Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Effect of Therapy on Choroidal Thickness in Patients With Obstructive Sleep Apnea Syndrome

Hasim Uslu, MD; Ayşe Yağmur Kanra, MD; Gulgun Cetintas, MD; Mehmet Gurkan Tatar, MD

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate effect of continuous positive airway pressure (CPAP) therapy on choroidal thickness in patients with obstructive sleep apnea syndrome (OSAS).

PATIENTS AND METHODS:

Thirty distinct eyes of 30 patients with OSAS were evaluated right before and 12 months after CPAP treatment in this prospective observational study. Choroidal thickness was measured at the fovea and with periodic intervals of 500 µm from the foveal center in both temporal and nasal directions using spectral-domain optical coherence tomography in enhanced depth imaging mode.

RESULTS:

The patients' mean age was 45.33 years ± 7.74 years, and there were eight females and 22 males. After CPAP therapy, the choroidal thicknesses were increased significantly at the subfoveal, 500 µm nasal to the fovea, 500 µm temporal to the fovea, and 1,000 µm temporal to fovea points (P < .05). However, none of retinal macular parameters were significantly different in statistical terms between the two measurements (P > .05).

CONCLUSIONS:

CPAP therapy had a significant influence on choroidal thickness in patients with OSAS, providing an increase in choroidal thicknesses after 12 months. The determination of an increase in choroidal thickness may be useful to reveal the effects of CPAP therapy and also may be one of the mechanisms to improve choroidal function.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:846–851.]

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate effect of continuous positive airway pressure (CPAP) therapy on choroidal thickness in patients with obstructive sleep apnea syndrome (OSAS).

PATIENTS AND METHODS:

Thirty distinct eyes of 30 patients with OSAS were evaluated right before and 12 months after CPAP treatment in this prospective observational study. Choroidal thickness was measured at the fovea and with periodic intervals of 500 µm from the foveal center in both temporal and nasal directions using spectral-domain optical coherence tomography in enhanced depth imaging mode.

RESULTS:

The patients' mean age was 45.33 years ± 7.74 years, and there were eight females and 22 males. After CPAP therapy, the choroidal thicknesses were increased significantly at the subfoveal, 500 µm nasal to the fovea, 500 µm temporal to the fovea, and 1,000 µm temporal to fovea points (P < .05). However, none of retinal macular parameters were significantly different in statistical terms between the two measurements (P > .05).

CONCLUSIONS:

CPAP therapy had a significant influence on choroidal thickness in patients with OSAS, providing an increase in choroidal thicknesses after 12 months. The determination of an increase in choroidal thickness may be useful to reveal the effects of CPAP therapy and also may be one of the mechanisms to improve choroidal function.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:846–851.]

Introduction

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized by recurrent episodes of upper respiratory tract obstructions during sleep that lead to episodes of intermittent hypoxia.1 Patients with OSAS have many ocular complications, including floppy eyelid syndrome, glaucoma, papillary edema, and central serous chorioretinopathy.2,3 OSAS is known as an important risk factor for vascular diseases, whereas the pathophysiological mechanism of impact has not been illuminated. In patients with OSAS, a reduction in the ventilatory drive caused by hypoxia and hypercapnia can be effective in development of a decrease in partial pressure of oxygen (pO2) and an increase in partial pressure of carbon dioxide (pCO2).4 Hypoxemia results in increased production levels of the vasoconstrictor endothelin. The endothelial cells also produce nitric oxide, known as a vasodilator.5,6 As a result, the endothelium-mediated vasodilator response is markedly impaired. The underlying factor in diseases associated with OSAS is due to the increased sympathetic nerve activity and vascular endothelial dysfunction caused by oxidative stress and reduced nitric oxide (NO) production.7 Additionally, autonomic vascular dysregulation is shown in some studies.8 Continuous positive airway pressure (CPAP) therapy improves vascular functions and reduces autonomic function abnormalities in OSAS patients.9 In a study, giving up the CPAP for 2 weeks in patients with OSAS undergoing long-term therapy showed that the morning heart rate increased significantly on the first day and continued rising over time without the therapy.10 Also, CPAP therapy decreases daytime blood pressure with hemodynamic changes associated with an increased NO production.11

The recent developments in optical coherence tomography (OCT) technologies have allowed more detailed choroid assessment, especially with the new technique called enhanced depth imaging OCT (EDI-OCT). There is an increase in the number of choroidal studies using EDI-OCT.12 However, the literature contains limited data on choroidal thickness evaluation in CPAP treated patients. In this study, we aimed at evaluating the effects of CPAP therapy on retinal macular and choroidal thickness in patients with OSAS using EDI-OCT.

