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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Results
  • Discussion
  • Disclosures
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

Here, we compared macular retinal and choroidal thickness in populations with and without Helicobacter pylori infection using a swept-source optical coherence tomography (SS-OCT) device, which is one of the recent milestones in the development of retinal and choroidal visualization.

Abstract

Around half of the world's population is infected with Helicobacter pylori (H. pylori), which is closely related to several ocular diseases. The study aims to evaluate the retinal and choroidal thickness changes in subjects with H. pylori infection by swept-source optical coherence tomography (SS-OCT). The ophthalmic examination and 13C-urea breath test (13C-UBT) were performed on all subjects participating in the cross-sectional study. The participants were divided into H. pylori (+) and H. pylori (−) groups depending on the 13C-UBT results. This study covered 2574 right eyes from 2574 subjects with H. pylori infection and 2574 right eyes from 2574 age- and sex-matched individuals without H. pylori infection. Out of the nine sectors of the early treatment diabetic retinopathy study (ETDRS) grid, the maximum retinal thickness was in the inner superior sector, while the minimum was in the center sector. The maximum choroidal thickness was in the inner superior sector, while the minimum was in the outer nasal sector. The choroid of each area of the ETDRS subfield in the H. pylori (+) group was significantly thicker than that in the H. pylori (−) group, but retinal thickness did not show any difference between the two groups. Increased choroidal thickness may be an early indicator of H. pylori-associated retinal or choroidal diseases.

Introduction

Helicobacter pylori (H. pylori) is a gram-negative bacterium that settles on the gastric epithelium surface and infects approximately 50% of the world's population1,2. The incidence of H. pylori infection varies from region to region, and infections are more common in societies with low socioeconomic status3. H. pylori infections are typically acquired during childhood, and a significant proportion of individuals infected with H. pylori do not exhibit any symptoms4. If left untreated, H. pylori can colonize throughout an individual's lifetime.

The main manifestations of H. pylori infection are chronic gastritis, peptic ulcer, gastric cancer, and MALT lymphoma2,5,6,7. Currently, the role of H. pylori has been shown in the pathogenesis of extra gastric pathologies, such as atherosclerosis, idiopathic thrombocytopenic purpura, urticaria, obesity, and iron-deficiency anemia8,9,10,11,12. Some studies have also demonstrated that H. pylori is associated with several eye diseases, including central serous chorioretinopathy13, blepharitis14, glaucoma15, and uveitis16.

As the tissue with the highest blood flow, the choroid provides oxygen and nutrition to the retina while removing metabolic waste17,18,19. Changes in retinal and choroidal thickness may occur due to systemic diseases18 and physiological conditions20 and may also contribute to ocular pathologies such as central serous chorioretinopathy21, diabetic retinopathy22, age-related macular degeneration23, uveitis24, glaucoma25, and myopia-related chorioretinal atrophy26. Thus, accurate measurements of retinal and choroidal thickness are of great significance for monitoring the onset and progression of the diseases. Swept-source optical coherence tomography (SS-OCT), a recent advancement in retinal and choroidal visualization, offers a noninvasive means of obtaining more precise images of the retina and choroid.

Currently, there have been limited studies examining the relationship between H. pylori infection and choroidal thickness, and the data in the literature are controversial19,27,28. Some authors have reported that choroidal thickness is related to H. pylori infection19, whereas others have not27,28. The present study aims to evaluate the associations between H. pylori infection and the thickness of the retina and choroid.

Protocol

This cross-sectional study was conducted at Huashan Hospital of Fudan University between September 2018 and April 2019. It was approved by the Institutional Review Board of Huashan Hospital, affiliated with Fudan University (No. KY2016-274). Informed consent was obtained from all participants prior to the examinations.

1. Inclusion criteria

  1. Collect all subjects' general conditions, including age, sex, and a history of systemic diseases (thyroid diseases, diabetes mellitus, hypertension, dyslipidemia). Inclusion criteria are as follows:
    1. Include participants aged 18-70 years without a history of systemic diseases noted in step 1.1.
  2. Collect all subjects' ocular conditions, including best-corrected visual acuity (BCVA), a history of eye diseases (retinal and choroidal diseases), and a history of ocular trauma or surgery. Inclusion criteria are as follows:
    1. Include participants with BCVA ≥ 20/25 Snellen.
    2. Include participants without a history of eye diseases.
    3. Include participants without a history of ocular trauma or surgery.

