SIGHT, The Story of Vision2

“Glaucoma is a condition which can slowly rob someone of their vision and they may not even notice until significant damage has already been done to their eyes. This is because it is usually painless and virtually symptomless until it is already too late. Glaucoma is one more reason why yearly eye exams are so important. Getting your eye pressures checked and having the eye doctor examine the physical appearance of a person’s optic nerves can help to screen for early warning signs of glaucoma which a person could have and not even know it and early diagnosis and treatment can make a difference in its prognosis.” Cheryl Murphy ODRESOURCES WebMD, Glaucoma, Topic Overview AllAboutVision.com, Glaucoma National Eye Institute, Facts About Glaucoma American Foundation for the Blind, Glaucoma Guide That All May Read... National Library Service for the Blind and Physically Handicapped (NLS) 201

Age Related Macular DegenerationAGE RELATED MACULAR DEGENERATIONAMD or age related macular degeneration is the leading cause of blindness in the over 65 year old in the US. It’s the result of a combination of early retinal damage from ultraviolet, genetics, nutrition and lifestyle, over the patient’s lifetime.Sumit Garg, MD, Medical Director and Assistant Professor of Ophthalmology, Gavin Herbert Eye Institute at the University of California IrvineDr. Garg describes AMD using the camera analogy. “When you 202

think about the eye, the eye works like a camera and each part is important in giving us an image that the brain can process into vision. The retina is the film in the back of the eye, the macula which is the center part of the retina. The macula is the high definition part of the film and macular degeneration is a degeneration of the retina in that specific area.It's an age related process for the most part and that's why it's called AMD or age related macular degeneration. The photo receptors cells in the base of the retina degenerate. Depending on the type of macular degeneration, wet versus dry, degeneration happens in different ways. The dry type is the more common type, approximately 90% of patients overall. Geographic atrophy, is the predominant type, cells go through an aging process and they get worn out. The more devastating type to vision is what is called wet macular degeneration. There's a break in the membrane or the layer between the retina and the choroid (blood vessels layer behind the retina) allowing new blood vessels to grow into the retina. When these vessels leak, this is called exudative macular degeneration and results in either blood or fluid in the retina and that causes a very acute massive drop in vision. AGE RELATED MACULAR DEGENERATION 203

00:00 / 00:00 “AMD interferes with the detailed center of your vision, occurs as ‘wet’ or ‘dry’ forms, each has its own type of treatment”, Juan Batlle, MD, Director, Centro Laser, Santo Domingo, Sumit Garg, MD, Medical Director, Gavin Herbert Institute, UC IrvineFor wet macular degeneration previously used laser treatment would also cause some damage like a blind spot, when cauterizing the vessel. Currently, the most common and the most effective treatment is what is known as a intravitreal injection and they inject a anti-VEGF (anti-vascular endothelial growth factor). It causes the blood vessels to regress thereby the fluid regresses, and you can actually restore and improve vision. The important thing to know about macular degeneration is that it affects the center of your vision. If a person with AMD looks at someone’s face they can't see the most important details, their smile, their nose, their eyes, and you sort of see what’s around it. This can become very debilitating and since macular degeneration effects both eyes, the result is only peripheral vision.Patients will first notice a distorted view of objects looked directly 204

at because the macula is changing shape. It affects the place on the retina that delivers crisp vision as well as color vision. As AMD progresses, a central blind spot develops that can get progressively larger.Treating the dry version is more difficult; it involves treatment to prevent progression. The plan includes no smoking, taking vitamins, vitamins for macular degeneration and UV protection. That means wearing sunglasses outdoors. Those are really the main stays of treatment for dry macular degeneration, since the retina cannot yet be restored.Statistically, the longer you live the more chance you have of things degenerating in your body and the retina is no different. We can safely say that there's going to be an increase in incidence of macular degeneration. The good thing is there is lots of work being done in macular degeneration to help target therapies for it; from vitamin supplements and ocular therapeutics to the exciting work in stem cell research.”EVERYDAY VISION WITH AMDThose with AMD have difficulty with any task requiring sharp detailed central vision, which is the majority of how we use our eyes. Since there is usually some peripheral vision, making objects larger so that they can be seen using the parts of the retina that still work can be helpful. A closed circuit TV (CCTV) can assist for reading by magnifying the print without distorting it. There are many agencies and clinics that can help identifying these kind of tools. However, a low vision exam, through a low vision specialist can better define the aids in the form of magnifiers and electronic 205

devices that might be helpful. See the section of this eBook titled, “Low Vision and the Visually Impaired and Blind” A TELESCOPE IMPLANT FOR MACULAR DEGENERATION(This links to the description of Dan Dunbar and his telescope implant for AMD) RESOURCES WebMD, Age Related Macula Degeneration Health Center AllAboutVision.com, What is Age Related Macular Degeneration National Eye Institute, AMD 206

American Foundation for the Blind, Glaucoma Guide That All May Read... National Library Service for the Blind and Physically Handicapped (NLS) AOA.org, Age Related Macular Degeneration VisionAware.org, For Seniors With Vision Loss 207

Corneal Disease, Eye Banking CORNEAL DISEASEClaes Dohlman MD PhD, Professor of Ophthalmology, Harvard Medical School. Dr. Dohlman is chief emeritus at the Mass Eye and Ear Infirmary, said “...I’m 91, still at it, working full time with translational research on corneas and particularly artificial corneas and other rescue procedures when corneal transplantation is not successful.The cornea is only a very tiny slice of tissue. It's only about 11 millimeter in diameter and half a millimeter in thickness, but it is crucial. Its transparency is crucial. If cloudy from disease or degeneration or accident or chemical or trauma, the cornea responds with scar formation and therefore we cannot get a good image formation on the retina and the patient is more or less blind.According to World Health Organization, corneal disease is the 208

second-most prevalent reason for blindness, after cataract. The reason is that most of the corneal blindness occurs in the developing world, in the poorest parts of the world where … there are the least resources. For instance, corneal ulcer, bacterial ulcers are ten times as common in Africa compared to here. We live in relatively clean countries with antibiotics, antivirals and antifungals readily available and we don't have that much problems with infections.The developing world in particular, but also the rich world, has together somewhere between four and eight million people blind, bilaterally blind, both sides, both eyes, blind from corneal disease. They're blind to the extent that only surgery can possibly help and the corneal transplant has been for more than 100 years the standard procedure and it has worked well and saved many, the sight of many people, and the lives of many people. But, the outcome is usually overrated based on outcome studies from this and other clean countries where corneal transplantation is easier.”KERATOCONUS - CROSS LINKING Ron Gaster MD, FACS, Gaster Eye Center“KERATOCONUS is a condition where the cornea becomes steeper and steeper, progressively over time. As it steepens and thins, it also becomes astigmatic. The cornea no longer curved like a basketball but is more curved like an asymmetric football. As you can imagine, if it's the front part of the eye and the main 209

