Nanotechnology breakthrough will lead to a better bionic eye for the blind

(c) American Chemical Society

 
Scientists from Hebrew University of Jerusalem researchers, in collaboration with colleagues from Tel Aviv University and Newcastle University, have developed a new light-sensitive film that could one day form the basis of a bionic eye (or an artificial retina) that could help people suffering from retinal damage or degeneration.

Eye drops for treatment of macular edema in Retinitis Pigmentosa and Usher's syndrome

A study published in Ophthalmologica by researchers from the Hospital de São João, Porto in Portugal has looked at the effect of dorzolamide versus ketorolac eye drops on macular edema in patients with Retinitis Pigmentosa (RP) and Usher's syndrome (US).

New therapy holds promise for restoring vision in Retinitis Pigmentosa and Leber Congenital Amaurosis

Scientists from the University of California, Berkeley and Lawrence Berkeley National Laboratory, along with those of University of Pennsylvania, have demonstrated restoration of visual function in animal models that can help restore sight in blind patients afflicted by diseases such as Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA).

Human stem cell-derived retinal cells show promise as treatment for macular diseases

Note: The post below is  from the study (pdf) published in The Lancet.

Since 1981, when pluripotential cell cultures were first derived by Evans and Kauffman, embryonic stem cells (ESC) have been regarded as a potential source of therapeutic cells for a wide range of diseases caused by tissue loss or dysfunction. Despite the great therapeutic potential, their plasticity and unlimited capacity for self-renewal raise concerns about serious safety issues, including the ability to form teratomas and other tumours, potential immune reactions, and the risk of differentiating into unwanted cell types. 

Sildenafil (Viagra) may not be safe in Retinitis Pigmentosa

Sildenafil (Viagra) is a PDE5 inhibitor in wide use for the treatment of erectile dysfunction. It is known to increase the level of cGMP, and ultimately increases penile response to sexual stimulation. Sildenafil preferentially inhibits PDE5 more than PDE6, both of which are expressed in the retina. Therefore, there is a potential for this drug to alter retinal function, not only in normal subjects, but also in patients with PDE6 gene mutations such as in some forms of RP. 

Stem cells close to cornea may help treat Macular Degeneration or Retinitis Pigmentosa

Scientists at the Southampton General Hospital and the University of Southampton have found a pool of stem cells around the corneal limbus that can be induced to become retinal cells. Such cells can then potentially be transplanted into the eye of the patient of macular degeneration or retinitis pigmentosa to stop the disease or even cure it.  

Gene therapy for childhood blindness

Genzyme has announced the establishment of a research collaboration with the University of Florida (UF) and the University of Pennsylvania to develop gene therapy for the treatment for Leber congenital amaurosis type 1 (LCA-1), which is usually diagnosed in children who are less than a year old, and patients remain severely visually impaired for the rest of their lives. This disease, which is the most common cause of childhood blindness, is a group of degenerative diseases of the retina caused by genetic mutations in one of 19 genes currently associated with the disorder. These genes encode proteins that play a variety of roles in the development and function of the retina, and a mutation in any one of them can cause visual impairment.

New genetic mutations in Bardet Biedl Syndrome identified

UK researchers have identified genetic mutations responsible for Bardet-Biedl Syndrome (BBS), a rare condition that causes blindness, opening the door for personalized treatment and tailored gene therapies.

What is Bardet-Biedl syndrome?
Bardet-Biedl syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

Is a whole eye transplant possible?

When we talk about an eye transplant, we usually refer to a cornea transplant, in the present day scenario. No one so far has been able to remove a complete eye from a donor, and transplant it into a recipient and make the eye function. But it looks like this is about to change...

EYLEA (aflibercept) injection receives FDA breakthrough therapy designation for diabetic retinopathy in patients with diabetic macular edema

Regeneron Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Eylea® (aflibercept) injection a breakthrough therapy designation for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME). The designation is based on positive results in two Phase 3 trials (VIVID-DME and VISTA-DME), in which Eylea demonstrated a statistically significant improvement
in a pre-specified measure of diabetic retinopathy in patients with DME after two years of treatment.

Increased risk of acute angle closure observed in patients with retinitis pigmentosa

Clinician scientists from Taiwan, in a large observational study of over 380 patients over a 15-year period, have observed increased risk of acute angle closure in patients with retinitis pigmentosa (RP). In addition, they also noticed that angle closure attack occurred earlier in life, with the risk higher in males, in patients with RP, compared to the general population where such an attack is more commonly seen in elderly females.

