new research on vitreous floaters

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Safer eye floater treatments come with a burst of nanobubbles

Between invasive surgery or risky laser therapy, people suffering from severe eye floaters have no great treatment options. now, with the development of a safer and less invasive nanoparticle-based therapy, people with floaters may finally get their vision and quality of life back..

Stephanie joined Drug Discovery News as an Assistant Editor in 2021. She earned her PhD from the University of California Los Angeles in 2019 and has written for Discover Magazine,...

Sometimes they sit just out of sight in the corner of your eye. Other times they waft across your vision, and when you shift your gaze to look at them, they fly out of sight. These pesky obstructions, commonly referred to as floaters, are a visual phenomenon caused by small clumps of collagen in the eye called vitreous opacities. 

While floaters are very common, they are typically unobtrusive enough that people ignore them. Sometimes, however, floaters can be so dark and numerous that they obscure large swaths of a person’s vision. These severe floaters impair people’s ability to drive, work, and simply enjoy their lives, often leading to depression (1).

“There are millions of people in the world suffering from floaters,” said Yannis Paulus, a vitreoretinal surgeon and clinician scientist at the University of Michigan. “Currently, they’re stuck with bad options,” he added. The only available treatments have a significant number of risks.

These treatments include vitrectomy, the surgical removal of the clear gel-like vitreous of the eye that contains the collagen clumps, and laser vitreolysis, shining high-energy light pulses directed at the fibers to break them apart. Vitrectomy is more effective than laser vitreolysis, but patients have experienced retinal tears, detached retinas, and vitreous hemorrhage with both treatments.

While investigating how to make vitrectomy and laser vitreolysis safer and more effective, scientists are also developing new nanobubble-based technologies that may prove even safer and less invasive than the current treatments, improving the quality of life for the many people around the world suffering from disruptive floaters.

Clumps of collagen

The most common cause of floaters is simply getting older. In young eyes, collagen fibers bound to hyaluronan molecules hold together the gel-like structure of the vitreous. As people age, the collagen and hyaluronan begin to dissociate, and the gel becomes more liquid-like, causing the collagen fibers in the vitreous to collapse onto each other and form clumps, which are perceived as floaters.

People over 60 years old often begin to see more floaters due to their vitreous pulling away from the back of the eye in a phenomenon called posterior vitreous detachment. But because this de-gelling process happens faster in people with nearsightedness, nearsighted people in their 20s, 30s, and 40s can also experience floaters.

For people who notice a sudden burst of many new floaters, ophthalmologists first check for any signs of retinal detachments or injuries to the eye. But after ruling out an acute cause, doctors usually suggest that people wait a few weeks or months to see if their floaters seem to fade or become less noticeable. Usually, people experience some neuroadaptation, and the brain tunes out the floaters. But if the floaters don’t get better and they continue to detrimentally affect daily life, people return to their doctors seeking help.

“Unfortunately, the most common form of treatment is to dismiss them and ignore them and send the patient home frustrated and unhappy,” said Jerry Sebag, a vitreoretinal surgeon and floaters researcher at the Vitreous Macula Retina (VMR) Institute. “I started to realize that these patients are being dismissed because we had no way of identifying if they really have a problem, or if they're just overreacting to something that we all experience.”

Sebag and his colleagues developed quantitative assessments to measure how floaters affect people’s vision. They demonstrated that they could use quantitative ultrasound to characterize the density of the entire vitreous with floaters showing up as points and lines of increased density (2). Sebag’s team also reported that floaters decreased a person’s contrast sensitivity , meaning that people with floaters were less able to distinguish between differences in shading and patterns (3).

“With a quantitative component, it enables you to classify conditions as mild, moderate, and severe,” said Sebag. “It enabled me to select patients for treatment.”

Surgical incisions clear out floaters

The most effective way to treat floaters is to physically remove them. By performing a surgery called a vitrectomy, surgeons remove the vitreous from the eye and replace it with a clear gel.

While there are risks of retinal tears and detachments during vitrectomy, “you can usually identify those problems during the surgery. If you see a torn retina, you can laser it during the operation,” said Jason Hsu, a vitreoretinal surgeon and researcher at Thomas Jefferson University.

Vitreoretinal surgeons have recently made improvements to vitrectomies to make these retinal tears less likely. For example, they now use smaller gauge instruments to perform the surgery, meaning that they can make smaller incisions. Sebag has adapted his vitrectomy procedure with this modification and improved the method so that it doesn’t induce a posterior vitreous detachment during the surgery. With these safety modifications, Sebag’s team reported in a clinical study of 195 eyes from 145 patients that vitrectomy led to a 94.1% reduction in vitreous echodensity, indicating successful removal of the vitreous opacities that cause the appearance of floaters (4). The patient’s contrast sensitivity also improved to the level of healthy control eyes after surgery. Out of the 195 eyes operated on, there were three retinal tears and three retinal detachments, but these were successfully repaired during the surgery.

While vitrectomy is relatively safe and effective at treating severe floaters, it does lead to an increased risk for developing cataracts (5). Because of this and because other long-term risks of vitrectomy are unknown, Sebag and other vitreoretinal surgeons hesitate to operate on younger patients.

“I just haven't followed people for 30 years, so I can't answer that question,” said Sebag. As an alternative to vitrectomy, some ophthalmologists turned to a risky and somewhat controversial treatment: laser vitreolysis.

An explosion in the eye

Rather than physically removing the vitreous opacities that cause floaters, some ophthalmologists have tried blasting them apart with pulses of a yttrium-aluminum-garnet (YAG) laser.

“It's not like a typical laser beam that we think of like in Star Wars or something where it's burning tissue. The YAG laser is like a little explosion in the eye,” said Hsu. “It’s almost like evaporating some of the tissue with this high concentrated energy.” This process breaks up large aggregates of collagen into smaller pieces, reducing the appearance of floaters.

Ophthalmologists have used YAG lasers for decades to remove cloudy layers of scar tissue that form after cataract surgery and in the treatment of specific kinds of glaucoma, but their use to treat floaters is relatively new and somewhat controversial.

In the only clinical trial so far investigating the effectiveness of YAG laser vitreolysis for floaters, 54% of the patients who received the YAG treatment reported improvement in the appearance of floaters (6). None of the patients in the trial experienced any adverse effects.

There are, however, substantial risks associated with YAG laser treatment. The laser energies needed to blast apart the fibers that cause floaters are double or triple that of the energies used for the other more routine uses of YAG lasers. Even with the higher energy laser pulses, a person may need to sit through multiple sessions of YAG laser treatment to effectively break up a bothersome floater. In some instances, surgeons have focused the laser too close to the front or back of the eye, causing direct damage to the lens or the retina.

Citing these concerns, Inder Paul Singh, an ophthalmologist at the Eye Centers of Racine and Kenosha, explained that newer YAG lasers allow for better illumination of the vitreous, which helps ophthalmologists more easily orient themselves in the eye, decreasing the risks of damaging vital structures.

“Not every floater is a good candidate for YAG laser vitreolysis,” he said, but for example, if “the floater is in the middle of the vitreous where you can correlate signs and symptoms well, this can be a fantastic opportunity to avoid something like a vitrectomy and not to make [the patient] suffer living with it.”

While Singh has had much success treating floaters with YAG vitreolysis in his practice, that has not been the case for many other doctors.

“There is no protocol to guide the use of YAG laser, either in terms of which patients to select or in terms of how to really do the treatment in a reproducible scientific fashion,” Sebag said. He is organizing a study on how to make YAG vitreolysis more reproducible and safer using quantitative ultrasonography, among other methods, to measure outcomes.

Singh agreed that proper training on how to perform YAG vitreolysis is integral to successful floater treatment.

“The laser is not unsafe. It’s we as doctors who can be unsafe,” he said. “It's important for doctors to feel comfortable understanding where they are in the vitreous and learning how to maximize that view.”

He and others are investigating the use of systems to track floaters more accurately in the vitreous and the use of the more efficient femtosecond laser rather than a YAG laser for floater treatment, which would decrease the number of laser sessions needed to destroy floaters.

With the current risks associated with both vitrectomy and laser vitreolysis, researchers are looking for new strategies to treat floaters.

Nanobubbles bust up floaters

Before presenting his research at the Academy of Medicine in Belgium years ago, Stefaan De Smedt, a drug delivery researcher at Ghent University, had never considered nanobubbles as the next frontier in eye floater treatment. He and his team were interested in using vapor nanobubbles, which are produced by shining a laser at nanoparticles, as a method to deliver nucleic acids into cells.

When scientists shine a laser of a certain frequency at nanoparticles that are close together, the nanoparticles absorb the energy from the laser, which heats up the solution surrounding the nanoparticles, causing the liquid to evaporate and create nanobubbles. These nanobubbles expand and then pop tens to hundreds of nanoseconds after they form (7), leading to the creation of a mechanical force that can poke a hole in a cell membrane.

“I was talking to an ophthalmologist, [and] he said maybe it could be useful as well to see whether this kind of nanobubbles could be valuable to destroy aggregates,” De Smedt said.