refracting surface, having it all distorted would cause distorted vision for the patient. As keratoconus progresses, a patient's vision gets worse and worse. Initially, it's treated with glasses. When they don't work, we try a contact lens, sometimes a soft contact lens, other times, it has to be a hard contact lens. In the past, when contact lenses didn't work the only alternative was a cornea transplant. The most exciting advance in keratoconus in the last 50 or 100 years has been the development of corneal cross-linking. In this corneal cross-linking, we strengthen and stiffen the cornea by a method where the epithelium (top layer) is removed. The cornea is saturated with riboflavin eye drops, which is vitamin B2. As long as the thickness of the cornea is over 400 microns, we then seal it with ultraviolet light, and it creates this cross-linking or strengthening of the collagen fibers so they no longer become ectatic or progressively get steeper.”Why does the cornea to steepen and thin?“That's a very good question, and we're really researching that now. Most likely it's just a function of the cells being not as strong and stiff as a normal person's, and the pressure in the eye either causes it to get steeper or they just get steeper naturally on their own.What are the end results if there's no treatment?If there's no treatment for keratoconus and it progresses, then the patient will eventually need a corneal transplant. We have various methods of doing that now. Sometimes we just remove the front part of the cornea and leave the back surface or the endothelium intact. That's called deep anterior lammelar keratoplasty. Other physicians do a full-thickness transplant. If we can stop it with corneal cross-linking, however, these patients won't need corneal transplants. When a patient needs a corneal transplant, it's a very good 210

procedure. We get very good results, but there can be complications associated with the procedure, so we try to avoid it. The World literature indicates that about 97% of patients who have corneal cross-linking end up stopping the progression of their disease. This is when the epithelium is removed, the result is excellent.(Editor’s note: for more information visit the National Kerataconus Foundation)KERATOPROSTHESES“In the developing world, donor material is often non-existing, eye banks non-existing, too expensive, and the follow-up is not possible, and lack of antibiotics, lack of contact lenses, this and that.We need something else as a reserve, as a rescue procedure, and we have worked for a number of years on a rather simpleminded concept, namely to replace the central cornea essentially with a clear window of plastic or other material. It is an obvious concept and as obvious as putting a window on a house to be able to see out. The trick has been, over the years, to get it to work and it has been very difficult and very subject to infections, exclusions, all kinds of calamities that not only makes the operation a failure, but also the eye is lost in the process.We have tried to work on that and we have achieved some improvement in the process and we have developed a little device of plastic that looks like a collar button and we put that into a corneal graft and then we suture that in place like a regular corneal graft. And the complications, of corneal complications of infections and tissue health and so on are now reasonably under control, but we have other problems in the back of the eye often with glaucoma and also, in the many severe cases, retinal detachment.The complication problems are not fully solved and the long-term 211

safety is not guaranteed, especially in the severe cases, but every year, we feel that we make some progress and I have a number of co-workers and we work on this as a team. Worldwide now, about 10,000 of these keratoprostheses, as we call them, made here have been implanted worldwide and I would estimate that in about half of them, it has changed the lives of the recipient or the patient, but we are continuing to work and I foresee that this will be a much more widespread rescue operation, a salvage procedure, when standard corneal transplant is not working.”CORNEAL TRANSPLANTSWalter Stark, MD, Professor of Ophthalmology, Director of the Cornea and Cataract Services, Johns Hopkins Hospital, Wilmer Eye Institute“The cornea is like a crystal of a watch, it’s a clear front surface of the eye that allows light to be transmitted and actually refracted to give good visual acuity. If the cornea is clear, and the rest of the eye is healthy, then usually the patient perceives good quality vision. The cornea is clear, because of the endothelial cells and the arrangement of the collagen fibrils. Collagen fibrils are tightly compacted and as long as they stay tightly compacted, then the cornea does not reflect light and remains clear. This all depends on the health of the endothelial cells that pool fluid out of the cornea, so in certain diseases such as Fuchs dystrophy or trauma, the endothelial cells become abnormal and the cornea swells and becomes opaque.”What is the most common element of the cornea disease, let’s 212

say in the first world versus what’s common in the third world?In the United States, the most common cause for the need for a corneal transplant is Fuchs corneal dystrophy. It’s an autosomal dominantly inherited disorder of the endothelial cells of the cornea, the cells that keeps the cornea clear and dehydrated. As people age that have this disorder, the cornea begins to swell and if it swells enough, the cornea becomes cloudy and the patients need partial thickness corneal transplant. We used to have to do a full thickness transplant, now we’re just transplanting the diseased cells, so this gives much faster rehabilitation to the patients.To do that we go inside the eye and take off the unhealthy endothelial cells and the eye banks usually prepare for us healthy endothelial cells from a donor who just donated their eyes. This is transported to us in transport tissue culture and media and very gently, we insert these new cells inside the eye. We usually get them to adhere by an air bubble. We use an air bubble to press the new cells up against the cornea and after about 20 or 30 minutes, it seems to adhere and function well and clear the cornea. So, this takes people who have visual disability or blindness and gives them back their sight. In the third world and developing countries, the major cause of corneal blindness would be climactic changes: wind, sand and dust and trauma. The patients do have Fuchs corneal dystrophy, but it’s not the major cause of blindness. In real developing countries, where trachoma still exists that causes scarring of the lids and the cornea and it’s a major cause of blindness.EYE BANKING 213

