Acoustic Manipulation of Intraocular Particles (#2018027)

Background

The fluid in the anterior and posterior chambers of the eye, known as the aqueous humor (AH), is a complex mixture of biological molecules that are actively working to vitalize and protect the surrounding non-vascularized tissues (i.e., trabecular meshwork (TM), lens, and corneal endothelium). The aqueous exits the eye either through the TM into Schlemm’s canal and aqueous veins (conventional pathway) or through the ciliary muscle and other downstream tissues (unconventional pathway).

In the healthy eye, flow of AH against resistance generates an average intraocular pressure (IOP), which is necessary to inflate the eye and maintain the proper shape and optical properties of the globe. Impairment in AH outflow might results in elevation of the IOP, a central tenet of several diseases and mainly glaucoma.

Glaucoma is a progressive optic neuropathy in which retinal ganglion cells and their axons die causing a corresponding visual field loss and ultimately blindness. An important risk factor is increased IOP, caused mainly due to decreased outflow of AH. One of the common causes for increased resistance to outflow of AH is due to accumulation of particles obstructing the TM.

Various conditions might result in formation or dispersion of particles of different shapes, sizes and trait circulation inside the AH and obstructing the TM including: fibrillary extracellular material in pseudoexfoliation syndrome (PXF), pigment particles in pigment dispersion syndrome (PDS) and erythrocytes and leukocytes in uveitis-hyphema-glaucoma syndrome. In addition to obscuration of the visual axis in the acute phase, these particles might cause a secondary open-angle glaucoma due to obstruction of the TM and the AH outflow resulting in increased IOP. Particles might also result in depositions in the corneal endothelium resulting in Krukenberg's spindle or corneal staining by red blood cells from longstanding hyphema. Although both medical and surgical treatment options exist for such complications, preventive treatments are lacking.

We developed a novel preventive treatment concept based on the idea that the scope of tissue interaction with the particles could be limited by controlling their movement within the AH using acoustic waves.

The Need

Various conditions result in accumulation of pathologic particles within the Aqueous Humor (AH) of the eye. There is a great medical need to control these particles and to minimize the clinical complications:

• Interaction with the trabecular meshwork (TM) resulting in gradual destruction of the normal architecture and as a result reduce the outflow of AH. These changes are a major risk for increased intraocular pressure and secondary open-angle glaucoma requiring lifelong medication and surgery in severe cases to prevent irreversible loss of vision. This form of glaucoma usually has a more serious clinical course and worse prognosis.
• The particles pose a problem for the examining physician in evaluating the patient and identifying pathology.
• The particles cause both visual disturbances and aberrant field of view.
• Particles might also result in depositions in the corneal endothelium resulting in Krukenberg's spindle or corneal staining from longstanding hyphema.

The most common causes are pseudoexfoliation syndrome which is most prevalent in northern Europe with up to 50% prevalence among Scandinavians, and pigmentary dispersion syndrome with an annual incidence of nearly 6% in the USA.

Elevation in intraocular pressure due to particle effect on the trabecular-meshwork is one of most common sequela of these conditions leading to glaucoma development and lifelong need for medication and ophthalmology follow-up and in some cases even surgery in order to prevent irreversible loss of visual fields and vision. The conversion rate to glaucoma in both these syndromes is estimated at up to 50% of cases.

The current clinical practice regarding the particle dispersion inside the AH composes mainly of a "wait and see" approach, only treating secondary complications, which can be detrimental, and offer no treatment options for the condition itself.

Our technology utilizes acoustic waves for non-invasive control over movement of these pathologic intraocular particles, preventing them from unwanted accumulation and obstruction of intraocular structures, or causing visual disturbances. The treatment, without causing any tissue damage, will not only help clear the field of vision and accelerate recovery, but will also be a preventive treatment which will significantly reduce if not prevent secondary complications, predominantly open-angle glaucoma.

The Innovation

Acoustic waves are used to manipulate and to sort biological cells and particles in 2D and 3D, study cell-cell interactions, to enrich cells and protein crystals, to selectively promote coalescence and to create ordered colloidal crystals. While manipulation of particles and biological cells is a well-used technology in various fields of research and in some medical fields like esthetics, using acoustic waves to control intraocular particles in order to treat serious ophthalmologic conditions has not been previously utilized.

By understanding the mechanism of particles accumulation and absorption in the anterior chamber, we have established a novel method and system to manipulate these particles and to reduce visual disturbances, corneal staining and the possibility to develop an open-angle glaucoma.

