Neuro-Ophthalmologic Manifestations of Obesity Hypoventilation Syndrome
Obesity Hypoventilation Syndrome
Obesity Hypoventilation Syndrome (OHS) is a sleep disorder characterized by hypoventilation both during sleep and wakefulness. Most commonly seen in patients with morbid obesity. OHS is associated with irregular breathing, elevated CO2, and obstructive sleep apnea (OSA).
OHS has been defined as the combination of obesity consisting of a body mass index (BMI) > 30 kg/m2), daytime hypercapnia obtained via arterial blood gas of a PaCO2 greater than or equal to 45mm Hg during wakefulness, and often the presence of sleep-disordered breathing such as OSA. 
The prevalence of OHS is approximately 0.15 to 0.3 percent in the general population in the United States. However, this prevalence varies greatly as BMI rises.  In patients with a BMI of 30 to 35 kg/m2, the prevalence of OHS is 8 to 12 %; in those with a BMI ≥ 40 kg/m2 the prevalence is 18 to 31%, and in those with a BMI ≥ 50, the prevalence is roughly 50%.
Obesity plays a significant role in the increasing prevalence of OHS in the United States due to the obesity epidemic. Those with increased BMI especially a BMI ≥ 50 are at additional risk for OHS.
OHS is common in those with severe Obstructive Sleep Apnea (OSA). OSA is characterized by collapse of the upper airway during sleep that leads to reduced oxygen saturation. Fat deposition around the upper airway and decreased lung volumes are distinct features that contribute to how obesity predisposes the upper airway to narrowing during sleep. Apnea-hypopnea index (AHI) scores ≥ 30 indicate severe apneas and are more likely to be associated with OHS.
Unlike OSA, males are not at increased risk compared to women for OHS. Presently, there is no race or ethnic-specific risk factor demonstrated to contribute to OHS. However, there continues to be speculation that African Americans may be at increased risk for OHS due to higher prevalence of morbid obesity in this demographic compared to others.
The pathophysiology of OHS is related to the following mechanisms: changes in the respiratory system due to obesity, changes to respiratory drive, and abnormalities in breathing during sleep.
Obesity related changes in the respiratory system lead to reduced lung volume, particularly a decreased functional residual capacity and decreased expiratory reserve volume. Excess adipose tissue exerts mechanical effects on the lungs by inhibiting full diaphragm range of motion and reducing lung compliance. The gas trapped due to premature airway closure generates positive end- expiratory pressure which leads to a ventilation/perfusion mismatch, with the development of partial collapse of the lower lobes of the lungs. Consequently, OHS patients tends to have a pronounced impairment in respiratory muscle strength and mechanics compared to patients with a similar BMI without OHS. This requires more work to breathe that needs to be compensated.
Alterations in respiratory drive arise due to the increased respiratory workload. Often times, patients will increase their respiratory drive to compensate for these changes and remain eucapnic. When this increased respiratory drive cannot be maintained, this allows for hypoventilation to occur. If hypoventilation continues to occur, then OHS leads to a secondary depression of respiratory centers and daytime hypercapnia.
Patients with OHS may experience OSA that consists of relatively long-lasting apneas with insufficient post-event ventilatory compensation that occur as a result of reduced activity in the respiratory centers.  This is an example of how the excess carbon dioxide associated with obstructive respiratory episodes while sleeping may contribute to hypoventilation.
The characteristic clinical presentation is a patient who complains of signs of upper airway obstruction during sleep, insomnia, and daytime hypersomnolence. These patients tend to be morbidly obese and present with severe sleep apnea with daytime hypercapnia as defined as PaCO2 > 45 mmHg obtained via arterial blood gas. Typically, there is a delay in diagnosis as OHS is diagnosed during a sleep study or pulmonary test around the 5th decade of life. OHS can also initially present when a patient reaches a high state of acuity such as during acute-on-chronic hypercapnic respiratory failure. Nocturnal obstructive breathing symptoms include snoring, gasping, hypoxemia during sleep, and nocturnal choking episodes. The major diurnal complaints are chronic fatigue, morning headaches, and dyspnea.
Assessing for OHS is important, in part due to its strong association with hypertension, metabolic disease, heart failure, coronary heart disease, pulmonary hypertension, polycythemia, and mood disorders.
While the precise mechanism of OHS related visual loss have not been completely defined, several studies have suggested an association between OHS and central retinal vein occlusion as well as papilledema.
Bilateral swelling of the optic disc that may be accompanied by hemorrhages and venous congestion. This is thought to occur due to the hypercapnia associated with OHS that leads to cerebral vasodilation which causes elevations in intracranial pressure and increased venous pressure at the optic head. Another hypothesis is that there are increases in intracranial pressure during sleep due to hypoxemia during apnea episodes in those with OSA.  Some have also considered that the compression of the transverse venous sinuses could be the cause of the elevated intracranial pressure.
