Ginkgo Biloba and Ocular Perfusion in Glaucoma

Ginkgo biloba extract (GBE) is a botanical supplement long studied for its circulatory and neuroprotective effects. In glaucoma – especially normal-tension glaucoma (NTG) where intraocular pressure is not elevated – vascular dysregulation and poor optic nerve perfusion are thought to contribute to retinal ganglion cell loss. GBE’s flavonoids and terpenoids (e.g. ginkgolides) may improve microcirculation, inhibit platelet-activating factor (PAF) and support neuronal health (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This article reviews GBE’s mechanisms of action, evidence for visual field and blood flow effects in glaucoma, relevant data from cognitive and cerebrovascular aging studies, and addresses safety (bleeding risk, drug interactions). We also outline optimal trial designs to test GBE in glaucoma patients.

Mechanisms of Action

Microcirculation and Vasodilation

Ginkgo’s polyphenolic flavonoids and terpenoids enhance small-vessel circulation. In vitro and clinical studies show that GBE improves blood rheology: it increases erythrocyte deformability, lowers fibrinogen, and reduces blood viscosity and elastic resistance (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). GBE also promotes endothelium-dependent vasodilation. For example, GBE increases nitric oxide (NO) and prostacyclin release, and can lower systemic vascular resistance (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In healthy elderly adults, intravenous GBE raised coronary artery blood flow and brachial artery flow‐mediated dilation (pmc.ncbi.nlm.nih.gov). Improved vasodilation and blood fluidity in small vessels could enhance ocular perfusion pressure and retinal capillary flow, which are often reduced in NTG (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Platelet-Activating Factor (PAF) Antagonism

Ginkgolides (B, A, C, J) in GBE are potent PAF receptor antagonists. In vitro, ginkgolides block PAF-induced platelet aggregation (a step in microthrombosis) (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This anti-thrombotic action can theoretically reduce microvascular ischemia in the optic nerve. However, clinically relevant effects are unclear: one lab study found 50% inhibition of human platelet PAF aggregation by ginkgolide B required ~2.5 μg/mL (much higher than blood levels achieved with standard doses) (pubmed.ncbi.nlm.nih.gov). Because PAF per se is a weak platelet activator, it remains uncertain if GBE meaningfully prolongs bleeding time or causes hemorrhage (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In short, ginkgo’s PAF antagonism may improve microcirculation, but does not appear to dramatically disrupt normal hemostasis at usual doses (pubmed.ncbi.nlm.nih.gov).

Neuroprotection and Antioxidant Effects

GBE contains flavonoid glycosides (quercetin, kaempferol etc.) with strong antioxidant activity. These can scavenge free radicals, stabilize mitochondria and inhibit oxidative apoptosis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Experimental studies show EGb761 (standard extract) protects mitochondrial membrane potential under stress and boosts ATP generation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). GBE also reduces low-grade inflammation: it suppresses inducible nitric oxide synthase and pro-inflammatory cytokines in neural tissues (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Such neuroprotective actions could plausibly slow retinal ganglion cell (RGC) death in glaucoma. Indeed, animal models suggest GBE counters glutamate excitotoxicity and oxidative injury to neurons (pmc.ncbi.nlm.nih.gov).

Clinical Evidence in Glaucoma

Visual Field Outcomes

Several small studies have tested GBE in NTG patients to see if visual fields stabilize. A prospective double-blind crossover trial of 27 NTG patients (40 mg GBE three times daily for 4 weeks) found significant short-term improvements in visual field indices: mean deviation (MD) and pattern SD both improved after GBE vs baseline (pubmed.ncbi.nlm.nih.gov). No IOP or systemic changes were seen. This suggests acute GBE may transiently enhance visual function in some cases. In a long-term retrospective study of 42 NTG eyes on GBE (80 mg twice daily), the rate of MD loss slowed from -0.62 to -0.38 dB/year over ~8–12 yrs of follow-up (post- vs pre-GBE), a significant improvement (pubmed.ncbi.nlm.nih.gov). Visual Field Index (VFI) loss also halved. These data imply GBE slowed glaucoma progression, especially in superior fields (pubmed.ncbi.nlm.nih.gov).