2. 13C-urea breath test

NOTE: Among the several noninvasive tests for the diagnosis of H. pylori infection, including stool antigen testing and serological testing, 13C-urea breath test (13C-UBT) is considered to be the gold standard with high sensitivity and specificity1,29.

  1. After an overnight fast, ask the participant to blow as indicated in the test kit. Collect a baseline breath sample.
  2. Have the subject take 75 mg of the 13C-urea substrate in a citric acid base at the 13C-UBT meal. Ask the participant again to blow 30 min after urea ingestion. Collect the breath sample.
  3. NOTE: This test is based on the urease produced by H. pylori present in the stomach, liberating carbon dioxide (CO2) from urea. The uptake of labeled urea leads to the generation of labeled CO2, which can subsequently be quantified in exhaled breath.
  4. Calculate the result expressed as the difference value between the two breath samples. Consider the test positive for H. pylori infection when the delta over baseline value was >3.5%.
    NOTE: False-negative results can occur in subjects taking proton pump inhibitors (PPIs) or antibiotics that interfere with the sensitivity of 13C-UBT30. To avoid a false-negative result, PPIs and antibiotics should be stopped for at least 3 months before 13C-UBT.
  5. Based on the 13C-UBT results, divide the participants into two groups: The H. pylori (+) group refers to those with H. pylori infection, and the H. pylori (−) group refers to those without H. pylori infection.

3. Swept-source optical coherence tomography imaging

  1. Open up the Power button of the SS-OCT device. Click the Radial Dia.6.0 mm Macula Overlap 4 button.
  2. Capture OCT images for every eye by scanning 100,000 A-scans/s between 8 a.m. and 10 a.m.
    NOTE: The retinal and choroidal thickness were defined, respectively, referring to previous articles (Figure 1)31,32.
  3. Generate thickness images of SS-OCT automatically based on the standard early treatment diabetic retinopathy study (ETDRS) subfield (Figure 2).
  4. Manually check each segmented layer line for every image to avoid automatic measurement errors31,32.
  5. Exclude the unclear OCT images due to unstable fixation or media opacity.

4. Statistical analysis

  1. Click on the statistical analysis software. Import the data into the software.
    NOTE: SPSS was used for statistical analysis. Continuous data was summarized using the mean ± standard deviation, while categorical data was presented as frequency (percentage).
  2. Compare continuous variables via the t-test, whereas categorical variables by the chi-square test. Define statistical significance as a p-value less than 0.05.
    NOTE: The analysis included only the right eyes, which were considered as a separate study unit.

Results

A total of 2574 right eyes of 2574 subjects who tested positive for H. pylori and 2574 right eyes of 2574 individuals who tested negative for H. pylori were evaluated. Table 1 lists the baseline characteristics of the participants. The male/female ratio was 1334/1240 in both the H. pylori (+) group and the H. pylori (−) group. The mean age was 42.68 ± 10.76 years (range, 18-70 years) in both groups.

Out of the nine sectors of the ...

Discussion

H. pylori infection has been related to many extra gastric disorders, such as neurological, dermatological, cardiovascular, and ocular diseases33. However, the pathogenesis of H. pylori-associated ocular diseases remains elusive. We used SS-OCT to measure macular retinal and choroidal thickness in subjects with and without H. pylori infection. The results showed that the choroidal thickness was significantly increased in subjects with H. pylori infection when co...

Disclosures

None of the authors has a financial or proprietary interest in any material or method mentioned.

Acknowledgements

This study was funded by grants from the National Natural Science Foundation of China (No. 81900879) and the Science and Technology Commission of Shanghai Municipality (No. 20Y11910800).

Materials

NameCompanyCatalog NumberComments
13C-urea breath test detectorRichen Force, Beijing, ChinaV505721
13C-urea breath test kitRichen Force, Beijing, ChinaH20061169
Ophthalmoscope66 Vision-Tech, Suzhou, ChinaV259204
Slit-lamp microscopeTopcon, Tokyo, Japan6822
SPSS softwareIBM, Chicago, USA ECS000143
Swept-source optical coherence tomographyTopcon, Tokyo, Japan185261
Visual chartYuejin, Shanghai, ChinaH24104

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Helicobacter PyloriRetinal ThicknessChoroidal ThicknessSwept source Optical Coherence TomographySS OCTOcular Diseases13C urea Breath TestCross sectional StudyETDRS GridDiabetic RetinopathyH Pylori InfectionChoroidal Diseases

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