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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 67  |  Issue : 1  |  Page : 9-16

Retinal vascular tortuosity in patients with obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome


1 Department of Chest Diseases, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission04-Oct-2017
Date of Acceptance28-Oct-2017
Date of Web Publication21-Mar-2018

Correspondence Address:
Rabab A El Wahsh
Menoufia University, 72427
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejcdt.ejcdt_5_17

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  Abstract 

Background Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are linked with microvascular changes. Retinal microvasculature can be examined in a direct noninvasive way.
Aim The aim was to evaluate tortuosity of the retinal vessels in patients with COPD, OSA, and overlap syndrome.
Patients and methods A total of 60 participants were included: 15 patients with OSA, 15 patients with COPD, 15 patients with COPD-OSA overlap syndrome, and 15 matched controls. All participants underwent digital retinal photography, polysomnography, arterial blood gases, spirometry, Epworth sleepiness scale, and STOP-BANG questionnaires.
Results Tortuosity of most retinal vessels was higher in all patient groups when compared with the control group, and tortuosity was more marked in the overlap syndrome group. There was a negative correlation between tortuosity of retinal vessels and PO2, O2 saturation, and minimum O2 saturation, and a positive correlation with PCO2, apnea hypopnea index, O2 desaturation index, BMI, and smoking index.
Conclusion Retinal vascular tortuosity occurs in OSA, COPD, and overlap syndrome. Retinal vascular tortuosity is correlated with arterial blood gases parameters, polysomnographic findings, smoking index, and BMI.

Keywords: chronic obstructive pulmonary disease, obstructive sleep apnea, overlap syndrome, retinal vascular tortuosity


How to cite this article:
El Wahsh RA, Yousif M, Ibrahim AM. Retinal vascular tortuosity in patients with obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome. Egypt J Chest Dis Tuberc 2018;67:9-16

How to cite this URL:
El Wahsh RA, Yousif M, Ibrahim AM. Retinal vascular tortuosity in patients with obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome. Egypt J Chest Dis Tuberc [serial online] 2018 [cited 2020 Apr 3];67:9-16. Available from: http://www.ejcdt.eg.net/text.asp?2018/67/1/9/228137




  Introduction Top


Obstructive sleep apnea (OSA) is commonly accompanied by endothelial changes and vascular comorbidities [1]. It is suggested that inflammatory processes, oxidative stress, and endothelial dysfunction may have roles in the mechanisms of vascular complications in patients with OSA [2].

Microvascular diseases like myocardial infarction and stroke occur also in patients with chronic obstructive pulmonary disease (COPD). Chronic hypoxia leads to an increase in hypoxia-inducible factor-1α, leading to increased production of many molecules such as endothelin-1 and vascular endothelial growth factor, which enhance new vessels formation and affect the blood–retina barrier [3].

In patients with OSA-COPD overlap syndrome, mortality was found to be greater than in patients having either disease alone. Both COPD and OSA were found to be associated with vascular endothelial changes, increased production of inflammatory mediators, and faster development of atherosclerosis [4].

The retina is a unique site where the microvessels can be imaged directly, giving a chance to study in vivo the anatomy and the occurrence and extent of abnormalities of the microvessels [5]. Therefore, the aim of the current study was to evaluate retinal vessel tortuosity in patients with COPD, OSA, and OSA-COPD overlap syndrome as an indicator of systemic microvascular affection in these diseases.


  Patients and methods Top


In this cross-sectional study, 60 adult patients were prospectively recruited from Sleep Disorders Unit at Chest Department, Menoufia University Hospitals, between February 2016 and August 2017. They were categorized into four groups (each included 15 participants): group I had patients with OSA, group II had patients with COPD, groups III had patients with COPD-OSA overlap syndrome, and group IV comprised apparently healthy age-matched and sex-matched participants as a control group. The exclusion criteria were as follows: concomitant diseases known to affect retinal vasculature (i.e. diabetes mellitus, hypertension, glaucoma, and dyslipidemia), history of prior retinopathy, cataract causing diminished visual acuity less than 20/40, opacities hindering imaging of the posterior segment, central sleep apnea, concomitant non-COPD chronic respiratory disease, domiciliary oxygen therapy, or noninvasive positive airway pressure therapy.

