Tear-based antibody tests may help diagnose ocular MG: Study
Tests offer 'promising alternative' to blood samples, researchers say
Using tears to test for self-reactive antibodies to help diagnose ocular myasthenia gravis (OMG) is more accurate than using blood samples, according to a study that found nearly all patients who tested negative for these antibodies in the blood had a positive result in tears.
“Tear-based testing offers a promising alternative for diagnosing [blood]-negative OMG cases,” the researchers wrote.
The study, “Anti-Acetylcholine Receptor antibodies in Tear for the Diagnosis of Ocular Myasthenia Gravis,” was published in the American Journal of Ophthalmology.
The muscle weakness and fatigue that characterize MG are caused by self-reactive antibodies that attack proteins in the neuromuscular junction, the place where nerves and muscles communicate. In most cases, those antibodies target the acetylcholine receptor (AChR), a protein on muscle cells that responds to nerve signals.
In some patients, MG symptoms are restricted to the muscles that control the eyes and eyelids. This form of MG is referred to as OMG. Common OMG symptoms include droopy eyelids (ptosis) and double vision (diplopia).
Antibody tests to confirm diagnosis
If MG symptoms are present, clinicians will test for self-reactive antibodies in the bloodstream to confirm the MG diagnosis. While anti-AChR antibodies are found in about 80% of people with generalized MG, a form of the disease marked by widespread muscle weakness and fatigue, more than half of those with OMG will test negative for these antibodies, which can delay the diagnosis.
That points to an “urgent need for novel, more sensitive, and non-invasive diagnostic approaches to improve early and accurate diagnosis of OMG,” the researchers wrote.
The research team, in China, set out to investigate whether tears can be used to test for anti-AChR antibodies as a diagnostic tool for OMG.
The study enrolled 52 newly diagnosed OMG patients, about half (46.2%) of whom were women. None had received sustained treatment before the study. Thirteen unaffected people were included as a control group.
The presence of Anti-AChR antibodies was assessed in blood and tear samples using a cell-based assay (CBA). As a comparison, patients also underwent a series of standard diagnostic tests for OMG, including ELISA for anti-AChR antibodies, repetitive nerve stimulation (RNS), and neostigmine, a medication that should ease symptoms if a person has MG.
Using CBA, tear samples showed a significantly higher positivity rate for anti-AChR antibodies than matched blood samples (80% vs. 42.3%). Based on these results, the tear-based CBA test for anti-AChR antibodies demonstrated a diagnostic accuracy of 93%, compared with 66% for blood-based CBA tests.
Anti-AChR antibody levels in tears were significantly higher in OMG patients than in controls, “highlighting the feasibility and potential clinical utility of tear fluid as a diagnostic medium for OMG,” the team wrote.
Of 42 OMG patients who tested negative for anti-AChR antibodies using the standard ELISA method, nearly all (83.3%) tested positive using the tear-based CBA test. However, fewer than half (40.5%) of those with a negative ELISA result tested positive using the blood-based CBA test.
While 10 patients tested negative using RNS, most (70%) tested positive for anti-AChR antibodies in tears using CBA, and half (50%) tested positive with blood-based CBA. Similarly, all nine patients who were negative on neostigmine tests had a positive result in tear-based CBA, with fewer than half (44.4%) being positive with blood-based CBA.
In an exploratory analysis, more patients with at least one eye-based symptom showed a higher tear CBA signal (26.2%) than those with ptosis (22.6%) or diplopia (23.4%) alone. In line with these findings, more patients with more than two non-eye muscle symptoms had higher CBA signals than those with fewer than two muscles affected (30% vs. 22.6%). More RNS-positive patients showed a higher CBA signal than RNS-negative patients (30% vs. 25%).
Still, no consistent association was found between anti-AChR antibody levels in tears and OMG severity.
That is “in line with previous reports that have shown a weak or absent association between serum anti-AChR antibody levels and disease severity,” the researchers wrote.
“Compared to [blood]-based detection, tear-based assays for anti-AChR antibodies demonstrate superior sensitivity in diagnosing OMG,” the team wrote. “Our findings support tear-based antibody testing as a promising diagnostic tool that may complement existing strategies for the early and accurate diagnosis of OMG.”
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