Research encouraging for controlling myopia by reshaping the eye’s front surface

Contact Lenses and Eyewear

Brien A. Holden, PhD, DSc, LOSc
Brien A. Holden

Persistent research in eye growth and refractive development bodes well for controlling myopia with orthokeratology (ortho-K).

“It has been known for some time that hyperopic defocus — for example, the image falling behind the retina — can stimulate axial elongation and, therefore, myopia in young animals, primates and children,” Brien A. Holden, PhD, DSc, LOSc, a scientia professor at the University of New South Wales and head of the Institute for Eye Research in Sydney, Australia, told Primary Care Optometry News in an interview.

A series of studies have evaluated the relative contributions of central and peripheral image position to stimulate the progress of myopia. “In fact, the whole issue of axial elongation producing myopia was discovered by a Nobel Prize winner in medicine (1981), Torsten Weisel, MD,” Prof. Holden said. “Dr. Weisel sutured eyelids closed to look at the development of vision in the brain. The eye elongated and became seriously myopic.”

Investigators followed that research with experiments in which they put lenses of different powers in front of the eyes of young monkeys. “This resulted in changes in the refractive error,” Prof. Holden said. “For a long time, everyone thought these changes were mediated by central vision. But a series of experiments by Earl L. Smith III, OD, PhD, and colleagues showed that even if the optic nerve was not intact, the elongation of the eye would take place with such stimuli. This means a local retinal phenomenon was driving the elongation of the eye.”

Removing central vision with a laser, for example, then repeating the experiment, resulted in eye growth to the predetermined power of the stimulus, “even without the central retina,” Prof. Holden said. “It has only been in the past few years that we realized the periphery is at least as important, if not more important, than the central area of the retina.”

Visual experience and eye growth

Dr. Smith, dean of the University of Houston, College of Optometry, has considerable research experience in the role of visual experience in regulating eye growth and refractive development. “The reason we have been studying this area is because there is a lot of evidence that suggests that visual experience promotes the development and progression of myopia,” he told PCON. “Our long-term objective is to try to understand how visual experience influences eye growth. With this understanding, we might be able to develop methods to optically manipulate visual experience in a way that would control or reduce the number of children becoming nearsighted.”

Dr. Smith conducts essentially all of his research with nonhuman primates (monkeys). “We use things as simple as a spectacle lens to manipulate the effective focus of the eye in a controlled manner,” he said. The investigators isolate specific factors to determine if they influence eye growth.

“We have found that you can predictably alter eye growth by changing the effective focus of the eye,” Dr. Smith said. “By placing a lens in front of the eye, at least within certain constraints, we are able to predictably change the eye growth — making the eye grow longer and nearsighted or shorter and farsighted.”

Dr. Smith and his colleagues observed such a finding in monkeys many years ago. For the past 5 to 10 years, the researchers have tried to understand in detail the performance properties of the mechanisms that mediate this response.

“We have found that the eye uses visual feedback associated with its refractive status — in essence, optical defocus — to regulate eye growth,” Dr. Smith said. “You can also manipulate eye growth by manipulating the effective focus of the eye. This leads to very simple clinical predictions. Unfortunately, though, in many cases when we try these simple clinical predictions, they do not work. That is where the details come in and why we are interested at looking at the performance properties of these mechanisms that operate in counterintuitive ways.”

Peripheral retinal conditions

Dr. Smith and his associates have found that the periphery of the retina contributes substantially to eyeball growth and “probably dominates eyeball growth, in contrast to the center of vision.”

The research team has also theoretically designed lenses to address this concern. “However, we have not undertaken a clinical trial of such a lens,” he said. “But we have placed these kinds of lenses on animals, and these lenses do the things that we think they should do. It is really quite simple. You put a lens on the eye and the eye grows to compensate for the lens. It is very exciting. We are taking advantage of the natural growth-controlling mechanisms of the eye.”

Nonetheless, many unanswered questions remain about how the eye responds to lenses, according to Dr. Smith. “So we are very interested in understanding in detail how signals from different parts of the eye contribute to eye growth.”

Meanwhile, ortho-K produces changes in the optical system “that are in the direction of what I feel will slow progression of myopia. However, I do not believe the exact shapes of the corneas that we are currently achieving are optimal for slowing progression of myopia and giving clear central vision. It should be possible to design lenses that actually optimize the antimyopia optical characteristics of the cornea.”  

Added Prof. Holden, “In ortho-K, the post ortho-K central cornea is relatively flat and the peripheral cornea relatively steep, thus creating curvature of the image that can eliminate peripheral hyperopia.”

Children’s study

In Hong Kong, Pauline Cho, BOptom, PhD, and colleagues fitted a group of children with overnight ortho-K lenses, then compared them with a matched group of children from a historical control, Prof. Holden said. “The investigators measured the axial length and the refractive error of the children before they were fitted,” he said.

