Abstract
Introduction
The two most common types of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn’s disease (CD). Although these diseases mainly affect the intestinal system, they can also affect other systems, especially the vascular system. The objective of this study is to evaluate ocular microvascular and structural changes in IBD.
Methods
A total of 42 patients with IBD (22 UC and 20 CD) followed in the gastroenterology clinic and 42 healthy controls matched for gender and age were enrolled in the study. All participants underwent optical coherence tomography angiography. Macular vessel density, central retinal, and choroidal thicknesses were measured.
Results
No significant differences were observed between IBD patients and control subjects as regards superficial vascular plexus density, deep vascular plexus density, and choriocapillaris vascular density, retinal and choroidal thickness in the macular area (p > .05). Although not statistically significant, vascular density generally increased. On the other hand, retinal and choroidal thickness were decreased.
Conclusion
It could be said that there is a reactive increase in retinal vascular density and a decrease in retinal and choroidal thickness as a result of atherosclerotic changes in IBD.
Keywords
Introduction
Ulcerative colitis (UC) and Crohn’s disease (CD) are the two dominant inflammatory bowel diseases that are frequently seen in the community, and affect the intestinal system. It has been reported that many substances play a role in the formation of inflammatory bowel diseases. Among these chemical molecules are matrix metalloproteinases, angiopoietin 1, nitric oxide (NO), tumoral growth factor, and vascular endothelial growth factor.1,2 These molecules are likely to affect the entire vascular system, including the eye.
Although these diseases mainly affect the intestinal system, they can also affect other systems, especially the vascular system. Zuhal et al. evaluated atherosclerosis and retrobulbar flow in patients with CD, and increased carotid intima-media thickness and increased ophthalmic artery resistivity index values were found. As a result, they reported that the vascular system was adversely affected by inflammatory bowel disease and that there might be a decrease in blood flow in the eye tissues. 3
Another study revealing the negative effect of UC and CD on the vascular system was conducted by Hatoum et al. They reported impaired NO-dependent dilatation and endothelial dysfunction in inflammatory bowel diseases. 4 In addition to the cardiovascular system and the eye vascular system changes, it has been reported in the literature that IBD also affects the choroid layer. 5
Optical coherence tomography angiography (OCTA) and fundus fluorescein angiography are two methods used for imaging the retina and choroidal vascular system. However, OCTA has been used more widely in recent years due to its non-invasiveness. In addition to the vascular system, it can show structural changes in the retina and choroid.6,7 By using OCTA, it is possible to view ischemic changes in the retina, neovascular formations, vascular occlusions, vascular changes in the choroid, and aneurysms. 8
Given the effects of bowel disease on the vascular system and ocular blood flow, we aimed to evaluate vascular density changes in retinal and choroidal tissues. To our knowledge, this is the first study to evaluate vascular density change in inflammatory bowel diseases.
Materials and methods
A total of 42 patients with IBD, 20 CD, and 22 UC, followed in the gastroenterology clinic and 42 healthy controls (HC) matched for gender and age were enrolled in this prospective study from Izmir University of Economics Medical Point Hospital.
The study adhered to the Declaration of Helsinki and was approved by the institutional review board of Bakircay University. (Decision No: 1016 - Search No: 996). Written informed consent was obtained from all participants.
Inclusion criteria for all participants were as follows: 1. Patients who were diagnosed with UC or CD according to the European Crohn’s and Colitis Organization Consensus and who read and signed the informed consent form were included in the study. 2. Patients without evidence of active or sequelae inflammation in the anterior and posterior segments of the eye were included in the study.
Exclusion criteria for all participants were as follows: 1. Presence of diseases that may affect the retinal and choroidal vascular structures such as coronary artery disease, heart diseases, and hypertension. 2. Presence of diseases such as nystagmus and tremor that may adversely affect scans 3. Patients with eye problems such as previous eye surgery, glaucoma, eye axial length less than 22 mm and longer than 26 mm, presence of corneal and lens disorders that may affect the quality of the scan. 4. Patients with smoking, consumption of more than one cup of coffee per day, and use of decongestant drugs that may affect the vascular system were not included in the study.
Systemic blood pressure (systolic and diastolic pressure), intraocular pressure (IOP) (Goldmann applanation tonometry), and eye axial length were measured in age and gender-matched study. Anterior segment and posterior segment examinations were performed with a slit lamp.
Vascular density, retinal and choroidal thickness were measured using spectral-domain OCTA, RTVue-XR Angiovue (Software V.2015.1.0.90, Optovue, Fremont, CA, USA). The OCTA machine can perform volumetric scans of the 6 × 6 mm macular area with a 320 × 320 A-scan sample density at an A-scan rate of 100,000 A-scans/sec, and uses the OCTA algorithm to generate angiogram tests. 9
Because the results of low-quality measurements were not reliable, rescans were made. Scans with a signal strength index of 60 and above were analyzed. Five areas divided centering on the macula are displayed and the blood vessel density of each area is indicated as percent. The diameter of the inner circle is 1 mm, and the diameter of the outside circle is displayed at 3 mm (Figure 1(a)–(c)). (a) Macular perfusion parameters of a 6 mm × 6 mm angiography scan size of superficial vascular plexus. (b) Section image shows structural OCT in the background and the superficial vascular plexus data as red overlay. (c) The vessel density of five areas of interest, including the fovea (1-mm diameter) and temporal, inferior, nasal, and superior quadrants.
