Obesity, and an unhealthy metabolic status in general, is associated with ocular motor CNP.  Photo: Getty Images.

Third, fourth and sixth ocular motor cranial nerve palsies (CNP) can have a significant impact on patients’ quality of life by producing diplopia and, even more seriously, by heralding cerebrovascular ischemic events. According to recent studies, there’s an association between ocular motor CNP and risk of subsequent stroke in both the general population and among those with diabetes. Because obesity prevalence is increasing globally and is a known risk factor for cardiovascular diseases and mortality, researchers recently assessed possible associations between obesity and CNP, concluding that obesity raises the risk of such events (Table 1).

The team analyzed a cohort of more than four million adults (ages 20 to 90) within South Korea’s National Health Insurance Service who attended health checkups between January 1 and December 31, 2009. These patients were followed through December 31, 2017. During this follow-up period, a total of 5,835 individuals were diagnosed with CNP. The researchers reported that general obesity (defined as a BMI ≥25kg/m2) was associated with an increased risk of CNP, and abdominal obesity (defined as a waist circumference ≥90cm in men and ≥85cm in women) also demonstrated increased hazard ratios. Overall, when compared with the cohort without either type of obesity, those with only general obesity, those with only abdominal obesity and those with both types had an increased risk of CNP.

“BMI and waist circumference had positive linear associations with the risk of ocular motor CNP after adjusting for potential confounders such as age and sex and health behaviors such as drinking, smoking and physical activity,” the researchers wrote in their paper. “The trend was still significant even after the additional adjustment for comorbidities such as diabetes, hypertension and dyslipidemia. General obesity and abdominal obesity were associated with a 1.25- and 1.24-times increased risk of ocular motor CNP, respectively.”

“Obesity is one of the major components of metabolic syndrome and an established risk factor for type 2 diabetes mellitus,” they continued. “Considering the high intercorrelation between the components of metabolic syndrome, adjustments for hypertension, diabetes and dyslipidemia might lead to an underestimation of the harmful effect of obesity on ocular motor CNP.”

The researchers say the precise mechanism of how obesity increases one’s risk of ocular motor CNP is unknown, but there are several potential ways in which it affects the development of ocular motor CNP:

  1. Obesity is associated with hypertension, diabetes and hyperlipidemia. These are known risk factors for ocular motor CNP caused by microvascular ischemia.

  2. Experimental and clinical research demonstrates that obesity induces a chronic inflammatory state, which affects neuroinflammatory processes, contributing to neurodegeneration.

  3. Caloric excess increases circulation of chylomicron-derived, very low-density lipoprotein triglycerides, which are hydrolyzed to long-chain fatty acids. These lipids are deposited along blood vessels, resulting in atherogenesis. All organs in the body also experience increased lipid load. Animal studies have shown that high-fat diets contribute to inflammatory mediators that can injure and penetrate the blood-nerve barrier and activate neurogenic inflammation. Lipid overload can also stress the nervous system and alter mitochondrial ATP, which is necessary for normal nerve physiology.

The researchers explained that in addition to obesity, an unhealthy metabolic status in general can affect the incidence of ocular motor CNP in people with normal body weight. Because the finding of both general and abdominal obesity demonstrated increased risk in the study, the researchers also suggested that the combined presence could have a “synergistic effect” on the development of ocular motor CNP.

“Obesity may be correlated with ocular motor CNP; however, it’s also a general indicator of suboptimal health,” the researchers wrote. “Ocular motor CNP is one of the various complications that can accompany obesity. However, at the same time, CNP may also suggest that other serious complications such as stroke are imminent or may occur within years in some patients. Considering these complex factors general, abdominal and combined obesity together along with metabolic components, we suggest that it would be possible to select high-risk patients and attempt more aggressive medical interventions.”

Table 1. Obesity and Risk of CNP

Obesity Rate (2015-2016)
Incidence of CNP (per 100,000 person-years) 

GeneralAbdominalThird Fourth Sixth
Korea 34.2%20.8%3.173.744.66 
United States 39.8%58.9%  4.00 5.73 11.30


Choi DD, Han K, Park K, et al. Association of obesity and incidence of third, fourth, and sixth cranial nerve palsies. Am J Ophthalmol. September 17, 2021. [Epub ahead of print].