July 2019

OUTSIDE THE OR

Research Highlight
Getting to the heart of potential statin use in the eye


by Maxine Lipner EyeWorld Senior Contributing Writer


Investigators have identified an enzyme, HMG-CoA reductase, that controls cholesterol metabolism.
Source: Kenneth Ooi, MD

 

In a recent study, investigators reviewed the literature and found that these drugs, which also have anti-inflammatory properties and vascular effects, may play a role in reducing the burden of ophthalmic conditions, such as dry eye, glaucoma, macular degeneration, diabetic retinopathy, and more.

While statins are well-known for their role in heart disease and controlling cholesterol, new research indicates they may also be helpful in ophthalmology. In a recent study,1 investigators reviewed the literature and found that these drugs, which also have anti-inflammatory properties and vascular effects, may play a role in reducing the burden of ophthalmic conditions, such as dry eye, glaucoma, macular degeneration, diabetic retinopathy, and more.
“It came to me that inflammation is the same everywhere,” said Kenneth Ooi, MD, the study’s primary author.
Knowing that inflammation is associated with dry eye and research indicates that there might be excess-free cholesterol in meibomian gland dysfunction in the lipid layer, Dr. Ooi decided to look into a potential statin connection.
“We did a pilot study2 of 10 patients with blepharitis and dry eye and got positive results with reduced corneal fluorescein staining and improved tear breakup times,” he said. “I had one patient who was able to keep her eyes open after treatment (without blinking) for 90 seconds.”
Dr. Ooi and fellow investigators in another study3 identified the enzyme that controlled cholesterol metabolism—HMG-CoA reductase—and identified its presence in meibomian glands, pilosebaceous glands of hair follicles, and vascular endothelium, Dr. Ooi reported.
“It had a positive control in terms of its presence in sebaceous glands of the skin,” he said.
They also reviewed the effect of oral statins on dry eye. In a large epidemiological study4 involving 1,680 participants, investigators examined whether taking oral statins at conventional dosing could reduce dry eye symptoms. No reduction was found to any one dry eye symptom, Dr. Ooi noted. But literature indicates that high systemic cholesterol is associated with meibomian gland dysfunction and dry eye.
“There are independent epidemiologic studies that have shown that in moderate to severe meibomian gland dysfunction in young to middle-aged patients, if there is no documented history of hypercholesterolemia, you’ll find more often than not there’s an association between these patients and hypercholesterolemia,” Dr. Ooi said. “These patients are more likely to have high cholesterol than the general population.”
There are also large epidemiological studies indicating that rosacea is associated with hypercholesterolemia, he said, adding that this could be impactful when treating young dry eye patients with high cholesterol. Practitioners could check for cholesterol levels and where appropriate, put these young patients on oral statins.
Another study5 investigators considered was one that showed an association between high cholesterol and increased risk of AMD. “We know that there’s an increased cholesterol content in drusen,” Dr. Ooi said. Those with higher HDL cholesterol had greater odds of having larger drusen. The idea is that if you can knock this down somewhat using a statin, the body is more able to cope in terms of resorption and the amount of drusen can be reduced, he noted.
Use of topical statins may also be helpful in corneal wound healing, as well as with scarring or closing over of trabeculectomy blebs.
“The effect on the ocular surface could be quite far-reaching,” he said, adding that there are also implications for a range of dry eye manifestations. For example, some of the inflammatory cytokine profiles are consistent with allergic conjunctivitis or allergic dry eye. There are also applications for post-refractive laser surgery dry eye.
Overall, statins show promise in a variety of areas due to their many modes of activity. They are anti-inflammatory, can lower VEGF, and can reduce inflammatory cytokines, Dr. Ooi said. Statins are also matrix metalloproteinase inhibitory as well as cholesterol lowering. This leaves possibilities open for statin use. “I think there are a lot both in the front of the eye and at the back of the eye with respect to topical and oral administration,” he concluded.

About the doctor

Kenneth Ooi, MD
Clinical senior lecturer
Save Sight Institute,
Sydney Eye Hospital Campus
University of Sydney
Sydney, Australia

Financial interests

Ooi: Dr. Ooi and his co-investigator Prof. Stephanie Watson have a patent on topical statins as novel tear film stabilizers.

References

1. Ooi KG, et al. Statins in ophthalmology. Surv Ophthalmol. 2019;64:401–432.
2. Ooi KG, et al. Efficacy and safety of topical atorvastatin for the treatment of dry eye associated with blepharitis: a pilot study. Ophthalmic Res. 2015;54:26–33.
3. Ooi KG, et al. HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line. Graefes Arch Clin Exp Ophthalmol. 2019;257:785–790.
4. Ooi KG, et al. Association of dyslipidaemia and oral statin use, and dry eye disease symptoms in the Blue Mountains Eye Study. Clin Exp Ophthalmol. 2019;47:187–192.
5. Colijn JM, et al. Increased high-density lipoprotein levels associated with age-related macular degeneration: evidence from the EYE-RISK and European Eye Epidemiology Consortia. Ophthalmology. 2019;126:393–406.

Contact information

Ooi: kenneth.ooi@sydney.edu.au

About the doctor

Kenneth Ooi, MD
Clinical senior lecturer
Save Sight Institute,
Sydney Eye Hospital Campus
University of Sydney
Sydney, Australia

Financial interests

Ooi: Dr. Ooi and his co-investigator Prof. Stephanie Watson have a patent on topical statins as novel tear film stabilizers.

References
1. Ooi KG, et al. Statins in ophthalmology. Surv Ophthalmol. 2019;64:401–432.
2. Ooi KG, et al. Efficacy and safety of topical atorvastatin for the treatment of dry eye associated with blepharitis: a pilot study. Ophthalmic Res. 2015;54:26–33.
3. Ooi KG, et al. HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line. Graefes Arch Clin Exp Ophthalmol. 2019;257:785–790.
4. Ooi KG, et al. Association of dyslipidaemia and oral statin use, and dry eye disease symptoms in the Blue Mountains Eye Study. Clin Exp Ophthalmol. 2019;47:187–192.
5. Colijn JM, et al. Increased high-density lipoprotein levels associated with age-related macular degeneration: evidence from the EYE-RISK and European Eye Epidemiology Consortia. Ophthalmology. 2019;126:393–406.

Getting to the heart of potential statin use in the eye Getting to the heart of potential statin use in the eye
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