A Novel Treatment for Floaters

Summary

The purpose of this article is to explain some pertinent technical aspects of the physiology and pathophysiology of the eye as it relates to vitreous opacities, followed by an overview of the current diagnostic and treatment options for floaters. I will then explain a non-invasive floater treatment that is not widely known and may be helpful to some people with symptomatic vitreous opacities. The article will finish by outlining a novel, image guided, robotically assisted, minimally invasive procedure as a potential cure for symptomatic vitreous opacities.

Background

Patients with symptomatic vitreous opacities (ie. symptomatic floaters) are an unserved patient population and medical market.

Symptomatic floaters have a significant negative impact on patients’ lives. They are similar to being surrounded by a swarm of small flies – practically impossible to ignore, and serve as a constant source of distraction and stress.

Having a few floaters is a very common symptom, and one that increases with age. If they are few in number, small, translucent, and/or peripherally located, they are relatively easy to ignore, and patients are able to accept their existence as a minor problem. My personal belief is in a threshold phenomenon, where are after a certain point the floaters are no longer able to be effectively ignored.

Floaters, particularly those in the bursa premacularis (BP) located immediately adjacent to the retina, are generally not visualized by ophthalmologists or optometrists during routine eye exams. Furthermore, standard evaluations of visual function are not significantly impacted. Importantly, floaters do not result in blindness or death, and floaters are painless. Given these diagnostic limitations, it is essentially impossible for an ophthalmologist to accurately determine which patients are over-reacting to a common and relatively minor issue, and which patients have a significantly distracting or even debilitating disease.

Moreover, there is no current standard treatment that is both safe and effective, making the distinction between minor and significant floater burden a moot point. Patients are told that they will likely adapt to the existence of floaters with time, and essentially learn to ignore the floaters. There is confirmation bias to this dogmatic belief as even patients with significant floaters will not continue to visit a physician if there is no reasonable treatment.

It is worth noting that patients with symptomatic floaters in the premacular bursa are much younger and healthier than the standard patient population for an ophthalmology practice, which is generally sufficiently busy with profitable procedures for older patients with objectively severe eye diseases. This also contributes a subtle bias against the impact of floaters on patients’ lives.

The truth is that patients with symptomatic floaters go to great lengths to minimize the impact of their floaters, in particular avoiding the outdoors as floaters are most noticeable in bright light. Floaters are more apparent when looking at source of light, for example when working on a computer or looking at a phone screen, which are common activities indoors. Floaters also cause straylight glare and contrast sensitivity, which can make reading more difficult due to the subtle blurring of letters.

It is safe to say that there is widespread anecdotal knowledge in the ophthalmologic community about the commonality of floaters as a chief complaint in clinical practice. However, the prevalence of symptomatic floaters in the general population as well as specific subpopulations remains unknown. It is unknown what number of people see ophthalmologists or optometrists for floaters. And it remains unknown the degree to which these patients are psychologically impacted by their disease, and how many would want to undergo a safe procedure to treat their disease. It is my belief that the number is at least in the tens of thousands, and likely much greater.

Physiology

A complete explanation of the anatomy and physiology of the eye is beyond the scope of this article.  Having said that, the following is pertinent information regarding the structures in the eye related to floaters in the premacular bursa.

The vitreous body is a gelatinous material surrounded by a cortex that fills the intra-ocular space.  The vitreous is more than 99% water and is transparent, limiting visualization in-vivo (ie. in live humans).  Within the vitreous, parallel collagen fibrils oriented in an anterior-posterior direction are separated by hyaluronan (HA) and water molecules, with additional molecules also present in lesser quantities.  HA is a glycosaminoglycan (GAG), a long unbranched polymer of disaccharide moieties, that is associated with water molecules but not chemically bound to them.  The HA and associated water molecules maintain the spaces between the collagen fibrils.

The vitreous “base” is located in the anterior aspect of the vitreous chamber and is defined as the region behind the lens.  The posterior aspect of the vitreous chamber is lined by the posterior vitreous cortex, and is approximately 100 μm at its thickest point.  