Eric Meinecke, resident and CEO of Georgia Eye Bank. ”An eye bank is an organization that honors the wishes of donors and their families by recovering eye tissue for transplantation and research. Most of the time an eye bank will recover the cornea, it's the outer front layer of the eye, sometimes we refer to it as the window of the eye. People that have dystrophies or blindness related to the cornea can be helped greatly by having a new window, a replacement window so that's what eye banks do. We recover that outer layer of the eye, process it, evaluate it, make sure it's safe for transplant and then we distribute it to a surgeon, an ophthalmologist trained in corneal transplant surgery to do the transplant procedure.“Eye banking in the United States is regulated by the US Food and Drug Administration. We are also accredited by the Eye Bank Association of America in Washington D.C. There are approximately 80 eye banks in the United States. Eye banking is a very small, non profit organization that serves a community of ophthalmologists and corneal specialists. Here at Georgia Eye Bank we have 35 full time staff members and we serve the entire state of Georgia. In the United States we are fortunate to have a surplus of donor tissue. That's because more awareness has been raised about eye donation and corneal transplantation. Now it's an elective surgery. An ophthalmologist will contact us and tell us that they have a patient that needs a corneal transplant and their going to schedule them for next Tuesday and our job as an eye bank is to 214

make sure they have a safe high quality donated eye cornea for that transplant surgery. Because we have a surplus in the United States that allows us to help eye banks or surgeons in other parts of the world so our eye bank and many other eye banks send tissue internationally. Every year we send tissue to India, to Kenya, to Saudi Arabia, the Middle East, and those are countries that do not have the eye banking system that we have, that we enjoy here in the United States.”What is the procedure for someone donating their tissue?“Many states including this state has a donor registry. When someone goes to the DMV to renew their license or get their license they can sign up to be a donor. A donor for organs as well as tissues and eyes. If they don't sign up on the registry then the family is given the option with the, the eye bank approaches the donor family and gives them options for donation. CORNEA 215

Cornea suspended in a carrier at an Eye Bank, available for transplantation. When a death occurs the hospital is required to call in to the organ procurement organization, the tissue bank, and the eye bank, and then we screen that patient to determine whether they are eligible or suitable to be a donor. We do screening for infection, communicable diseases like HIV and hepatitis... The hospital makes what we call a referral and then we will talk with the donor family, coordinate with the coroner, medical examiner if they were involved as well as the funeral home. The recovery of the eye tissue only takes about 45 minutes and it's done at the hospital, can be done at the mortuary or at the coroner’s office.”What would disqualify a donor?“The biggest concern when we are talking about a cornea transplantation is infectious disease so everything is aimed at the recipient in terms of safety. From the very first phone call to the time we deliver the eye tissue to the surgery center we are focused on screening and evaluating for infectious disease. Contraindications for eye donations or corneal transplantation would be HIV, Hepatitis, Septicemia. There's also some behavioral 216

histories, drug use, some travel exclusions. So we want to make sure that the eye tissue that we provide is safe for transplantation.”What is the common misnomers or what disqualifies someone transplantation?“Probably the biggest misnomer is cancer. A lot of people believe that if they have cancer they are not going to be suitable donor because the cancer would be spread from themselves to the recipient and that just isn't the case with ocular tissue. Lung cancer, liver cancer, breast cancer, all those are not rule outs or contraindications for transplant. If the cancer involves the eye directly then yes, that would not be a suitable cornea donor but most cancers do not involve the eye.” For the average American reading this, why should they care? “Corneal transplantation is a miracle. Being able to help a donor family through a loss, through their grief and being able to recover and honor those wishes, recovering that eye issue, evaluate it and help recipients with their vision, helping them return to a normal life; driving a car, seeing their children. Our mission is an amazing one and we get to help people on both sides and that's why I love eye banking.”CORNEAL TRANSPLANTS (cont’d)“In the United States 20 or 30 years ago, patients had to wait months to years to get a corneal transplant. With the development of eye banking and processing of tissue and sterility and controls, patients wait now a few days to weeks, but the eye banking system is not well developed in developing countries. We do supply from the United States about 18,000 corneas a year, but worldwide, there are a million people blinded from corneal disease, so it’s just barely dents the need for corneal transplantation.” 217

In developing countries, how is the community at large educated to overcome religious or spiritual belief?“We have worked with the local communities and the religious leaders to encourage them to come out and say that it is not against the religion to give the cornea. That does not disfigure the body, just the cornea is taken not the whole eye. Most of the countries now, they allow obtaining of the corneas with permission from the family for cornea transplantation. If that’s not possible, then we try and supply those patients and surgeons with extra corneas that we have in the United States. In the United States, there are about 45 to 46,000 corneal transplants done each year. We do obtain about 65 to 68,000 corneas, so if they’re not going to be used in the United States or if there’s not an emergency need at that particular time, we want to make sure that the cornea is used to the benefit of the patient somewhere. We’ll go to all means to make sure that that cornea is transported to Israel, to Saudi Arabia or to Europe for use to the benefit of patients.The gift of a cornea is a gift of sight. in a conversation with patients and their families... this is the only positive thing that takes place along with a death, which is a sad event. This is not only giving two patients the ability to see, it’s the continuation of life of part of the person who’s died; continuation of a healthy cornea in the patient who is a recipient. We look at it as giving the patients the opportunity or their patient’s family the opportunity to not only help those who are visually blind from corneal disease, but also give some satisfaction that they’re helping cure or prevent blindness.” Walter Stark, MD, Professor of Ophthalmology, Director of the Cornea and Cataract Services, Johns Hopkins Hospital, Wilmer Eye InstituteSTEM CELL THERAPY 218

Sayan Basu, MD, Consultant and Scientist, LV Prasad Eye Institute“This patient with a corneal scar in the left eye, an infectious keratitis will be treated with stem cells. This a new experimental therapy uses the patient’s own stem cells to cure the corneal stromal disease.”CORNEAL STEM CELL SURGERY 00:00 / 00:00 “In the absence of enough donor corneal tissue, stem cells from the patient are used to regenerate their own cornea to restore clear vision.” Gullapalli Nag Rao, Founder, LV Prasad Eye Institute, Sayan Basu, MD, Consultant and Scientist, LV Prasad Eye Institute 219