Intrigued by the possibility, De Smedt and his postdoctoral fellow Félix Sauvage began testing the ability of vapor nanobubbles produced by different kinds of nanoparticles to destroy the collagen aggregates that cause floaters. In a new study published in Nature Nanotechnology , De Smedt and Sauvage, working in collaboration with Sebag, Paulus, and others, reported the success of nanobubbles produced by gold nanoparticles and an ophthalmologic dye to destroy collagen aggregates in vivo for the first time (8).

The researchers demonstrated that both gold nanoparticles coated in hyaluronan and the ophthalmologic dye indocyanine green (ICG) preferentially bound to and destroyed human vitreous opacities that had been isolated from vitrectomy patients in Sebag’s practice. Because the particles specifically bound to the collagen aggregates, the creation of nanobubbles only occurred at the aggregates. This means that even if the laser shines on a place in the eye with no nanoparticles or dye, no nanobubbles will be created to potentially damage other structures in the eye.

“The threshold to generate bubbles is very high,” explained Sauvage. “We have a selective manner to trigger the generation of bubbles.”

Encouraged by how well their technology worked in an ex vivo system, De Smedt’s team searched for the best animal model to test it in vivo . This proved to be somewhat of a challenge, because, as Paulus quipped, “you don't have a mouse telling you that it has floaters in its vision.”

The team finally landed on rabbits with their relatively large eyes, which are closer in size to those of humans, making them ideal models.

De Smedt, Sauvage, and their colleagues injected rabbit eyes with collagen fibers to give the rabbits vitreous opacities, then they either injected the gold nanoparticles or ICG and shined laser pulses into the rabbits’ eyes. They found that they only needed to use an average of five laser pulses to completely remove the collagen aggregates.

“When we saw that data about how effective it was, it was pretty stunning to me,” said Paulus. When the team assessed the safety of their technique, they found that it had no adverse effects on the rabbits’ retinas.

Because the nanoparticles and dye bind directly to the collagen fibers, the researchers could remove the vitreous opacities from locations in the eye that would be impossible using a YAG laser, such as close to the retina. Similarly, the aggregation of the particles allowed the researchers to use a lower energy laser to induce nanobubbles than that required for a YAG laser to break up fibers, vastly improving safety. 

This technology also improves on vitrectomy because it does not require a risky surgery, rather simply an injection of nanoparticles or dye into the eye. Eye injections are a common procedure for vitreoretinal surgeons, Paulus added.

“It's taking two things that we do in essence almost independently — these eye injections and the laser — and combining them,” he said.

Moving forward, De Smedt and his team are interested in investigating the pharmacokinetics of their gold nanoparticles and ICG in humans. While both gold nanoparticles and ICG are biocompatible, only ICG is biodegradable, making it the more likely of the two to move forward into future human clinical trials.

“Certainly, there's additional work in terms of clinical trials that we need to do before this is readily available for everyone, but I think it would really be a game changer in terms of the ability to treat these floaters in a manner that's minimally invasive with low risk. And I think it would really transform our care for patients,” said Paulus.

Although De Smedt did not initially set out to develop new treatments for floaters, he now understands what a non-invasive and effective treatment would mean for people suffering from floaters. After his team published their first paper on nanoparticles and floaters (9), he and Sauvage received hundreds of questions from people all over the world asking about the potential of the technology to treat floaters.

“I try to imagine how it feels to open your eyes and to feel always depressed about the fact that you cannot really see,” De Smedt said. “It can contribute to giving vision back to people, which means to give quality of life.”

• Kim, Y-K. et al. Psychological Distress in Patients with Symptomatic Vitreous Floaters. Journal of Ophthalmology   2017 , 3191576 (2017).
• Mamou, J. et al. Ultrasound-Based Quantification of Vitreous Floaters Correlates with Contrast Sensitivity and Quality of Life. Investigative Ophthalmology & Visual Science  56 , 1611-1617 (2015).
• Garcia, G.A. et al. Degradation of Contrast Sensitivity Function Following Posterior Vitreous Detachment. American Journal of Ophthalmology  172 , 7-12 (2016).
• Sebag, J. et al. Long-Term Safety and Efficacy of Limited Vitrectomy for Vision Degrading Vitreopathy Resulting from Vitreous Floaters. Ophthalmology Retina   2 , 881-887 (2018).
• Yee, K.M.P. et al. Incidence of Cataract Surgery after Vitrectomy for Vitreous Opacities. Ophthalmology Retina   1 , 154-157 (2017).
• Shah, C.P. & Heier, J.S. YAG Laser Vitreolysis vs Sham YAG Vitreolysis for Symptomatic Vitreous Floaters: A Randomized Clinical Trial. JAMA Ophthalmol   135 , 918-923 (2017).
• Xiong, R. et al. Comparison of gold nanoparticle mediated photoporation: vapor nanobubbles outperform direct heating for delivering macromolecules in live cells. ACS Nano   8 , 6288-6296 (2014). 
• Sauvage, F. et al. Laser-induced nanobubbles safely ablate vitreous opacities in vivo. Nat Nanotechnol (2022).
• Sauvage, F. et al. Photoablation of Human Vitreous Opacities by Light-Induced Vapor Nanobubbles. ACS Nano   13 , 8401-8416 (2019).

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• Published: 17 March 2022

Laser-induced nanobubbles safely ablate vitreous opacities in vivo

• Félix Sauvage   ORCID: orcid.org/0000-0002-8065-4439 1   na1 ,
• Van Phuc Nguyen   ORCID: orcid.org/0000-0001-7466-1483 2 , 3   na1 ,
• Yanxiu Li 2 ,
• Aranit Harizaj 1 ,
• J. Sebag   ORCID: orcid.org/0000-0001-8648-5747 4 , 5 ,
• Dimitri Roels 6 ,
• Viktor Van Havere 1 ,
• Karen Peynshaert   ORCID: orcid.org/0000-0002-2987-4938 1 ,
• Ranhua Xiong   ORCID: orcid.org/0000-0001-9917-8949 7 ,
• Juan C. Fraire   ORCID: orcid.org/0000-0002-4887-2161 1 ,
• Marie-José Tassignon 8 ,
• Katrien Remaut   ORCID: orcid.org/0000-0002-2244-1339 1 ,
• Yannis M. Paulus   ORCID: orcid.org/0000-0002-0615-628X 2 , 9 ,
• Kevin Braeckmans   ORCID: orcid.org/0000-0002-7993-6295 1 &
• Stefaan C. De Smedt   ORCID: orcid.org/0000-0002-8653-2598 1 , 7  

Nature Nanotechnology volume  17 ,  pages 552–559 ( 2022 ) Cite this article

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• Nanobiotechnology
• Nanoscience and technology

In myopia, diabetes and ageing, fibrous vitreous liquefaction and degeneration is associated with the formation of opacities inside the vitreous body that cast shadows on the retina, appearing as ‘floaters’ to the patient. Vitreous opacities degrade contrast sensitivity function and can cause notable impairment in vision-related quality of life. Here we introduce ‘nanobubble ablation’ for safe destruction of vitreous opacities. Following intravitreal injection, hyaluronic acid-coated gold nanoparticles and indocyanine green, which is widely used as a dye in vitreoretinal surgery, spontaneously accumulate on collagenous vitreous opacities in the eyes of rabbits. Applying nanosecond laser pulses generates vapour nanobubbles that mechanically destroy the opacities in rabbit eyes and in patient specimens. Nanobubble ablation might offer a safe and efficient treatment to millions of patients suffering from debilitating vitreous opacities and paves the way for a highly safe use of pulsed lasers in the posterior segment of the eye.

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Acknowledgements

This research was supported by the Research Foundation Flanders (FWO, 12X3222N, F.S.).

Author information

These authors contributed equally: Félix Sauvage, Van Phuc Nguyen.

Authors and Affiliations

Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

Félix Sauvage, Aranit Harizaj, Viktor Van Havere, Karen Peynshaert, Juan C. Fraire, Katrien Remaut, Kevin Braeckmans & Stefaan C. De Smedt

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA

Van Phuc Nguyen, Yanxiu Li & Yannis M. Paulus

NTT-Hitech Institutes, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam

• Van Phuc Nguyen

VMR Institute for Vitreous Macula Retina, Huntington Beach, CA, USA

Doheny Eye Institute/UCLA, Los Angeles, CA, USA

Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium

Dimitri Roels

Joint Laboratory of Advanced Biomedical Materials, International Innovation Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, China

Ranhua Xiong & Stefaan C. De Smedt

Department of Ophthalmology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium

Marie-José Tassignon

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

• Yannis M. Paulus

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Contributions

F.S., K.B. and S.C.D.S. conceived the concept of nanobubble ablation of vitreous opacities. F.S., V.V.H., R.X. and A.H. performed and analysed the in vitro/ex vivo experiments. R.X. and K.B. designed the optical set-up. J.S. contributed to the writing of the manuscript and performed vitrectomies. J.C.F. synthesized and characterized the AuNPs. V.P.N. and Y.L. performed the experiments in rabbits. F.S., V.P.N. and Y.L. performed the analysis of the experiments in rabbits (OCT, PAM, histology and ERG). F.S., S.C.D.S., V.P.N. and Y.M.P. designed the in vivo experiments. K.R., D.R., M.-J.T., K.P., K.B., J.S., Y.M.P., A.H. and S.C.D.S. advised and provided guidance on experiments and data analysis. All authors discussed the experimental results and jointly wrote the manuscript.

