Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy: Demographics, Risk Factors, and Visual Outcomes.

BACKGROUND: Although nonarteritic anterior ischemic optic neuropathy is a well-known cause of vision loss, it typically presents unilaterally. Simultaneous, bilateral nonarteritic anterior ischemic optic neuropathy (sNAION) is rare and poorly studied in comparison. This study seeks to characterize the clinical features and risk factors of patients with sNAION compared with unilateral NAION (uNAION). METHODS: In this retrospective case-control study, we reviewed 76 eyes (38 patients) with sNAION and 38 eyes (38 patients) with uNAION (controls) from 4 academic institutions examined between 2009 and 2020. Demographic information, medical history, medication use, symptom course, paraclinical evaluation, and visual outcomes were collected for all patients. RESULTS: No significant differences were observed in demographics, comorbidities and their treatments, and medication usage between sNAION and uNAION patients. sNAION patients were more likely to undergo an investigative work-up with erythrocyte sedimentation rate measurement ( P = 0.0061), temporal artery biopsy ( P = 0.013), lumbar puncture ( P = 0.013), and MRI ( P < 0.0001). There were no significant differences between the 2 groups for visual acuity, mean visual field deviation, peripapillary retinal nerve fiber layer thickness, or ganglion cell-inner plexiform layer thickness at presentation, nor at final visit for those with ≥3 months of follow-up. The sNAION eyes with ≥3 months of follow-up had a smaller cup-to-disc ratio (CDR) at final visit ( P = 0.033). Ten patients presented with incipient NAION, of which 9 suffered vision loss by final visit. CONCLUSION: Aside from CDR differences, the risk factor profile and visual outcomes of sNAION patients seem similar to those of uNAION patients, suggesting similar pathophysiology.

Leptin decreases de novo lipogenesis in patients with lipodystrophy.

De novo lipogenesis (DNL) plays a role in the development of hepatic steatosis. In humans with lipodystrophy, reduced adipose tissue causes lower plasma leptin, insulin resistance, dyslipidemia, and ectopic triglyceride (TG) accumulation. We hypothesized that recombinant leptin (metreleptin) for 6 months in 11 patients with lipodystrophy would reduce DNL by decreasing insulin resistance and glycemia, thus reducing circulating TG and hepatic TG. The percentage of TG in TG-rich lipoprotein particle (TRLP-TG) derived from DNL (%DNL) was measured by deuterium incorporation from body water into palmitate. At baseline, DNL was elevated, similar to levels previously shown in obesity-associated nonalcoholic fatty liver disease (NAFLD). After metreleptin, DNL decreased into the normal range. Similarly, absolute DNL (TRLP-TG × %DNL) decreased by 88% to near-normal levels. Metreleptin improved peripheral insulin sensitivity (hyperinsulinemic-euglycemic clamp) and lowered hemoglobin A1c and hepatic TG. Both before and after metreleptin, DNL positively correlated with insulin resistance, insulin doses, and hepatic TG, supporting the hypothesis that hyperinsulinemia stimulates DNL and that elevated DNL is integral to the pathogenesis of lipodystrophy-associated NAFLD. These data suggest that leptin-mediated improvement in insulin sensitivity increases clearance of blood glucose by peripheral tissues, reduces hepatic carbohydrate flux, and lowers insulinemia, resulting in DNL reductions and improvements in hepatic steatosis and dyslipidemia.