Dr. Basu says, “We are trying to find a simple solution where you not have to depend on the donor corneal tissue because that's our kind of bottleneck, that's the limiting step. If we can use stem cells, preferably from the patient’s own cornea to help regenerate the cornea, instead of replacing the scar tissue, so that the tissue becomes transparent again. The procedure that we are delivering is in collaboration with professor James Funderburgh PhD (University of Pittsburgh, School of Medicine). We call this the Funderburgh Procedure which places stem cells on the corneal stomata, after removing the epithelium. The stem cells are basically in the fiber glue, and we just put a drop of glue on the cornea. The procedure can be done under topical anesthesia, it really doesn't require the eye to be completely anesthetized. We just treat the center of the scar and so we mark out the area of the cornea that we are going to treat, then we gently hold the eye with the blade, scrap away the superficial layer of the cornea, which is the epithelium and create a epithelium defect. and apply the stem cells. A biological glue and the stem cells make up this gel; fibrin and thrombin. the same gel effectively that forms in blot clots. The stem cells get incorporated into the cornea. this gel basically is quite thick and it doesn't get dislodged because it sticks to the cornea, and the epithelium grows over it and the gel allows the cells to get incorporated into the cornea matrix. and then these gels have good healing properties and can moderate scars.We put a soft bandage contact lens. The patient just gets prophylactic antibiotics and it takes about 4 to 6 weeks for the stem cells to start working. So once the stem cells get incorporated into the corneal stroma they start to eat away the scar blocking vision. As it eats away the white tissue of the scar it is also re-layering new tissue. This new tissue is just like the normal corneal matrix in that it is transparent and it can let light pass through, fall on the retina 220

and the patient can see.”RESOURCES LV Prasad Eye Institute AllAboutVision.com, Cornea Transplant, What to Expect National Keratoconus Foundation WebMD, Keratoconus American Optometric Association, Keratoconus 221

SECTION 5 Retinal Disease, DetachmentCENTRAL VEIN OCCLUSION Louis J. Fox, BA, University of Pittsburgh, JD, Boston University Law SchoolTell us how you learned that you had a central retinal vein occlusion? “The first time I noticed it was December of 1999. I was in Florida and we were standing on the outside patio and looking out in the ocean. There was a boat out there and for some reason I happened to wave my hand in front of my right eye. I noticed that my vision, when I blocked this one eye, there was a difference, there was something wrong. I had no idea what it was, had no doctor or know an ophthalmologist. Through a close friend and number of visits, the doctors diagnosed that I had just central retinal vein occlusion, or as they said to me, I just had a stroke in my eye. And three years later it happened in my other eye. It can correct itself and go away or in my case, it didn’t, and can get 222

progressively worse. In my very very unlucky case it can happen bilaterally, in my other eye which is unusual. Not rare, but it is unusual to have it in both eyes.”Can you explain Central Retinal Vein Occlusion?“In our physiology the arteries bring fresh oxygenated blood to the organs and in this case the central retinal artery brings oxygenated blood to the retina, the optic nerve, and other parts of the eye. The central vein takes the deoxygenated blood away from the eye. In my case, there is a blockage in the central retinal vein. Fortunately, central retinal arterial blockage causes almost instant irretrievable blindness. In central retinal vein occlusions, you don't necessarily have to lose your vision, it can either fix itself, or it can progress overtime and slowly cause your vision to erode. The causes they believe are a clot in the vein in the back of the eye, within the optic nerve. The central retinal vein isn't draining the blood out of the eye and as a result it causes a backup, it causes the photoreceptors to get sick and die, and it can cause damage to the optic nerve through ischemia, the lack of oxygen.”What's is your vision like?“Not good. For example, we are sitting probably eight feet apart. I can't really see you, I see your head because I can see contrast. It's hard to see definition. And near vision is inhibited. I use a magnifier to read, and I use different tools, but subjectively, what I call the vision is highly limited. I can still see contrast, but no color, I couldn't describe what you look like at all.”You’ve contributed to help create the Center for Vision Restoration, why?“About 4 and a half years ago one Sunday morning. Dorothy, my wife, was watching it and said, \"you've got to come and see this.\" They had a special program on regenerative medicine. They were talking about the University of Pittsburgh and Wake Forest 223

University.In the course of the discussion they mentioned that they wanted to develop a program in ophthalmology. At that time I had been suffering from central retinal vein inclusion, both eyes, for several years. Being a Pitt graduate, I immediately made a few calls and got directed to the McGowan Institute. From that learned what the University wanted to do... that they were very interested in establishing a specific center for regenerative medicine in ophthalmology.. I subsequently flew to Florida I met with several of the Pitt and McGowan people and was very attracted to what they wanted to do. They were really talking my language, talking about translational medicine. Getting it from the bench to the patient. I found that very attractive. I liked the dynamics, the chemistry, and that's how it started. A WHOLE EYE TRANSPLANT INVESTIGATION SEEMED LOGICAL 00:00 / 00:00 Louis J. Fox, BA, JD describes the formation of the Fox Center for Vision Restoration 224

Taking bench research to the patient is difficult, correct?As a person whose spent his life in the physical commodity trading merchant banking world, there's no concept of constant meetings, what have is trading that takes place on a 24/7 basis.The way science works, to its credit, is that they have to go through this enormously lengthy process to get to the right ending. Unfortunately it takes a lot of time, and for the patient it's very frustrating. For some, the FDA is like the boogieman. However, I have a different of the FDA because of the interaction that I've had separately and subsequently in developing a company to work on the issue of central retinal vein occlusion. Frankly I found the FDA to be cooperative, responsive. I approached it as a small company, as a virtual company owner. I approached them as our partner. We needed them and they responded.”What’s the future?“Well, at the moment we're looking at two specific projects. When you mentioned ten years out... we are talking about the concept of the whole eye transplant. It’s is a very audacious project and we have put together the beginning of a collaboration with other institutions to develop that. That's pretty aggressive and pretty wishful but I think it's quite possible. The idea of the whole eye transplant really came out of the University from one of the transplant surgeons who is very much involved and did the single and double hand transplant. The University is known historically as one of the leading transplant centers in the United States if not the world. So it was a natural thing, why not transplant the eye since we have all that technology. The Fox Center is unique in its structure because it's really a center based on a three legged stool. One leg is the McGowan Institute of Regenerative Medicine, one leg is the University of 225

Pittsburg Medical Center, UPMC, and the third leg the University of Pittsburg. The Fox Center sits on top of that and draws from the faculties of all three. Even though we are focused solely in ophthalmology, we get the benefit of all these other areas of medicine that the University is well known for. There are many institutions including our own, working on the concept of the artificial retina, replacing the retina, or transplanting the retina, whether it's through the development of stem cells or genetic engineering. These two projects draw on the deep resources supporting the Fox Center.RETINAL DETACHMENTCHANGES IN VISION REQUIRE AN IMMEDIATE VISIT TO THE DOCTOR 00:00 / 00:00 Eddie Leavell describes his experience with his detached retina, Juan Batlle, MD, Centro Laser, Santo Domingo describes one instance of retinal tears when the vitreous pulls away from the retina causing a tear. 226