An informed patient’s consent and an approval from Menoufia University Ethics Committee were obtained before the study. Each participant underwent a full-night sleep study using Embla S4000 Medcare (Reykjavik, Iceland), which includes recording of airflow (using nasal cannula and thermistor), pulse oximetry, respiratory movements (using respiratory inductive polysthmography belts), sleep staging (using the electroencephalography, electro-oculography, and electromyography of the chin) besides recording of snoring, body position, bilateral tibialis anterior muscles, and ECG. Before the beginning of the study, participants were asked to answer a sleep questionnaire including STOP-BANG score and the Epworth sleepiness scale (ESS). All findings were interpreted in concordance with updated international scoring rules [6],[7].

On the second day of the sleep study, an arterial blood gases (ABG) analysis was done followed by spirometry [forced vital capacity (FVC) maneuver]. Spirometric testing was done using ‘Quark PFT3’ (COSMED, Rome, Italy). Each participant was asked to make a maximal expiratory effort starting from a position of maximal inspiration and ending at complete expiration [8].

Patients with COPD were diagnosed based on the Global Initiative for Chronic Obstructive Lung Disease criteria when they were clinically stable [forced expiratory volume in 1 s (FEV1)/FVC <0.70] [9].

Ophthalmic examination

All participants were examined in the ophthalmology clinic for testing visual acuity, intraocular pressure (IOP), and slit lamp biomicroscopy with dilation and fundus photography using a Topcon fundus camera (Topcon, Oakland, New Jersey, USA). Measurements of the temporal retinal arcades were done using image software (National Institutes of Health, Bethesda, Maryland, USA). A circle with a diameter of 10 disc diameters (10 DD) was drawn with its center on the optic disc. Superior and inferior arteriolar and venular arcades were measured individually starting from the optic disc margin to the crossing point of the 10 DD circle, with measurement of the arc and chord lengths of each vessel segment at the10 DD points. Tortuosity was calculated by dividing the arc length by the chord length at each [10] ([Figure 1]).
Figure 1 Demonstration of the retinal vessels and the method of calculation of the vascular tortuosity.

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Statistical methods

Data were analyzed using the IBM SPSS statistics software version 23. Quantitative data were expressed as mean±SD and analyzed using analysis of variance test to evaluate variables among all groups. Least significant difference post-hoc test was used to compare between each two groups. Qualitative data were expressed as frequency and percentage and analyzed using χ2-test. Pearson’s correlation coefficient was used to analyze the correlation of different variables. Level of significance was set at P less than or equal to 0.05.


  Results Top


The four groups were matched regarding age and sex. There was a significant difference regarding smoking index between OSA group and each of COPD group and overlap syndrome group, between COPD and overlap syndrome groups, and between control group and each of COPD and overlap syndrome groups.

There was a statistically significant difference regarding BMI between COPD group and each of OSA group and overlap syndrome group, and also between control group and all patient groups ([Table 1]).
Table 1 Sociodemographic data of studied groups

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There was a statistically significant difference regarding pH between OSA group and each of COPD and overlap syndrome groups and between overlap syndrome group and control group.

There was a statistically significant difference regarding PO2 between overlap syndrome and each of OSA and COPD groups, and between control group and each of patient groups. Besides, O2 saturation showed a statistically significant difference between each of the patient groups and the other two groups, and between control group and each of patient groups.

Regarding PCO2, there was a statistically significant difference between each of the patient groups and the other two groups, and between control group and each of COPD and overlap syndrome groups, whereas HCO3 level showed a statistically significant difference between OSA group and each of COPD and overlap syndrome groups and between control group and each of patient groups ([Table 2]).
Table 2 Arterial blood gases findings in different groups

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Regarding STOP-BANG questionnaire, there was a nonsignificant difference between COPD and OSA groups, whereas other comparisons showed a significant difference. ESS demonstrated a nonsignificant difference between OSA and overlap syndrome groups, whereas other comparisons demonstrated a significant difference. Apnea hypopnea index (AHI) was 48±26.77, 2.8±1.42, 68±20.27, and 2.93±1.28 in OSA, COPD, overlap syndrome, and control groups, respectively. O2 desaturation index was highest and minimal O2 saturation at night was least in patients with overlap syndrome followed by patients with OSA ([Table 3]).
Table 3 Sleep parameters in the studied groups

