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Optogenetics: Can This Innovative Gene Therapy Treat Degenerative Retinal Disease and Possibly Restore Sight?

The PLoS Biology logo

A research group of Swiss and German scientists has restored vision to mice with a condition similar to retinitis pigmentosa (RP) by introducing engineered light-sensing proteins into their eyes, via a process known as optogenetics. Optogenetics is a still-experimental treatment for a variety of blinding retinal disorders that uses gene therapy to enable retinal and brain cells to respond to light.

According to the researchers, "… optogenetic gene therapy, which selectively introduces genes encoding light-sensitive proteins into surviving retinal cells to act as "replacement light sensors," holds considerable therapeutic potential: treatment is ambulant [i.e., enabling the person move about while being treated], long-lived, and has the theoretical potential to recover high-resolution vision across the entire visual field."

As explained by IFL Science, "When people lose light-sensing cells over a period of time … vision cells in deeper layers of the eye remain intact. While these cells cannot sense light, many of the signaling pathways are the same. It is in these deeper cells—known as retinal cells—that the researchers were able to insert the new light-sensing proteins, which can then use the already existing pathways to allow the cells to sense light."

This "proof of concept" research is in its earliest stages and has been conducted only with laboratory mice. Nevertheless, this concept shows promise for persons with RP, macular degeneration, and diabetic retinopathy.

About the Research

The study, entitled Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool (explained below), has been published in the May 7, 2015 edition of PLoS Biology, an international, peer-reviewed, open-access online journal, published monthly by the Public Library of Science (PLoS). The PLoS is a non-profit organization of scientists and physicians who are committed to making the world's scientific and medical literature a freely available public resource.

The authors are Michiel van Wyk, Justyna Pielecka-Fortuna, Siegrid Löwel, and Sonja Kleinlogel, from the University of Bern, Switzerland and the University of Göttingen, Germany.

About Retinitis Pigmentosa

Retinitis pigmentosa (RP) is part of a large group of hereditary retinal conditions or dystrophies, involving one or several layers of the retina. RP occurs in approximately 1 in 4,000 people in the United States. At present, there is no cure.

A scene as it might be viewed by a person with retinitis pigmentosa

Most individuals with RP initially experience difficulty with night vision and in low light levels. Central (straight ahead) vision is usually retained until late in the course of the disease, while peripheral (or side) vision becomes progressively more constricted, resulting in "tunnel vision" (pictured above).

Primarily, the retinal rod cells – light-sensitive, specialized retinal receptor cells that activate at low light levels and provide night vision – are involved, but there may also be some involvement of the retinal cone cells, which function best in relatively bright light and provide color vision and greater visual acuity than do rod cells.

You can read more about retinitis pigmentosa research at What Is Retinitis Pigmentosa? by Frank J. Weinstock, MD, FACS at the VisionAware website.

More about the Research

From Optogenetics Restores Vision of Lab Mice, Could Soon Cure Acquired Blindness in Humans, via Medical Daily:

What our brains interpret as vision is actually the response of specialized cells in the eyes, known as retinal cells, to light stimuli. In those who were not born blind but rather acquired blindness over their lifetime, these retinal cells no longer function correctly because their light-sensing proteins are damaged. In the study, currently published in PLOS Biology, a team of researchers from the University of Berne in Switzerland attempted to replace the non-functioning cell parts with their own lab-engineered proteins, which they named Opto-mGluR6.

What sets Opto-mGluR6 apart from light-sensitive proteins occurring naturally in the eye is that these are particularly resilient to the effects of light. This means that their strength remains constant regardless of how much or how often they are hit with light. While Opto-mGluR6 is not the first lab-engineered light-sensitive protein, it differs from past models because it does not require a potentially damaging amount of light intensity in order to function.

Along with working under normal light stimuli, this novel protein also differs from past models because it is likely to be "invisible" to the host's immune system, iflscience reported. This invisibility is advantageous because it means that the host's body will likely not recognize the protein as an invading entity and unleash an attack.