Juan Batlle, MD, Director, Centro Laser, Santo Domingo“The cavity that we have in the back of the eye is known as the vitreous chamber. It is filled with vitreous humor.It's like a gel but not exactly a gel, there are actually fibrils, microscopic fibrils that adhere the the vitreous to the retina. Now the vitreous is a part this architecture of skeleton of the eye. But it also has optical properties because it's transparent and allows light to go through. Can you imagine if this fills up with blood, the eye will go immediately blind and this is what happens in diabetes. More frequently the vitreous will separate from the retina as we get older and then we start seeing these little floaters in front of our eyes that we follow and they’re still there. These floaters are actually the places where the vitreous was adherent to the optic nerve, the macula or the retina periphery. In separation sometimes it will tear the retina and if we do a retinal tear we are to get a retinal detachment. Part of the modern treatment of retinal pathology, when the separation of the vitreous occurs, called a posterior vitreous detachment, is to look carefully to exclude the possibility of a tear. If there is a tear we treat it with a laser to seal and prevent the detachment. If the patient is not aware of the tear or does not have access to eye care, the retina will detach before he gets proper eye care. That’s unfortunate since the treatment of the tear, with a laser is 227

a ten minutes office procedure but the treatment for the retinal detachment is an operation. The operation involves an operating theater, removal of the vitreous, replacing it with fluid or gas or silicone oil, laser procedures, all very costly. And, the prognosis is not as good. So if you seal the tear with a laser before the retina detaches that eye will go back to 20/20. But if you detach the retina and it's been detached for two, three months which is typical in emerging countries, in spite of your ability to reattach the retina, visual acuity will be very poor. RESOURCES All About Vision, Detached RetinaA detached retina is a serious and sight-threatening event, occurring when the retina becomes separated from its underlying supportive tissue. The retina cannot function when these layers are detached. And unless the retina is reattached soon, permanent vision loss may result. 228

Whole Eye Transplant? Larry Benowitz. PhD, Professor of Neurosurgery and Ophthalmology, Harvard Medical School, F.M. Kirby Neurobiology Center.What are some of the difficulties dealing with neurons, what condition occurs when a nerve is cut?“Throughout the central nervous system, that includes the brain, the spinal chord, the eyes, the optic nerves, these nerves pathways cannot regenerate if they are injured. That is to say, the nerve fibers, the axons that originate in nerve cells can't grow 229

back if injured. They have some ability to sprout, form local side branches but the ability to grow over long distances, once they've been injured, is pretty much lost after early stages of development. This situation is quite different from our peripheral nerves that run from our spinal chord or from the so called ganglion that sits right outside the spinal chord. If those fibers are injured they can grow again. But within the brain spinal chord, optic nerve, there is very very little regrowth after injury. As result, people who have had traumatic damage to the optic nerve or people who have had ischemic injury to the optic nerve or people who have suffered vision lose for other reasons... There's virtually no possibility of visual recovery. That happens in glaucoma as well. The optic nerve is damaged; the ganglion cells begin to die subsequently. That lose of vision is not recoverable. So, this represents an immense clinical problem and the optic nerve, by virtue of it being the most accessible part of the central nervous system, is often used as a model system to understand basic principles about nerve regeneration. That is, to try to identify the factors that normally keep nerve fibers from regenerating and to try to develop ways of reversing that situation and promoting regeneration.”Does nerve regeneration advances and spinal column research suggest possibilities? “Whether it is damage to the optic nerve, or ischemic damage of the optic nerve, traumatic damage to the optic nerve, even glaucoma or other sources, loss of the photoreceptors, loss of the pigment epithelial cells... Whatever the source of the damage, a very kind of daring and futuristic and perhaps crazy approach would be to replace the whole eye, to do a whole eye transplantation. 230

...There were early steps at this idea back in the late 1800s in fact, but there are immense problems. The primary problem is if you take an eye from a donor, presumably, you know, post mortem. First off, you have to keep the cells alive. The cells in the eyes particularly the neurons that project, that collect visual information and send those nerve fibers back into the brain are very very delicate and they'll begin dying within, one sees the first signs of pathology within hours after injuring their nerve fiber and within a few days they begin to die. So first off what one has to discover is to maintain those cells, their viability, keep them alive. But, the bigger problem that had seemed impossible was to get those nerve cells from a donor eye to grow back into the recipients brain. The nerve cells in the eye, the retinal ganglion cells... these are the cells that collect visual information from the photo receptors, from the interneurons, amacrine cells, bipolar cells... They collect that information and then send it on into the brain, their nerve fibers, their axons run through the optic nerve. So one major problem is that as soon as those axons are injured pathological processes get set into action and we can detect changes as early as one hour after injuring those nerve fibers. We can start detecting changes in the retina. Those changes lead to a cascade of events and within a few days one starts seeing those nerve cells just dying off. And of course, when they are gone their irreplaceable. We don't know how to replace them yet. So, one major challenge is to keep those cells alive. To figure out what is the sequence of events that leads to the death of these cells. We know many components of it, we don't quite understand how they all fit together. We don't quite understand how to intercede to keep these cells healthy and alive for a long periods of time after, after explant. We know many components of it but perhaps not enough yet. That is number one. Perhaps the even bigger problem is that even if those cells are maintained alive we have the issue that they normally cannot 231

regrow those nerve fibers into the recipient nervous system. It's the same problem of regeneration. The thing that seems to have restored some optimism to this idea is the success that some laboratories, including ours, have had in promoting regeneration. It maybe possible, in principle, to get those nerve fibers to grow back again into the brain. Of course, one would want the numbers to be much greater. One would want to show that those nerve fibers are really forming a very precise patter of connections so that the visual world gets represented in the brain in an orderly fashion. So these are many empirical questions that we really won't be able to answer until we start working on it. But this is from the kind of, um, neurological point of view. The question of neuro-integration, integrating that visual information back into the brain. There are many other problems as well. Such as, is reconnecting the vascular supply to the donor eye. The eye receive an enormous blood supply and of course this is necessary because of the very high rate of metabolism of the cells in the eye. Reconnecting the vasculature so that the recipients blood supply is, is providing the blood supply to the eye, the arterial system, the venous system, that all has to be reestablished. Then there's another huge problem of immune rejection that is of course that there is likely to be incompatibility between the donor tissue and the recipient. The problem of inflammation initially when this transplant is done. So there are many areas of, of biology and medicine that come into play and we have now put together a research consortium. Just recently. That includes people with expertise in all of these areas. Ocular immunologist, people who know a lot about inflammation, people who know a lot about immune rejection, people who know about reconnecting the vascular supply... People like Jeff Goldberg and myself 232

