August 2018

NEWS & OPINION

Eyeing the ocular microbiome


by Vanessa Caceres EyeWorld Contributing Writer

“The opportunity to reduce inflammation, improve healing, and potentially deliver treatments for various conditions exists, but it will require low doses to be used, and only after safety is assured.”
—Gregor Reid, PhD


Does current research provide insights to help with treatment of common eye problems?

Growing knowledge about the human microbiome has provided insights into bowel disease, autoimmune conditions, glycemic control, and a variety of other areas.
“The human microbiome has benefited from probiotic research that preceded it, as it provided a basis to go and examine the microbial contents of human sites,” said Gregor Reid, PhD, chair of human microbiology and probiotics, Lawson Health Research Institute, and professor of microbiology & immunology and surgery, University of Western Ontario, London, Canada. Dr. Reid has studied probiotics for 35 years.
“The Human Microbiome Project told us exactly what we expected, that humans harbor many microbes and the composition differs in all of us, while many functions are shared,” Dr. Reid explained.
Yet are there any implications within microbiome research for eye health?
Although the number of studies is still small, some researchers are discovering more about the ocular microbiome and its effects on dry eye disease, uveitis, infection, and other ocular conditions.
Last month, EyeWorld described how human microbiome research has slowly moved its way into ocular research. This month, EyeWorld shares more examples of studies that focus on the eye’s microbiome and specific implications, both present and future, for ophthalmology. Here is a sampling of the research underway to investigate the ocular microbiome and its effects on specific eye diseases and conditions.

Dry eye and MGD

A pilot study that evaluated the effects of probiotic supplementation on the tear film found that the strains were effective in reducing dry eye syndrome, according to Chisari et al.1 They used a mix of Saccharomyces boulardii MUCL 53837 and Enterococcus faecium LMG S-28935 and after a run-in period, randomized patients into a control group (n=30) receiving a substitute tear and a treatment group (n=30) receiving the substitute tear and the probiotic. Schirmer test I and II test results improved in the treatment group, and there was a reduction in bacterial growth strains.
In a prospective, cross-sectional study by Watters et al. that focused on meibomian gland dysfunction (MGD), 157 participants were classified as normal or as having mild or moderate to severe MGD.2 Lid margin swabs both before and after gland expression were isolated and identified. Both participants with and without MGD showed a similar microbiome; there also was a higher incidence of Staphylococcus aureus than anticipated across all severity groups. “Similarity in microbiome profile, irrespective of meibomian gland dysfunction severity, anterior blepharitis presence, or contact lens wear suggests potential for commonality in treatment,” the researchers wrote.

Rhinoconjunctivitis

A group of individuals using probiotics had an improvement in rhinoconjunctivitis-specific quality of life during allergy season.3 Specifically, researchers tested Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 as a probiotic capsule compared with placebo to measure the effects on the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ). There were 173 participants in the study. There was an improvement in the MRQLQ global score from baseline to pollen peak in the probiotic group (–0.68) compared with the placebo group (–0.19; P=0.0092). The associated mechanism for how the probiotics helped patients was unclear to researchers.

Glaucoma

The findings of a study from Astafurov et al. suggested that the oral microbiome may contribute to glaucoma pathophysiology.4 The researchers used mouthwash specimens from glaucoma and control subjects and analyzed them for the amount of bacteria. Also in the study, low-dose subcutaneous lipopolysaccharide (LPS) was given in two separate animal models of glaucoma to determine a possible pathogenic mechanism. Researchers also assessed glaucomatous neurodegeneration in the retina and optic nerve 2 months later and analyzed changes in gene expression of toll-like receptor (TLR) 4 signaling pathway and complement along with microglial numbers and morphology in the retina and optic nerve. They found that patients with glaucoma had higher bacterial oral counts compared with controls (P<0.017) and that low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. “Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage,” the researchers wrote. The finding that commensal bacteria may have a role in glaucoma pathology could be relevant to other chronic neurodegenerative disorders, the researchers concluded.

