Topouzis and associates’ observation that increased intraocular pressure (IOP) was the only risk factor associated with both primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (XFG) in the Thessaloniki Eye Study is interesting because recent evidence indicates that the prevalence of Helicobacter pylori (H. pylori) infection in glaucoma patients of this area is equally high, thereby representing a common denominator underlying both POAG and XFG in Thessaloniki.

It is known that current H. pylori infection may induce irregular humoral and cellular immune responses that, because of the sharing of homologous epitopes (ie, molecular mimicry), cross-react with components of nerves, thereby triggering and possibly perpetuating neural tissue damage observed in neurodegenerative diseases, including glaucoma.

In 2001, by using histologic analysis, representing the practical gold standard for H. pylori infection diagnosis, we documented for the first time a high prevalence of H. pylori infection in Thessaloniki patients with POAG and XFG, establishing a relationship between H. pylori infection and glaucoma. These results may indicate either that a common factor that causes susceptibilities to both glaucoma and H. pylori infection or that H. pylori may be a causal factor for developing glaucoma. In a subsequent study, we reported a beneficial effect of H. pylori eradication on glaucoma progression, including reduction in intraocular pressure mentioned by the authors, suggesting a possible causal link between the bacterium and glaucoma. Moreover, we reported an increased H. pylori- specific immunoglobulin G antibody concentration in the aqueous humor of patients with POAG and XFG; the concentration of this antibody correlated with the degree of vertical cupping, possibly indicating the severity of glaucomatous damage. Recently, we also showed for the first time the detection of H. pylori bacteria in the trabecula and iris of POAG patients, indicating that the bacterium is present locally and possibly is directly implicated in glaucomatous damage.

Reports from other ethnic populations also showed a relationship between glaucoma and H. pylori infection, although this has not been confirmed by all the relevant studies published so far, and thus this association may apply only to a limited subpopulation of glaucoma patients; similar observations have been made in Korea, China, India, Turkey, and Iran.

H. pylori infection, by releasing several inflammatory mediators, could induce blood-brain barrier (BBB) and blood-ocular barrier breakdown, thereby being involved in the pathogenesis of neuropathies, including glaucoma. For instance, H. pylori indirectly may affect the brain through the release tumor necrosis factor α acting at a distance; tumor necrosis factor α is involved in BBB disruption through the upregulation of matrix metalloproteinases. Furthermore, H. pylori circulating antibodies may also enter the aqueous circulation as a result of BBB and blood-ocular barrier disruption, possibly contributing to glaucoma progression; when serum-specific antibodies access the brain, they are capable of killing retinal cells. Likewise, an influx of H. pylori -infected monocytes, owing to defective autophagy resulting in H. pylori replication in autophagic vesicles, through the disrupted BBB and blood-ocular barrier may lead to glaucoma neuropathy; H. pylori vacuolating toxin A (VacA) promotes intracellular survival of the bacterium and modulates host immune responses. Finally, because the oral cavity may act as a permanent reservoir for H. pylori , this bacterium may reach the eye through the nasal cavity, causing ophthalmic pathologic changes and possibly including glaucoma.

It thus would be interesting to know if the authors have considered H. pylori infection as a risk factor involved in POAG and XFG progression in their Thessaloniki Eye Study participants, who are expected to exhibit a high prevalence of H. pylori infection.