Can Ginkgo Biloba Slow Glaucoma Over the Long Run?

Summary

A retrospective clinical study published in the Journal of Glaucoma evaluated whether long-term treatment with Ginkgo biloba extract (GBE) was associated with slower visual field progression in patients with normal-tension glaucoma (NTG). The researchers reviewed 42 eyes from 42 treated NTG patients who had at least five visual field tests over more than four years both before and after starting GBE.

After GBE treatment, the estimated rates of visual field change improved significantly for mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). The study had a mean total follow-up of 12.3 years. Importantly, intraocular pressure before and after GBE treatment was not significantly different, suggesting that the observed change in visual field progression was not explained by a major additional reduction in IOP.

The authors concluded that GBE administration appeared to decelerate visual field damage in NTG, particularly in the superior central visual field. However, because the study was retrospective and had a small, selected sample, it cannot establish that GBE itself caused the slower progression.

Key Takeaways

·       The study examined the long-term effect of Ginkgo biloba extract on visual field progression in normal-tension glaucoma.

·       Forty-two eyes from 42 patients were included in the retrospective analysis.

·       Patients received 80 mg of Ginkgo biloba extract twice daily.

·       The mean follow-up period was 12.3 years, with more than four years of observation before and after GBE treatment.

·       The estimated rate of change in MD improved from 0.619 dB/year before GBE to 0.379 dB/year after GBE.

·       The estimated rate of change in PSD improved from 0.626 dB/year to 0.342 dB/year.

·       The estimated rate of change in VFI improved from 2.153%/year to 1.212%/year.

·       The difference in IOP before and after GBE treatment was not statistically significant.

·       The greatest regional improvement was observed in zone 1, corresponding to the superior central visual field.

·       No ocular or systemic adverse events related to GBE were reported in this study cohort.

·       The study suggests GBE may be a complementary therapy, but it does not show that GBE stops glaucoma progression.

Why Is This Study Important?

Normal-tension glaucoma is a form of open-angle glaucoma in which untreated and treated IOP measurements remain within the normal range. Although lowering IOP remains an important treatment strategy, some patients continue to show glaucoma progression despite pressure reduction.

The authors discuss both mechanical and vascular explanations for glaucoma damage. The vascular theory proposes that insufficient vascular supply to the optic nerve may contribute to injury. The study notes that reduced ocular blood flow and systemic factors such as low blood pressure, orthostatic or nocturnal hypotension, migraine, Raynaud phenomenon, and sleep apnea have been associated with NTG.

This background provides the rationale for investigating Ginkgo biloba extract. Previous clinical and experimental studies cited by the authors had reported effects on ocular blood flow and possible neuroprotective effects. The 2013 study asked a different and clinically important question: whether long-term GBE administration was associated with a change in the rate at which visual field damage progressed.

What Is Ginkgo Biloba Extract?

Ginkgo biloba extract is derived from the leaves of the Ginkgo biloba tree. In the study, patients received 80 mg twice daily. The authors describe several possible mechanisms for GBE, including effects on blood flow, platelet-activating factor, oxidative stress, and neuroprotection.

The paper specifically discusses the possibility that GBE may improve blood flow through effects on blood viscosity and platelet-activating factor, while also reducing oxidative stress and scavenging free radicals. These mechanisms were presented as possible explanations for the findings rather than as mechanisms proven by this study.

Study Design

Type of Study

·       Retrospective clinical study

·       Medical-record review

·       Long-term before-and-after comparison within the same patients

·       Statistical analysis using a linear mixed-effects model with unequal random-effect variances

Who Participated?

The investigators reviewed patients diagnosed with NTG at the glaucoma clinic of Samsung Medical Center between January 1, 1996 and January 1, 2011 who received 80 mg of GBE twice daily.

·       42 eyes from 42 patients

·       19 males and 23 females

·       Mean age at diagnosis: 47.1 ± 11.1 years

·       Mean baseline IOP: 16.1 ± 2.3 mm Hg

·       Mean follow-up: 12.3 years

·       At least 5 visual field tests and more than 4 years of follow-up were required before and after GBE treatment

In patients with bilateral NTG, one eye was randomly selected for inclusion. Patients with conditions that could interfere with visual field assessment or optic-disc interpretation were excluded, including significant visual acuity loss, more severe lens opacity, certain abnormal optic-disc appearances, other ocular or systemic disorders affecting the assessment, and cataract surgery during follow-up.

Background Glaucoma Treatment

Patients were treated according to the clinic's routine NTG management. The initial treatment was betaxolol twice daily. If the target of a 20% reduction in initial IOP was not achieved, treatment could be changed to once-daily latanoprost, with brimonidine added if necessary. The study therefore evaluated GBE in patients who were also receiving conventional IOP-lowering therapy.

How Did Researchers Measure Visual Field Progression?