The team introduced the engineered proteins into the eyes of blind mice using a modified virus. This method ensured that the protein could go directly to the surviving vision cells located deep within the eye. Opto-mGluR6 then replaced the no longer functioning photoreceptors and, in turn, restored the animals' vision. The results are promising and the team hopes to reproduce the effects in human subjects.

More about the Study from PLoS Biology

From the article Discussion:

An ideal therapy for patients suffering from photoreceptor degeneration will not only restore the light sensitivity of the retina but will (a) also function at environmental light intensities, (b) be physiologically compatible with the surviving inner retina, (c) conserve a natural range of retinal ganglion cell (RGC) trigger features, and (d) be devoid of toxic and immunogenic [i.e., generating an immune response] side effects.

[Editor's note: Retinal ganglion cells (RGCs), are neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.]

All of this should be accomplished with a minimally invasive and safe clinical technology. Opto-mGluR6, which overcomes most shortfalls of existing optogenetic tools, meets most of these criteria and enhances the clinical feasibility of optogenetic vision recovery.

We showed that Opto-mGluR6 targeted to retinal [cells] of mice suffering from photoreceptor degeneration not only recovers light sensitivity in RGCs at moderate light intensities but also reestablishes diverse RGC light responses comprising ON, OFF, ON-OFF, sustained, and transient responses.

Additional Information


Topics:
Low Vision
In the News
Medical Updates
Clinical Trials
Diabetes and diabetic retinopathy
Macular Degeneration
Retinitis Pigmentosa

Can a Drug to Treat Parkinson’s Disease Also Prevent Macular Degeneration?

The ARVO logo

The treatment of wet age-related macular degeneration (AMD) has – by all accounts – been revolutionized by the successful use of the injectable drugs Eylea, Lucentis, and Avastin. Successful treatments for dry AMD remain more elusive, although stem cell clinical trials in progress show promise. Despite these impressive treatment gains, however, methods for the prevention of AMD remain elusive.

At the 2015 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), a group of American researchers presented data suggesting that L-DOPA (levodopa), a drug used to treat Parkinson's disease, may be useful in both preventing and delaying AMD. ARVO is an international organization that encourages and assists research, training, publication, and dissemination of knowledge in vision and ophthalmology, including low vision.

About the Research

This poster presentation at the ARVO annual meeting, entitled Inverse [i.e., the opposite or reverse] association between L-DOPA and age-related macular degeneration, was authored by Kamyar Vaziri, Stephen G. Schwartz, Thomas B. Connor, Andrew A. Moshfeghi, Darius M. Moshfeghi, Krishna S. Kishor, Harry W. Flynn, Joseph Carroll, Murray Brilliant, and Brian S. McKay, who represent the following institutions: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine; Medical College of Wisconsin; Retina Associates of Kentucky; Stanford Byers Eye Institute, Palo Alto, CA; University of Wisconsin, Marshfield; and the University of Arizona.

About Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. "Atrophy" refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula – the small sensitive area in the center of the retina that provides clear central vision – causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

Geographic atrophy is the most severe and advanced form of dry AMD, involving patches of cells in the retina that have degenerated or died off. "Atrophy," in this case, refers to the degeneration of the deepest cells of the retina, called the retinal pigment epithelium (RPE). "Geographic" refers to any condition whose shape resembles the irregular outline of a land mass, such as the atrophied portion of the retina.

Current treatments for dry AMD include a number of non-drug-related measures, including (a) nutritional supplements recommended by the Age-Related Eye Disease Study 2 (AREDS2), and (b) controlling a range of lifestyle factors, including diet, weight, blood pressure, smoking, and ultraviolet light exposure.

About Wet Age-Related Macular Degeneration (AMD)

retina with wet AMD

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization or CNV (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

The focus of current drug treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments and include Lucentis, Eylea, and Avastin. They are administered by injection directly into the eye after the surface has been numbed.

