May 2018

NEWS & OPINION

Presentation spotlight
New drug regimen uses Ginkgo biloba extract to alleviate dry eye


by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer

A novel oral drug combination marshals the effects of increased antioxidant activity and reduced excitotoxicity to effectively reduce dry eye

Physicians are still trying to solve the painful and frustrating problem of dry eye, despite approaching this disease from various angles. Current research targets the disease pathophysiology and is exploring novel therapies such as secretagogues, topical androgens, and new anti-inflammatory drugs. Dry eye is a common occurrence, linked to hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal glands.
This multifactorial disease of the tears and the ocular surface results in discomfort, visual disturbance, and tear film instability that threatens to damage the ocular surface. It can affect any aspect of the functional unit that is comprised of the ocular surface, meibomian glands, the main lacrimal gland, and the innervation between them, and has many features in common with autoimmune disease. Dry eye is triggered by stress to the ocular surface, such as environmental factors, infection, endogenous stress, antigens, and genetic factors, and perpetuated through the body’s inflammatory response, causing a vicious cycle of damage to the ocular surface and inflammation.1

Novel approach to dry eye

According to a study that was presented as an e-poster at the XXXV Congress of the ESCRS, oral Ginkgo biloba extract effectively achieved symptomatic relief of dry eye in the study group, suggesting a feasible, highly successful new approach to the problem. “We think that oral Ginkgo biloba extract combined with cyclosporine eye drops is the new approach to relieve dry eye symptoms through stabilizing the activated nervous system,” according to the study’s first author Ji-Hyun Kim, MD, Seoul St. Mary’s Hospital, Seoul, Korea.
The investigation based its premise on Ginkgo biloba’s antioxidant activity and inhibition of excitotoxicity of the ocular surface, combined with immunosuppressant cyclosporine eye drops, to achieve the desired effect. Ginkgo biloba is known to have an effect on blood flow and a soothing effect on overwrought nerve receptor sites. Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters, due to receptor overactivation.
The study included 32 patients who underwent cataract surgery and were followed for 3 months thereafter. Sixteen of the patients received therapy with oral Ginkgo biloba extract and topical cyclosporine 0.05%. A control group was comprised of 16 patients who received topical cyclosporine 0.05% only.
The outcome assessment involved: tear film breakup time with 2 µL of 1% fluorescein solution instilled; Schirmer II test using 0.5% proparacaine hydrochloride; keratoepitheliopathy score; and the tear clearance rate ((log2)-1).

What happened?

At baseline, the control group had a mean tear film breakup time of 10.08 ± 1.55 s compared to 7.05 ± 2.26 s obtained 1 month after the initiation of treatment, which reverted to 9.86 ± 2.53 s in the course of the second and third months after surgery. The mean baseline Schirmer’s test in the control group was 10.76 ± 2.60 mm compared to 6.70 ± 3.19 mm 1 month after surgery, and roughly 10 mm in the second and third months after treatment initiation. Controls had a baseline keratoepitheliopathy score of 0.24 ± 0.43, which changed to roughly 0.19 at 1 month, and back to 0.24 ± 0.43 at the 2-month point. The tear clearance rate of 5.97 ± 1.14 ((log2)-1) sunk to 3.51 ± 0.69 ((log2)-1) in the first month, rising back to 5.35 ± 1.42 ((log2)-1) in the second month of treatment, with similar values in the third postoperative month.
The Ginkgo biloba group had a baseline mean tear film breakup time of 4.15 ± 0.88 s, a mean Schirmer’s test score of 4.20 ± 0.89 mm, a keratoepitheliopathy score of 2.35 ± 1.31, and a mean tear clearance rate of 3.45 ± 0.69 ((log2)-1). One month after surgery and the oral Ginkgo biloba/cyclosporine regimen, the mean tear film breakup was 4.25 ± 0.79 s, remaining steady at about 4.15 ± 0.75 s during the second and third postoperative months. The Schirmer’s test was 4.05 ± 0.83 mm after 1 month, 4.10 ± 0.85 mm after 2 months, and 4.15 ± 0.88 mm after 3 months of treatment. Keratoepitheliopathy scores were 3.2 ± 1.82 at 1 month after treatment, which decreased to 1.80 ± 1.28 by 3 months after treatment. The tear clearance rate 1 month after treatment was 3.25 ± 0.79 ((log2)-1), 3.30 ± 0.66 ((log2)-1) at 2 months, and 3.40 ± 0.68 ((log2)-1) after 3 months of treatment.
Dr. Kim explained that although there was no significant difference between the two groups in the objective evaluation index, symptomatic improvement was greater in the Ginkgo biloba group clinically. While a longer follow-up was suggested, he was confident that oral Ginkgo biloba extract combined with cyclosporine eye drops represents a feasible new treatment option to relieve the dry eye symptoms. “Dry eye symptoms arise after an environmental insult, inflammation, and hyperosmolarity activated nociceptors (nociceptive pain),” Dr. Kim said. “Chronic changes can occur in the peripheral and central nervous system and lead to chronic dry eye symptoms. Also, after cataract surgery, the corneal incision causes damage to the normal corneal sensory nerve, resulting in corneal sensation and secondary decrease in tear secretion.”

Ginkgo biloba for eyes

Ginkgo biloba contains multiple compounds such as flavonoids and terpenoids that are thought to contribute to its neuroprotective and vasotropic properties. It has been used as a common treatment in traditional Chinese medicine thanks to its antioxidant effects, mostly to achieve clearer thinking and improved memory. However, Ginkgo biloba has gained some attention in ophthalmology as well. One study demonstrated that Ginkgo biloba significantly increased end diastolic velocity in the ophthalmic artery in glaucoma patients compared to placebo and was deemed deserving of further investigation for neuroprotection for possible application in the treatment of glaucomatous optic neuropathy and other ischemic ocular diseases.2
Another report that supported the use of Ginkgo biloba in glaucoma claimed the substance had several biological actions that combine to make it a potentially important agent in glaucoma treatment, such as improved central and peripheral blood flow, reduction of vasospasm, reduction of serum viscosity, antioxidant activity, platelet activating factor inhibition, inhibition of apoptosis, and inhibition of exitotoxicity.3

References

1. Messmer EM. The pathology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int. 2015;112:71–81.
2. Chung HS, et al. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther. 1999;15:233–40.
3. Ritch R. Potential role for Ginkgo biloba extract in the treatment of glaucoma. Med Hypotheses. 2000;54:221–35.

Editors’ note: Dr. Kim has no financial interests related to his comments.

Contact information

Man-Soo Kim: mskim@catholic.ac.kr

New drug regimen uses Ginkgo biloba extract to alleviate dry eye New drug regimen uses Ginkgo biloba extract to alleviate dry eye
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