After following the children’s progress, the increase in nearsightedness in the ortho-K group “was significantly less than in the matched group, whose refractive error increased substantially more without wearing ortho-K lenses.”

The axial length increase among ortho-K children was only about one-third of the control group.

“The cornea of a child with ortho-K has been changed in such a way that the image is more curved, so that the peripheral image is brought in front of the retina or on the retina,” Prof. Holden said. “I am encouraged that we can control today’s myopia with ortho-K, based on the basic laboratory experiments and the ortho-K results to date. However, there needs to be a proper randomized, controlled clinical trial.”

Prof. Holden noted there is “quite a groundswell” against claiming an ortho-K effect until those studies are completed, “because you can always encounter a situation where the eyes regress or where you don’t have the confidence in the data, unless you have a control group that is contemporaneous.”

Dr. Cho’s control group comprised children she had studied previously who wore spectacles. “So with these caveats, ortho-K is encouraging but not conclusive, even though reports of Dr. Jeff Walline’s work from Ohio State University seem to confirm Dr. Cho’s findings,” Prof. Holden said.

Still, Prof. Holden said controlling myopia with an optical intervention is one of the most exciting areas for research in vision. Through the ages, there have been varied attempts to control the progress of myopia, ranging “from the Chinese wearing bags of small pieces of lead on their eyes while sleeping to people trying to change the shape of their eye with physical pressure,” Prof. Holden said.

 “Nothing has been very successful up until this point. But with the finding that peripheral image position is very important, it leads to the possibility that you can keep the central vision clear and alter the peripheral image, for a substantial effect on the progress of myopia. With nearly 2 billion people with myopia, and high myopia increasing the risk of retinal pathology, cataract and glaucoma, real progress in this area will have immense significance.”

For more information:
  • Brien A. Holden, PhD, DSc, LOSc, is a scientia professor at the University of New South Wales and head of the Institute for Eye Research. He can be reached at Level 4, Rupert Myer Bldg., University of New South Wales, NSW Sydney 2052 Australia; (61) 2-9385-7418; fax: (61) 2-9385-7401; e-mail: b.holden@ier.org.au.
  • Earl L. Smith III, OD, PhD, is dean of the University of Houston, College of Optometry. He can be reached at University of Houston, College of Optometry, 505 J Davis Armistead Bldg., Houston, TX 77204-2020; (713) 743-1899; (713) 743-0965; e-mail: esmith@uh.edu.

Brien A. Holden, PhD, DSc, LOSc
Brien A. Holden

Persistent research in eye growth and refractive development bodes well for controlling myopia with orthokeratology (ortho-K).

“It has been known for some time that hyperopic defocus — for example, the image falling behind the retina — can stimulate axial elongation and, therefore, myopia in young animals, primates and children,” Brien A. Holden, PhD, DSc, LOSc, a scientia professor at the University of New South Wales and head of the Institute for Eye Research in Sydney, Australia, told Primary Care Optometry News in an interview.

A series of studies have evaluated the relative contributions of central and peripheral image position to stimulate the progress of myopia. “In fact, the whole issue of axial elongation producing myopia was discovered by a Nobel Prize winner in medicine (1981), Torsten Weisel, MD,” Prof. Holden said. “Dr. Weisel sutured eyelids closed to look at the development of vision in the brain. The eye elongated and became seriously myopic.”

Investigators followed that research with experiments in which they put lenses of different powers in front of the eyes of young monkeys. “This resulted in changes in the refractive error,” Prof. Holden said. “For a long time, everyone thought these changes were mediated by central vision. But a series of experiments by Earl L. Smith III, OD, PhD, and colleagues showed that even if the optic nerve was not intact, the elongation of the eye would take place with such stimuli. This means a local retinal phenomenon was driving the elongation of the eye.”

Removing central vision with a laser, for example, then repeating the experiment, resulted in eye growth to the predetermined power of the stimulus, “even without the central retina,” Prof. Holden said. “It has only been in the past few years that we realized the periphery is at least as important, if not more important, than the central area of the retina.”

Visual experience and eye growth

Dr. Smith, dean of the University of Houston, College of Optometry, has considerable research experience in the role of visual experience in regulating eye growth and refractive development. “The reason we have been studying this area is because there is a lot of evidence that suggests that visual experience promotes the development and progression of myopia,” he told PCON. “Our long-term objective is to try to understand how visual experience influences eye growth. With this understanding, we might be able to develop methods to optically manipulate visual experience in a way that would control or reduce the number of children becoming nearsighted.”

Dr. Smith conducts essentially all of his research with nonhuman primates (monkeys). “We use things as simple as a spectacle lens to manipulate the effective focus of the eye in a controlled manner,” he said. The investigators isolate specific factors to determine if they influence eye growth.