Superficial vascular density (SVD) measurements were made at a depth of 2.6µ and 15.6µ from the internal limiting membrane (ILM) and deep vascular density (DVD) tests were made at a depth of 15.6µ and 70.2µ from the ILM. Choriocapillaris vessel density measurements were made at a depth of 30 μm and 60 μm from the RPE, all calculations made automatically by the device. 10
Wavelength and light source differences can lead to variable detection of choroidal vasculature in different devices. 11 Central macular thickness (CMT) and basement membrane-sclerochoroidal interface distance (BM-SCI) were automatically measured. In the study, CMT was mentioned as retinal thickness and BM-SCI as choroidal thickness.
Statistical analysis
Statistical analyses were performed with IBM SPSS for Windows Version 21.0 software. Numerical variables were expressed as mean ± SD. Categorical variables were summarized as numbers and percentages. The estimated sample size was calculated using the G*Power program.
The confidence interval was 95%, the power of the study was 80%, and the minimum sample size was 39. The normality of the distribution and variance homogeneity of continuous variables was evaluated with the aid of the Kolmogorov-Smirnov test and Levene’s test, respectively. Independent samples t test was used for data with normal distribution, and Mann Whitney U test was used for data, not with normal distribution. A p-value of 0.05 was considered to reflect statistical significance.
Results
The demographic and clinical characteristics of the groups.
Values are mean ± SD, (*p ≤ .05), IBD, Inflammatory bowel diseases; IOP, Intraocular pressure; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; AL, axial eye length.
SVD, DVD, CCVD, CMT and BM-SCI values.
Values are mean ± SD, (*p ≤ .05), IBD, Inflammatory bowel diseases; SVD, Superficial vascular density; DVD, Deep vascular density; CCVD, Choriocapillaris vascular density; CMT (µm), Central macular thickness; BM-SCI, Basement membrane-sclerochoroidal interface distance.
However, we found increased vascular density in 12 of the 15 areas evaluated in the IBD patients, excluding three including superficial vascular plexus density and choriocapillaris vascular density in the superior area, and deep vascular plexus density in the inferior area.
Discussion
We performed this study to evaluate retinal and choroidal microvascular changes in inflammatory bowel diseases. Chronic microvascular dysfunction alongside endothelial deterioration has a role in mesenteric ischemia and the IBD process. Restricted blood flow is another factor in wound healing and inflammation.3,4 It was reported that resistant ulcers in inflammatory bowel diseases are the result of deterioration in the microvascular system. 12
So, many studies have been conducted to reveal microvascular disorders, endothelial disorders, and atherosclerotic processes.13,14 In one of these studies, Cheung et al. 15 revealed that the velocity of blood flow in the retina could be connected to microvascular function. In addition, the presence of impaired ocular blood flow could be an indicator of progression in cardiovascular diseases in inflammatory bowel diseases.3,15
Similarly, Keles et al. 16 demonstrated that accelerated atherosclerosis which can be shown by the increased resistivity index of the ophthalmic artery is found in chronic inflammatory diseases. Inspired by these studies on atherosclerotic and ocular blood flow, we looked at how this atherosclerotic process and IBD affect retinal vascular density. In our study, although not significant, we found increased vascular density in retinal layers. We thought that the reason for an increase in retinal vascular density would be retinal ischemia due to atherosclerotic processes in the ophthalmic artery, which was previously reported. Also, retinal thickness was reduced in IBD patients. Chronic ischemia of the retina could be the possible cause.
It is well known, ocular inflammation is a frequent extraintestinal manifestation of inflammatory bowel disease. Increased choroidal thickness has been demonstrated in some systemic autoimmune and inflammatory disorders including Vogt-Koyanagi-Harada disease, and Behçet disease.17,18 However, Onal et al. evaluated choroidal thickness in patients with inflammatory bowel disease and showed that choroidal thickness was thinner in IBD patients. But it was not statistically significant. 5 They measured the choroidal thickness manually, but we automatically took measurements from the subfoveal area. Similarly, we found the choroidal thickness thinner in IBD patients. An important reason for the thinning of the choroidal thickness could be chronic ischemia due to atherosclerotic processes. These patients had not an attack of uveitis previously could be another reason for thinning in the choroidal thickness. Therefore, a choroidal thickness increase due to uveitis was not expected.
The limitations of the study are: 1. Patients with uveitis were not included in the study. Therefore, the effect of uveitis attack on choroidal thickness could not be evaluated. 2. If the resistivity index of the ophthalmic artery could be measured, we could interpret atherosclerotic processes more comprehensively. 3. More homogeneous study group could be formed by taking only one of the UC or CD patients. 4. Small sample size. With larger series, results can be evaluated better.
Conclusions
In conclusion, no significant difference was observed in retinal vascular density, choroidal vascular density, and retinal and choroidal thickness. On the other hand, vascular density generally increased, while retinal and choroidal thickness decreased. These results may show that eye tissues are affected due to atherosclerosis and ischemia rather than inflammatory processes, especially in patients who do not have an uveitis attack.
Footnotes
Acknowledgements
We really appreciate to the staff of the ophthalmology department.
Author contributions
SB and AYT are the authors who compiled and design the manuscript. SB wrote the manuscript. AYT critically reviewed the manuscript to finalize the structure as well as contents of the manuscript. Finally all the authors have carefully read and approved the manuscript.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