Corresponding authors

Correspondence to Yannis M. Paulus , Kevin Braeckmans or Stefaan C. De Smedt .

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The authors declare no competing interests.

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Supplementary video 1.

ICG (0.5 mg ml −1 ) mixed with exogenous collagen opacities (0.02 mg ml −1 ) locally generate VNBs leading to their mechanical destruction.

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ICG (0.5 mg ml −1 ) mixed with opacities obtained in patients during vitrectomy locally generate VNBs leading to their mechanical destruction.

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Source data fig. 3.

Number of pulses needed for the destruction of collagen fibres as a function of the fluence and type of photosensitizer.

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Source data of electroretinograms (b-wave amplitude and implicit time).

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Sauvage, F., Nguyen, V.P., Li, Y. et al. Laser-induced nanobubbles safely ablate vitreous opacities in vivo. Nat. Nanotechnol. 17 , 552–559 (2022). https://doi.org/10.1038/s41565-022-01086-4

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DOI : https://doi.org/10.1038/s41565-022-01086-4

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October 2023 | Features

Managing Vitreous Floaters

The latest advances in imaging and surgery can help patients with vision degrading myodesopsia..

J. Sebag, MD, FACS, FRCOphth, FARVO

AT A GLANCE

• Studies show that patients with vision degrading myodesopsia (VDM) would be willing to exchange 1 year of each remaining decade of life just to be rid of their floaters.
• Vitrectomy is a safe and effective treatment for VDM and can normalize contrast sensitivity within 1 week of surgery.
• Researchers are investigating the use of nanoparticles to enhance laser ablation of vitreous opacities.

Vitreous floaters are a common symptom, estimated in one survey to affect two out of every three individuals, with one in three reporting visual impairment. 1 When vitreous floaters measurably degrade vision, the diagnosis of vision degrading myodesopsia (VDM) can be established based on objective, quantitative criteria. 2 The psychological features of depression and perceived stress associated with VDM have been extensively documented. 3-5 Studies have further determined that patients with VDM would be willing to exchange 1 year of each remaining decade of life just to be rid of their floaters. 6 This article explains the pathophysiology of VDM and the emerging treatment approaches.

THE AGING PROCESS

Vitreous is a clear gel in youth but undergoes significant structural changes with aging and myopia. 7 The gel state and transparency of normal vitreous result from an intricate interaction between collagen and hyaluronan, which are initially homogeneously distributed throughout the vitreous body (Figure 1). 8 Vitreous opacification results from fibrous liquefaction, a progressive process that begins in youth and advances more rapidly in myopic eyes, leading to myopic vitreopathy (Figure 2, Video 1). 7,9,10 Fibrous liquefaction features dissociation of hydrophilic hyaluronan molecules from collagen, resulting in the formation of liquid vitreous and crosslinking/aggregation of vitreous collagen into structures that interfere with light passing through the center of the eye, casting perceptible shadows. When fibrous liquefaction of the vitreous body occurs in tandem with dehiscence of vitreoretinal adhesion, the result is a posterior vitreous detachment (PVD), the most common cause of vitreous floaters and VDM. 2,11,12

Figure 1. Postmortem dissection of the sclera, choroid, and retina off the vitreous body, which remained attached to the anterior segment of a 9-month-old child. Although the fresh, unfixed specimen is composed of 98% water and situated on a surgical towel in room air, its solid gel consistency is maintained by the collagen/hyaluronan matrix. Reprinted with permission from Sebag J. Vitreous—in Health & Disease. Springer; 2014.  Specimen courtesy of the New England Eye Bank.

Click to view larger

Figure 2. Postmortem darkfield slit microscopy of whole human vitreous with the sclera, choroid, and retina dissected off the vitreous body. The vitreous bodies of an 11-year-old (A) and a 14-year-old (B) feature a homogeneous structure with no significant light scattering, except at the periphery where the vitreous cortex is comprised of a dense matrix of collagen fibrils (see Figure 3). The vitreous structures of a 56-year-old (C) and a 59-year-old (D) feature macroscopic fibrils in the central vitreous body with an anteroposterior orientation. In the eyes of an 88-year-old (E, F), central vitreous fibers are thickened and tortuous. Adjacent to the large fibers are areas of liquid vitreous, at times forming pockets called lacunae. Reprinted with permission from Sebag J. Vitreous—in Health & Disease. Springer; 2014. 

Video 1. Myopic Vitreopathy. Video courtesy of Carl Glittenberg, MD, and Susanne Binder, MD

Even in the absence of the pathologic effects of anomalous PVD, the separation of the posterior vitreous cortex from the inner limiting membrane (ILM) can significantly disturb vision, due to light scattering. This is caused by the high density of collagen fibrils in the outer vitreous and/or folding of the outer vitreous, which is forced into a smaller surface area after separation from the ILM (Figure 3, Video 2). Opacities in the central vitreous and the outer shell of the vitreous body result in floaters and, in advanced cases, VDM.

Figure 3. Scanning electron microscopy of the posterior aspect of the posterior vitreous cortex demonstrates dense packing of collagen fibrils (white bar = 10 μm). Reprinted with permission from Sebag J. Vitreous—in Health & Disease. Springer; 2014 .

Video 2. Posterior Vitreous Folds After PVD. Video courtesy of Martin Snead, MD

VISUAL SIGNIFICANCE

Recent investigations have determined that floaters can have a measurable effect on vision. While visual acuity is unaffected, studies have detected profound degradation in contrast sensitivity; one study found contrast sensitivity declined by 91% compared with age-matched controls. 12 Investigations have correlated this degradation in contrast sensitivity with PVD, vitreous density by ultrasonography, and quality of life as measured by the National Eye Institute Visual Function Questionnaire. 10,13,14 With the advent of quantitative ultrasonography to objectively assess vitreous structure and by measuring contrast sensitivity to evaluate visual function, clinicians are now able to quantitatively determine VDM severity to help guide management.

TREATMENT ADVANCES

Although Nd:YAG laser vitreolysis has been widely employed to treat vitreous opacities, no definitive studies prove its efficacy. 12,15-19 Thus, the United Kingdom National Institute for Health and Care Excellence (NICE) concluded that evidence on the safety and efficacy of Nd:YAG laser vitreolysis in the treatment of vitreous floaters is inadequate in quality and quantity. NICE officially recommended that Nd:YAG laser vitreolysis should only be used in the context of research and be done by retina specialists. 20

In contrast, vitrectomy is a safe and effective treatment for VDM. 12,21-23 In one study of 139 consecutive cases, contrast sensitivity normalized within 1 week of surgery and remained normal for years thereafter. 23 Moreover, vitrectomy for VDM was found to be more cost-effective than cataract surgery, amblyopia therapy, and retinal detachment (RD) repair. 24

To mitigate complications such as cataract and RD, limited vitrectomy was developed to preserve 3 mm to 4 mm of retrolental gel vitreous and avoid surgical PVD induction. In a series of 195 cases, the incidence of retinal tears and RD was markedly reduced to 1.5% compared with traditional vitrectomy with surgical PVD induction, which has a reported incidence of 30% for retinal tears and 6.8% to 10.9% for RD. 23,25-27 Furthermore, the historically high incidence of cataract surgery following vitrectomy for floaters was reduced to 18% (mean follow-up of 20 months) in one study and 16.9% (mean follow-up of 32 months) in a larger study of limited vitrectomy for VDM. 23,28 In these studies, cataract surgery was required in patients with a mean age of 64 ± 7 years. Importantly, when cataract surgery was performed, there were no complications related to the previous limited vitrectomy, perhaps due to the preservation of intact anterior gel vitreous.

PHARMACEUTICAL INTERVENTION

Despite the demonstrated safety and efficacy of limited vitrectomy for VDM for vitreous floaters, advanced therapeutics may be able to address this issue in the future. Pharmacologic vitreolysis has been approved for treating vitreomacular traction but has not been tested in VDM. 29-31

One interesting approach is the use of nanoparticles to enhance laser ablation of vitreous opacities. Designed with gold cores coated with hyaluronic acid, these nanoparticles have an affinity for vitreous collagen. Once bound to collagenous opacities and the detached posterior cortex, they absorb laser energy at levels 1,000 times lower than that which is currently employed for Nd:YAG laser vitreolysis and produce nanobubbles that ablate vitreous opacities. In vitro experimentation followed by in vivo investigations in rabbits have demonstrated efficacy and safety. 32,33

CLINICAL IMPLICATIONS

Our past inability to properly evaluate the structural changes within the vitreous body and their effect on visual function has hampered our willingness to consider vitreous floaters as a disease. While most patients consider floaters a nuisance, some patients may have VDM. We must treat such patients with the same respect and consideration we afford to patients with other vitreoretinal diseases. In addition, we must commit ourselves to the development of novel diagnostic tools and therapeutics to address VDM and improve the quality of life for millions of patients worldwide.

Acknowledgments: Research discussed in this article was supported by the VMR Research Foundation. Alfredo A. Sadun, MD, PhD, FARVO, graciously reviewed this article.

