The Sensitivity, Specificity, and Predictive Values of Serum Angiotensin-Converting Enzyme and Lysozyme in the Diagnosis of Sarcoid Optic Neuropathy.

BACKGROUND

This study describes the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum angiotensin-converting enzyme (s-ACE), and serum lysozyme in the diagnosis of sarcoid optic neuropathy (SON).

METHODS

We retrospectively reviewed the electronic medical record (EMR) of adult patients evaluated by neuro-ophthalmologists at Froedtert Hospital and the Medical College of Wisconsin clinics with a diagnosis of optic neuropathy (ON) from January 1, 2012, through July 1, 2023, who had s-ACE and/or serum lysozyme levels assessed. Potential patients for inclusion were identified using institutional data search tools. We then manually reviewed the EMR of each patient to verify whether inclusion parameters were met, and to gather relevant demographic and clinical data including s-ACE and lysozyme levels, and ON etiology. For the diagnosis of "Probable" or "Definite" SON, we relied on previously published consensus criteria for the diagnosis of neurosarcoidosis from the Neurosarcoidosis Consortium Consensus Group. The sensitivity, specificity, PPV, and NPV of s-ACE and lysozyme in the diagnosis of SON were calculated. For patients determined to meet criteria for a diagnosis of SON, we extracted additional data from the EMR including tissue biopsy location/s and findings; whether sarcoidosis diagnosis was already established before presentation with ON; whether the patient was taking corticosteroids or ACE-inhibitor (ACE-I) therapy at the time of laboratory evaluation; cerebrospinal fluid ACE (CSF-ACE) level; results of chest imaging; and results of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET) scans.

RESULTS

A total of 706 patients with ON were included. Of these 706 patients, 395 (56%) were women and 311 (44%) were men, with a median age of 51 years (range: 18-90). All 706 had an s-ACE level available, while 110 also had a lysozyme level available. Fourteen of the 706 (2%) patients met criteria for a diagnosis of "Probable" (n = 13) or "Definite" (n = 1) SON. Of these, 7 (50%) were women and 7 (50%) were men, with a median age of 42 years (range: 19-60). Seven of the 14 (50%) patients had a previously established diagnosis of sarcoidosis before presenting with ON. We found a sensitivity for s-ACE in diagnosing SON of 21.4%, and a specificity of 97%. The PPV of s-ACE was 12.5%, and the NPV was 98.4%. For lysozyme, we found a sensitivity of 33.3%, a specificity of 98%, PPV of 60%, and NPV of 94.3%.

CONCLUSIONS

In diagnosing SON, we have found s-ACE to have a sensitivity of 21.4%, and a specificity of 97%. The PPV of s-ACE was 12.5% and the NPV was 98.4%. We have determined lysozyme in this setting to have a sensitivity of 33.3% and a specificity of 98%. The PPV of lysozyme was 60% and the NPV was 94.3%. The fact that s-ACE and lysozyme have low sensitivity for the diagnosis of SON indicates that neither of these tests is suitable as a general screening tool in this setting.