Association between Helicobacter pylori infection and primary open-angle glaucoma

The pathological processes of primary open-angle glaucoma is unknown. Several studies show the relation between Helicobacter pylori infection and primary open-angle glaucoma. The purpose of this study was to assess the association between H. pylori infection and primary open-angle glaucoma. Forty patients of diagnosed primary open-angle glaucoma were selected as case and 40 participants without primary open-angle glaucoma were selected as control as per inclusion and exclusion criteria. Complete clinical evaluation including history, physical examination, relevant ocular examinations and laboratory investigations were performed. Serologic evidence of H. pylori infection was found in 75% of patients with primary open-angle glaucoma and 30% of patients without primary open-angle glaucoma which achieved statistically significant difference (p=0.000, OR=7.00 and CI 95% =2.61-18.74). 13C urea breath test was positive in 70% in case group and 37.5% in control group which also achieved statistically significant difference  (p=0.003, OR=3.89 and CI 95% =1.53-9.87). The findings revealed significant association between H. pylori infection and primary open-angle glaucoma. 
 


Introduction
Primary open-angle glaucoma is the most common cause of irreversible blindness worldwide. 1It is usually bilateral which is adult onset characterized by an intraocular pressure more than 21 mmHg at some stage, glaucomatous optic nerve damage, an open anterior chamber angle, characteristic visual field loss as damage progresses, absence of signs of secondary glaucoma or a non-glaucomatous cause for the optic neuropathy.The pathologic processes of glaucoma still remains hidden in many points.Agedness, hereditary and raised intraocular pressure may be responsible factors.Changes in endothelin-dependent vascular regulation, cytokine-dependent platelet aggregation which impaired ocular blood flow, influencing apoptotic process and apoptotic loss of optic disk neurons and other autoimmune mechanisms which may induce and/or exacerbate glaucomatous optic neuropathy.Helicobacter pylori is a Gram negative bacterium which causes many upper gastrointestinal diseases.It mainly resides in the stomach, but it also produces a systemic host immunologic response and the release of various vasoactive and pro-inflammatory substances.Thus, H. pylori may be partly responsible for the occurrence of diseases in extradigestive areas such as ischemic heart disease, cardiovascular disease, Raynaud's phenomenon and migraine.
Another likely association is the glaucoma which thought to linked with H. pylori through some mechanisms include: Stimulating aggregation of platelet and platelet-leucocyte, stimulating release of pro-inflammatory and vasoactive substances, inducing cross mimicry between endothelial and H. pylori antigens and promoting apoptotic process. 5Recently various debate about their association. 6Some studies in Greece, china, Iran, and Australia have reported relatively higher association between H. pylori infection and open-angle glaucoma. 7-11However, other studies in Canada and Iran have not reported statistically significant differences between them. 12-14Other studies found that eradication of H. pylori may be beneficial in the management of chronic open-angle glaucoma. 15hinking about these dispute, this study was done to compare the association of H. pylori infection in patients having primary open-angle glaucoma and control group of participants.

Association between Helicobacter pylori infection and primary openangle glaucoma
Sayaka Sultana, Nazneen Khan, Chonchol Kumar Ghosh, Ahmed Abu Saleh and Md.Shafiqul Islam were age between 40-80 years, intraocular pressure ≥21 mmHg, open anterior chamber angle in gonioscopy, optic nerve head changes as glaucomatous, visual field changes such as generalized depression, paracentral scotoma, nasal step.The patient with history of angle closure glaucoma or other kinds of glaucoma, diabetes mellitus, severe systemic disease and neoplasm, other serious eye diseases (corneal opacity, uveitis, central serous chorioretinopathy), previous gastric surgery or treatment of H. pylori eradication were excluded from the study.Inclusion criteria of the controls were age between 40-80 years, intraocular pressure <21 mmHg, normal perimetry, without any glaucomatous optic nerve changes and normotension.The patient with history of angle closure glaucoma or other kinds of glaucoma, diabetes mellitus, severe systemic disease and neoplasm, serious eye disease (corneal opacity, uveitis, central serous chorioretinopathy), previous gastric surgery or treatment of H. pylori eradication were excluded from the control.The purpose and procedures were briefly explained to all participants.Following inclusion and exclusion criteria, samples were collected by purposive sampling.
The complete clinical evaluation including history, physical examination, relevant ocular examinations, fundus examination, some special ocular examinations likeintraocular pressure, visual field analysis, gonioscopy were done.