1. Webb BF, Webb JR, Schroeder MC, North CS. Prevalence of vitreous floaters in a community sample of smartphone users. Int J Ophthalmol . 2013;6(3):402-405.

2. Sebag J. Vitreous and vision degrading myodesopsia. Progr Ret Eye Res . 2020;79:100847.

3. Spielberger CD, Gorsuch RL, Lushene R, et al. Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press; 1983.

4. Cipolletta S, Beccarello A, Galan A. A psychological perspective of eye floaters. Qual Health Res . 2012;22(11):1547-1558.

5. Kim YK, Moon SY, Yim KM, et al. Psychological distress in patients with symptomatic vitreous floaters. J Ophthalmol . 2017;191576.

6. Wagle AM, Lim WY, Yap TP, et al. Utility values associated with vitreous floaters. Am J Ophthalmol . 2011;152(1):60-65.

7. Sebag J. The Vitreous - Structure, Function, and Pathobiology. Springer-Verlag; 1989.

8. Chew L, Sebag J. Vitreous. In: Adler’s Physiology of the Eye. 12th Ed [in press]. Elsevier; 2023.

9. Nguyen N, Sebag J. Myopic vitreopathy – significance in anomalous PVD and vitreoretinal disorders. In: Myopia & Related Diseases. Midena, ed. Ophthalmol Comm Soc ; 2005:137-145.

10. Nguyen JH, Nguyen-Cuu J, Mamou J, Routledge B, Yee KMP, Sebag J. Vitreous structure and visual function in myopic vitreopathy causing vision-degrading myodesopsia. Am J Ophthalmol . 2021;224:246-253.

11. Sebag J, Yee KMP, Huang L, Wa C, Sadun AA. Vitrectomy for floaters – prospective efficacy analyses and retrospective safety profile. Retina . 2014;34(6):1062-1068.

12. Sebag J. Methodological and efficacy issues in a randomized clinical trial investigating vitreous floater treatment. JAMA Ophthalmol . 2018;136(4):448.

13. Garcia G, Khoshnevis M, Yee KM, Nguyen-Cuu J, Nguyen JH, Sebag J. Degradation of contrast sensitivity following posterior vitreous detachment. Am J Ophthalmol . 2016;172:7-12.

14. Mamou J, Wa CA, Yee KM, et al. Ultrasound-based quantification of vitreous floaters correlates with contrast sensitivity and quality of life. Invest Ophthalmol Vis Sci . 2015;56:1611-1617.

15. Nguyen JH, Nguyen-Cuu J, Yu F, et al. Assessment of vitreous structure and visual function after neodymium:yttrium-aluminum-garnet laser vitreolysis. Ophthalmology . 2019;126(11):1517-1526.

16. Ivanova T, Jalil A, Antoniou Y, et al. Vitrectomy for primary symptomatic vitreous opacities: an evidence-based review. Eye . 2016;30:645-655.

17. Milston R, Madigan M, Sebag J. Vitreous floaters - etiology, diagnostics, and management. Surv Ophthalmol . 2016;61(2):211-227.

18. Kokavec J, Wu Z, Sherwin JC, et al. Nd:YAG laser vitreolysis versus pars plana vitrectomy for vitreous floaters. Cochrane Database Syst Rev . 2017;6(6):CD011676.

19. Lim JI. YAG laser vitreolysis—is it as clear as it seems? JAMA Ophthalmol . 2017;135(9):924-925.

20. NICE. YAG laser vitreolysis for symptomatic vitreous floaters. October 26, 2022. Accessed March 20, 2023. bit.ly/3OYraWI

21. Delaney YM, Oyinloye A, Benjamin L. Nd:YAG vitreolysis and pars plana vitrectomy: surgical treatment for vitreous floaters. Eye . 2002;16(1):21-26.

22. Mason III JO, Neimkin MG, Mason IV JO, et al. Safety, efficacy, and quality of life following sutureless vitrectomy for symptomatic vitreous floaters. Retina . 2014;34(6):1055-1061.

23. Sebag J, Yee KMP, Nguyen JH, Nguyen-Cuu J. Long-term safety and efficacy of vitrectomy for vision degrading myodesopsia from vitreous floaters. Ophthalmol Retina . 2018;2(9):881-887.

24. Rostami B, Nguyen-Cuu J, Brown G, Brown M, Sadun A, Sebag J. Cost-effectiveness of limited vitrectomy for vision degrading myodesopsia. Am J Ophthalmol . 2019;204:1-6.

25. Tan HS, Mura M, Lesnik Oberstein SY, Bijl HM. Safety of vitrectomy for floaters. Am J Ophthalmol . 2011;151(6):995-998.

26. Schulz-Key S, Carlsson JO, Crafoord S. Long-term follow-up of pars plana vitrectomy for vitreous floaters: complications, outcomes, and patient satisfaction. Acta Ophthalmol . 2011;89(2):159-165.

27. de Nie KF, Crama N, Tilanus MA, et al. Pars plana vitrectomy for disturbing primary vitreous floaters: clinical outcome and patient satisfaction. Graefe’s Arch Clin Exp Ophthalmol . 2013;251(5):1373-1382.

28. Yee KM, Tan HS, Lesnick-Oberstein SY, et al. Incidence of cataract surgery after vitrectomy for vitreous opacities. Ophthalmol Retina . 2017;1:154-157.

29. Sebag J. Pharmacologic vitreolysis (Guest Editorial). Retina . 1998;18:1-3.

30. Sebag J. Pharmacologic vitreolysis – premise and promise of the first decade. Retina . 2009;29(7):871-874.

31. Sebag J. Pharmacologic vitreolysis. In: Sebag J, ed. Vitreous—in Health & Disease. Springer; 2014:799-816.

32. Sauvage F, Fraire JC, Remaut K, et al. Photoablation of human vitreous opacities by light-induced vapor nanobubbles. ACS Nano. 2019;13(7):8401-8416.

33. Sauvage F, Nguyen VP, Li Y, et al. Laser-induced nanobubbles safely ablate vitreous opacities in vivo. Nat Nanotechnol . 2022;17(5):552-559.

Senior Research Scientist, Doheny Eye Institute, Pasadena, California Professor of Clinical Ophthalmology, Department of Ophthalmology, Geffen School of Medicine, University of California Los Angeles, Los Angeles Founding Director, VMR Institute for Vitreous Macula Retina, Huntington Beach, California [email protected] Financial disclosure: Past Consultant (Alcon, Bayer, Bausch + Lomb, Genentech/Roche, ThromboGenics); Patents - Minority (Nanobubble Technology, Quantitative Ultrasonography)

October 2023

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• / March 2018
• / To Treat—or Not to Treat—Vitreous Floaters

To Treat—or Not to Treat—Vitreous Floaters

• Mark Complete

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Pick virtually any ophthalmol­ogist’s practice and you’ll find patients who complain of vitre­ous floaters. When, if ever, should these patients receive treatment? Like most of his colleagues, Chirag P. Shah, MD, MPH, with Ophthalmic Consultants of Boston, prefers observation in 99.9% of these cases. “However,” he said, “I do think that paradigm is slowly changing.”

A combination of more sophisti­cated patient selection and enhanced technology and techniques may be diminishing some concerns about the risks of surgery for vitreous floaters. And although a recent study 1 conducted by Dr. Shah also suggested that YAG vit­reolysis may offer benefits for troublesome floaters, it also raises questions about its efficacy and safety, as well as the necessity for multiple costly sessions.

Three vitreoretinal surgeons offer their perspectives on whether, and how, to treat vitreous floaters.

Troublesome Vitreous Floaters

Vitreous floaters may occur following a retinal tear, retinopexy, scleral buckling, or vitreous hemorrhage associated with a tear, said Gaurav K. Shah, MD, with The Retina Institute in St. Louis, Mis­souri. But most patients who experi­ence vitreous floaters fall into 2 groups: those with a posterior vitreous detach­ment (PVD) or myopic vitreopathy.

PVD and myopic vitreopathy. People in their 50s, 60s, or 70s may develop a PVD and have more significant floaters, said Dr. Chirag Shah. “Most of the time, patients can cope with them because the brain neuroadapts. But a certain percentage of patients continue to be bothered by the floaters.” People in their 20s and 30s may also develop opacities in their vitreous as a result of myopia, said Jerry Sebag, MD, at VMR Institute for Vitreous Macula Retina in Huntington Beach, California.

Impact of light. “Because the impact is greater in bright light, individuals with floaters—often younger people—typically complain about the inability to work long hours on computers,” said Dr. Sebag. In addition, snow reflections, bright skies, and looking at the ocean may be bothersome. “I’ve had patients tell me they’ve stopped camping, fish­ing, or skiing because they no longer find these activities pleasurable. Some even tell me they can’t wait to go to sleep at night.”

Why worse for some? Why some people are more afflicted than others is not fully understood, said Dr. Sebag. It may be connected to more than 1 factor, he said, such as biochemistry and the effects of aging, genetics, hormones, and the ability to neuroadapt. “For example, some have a denser posterior vitreous cortex, and these people won’t be able to adapt well to their floaters.”