Patients and Methods

Design and Patients

This prospective, observational study was performed at our Department of Ophthalmology from May 2013 to December 2016. Patients were recruited from the sleep center of Sureyyapasa Chest Diseases Hospital. Prior to the study, the ethics committee of Fatih University approved the study protocol. All procedures were performed according to the tenets of the Declaration of Helsinki. All patients provided written informed consent.

All patients underwent a complete ophthalmic examination that included best-corrected visual acuity (BCVA) testing using Snellen charts, slit-lamp biomicroscopy, refraction, intraocular pressure (IOP) measurement with Goldmann applanation tonometry, a dilated funduscopic examination, axial length measurement by the IOLMaster (Carl Zeiss Meditec, Dublin, CA), and central corneal thickness measurement with the Pentacam (Oculus, Wetzlar, Germany).

The inclusion criteria for all participants consisted of BCVA of 8/10 or better, refractive error (in spherical equivalent) within ±3 diopters, intraocular pressure under 21 mm Hg, and without retinal or optic disc anomalies. The exclusion criteria were: patients with OSAS with associated comorbidities (including cardiovascular disease, metabolic syndrome, and diabetes), glaucoma, chronic uveitis, optic neuropathy, history of any ocular surgery, central apnea, and history of any neuro-degenerative disease.

Polysomnography (PSG)

All patients with OSAS underwent full-night polysomnography (Comet-PLUS, Grass Technologies, West Warwick, RI), which recorded the following parameters: electrocardiogram; central, temporal, and occipital electroencephalogram; bilateral electro-oculogram; sub-mental and anterior tibialis electromyogram; nasal air flow (using a nasal cannula and pressure transducer); naso-oral air flow (using a thermistor); and respiratory effort (using chest and abdominal piezoelectric belts). Oxygen saturation was monitored using a pulse oximeter. Apneas were defined in compliance with the international standards that were established by the Report of an American Academy of Sleep Medicine Task Force published in 1999.13 OSAS is categorized as mild, moderate, and severe according to the apnea-hypopnea index (AHI) values of five to 14 events per hour, 15 to 29 events per hour, and 30 events or more per hour, respectively.

CPAP Titration

CPAP titration was done using a mask and apparatus (VPAP Tx; RESMed, San Diego, CA). The initial pressure was set at 4 cm H2O in the CPAP titration. CPAP levels were increased gradually until all abnormal respiratory events ended. The appropriate pressure for the patient was determined observing that no abnormal respiratory events, snoring vanished, and no arousals in different sleep stages and positions. The pressure is increased and decreased, monitoring for abnormal sleep events, arousals, and snoring until the effective CPAP pressure was determined. CPAP compliant was accepted if the device was used for at least 4 hours per night and least 20 hours per week. Entire analysis was done according to the guidelines of the American Academy of Sleep Medicine.14

OCT Measurements

All participants with undilated pupils were examined with the Cirrus HD-OCT 4000 (Carl Zeiss Meditec, Dublin, CA). The high-definition five-line raster scan of the EDI pattern was used to obtain high-quality images of the macular choroid. Only those images with signal strengths exceeding seven were selected for the study. The scan pattern is a 6-mm line consisting of 4,096 A-scans. EDI-OCT measurement has been previously described.12 Choroidal thickness was measured perpendicularly from the outer border of the hyperreflective retinal pigment epithelium (RPE) to the inner border of the choroidal scleral junction at seven locations: the foveal center (SFCT) and at 500 µm intervals from the center to the nasal (N 500, N 1,000, N 1,500) and temporal directions (T 500, T 1,000, T 1,500), using Cirrus manual measurement tools (Figure 1). The average values of two different measurements made by two masked physicians was taken; the differences between readings of the masked physicians were found to be within 10% of the mean. All measurements were performed between 8:00 AM and 2:00 PM because of diurnal variation.15–16 The macular cube (512 × 128) protocol was used to acquire retinal macular thickness measurements. A mean retinal thickness map of nine zones from the internal limiting membrane to the RPE was automatically measured. The standard retinal subfields are central, inner superior, inner nasal, inner inferior, inner temporal, outer superior, outer nasal, outer inferior, and outer temporal. The second OCT examination after 12 months of treatment were evaluated similarly.

Optical coherence tomography scan showing the choroidal thickness at seven locations (A) and fundus five-line raster photograph (B).

Figure 1.

Optical coherence tomography scan showing the choroidal thickness at seven locations (A) and fundus five-line raster photograph (B).