Serologic assays
For the determination of serum levels of anti-pylori IGg antibody, blood samples were collected and evaluated by ELISA method (DRG H. pylori IgG kit-EIA-3057) (positive if anti H-pylori IgG level >20 U/ mL).

Urea breath test
After an abstinence of proton pump inhibitor for 14 days and fasting for 2 hours, all patients were subsequently subjected to a 13 C-urea breath test, performed accordance with the manufacturer's recommendations (HCBT-01, Headway 13 C-Urea Breath Analyzer, China).Patient went through for procedure: a) Blow up the first collection bag; b) take one 13 C-urea capsule (75 mg urea); c) wait for 30 min; d) blow up the second collection bag and e) test two bags of breath samples with the analyzer.The results were obtained on-site and expressed as positive or negative.

Statistical analysis
All data were analyzed by using statistical package for social sciences (SPSS).Associations between two variables were measured by Chi-square test.A probability 'p' value of 0.05 or less was considered as significant.Strength of association was determined by estimating odds ratio (OR) and their 95% confidence intervals (CI).

Results
The mean age of the patients of both groups were similar.Positive serology of H. pylori infection was found in 75% of patients with primary open-angle glaucoma and 30% of patients without primary open-angle glaucoma, which was statistically significant (p=0.000,OR=7.00 and CI 95% =2.61-18.74). 13C-urea breath test was positive in 70% in case group and 37.5 % in control group, which was significant (p=0.003,OR=3.89 and CI 95% =1.53-9.87).
The mean intraocular pressure in right eye and left eye of the patients primary open-angle glaucoma were 21.8 ± 1.6 and 21.8 ± 1.30 mm of Hg respectively whereas in control group, the values were 11.2 ± 2.5 and 11.2 ± 2.5 mm of Hg respectively for right eye and left eye (Table II).The p value was found significant (<0.01).

Discussion
Comparing serology and urea breath test results reveals significantly higher prevalence of H. pylori infection in patients with primary open-angle glaucoma.
In the last few years, many studies had conducted for the relationship between H. pylori infection and  In the previous studies, only serological method (ELISA) was used to detect H. pylori infection because it's a simple test and good for population studies.But it conveys high false positive rates. 23, 24esides, urea breath test shows higher sensitivity (91.4%) and higher specificity (93.8%) respectively and accuracy (90-93%) which was nearer with the values for histological examination in the elderly. 25herefore, we preferred the 13 C-urea breath test and serological method both.Endoscopic biopsy is an invasive method and noninvasive tests are more accessible for screening. 1eece done the larger period study of this association, used histologic analysis, rapid urease slide test (CLO test) for biopsy, saliva samples and serologic tests, found more frequency of H. pylori in glaucoma patients than anemic control group (p<0.001). 8Other study announced that eradication of H. pylori effectively upgrade glaucoma parameters (p<.001 for intraocular pressure; p≤0.01 for visual field), giving the idea about their causal relationship. 15Another article explained the inductive theory of apoptosis with H. pylori infection. 6nother study gave the idea about their possible genetic relationship, proposed this infection as an environmental risk factor for primary open-angle glaucoma. 6Another study in china performing 13  In Bangladesh, the prevalence of H. pylori infection is high.More than 90% apparently healthy adults have antibody to H. pylori in the blood. 28ssible explanation of this association is the autoimmune reaction, stimulating platelet and platelet leucocyte aggregation, releasing vasoactive and pro inflammatory factors, sharing common genetic factors which causes apoptosis, impaired ocular circulation, ultimately induces or aggravate glaucomatous damages. 1

Conclusion
There is significant association between H. pylori infection and primary open-angle glaucoma.

Table I Demographic characteristics, gender, antibody titre and 13 C-urea breath test positivity
13,11aucoma (p=0.88 for H. pylori and p=0.67 for Cag-A).12Otherdisagreeingstudiesabout the relation between H. pylori infection and primary open-angle glaucoma carried out in Canada and Iran.13,11Regarding this conflicting results, we used both methods serological test and urea breath test for more accuracy.