January-February 2020

CORNEA

Research Highlight
Biofilm formation compared among three punctal occluders for dry eye


by Vanessa Caceres Contributing Writer






This image series shows a punctal occluder that is beginning to extrude and a closeup of another extruding plug. Lissamine green staining shows the irritation on the upper punctum from the plug in the lower punctum.
Source: Henry Perry, MD

 

Punctal occluders are commonly used to treat dry eye disease, but biofilm formation can be a problem with such occluders, leading to infection, inflammation, and intolerance.
This led Michael Hadjiargyrou, PhD, and coresearchers to evaluate biofilm formation on three different types of punctal occluders. The in vitro study found that biofilm was more common on a punctal occluder with the smoothest but grooved surface compared with two others that had rougher surfaces.1
“Punctal occluders are particularly effective in patients with aqueous insufficiency and [dry eye disease], because they prevent outflow of tears through the punctum and preserve the natural tear lake,” the researchers wrote.
The term biofilm was described in 1978 by William Costerton, PhD, as “surface-attached microbial agglomerations,” or a capsular polysaccharide that enables bacteria to attach to a device, according to the study. “The scaffold of the biofilm not only insulates bacteria from anti-infectives, disinfectant systems, and even our own white cells but also facilitates further bacterial adhesion and colonization,” they wrote. Researchers focused on Staphylococcus aureus as the most common bacteria found on punctal occluders.
Comfortear (Delta Life Sciences), Parasol (Odyssey Medical), and Quintess (Alphamed), hydrophobic, silicone-based occluders that are 0.9 mm at the greatest diameter, were used in the study. “All three have a flat head, a thin neck, a thick cone-shaped base, and a central lumen,” the researchers wrote.
Each type of occluder was placed in 5 mL of nutrient broth with S. aureus cells, and the cultures were placed in a shaking 37-degree Celsius incubator. Each day for 7 days, 5 mL of the growing bacteria were removed and replaced with an equal amount of fresh nutrient broth so existing bacteria could continue to grow.
After 7 days of exposure, the occluders were removed from the culture and placed in a microcentrifuge tube. Histological staining was then performed to help quantify the bacterial biofilm formation.
Scanning electron microscopy (SEM) was used to evaluate the presence of bacteria and overall biofilm formation.
During the exposure to bacteria, four occluders of each type were used. Three of each type were used for the staining, while the fourth one was used for SEM.

The results

There was an approximately three-fold statistically significant difference detected in the quantity of S. aureus between the Odyssey and Alphamed occluders, with more found on the Odyssey, the researchers reported. There was an approximately two-fold difference between the Odyssey and Delta occluders, but it was not statistically significant.
Using SEM, the Odyssey occluder appeared to be the smoothest one, followed by the Delta, which researchers described as “flat but not as smooth.” The Alphamed occluder had a rougher surface and four reservoir indentations.
The use of higher magnification images showed the presence of individual bacteria in all three occluder types, with the Odyssey having the greatest amount and extent of colonization. Although there were bacteria on the Alphamed occluder, there was no detectable biofilm formation, just individual cells.

Surprising results

Researchers discussed a possible link between occluders and infections.
“As bacterial infection is a rare but serious complication of punctal plug insertion, these findings lend credence to the possibility of occluders being the source for recurrent conjunctival and canalicular infections due to biofilm adhesion, and in addition, may allow for a faster re-accumulation of biofilm on eyelids that have undergone a mechanical or electromechanical lid scrub. In essence, the occluders would act as a nidus for biofilm reformation with cloistered colonies of S. aureus,” they wrote.
It was not completely clear why the Odyssey occluder had more bacterial growth. There may be a connection with its shape, which is designed to open inside the puncta and fit the shape of the tear duct. “It is possible that pooling of the material within this umbrella-like cavity leads to a statistically significant difference in the quantity of bacteria when compared with the two other occluders,” according to the study.
The Odyssey’s smooth surface seemed contrary to biofilm formation. “I would have expected that the roughest one would show us the most extensive biofilm formation,” Dr. Hadjiargyrou said.
“When looking at the occluders with the highest power, there were small furrows in the smoothest occluder that mimicked the size of the bacteria,” said fellow study researcher Henry Perry, MD. “Therefore, the smoothest occluder may actually have provided a better substrate for bacteria.”
The study results were surprising to Ming Wang, MD. “The fact that simple changes between the surface design of these devices could affect bacteria growth is something that has not been previously explored, to my knowledge,” he said.

Clinical implications?

Because the study was in vitro and only evaluated one bacterial strain, Dr. Wang does not think there are clinical implications from the research yet. “It would be very interesting to see a follow-up study designed to monitor for bacterial growth in vivo, in a clinical setting,” he said.
However, Dr. Wang does think that overall, ophthalmologists may want to treat uncontrolled blepharitis before using a silicone permanent plug. “If not, the existing bacteria overgrowth and biofilm from blepharitis may colonize on the plug, leading to more long-term issues,” he said.
Temporary punctal occlusion could be another option as this type of occlusion will eventually dissolve and would not significantly gather bacteria, Dr. Wang said.
Careful patient selection for punctal occluders is also critical, Dr. Perry said. “Since occluders function best in patients who have aqueous deficiency, Schirmer 1 testing [without anesthesia] is essential,” he said.
Clinically, Dr. Perry has found little difference among the occluders in the study. They all performed well for months and sometimes for years. Dr. Perry occasionally uses occluders with patients; he more commonly uses dissolving intracanalicular plugs in addition to punctal cautery.

About the doctors

Michael Hadjiargyrou, PhD
Professor and chair
Department of Biological & Chemical Sciences
New York Institute of Technology
Old Westbury, New York

Henry Perry, MD
Ophthalmic Consultants
of Long Island
Rockville Centre, New York

Ming Wang, MD
Wang Vision 3D Cataract & LASIK Center
Nashville, Tennessee

Contact

Hadjiargyrou: mhadji@nyit.edu
Perry: hankcornea@gmail.com
Wang: susan@arlenehowardpr.com

Reference

1. Hadjiargyrou M, et al. Differential bacterial colonization and biofilm formation on punctal occluders. Materials. 2019;12.

Relevant disclosures

Hadjiargyrou: None
Perry: None
Wang: None

Biofilm formation compared among three punctal occluders for dry eye Biofilm formation compared among three punctal occluders for dry eye
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