David Hutton

Patients with a specific form of age-related macular degeneration (AMD), a leading cause of blindness in the United States, are also highly likely to have either underlying heart damage from heart failure and heart attacks, or advanced heart valve disease, or carotid artery disease associated with certain types of strokes, according to a new study from New York Eye and Ear Infirmary of Mount Sinai.

According to a news release, this research, published November 17 in 

, is the first to identify which types of high-risk cardiovascular and carotid artery disease are linked to the eye disorder. The findings could prompt increased screening to save vision, diagnose undetected heart disease, and prevent adverse cardiovascular events.

“For the first time, we have been able to connect these specific high-risk cardiovascular diseases to a specific form of AMD, the one with subretinal drusenoid deposits (SDDs),” lead author R. Theodore Smith, MD, PhD, a professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai, said in a news release.

Smith noted that the study is the first strong link between the leading cause of blindness, AMD, and heart disease, the leading cause of death worldwide.

“Furthermore, we also have strong evidence for what actually happens: the blood supply to the eye is directly diminished by these diseases, either by heart damage that diminishes blood supply throughout the body, or from a blocked carotid artery that directly impedes blood flow to the eye,” he said in the news release. “A poor blood supply can cause damage to any part of the body, and with these specific diseases, the destroyed retina and leftover SDDs are that damage. Retinal damage means vision loss, and can lead to blindness.”

According to the news release, AMD is the leading cause of visual impairment and blindness in people over 65 and is the result of damage to the central area of the retina called the macula, which is responsible for reading and driving vision. One major form of early AMD consists of small yellow cholesterol deposits called drusen, which form under a part of the retina called the retinal pigment epithelium (RPE). They can deprive the retina of blood and oxygen, leading to vision loss.

Drusen formation can be slowed by appropriate vitamin supplementation. The other major form of early AMD, subretinal drusenoid deposits (SDDs), are less well-known, and require high-tech retinal imaging to detect. These deposits contain a different form of cholesterol, and form above the RPE, and just beneath the light-sensitive retina cells, where the damage occurs and vision is lost. There is no known treatment for SDDs. Dr. Smith and a team of Mount Sinai researchers initially found that patients with cardiovascular disease or stroke were more likely to have SDDs. That first-of-its-kind research was published in the July issue of 

 This new study expands on that previous work, looking at a larger patient population, and identifies the specific severe forms of heart disease and carotid artery disease that caused the SDDs of AMD.

Researchers analyzed the eyes of 200 AMD patients with retinal imaging to determine which patients had SDDs. Patients answered a questionnaire about their history of cardiovascular disease. Of the 200 patients, 97 had SDDs and 103 had drusen only. Forty-seven of the 200 had severe heart disease (19 had heart damage from heart failure or heart attack, 17 serious valve disease, and 11 stroke stemming from the carotid artery). Forty of the 47 (86 percent) had SDDs. By contrast, of the 153 AMD patients who did not have these severe diseases, 57 had SDDs (43 percent). The researchers concluded that AMD patients with these severe cardiovascular diseases and stroke were nine times more likely to have SDDs than those without them.

“This work demonstrates the fact that ophthalmologists may be the first physicians to detect systemic disease, especially in asymptomatic patients,” says co-investigator Richard B. Rosen, MD,cChief of the Retina Service for the Mount Sinai Health System. “Detecting SDDs in the retina should trigger a referral to the individual’s primary care provider, especially if no previous cardiologist has been involved. It could prevent a life-threatening cardiac event.”

The next step is for researchers to focus on patients in cardiology and neurology clinics to further examine varying degrees of cardiovascular and carotid disease and assess that possible relationship of disease severity to AMD with SDD.

This study was funded by a Regeneron Pharmaceuticals Investigator-Initiated Study, Research to Prevent Blindness Challenge Grant, the Macula Foundation, a Bayer-Global Ophthalmology Award, and the International Council of Ophthalmology-Alcon Fellowship.

This article originally appeared on Ophthalmology Times.

Articles

Mount Sinai study is the first to identify that heart attack, stroke and heart failure are linked to a specific type of age-related macular degeneration.

Forms of Cardiovascular Disease Tied to Blinding Eye Disease

Regular use of drugs to lower cholesterol and control type 2 diabetes may lessen the risk of the degenerative eye disease associated with aging, known as AMD, finds a pooled data analysis of the available evidence, published online in the 

According to a news release, these common drugs are linked to lower prevalence of AMD (age related macular degeneration) in European populations, the results show.

AMD is the leading cause of severe visual impairment among older people in high-income countries. In Europe alone, 67 million people currently have the condition, with new cases projected to soar over the next few decades as populations age.