Statistical Analyses

SPSS statistical software, version 18.0 for Windows (SPSS, Chicago, IL), was used for statistical analysis. Only the one eye for analysis was randomly selected. The normality of distribution of the study sample was assessed with the Shapiro–Wilk test. The measured data are presented as the means ± standard deviations for normally distributed variables. The measurements between the before and after CPAP treatment were compared using the paired sample t-test. Only P values of less than .05 were considered statistically significant.

Results

A total of 35 patients were recruited consecutively in the study, but five patients were excluded due to discontinued CPAP treatment and lack of communication treatment with patients. Consequently, 30 eyes of 30 patients with OSAS (eight female, 22 male) were included in the study. The demographic and clinical characteristics of the subjects are shown in Table 1. The mean age of the patients was 45.33 years ± 7.74 years, ranging between 38 years and 55 years. The mean values of AHI, mean SpO2, lowest SpO2, and ODI were 43.94 ± 29.89 (seven to 116.9) times/hour, 91.47% ± 4.58% (75% to 97%), 74.36% ± 11.91% (30% to 86%), and 43.99% ± 31.65% (3.4% to 117%), respectively.

Demographic, Polysomnographic, and Ophthalmologic Characteristics of Subjects

Table 1:

Demographic, Polysomnographic, and Ophthalmologic Characteristics of Subjects

The comparison of the mean choroidal thickness measurements between the before and after CPAP treatment is presented in Table 2. CPAP therapy caused a significant increase in the choroidal thickness, compared with baseline, at measurement points of SFCT, N 500, T 500, and T 1,000 (P < .05 for all). However, the changes seen in the choroidal thickness at three measurement points were not statistically significant after CPAP treatment (P > .05).

Changes of Choroidal Thickness After Continuous Positive Airway Pressure Treatment

Table 2:

Changes of Choroidal Thickness After Continuous Positive Airway Pressure Treatment

The comparison of retinal macular thickness parameters for before and after the CPAP therapy is presented in Table 3. The reduction seen in the retinal macular thickness was not statistically significant after CPAP treatment (P > .05). The changes in choroidal thickness at each interval for before and after the CPAP therapy were presented in Figure 2.

Changes of Retinal Macular Thickness Measurements After Continuous Positive Airway Pressure Treatment

Table 3:

Changes of Retinal Macular Thickness Measurements After Continuous Positive Airway Pressure Treatment

The differences between before and after treatment in choroidal thickness values.

Figure 2.

The differences between before and after treatment in choroidal thickness values.

Discussion

The goal of this study was to assess the presence of thickness changes in the choroidal of patients with OSAS after at least 12 months of CPAP treatment. OSAS is characterized by intermittent upper airway obstruction during sleep, with concurrent hypoxia and hypercapnic acidosis. Recurrent hypoxia and reperfusion episodes can suppress circulating nitric oxide levels, which have potent effects on endothelial relaxation.17 On the other hand, hyperoxia causes vasoconstriction of retinal vessels and reduces blood flow, but hypoxia and hypercapnia are effective in the opposite way.18 Although the influence of O2 and CO2 is well-known on retinal circulation, it is not fully understood for choroidal circulation.19 In patients with OSAS, nitric oxide has been implicated in the pathogenesis of vascular disease that causes impaired vasodilatation.20

The choroid circulation of the eye is one of the highest rates of blood flow in the human body. The choroid has several important functions, including the production of oxygen and nutrients to the avascular outer retinal layers.21 Consequently, a structurally and functionally normal choroidal vasculature is essential for the function of the retina. Recently, several studies using spectral-domain OCT reported that there is a remarkable relationship between OSAS and choroidal thickness. Xin et al. demonstrated that the subfoveal and nasal choroidal thickness was thinning in severe OSAS patients.22 Karalezli et al. reported that the decreased choroidal thickness of patients with severe OSAS might be related to the autonomic dysregulation associated with this disease.23

CPAP is still recognized as the gold standard treatment and is highly effective in controlling symptoms, improving quality of life and reducing the clinical sequelae of sleep apnoea.24 The improvement in sympathetic activity is one likely mechanism for the changes in blood pressure seen with CPAP treatment. CPAP therapy effectively reduces the excessive sympathetic activity induced by hypoxia, and regulates sympathovagal balance.25 In addition, previous studies have reported that long-term CPAP therapy can decrease the risk of developing cardiovascular disease and can effectively reduce blood pressure.26 The literature concerning the association of CPAP therapy and systemic abnormalities revealed positive results. However, the relationship between CPAP therapy and ocular manifestations is unclear. Taken into account together these results suggest that the effects of OSAS on choroidal thickness could be decreased with CPAP therapy. Our data reveal that CPAP therapy causes an increase in choroidal thickness after 12 months in the patients with OSAS. In summary-based studies published previously, the effects of CPAP therapy was the regulation of the sympathetic nerve system activation and endothelial dysfunction. We can consider that the reason for the increase of CT is the effects of CPAP therapy. We suppose that this result is also due to the regulation of the sympathetic nerve system activation and endothelial dysfunction.