The association between RP and glaucoma was first proposed in 1862. Since then, it has been considered a difficult diagnosis to make in patients with RP due to coexistent changes such as retinal nerve fiber layer defect and visual field defect in RP, which are also seen in patients with glaucoma.

As is known, RP is a major cause of blindness in adults. Intraocular pressure (IOP) elevation may aggravate the visual impairment in RP patients with preexisting retinal and optic nerve dysfunction. Acute angle closure, the major risk factor for blindness among angle closure eyes, may cause particularly devastating damage to RP patients. Angle closure related IOP elevation is preventable by timely intervention to widen the drainage angle in susceptible eyes.




Advice: If you are a patient with RP, It is a good idea to get a check done by your retina specialist if you ever feel your vision has reduced suddenly from the previous state, or you have significant pain in or around the eye/s.

Source

Japanese woman is first recipient of next-generation iPS stem cells for macular degeneration

A Japanese woman in her 70s has become the first person in the world to receive retinal cells derived from induced pluripotent stem cells (iPS). In a two-hour procedure on September 12, 2014, a team of three eye specialists lead by Dr Yasuo Kurimoto of the Kobe City Medical Center General Hospital, Japan, implanted a 1.3 by 3.0 millimetre sheet made of retinal pigment epithelium (RPE) cells into one eye of this patient, who was diagnosed with age-related macular degeneration (AMD).

A detailed molecular map for eye disease

Understanding eye diseases is tricky enough. Knowing what causes them at the molecular level is even more confounding.

To understand eye diseases better, University of Iowa (UI) researchers have created the most detailed map to date of a region of the human eye long associated with blinding diseases, such as age-related macular degeneration. The high-resolution molecular map catalogs thousands of proteins in the choroid, which supplies blood and oxygen to the outer retina, itself critical in vision. By seeing differences in the abundance of proteins in different areas of the choroid, the researchers can begin to figure out which proteins may be the critical actors in vision loss and eye disease.

Treatment efficacy of topical unoprostone isopropyl in patients with retinitis pigmentosa

A study was conducted by Dr Akiyama & associates from the Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka in Japan to evaluate the treatment effect of topical unoprostone isopropyl (unoprostone) (in the form of eye drops) on patients with retinitis pigmentosa (RP). This medication is currently used in glaucoma.

Forty patients with typical forms of RP were included in the study, out of which 17 patients were treated with 0.12% topical unoprostone twice daily in a randomly selected eye. The efficacy of the treatment was monitored by visual acuity and visual field testing using the Humphrey Field Analyzer (HFA). In addition, 12 RP patients who were included this study and 12 normal subjects were evaluated in terms of their macular blood flow of both eyes after instillation of unoprostone using the laser speckle method. 

Is Valproic Acid effective in treating patients with Retinitis Pigmentosa?

There have been some reports in academic journals about the use of Valproic acid (VPA) in Retinitis Pigmentosa (RP). We thought we can review the current status of these trials and evaluate where we stand in the outcomes.

Is docosahexaenoic Acid (DHA) effective as treatment for patients with X-Linked Retinitis Pigmentosa?

X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression is considered to be a meaningful outcome.

A study was conducted in Dallas, Texas, at the Retina Foundation of the Southwest, and others, to determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa as measured by cone electroretinography (ERG).
 

Iodine supplement may limit or reduce extent of macular thicking in patients with Retinitis Pigmentosa

Current treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) are not always effective, may lead to adverse effects, and may not restore visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce CME in RP. 

A study was orgnized at the Berman-Gund Laboratory for the Study of Retinal Degenerations, in the Department of Ophthalmology at Harvard Medical School, Massachusetts Eye and Ear Infirmary (MEEI) in Boston, to determine whether central foveal thickness (CFT) in the presence of CME is related to dietary iodine intake, which was inferred from urinary iodine concentration (UIC) in nonsmoking adults with RP.

Blind veteran shows how he sees world through photography

By the time an inherited eye disease crossed into legal blindness in 2009, Ed Waldrop had already lost the ability to drive and he feared countless other freedoms would soon be next. But what he lost in sight, he gained in a seize-the-day attitude that revived a long-buried, if now unlikely, ambition to make visual art.

(c) JON-MICHAEL SULLIVAN

In the past three years, the Au­gusta Air Force veteran, who serves as the health chaplain at the Charlie Norwood VA Medical Center, has used what free time he has to transform nature, architecture and vintage cars into unique compositions consistent with how he sees the world.