Moreover, according to the news release, AMD affects central vision and the ability to see fine detail. Various genetic and environmental factors associated with aging are thought to trigger AMD, but it’s still not clear how best to prevent it or slow its progression.

Previously published research suggests that drugs to lower cholesterol, control diabetes, and dampen down inflammation may help to lessen the risk of developing AMD, but these findings were partly contradictory and based on small numbers of participants.

In a bid to get round these issues, the researchers pooled the results of 14 population-based and hospital-based studies, involving 38,694 people from France, Germany, Greece, Ireland, Italy, Norway, Portugal, Russia and the UK.

The studies were part of the European Eye Epidemiology (E3) consortium, a collaborative pan European network, the principal aim of which is to develop and analyze large-pooled datasets to further the understanding of eye disease and sight loss.

Participants were all over the age of 50 and taking at least one of the following types of drug to: lower cholesterol, including statins; control diabetes, including insulin; to dampen down inflammation, excluding steroids; and Levodopa, used to treat movement disorders caused by neurodegenerative disease.

The prevalence of AMD ranged from 12% to 64.5% across the included studies—9332 cases in total—while the prevalence of advanced (late) AMD ranged from 0.5% to 35.5%—951 cases in total.

The pooled data analysis showed that drugs to lower cholesterol or control diabetes were associated with, respectively, 15% and 22% lower prevalence of any type of AMD, after accounting for potentially influential factors.

No such associations were found for any of the other types of drug or for advanced AMD, in particular, although there were only a relatively small number of such cases, note the researchers.

Theirs is the first large pooled data analysis of its kind to use individual level data from various population-based and hospital-based studies, highlight the researchers.

“Yet, further longitudinal data are needed to confirm our findings, which are inherently limited by using cross-sectional data only and cannot infer causality,” they caution.

But the findings point to a likely key role for metabolic processes in the development of AMD, which may offer potential new avenues for treatment and have implications for public health messaging, they suggest.

“Our study suggests that regular intake of [lipid lowering] and antidiabetic drugs is associated with reduced prevalence of AMD in the general population. Given a potential interference of these drugs with pathophysiological pathways relevant in AMD, this may contribute to a better understanding of AMD aetiology,” they conclude.

1. Matthias M. Mauschitz, Timo Verzijden, Alexander K. Schuster, Hisham Elba, Norbert Pfeiffer, et.al. Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans. 

Published October 2022. DOI: 10.1136/bjo-2022-321985.

According to a study, use is linked to a lower prevalence of age-related macular degeneration in European populations.

Risk of Degenerative Eye Disease of Aging May Be Reduced by Cholesterol and Diabetes Drugs

NEXGEL Inc. announced this week it has developed a new, proprietary hydrogel eye patch to treat amblyopia, a type of poor vision that typically occurs in one eye but can occur in both eyes (also called lazy eye).

According to the company, the patch is expected be available for ophthalmologists and optometrists to offer to their patients in the first half of 2023.

The company noted in a news release that amblyopia is present in approximately 2% to 4% of the U.S. population. According to the National Eye Institute, it is the most common cause of visual impairment in childhood and affects approximately two to three children out of every 100. The global amblyopia treatment market is forecast to exceed $6 billion by 2027.

Unlike the current standard-of-care patching for amblyopia, NEXGEL’s hydrogel patch is much gentler on the skin and is manufactured without the use of harsh chemicals or painful adhesives.

According to Leonard Nelson, MD, FACS, the most effective eye patches for the treatment of amblyopia are placed directly on the skin covering the eye, however, traditional eye patches for amblyopia are difficult to adjust and remove, pulling at and irritating the thin skin around the eye.

“For children, the associated discomfort often leads to poor compliance and suboptimal treatment,” Nelson, co-director of the Pediatric Ophthalmology Department and Director of the Strabismus Center at Wills Eye Hospital, said in the news release. “NEXGEL’s unique hydrogel technology is the innovation that pediatric ophthalmologists have been waiting for. The patches are gentle, can be worn for long periods of time without experiencing any pain or discomfort and are easily removable and replaceable – exactly what we need to treat our pediatric patients.”

Moreover, Adam Levy, NEXGEL’s CEO pointed out that the company’s ability to quickly develop this patch after learning about the growing need for a better amblyopia treatment product in the market is a hallmark of its hydrogel technology and is just another example of its many applications across healthcare, particularly at the interface between a medical device and the patient’s skin.

“Parents and doctors have been searching for a superior solution to treat this condition for pediatric patients, and we look forward to bringing our product to market in early 2023,” he said in the statement.