The premacular bursa (aka posterior precortical vitreous pocket (PPVP), bursa premacularis (BMP, BP)) is a liquefied lacuna anterior to the macula in the retina that is present physiologically in the vitreous of adults.  The anterior border is vitreous gel and the posterior border is the posterior vitreous cortex attached to the retina that is thinnest at the fovea.  The height of the premacular bursa is the distance between fovea and the anterior border.

The premacular bursa extends skyward/anteriorly (and superonasally) as Clouquet’s canal (aka hyaloidal tract of Eisner) in the preoptic area of Martegiani, terminating behind the lens in the space of Erggelet/Berger.  The connection with Cloquet’s canal is nasal and superior with a septum present.  On vertical images, the height of the premacular bursa greater superiorly than inferiorly.  A supramacular bursa has been described as anterior to the premacular bursa and present in nearly 90% of patients.

The premacular bursa can be visualized by Swept Source Optical Coherence Tomography (SS-OCT) in 100% of eyes without posterior vitreous detachment (PVD).  The premacular bursa is described as “boat-shaped” or “wedge-shaped” on horizontal images, and measures 3000 -10,000 μm in width and length, with an average of 6000 – 7000 μm, and the mean height averages 400-700 μm.   The anterior border of the premacular bursa increases by approximately 200 μm when the patient is in the supine position.

The volume of premacular bursa measures 6.84 μL and volume of adjacent area of Martegiani measures 3.06 μL.  The volume of the posterior vitreous is 4 mL (4000 μL), comprising about 80% of the volume of the globe.

Pathophysiology

There are many causes of floaters, including what patients may perceive as floaters however are not vitreous opacities.  Most cases of vitreous floaters in the mammalian eye are thought to arise from two causes; the introduction of exogenous material during hemorrhage or inflammation, and degenerative molecular rearrangements of vitreous collagen fibrils that results in localized aggregations.  Other causes of floaters also possible, however these are less common, may be temporary, and are not the focus of this article/information which are floaters in the premacular bursa.

It is worth mentioning that the most common cause of floaters is posterior vitreous detachment (PVD).  The posterior vitreous cortex detaches from the retina due to decreased volume of the vitreous.  This generally happens in an older patient population and will not be the focus of this article.  Patients with an increase in floaters should always have an emergent ophthalmological evaluation due to risk of PVD associated retinal break/tear that may cause permanent blindness.

Younger patients have vitreous floaters because of collagen cross-linking known as syneresis, not because of PVD.  Posteriorly located vitreous opacities often cause the most disturbing symptoms.  This is because they are located immediately in front of the retina, which makes a tiny opacity appear large, dark, and sharp.

Liquid vitreous forms when hydrophilic HA dissociates from the collagen and retains the water molecules, forming lacunae pools. No longer separated by HA, collagen cross-links, aggregates, and forms floaters. It is unclear if these steps occur in order (and if so, which occurs first) or simultaneously.  This process can be induced by the introduction of oxygen free radicals which may damage HA, damage collagen, and/or initiate the dissociation of collagen and HA.

HA synthesis appears to be induced by estrogen. Conversely, estrogen depletion decreases HA synthesis, which results in decreased HA and water in the vitreous.  This results in vitreoretinal traction as well as allows collagen to cross-link and form floaters.

The average floater is 100 micrometers (μm) = 0.1 millimeter (mm) in diameter.  This is approximately the 70 μm width of the average human hair. 

Current Diagnostic Options

Primary limitations of imaging the vitreous in-vivo (ie. in live humans) are its transparency and near continuous movement.

Ophthalmoscopy (Direct and Indirect techniques)

The clinician is unable to visualize floaters in the premacular bursa due to their small size and location.

Ultrasonography

Limited size accuracy and resolution due to wavelength minimum of 200 μm, which is larger than most floaters.

Scanning Laser Ophthalmoscopy (SLO)

Can demonstrate anterior and central vitreous opacities, however limited posterior visualization and limited resolution restrict its usefulness for visualizing floaters.