“We have found that you can predictably alter eye growth by changing the effective focus of the eye,” Dr. Smith said. “By placing a lens in front of the eye, at least within certain constraints, we are able to predictably change the eye growth — making the eye grow longer and nearsighted or shorter and farsighted.”

Dr. Smith and his colleagues observed such a finding in monkeys many years ago. For the past 5 to 10 years, the researchers have tried to understand in detail the performance properties of the mechanisms that mediate this response.

“We have found that the eye uses visual feedback associated with its refractive status — in essence, optical defocus — to regulate eye growth,” Dr. Smith said. “You can also manipulate eye growth by manipulating the effective focus of the eye. This leads to very simple clinical predictions. Unfortunately, though, in many cases when we try these simple clinical predictions, they do not work. That is where the details come in and why we are interested at looking at the performance properties of these mechanisms that operate in counterintuitive ways.”

Peripheral retinal conditions

Dr. Smith and his associates have found that the periphery of the retina contributes substantially to eyeball growth and “probably dominates eyeball growth, in contrast to the center of vision.”

The research team has also theoretically designed lenses to address this concern. “However, we have not undertaken a clinical trial of such a lens,” he said. “But we have placed these kinds of lenses on animals, and these lenses do the things that we think they should do. It is really quite simple. You put a lens on the eye and the eye grows to compensate for the lens. It is very exciting. We are taking advantage of the natural growth-controlling mechanisms of the eye.”

Nonetheless, many unanswered questions remain about how the eye responds to lenses, according to Dr. Smith. “So we are very interested in understanding in detail how signals from different parts of the eye contribute to eye growth.”

Meanwhile, ortho-K produces changes in the optical system “that are in the direction of what I feel will slow progression of myopia. However, I do not believe the exact shapes of the corneas that we are currently achieving are optimal for slowing progression of myopia and giving clear central vision. It should be possible to design lenses that actually optimize the antimyopia optical characteristics of the cornea.”  

Added Prof. Holden, “In ortho-K, the post ortho-K central cornea is relatively flat and the peripheral cornea relatively steep, thus creating curvature of the image that can eliminate peripheral hyperopia.”

Children’s study

In Hong Kong, Pauline Cho, BOptom, PhD, and colleagues fitted a group of children with overnight ortho-K lenses, then compared them with a matched group of children from a historical control, Prof. Holden said. “The investigators measured the axial length and the refractive error of the children before they were fitted,” he said.

After following the children’s progress, the increase in nearsightedness in the ortho-K group “was significantly less than in the matched group, whose refractive error increased substantially more without wearing ortho-K lenses.”

The axial length increase among ortho-K children was only about one-third of the control group.

“The cornea of a child with ortho-K has been changed in such a way that the image is more curved, so that the peripheral image is brought in front of the retina or on the retina,” Prof. Holden said. “I am encouraged that we can control today’s myopia with ortho-K, based on the basic laboratory experiments and the ortho-K results to date. However, there needs to be a proper randomized, controlled clinical trial.”

Prof. Holden noted there is “quite a groundswell” against claiming an ortho-K effect until those studies are completed, “because you can always encounter a situation where the eyes regress or where you don’t have the confidence in the data, unless you have a control group that is contemporaneous.”

Dr. Cho’s control group comprised children she had studied previously who wore spectacles. “So with these caveats, ortho-K is encouraging but not conclusive, even though reports of Dr. Jeff Walline’s work from Ohio State University seem to confirm Dr. Cho’s findings,” Prof. Holden said.

Still, Prof. Holden said controlling myopia with an optical intervention is one of the most exciting areas for research in vision. Through the ages, there have been varied attempts to control the progress of myopia, ranging “from the Chinese wearing bags of small pieces of lead on their eyes while sleeping to people trying to change the shape of their eye with physical pressure,” Prof. Holden said.

 “Nothing has been very successful up until this point. But with the finding that peripheral image position is very important, it leads to the possibility that you can keep the central vision clear and alter the peripheral image, for a substantial effect on the progress of myopia. With nearly 2 billion people with myopia, and high myopia increasing the risk of retinal pathology, cataract and glaucoma, real progress in this area will have immense significance.”

For more information:
  • Brien A. Holden, PhD, DSc, LOSc, is a scientia professor at the University of New South Wales and head of the Institute for Eye Research. He can be reached at Level 4, Rupert Myer Bldg., University of New South Wales, NSW Sydney 2052 Australia; (61) 2-9385-7418; fax: (61) 2-9385-7401; e-mail: b.holden@ier.org.au.
  • Earl L. Smith III, OD, PhD, is dean of the University of Houston, College of Optometry. He can be reached at University of Houston, College of Optometry, 505 J Davis Armistead Bldg., Houston, TX 77204-2020; (713) 743-1899; (713) 743-0965; e-mail: esmith@uh.edu.