Styloidogenic jugular venous compression syndrome has been recently described as a new cause of idiopathic intracranial hypertension. We present a 69-year-old patient, without other relevant medical history, presenting with 3 years of positional headache associated with decreased vision when reading and while turning her head to the right or left. She also reported pulsatile low-frequency tinnitus. Papilloedema was noted on the physical examination and, on imaging, an enlarged styloid process that induced jugular vein compression. The patient underwent styloidectomy with resolution of her symptoms and normalisation of her visual fields.

PURPOSE: Lebers hereditary optic neuropathy (LHON) is the most common mtDNA optic neuropathy. It most frequently causes dense bilateral central scotomas that are often characterized in clinical studies by Humphrey visual field testing (HVF) using a stimulus size III. This provides numerical quantification of the visual field defect using the mean deviation. However, this size III testing strategy has limitations. We used stimulus size V to monitor these patients and evaluated intertest variability and dynamic range to determine the testing reliability and reproducibility. METHODS: This was a longitudinal retrospective cohort study comparing Stimulus III and Stimulus V HVF of 62 LHON patients who had reached the plateau stage of the disease. The intertest variability and mean defect were calculated for both stimulus sizes for 38 patients. The mean defect for stimulus size V was calculated using an algorithm developed by the University of Iowa Visual Field Reading Center. RESULTS: Stimulus size V HVFs had lower inter-test variability as measured by mean defect standard deviation (Z = 169, P < 0.01). The floor effect seen with Stimulus III HVF in LHON, was less pronounced with Stimulus V HVF. The correlation of stimulus size III and V mean defect was strong (r = 0.90, P < 0.01), and a mathematical model was constructed to calculate the Stimulus size V mean defect from the Stimulus size III results (MDstimV = 0.988 x MDStimIII + 1.35, R2 = 0.82 P < 0.01). CONCLUSIONS: Stimulus size V HVF had lower intertest variability and a better dynamic range than Stimulus size III HVF in LHON patients. This makes the stimulus V HVF a more reliable metric to follow LHON patients especially in clinical trials. The mathematical model presented can be used to generate a Stimulus V equivalent mean defect from Stimulus III HVFs. TRANSLATIONAL RELEVANCE: Using Stimulus V HVF in LHON patients increases its ability to detect and quantify a response to treatment, making it a useful metric for future LHON clinical trials and the clinical setting.

Background

Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities.

Methods

This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS.

Results

Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening.

Conclusion

OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.