Drugs to Treat Parkinson's Disease

The following definitions of substances and drugs related to Parkinson's disease are relevant to this research:

  • Amino acids: The building blocks of protein. They carry out many important bodily functions, such as giving structure to cells and transporting and storing nutrients.
  • Dopa: An amino acid that is formed in the liver and converted to dopamine in the brain
  • Dopamine: A form of dopa that acts as a neurotransmitter in the brain, carrying a signal from one nerve cell to the next
  • Levodopa, or L-DOPA: A medication used to treat Parkinson's disease, which is associated with low levels of dopamine. Levodopa is converted to dopamine in the brain. The resulting increase in dopamine improves nerve signal conduction and lessens the movement disorders associated with Parkinson's, including stiffness, tremors, spasms, and poor muscle control.

About the Research

From Parkinson's disease drug delays onset of age-related macular degeneration, via Medical News:

L-DOPA, a routine drug taken by patients with Parkinson's disease, has been found to delay the onset of age-related macular degeneration. The research [was] presented at the 2015 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) Denver, Colorado.

In a study investigating over 15 million people, individuals taking L-DOPA were significantly less likely to develop AMD, and when they did, the age of onset was significantly later. These results suggest L-DOPA may be useful in both preventing and delaying the disease.

More from The ARVO Conference Presentation

From the presentation abstract:

Methods: Using the International Classification of Diseases, Ninth Revision codes (ICD-9), we retrospectively compared the age of first diagnosis of AMD between patients taking or not taking L-DOPA, utilizing cohorts of patients from two Marshfield Clinic Research databases (including 20,000 and 17,000 patients) and the insurance claim-based Truven MarketScan databases from the years 2007-2011 (approximately 87 million outpatient individuals).

In addition, a retrospective cohort of 2,006 AMD patients was reviewed, and a prospective cohort of 47 Parkinson's disease patients treated with L-DOPA were given comprehensive eye examinations; both cohorts were at Medical College of Wisconsin.

(Note: A retrospective study has limitations because it collects data from past records and does not follow up with patients in the present. A prospective study, on the other hand, studies and measures a group of individuals over time and follows up with study patients in the future.)

Results: In the two Marshfield Clinic samples, the mean ages of first AMD diagnosis in patients not treated with L-DOPA were 71.2 years and 71.1 years, and the mean ages of first AMD diagnosis in patients treated with L-DOPA were 79.3 years and 79.3 years respectively.

From the MarketScan databases, the mean age at first AMD diagnosis in patients not treated with L-DOPA was 71.4 years, and the mean age of first AMD diagnosis in patients treated with L-DOPA was 79.3 years.

Using the subpopulation of patients with ophthalmic ICD-9 codes, it was found that after controlling for age and gender, patients with a prescription history of L-DOPA were significantly less likely to have a diagnosis of AMD. In the retrospective cohort of 2,006 AMD patients, only 19 were using L-DOPA, and all 19 were diagnosed with AMD prior to initiating L-DOPA. In the prospective cohort of 47 Parkinson's disease patients, 7 patients with early AMD were diagnosed, which is fewer than expected for this age group.

Conclusion: Collectively, these results suggest an inverse [i.e., the opposite or reverse] relationship between L-DOPA treatment and incidence of AMD. If these results can be confirmed, L-DOPA and its intermediaries may provide future drug targets in the prevention or treatment of AMD.

VisionAware will provide updates on this important research as they become available.

Additional Information


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In the News
Health
Medical Updates
Macular Degeneration

The New Low Vision Focus @ Hadley Program for Older Adults with Low Vision

This month, The Hadley School for the Blind is launching the innovative and highly anticipated Low Vision Focus @ Hadley program for older adults who have low vision. The mission of Hadley is to promote independent living through lifelong distance education programs for people who are blind or visually impaired, their families, and blindness and low vision service providers.

A newly-revised series of 10 audio lessons is the core component of the Low Vision Focus @ Hadley program. Each lesson is approximately 30 minutes long and available on a CD (pictured below), which is mailed directly to the person with low vision after speaking with a Hadley intake coordinator to determine which lesson(s) best meet his or her needs. The CDs are free for each person to keep. The initial mailing is limited to two CDs, with additional lessons available upon request.