working on the regeneration side, other people working on the regeneration side. Perhaps bringing in things that are being discovered in other laboratories around the world, people with expertise in keeping cells alive, people who have discovered some of the neuropath ways, some of the molecular pathways that are important in maintaining the viability of cells are apart of this team. So far, we've only talked once. So it's really at it's infancy, but there is a lot of excitement being generated and I don't think we are so optimistic as to think that we are really going to accomplish this in the near future, in the very near future. But we think at least, we are going to discover what problems need to be dealt with along the way and so we are hoping to pursue several tracks and parallel.”The F.M. Kirby Neurobiology Center, together with the Neurobiology Program at Boston Children’s Hospital, is the largest basic neuroscience research enterprise at a U.S. hospital. It incorporates basic and translational neuroscience research, focusing primarily on developmental neurobiology.WHOLE EYE TRANSPLANT Joel Schuman, MD, Professor and Chairman of Ophthalmology Department, University of Pittsburgh, Director of UPMC Eye Center and Louis J. Fox Center for Vision Restoration. 233

“The eye is tremendously complex as well as beautiful. Some people say that the brain is actually an extension of the eye. That's not that far off because the signals from the eye go to the brain, where the vision is processed, but in the eye itself, you have a system that focuses light and a system that receives that light signal, converts it to a chemical energy and then to electricity, and then it processes that information across three different levels before it ever gets sent to the brain. Then once the information gets to the brain, it gets processed in many different locations. It's not just in one location called the visual cortex, but rather you have the information being processed throughout the brain with a lot of crosstalk between the nerve cells in the brain. It's that complexity of the eye that really makes it difficult to regenerate the tissue and to restore vision. What are going to be the goals and future achievements at the Fox Center?The Fox Center is really broadly designed. We're interested in vision restoration across the board. It doesn't matter where in the eye the disease is, we try to be as broad as we can in terms of our approach. We're agnostic in terms of what the solution is so whether it's gene therapy, or some sensory substitution technology, or a small molecule, or stem cell therapy, it really doesn't matter. As long as we are able to restore the perception of vision. We think that within the next five years, we'll see stem cell based therapies for corneal blindness. There are experiments, clinical studies, going on now in India that are based on findings that have come out of the Fox Center, specifically work by Jim Funderburgh. It seems like the cells that Jim Funderburgh discovered and has been working with actually rebuild the cornea which is quite amazing. I also would say that in the next five to ten years, we'll see stem cell based therapy for curing the high pressure that we see in glaucoma. In other words, 234

using stem cells to regenerate and rebuild the outflow system, the trabecular meshwork, Schlemm's canal, the way that fluid gets from inside the eye back into the bloodstream. That's one of the things that is diseased in glaucoma, so that tissue, the drain of the eye is not working properly and pressure builds up. By using the stem cell therapy, we think that we will be able to restore normal function to that tissue and restore normal eye pressure. I think it will take a little bit longer to provide cures for retinal diseases. The reason that I say that is the retina is a significantly more complex structure. It is part of the central nervous system and there is processing that occurs within the retina that makes it, again, more complicated in terms of repairing. We think that there will be a variety of approaches and it will encompass all of the ones that I've talked about, stem cell gene therapy, small molecule, and technology based. The same goes for the restoring the function of the optic nerve. One of the projects that we're doing is whole eye transplant. We've assembled a group of investigators from the best universities in the world. They're from University of California San Diego, from Harvard, from University of Minnesota, from Johns Hopkins University, from the Vision Institute in Paris, the list goes on. These are the 'best of the best' in terms of the surgery that would be needed to do whole eye transplantation, the science that will be needed in order to regenerate the optic nerve, the science that will be necessary in order for us to make sure that the information coming back to the brain is understood by the person who gets the eye transplant, and also people who are expert in immunology who will help to ensure that we don't reject an eye that's transplanted. This is actually a do-able project. I say that because, if you dissect down the project itself, we've already got a model of eye transplantation. In other words, our surgeons who do complex tissue allografting, are already able to take an eye from one animal and transplant it into the other animal and keep that eye 235

alive. All of the tissue in the eye looks pretty good with the exception of the optic nerve which dies. That's an exciting model. Being able to use that as a scaffold on which to build for optic nerve regeneration and also these immunological studies is going to be very important.”Is the reason why you're going after the whole eye, is that the nerve, if you can get it to re-attach, that’s much easier than trying to deal with the microscopic level of the retina? What else?That's absolutely right. The eye is a beautifully designed organ. The complexity of this organ is very, very high. By doing a whole eye transplant, we bypass a lot of that complexity. We still are left with the problem of regenerating the optic nerve which is a pretty serious problem. We bypass the problem of regrowing the retina, for instance. Another project that we're involved with is visual cortical neuroprosthesis. We're approaching these two very disparate ways of restoring visual perception in parallel. One is the whole eye transplant, another is using technology to provide the information directly to the brain so that we will be able to give that visual percept, not as just flashes of light or what we call phosphenes, but as a true visual perception as you and I experience vision. That means that we need to understand how the brain processes that information that's coming to it from the eye. That is going to take some very basic work in order to understand all of the interconnections that a bit of visual information goes through before it's perceived as vision. We're encouraged by the fact that we can do something called sensory substitution and still give people an experience of the visual world that is not true visual perception, but it is an experience of the visual world. In terms of the visual cortical neuroprosthesis, our goal is to be able to use technology that would essentially plug directly into the brain and provide a true visual percept.” 236

Dry EyeDRY EYEAdapted from Dry Eyes, Linda Conlin, ABOC, NCLEC, 20/20 Magazine, Oct 2013, Jobson Medical Information LLC) Dry eye syndrome is the lack of sufficient lubrication and moisture on the surface of the eye because of decreased quality or quantity of tears. As a result, patients suffer constant discomfort from eye irritation. Symptoms include persistent dryness, scratchiness, burning, foreign body sensation, blurred vision, light sensitivity and, surprisingly, tear overproduction. Fifty percent of contact lens dropouts are associated with discomfort from dry eye. The syndrome is more common in smokers and women. CLIDEWith the prevalence of the syndrome an acronym developed, but unlike most acronyms, this one, CLIDE, describes describes two issues. The first is for the condition known as Contact Lens-Induced Dry Eye, and the second is for the causes of dry eye: Climate, Drugs, Environment.1 The acronym becomes a handy tool to understand the causes of dry eye. 237

