Photo Credit: Naeblys

Comorbidities worsen outcomes and optic neuritis-related neurodegeneration in multiple demyelinating disorders, including NMOSD and AQP4-NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD) are all conditions in which optic neuritis (ON) occurs frequently, according to research published in the European Journal of Neurology. Further, comorbidities are common in NMOSD, MOGAD, and DN-NMOSD, and the development of ON often leads to severe neurodegeneration and blindness.

Terry J. Smith, MD, and colleagues aimed to determine the impact of comorbidities on the course of aquaporin-4 antibody-positive NMOSD (AQP4 NMOSD), MOGAD, and DN-NMOSD, as well as their association with ON outcomes. The study team used optical coherence tomography (OCT) to examine retinal pathology.

The researchers enrolled 442 patients from CROCTINO, the Collaborative Retrospective Study of Retinal Optical Coherence Tomography in Neuromyelitis Optica, including 360 with AQP4-NMOSD, 49 with MOGAD, and 33 with DN-NMOSD. Patients were classified based on comorbidity burden, either one or more than two, the latter of which the researchers defined as multiple comorbidities, and then further classified based on the presence of autoimmune disorders and cardiovascular comorbidities/related risk factors.

Comorbidity Burden & OCT Results

Patients with AQP4-NMOSD had the highest percentage of comorbidities (43.5%), with an equal split between single and multiple comorbidities in this group. Fewer patients with MOGAD had comorbidities (40.8%), but more patients in this group (75.0%) had a single comorbidity compared with multiple comorbidities (25.0%). Patients with DN-NMOSD had the fewest percentage of comorbidities (36.4%), with an even split between single and multiple comorbidities.

Patients with AQP4-NMOSD were also more likely to have multiple comorbidities (50.0%) compared with those with MOGAD (25.0%; P=0.03) and more autoimmune disorders (40.4%) than those with MOGAD (20.0%) and DN-NMOSD (0%; P=0.004).

Cardiovascular comorbidities and related risk factors were reported among 34.8% of patients with AQP4-NMOSD, 50.0% of patients with MOGAD, and 33.3% of patients with DN-NMOSD, and Dr. Smith and colleagues found that patients with comorbidities had worse outcomes. The Expanded Disability Status Scale (EDSS) score was higher in MOGAD (3.0 vs 2.0; P=0.006) and DN-NMOSD (5.0 vs 2.0; P=0.008) in patients with versus without comorbidities. Patients with AQP4-NMOSD and cardiovascular comorbidities/related risk factors also had higher rates of ON relapses than those with autoimmune disorders (1.06±3.33 vs 0.49±0.98; P<0.001).

OCT results showed decreased inner nuclear layer thickness in patients with AQP4-NMOSD and comorbidities compared with AQP4-NMOSD and no comorbidities (P=0.047), a finding that was more pronounced for cardiovascular comorbidities/related risk factors (P=0.009).

Impact of Comorbidities on Disease Outcomes

The primary finding from the study is that patients with AQP4-NMOSD were more likely to have multiple comorbidities compared with patients with MOGAD, according to Dr. Smith and colleagues.

“Importantly, comorbidities in AQP4-NMOSD were more likely to be of autoimmune origin compared to MOGAD or DN-NMOSD. These relationships were independent of age,” the researchers wrote. “In patients with MOGAD or DN-NMOSD and comorbidities, cardiovascular comorbidities and related risk factors were associated with more severe disability (higher EDSS) and, in patients with AQP4-NMOSD, with a higher annual ON relapse rate.”

The results indicate that comorbidities hurt clinical outcomes in this population, they continued.

“Further research is needed to explore the mechanisms through which systemic diseases affect retinal structures and to enhance the sensitivity of OCT technology in detecting subtle changes to validate these observations would be an obvious continuation,” Dr. Smith and colleagues wrote. “Comorbidities may influence NMOSD, MOGAD, and DSDN-NMOSD-related treatment effectiveness, safety, tolerability, and adherence. Therefore, knowledge of comorbid conditions is critical. Refining comorbidity management strategies will be crucial to better address the overall health and vision preservation needs of these patients.”