The audio lessons include the following topics of interest:

a Hadley CD
  • Making the Kitchen User-Friendly
  • Getting Around in the House
  • Basic Tactile Marking
  • Going Out with a Friend
  • Doing Simple Kitchen Tasks
  • Keeping Prescriptions in Order
  • Low Vision Cooking
  • Looking Your Best
  • Going Out for a Meal
  • Simple Home Modifications

More about the Low Vision Focus @ Hadley Program

From the Low Vision Focus @ Hadley website:

Did you know that one out of every six seniors experiences age-related vision loss due to conditions such as macular degeneration, glaucoma, diabetes, or cataracts? These conditions often result in low vision. As your vision loss progresses, it often becomes necessary to relearn how to conduct normal daily activities such as reading the mail, shopping, cooking, watching TV and paying the bills.

The great news is that there are lots of techniques that can help you in managing your low vision. These include adjusting lighting; using contrasting colors, sounds and smells; magnification; tactile (by touch) markings; and simple safety precautions.

The Low Vision Focus @ Hadley program is designed to help you maintain your independence in your home by sharing practical ways to address daily living skills made difficult by low vision. Hadley is a nonprofit organization that has been supporting people with vision loss for nearly a century.

We are pleased to offer a series of free audio recordings available on CD that provide you with the tips and tricks needed to continue living well with low vision. They range from marking your stove or oven and managing medications to indoor mobility and using adaptive devices.

The Low Vision Focus @ Hadley program is designed to help older adults living with low vision maintain their independence by sharing practical ways to address daily living skills made difficult by vision. The program is unique in that it offers adults with low vision the opportunity to learn, and take advantage of, these resources from the comfort of their own homes, at a time that is convenient for them, with the benefit of one-on-one counseling and support, at no cost.

In addition, adult children of parents who are living with low vision are encouraged to take advantage of the resources offered by the program to aid their parents in the adjustment process. While many of the people who are living with low vision are seniors, the program is open to any individual who is experiencing sight loss. Adults with low vision and professionals also are encouraged to use the program to develop new low vision support groups in local communities or to sustain existing support group networks.

For More Information

For additional information about the Low Vision Focus @ Hadley program, you can visit the program website at www.lowvisionfocus.org or call toll-free at 1-855-830-5355.

More about Hadley School for the Blind from VisionAware


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Low Vision
Education
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Our Readers Want to Know: What is the Difference between an Ophthalmologist and an Optometrist?

Editor's note: One of the many benefits associated with an online information center and website, such as VisionAware, is the ability to track readers' search terms [i.e., information readers are seeking as they search the Internet]. Since the earliest days of VisionAware.org, the following questions about eye doctors and eye care consistently rank within the top ten searches and are especially relevant during Healthy Vision Month:

  • What are the different kinds of eye doctors?
  • What is the difference between an ophthalmologist and an optometrist?

Ophthalmology and Ophthalmologists

American Academy of Ophthalmology logo

What is ophthalmology?

Ophthalmology is a branch of medicine that specializes in the anatomy, function, and diseases of the eye.

What is an ophthalmologist?

  • An ophthalmologist is a medical or osteopathic physician who specializes in the medical and surgical care of the eyes and the prevention of eye disease. An ophthalmologist diagnoses and treats refractive, medical, and surgical problems related to eye diseases and disorders.
  • Ophthalmologists are licensed by state regulatory boards to practice medicine and surgery, as well as deliver routine eye care.
  • An ophthalmologist will have the initials "M.D." (Doctor of Medicine) or "D.O." (Doctor of Osteopathy) after his or her name.

What does an ophthalmologist do?

  • Ophthalmologists are trained to provide the full spectrum of eye care, from prescribing glasses and contact lenses to complex and delicate eye surgery.
  • Ophthalmologists treat eye diseases, prescribe medications, and perform all types of surgery to improve, or prevent the worsening of, eye and vision-related conditions.