The incidence of dry eye increases in dry, dusty, windy and cold climates. Of the top 20 U.S. cities for dry eye, Las Vegas ranks first and five Texas cities are included in the group as one might expect, but so were Boston and Newark, NJ. Dry eye is so prevalent in Texas that a vision center specializing in dry eye treatment sponsors a Dry Eye Index on the local news in Amarillo, much the way other cities report heat indices or wind chill factors. The Dry Eye Index indicates grades of environmental conditions that result in dry eye symptoms progressing from “clear” to “comfortable” to “uncomfortable” to “miserable”. In these cities, the effects of drying can take dramatic turns, especially for individuals working outside. Denver, also on the top 20 list, had a wind storm during a baseball game that affected Atlanta Braves first baseman, Freddie Freeman. Dust and dirt blew everywhere. Freeman changed his contact lenses six times during the game and wore sunglasses. At some point during the lens changes, he scratched his cornea, forcing him to wear glasses until it healed. During that time, Freeman’s batting average dropped 50 points. He finished the 2012 season with an average of .259 versus .282 in 2011. Drugs-such as antihistamines, antidepressants, antihypertensives which are frequently diuretics, Parkinson’s medications and oral contraceptives-can result in dry eye as a side effect. Aside from climate, environments with dry heat or air conditioning can contribute to dry eye. Other factors that produce dry eye include insufficient blinking as can occur with computer use, long term contact lens wear, eyelid disease, tear gland deficiency, aging, menopause and diseases such as lupus, rheumatoid arthritis, ocular rosacea and Sjӧgren’s syndrome.Sjӧgren’s syndrome is a disorder of the immune system characterized by dry eyes, dry mouth and fatigue. It is commonly associated with rheumatoid arthritis and lupus, and results in a decreased production of tears, saliva and sweat. It occurs more often in women over age 40, and is treated with increased water 238

intake, eye drops and drugs. Sjӧgren’s syndrome gained national attention in the late summer of 2011 when tennis pro Venus Williams, then 31, announced she suffered from the syndrome and its symptoms. Williams cited fatigue as the reason she withdrew from her 13th U.S. Open. CLIDE also is an acronym for Contact Lens-Induced Dry Eye. In this condition, the presence of the contact lens, as well as decreased corneal sensitivity from long term contact lens wear, disrupts normal tear film, resulting in a shorter break up time. The practitioner has a variety of contact lens options within the categories of rigid and soft lenses to address dry eye.TEARSThe quality and quantity of tears are the critical factors in dry eye syndrome. The tear film consists of three layers: lipid, aqueous and mucin. The outer, lipid layer is oily and prevents the evaporation of tears. It is manufactured by the meibomian glands located on the lid margins. The middle, aqueous layer is the largest portion of the tear film, contains dissolved sticky proteins or mucins, and supplies oxygen to the cornea. The lacrimal glands above the outer canthus secrete this layer of the tear film. The inner, mucin layer-which is produced by the goblet cells in the conjunctiva- keeps the highest concentration of mucins at the surface of the eye. Mucins help stabilize and spread tear film.DRY EYE CLASSIFICATIONThe National Eye Institute has identified two classifications of dry eye syndrome based on the type of tear deficiency: aqueous tear deficiency (ATD) and evaporative tear deficiency (ETD). Aqueous tear deficiency, also called keratitis sicca, is an insufficiency in the aqueous or watery layer of tears and is the most common type of dry eye. 239

Evaporative tear deficiency is an insufficiency of the lipid or oily tear layer which functions to slow tear evaporation. Patients can suffer from a combination of both ATD and ETD.TESTINGEye care practitioners (ECPs) commonly use two tests to classify dry eye syndrome: the Schirmer test and the Break Up Time test. The Schirmer test evaluates the quantity of tears. The practitioner places the folded end of a thin strip of filter paper inside the lower lids of both eyes. After five minutes, the practitioner evaluates the moisture of the eye by observing how much of the filter paper became wet through capillary action. Fifteen millimeters or more is considered normal, nine to 14 millimeters indicates mild insufficiency, four to eight millimeters indicates moderate insufficiency and less than four millimeters indicates a severe condition. The B.U.T. (Break Up Time) test evaluates tear quality by measuring how long it takes for dry spots to appear on the cornea after a blink. The ECP applies fluorescein to the patient’s eye and then observes the tear film after a blink while the patient tries to avoid the next blink. The practitioner counts by seconds until a dry spot appears. A break up time of more than 10 seconds is normal, from five to 10 seconds is marginal, and less than five seconds is low. TREATMENTSWhile no cure for dry eye syndrome presently exists, ECPs can help patients manage the symptoms. For mild cases, this can be as simple as encouraging the patient to drink more water. Adult women should have 91 ounces or about 12 glasses of water a day, while men should have 125 ounces or 16 glasses. Studies have shown that increasing omega-3 and vitamin A intake is beneficial. Both of those nutrients are found in some fish oils and maintain mucous membranes. Severe or prolonged vitamin A 240

deficiency is characterized by dry eye and changes to the cornea that can result in corneal ulcers, scarring and blindness. Other things patients can do to alleviate dry eye symptoms include wraparound sunglasses with side shields, indoor air filters and humidifiers, checking with their doctors to change medications that have dry eye as a side effect, and resting their eyes during visually demanding tasks.9 Remind patients of the 20/20/20 rule. After 20 minutes of a visually demanding task such as reading or computer work, rest the eyes for 20 seconds by gazing at a point 20 feet away.BlinkBlinking is an important part of keeping the eye moist and lubricated. Blinking facilitates tear drainage, eliminates debris, spreads lipids across the tear film and nourishes the cornea. Research indicates that patients with dry eye have a higher blink rate, and a higher blink rate is associated with a shorter tear break up time. Artificial TearsArtificial tears or contact lens rewetting drops may be all that is needed to alleviate the symptoms of mild dry eye. However, drops containing preservatives may cause irritation and patients shouldn’t use them more than four times a day. Patients can use non-preserved drops in single use vials more often. When contact lens wearers use artificial tears, they should remove their lenses and wait 15 minutes before re-inserting them. Patients can also use ointments applied before sleeping. Instruct patients that drops to “get the red out” are vasoconstrictors and may not lubricate the eye. What’s more, a tolerance to the drops can build up and result in more redness.For some dry eye patients, such home and OTC remedies will mask the problem for a short time, and other measures need to be taken. For instance, blepharitis, an inflammation of the lid 241

