It was with great interest that we read the article by Guo et al.
1 in which authors conclude that in newly diagnosed Chinese patients affected by normal-tension glaucoma (NTG),
Ginkgo biloba extract (GBE) has no effect on mean defect and contrast sensitivity. These results are in contrast with our previous results,
2 but we think that differences in patient selection can partially explain these negative results.
Firstly, eligibility criterion based on intraocular pressure (IOP) was assessed throughout a diurnal curve, with no measurement taken at nighttime or at least in supine position. In our trials we deemed mandatory to limit the risk of false diagnosis of NTG with IOP values of more than 21 mm Hg during either daytime or nighttime, because it accounts for between 11% and 20% of the suspected cases of NTG.
3 This is a standard procedure for the diagnosis of NTG for either clinical or research purposes.
Secondly, NTG is a group of optic neuropathies sharing a slow progressive degeneration of retinal ganglion cells and their axons, resulting in typical optic disc damage, visual field defects compatible with the glaucomatous cupping. The requirement that the disease be progressive is controversial, since NTG usually is a progressive disease, although this may not be manifest for several years. Nevertheless, the progressive nature of the disease should always be borne in mind, because this will help distinguish true NTG from an isolated ischemic event that may mimic it in terms of optic disc and visual field appearances.
4 Differently from our study, Guo et al.
1 did not report on the progressive nature of disease, since they recruited patients at first diagnosis of NTG.
Thirdly, we excluded patients with systemic and/or local treatments to avoid any interference of concomitant therapies, and to better understand the effect of GBE administration. No mention is made by Guo et al.
1 about the absence of systemic treatments. Since several systemic treatments can strongly affect peripheral vascular autoregulation, thus interfering with vasodilatory properties of GBE,
5 this could explain the lack of efficacy of GBE on visual field and contrast sensitivity. Furthermore, it is well established that the use of some topical hypotensive drugs can result in a significant reduction of blood and/or ocular perfusion pressures, despite the lowering of IOP.
6,7 It would be important to know whether NTG patients enrolled in the study were receiving treatment with topical β-blockers or α-agonists, because a further reduction of ocular perfusion pressure induced by these drugs should be responsible for the observed lack of effect of GBE.
Again, patients were not investigated for Raynaud's syndrome and other peripheral vascular diseases, common in Caucasian populations affected by NTG. In our previous investigation on GBE, the number of patients affected by Raynaud's syndrome was 18 of 27 (66.6%). Only in these eyes did GBE administration induce an improvement of visual field damage (
Fig.). In fact, cerebral small-vessel ischemia is more common in NTG patients than in normal subjects.
8 It is therefore reasonable to assume that GBE administration improves not only visual field indices via increased cerebral blood flow, but also ocular blood flow, and thereby retinal sensitivity, as well as concentration and alertness.
In conclusion, we applaud the efforts to confirm our previous experience with GBE for the treatment of NTG patients. Differences in patient selection and introduction of several confounders (i.e., local and systemic medical therapies) do not allow to conclude that GBE is not effective as an adjuvant alternative treatment for NTG, whereas our data strongly support that GBE is able to induce an improvement of visual field damage in some NTG patients, by resolving peripheral vasospasm, and improving ocular perfusion.