Factors that predict visual disability in NMOSD are many: Study
Fndings may help ID those at high risk, who need more active treatment
Having optic neuritis — inflammation of the nerves that relay information between the eyes and the brain — as a first symptom of neuromyelitis optica spectrum disorder (NMOSD) is one of the factors that predict visual disability in up to five years, according to a study in China.
Other strong predictors include a severe first attack, a higher rate of relapses before immunosuppressant treatment, and a lack of ongoing immunosuppressive treatment.
The findings may help doctors identify those at high risk for visual disability and who “need more active treatment and management to avoid unfavorable outcomes,” the researchers wrote in “Visual disability in neuromyelitis optica spectrum disorders: prognostic prediction models,” which was published in Frontiers in Immunology.
NMOSD occurs when the immune system mistakenly attacks and damages the optic nerves and the spinal cord. These attacks are most commonly driven by antibodies against a protein called aquaporin-4 (AQP4) and lead to problems with vision and movement. Each attack or relapse causes new damage that builds up over time, sometimes leading to vision loss and paralysis.
“Attacks of NMOSD can result in the accrual of severe visual disability over time,” the researchers wrote, adding data suggest nearly half of patients have vision loss in one or both eyes within five years. As such, “recognizing the risk factors for poor prognosis in the early stages is vital for preventing potential disability.”
Identifying predictors of visual disability in NMOSD
To identify predictors of visual disability in one, three, or five years, researchers in China reviewed the medical records of 640 patients who visited their medical center between January 2015 and January 2022. All had been tested for anti-AQP4 antibodies and had follow-up data covering at least six months.
The patients’ mean age at disease onset was 38 (range, 8-76). Most were female (87.3%) and tested positive for anti-AQP4 antibodies (89.4%). They were followed for a median of 68 months (about 5.7 years), during which 70.6% received maintenance treatment with immunosuppressants to help prevent relapses.
During follow-up, 161 patients (25.2%) developed visual disability, defined as blindness in the worst eye for more than six months.
These patients were significantly more likely to have optic neuritis as a first symptom and a severe first attack than those without visual disability. A significantly greater proportion in the disabled group also tested positive for anti-AQP4 antibodies and had more frequent relapses before immunosuppressive treatment.
The researchers used two statistical methods to identify predictors of visual disability. The first, called Lasso regression, selects the most important features in a dataset by eliminating the least relevant ones.
Using this method, the team isolated four predictors: optic neuritis at disease onset, higher annual relapse rate prior to treatment, lack of maintenance immunosuppressive treatment, and a severe first attack.
The second method, multivariate Cox regression, helps understand how each predictor affects risk while accounting for the influence of other variables. This analysis identified the same predictors as Lasso plus two additional ones — testing positive for anti-AQP4 antibodies and older age at the onset of disease.
Patients who had optic neuritis as a first symptom were nearly three times as likely to have visual disability later in life as those who didn’t. Having an initial severe attack was associated with a 93% higher risk of vision loss and a higher relapse rate before immunosuppressive therapy increased such risk by 85%. Being on immunosuppressants reduced the risk by 90%.
Regarding the new predictors, anti-AQP4 antibody positivity was linked to a nearly three times higher risk of vision loss and “every additional [one] year of onset age increased the risk of visual disability by 1%,” wrote the researchers, who developed two models, represented as a type of diagram called a nomogram, to estimate how likely it is for someone with NMOSD to have visual disability in one, three, or five years.
They calculated risk scores for each patient and determined a cutoff point to distinguish those of high and low risk. The models were relatively accurate at predicting future visual disability, meaning they may help doctors estimate a patient’s risk.
“This study reported predictors of visual disability and generated nomograms,” the researchers wrote, adding that, for patients with these predictors, “immunosuppression therapy needs to be performed at an early stage.” More research that follows patients over time is needed to confirm the findings, they said.