Dynamic Light Scattering (DLS)

Laser based technology that can measure the average size of particles from 3 nm to 3 um in the vitreous.  However, does not directly visualize vitreous opacities and does not appear to be useful in surgical guidance. 

Optical Coherence Tomography (OCT)

Utilizes broadband light source, divided into a reference and a sample beam, to obtain information on the tissues from the reflected waves interference patterns.

Spectral Domain (SD-OCT)

Use near-infrared wavelengths of around 850 nm with point of maximum sensitivity (known as the “zero delay line”) located in the vitreous.  Axial scanning speeds of 20,000-52,000 A-scans per second with an axial resolution of 5-7 μm.  Imaging depth limited to 1.5-1.9 mm.  Some SD-OCT devices have automated eye-tracking.

Swept Source (SS-OCT)

Became available in clinical practice in 2012.  Twice as fast as SD-OCT and superior to SD-OCT for visualizing the vitreous.,  Uses center wavelengths of 1040-1060 nm with a scan rate of 100,000 Hz, allowing for deeper penetration into the choroid and sclera.,  Axial resolution of 8 μm and lateral resolution of 20 μm.  Imaging depth up to 2.6 mm.  Imaging length and width up to 18 x 18 mm.  Able to visualize the entire premacular bursa.  En-face imaging: 3D reconstructions in a fundus projection.  Able to be optimized to image the posterior vitreous and can accurately display vitreous opacities that correspond with visible floaters in symptomatic patients.

Current Standard Treatment Options

Neodymium:yttrium-aluminum-garnet (YAG) laser 

Limited effectiveness in studies.  Unable to be used for floaters in the premacula bursa, the site of the most bothersome floaters.

Pars plana vitrectomy +/- PVD induction

Numerous possible severe complications plus nearly guaranteed cataracts requiring future surgery.  Nearly non-existent long term studies (>2-10 years) despite the procedure being performed for decades is highly suggestive of under-reported long term complications.

Utilizes 3 ports: light source, infusion line, vitrector.  More ports increases likelihood of complications such as hypotony and infection.

Vitrectomy must be performed due to the limitations of accuracy of an unaided surgical hand.  The location of vitreous floaters in the premacular bursa prevents safe targeted removal as there would be danger of injuring the retina with the surgical instruments.

Noninvasive Treatment Option

Atropine eye drops 

Atropine dilates the pupils to decrease or eliminate the perception of floaters.  Using a dilute solution of atropine can be a very effective treatment for people with symptomatic floaters.  However, it does not completely eliminate the perception of all floaters.  It also has a limited time of action and a variable response that changes over time.  Notably, it has decreased effectiveness with increased side effects when repeating the dose in a short interval.  The side effects include light sensitivity, glare around light sources, and presbyopia that changes over time requiring multiple strengths of reading glasses.  There is also the risk of accommodative esotropia and acute angle glaucoma.

Novel Preceyes Treatment

Combines SS-OCT imaging with Preceyes robotic needle guidance for a precise image guided vitrectomy of floaters in the premacular bursa.  Preceyes is a company based in the Netherlands that has developed a robotic assistant for eye surgery.  The system provides surgeons with a precision better than 20 μm to position and hold instruments.

This novel treatment would require a single small needle puncture utilizing a dual bore injection needle to exchange fluid.  The treatment does not require a second port to administer saline as less than 1% of vitreous is removed.  The treatment also does not require a third port for a light source, as the surgeon would utilize the SS-OCT via the pupil to guide the surgical needle.

There is minimal expectation of pressure change if removal of fluid/opacities from bursa even without simultaneously replacing with saline as the amount is less than 1% of the vitreous volume.  However, if fluid and vitreous opacities aspirated from the premacular bursa without replacement of fluid, the pocket will likely quickly collapse, inhibiting the aspiration of remaining opacities.  As such, it is likely that a dual bore injection needle would be required.  It is notable that some opacities may be anchored to the vitreous border of the premacular bursa, possibly inhibiting safe aspiration.

This proposed image guided, robotically assisted, minimally invasive procedure offers a potentially safe cure to patients suffering from symptomatic vitreous opacities.