Underweight, but Not Obesity, Linked to Glaucoma Progression

A higher body mass index (BMI) was significantly associated with slower rates of retinal nerve fiber layer change among patients with glaucoma, while those with underweight had significantly faster rates of structural loss, according to a retrospective cohort study.

At a mean follow-up of 4.7 years, patients with higher BMI had slower rates of retinal nerve fiber layer change (0.014 μm/year slower per each 1 kg/m² higher, 95% CI 0.003-0.246, P=0.011) versus those with normal weight in an adjusted analysis, reported Felipe Medeiros, MD, PhD, of Bascom Palmer Eye Institute at the University of Miami, and colleagues.

Underweight patients had significantly faster rates of retinal nerve fiber layer loss (-0.768 µm/year, P=0.002) compared with patients with normal weight, they noted in the British Journal of Ophthalmology.

In other findings, there were no significant associations between tobacco and alcohol use and glaucoma progression (P=0.473 and P=0.471, respectively).

Victoria Tseng, MD, PhD, of the University of California Los Angeles, who wasn't involved with the study, told MedPage Today that the finding that links underweight to more progression appears to be the most significant. However, "the magnitude of change is not large," she said. "Based on the findings, if someone were to gain enough weight to be classified as normal weight rather than underweight, it would take several years for this to produce a clinically significant difference in the risk of glaucoma."

As the study authors noted, "compelling research" has linked obesity, smoking, and alcohol use to diabetic retinopathy and age-related macular degeneration, but there's no consensus on any connection to glaucoma. All three of these factors have been linked to higher risk of glaucoma, they added, but studies have also suggested that heavy smoking and obesity actually have protective effects.

"One of the challenges is the measurement of total amount of tobacco and alcohol consumed, as this is generally based on recollection of the participant and is subject to error and bias," Tseng said.

It's not unusual for studies to link obesity to protective effects against some diseases. For years, researchers have tried to understand or debunk the "obesity paradox" -- the apparent link between excess weight and lower mortality in heart disease and some other medical conditions.

As for underweight, a 2021 report noted that "thinness is an overlooked phenomenon in terms of causality, health risks and associated pathologies, which are much less explored compared to those associated with overweight and obesity."

In this study, the apparent protective effect of obesity vanished in the stratified analysis and in an analysis in which 20 underweight patients were excluded. In that analysis, "the coefficient for BMI remained of similar magnitude (0.011 μm/ year slower per 1 mg/kg² higher), although it did not reach statistical significance (P=0.053)," Medeiros and team wrote. "Of note, the small magnitude of the coefficient indicates a very small effect which would represent a small 0.05 μm/year difference for a 5 mg/kg² change."

As for the link between underweight and glaucoma progression, the researchers suggested that a low BMI may be a sign of poor health in some cases. "It is possible that severely underweight subjects included in our study may have had a higher prevalence of serious coexisting systemic disorders that led to severe weight loss and could also affect risk of glaucoma deterioration."

Tseng noted that the study used valid research methods and had a large study population. "The measurement of glaucoma progression through changes in the retinal nerve fiber layer thickness on optical coherence tomography scans is practical and based on a clinical tool that is routinely used in the management of glaucoma patients," she said.

As for the lack of a link between tobacco/alcohol consumption and glaucoma progression, she pointed out that "it's possible that there are microscopic amounts of damage to the optic nerve that do not translate to a clinically significant difference in the risk or severity of glaucoma. It is also possible that tobacco and alcohol do not preferentially damage the optic nerve as much as they do other parts of the body," such as the lungs in tobacco users and the liver in alcohol users.

For this study, Medeiros and colleagues tracked 2,839 eyes of 1,584 patients with glaucoma from the Duke Ophthalmic Registry. Mean age was 67, 56.4% were women, 59.7% were white, and 32.4% were Black. Mean intraocular pressure during follow-up was 15.7 mm Hg. Of the patients, 34.3% had obesity (a BMI of 30 or higher), 43.2% had ever smoked, and 54.5% had ever consumed alcohol.

Patients had at least two spectral-domain optical coherency tomography tests over a minimum 6-month follow-up. Self-reported history of alcohol and tobacco consumption was taken from electronic health records.

As for study limitations, the researchers noted that tobacco/alcohol use was based on self-reported data, and there was no information available on when patients stopped smoking. In addition, the study relied solely on BMI as a measurement of obesity. They also pointed out that only two of the 20 underweight patients were men, and "the hazardous effect of lower BMI was not seen" in them (P=0.340).

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