To read more, read the article in The Augusta Chronicle. 

epiCam, a camera for screening diabetic retinopathy being developed by Epipole, may save sight of millions

Epipole is building a mass market diabetic retinopathy monitoring and screening platform usable by both clinicians and non-clinicians in a home or social environment. The system will provide monitoring capabilities as well as a portable, low cost tool for clinicians for tele-medicine applications.

The platform consists of three parts:

1. A retinal fundus camera tuned specifically to this task.
2. Safe Cloud based storage for all images.
3. A sophisticated piece of software usable by non-clinicians which can run in limited-compute environments.

Diabetes, as is well known, has become a major public health concern. A significant number of those affected with this disease are likely to suffer from diabetic retinopathy. To understand the significance of the problem we face, here are some statistics from ARVO 2011 for the year 2010 (with expected numbers in 2030 in parentheses). 

• 100.8 (154.9) million people with diabetic retinopathy

• 20.6 (31.7) million with proliferative diabetic retinopathy

• 21.3 (32.8) million with diabetic macular edema and

• 33.4 (51.3) million with vision-threatening diabetic retinopathy.

More about epiCam here. 

Launch of a new alliance for global assessment of diabetic retinopathy

A new project has been launched to assess the awareness, treatment and implications of diabetic retinopathy globally. Results are intended to inform decision-making and policy development around this common and serious complication of diabetes.

Project partners, the International Federation on Ageing (IFA) and the International Diabetes Federation (IDF), working in collaboration with the New York Academy of Medicine (NYAM) and the International Agency for the Prevention of Blindness (IAPB) will gather evidence on knowledge, policies, standards of care, and supportive services for retinopathy across 40 countries.

Retinopathy is one of the most common complications associated with diabetes and one of the major causes of adult blindness. Up to 11% of adults with diabetes have Diabetic Macular Edema (DME), a specific type of diabetic retinopathy. According to the IDF Diabetes Atlas 6^th edition, there are large variations in the estimates of retinopathy prevalence in people with known diabetes, with estimates ranging from 11 to 45% worldwide in people with type 1 and type 2 diabetes.

The global assessment of retinopathy has two substantive and connected phases:

1. Phase I comprises approximately 120 interviews in eight countries representative of low, middle and high socio-economic status to better understand the level of awareness of: retinopathy as a condition and common complication of diabetes; the access, availability and pathway to retinopathy services; and the existence and content of relevant governmental policy.

2. Phase II is the implementation of a survey in 40 countries, which will be formulated based on the data gathered in Phase I. The survey aims to garner statistically significant evidence intended to assist in the development of effective governmental policy.

The project will culminate in the production of a barometer report and a compendium of resources designed to increase awareness, as well as to inform policy and practice related to diabetic retinopathy and vision loss across countries.

This project is financially supported by Bayer Pharma AG. Bayer is not involved in the analysis of the findings.

Source

Notal Vision's ForeseeHome AMD Monitor receives FDA clearance

Notal Vision's ForeseeHome™ AMD Monitor has received Section 510 (k) clearance from the U.S. Food and Drug Administration (FDA).

The ForeseeHome AMD Monitor is the first ophthalmic device linking patients and doctors between eye exams for ongoing monitoring of age-related macular degeneration (AMD). 

Patients complete a frequent but brief exam on their ForeseeHome AMD Monitor, in the comfort of their own home, and data is transmitted to the patients' eye care physician and the Notal Vision Data Monitoring Center.  The award winning ergonomic design of the ForeseeHome AMD Monitor is comfortable and easy to use for patients at risk of vision loss from wet AMD.

Wet AMD is the leading cause of blindness in people over the age of 60 in the western world. Recent breakthroughs in treatments place even greater importance on early detection, which can reduce the risks of vision loss associated with wet AMD.  Frequent monitoring is critical in detecting disease onset as early as possible and the ForeseeHome AMD Monitor is the first home monitoring device for following patients at risk of vision loss, offering hope for early intervention through early detection.

Numerous clinical studies have demonstrated the ForeseeHome AMD Monitor is an accurate and reliable tool for frequent monitoring of patients at risk for vision loss from wet AMD.

FDA Indication for Use: 

ForeseeHome is intended for use in the detection and characterization of central and paracentral metamorphopsia (visual distortion) in patients with age-related macular degeneration as an aid in monitoring progression of disease factors causing metamorphopsia including, but not limited to choroidal neovascularization (CNV). It is intended to be used at home for patients with stable fixation. ForeseeHome is not intended to diagnose; diagnosis is the responsibility of the prescribing eye-care professional.

