge University I noticed that his paralysis did not stop the tears in his eyes. I was moved, I learned from him and the others and I missed them, their image and legacy stayed with me. I had two interests grown stronger in that summer. I was determined to help those who were impaired and to continue my ophthalmic studies. I spent a great deal of time during the academic year at Cambridge England observing ophthalmological procedures at Addenbrooke's hospital. It was only interrupted when the Massachusetts Institute of Technology (MIT) offered me to continue with my Ph.D. in Cambridge, USA. I and my myopia research moved to Cambridge USA with new amunition from Cambridge England.

From Cambridge to Cambridge

The names, pictures, locations and events described here are all real. Any interested and named party wishing to make an addition or correction please contact the author.