How is an ophthalmologist educated and trained?

  • In addition to four years of medical school and one year of internship, all ophthalmologists spend a minimum of three years of residency (hospital-based training) in ophthalmology.
  • During residency, ophthalmologists receive specialized training in all aspects of eye care, including prevention, diagnosis, and medical and surgical treatment of eye conditions and diseases.
  • Often, an ophthalmologist spends an additional one to two years training in a subspecialty, or a specific area of eye care, such as glaucoma or pediatric ophthalmology.
  • All ophthalmologists are required to fulfill continuing education requirements to stay current regarding the latest standards of care.

More Information about Ophthalmology

  • For more information, you can visit the American Academy of Ophthalmology website.
  • The EyeSmart® public awareness campaign, sponsored by the American Academy of Ophthalmology, helps Americans to take charge of their eye health; know their risk factors for eye diseases; and understand how ophthalmologists can help prevent, diagnose, and treat eye conditions.

Optometry and Optometrists

American Optometric Association logo

What is optometry?

Optometry is a vision care specialty that is concerned with the health of the eyes, the visual system, and related structures.

What is an optometrist?

  • An optometrist is a health care professional who specializes in function and disorders of the eye, detection of eye disease, and some types of eye disease management. An optometrist conducts eye examinations, prescribes corrective contact lenses and glasses, and diagnoses and treats eye diseases and disorders.
  • Optometrists are licensed by state regulatory boards that determine their scope of practice, which may vary from state to state.
  • An optometrist will have the initials "O.D." (Doctor of Optometry) after his or her name.

What does an optometrist do?

  • Optometrists are trained to examine the eyes for visual defects, diagnose problems or impairments, prescribe corrective lenses, and provide certain types of treatment.
  • Many (but not all) U.S. states have passed legislation that allows optometrists to perform certain surgical procedures, such as laser treatment; administer injections, such as local anesthesia or treatment for macular degeneration; and prescribe additional diagnostic, therapeutic, and oral medications. Visit the American Optometric Association website to determine if your state permits optometrists to perform these additional procedures.

How is an optometrist educated and trained?

  • Prior to admittance into optometry school, optometrists typically complete four years of undergraduate study, culminating in a bachelor's degree.
  • Optometrists then complete a four-year postgraduate program in optometry school to earn the Doctor of Optometry degree.
  • Some optometrists go on to complete one- to two-year residencies with training in a specific sub-specialty area, such as pediatric or geriatric eye care, specialty contact lens, ocular disease, or neuro-optometry.
  • All optometrists are required to fulfill continuing education requirements to stay current regarding the latest standards of care.

More Information about Optometry

Low Vision Specialist

  • Many optometrists and some ophthalmologists have additional credentials or specialization in low vision testing, diagnosis, and treatment, and are trained to conduct low vision eye examinations and prescribe special low vision optical devices.
  • If you're experiencing significant vision loss, a low vision specialist can determine whether special optical and non-optical devices, improved lighting, or other types of specialized services and equipment can help make the best use of your remaining vision.
  • You can find a listing of low vision specialists in the "Low Vision Services" category in the VisionAware Directory of Services.

In addition to the low vision professionals in the Directory listings, you can find low vision providers through the following directories:

Locate an Eye Care Professional in Your Area


Topics:
Low Vision
In the News
Health

Maintaining Your Ocular Lenses Help Ensure Longevity and Enjoyment

Editor's note: As we end Women's Eye Health and Safety Month, Empish Thomas talks about the cosmetic reasons for her choice to wear ocular lenses and the vital importance of properly caring for them.

Decision to Wear Ocular Lenses

Side view of an ocular lens

In 2012, I made a radical decision, to stop wearing dark sunglasses and start wearing ocular lenses. It was a huge step for me because I had been wearing sunglasses for such a long time. But I felt it was the right decision. I wanted to do it because of cosmetic reasons. I wanted my face to have a more natural look and I wanted to feel better about my appearance. My decision had nothing really to do with any medical problems I was having with my eyes. I openly shared about this transition in a blog post for VisionAware called “They Look So Real!