Source

Contact lens allows the blind to 'see'

Engineers in Israel are developing a contact lens they say will allow the blind to recognize
objects by feel rather than sight. The lens is being designed to translate electrical signals into 
shapes on the cornea, producing a tactile effect similar to Braille on the fingertips.





Source

News Bulletin

• Monthly injections may not be necessary for patients with age-related macular degeneration. http://goo.gl/uldMFv

• Converting stem cells to eye tissue could restore sight. http://goo.gl/pJeuiv

• Post-operative healing aided by new gel-based eye fluid. http://goo.gl/YA1B04

• Reversible glue bandage could save injured soldiers' vision. http://goo.gl/fwD2e0

Ohr Pharmaceutical initiates Investigator sponsored trial of squalamine eye drops in diabetic macular edema

Ohr Pharmaceutical, Inc., a research and development company with a primary focus in ophthalmology, has announced the initiation of a Phase II investigator sponsored clinical trial, OHR-005, testing Squalamine eye drops in patients with diabetic macular edema (DME).

The current standards of care for DME include chronic treatments of VEGF inhibitors administered directly into the eye via an injection. Squalamine eye drops may potentially represent a less-invasive treatment option for patients suffering from diabetic macular edema, as per the investigators of this trial. 

OHR-005 is a randomized, placebo controlled, investigator sponsored, multicenter Phase II clinical trial evaluating the effect of Squalamine Eye Drops in patients with DME. The primary endpoints will measure change in retinal thickness and change in Best Corrected Visual Acuity (BCVA) over 24 weeks. Secondary objectives include additional BCVA measurements, change in foveal thickness, evaluation of the need for rescue injections of ranibizumab (Lucentis®) and an assessment of the safety and tolerability of Squalamine Eye Drops. The trial is designed to enroll up to 30 subjects at 3 sites in the United States. Patients will be randomized to receive a single injection of ranibizumab at baseline followed by treatment with either Squalamine lactate ophthalmic solution 0.2% or placebo ophthalmic solution, administered QID for 24 weeks.

Squalamine is an anti-angiogenic small molecule with a novel intracellular mechanism of action, which counteracts multiple growth factors implicated in the angiogenesis process. Ohr Pharmaceutical has developed a novel eye drop formulation of Squalamine for the treatment of wet-AMD, designed for self-administration, which may provide several potential advantages over the FDA approved current standards of care, which require intravitreal injections directly into the eye. The drug, using an intravenous administration in over 250 patients in Phase I and Phase II trials for the treatment of wet-AMD, showed favorable biological effect and maintained and improved visual acuity outcomes. In May 2012, the Squalamine Eye Drop program was granted Fast Track Designation by the FDA. A Phase II randomized, double blind, placebo-controlled study (OHR-002) to evaluate the efficacy and safety of Squalamine Eye Drops for the treatment of wet-AMD has completed enrolling patients. Three additional investigator sponsored trials (IST) are evaluating Squalamine eye drops for the treatment of proliferative diabetic retinopathy, retinal vein occlusion and diabetic macular edema, with one additional IST expected to be initiated in diabetic macular edema in the second calendar quarter of 2014.

Source

New technique to determine gene carriers for autosomal recessive retinitis pigmentosa

Scientists from Bascom Palmer Eye Institute and Duke University Medical Center have developed a non-invasive technique to determine if individuals carry a gene for the autosomal recessive type of retinitis pigmentosa. 

The work was being presented at the 2014 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Orlando, Florida.

The technique involves collecting a patient's urine and measuring the ratio between specific compounds. The non-invasive process makes subsequent testing clinic-friendly, especially for children being screened.

In search of quantitative biomarkers for the disease, the authors checked on the urinary and plasma dolichol profiles in autosomal recessive RP (arRP) patients and carriers with mutations in the DHDDS gene encoding dehydrodolichol diphosphate synthase, a key enzyme in dolichol biosynthesis. Dolichols are long chain polyisoprenoid alcohols composed of 17-21 isoprene units.

Mutations in the DHDDS gene lead to a characteristic shortening of plasma and urinary dolichols, which, as per the authors of this study, can be used as a functional readout of the enzyme. Urinary and plasma D18/D19 ratios reliably determine if a DHDDS genotype is disease-causing. 

D18/D19 ratio is a viable objective functional biomarker and can be readily adapted as a clinical test for arRP diagnosis and carrier screening with DHDDS or other genetic mutations that impair dolichol biosynthesis.