What is clear, he said, is that many of these patients feel ignored by the med­ical profession. “What they are com­plaining about may not fit neatly into our diagnostic boxes, but that doesn’t mean they don’t have a problem.”        

Evaluating Vitreous Floaters

Fewer than 5% of Dr. Chirag Shah’s patients complain of floaters. Given that not all floaters are created equally, he said, it’s important to demonstrate a correlation between what the patient is experiencing and what the physician is seeing. “Deciding who to treat ends up being the key to success.”

Basic exams. Why do physicians underestimate serious symptoms of vitreous floaters? “One reason is that we usually check patients’ visual acuity and visual fields,” said Dr. Chirag Shah, “but we don’t check contrast sensitivity, which can be degraded by significant floaters.” Also, floaters may move into the patient’s central vision, affecting their ability to read or drive, but doc­tors rarely check reading speed.

Dr. Sebag was the first to discover that patients with significant vitreous floaters are bothered with decreased contrast sensitivity function. 2-4  He coined the diagnostic term “vision-degrading vitreopathy” to help distin­guish debilitating floaters from those that are relatively benign. “Screening with vitreous-specific questionnaires, structural assessments with ultrasound, and contrast sensitivity functional (CSF) assessments give me the ability to diagnose vision-degrading vitreopathy and make me more comfortable about offering treatment,” he said.

Floaters questionnaire. Dr. Sebag and colleagues devised a screening tool called the Vitreous Floaters Functional Questionnaire (VFFQ) to help evalu­ate the impact of floaters on patients’ quality of life. “We’ve shown a statisti­cally significant correlation between the VFFQ and the National Eye Institute’s (NEI’s) Visual Function Questionnaire, a gold standard for assessing vision in more general terms,” he said. In addition, there is a high correlation among the results of the VFFQ and CSF and the density of the vitreous body as assessed by ultrasound.

Contrast sensitivity function. A CSF assessment provides a functional evaluation of the impact of vitreous (as well as cornea or lens) opacification on vision, by measuring the ability to distinguish shades of gray, said Dr. Sebag. One of his studies found that patients with bothersome floaters had a 67% reduction in CSF compared with age-matched controls. 2

“These days, I never operate on someone with normal CSF,” said Dr. Sebag. More than 140 patients with abnormal CSF on whom he has per­formed vitrectomy attained normal CSF within 1 week of surgery. 2-4 Dr. Sebag has followed these patients for an average of nearly 3 years; during this time, their CSF has remained normal.

Quantitative ultrasound (QUS). Dr. Sebag also advocates the use of quanti­tative ultrasound, which gives an index of the structure of the vitreous body. “The quantitative ultrasound measure­ments we perform clearly show that the greater the density of the vitreous, the more patients are bothered by their floaters,” he said. He added that QUS is also a useful way to show patients what’s going on inside their eyes and to assess the effectiveness of vitrectomy.

Wide-angle color photography. In his clinical study, Dr. Chirag Shah used wide-angle color photography to visualize floaters. “Oftentimes, patients would look at their color photographs and say, ‘That’s the bug-like floater that keeps going in and out of my vision,’” he said. “If a patient had significant symptoms but the photograph was crystal clear except for a few normal vitreous wisps, that patient may not be easy to satisfy.”

OCT. To assess floaters, Dr. Gaurav Shah takes optical coherence tomogra­phy (OCT) infrared video scans. “This allows us to see what the patients are seeing,” he said. “If I do a video scan and don’t see much, the patient’s symptoms are not from the eye, and I won’t treat them with vitrectomy. If patients truly have something, it is a very dramatic demonstration of their symptoms.”

Vitrectomy for Troublesome Floaters

“Vitrectomy is valuable for some pa­tients with floaters, but I tend to reserve it only for those with the most debili­tating floaters because of the potential side-effect profile,” said Dr. Chirag Shah. Vitrectomy is invasive, agreed Dr. Gaurav Shah. “But it has evolved and been vindicated by improvements in technology and technique. My patients have been ecstatic with the results, although it’s first critical to determine that they are truly symptomatic and have been given a chance to neuroadapt or to allow the floaters to resolve.”

Exclusion criteria. Dr. Sebag uses the VFFQ, CSF, and QUS to select the best candidates for vitrectomy. “I don’t take surgery lightly,” he said, explaining that he’s performed only about 200 surgical floater cases in over 8 years. “I rarely meet someone and say, ‘Let’s operate.’” In fact, he said the average time be­tween the first onset of symptoms and surgery is more than 30 months.

Dr. Gaurav Shah uses slightly differ­ent criteria for excluding patients.“I exclude patients who are phakic, who have 360 degrees of lattice or a lot of peripheral retinal problems, or who have expectations that are way beyond what the surgery can provide.” To help assess expectations, he asks his patients, “If you are driving on a road and the entire windshield is clear except for one little spot, does that bother you?” If the answer is “yes,” he is more concerned about the ability to please the patient with surgery.

Risks of vitrectomy. “With vitrecto­my, you are creating 3 holes in the eye,” said Dr. Chirag Shah, “which carries a small risk of infection.” Vitrectomy also accelerates cataract formation, because of increased oxygen concentration in the vitreous cavity following removal of the vitreous. “But for me, retinal detachment is the most concerning risk, with published reports as high as 10.9%,” he said.

Presenting vitrectomy findings from 151 eyes at the 2016 Academy annual meeting, Dr. Sebag reported no cases of endophthalmitis or hypotony; 1 case each of glaucoma, cystoid macular edema, and retinal break; 2 cases of retinal de­tachments that were surgically corrected; and 6 cases of vitreous hemorrhage, which all cleared spontaneously.

Reducing risks. Dr. Gaurav Shah has found that being discerning in choosing patients has resulted in fewer complications. Operating on 5 to 10 floaters patients last year, he has had no patients experience retinal tears or de­tachments. The key, he said, is 27-gauge topical vitrectomy, which minimizes complications with blocks and intraoperative issues. Dr. Sebag also credits the development of sutureless, small-gauge vitrectomy in reducing risks, as well as a couple of other techniques.

Reduce risk of endophthalmitis. To this end, Dr. Sebag creates highly beveled incisions and uses nonhollow probes for cannula extraction.

Leave a little vitreous. “I have modified my approach by leaving a few milli-meters of vitreous behind the lens. The antioxidants in the vitreous gel help mitigate cataract formation,” Dr. Sebag said. He and his colleagues compared the incidence of cataract using this modified approach with extensive vitrectomy, which is used at the Uni­versity of Amsterdam. At 24 months, the incidence of cataract was 35% with the modified approach and 87% with the extensive approach. The time until cataract formation was also 5 months longer with a limited vitrectomy. 5

Two philosophies on surgical PVD. Younger patients have vitreous floaters because of collagen cross-linking in the vitreous body, not because of PVD, said Dr. Sebag. To reduce the risk of tears in these patients, he recommends simply removing the central vitreous and not separating the posterior vitreous from the retina. By contrast, Dr. Gaurav Shah said that he always creates a complete PVD because he’s concerned that con­tracture of the residual cortical vitreous may cause problems in the future. That has not been the case in Dr. Sebag’s experience of 200 cases, where only 1% experienced retinal detachment.

YAG Laser Vitreolysis for Troublesome Floaters

Before conducting the first random­ized clinical trial of YAG vitreolysis for symptomatic Weiss ring floaters, Dr. Chirag Shah wondered whether lasers could provide a niche between perform­ing vitrectomy and doing nothing. “I was very skeptical going into the study, and I’m not currently performing this procedure,” he said, “but the study has shown me that YAG vitreolysis may have some value.”

Laser study results. In the trial, 54% of the laser group reported symptom improvement after 1 treatment. In ad­dition, no differences in adverse events were identified between the laser and sham groups. 1 “We need to do larger studies of longer duration to determine the best candidates and the number of treatments needed, as well as [the treat­ment’s] true risks and benefits,” said Dr. Chirag Shah.

Although more than half of the patients in Dr. Chirag Shah’s study reported significant or complete res­olution of their vitreous floaters, only about one-third of patients in an earlier study by Delaney et al. reported similar results. 6 “We used a higher laser power in our study, which may account for the differences in response,” said Dr. Chirag Shah. “At a lower power, you’re doing more fractionating, but when you turn the power up, you form plasma and can see the tissue vaporize into gas bubbles.”

Dr. Sebag, however, disputes this assertion, saying that YAG laser does not vaporize tissue. “YAG lasers are photodisruptors,” he said. “They take something large and break it into smaller pieces.”

Anomalous? In Dr. Chirag Shah’s trial, 8 patients self-reported zero im­provement out of a scale of 100 despite color photography showing significant or complete objective improvement. “Some patients recognized that the floater was virtually gone, but a little speck that was mobile, possibly more than previously, annoyed them to the same degree as their large floater did,” he said.

Exclusion criteria. In Dr. Chirag Shah’s study, the following patients were excluded: those with Snellen best-corrected visual acuity worse than 20/50 in the nonstudy eye; history of retinal tear, retinal detachment, uveitis, diabetic retinopathy, macular edema, retinal vein occlusion, or aphakia in the study eye; and history of glaucoma or high intraocular pressure.