There are several important strengths of our study. Firstly, because the association between OSAS and multiple comorbidities can be synergistic effects on measurement parameters, we investigated effect of CPAP therapy on choroidal thickness in OSA patients without associated comorbidities (including cardiovascular disease, metabolic syndrome, and diabetes). Secondly, according to our knowledge, this study was the first to evaluate the changes of CPAP therapy on the choroidal thickness in patients with OSAS using the EDI-OCT. However, our study has several limitations. The main shortcoming of our study is that the study is not have a normal control group composed of subjects without OSAS. Additionally, the effect of the CPAP treatment on choroidal thickness may have been influenced by ocular blood flow changes, and we did not undertake a blood flow analyzer to document any changes of structural or functional. Until now, automatic choroidal segmentation is not available, and the measurements were taken manually, which is a source of bias. These can be achieved in a further study based on the preliminary findings of study.

In conclusion, CPAP therapy had a significant influence on choroidal thickness in patients with OSAS, providing an increase in choroidal thickness after 12 months. The determination of an increase in choroidal thickness may be useful to reveal the effects of CPAP therapy and also may be one of the mechanisms to improve choroidal function.

References

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Demographic, Polysomnographic, and Ophthalmologic Characteristics of Subjects

Subjects (n = 30)Mean ± SD(Minimum / Maximum)
Eye (Right / Left)16/14-
Sex (Male / Female)22/8-
Age, Years (Range)45.33 ± 7.74(38 to 55)
IOP, mm Hg15.90 ± 1.92(14 to 19)
CCT, µm532.10 ± 31.78(462 to 587)
Axial Length, mm23.22 ± 0.84(21.15 to 25.37)
BMI, kg/m231.44 ± 5.72(23 to 46)
AHI (Times / Hour)43.94 ± 29.89(7 to 116,9)
Mean SpO2 (%)91.47 ± 4.58(75 to 97)
Lowest SpO2 (%)74.36 ± 11.91(30 to 86)
ODI (%)43.99 ± 31.65(3.4 to 117)

Changes of Choroidal Thickness After Continuous Positive Airway Pressure Treatment

Before CPAPAfter CPAP
Thickness (µm)Mean ± SDMean ± SDP Value
N 1,500219.70 ± 42.90226.40 ± 42.570.37
N 1,000242.97 ± 46.67248.47 ± 42.800.49
N 500258.40 ± 42.13277.77 ± 43.660.01
SF292.13 ± 46.82313.57 ± 46.410.01
T 500251.97 ± 49.64273.80 ± 42.360.01
T 1,000228.67 ± 51.22244.07 ± 41.120.03
T 1,500200.33 ± 59.06215.73 ± 54.570.23

Changes of Retinal Macular Thickness Measurements After Continuous Positive Airway Pressure Treatment

Before CPAPAfter CPAP
Thickness (µm)Mean ± SDMean ± SDP Value
Central263.33 ± 20.58258.40 ± 22.13.18
Inner Temporal318.37 ± 14.41317.23 ± 13.95.63
Outer Temporal267.57 ± 12.20267.27 ± 11.97.87
Inner Nasal336.00 ± 17.12333.27 ± 14.81.22
Outer Nasal305.40 ± 17.61301.90 ± 24.74.41
Inner Superior333.47 ± 16.78332.03 ± 15.82.50
Outer Superior284.60 ± 22.68284.03 ± 12.70.88
Inner Inferior327.17 ± 21.88329.50 ± 14.77.57
Outer Inferior274.63 ± 14.59273.90 ± 11.06.78
Authors

From Sultanbeyli World Eye Hospital, Department of Ophthalmology, Istanbul, Turkey (HU, AYK); Süreyyapaşa Thoracic Diseases and Thoracic Surgery Hospital, Istanbul, Turkey (GC); and Çağın Eye Hospital, Department of Ophthalmology, Istanbul, Turkey (MGT).

The authors report no relevant financial disclosures.

Address correspondence to Ayşe Yağmur Kanra, MD, Sultanbeyli World Eye Hospital, Hasanpaşa mah. Fatih Blv. No: 41, 34920 Istanbul/Turkey; email: ygurturk@yahoo.com.

Received: March 22, 2018
Accepted: October 02, 2018

10.3928/23258160-20181101-05

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