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Visual acuity and IOP in both eyes did not differ significantly among the studied groups ([Table 4]).
Table 4 Visual acuity and intraocular pressure in different groups

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Regarding right superior artery tortuosity, there was a nonsignificant difference between OSA and COPD groups and between COPD and control groups. Other comparisons revealed significant differences. Regarding left superior artery, right superior vein, and left superior vein tortuosity, there was a nonsignificant difference between OSA and COPD groups. Other comparisons revealed significant differences. Regarding right inferior artery and left inferior artery tortuosity, there was a nonsignificant difference between COPD and overlap syndrome groups. Other comparisons found significant differences. Regarding right inferior vein and left inferior vein tortuosity, there was a significant difference among all groups ([Table 5]).
Table 5 Retinal vascular tortuosity in different groups

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There was a significant negative correlation between tortuosity of all retinal vessels and both PO2 and O2 saturation. PCO2 and AHI correlated positively with tortuosity of all retinal vessels. Tortuosity of some retinal vessels correlated positively with O2 desaturation index, BMI, and smoking index, and negatively with minimum O2 saturation ([Table 6]).
Table 6 Correlation between retinal vascular tortuosity and different parameters

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  Discussion Top


In COPD, hypoxia and systemic inflammation are thought to have detrimental effects on fine ocular structures, such as choroid, macula, retinal nerve fiber layer, and retinal vascular vessels [11].

Many ocular manifestations have been linked to OSA such as floppy eyelid syndrome, normal tension glaucoma, primary open angle glaucoma, optic disc edema, and nonarteritic anterior ischemic optic neuropathy; most of them have possible vascular etiologies. During apneas, intermittent blood pressure alterations and hypoxemia might happen with repeated oxyhemoglobin desaturations [12],[13],[14],[15].

The retinal microvessels are similar in structure and function to the micovevessels in all body organs [16], yet, they have the advantage that they can be directly visualized and studied.

Increased tortuosity of the retinal vessels is found in participants with old age, high BMI, diabetes, hypertension, and hypoxia [17],[18]. In the current study, we examined the retinal microvasculature in patients having COPD, OSA, and OSA-COPD overlap syndrome of as a trial to evaluate the possible microvascular complications associated with these diseases.

The study was conducted on 60 participants divided into four groups: 15 patients with OSA, 15 patients with COPD, 15 patients with overlap syndrome, and 15 apparently healthy participants used as a control group.

The studied four groups were matched regarding age and sex. The highest smoking index was found in patients with overlap syndrome followed by the patients with COPD. BMI was significantly higher in OSA and overlap syndrome groups than the other two groups ([Table 1]).

Cigarette smoking by itself can cause systemic inflammation, and it contributes to a low grade of continuous systemic inflammation in vulnerable persons. Cigarette smoke causes oxidative stress and results in the local up-regulation of the synthesis of inflammatory cytokines [19]. Obesity is considered a state of low-grade systemic inflammation with multiple inflammatory peptides, and this may explain to an extent the obesity-associated comorbidities [20].

In the current study, ABG measurement showed that patients with overlap syndrome had the least pH, PO2, and SO2 and the highest PCO2 and HCO3 levels ([Table 3]).

Patients with OSA-COPD overlap syndrome have a greater risk of morbidity and mortality when compared with those with isolated COPD or OSA [21].

The current study demonstrated that AHI and O2 desaturation index were highest in overlap syndrome group followed by OSA group; the least O2 saturation at night was found in overlap syndrome group. STOP-BANG score showed a nonsignificant difference between OSA and COPD groups. Other comparisons showed significant differences. As regarding ESS score, a nonsignificant difference was demonstrated between OSA and overlap syndrome groups. Other comparisons showed significant differences ([Table 3]).

Severe nocturnal hypoxemia was observed in overlap syndrome than in isolated COPD or OSA [21].

On comparing patients with OSA and those with overlap syndrome, Chaouat et al. [22] found that patients with overlap syndrome did not differ from the rest of patients by their AHI, but nocturnal hypoxemia was more profound in overlap syndrome group than in isolated OSA group.

Visual acuity and IOP in the two eyes did not differ significantly among the studied groups ([Table 4]).

In this study, tortuosity of most retinal vessels was demonstrated to be higher in all patient groups compared with the control group ([Table 5]).