follicles, blocks production of the oily component of tears. One way to reduce the inflammation is to gently rub the lids with a warm washcloth, then massage the lids near the base of the lashes with baby shampoo or lid scrubs.22 Taking a different aim at inflammation, Allergan introduced Restasis® cyclosporine emulsion in 2003 to treat dry eye symptoms. It is an immunosuppressant that reduces inflammation, and in this way, it helps increase natural tear production. Patients need to administer the drops only twice a day, and it can be used in conjunction with artificial tears. MEIBOMIAN GLAND DYSFUNCTIONDonald Korb OD, Chief Technology Officer and Co-Founder, TearScience, North Carolina. What are tears and why are they important?“The eye is really a unique organ. Its requirements are optically to provide one of the finest optical surfaces in the entire world... and it's all dependent upon the cornea. The cornea is made out of cells and cells have to be replaced. To protect this and to polish it into an absolutely clear surface, we have tears. Tears are not simple. There's over 100 different substances in tears. They are remarkably complicated and they have to sit in a thin film on the front of the eye and defy gravity. 242

They also can evaporate, so the evaporation is protected by an oil layer, which sits right on top of the liquid phase and that oil layer is formed and produced by glands in the eyelids. There's approximately 20 to 25 MEIBOMIAN glands in the lower lid and 20 to 25 meibomian glands in the upper lid. Their job is to produce this wonderful lipid (an oil), which prevents evaporation.If you don't have adequate oil, then the tear film evaporates. When the tear film evaporates, you have a condition that stresses the entire system and then there’s inflammation and all the other problems of dry eye. So the tear films job is not only to make a great optical surface, but it's also to preserve that optical surface from trauma, and from drying out, so that it remains viable indefinitely.”What are some of the complications with our tears and our tear ducts?“The complications are just being really understood. Complications with tears can actually, at one end of the spectrum, lead to severe neuropathic pain. These are the individuals who come in and say, \"my eyes just hurt, and they hurt, and they hurt.\" They don't have adequate tears to protect the ocular surface. The nerves are constantly stimulated, and overstimulated. This over stimulation results in inflammation and now begin to hurt. And, when they are so severely over stimulated, it's quite possible for them to have sensation, without that stimulus.Individuals will come into the office and say, \"the only time I have relief, doctor, is when I close my eyes.\" Well that tells us that when we take the evaporated stress off ... that they have enough tears to protect it, and the nerves quiet down so that they don't have pain. But they may also say, \"even when I close my eyes, my eyes just hurt, and hurt, and hurt.\" And frequently, that pain is called neuropathic pain. We're very indebted to Perry Rosenthal, MD (Children's Hospital, Boston Eye Pain Foundation) for chronic pain 243

research.At the other end of the polar spectrum, we have a tear that can protect itself, except under stress. Stress could be wind that increases the rate of evaporation. But we now have a lot of electronic devices. And what do electronic devices do? They cause us to stare, and stare, and stare. All that time you're getting evaporated stress. When you have evaporated stress ... that leads to what we just discussed. Namely stimulation of the corneal nerves, and you start the whole cycle.Individuals are very fortunate when, if the stimulus is removed, the pain goes away. But the terminal end stages, as we're finding out, are that the pain frequently doesn't go away. Particularly with older individuals.”What are some of the symptoms that someone might have that would relate to a dry eye, or a lack of tears?“There are 2 distinct types of symptoms. If individuals feel scratchy, grittiness, sandiness, mechanical types... they probably have a lack of lubrication, there isn't adequate fluid. That's in contrast to a completely different phenomenon, where people say \"my eyes sting, they burn, they feel warm.\" To test for that is very simple. Try this, \"blink one, blink two... don’t blink, stare... hold it, hold it... and count stare one, stare two, stare three, stare four, stare five, stare six, stare seven, stare eight, stare nine, stare ten, stare eleven, stare twelve, stare thirteen, stare fourteen ... okay, we'll stop.\" What do you feel when you blinked?\" Did you have any sensation before you blinked? Burning, probably. That's the beginning of evaporated stress. When individuals get on a computer, and they don't blink for 20, 30, 40 seconds, they have evaporated stress. Now the question is, why don't they feel it? The sensation on the corneal nerves is suppressed, and we don't understand that process yet. However, 244

what we do know, is that that causes evaporated stress, and that starts a cascade. If it carries on long enough, without blinking, we have a thinning of the tear film. We also don't have the lipid secretion, because it's blinking that actually pumps these glands so that they release their lipids onto the eye.”So what are some of the solutions for lack of tears?“It was always thought that just put on artificial tears and they would help a little bit. They're particularly good for the person who has temporary dry eyes. Now, what is temporary dry eyes? It's when it's induced by stress. By stressful situations. You're on a computer, so if you put a couple of drops on the eyes, it wets them and it prevents this evaporated stress. The are specialty oil and water emulsions. It's a palliative treatment. It does not get at the root cause. We know that over 85% of all dry eye in the country is caused by a lack of meibomian gland secretion. In 1980, we published a paper and named the condition ‘meibomian gland dysfunction’. We found that the cause to be internal obstruction.Working with a team of engineers, we were able to develop a device, called LipiFlow. It heats the inside of the lids which allow us to melt the obstruction while we press from the outside. Once the obstruction is melted, takes 12-minutes, we not only hope to remove the obstruction, but hope to evacuate all of the contents. This has been on the market about two and a half years. About 35,000 people today have been treated with a high degree of success. This brings great pleasure because people we could never treat before successfully can now be treated. This procedure can last anywhere between six months and years, depending on the severity of the case.” Dr. Korb goes on to say that this treatment doesn’t remove the requirements for constant blinking to wet the eyes, move the tears and pump the meibomian glands. Without doing that, the treatment won’t last as long.” 245

RESOURCES All About Vision, Understanding Dry Eye Syndrome 246

CHAPTER 12 Think About Your EyesThink About Your Eyes is a national public awareness campaign, presented by The Vision Council and the American Optometric Association, designed to educate the public on the benefits of vision health and promote the importance of getting an annual comprehensive eye exam. 247

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