The pathogenesis of neurodegeneration in OSA syndrome is unclear. Intermittent upper airway obstruction in OSA patients during sleep can increase carbon dioxide levels while decreasing oxygen levels, thereby reducing the oxygen saturation during a variable period of sleep. These alterations induce oxidative stress, and lead to increased vascular resistance and endothelial dysfunction. Hypoxia and hypercapnia episodes cause autonomic, hemodynamic, and neurorendocrine changes.
28,29 Obstructive sleep apnea syndrome is associated with neurovascular disease, cardiovascular disease, arterial hypertension, pulmonary hypertension, arrhythmia, and other systemic disorders.
30
The oxygenation-reoxygenation process in OSA syndrome can compromise normal vascularization and perfusion of the ONH similar to glaucoma, based on the vascular theory proposed by Anderson.
31 This theory suggests that the damage to the ONH in glaucoma is caused, at least in part, by persistent or temporary ischemia. Failure of the blood supply from the posterior ciliary arteries to the short posterior ciliary arteries could lead to nonperfusion of the anterior part of the ONH and neuronal ischemia. The affected ONH microcirculation would interfere with axonal nutrition and axoplasmic flow. Calvo et al.
32 reported that abnormal retrobulbar blood flow velocities measured by color Doppler ultrasound may be a risk factor for conversion to glaucoma. On the other hand, Lin et al.
33 recently suggested that OSA is associated with an increased risk of a subsequent diagnosis of open-angle glaucoma during a 5-year follow-up period after the diagnosis of OSA.
We hypothesized that these vascular phenomena could affect VF and ONH morphology in OSA patients and that such changes could be measured by SAP and OCT, respectively. Retinal sensitivity was reduced in OSA patients compared with the control group, although we detected no significant differences in the RNFL thickness measurements. The topographic correspondence between VF regions and RNFL thickness in humans is moderate in glaucoma patients due to the high variability of normal human ONH morphology and the intertest variability of SAP.
34–36 The agreement between the SAP and OCT results in OSA patients is expected to be similar to that in healthy individuals.
34–38
Previous studies using different imaging techniques to measure RNFL thickness in OSA patients described contradictory results.
39–44 Some studies reported decreased RNFL thickness in OSA patients, in contrast to the present results,
39,40,42 whereas others found no correlation between RNFL thickness and AHI.
42 Still others observed a significant decrease in the RNFL thickness in patients with severe OSA.
44 All of these findings, however, were based on different imaging technologies than used in the present study. We measured the RNFL thickness with a spectral-domain OCT (Cirrus), whereas time-domain OCT
40,41,43 or scanning laser polarimetry
39,42 were used in the previous studies.
If outcomes of VF or OCT differed between groups, these parameters could potentially be used as biomarkers for neuronal damage in OSA patients. Although we detected no changes in the peripapillary RNFL thickness measured by OCT, there were differences in the retinal sensitivity and VF indices. Patients with OSA exhibited diffuse decreased retinal sensitivity without localized VF defects typical of other pathologies such as glaucoma. This generalized reduction of the threshold values, particularly in the peripheral VF, could be explained by diffuse vascular damage to the retinal ganglion cells, causing axonal loss and VF depression. This injury to the retinal ganglion cells may lead to dysfunction of the visual pathway that could be identified by a functional test, such as SAP, while the anatomy is relatively unaffected and therefore undetected by a structural test, such as OCT. Moreover, OSA patients (especially those with more advanced disease) may have experienced at least one apnea/hypopnea event during the VF examination, which could decrease attention and impair testing ability, resulting in reduced retinal sensitivity, even when the SAP reliability criteria were maintained within normal limits.
Quantitative variables MD, PSD, and VFI could be used to monitor the progression of the disease, treatment with oxygen therapy, or noninvasive mechanical ventilation.
45 The main criterion to begin treatment with continuous positive airway pressure (CPAP) is a graduated severity of OSA syndrome (moderate and severe). Thus, any changes detected in the VF could help to support the decision to begin CPAP in OSA patients.
Huseyinoglu et al.
44 also reported worse MD and PSD (Octopus perimetry) in OSA subgroups compared to a control group. Lin et al.,
40 however, found no differences in the MD of SAP (30-2 strategy) between OSA patients and healthy controls. Different study designs and populations, inclusion and exclusion criteria, tests performed, and the level of OSA damage make it difficult to compare the results among several studies.
A limitation of the present study was that the control group did not undergo an overnight sleep study and we assumed that they had no apnea/hypopnea events per hour. Ideally, they should have also undergone a polysomnographic evaluation for one night, but this evaluation is costly and we could not justify its inclusion in the study protocol because the criteria used to select the control group minimized the possibility of including an OSA patient by chance (exclusion criteria for the control group: obesity and symptoms related to OSA). Nevertheless, if all controls were chosen according to a strictly normal sleep study, we would have selected a “super-healthy” control group. In addition to the effect size (difference between groups), these factors would probably lead to a larger retinal sensitivity reduction than the one observed.
In the present study, OCT did not demonstrate neurodegenerative changes in OSA patients, but retinal sensitivity was significantly reduced in OSA patients compared with healthy subjects. Given the issues related with subjective perimetry, studies employing objective functional testing (e.g., electrophysiology test) are warranted, as well as further prospective longitudinal studies to clarify the role of VF and OCT as a neurodegenerative marker in OSA syndrome.
Clinicians should be aware that OSA patients may have nonglaucomatous VF defects, which should be differentiated from true glaucomatous optic neuropathy.