By contrast, larger reviews find no clear benefit on field metrics. A 2025 systematic review of 8 trials (428 subjects) concluded that GBE did not significantly change IOP, MD, or CPSD compared to controls (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Some included trials reported no VF improvement (pmc.ncbi.nlm.nih.gov). In meta-analysis, topical IOP was unaffected and field parameters were statistically unchanged (pmc.ncbi.nlm.nih.gov). Thus, while individual studies hint at utility, overall evidence is inconclusive. It is notable that trials often have short follow-up (median ~4 months) and mixed populations, which limits power to detect field changes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Ocular Blood Flow

GBE’s rheological and vasodilatory effects have been documented in glaucoma patients. A randomized placebo-controlled trial in 30 NTG eyes found that 4 weeks of 80 mg GBE twice daily raised peripapillary blood flow. Mean flow, volume and velocity all trended upward in treated eyes; statistically significant increases occurred in blood flow at multiple sectors (especially superior nasal and temporal rims) and flow velocity in inferior and superior temporal rims (pmc.ncbi.nlm.nih.gov). The authors concluded that GBE “appears to have a desirable effect on ocular blood flow in NTG patients” (pmc.ncbi.nlm.nih.gov). Other studies in healthy subjects also report ocular perfusion gains: short courses of GBE boosted end-diastolic velocity in the ophthalmic artery and increased capillary density on OCT-angiography (pmc.ncbi.nlm.nih.gov). In one Korean study, 120 mg GBE daily for 4 weeks increased retinal microcirculatory flow and velocity (pmc.ncbi.nlm.nih.gov).

Systematic reviews note that GBE augments blood flow through NO-mediated vasodilation and reduced vasospasm, potentially easing ischemic stress on RGCs (pmc.ncbi.nlm.nih.gov). For instance, GBE increases NO levels (leading to histamine/bradykinin release) and suppresses renin-angiotensin vasoconstriction (pmc.ncbi.nlm.nih.gov). Multiple small trials summarized by Prinz et al. (2025) report significant increases in doppler flow and capillary perfusion after GBE (pmc.ncbi.nlm.nih.gov). In theory, better optic nerve head blood supply could protect against glaucomatous damage. However, these studies tend to be short-term, and it remains uncertain if the ocular flow improvements translate into long-term field preservation.

Null and Mixed Findings

Not all trials find biochemical changes. The 2025 meta-analysis found no significant IOP or field benefit from GBE (pmc.ncbi.nlm.nih.gov). Similarly, some retrospective reports (e.g. Park et al.) saw stable or minimal field changes with GBE supplementation. Prinz et al. (2025) remark that heterogeneity in glaucoma subtype and follow-up likely blunted apparent effects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). They note that even where ocular blood flow rose, visual field MD did not improve in many studies (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, positive case-series coexist with trials showing no significant VF change (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Ginkgo in Aging, Stroke, and Cognition

GBE has been widely studied for cognitive and cerebrovascular health. In aging and dementia trials, standardized GBE (EGb 761) often improved memory and cognition relative to placebo (pmc.ncbi.nlm.nih.gov). Long-term studies in Alzheimer’s and mild cognitive impairment found modest gains in memory tests and global functioning (pmc.ncbi.nlm.nih.gov). A 2023 pilot RCT in 201 stroke survivors (240 mg/d for 6 months) showed better cognitive recovery (MoCA score gain ~2.9 vs 1.3 points, p<0.005) with GBE than control (pmc.ncbi.nlm.nih.gov). GBE also enhanced verbal recall and processing speed in that trial. Clinically, GBE’s improvements in cerebral blood flow and executive function have been documented (pmc.ncbi.nlm.nih.gov).

Cardiovascularly, GBE appears to stabilize vascular plaques and improve metabolic markers in older patients (pmc.ncbi.nlm.nih.gov). It even modestly lowers blood pressure in hypertension (via vasodilation). Overall, GBE is thought to target age-related vascular and neurodegenerative processes. These findings lend plausibility to a longevity angle in glaucoma: enhanced cerebrovascular health may parallel optic nerve benefits. However, it’s important to stress that GBE trials in neurodegeneration have had mixed results and often use higher doses (e.g. 240–480 mg/day) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Safety and Bleeding Risk

Ginkgo is generally well-tolerated, but bleeding concerns merit caution. Theoretically, PAF antagonism and platelet effects might increase hemorrhage risk. In practice, clinical data are mixed. A large VA database study found that patients on warfarin who also took ginkgo had a significantly higher bleeding risk (hazard ratio ≈1.38, p<0.001) compared to warfarin alone (pmc.ncbi.nlm.nih.gov). Likewise, a recent PLOS One analysis (n≈2700) showed that concomitant GBE use was associated with an 8% relative increase in bleeding symptoms (OR~1.08, p<0.001) especially when combined with antiplatelet or NSAID drugs (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These interactions were notable with aspirin, clopidogrel, celecoxib and others (pmc.ncbi.nlm.nih.gov).