Risks and costs of laser. “To my knowledge, just a handful of doctors are doing YAG vitreolysis, and with variable results,” said Dr. Chirag Shah. With no dedicated insurance code, the procedure is done off-label, he said. In his study, Dr. Chirag Shah only did 1 treatment session because he could not treat patients with 2 sham lasers without unmasking them. “In the real world, patients may require 2 or more laser sessions to vaporize the majority of their floaters.”

With YAG vitreolysis, there is a risk of glaucoma, retinal tear, retinal detachment, cataract if you hit the lens, and retinal damage if you hit the retina, said Dr. Chirag Shah. To minimize risks of lens or retinal damage, he recommends ensuring a safe distance between the focal point of the laser and the retina and crystalline lens. In the study, he required the Weiss ring floater to be 5 mm posterior to the posterior capsule of the crystalline lens and 3 mm anterior of the retina, as measured by B-scan ultrasonography.

Dr. Gaurav Shah has not personally used laser for floaters but is concerned that it may be a time-consuming procedure, and he noted, “Although laser appeared quite safe in this recent laser study, it may have potential drawbacks.”

He added, “It’s important to remem­ber that the vast majority of patients don’t require intervention. However, there are those who are truly symptom­atic and might require a procedure—and, even more importantly, [who may benefit from] a conversation that acknowledges their pathology.”

 ___________________________

1 Shah CP, Heier JS . JAMA Ophthalmol. 2017;135(9):918-923.

2 Sebag J et al. Retina . 2014;34(6):1062-1068.

3 Garcia GA et al. Am J Ophthalmol. 2016;172:7-12.

4 Milston R et al. Surv Ophthalmol. 2016;61(2):211-227.

5 Yee KMP et al. Ophthalmol Retina. 2017;1(2):154-157.

6 Delaney YM et al. Eye (Lond). 2002;16(1):21-26.

___________________________

Dr. Sebag is a vitreo-retinal specialist at the VMRInstitute for Vitreous Macula Retina in Hun­tington Beach, Calif., and professor of clinical ophthalmology at the Doheny Eye Institute in Los Angeles. Relevant financial disclosures: Abbott Labs: C; Johnson & Johnson: C.

Dr. Chirag Shah is a retina specialist at the Ophthalmic Consultants of Boston; fellowship codirector of the combined Tufts New England Medical Center/Ophthalmic Consultants ofBoston vitreoretinal surgery fellowship; and assistant professor at Tufts University School of Medicine, all in Boston. Relevant financial disclosures: Ellex: L.

Dr. Gaurav Shah is a retina specialist and codirec­tor of the retina fellowship at The Retina Institute in St. Louis, Mo. Relevant financial disclosures: None.

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A New Pharmacological Vitreolysis through the Supplement of Mixed Fruit Enzymes for Patients with Ocular Floaters or Vitreous Hemorrhage-Induced Floaters

Affiliations.

• 1 Department of Pharmacy, Tajen University, Pingtung 907, Taiwan.
• 2 Unique Biotechnology Co., Ltd., Kaohsiung 800, Taiwan.
• 3 Graduate Institute of Health Care, Meiho University, Pingtung 912, Taiwan.
• 4 Department of Ophthalmology, National Defense Medical College, Saitama 359-8513, Japan.
• 5 Department of Ophthalmology, Fooying Unversity Hospital, Pingtung 928, Taiwan.
• PMID: 36431188
• PMCID: PMC9695351
• DOI: 10.3390/jcm11226710

Purpose: Ocular floaters caused by vitreous degeneration or blood clots may interfere with various visual functions. Our study investigated the pharmacologic effects of oral supplementation of mixed fruit enzymes (MFEs) for treating spontaneous symptomatic vitreous opacities (SVOs) and those secondary to vitreous hemorrhage (VH). Methods: 224 patients with monocular symptomatic vitreous opacities (SVOs) were recruited between September and December 2017 and received oral supplementation of MFEs (190 mg bromelain, 95 mg papain, and 95 mg ficin) for 3 months in a double-blind clinical trial. Participants were divided according to the etiology of the SVOs, spontaneous (experiment 1) versus VH (experiment 2), and then randomly assigned into four treatments groups: one group received oral vitamin C, as a placebo; and the other 3 groups received 1 capsule per day (low dose), 2 capsules per day (middle dose), or 3 capsules per day (high dose) of MFEs. The number of SVOs was determined at baseline and then 1, 2, and 3 months after initiating treatment. Further, in cases secondary to VH, the changes in corrected distance visual acuity (CDVA) were assessed after 3 months. Second, we compared the free radical scavenging capabilities of each substance: vitamin C, bromelain, papain, ficin, and MFEs (combination of bromelain, papain, and ficin) by DDPH assay. Finally, SVOs-related symptoms and satisfaction with the treatments were evaluated at the last follow-up visit Results: In experiment 1, the disappearance rate of SVOs was 55%, 62.5%, and 70% after taking 1, 2, and 3 capsules daily, respectively (total p < 0.001), in a dose-dependent manner. In experiment 2, the disappearance rate of VH-induced SVOs was 18%, 25%, and 56% (p < 0.001) after 1, 2, and 3 capsules of the supplement daily, respectively. Additionally, the patients’ vision elevated from 0.63LogMAR to 0.19LogMAR (p = 0.008). Conclusions: A pharmacological approach using a high dose of oral supplementation with MFEs (bromelain, papain, and ficin) was effective in reducing vitreous opacities, even after intraocular hemorrhage. Furthermore, pharmacologic vitreolysis with MFEs supplementation showed high patient satisfaction, and also improved CDVA in patients with vitreous hemorrhage-induced floaters

Keywords: bromelain; ficin; ocular floater; papain; pharmacologic vitreolysis; vitreous hemorrhage.

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15 Oct New study proves effectiveness of a non-surgical, dietary solution for ‘Eye floaters’

A new study published in the Translational Vision Science and Technology (TVST), an ARVO journal, has revealed that targeted nutrition can significantly reduce ‘eye floaters’ as well as their associated discomforts. This study reports the outcomes of the Floater Intervention Study (FLIES), which was led by the Nutrition Research Centre Ireland (NRCI, Waterford Institute of Technology), in collaboration with local optometrists and the Institute of Eye Surgery at UPMC Whitfield Hospital.

Floaters are spots in your vision like black or grey specks, strings, or cobwebs that drift about when you move your eyes. According to the National Eye Institute, “almost everyone develops floaters as they get older”, but floaters can also occur from a very young age and especially in short-sighted people. Most eye floaters are caused by age-related changes in the vitreous (the jelly part of the eye). Floaters are painless and mostly harmless, but they regularly cause significant visual discomfort and, at times, mental stress for the sufferers. In some cases, floaters may be associated with retinal tears, a potential sight-threatening complication that requires immediate medical attention.

The FLIES trial is the first double-blind, placebo-controlled clinical trial in patients with primary floaters that demonstrated reduction in floater suffering as well as improvements in visual function in the active group compared to placebo, following a 6-month dietary intervention with a formulation consisting of 125mg l-lysine, 40mg vitamin C, 26.3mg Vitis vinifera extract, 5mg zinc, and 100mg Citrus aurantium.

Dr. Emmanuel Ankamah, the main researcher on the FLIES trial, says “I am delighted to see the outcomes of this exciting trial published in TVST, a high impact journal in vision science. Indeed, this trial provides the evidence to support the use of targeted nutritional intervention as a management strategy for vitreous floaters. This gives us more confidence that using antioxidative and antiglycation micronutrients can improve vitreous health.”

According to Professor John Nolan, the Director of the NRCI and Principal Investigator of the FLIES trial, “This study is very interesting, as it is the first of its kind to examine the benefits of nutritional supplementation for patients suffering with vitreous floaters. Notably, a large percentage of patients (77%) on the active supplement demonstrated a reduction in vitreous floaters and associated improvements in vision-related quality of life was seen in 67% of patients. So, while not all participants on the active arm of the trial experienced improvements, this work provides clear evidence that this nutritional intervention is effective for certain patients. We look forward to continuing our studies on this important area of research. While we are hopeful that this research will inform eye-care, and offer an option to eye-care professionals and patients to enhance the health of the vitreous, we strongly advise that patients seek advice from a qualified eye-care professional.”

The FLIES trial was sponsored by Waterford Institute of Technology and ebiga-VISION GmbH through a WIT Co-Fund PhD scholarship (WD_2007_43). To read the newly published study, which is open access and freely available for download, see the manuscript link at Publication https://tvst.arvoj ournals.org/article.aspx?artic leid=2777982

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• Félix Sauvage Department of Pharmaceutics, Universiteit Gent, Gent, Belgium
• Van Phuc Nguyen Kellog Eye Center, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
• J Sebag VMR Institute, Huntington Beach, California, United States
• Juan Fraire Department of Pharmaceutics, Universiteit Gent, Gent, Belgium
• Katrien Remaut Department of Pharmaceutics, Universiteit Gent, Gent, Belgium
• Kevin Braeckmans Department of Pharmaceutics, Universiteit Gent, Gent, Belgium
• Yannis Mantas Paulus Kellog Eye Center, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
• Stefaan De Smedt Department of Pharmaceutics, Universiteit Gent, Gent, Belgium
• Footnotes Commercial Relationships   Félix Sauvage , None; Van Phuc Nguyen , None; J Sebag , None; Juan Fraire , None; Katrien Remaut , None; Kevin Braeckmans , None; Yannis Paulus , None; Stefaan De Smedt , None
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Félix Sauvage , Van Phuc Nguyen , J Sebag , Juan Fraire , Katrien Remaut , Kevin Braeckmans , Yannis Mantas Paulus , Stefaan De Smedt; Gold nanoparticles for the treatment of eye floaters by light-induced vapor nanobubbles. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3307.