Tips on Care and Maintenance

Well, in these passing years I have had no regrets about my decision and have grown to really love my ocular lenses because they really do look so real. But with that being said, there is work to be done when wearing ocular lenses or what some people commonly call prosthetic or fake eyes. In the next few paragraphs I want to share some common tips on care and maintenance of ocular lenses. These tips are good to follow to keep your lenses in good shape and keep your eyes safe. If you are wearing ocular lenses or considering doing so, I hope these tips will be helpful.

Empish inserting her ocular lens
  1. One of the first things I did when I started wearing my ocular lenses was to get clear instructions from the ocularist. He gave me both verbal and written instructions on how to properly clean, wear and maintain my lenses. These instructions were important to follow not only so that my lenses could last but to keep my natural eyes safe and free from damage or complications.
  2. Since my ocular lenses were designed to fit my eyes only, I wear them day and night so I don’t have to remove them very often. Initially I removed them more often while going through the adjustment process. Since my natural eyes had shrunk and my eyelids had closed for some time it took a while for my eyes to get use to a foreign object inserted over top of my eyeball. I would wear them during the day and then remove at night. Today I wear them day and night; only removing them for proper cleaning. I was advised the less handling of the prosthesis the better.
  3. When it comes to cleaning, I clean my ocular lenses once a week. But it can vary with each person depending on the amounts of tear, mucus and protein deposits and debris. Taking care and cleaning your lenses will not only keep them looking natural but increase their longevity. First wash your hands thoroughly. Next, remove the lenses either with your fingers or with a suction cup. Softly wash lenses with warm water and mild soap like baby shampoo. Do not clean the lenses with any solvents, hand sanitizer or alcohol because these chemicals may damage the lenses and your eyes and eye socket. Gently rub the lenses thoroughly then rinse clean. Next, dry with soft towel. Before inserting lenses back into your eye sockets it is a good idea to clean them too. You can take a washcloth and gently lift the eye lid and clean the area including the eyelashes. Then insert lenses into eye socket. To avoid dry eyes, my ocularist recommended using some mineral water. So I squeeze a few drops over each lens before inserting.
  4. Even with proper cleaning, over time heavy surface deposits formed by tears, protein and mucus, can present a dull film. This dull film can cause irritation and can also be a sign that it is time to get your lenses polished. It is advised to get ocular lenses polished at least once a year; or sometimes every six months depending on the buildup. During this appointment the ocularist will polish the lenses, check them for any needed adjustments and answer any questions you might have about care and maintenance.
  5. Although you can properly clean, maintain and polish ocular lenses, they do not last forever. Depending on your ocularist, lenses will have to be replaced every 3-7 years. This might be due to the fact that your natural eyeball has shrunk more causing the lens to no longer fit snuggly. Or the tissue in the eye socket can change causing the lenses to become scratched or damaged. Another cause is the natural deterioration of the lenses’ plastic and pigmentation. Other factors can be your age, overall health and lifestyle.
  6. While writing this post I scheduled my next appointment to see my ocularist. I have noticed that my right lens keeps moving around and I have to keep adjusting it. This might be due to more shrinkage and time for a new fitting. But only through a conversation will I know for sure. It is so important when wearing ocular lenses that when you notice changes that you talk with your ocularist so that they can check and make any adjustments. This will insure proper fitting, longevity and overall enjoyment of your lenses.

Let's Discuss Maintenance Tips

Wearing ocular lenses has been an enjoyable experience for me. The cleaning, care and maintenance can sometimes be a bit of an inconvenience but I would not go back to dark sunglasses for anything.

So, do you wear ocular lenses? If so, did you find my tips helpful?

Are there other tips or suggestions you use to keep your lenses clean and well-maintained? Share your comments with us.

More Information About Prosthetic Eyes

Ocular Prothesis

Hygiene Care for the Ocular Prosthesis


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