This article originally appeared on Ophthalmology Times. 

According to NEXGEL, the patch is expected be available for ophthalmologists to offer to their patients in the first half of 2023.

Treating Amblyopia with a Hydrogel Patch

Outlook Therapeutics Inc. today announced it has re-submitted its Biologics License Application (BLA) to the FDA for ONS-5010, an investigational ophthalmic therapy which, if approved, will be branded as Lytenava (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).

Russell Trenary, President and CEO of Outlook Therapeutics, noted in a press release that the company has worked over the past three months to provide the additional required information that was not included in the company’s March 2022 BLA submission, to address requests from the Agency to ensure the BLA is complete for acceptance and review.

“We believe that this re-submission addresses each of the comments and recommendations from the Agency, and we are confident in the revised BLA application,” he said in the statement. “We remain committed to bringing ophthalmic bevacizumab to market, which if approved, can provide retina patients with an on-label treatment option that helps patients avoid the health risks associated with unapproved repackaged oncologic IV bevacizumab.”

According to the company, ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability.

If approved, ONS-5010 can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

The company also noted in the news release that bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

Terry Dagnon, chief operations officer of Outlook Therapeutics, noted in the release that the company’s NORSE TWO pivotal trial for ONS-5010 showed efficacy and clinical relevance coupled with a robust safety profile, and company officials are confident that the investigational drug, if approved, will be a valuable therapeutic option to treat retina diseases.

“ONS-5010 is designed and manufactured to be fully compliant with FDA’s criteria for ophthalmic biologics to meet the public health need for an FDA-approved ophthalmic formulation of bevacizumab,” Dagnon said in a statement.

In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics has continued its commercial launch planning. These activities include establishing best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Ajinomoto Bio-pharma Services for finished drug product. Outlook Therapeutics is also actively building out its distribution and commercial capabilities.

According to the company, the BLA re-submission is based on the totality of data from Outlook Therapeutics’ wet AMD clinical program for ONS-5010, which consists of three completed registration clinical trials - NORSE ONE, NORSE TWO and NORSE THREE – as well as a Phase 1 pharmacokinetic clinical trial and the necessary pre-clinical testing.

NORSE ONE was a clinical experience trial involving 61 wet AMD participants at nine trial sites in Australia. It compared ONS-5010 to ranibizumab (LUCENTIS®) as a treatment for wet AMD. NORSE ONE showed the first markers of efficacy and safety in humans for ONS-5010 ophthalmic bevacizumab. In the trial, ONS-5010 efficacy and safety data were consistent with historical published studies of bevacizumab in ophthalmology. NORSE ONE also supported the trial design and inclusion/exclusion criteria established for NORSE TWO, the pivotal Phase 3 registration clinical trial.

The NORSE TWO Phase 3 pivotal trial enrolled a total of 228 wet AMD patients at 39 clinical trial sites in the United States. It was designed as a superiority study comparing the safety and efficacy of ONS-5010 ophthalmic bevacizumab dosed monthly against ranibizumab (LUCENTIS®) dosed according to the PIER dosing regimen described in the LUCENTIS® label. The trial data met both their primary and secondary endpoints with high statistical significance and clinical relevance. For its primary endpoint, 41.7% (p = 0.0052) of patients gained at least 15 letters of vision, and for its secondary endpoints 56.5% (p = 0.0016) of subjects gained ≥ 10 letters of vision and 68.5% (p = 0.0116) gained at least 5 letters. The key secondary endpoint was met: mean change in BCVA from baseline to Month 11, which was 11.2 letters gained compared to 5.8 letters gained in the ranibizumab arm (p = 0.0043). The NORSE TWO data also showed that the drug was well-tolerated, consistent with previously reported data for ONS-5010 and prior research.

NORSE THREE was an open-label safety study of ONS-5010 in 197 patients conducted in the United States to provide the necessary number of retina patients dosed with ONS-5010 to complete the requirements for the BLA submission.

Safety results across the first three NORSE trials demonstrated a strong benefit-to-risk safety profile. Across all three ONS-5010 registration trials, there was only one ocular inflammation adverse event, which was reported in NORSE TWO; the event was treated topically and resolved without sequelae. The most common adverse reaction (≥ 5%) reported in patients receiving ONS-5010 was conjunctival hemorrhage associated with the needle injection procedure (5%). These safety findings continue to support minimal ocular inflammation and safety signals consistent with what was previously reported in the 2011 CATT trial (National Eye Institute) and other large adequate and well-controlled ophthalmic studies of bevacizumab.