Central Retinal Vein Occlusion
Patients with OHS may exhibit venous tortuosity and dilation, flame hemorrhages, and mild optics disc or macular edema in one or both eyes. Although the precise pathogenesis remains ill-defined, several hypotheses have been proposed: first, the hypoxemia-induced vasodilation of the central retinal artery may compress the central retinal vein due to their close proximity in the same adventitial sheath; second, the papilledema and elevated venous pressure in the optic nerve head could cause plasma leakage into the interstitial space leading to local hyper-viscosity which may exacerbate the development of RVO by slowing retinal circulation; and third, the respiratory effects of OHS may lead to sleep fragmentation in turn activating the sympathetic nervous system and causing an elevation in arterial blood pressure. Together these changes explain RVO development in patients with OHS.
Given the strong association between obesity hypoventilation syndrome and severe obstructive sleep apnea, clinicians should also suspect OHS when caring for patients that present with the diseases below as these are associated with severe OSA. FES and NAION are discussed in greater detail as they are commonly seen in Neuro-ophthalmology.
•Floppy eyelid syndromes (FES)
•Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)
•Central Serous Chorioretinopathy (CSCR)
Floppy Eyelid Syndrome (FES)
A condition where the upper eyelid becomes elastic and is easily folded upward. The prevalence of FES in patients with OSA is roughly 2%-33%. In patients with OSA, FES is hypothesized to be due to mechanical trauma to the eyelids during sleep. FES tends to be found commonly in obese patients due to their weak tarsus muscle. The affected eye is normally on the same side that the patient sleeps on. If both eyes are affected, it may suggest that the patient either interchanges sides or they sleep face down.
Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)
Sudden and painless unilateral vision loss, edema of the optic disk, and relative afferent pupillary defect. Patients with OSA are 16% more likely than patients without OSA to develop NAION. It is hypothesized that patients with OSA are susceptible to developing NAION due to the combination of hypoxia, oxidative stress, and increased intracranial pressure (ICP) during apnea episodes making it relevant to our understanding of OHS as well. 
A thorough Medical History and Physical examination are essential for diagnosing OHS.
A history consisting of a diagnosis of OSA, loud snoring, nocturnal choking episodes with witnessed apneas, excessive daytime sleepiness, morning headaches, hypoxemia while awake and more severe hypoxemia during sleep should cause one to suspect OHS.
Classic physical examination findings include an enlarged neck circumference, a crowded oropharynx, a prominent pulmonic component of the second heart sound on cardiac auscultation, and lower extremity edema.
|•Presence of hypoventilation during wakefulness (PaCO2 more significant than 45 mmHg) as measured by arterial PCO2, end-tidal PCO2, or transcutaneous PCO2.|
|•Presence of obesity (body mass index or BMI greater than 30 kg/m^2; more significant than the 95th percentile for age and sex for children).|
|•Hypoventilation is not primarily due to lung parenchymal or airway disease, pulmonary vascular pathology, chest wall disorder (other than mass loading from obesity), medication use, neurologic disorder, muscle weakness, or a known congenital or idiopathic central alveolar hypoventilation syndrome.|
OHS treatment tends to be directed to the underlying pathophysiological factors contributing to hypoventilation. Common therapies include weight loss, continuous positive airway pressure (CPAP), and tracheostomy.
Substantial weight loss either by conventional weight loss or by surgical therapy has been shown to improve lung function, respiratory muscle strength, and sleep-disordered breathing. Consequently, weight loss remains amongst first line therapies for managing OHS.
CPAP facilitates a physical pressure support that prevents collapse of the airway during sleep and has been shown to be effective in reducing symptoms of OHS. As a result, CPAP tends to be favored over noninvasive ventilation methods.
For more precise treatment of OHS, the patient’s characteristics should be taken into consideration when selecting the most appropriate mode of PAP therapy. For example, CPAP could be first-line treatment for OHS patients with concomitant severe obstructive sleep apnea as indicated by an AHI score ≥ 30. However, noninvasive ventilation (NIV) could be better suited as first-line therapy for OHS patients who present with milder forms of OSA or no apneas at all. Furthermore, if patients initially started on CPAP have no favorable response to therapy despite appropriate adherence to CPAP treatment, clinicians should consider changing them to NIV therapy.
Although it has fallen out of favor since the development of CPAP, tracheostomy can reduce obstructive events associated with sleep-disordered breathing as it requires the bypassing of the upper airway. While this procedure may improve alveolar ventilation and waking PaCO2, some patients may not return to a eucapnic state post tracheostomy as it does not affect the production of CO2 and muscle weakness characteristic of OHS. In present day, tracheostomy is reserved for clinical scenarios in which other treatment options have failed to improve symptoms in patients with OHS. 
Clinicians should recognize the clinical features of both OHS and OSA and their potential role in ophthalmic disorders including NAION, Papilledema, and CRVO.
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