Uveitis and ocular inflammatory disease

A review article concluded that intestinal microbiota are potentially crucial in propagating inflammatory diseases of the eye and can be targeted for therapeutic benefit.5 The author shares how several researchers have shown the importance of the intestinal microbiome in the pathogenesis of uveitis and that in some studies, alteration of the microbiota with oral antibiotics led to decreased uveitis severity. Yet other researchers showed that a commensal bacterial antigen activates retina-specific autoreactive T cells, which may indicate a commensal uveitis trigger. “Strategies that might be effective for targeting the intestinal microbiota might involve several approaches, including the use of antibiotics, drugs that supplement beneficial bacterial components or target inflammatory bacterial strains, dietary strategies, or microbial transplantation,” Lin concluded.

Contact lens wear and ocular microbiota

To help determine if contact lens wear is associated with ocular microbiota changes, Shin et al. compared the bacterial communities of the conjunctiva and skin under the eye from 58 subjects.6 Dry conjunctival swabs from contact lens wearers had more variable and skin-like bacterial community structures, with a higher presence of Methylobacterium, Lactobacillus, Acinetobacter, and other bacteria. Although the results show that contact lens wear alters the microbial structure of the ocular conjunctiva, more research is needed to find out if the microbiome structure provides less protection from infection, the researchers concluded.

Bringing it together

It is too early to recommend specific treatments with the attempt to change the makeup of the ocular microbiome, said Ming Wang, MD, PhD, Wang Vision 3D Cataract & LASIK Center, Nashville, Tennessee. “This appears to be because as a field, we still do not understand the significance of the bacteria that reside on the eye and how we can alter this to promote good health,” he said.
“Unfortunately, research on the ocular microbiota still lags behind other body sites such as the gut, skin, and oral cavity, and large-scale double-blinded studies are ultimately needed to make solid recommendations on this subject,” said Rupa Shah, MD, ReVision LASIK & Cataract Surgery, Columbus, Ohio.
That said, improved eyelid hygiene and cleaning along the eyelids can help to reduce bacterial proliferation in that area, and that could lead to a restoration of normal healthy bacteria on the cornea and conjunctiva, Dr. Wang said.
Ophthalmologists can continue to advise patients to avoid extended contact lens wear and maintain good contact lens hygiene, Dr. Shah said. “Furthermore, one should avoid harsh chemicals in the periocular region that could alter our natural microbiome and could contribute to pathologic states,” she said.
It is too early to say if probiotics—either geared toward the eye or taken orally—can improve ocular health, and Dr. Reid was not aware of any research until now that has led to inserting probiotic strains in the eye.
“The opportunity to reduce inflammation, improve healing, and potentially deliver treatments for various conditions exists, but it will require low doses to be used, and only after safety is assured,” Dr. Reid said. “Probiotic strains don’t tend to colonize, so the intent would be to manipulate the function and output of the existing microbiota or the metabolic activity that is causing disease.”
However, a continued focus on the ocular surface microbiome will enhance understanding of the role of homeostasis microorganisms in ophthalmic disease and may inspire the development of new probiotic- based therapies to prevent and treat ocular disease, noted Lu and Liu in their report.7

References

1. Chisari G, et al. Aging eye microbiota in dry eye syndrome in patients treated with Enterococcus faecium and Saccharomyces boulardii. Curr Clin Pharmacol. 2017;12:99–105.
2. Watters GA, et al. Ocular surface microbiome in meibomian gland dysfunction. Clin Exp Ophthalmol. 2017;45:105–111.
3. Dennis-Wall JC, et al. Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial. Am J Clin Nutr. 2017;105:758–767.
4. Astafurov K, et al. Oral microbiome link to neurodegeneration in glaucoma. PLoS One. 2014;9:e104416.
5. Lin P. The role of the intestinal microbiome in ocular inflammatory disease. Curr Opin Ophthalmol. 2018;29:261–266.
6. Shin H, et al. Changes in the eye microbiota associated with contact lens wearing. MBio. 2016;7:e00198.
7. Lu LJ, Liu J. Human microbiota and ophthalmic disease. Yale J Biol Med. 2016;89:325–330.

Editors’ note: The physicians have no financial interests related to their comments.

Contact information

Park
: lisa.park@columbia.edu
Reid: gregor@uwo.ca
Shah: rupas@revisioneyes.com
Wang: drwang@wangvisioninstitute.com

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