• A device and a method for non-invasive manipulating particles using standing acoustic waves in the anterior chamber of the eye.
• A novel ocular non-invasive device using acoustic waves for treating secondary complications (e.g. glaucoma) and visual disturbance (e.g. hyphema, asteroid hyalosis and vitreous floaters) which caused by the accumulation of particles within the anterior chamber of the eye.
• A device that facilitates targeted therapy by directing intraocular drugs to the appropriate site using acoustic waves.
• A software which analyze the dispersion of particles, create a treatment plan and execute it by acoustic waves manipulation.
• A software that enables personalized treatment to the specific needs of the patient.

Advantages

• An option of treatment for the condition itself, the accumulation of particles within the TM, not just the treatment of secondary complications, which is the only treatment available today (no direct competitors).

• The use of acoustic wave manipulation allows non-invasive treatment at low power density and relatively cheap equipment.

• Fast trek to regulatory process (510K FDA approval process), The FDA as already approved similar methods for other medical fields.
• Short time to market.

The Product

• An AUTOMATIC STAND ALONE device to be used in ophthalmology clinics by physicians, with the capability of customized protocol treatment and tracking for every patient's unique needs.
• An in-house Device to be used by patients for a routine treatment. That monitor and forwards details directly to the personal patient's physician for immediate update of the treatment protocol.

Development Stage

• We have developed a prototype acoustic resonator and demonstrated proof of concept and efficacy in animals.
• Furthermore, our initial results demonstrate the safety of the product and procedure in animals.
• We are developing protocols and algorithms to evaluate personalized treatment.

The Market

The direct ophthalmology market for acoustic manipulation of particles includes the following segments:

• Patient with Pseudoexfoliation (PXF) syndrome:

Open-Angle Glaucoma (OAG) accounting for about 80-90% of all glaucoma cases and Pseudoexfoliation (PXF) syndrome, also called exfoliation syndrome (XFS), is the most common identifiable cause of open-angle glaucoma worldwide, nearly 30% of glaucoma cases.

PXF syndrome may affect up to 30% of people over 60 years of age worldwide and in eyes with PXF syndrome, the probability of converting to glaucoma is about 30% to 40% in 10 years.

• Patient with Pigment dispersion syndrome (PDS):

PDS is another relatively common form of secondary open angle glaucoma with an annual incidence of almost 6% in the USA. This condition typically occurs in younger patients, between the ages of 20 and 45. Patients are more often male and tend to be nearsighted. That gives at least 20 additional years during which the typical patient with pigmentary glaucoma needs to manage the disease. In the Western world, pigmentary glaucoma (PG) represents 1–1.5% of total glaucoma cases and, due to its early age of onset, is the most common cause of nontraumatic glaucoma in young adults making it an important cause of debilitating blindness.

• Patient with Ocular inflammatory disorders (uveitis):

The prevalence of uveitis has been estimated at approximately 115 people per 100,000 in the United States and at 38-730 people per 100,000 worldwide. Approximately 20% of uveitis patients develop glaucoma and it can be as high as 46% in patients with chronic uveitis.

• Patient with Hyphema:

In North America, the incidence of hyphema is 17-20 cases per 100,000 people per year. Rebleeding occurs in 4–35% of hyphema cases and is a risk factor for glaucoma. The young population is most affected. Approximately 77% are younger than 30 years. The peak incidence is in people aged 10-20 years.

Young children with traumatic hyphema are at an increased risk of developing amblyopia, an irreversible condition.

Based on these percentages, the number of people affected by PXF is about 280 million, uveitis is 57 million and Hyphema is 1.7 million worldwide; and PDS is 700K in the western world. We anticipate that at least 25% of Ophthalmological clinics will purchase our device, therefore, the potential for the clinic market is 1-3 Billion USD, estimating that the price of our clinic-type devices will be 10-30K USD; and the market share of in-house devices may, over the first few years, reach 10% of diagnosed patients, this puts its potential at 1-2 Billion USD, estimating that our in-house price of the device will be 1-2K USD.

PXF and PDS Glaucoma is more resistant to medical therapy. Topical medicines tend to be less effective, which is why patients affected by them usually undergo laser or surgical therapy. Patients with PXF or PDS glaucoma, however, may present a greater risk of surgical complications. For this reasons, we believe our device will integrate as a primary treatment solution for these patients.

The leading open-angle glaucoma therapeutics companies include Aerie Pharmaceuticals Inc., Allergan Plc, Bausch Health Companies Inc., Novartis AG, and Pfizer Inc.