Source

Coffee may prevent hypoxia-induced retinal degeneration

Retina is one of the most metabolically active tissues in the body, consuming oxygen more rapidly than any other tissues, including the brain. Therefore, it is susceptible to a variety of diseases caused by oxidative stress, including age-related macular degeneration, diabetic retinopathy, and glaucoma - all of which can lead to partial or complete blindness.

One mechanism of retinal degeneration is hypoxia, a reduction in retinal oxygen supply caused by pathologies such as central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease, and some types of glaucoma that cause vascular eye diseases. Retinal hypoxia can negatively impact both tissue function and cell viability, and is a potential risk factor for sight-threatening disorders. Hence there has been a great interest in identifying neuroprotective compounds that inhibit hypoxia. Particularly promising in this capacity are natural products and phytochemicals that act as antioxidants and can be taken regularly without causing significant side effects.

One important group of neuroprotectants comprises derivatives of chlorogenic acid (CGA) found in a variety of edible plants, including tea, fruits, and vegetables, with the major source of intake in humans being coffee. Collectively, these phenolic phytochemicals are known to have hepatoprotective, antibacterial, anti-inflammatory, DNA protective, and anticancer activities, among others. Several studies have also suggested that the antioxidant properties of CGA make it a powerful neuroprotectant.

In raw coffee, CGA amounts to about 4–12% of raw coffee, while a 200 mL cup of prepared coffee contains 200 mg of total CGA. Coffee consumption appears to decrease the risk of developing chronic diseases such as Parkinson’s, prostate cancer, and diabetes. It also reduces the extent of cognitive declines associated with aging. The current study was designed to investigate whether coffee and, in particular, its main polyphenol, CGA, has protective effects against the degeneration of retinal ganglion cells (RGC), both in vitro and in vivo.

The researchers found that CGA significantly reduced the negative effect of the hypoxic agent on the cells being studied, with cell viability increasing with more CGA pretreatment. Also in animal models that mimic glaucoma, where the inner plexiform layer appears thinned, pretreatment with CGA reduced the amount of thinning seen. The authors also noted reduction in ganglion cell apoptosis.

This study demonstrates that CGA and coffee extract are responsible for reduction of the RGC apoptosis induced by hypoxia. Thus, coffee consumption may provide additional health benefits by preventing retinal degeneration.

Sources: Journal of Agricultural and Food Chemistry

DENAQ, a new chemical that may restore sight in retinitis pigmentosa and macular degeneration

Scientists from the University of California, Berkeley report on a chemical ‘photoswitch’ named DENAQ that may be a potential drug for treating patients suffering from blinding diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

RP and AMD are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. In the paper published in Neuron, the authors led by Dr Richard H Kramer report about a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight, compared to earlier attempts at photoswitch that required very bright ultraviolet light, making it unsuitable for use in patients. In experiments conducted on three-month to six-month-old healthy mice, and on mice carrying a mutation causing nearly all their rods and cones to degenerate by the time they were a month old, a single intraocular injection of DENAQ has been able to photosensitize the blind retina for about 3 days, restoring electrophysiological and behavioral responses with no toxicity. DENAQ also is able to rapidly turns itself off, allowing rapid repeated stimulation of the retina. The researchers compared the retinae of DENAQ-injected mice to untreated healthy mice and found no signs of toxicity for up to 30 days after the injection.

Retinas with damaged rods and cones are subject to several morphological and biochemical changes, making them different from a healthy retina in more than one way. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated or dead photoreceptors. Apparently, the degenerated outer retinal cells help in DENAQ photosensitization due to changes in electrophysiological characteristics, while the presence of intact photoreceptors possibly prevent this action. This appears to give it significant advantage, since this selective action on diseased tissue alone may potentially reduce side effects on healthy retina.

DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.

The researchers plan on conducting more experiments, including in larger animals before its safety can be established and any clinical trials can be considered.

To watch a video of Dr Kramer explaining his work, click here.

Sources: Neuron, Univ of California, Berkeley, Kramer Lab, The Scientist

Editor's note: The drug appears to have an exciting potential to help patients with retinitis pigmentosa and age-related macular degeneration. There are two thoughts though. 

1. Such a drug may only work in advanced stages of the disease, considering we will have to wait for the retinal cells to die before it can act.

2. We also need to know how long the effect of one injection lasts. Such treatment may require repeat injections over a long-term, something similar to Lucentis or Avastin.