Humphrey Visual Field Testing

Visual fields were measured using the Humphrey Visual Field Analyzer 30-2 program. Testing was performed at diagnosis and three months later, followed by testing every six or twelve months. Reliable tests required fixation loss below 20% and false-positive and false-negative rates of 15% or less.

The researchers analyzed three major measures of visual field status and progression:

·       Mean deviation (MD): a summary measure of how much the patient's visual field differs from an age-corrected normal reference.

·       Pattern standard deviation (PSD): a measure that reflects localized irregularity in the visual field.

·       Visual field index (VFI): a percentage-based measure designed to reflect the functional importance of visual field loss.

Regional Analysis

The researchers also analyzed mean total deviation (mTD) in 10 zones corresponding to the glaucoma hemifield test. This allowed them to determine whether changes in progression were concentrated in particular regions of the visual field.

Results

Visual Field Progression Slowed After GBE

The central finding was a significant improvement in the estimated rates of visual field change after GBE administration. The regression coefficients became less negative for MD and VFI and less positive for PSD, indicating slower progression.

The authors reported that the progression rates improved significantly for all three measures. However, MD and VFI still indicated ongoing deterioration after GBE, while PSD remained positive. The authors therefore interpreted GBE as slowing progression rather than stopping it.

IOP Did Not Change Significantly

Post-treatment IOP before GBE administration averaged 14.4 ± 1.6 mm Hg, compared with 14.3 ± 1.3 mm Hg after GBE administration. This difference was not statistically significant (P = 0.509).

This is important because the visual field progression results occurred without a significant additional reduction in IOP. The study therefore raises the possibility that the association with slower progression could involve mechanisms other than further pressure lowering, although the retrospective design cannot establish the mechanism.

Where Was the Greatest Regional Effect?

Among the 10 visual field zones analyzed, zone 1 showed a statistically significant improvement in the rate of change in mean total deviation. The regression coefficient changed from 0.897 ± 0.105 to 0.176 ± 0.192 dB/year after GBE administration (P = 0.0024).

The authors identified zone 1 as corresponding to the superior central visual field. They noted that NTG commonly produces defects closer to fixation and that many eyes in their cohort had superior visual field defects.

Safety

No ocular or systemic adverse events related to GBE were described in the study cohort during follow-up. The authors noted that this finding was consistent with a previous placebo-controlled, double-blind, randomized clinical trial cited in their paper.

What Do the Results Mean?

The study's findings suggest an association between GBE administration and a slower rate of visual field deterioration in patients with NTG. This is different from demonstrating an improvement in vision. In fact, the authors explicitly state that GBE did not stop visual field progression.

The findings are potentially important because the observed change occurred without a significant difference in IOP before versus after GBE. The authors hypothesized that GBE's possible effects on ocular blood flow and its reported neuroprotective properties could contribute to the result.

The study therefore supports the idea that factors beyond IOP may be relevant to NTG progression. However, the study was not designed to prove that vascular improvement or neuroprotection caused the slower progression.

Study Limitations

Retrospective Design

The study was based on existing medical records rather than a prospective randomized intervention. This means that factors associated with the decision to use GBE, changes in treatment, patient characteristics, or clinical follow-up could have influenced the results.

Small Sample Size

Only 42 eyes from 42 patients met the strict inclusion criteria. A larger study would provide greater statistical power and would make the findings easier to generalize.

Selected Patient Population

The study included patients who had at least five visual field tests and more than four years of follow-up both before and after GBE. Advanced glaucomatous damage was excluded. The authors also noted that the study was conducted at a tertiary medical center, where many patients had been referred because of continued progression despite treatment. These features may limit how broadly the results can be applied.

No Randomized Placebo-Controlled Comparison

Because there was no randomized placebo group, the study cannot determine with certainty that GBE caused the change in progression rate. The before-and-after comparison is useful for generating evidence and hypotheses, but it is less definitive than a prospective randomized controlled trial.

The Bottom Line

The 2013 Lee study found that patients with normal-tension glaucoma experienced significantly slower rates of visual field deterioration after beginning Ginkgo biloba extract, based on a retrospective analysis of long-term clinical records. The improvement was seen in MD, PSD, and VFI, with the strongest regional finding in the superior central visual field.

The findings are encouraging but should be interpreted cautiously. The study does not prove that Ginkgo biloba caused the slower progression, and it does not show that GBE stops glaucoma or replaces IOP-lowering treatment. The authors considered GBE a potentially favorable complementary treatment and called for interpretation in light of the study's retrospective design and limitations.

Study Reference

Lee J, Sohn SW, Kee C. Effect of Ginkgo biloba Extract on Visual Field Progression in Normal Tension Glaucoma. Journal of Glaucoma. 2013;22(9):780–784. doi:10.1097/IJG.0b013e3182595075.