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Purpose : Vitreous opacities are collagen aggregates that form in the vitreous body due to myopia and/or age-related structural changes (i.e. fibrous liquefaction) which cast shadows on the retina, impacting vision. Current therapies are based on laser treatment with an yttrium garnet laser (YAG) or vitrectomy The efficacy of YAG laser vitreolysis is unproven and vitrectomy remains invasive with associated side effects). We propose a nanotechnology-based treatment of floaters using the plasmon properties of gold nanoparticles (AuNPs). AuNPs bind to vitreous opacities, and when exposed to pulsed-laser light (typically a nanosecond laser), heat up and generate vapour nanobubbles (VNBs) due to the evaporation of the surrounding water. These VNBs then burst, providing sufficient mechanical energy to fragment and destroy the opacities.

Methods : In Vitro : Type I collagen fibers were prepared as artificial floaters and human vitreous opacities were obtained from patients after vitrectomy. Samples were mixed with Hyaluronic (HA) coated AuNPs (10 nm) and irradiated with a pulsed laser (<7ns; 561 nm) at different fluences. Dark field imaging was performed to assess effects. In Vivo : Type I collagen fibers were injected intravitreally in rabbits so that they were located close to the retina (<500 µm). 5 days later, HA-AuNPs were injected. Three days after the injection of AuNPs, fibers were irradiated with a nanosecond laser (<7ns; 530 nm). Photoacoustic imaging was performed to assess binding of gold on the injected fibers, and optical coherence tomography was performed to assess destruction of the fibers.

Results : HA-AuNPs can diffuse in the vitreous and bind to collagen fibers and vitreous opacities. Type I collagen fibers and vitreous opacities could be completely destroyed in vitro and ex vivo at a fluence of 4.5 J/cm 2 . In vivo , collagen fibers could be destroyed after 7 scans at a fluence of 1.9 J/cm 2 . Preliminary retinal toxicity assesment (TUNEL and H&E staining) did not reveal significant changes compared to untreated rabbits.

Conclusions : This approach can effectively and rapidly destroy vitreous opacities ex vivo and collagen fibers in vivo , using lower energy levels than YAG therapy and paves the way for the vitreolysis with pulsed-lasers and nanotechnologies

This is a 2021 ARVO Annual Meeting abstract.

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• Eye floaters

As you age, the vitreous — a jelly-like material inside your eyes — liquifies and contracts. When this happens, microscopic collagen fibers in the vitreous tend to clump together. These scattered pieces cast tiny shadows onto your retina. The shadows you see are called floaters.

Eye floaters are spots in your vision. They may look to you like black or gray specks, strings, or cobwebs. They may drift about when you move your eyes. Floaters appear to dart away when you try to look at them directly.

Most eye floaters are caused by age-related changes that occur as the jelly-like substance (vitreous) inside your eyes liquifies and contracts. Scattered clumps of collagen fibers form within the vitreous and can cast tiny shadows on your retina. The shadows you see are called floaters.

If you notice a sudden increase in eye floaters, contact an eye specialist immediately — especially if you also see light flashes or lose your vision. These can be symptoms of an emergency that requires prompt attention.

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Symptoms of eye floaters may include:

• Small shapes in your vision that appear as dark specks or knobby, transparent strings of floating material
• Spots that move when you move your eyes, so when you try to look at them, they move quickly out of your line of vision
• Spots that are most noticeable when you look at a plain bright background, such as a blue sky or a white wall
• Small shapes or strings that eventually settle down and drift out of the line of vision

When to see a doctor

Contact an eye specialist immediately if you notice:

• Many more eye floaters than usual
• A sudden onset of new floaters
• Flashes of light in the same eye as the floaters
• A gray curtain or blurry area that blocks part of your vision
• Darkness on a side or sides of your vision (peripheral vision loss)

These painless symptoms could be caused by a retinal tear, with or without a retinal detachment. This is a sight-threatening condition that requires immediate attention.

• Mayo Clinic Minute: What are eye floaters?

Jason Howland: Having vision problems? Do you see black or gray specks, strings or cobwebs that drift about when you move your eyes? It could be eye floaters.

Amir Khan, M.D., Consultant, Ophthalmology, Mayo Clinic: In the back of our eyes, we have a substance called "the vitreous." When we're young, it's a firm clump of jelly. As we age, this firm clump of jelly can liquefy and break up into smaller pieces. Those smaller pieces are what you may notice as floater.

Mr. Howland: Eye floaters are more common as you get older and if you're nearsighted. The biggest concern – they can cause retinal tears.

Dr. Khan: If a tear develops in the retina, fluid can get in underneath that tear and just lift the retina off like wallpaper off a wall and that's a retinal detachment.

Mr. Howland: And that can cause blindness, which is why it's especially important to have a dilated eye exam within days of noticing new floaters or changes in vision. Most eye floaters don't require treatment, but your eye doctor likely will recommend regular eye exams to ensure the condition doesn't worsen.

For the Mayo Clinic Newsnetwork, I'm Jason Howland.

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Retinal detachment

Retinal detachment describes an emergency situation in which a thin layer of tissue (the retina) at the back of the eye pulls away from the layer of blood vessels that provides it with oxygen and nutrients. Retinal detachment is often accompanied by flashes and floaters in your vision.

Eye floaters may be caused by vitreous changes related to aging or from other diseases or conditions:

Age-related eye changes. The vitreous is a jelly-like substance made primarily of water, collagen (a type of protein) and hyaluronan (a type of carbohydrate). The vitreous fills the space in your eye between the lens and retina and helps the eye maintain its round shape.

As you age, the vitreous changes. Over time, it liquifies and contracts — a process that causes it to pull away from the eyeball's inside surface.

As the vitreous changes, collagen fibers within the vitreous form clumps and strings. These scattered pieces block some of the light passing through the eye. This casts tiny shadows on your retina that are seen as floaters.

• Inflammation in the back of the eye. Uveitis is inflammation in the middle layer of tissue in the eye wall (uvea). Posterior uveitis affects the back of the eye, which includes the retina and an eye layer called the choroid. The inflammation causes floaters in the vitreous. Causes of posterior uveitis include infection, autoimmune disorders and inflammatory diseases.
• Bleeding in the eye. Bleeding into the vitreous can have many causes, including retinal tears and detachments, diabetes, high blood pressure (hypertension), blocked blood vessels, and injury. Blood cells are seen as floaters.
• Torn retina. Retinal tears can happen when a contracting vitreous tugs on the retina with enough force to tear it. Without treatment, a retinal tear may lead to retinal detachment. If fluid leaks behind the tear, it can cause the retina to separate from the back of your eye. Untreated retinal detachment can cause permanent vision loss.
• Eye surgeries and eye medications. Certain medications that are injected into the vitreous can cause air bubbles to form. These bubbles are seen as shadows until your eye absorbs them. Silicone oil bubbles added during certain surgeries on the vitreous and retina also can be seen as floaters.

Risk factors

Factors that can increase your risk of eye floaters include:

• Age over 50 years
• Nearsightedness
• Complications from cataract surgery
• Diabetes complication that causes damage to the blood vessels of the retina (diabetic retinopathy)
• Eye inflammation
• What are floaters and flashes? American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/what-are-floaters-flashes. Accessed May 26, 2022.
• Floaters. National Eye Institute. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/floaters. Accessed May 26, 2022.
• Floaters. Merck Manual Professional Version. https://www.merckmanuals.com/professional/eye-disorders/symptoms-of-ophthalmologic-disorders/floaters. Accessed May 26, 2022.
• Buttaravoli P, et al., eds. Floaters. In: Minor Emergencies. 4th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed May 26, 2022.
• Uveitis. National Eye Institute. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/uveitishttps://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/uveitishttps://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/uveitis. Accessed May 26, 2022.
• What is a vitrectomy. American Academy of Ophthalmologists. https://www.aao.org/eye-health/treatments/what-is-vitrectomy. Accessed May 26, 2022.
• Lin T, et al. The efficacy and safety of YAG laser vitreolysis for symptomatic vitreous floaters of complete PVD or non-PVD. Ophthalmology and Therapy. 2022; doi:10.1007/s40123-021-00422-6.
• Charles S. Vitreous. In: Vaughan & Asbury's General Ophthalmology. 19th ed. The McGraw-Hill Companies; 2018. http://accessmedicine.mhmedical.com. Accessed May 27, 2022.
• Chodnicki K (expert opinion). Mayo Clinic. June 6, 2022.