The mechanism of increased retinal vascular tortuosity in OSA depends on multiple factors. Apneas lead to significant intermittent surges in arterial blood pressure, increased venular pressure, and increased intracranial tension which can cause tortuosity owing to increased shear stress on vascular walls [23]. Moreover, patients with OSA may have hypercapnia which has been confirmed to be linked with increased retinal arteriolar and capillary blood flow [24]. The changes of retinal blood flow may be related to deficient cerebral autoregulation in OSA making ophthalmic vessels more liable to shear stress during pressure swings in arterioles and venuoles during apneas. These added factors may result in increased blood flow or blood volume in the retinal vessels causing tortuosity [25].

Chronic and recurrent hypoxia results in marked increase in monocytes and neutrophils, leading to widespread inflammation, and increase in the formation of inflammatory cytokines and levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein [26],[27].

Mohsenin et al. [1] photographed retinal vessels in nine patients with OSA and seven controls and concluded that patients with OSA had higher retinal vascular tortuosity compared with controls.

Samuel et al. [28] in their study conducted on 20 patients with OSA found that only 20% of them had retinal vascular changes, with no significant predilection for race, sex, length of diagnosis, or degree of obesity.

Chew et al. [29] found that patients with COPD had more microvascular retinopathy than other hospital patients and concluded that COPD is an independent risk factor for microvascular retinopathy after exclusion of other confounding factors as sex, blood pressure, smoking, and diabetes duration. Retinal arterioles and venules were wider in patients with COPD than other hospitalized patients [29].

McKay et al. [30] photographed retinal vessels in patients with COPD and proved that there was dilatation of both retinal arterioles and venules in comparison with controls. They also found that this dilatation was independent of age, sex, smoking, or blood pressure [30].

In the multiethnic study of atherosclerosis lung study, it was found that the caliber of retinal venules increased in COPD (3397 patients) and was inversely associated with the FEV1 and FEV1/FVC ratio independent of smoking, biomarkers of inflammation, diabetes, and other risk factors for microvascular disease [31].

Adžić-Zečević et al. [32] assessed retinal vascular alterations in patients with chronic respiratory insufficiency by direct and indirect ophthalmoscopy and fluoresceine angiography and found variable grades of vascular changes in those patients when compared with COPD and bronchial asthma patients without respiratory failure. They emphasized that direct effect of hypoxemia and hypercapnia on the wall of arterioles, venules, and capillaries results in a severe vasodilatation with raised permeability of the walls leading to clinically evident changes in the retina [32].

There was a significant negative correlation between tortuosity of all retinal vessels and both PO2 and O2 saturation. PCO2 and AHI correlated positively with tortuosity of all retinal vessels. Tortuosity of some retinal vessels correlated positively with O2 desaturation index, BMI, and smoking index, and negatively with minimum O2 saturation ([Table 6]).

Smoking has an effect on the blood vessels, and the pathogenesis may include oxidative stress, endothelial malfunction, hypoxemia, and abnormal autonomic regulation [33]. Hypercapnea has been linked to increased retinal arteriolar and capillary blood flow [24].In their study on 133 patients with severe OSA, Wang et al. [34] found that AHI correlated with retinal vascular abnormalities in the form of arteriolar to venular ratio. In patients with both OSA and diabetes, the AHI and level of oxygen desaturation have been correlated with the degree of diabetic retinopathy [35].

The importance of the current findings is that retinal vascular changes can preceed cardiovascular and cerebrovascular diseases and hence, can be used as a diagnostic and prognostic predictor for them [36]. It should be taken into consideration that compared with traditional noninvasive tests of cardiovascular diseases, studies on retinal vessels carry higher sensitivity [37].

Retinal vascular changes were found to be associated with the incidence and severity of hypertension, coronary heart disease, and cerebrovascular stroke, and increased mortality [38],[39].

Moreover, in light of the recent associations made between vein occlusion and OSA, it is possible that increased vascular tortuosity may result in turbulence or stasis of blood flow making these patients more vulnerable to retinal occlusive disease [40].


  Conclusion Top


Digital photographing of retinal microvasculature is an easy and reliable method for assessment of systemic microvasculature. Retinal vascular tortuosity occurs in OSA, COPD, and overlap syndrome. Retinal vascular tortuosity is correlated with ABG parameters, polysomnographic findings, smoking index, and BMI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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