Meta-analyses of coagulation parameters, however, report no clear change in bleeding times or clotting factors from GBE alone (pmc.ncbi.nlm.nih.gov). Some experts note that typical GBE doses are unlikely to significantly affect coagulation tests (pmc.ncbi.nlm.nih.gov). Yet sporadic case reports link GBE to severe bleeding events (including intracerebral hemorrhage) (pmc.ncbi.nlm.nih.gov). Given these signals, GBE should be used cautiously in patients on anticoagulants (warfarin, DOACs) or antiplatelets, and atop NSAIDs. Physicians often recommend stopping GBE 1–2 days before surgery to avoid bleeding risk (pmc.ncbi.nlm.nih.gov).

Aside from bleeding, GBE has few serious side effects. Mild adverse effects may include GI upset, headache or palpitations. Because GBE can induce metabolism of certain drugs (via CYP enzymes) and alter platelet function, potential drug interactions must be considered (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, while GBE’s clinical safety profile is generally favorable, high-risk patients (coagulopathy, anticoagulant use) should be monitored closely.

Designing Clinical Trials in Glaucoma

Future trials should be rigorous yet feasible. We recommend randomized, placebo-controlled parallel trials in NTG patients (who stand to benefit most from vascular therapies). Key elements include:
- Long duration (e.g. ≥2 years) to capture visual field slope changes.
- Adequate sample size powered for perimetry endpoints (mean deviation, visual field index) and neuroretinal measures.
- Stable IOP management in both arms to isolate GBE effects.
- Use of standardized GBE (e.g. EGb 761) at a consistent dose (likely ≥120–240 mg/day, based on cognitive trials).
- Endpoints: Primary outcomes should include visual field progression (MD slope, proportion of eyes with >3 dB loss) and/or OCT measures of nerve fiber thickness. Secondary outcomes could be ocular blood flow (using laser Doppler or newer OCT-angiography), contrast sensitivity or color vision tests, and quality-of-life scales. Recording any cognitive or vascular events (e.g. TIA/stroke) may provide longevity insights.
- Stratification by risk factors (e.g. baseline perfusion pressure, presence of migraine/PVD) could identify subgroups who benefit most.
- A run-in or crossover design might be used for early-phase flow studies (as in Park 2011) to confirm biomarker changes before committing to large outcome trials.

Using objective blood flow imaging (Doppler, OCT-A) as an early pharmacodynamic endpoint can help establish proof-of-mechanism. Trials should pre-specify safety monitoring, especially bleeding parameters and INR if on warfarin. Finally, blinding and placebo controls are essential given the subjective nature of some visual function tests. With careful design, a definitive trial could settle whether GBE adds benefit in NTG beyond standard glaucoma therapy.

Conclusion

Ginkgo biloba extract has a plausible biological rationale for use in glaucoma: it can improve microvascular blood flow, modulate coagulation factors, and protect neurons from oxidative stress (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Small studies report better ocular perfusion and even slowed field loss in NTG with GBE (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). However, systematic analyses find no firm evidence of visual field benefit or IOP reduction (pmc.ncbi.nlm.nih.gov), and some patients see no change at all. The divergence likely reflects study limitations (short follow-up, small cohorts) rather than absence of effect.

In the aging brain, GBE has shown modest cognitive and cerebrovascular benefits (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). If similar protective mechanisms operate in the optic nerve, long-term GBE might help preserve vision. Yet safety remains a concern: GBE’s antiplatelet activity can augment bleeding risk, especially with anticoagulants or antithrombotics (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Practitioners should weigh these factors. For glaucoma patients interested in GBE, a discussion of potential (though unproven) vascular benefits versus bleeding risk is warranted. Ultimately, well-designed clinical trials are needed. Ideal studies will enroll NTG patients on stable IOP therapy, use objective perfusion and function endpoints, and run long enough to track field progression. Only then can we determine if Ginkgo biloba is a safe and effective adjunct for ocular perfusion and visual field preservation in glaucoma.