News from Mayo Clinic

• Mayo Clinic Minute: What are eye floaters? Jan. 16, 2023, 03:30 p.m. CDT
• Mayo Clinic Q and A: Most eye floaters caused by age-related changes Nov. 13, 2022, 12:00 p.m. CDT
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Optegra Leads the Way in Successful New Treatment for Floaters

3 June 2021

By Author: Alex J Shortt

Medically reviewed on 17-August-2023

Specialist eye hospital group, Optegra, is leading the way in developing a new method to treat floaters , an eye condition which mainly affects young adults whom to date have been told there is little or no treatment and whose distressing symptoms are frequently dismissed.

Symptoms of floaters include dots, shadows or long strands blocking everyday vision , caused by debris floating in the eye’s vitreous solution and which disturb clear sight at all times, often leading to a huge impact on confidence, attitude and outlook of the sufferer.

Niall Patton, Consultant Surgeon at the Optegra Manchester Eye Hospital , utilises micro-incision sutureless surgery, called vitrectomy (which involves removing the vitreous fluid behind the lens of the eye) for patients with floaters, with remarkable results.

He explains: “Floaters can torment people as these ‘clouds’ in their vision move as their eyes move, so sufferers will constantly have their vision affected. Whilst for many patients, floaters are an everyday part of life and do not bother them, in a significant percentage of individuals, this can lead to substantial detriment to a patient’s quality of life and can even result in depressive symptoms. Sufferers may become withdrawn, or seek psychiatric help. Some individuals can be concerned that they are imagining the symptoms, but they are real.

“The long standing view has been that little can be done for these sufferers, but by applying the very latest modern sutureless techniques to this condition, patients can often have their lives transformed with complete alleviation of their symptoms.

“We have now removed floaters on a number of patients, with excellent results. Because we largely use suture-free surgery, recovery can be very quick, often within a few days/weeks and the patients notice almost immediately that their floaters are gone. What once was a long, difficult and potentially hazardous operation is becoming as reliable and as routine as cataract surgery , usually taking less than an hour to complete. It is fantastic that we can make a dramatic impact on patients’ quality of life.”

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Caroline Broadley, 33, from the Wirral, started suffering from floaters when she was seven months pregnant. Describing a big black mark in her eye, constantly whizzing around, Caroline felt that the latter stages of pregnancy and early months with her daughter were spoilt with anxiety and depression.

She says: “This floater was not just affecting my vision, it was affecting my sanity. I felt like I was going mad as my doctor and my local hospital just told me I was hormonal, and I should go away and take some vitamin C!

“I knew it was so much more than that, but people don’t realise how serious floaters can be. I got to the point I was too anxious to leave the house, and would sit in a darkened room hour after hour – as natural daylight made my vision even worse. I just wanted to sleep to escape it.”

After six months, and having been put on anti-depressants, Caroline had the vitrectomy with Mr Patton. She says: “It was amazing. Having become almost agoraphobic for six months, my vision was suddenly crystal clear. I felt as though I got my life back – and could enjoy my daughter, enjoy the sunshine and start living again.”

Floaters are present in the vitreous behind the lens, and move with the eye to disrupt vision. The procedure takes up to one hour, and removes this fluid, taking the floaters with it. Results can be seen within a few days, and full impact within a matter of weeks.

Martin Baldwin, 56, managing director of a mobility aid company in Lancashire, suffered for three years with floaters, and became desperate to find a solution. He explains: “After previous emergency eye surgery for retinal problems, I was left with floaters and told I had to just put up with them. But it felt like a cloud over my central vision, and I would move my eyes around to shift the cloud, but it would pop straight back into the centre of my eye. It’s as though it was on a piece of elastic and would always ping back into place.

“Having always had great vision, it was incredibly frustrating to have this affecting my computer work, my driving, everything I did. I was even contemplating going to America to explore treatment options, when I discovered Niall Patton at Optegra. It was a life changing operation for me – these floaters were driving me mad, I could not escape them, and now thanks to this new procedure I can see as well as I could in my twenties!”

For information on this treatment, please contact us online to arrange a free consultation or call 0800 086 1064.

Notes to editors:

1) Optegra is committed to the world-wide development of eye sciences and championing the latest innovations in vision correction.

Optegra does this by partnering with leading UK universities in the research and development of the next generation of ophthalmic services and technologies.

Optegra operates five private eye hospitals: Surrey Eye Hospital (Guildford), Birmingham Eye Hospital (Aston), Yorkshire Eye Hospital (Apperley Bridge and Laser Eye Centre in Leeds City Centre); Solent Eye Hospital (Whiteley) and Optegra Manchester Eye Hospital, (Didsbury).

All are supported by over 60 consultant level ophthalmic surgeons who provide a wide range of ophthalmic procedures including: Clarivu (refractive lens exchange), laser vision correction, cataract removal, glaucoma, AMD and cosmetic procedures.

2) Floaters  are small pieces of debris that ‘float’ in the vitreous humour of the eye. They occur behind the lens (the transparent window through which light enters the eye), and in front of the retina (the light sensitive tissue that lines the back of the eye). Vitreous humour is a clear, jelly-like substance that fills the space in the middle of the eyeball. It is 99% water and 1% substances that help to maintain the shape of the vitreous. Floaters cast shadows on the retina, and it is these shadows which people can see.

3) Niall Patton MB ChB, MD, FRCOphth; Consultant Ophthalmologist, Cataract and Vitreoretinal Surgeon, Optegra Manchester Eye Hospital. Niall graduated in Medicine from the University of Manchester in 1996. He completed his ophthalmic surgical training at the Manchester Royal Eye Hospital and the Princess Alexandra Eye Pavilion, Edinburgh. In addition, he has undertaken four years of specialist Vitreoretinal surgical fellowship training at the Lions Eye Institute, Western Australia, Princess Alexandra Eye Pavilion, Edinburgh, Tennant Eye Institute, Glasgow and Moorfield’s Eye Hospital, London. In addition to his clinical expertise, Niall Patton has completed ophthalmic research in a variety of different ophthalmic fields and has been successful in procuring research grants from the Royal College of Surgeons, Edinburgh. His research culminated in the award of a Doctorate from the University of Manchester in 2006. He has spoken at national and international ophthalmology meetings, including the United States, Australia, and Europe. In addition to 49 peer-reviewed publications in ophthalmic journals, he has also co-authored a chapter of a textbook and has served as a reviewer for major international ophthalmology journals, including Investigative Ophthalmology & Visual Science, Ophthalmology, Archives of Ophthalmology & Journal of Applied Physiology.

Mr Shortt is a leading ophthalmic surgeon and an expert in the fields of cornea, cataract and refractive surgery.

Medically Reviewed Date: 17th August 2023

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At a glance: Floaters

Small dark spots or squiggly lines that float across your vision

Dilated eye exam

None (in most cases), surgery

What are floaters?

Floaters are small dark shapes that float across your vision. They can look like spots, threads, squiggly lines, or even little cobwebs.

Most people have floaters that come and go, and they often don’t need treatment. But sometimes floaters can be a sign of a more serious eye condition. So if you notice new floaters that appear suddenly and don’t go away, it’s important to tell your eye doctor.

What are the symptoms of floaters?

Floaters move as your eyes move — so when you try to look at them directly, they seem to move away. When your eyes stop moving, floaters keep drifting across your vision.

You may notice floaters more when you look at something bright, like white paper or a blue sky.

Am I at risk for floaters?

Almost everyone develops floaters as they get older, but some people are at higher risk. You’re at higher risk if you:

• Are very nearsighted
• Have diabetes
• Have had surgery to treat cataracts

What causes floaters?

Floaters usually happen because of normal changes in your eyes. As you age, tiny strands of your vitreous (the gel-like fluid that fills your eye) stick together and cast shadows on your retina (the light-sensitive layer of tissue at the back of the eye). Those shadows appear as floaters.

Sometimes floaters have more serious causes, including:

• Eye infections
• Eye injuries
• Uveitis (inflammation in the eye)
• Bleeding in the eye
• Vitreous detachment (when the vitreous pulls away from the retina)
• Retinal tear (when vitreous detachment tears a hole in the retina)
• Retinal detachment (when the retina gets pulled away from the back of the eye)

When to get help right away

Sometimes new floaters can be a sign of a retinal tear or retinal detachment — when the retina gets torn or pulled from its normal position at the back of the eye.

Symptoms can include:

• A lot of new floaters that appear suddenly, sometimes with flashes of light 
• A dark shadow (like a curtain) or blurry area in your side or central vision

Retinal tear or detachment can be a medical emergency . If you have these symptoms, it’s important to go to your eye doctor or the emergency room right away.

How will my eye doctor check for floaters?

Your eye doctor can check for floaters as part of a dilated eye exam. Your doctor will give you some eye drops to dilate (widen) your pupil and then check your eyes for floaters and other eye problems.

This exam is usually painless. The doctor may press on your eyelids to check for retinal tears, which may be uncomfortable for some people.

What’s the treatment for floaters?

Treatment for floaters depends on the cause. If your floaters are caused by another eye condition, you may need treatment for that condition.

If your floaters are caused by aging and they don’t bother you, then you probably won’t need any treatment.

If your floaters make it hard to see clearly and interfere with your daily life, your eye doctor might suggest a surgery called a vitrectomy to remove the floaters. Talk with your doctor about the risks and benefits of this surgery.  

Last updated: November 15, 2023