As the company previously announced, if ONS-5010 receives FDA approval, Outlook Therapeutics plans to submit a supplementary application (sBLA) for approval to provide the product in a pre-filled syringe that is free from liquid silicone oils and that meets the FDA’s specifications for ophthalmic use.

To support the anticipated submission of this sBLA, the company noted that it is conducting its NORSE SEVEN clinical trial to compare the safety of ONS-5010 in vials versus ONS-5010 in pre-filled syringes. NORSE SEVEN is expected to enroll approximately 120 subjects with visual impairment due to retinal disorders. Patients will be treated for three months, and patient enrollment in the arm of the study receiving ONS-5010 in vials has already been completed.

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases.

BLA Resubmitted for Investigational Ophthalmic Therapy from Outlook Therapeutics Inc. 

Oyster Point Pharma Inc. today announced that the largest Medicare pharmacy benefit manager in the United States will add its varenicline solution nasal spray (Tyrvaya) for the treatment of dry eye on its Medicare Part D formularies, effective September 1.

According to Jeffrey Nau, PhD, MMS, president and CEO of Oyster Point Pharma, the milestone will further expand patient access and enable continued momentum in eye care professionals prescribing the nasal spreay for the treatment of dry eye disease.

“In the United States, almost half of the total dry eye disease prescriptions are covered by Medicare, and we believe TYRVAYA provides a truly compelling treatment option,” he said in a statement. “We are committed to growing patient access and are looking forward to continue engaging with Medicare Part D health plans.”

The FDA in Ooctober 2021 approved the varenicline solution nasal spray for the treatment of the signs and symptoms of dry eye disease.

According to the company, varenicline solution nasal spray 0.03 mg is a selective cholinergic agonist that is FDA-approved to treat the signs and symptoms of dry eye disease as a multidose nasal spray. The parasympathetic nervous system, the "rest and digest" system of the body, controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose.

The company noted that the efficacy of the spray in dry eye disease is believed to be the result of varenicline's activity at heteromeric sub-type(s) of the nicotinic acetylcholine (nACh) receptor where its binding produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film as a treatment for dry eye disease. Varenicline binds with high affinity and selectivity at human α4β2, α4α6β2, α3β4, α3α5β4 and α7 neuronal nicotinic acetylcholine receptors. The exact mechanism of action is unknown at this time.

Oyster Point Pharma Inc. announced that the largest Medicare pharmacy benefit manager in the United States will add its varenicline solution nasal spray for the treatment of dry eye.

Varenicline Solution to Be Covered by Key Medicare Pharmacy Benefit Manager

According to the company, its expanded patient access programs include more eligible patients with dry eye disease.

Oyster Point Pharma Inc. this week announced the expansion of patient access to varenicline solution (Tyrvaya) nasal spray and provided an update on the commercial performance of TYRVAYA in the United States.

The company noted that it continues to expand access to varenicline solution for patients with dry eye disease. As of July 2022, varenicline solution is now covered by commercial prescription drug plans managed by the nation’s top three pharmacy benefit manager group purchasing organizations.

The company in July expanded patient access programs to include more eligible patients. For further details, please see the company’s patient access website at www.tyrvaya-pro.com.

According to the company, it continues to expect to further expand access to varenicline solution with coverage for Medicare Part D patients in 2023, and as early as Q4 2022.

The expansion of patient access to varenicline solution comes as the company continues to build upon its launch success. The company also noted that since its July 1 launch, varenicline solution prescriptions have already been written by approximately 7400 eye care prescribers (ECPs) out of the approximately 21,000 total ECPs targeted by the company’s field-based sales resources.

Moreover, the company noted that based on third-party data, among ECPs who have written a commercial varenicline solution prescription, varenicline solution has reached approximately 21% market share of commercial new-to-brand prescriptions (NBRx) as of the week ending July 1, 2022, driven by strong utilization among ECPs. Notably, this result was achieved in just eight months since the launch of varenicline solution in the U.S.

“We are very pleased with the continuing progress in securing commercial coverage for TYRVAYA,” said Jeffrey Nau, PhD, MMS, president and CEO of Oyster Point Pharma. “We are encouraged by the overwhelmingly positive feedback received to date from patients and eye care professionals alike. We recognize that despite growing commercial coverage for TYRVAYA, some patients who suffer from dry eye disease may also have insufficient insurance coverage or insurance plans with high deductibles and/or co-insurance.”

Nau explained that the expanded patient access program aligns with the company’s commitment to optimize access to varenicline solution for as many eligible patients as possible.

Oyster Point Pharma Inc. this week announced the expansion of patient access to varenicline solution (Tyrvaya) nasal spray.