Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). Objective: To investigate whether there is an association between semaglutide and risk of NAION. Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023. Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION. Results: Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001). Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Posterior Ischemic Optic Neuropathy in the Setting of Cocaine-Induced Orbital and Sinonasal Inflammation.

Intranasal cocaine abuse can lead to significant sinus and orbital complications, including optic neuropathy. A 46-year-old man with a history of recurrent cocaine-induced sino-orbital inflammation and infection with bony destruction presented with acute, painless, vision loss. Examination revealed no light perception vision. MRI of the orbits demonstrated new restricted diffusion of the right optic nerve on diffusion-weighted imaging and apparent diffusion coefficient sequences, consistent with posterior ischemic optic neuropathy. This is the first among cases of cocaine-induced optic neuropathy in the literature to illustrate ischemic changes on MRI in the optic nerve, highlighting the utility of diffusion-weighted imaging/apparent diffusion coefficient sequences when optic neuropathy is suspected and further suggesting an underlying ischemic etiology in similar cases.

Non-arteritic Anterior Ischemic Optic Neuropathy with Macular Star following COVID-19 Vaccination.

PURPOSE: To report a case of non-arteritic anterior ischemic optic neuropathy (NAAION) with macular star after receiving the second dose of SARS-CoV-2 vaccination. METHOD: Case report. OBSERVATION: A 51-year-old male presented with acute visual disturbances one day after the second dose of BNT162b2 mRNA SARS-CoV-2 vaccination. At presentation, best corrected visual acuity (BCVA) was 20/25 right eye (OD) and counting fingers at 3 feet left eye (OS). Anterior segment examination was normal in both eyes. Dilated fundoscopy was unremarkable OD, however, it disclosed optic nerve swelling and subretinal fluid OS. Patient was treated with a gradual tapering dose of oral prednisone over 1 month. At the five-week follow-up visit, optic disc swelling and subretinal fluid resolved with minimal improvement in BCVA to 20/400 OS. CONCLUSION: It is unclear whether COVID-19 vaccination was the triggering agent to the NAAION or just a coincidence, yet ophthalmologists should be aware of such a possible association.

Ischemic Optic Neuropathy After Administration of a SARS-CoV-2 Vaccine: A Report of 2 Cases.

BACKGROUND Since the start of vaccination efforts against COVID-19, several presumed secondary ocular events have been described. We present 2 cases of non-arteritic anterior ischemic optic neuropathy (NA-AION) in patients whose symptoms appeared in the first 2 weeks after administration of the Pfizer-BioNTech COVID-19 mRNA BNT162b2/Cominarty vaccine. CASE REPORT The first patient was a 53-year-old man who presented visual field disturbance in the right eye 7 days after the first vaccine dose, and who consulted a physician 10 days after the second dose, when he experienced loss of vision in the left eye. After a full examination, bilateral anterior optic disc neuropathy was diagnosed. The second patient was a 65-year-old man who presented anterior optic disc neuropathy 12 days after his first vaccination. In both cases, arteritic origin was ruled out due to absence of systemic symptoms and because of normal levels of C-reactive protein and erythrocyte sedimentation rates. CONCLUSIONS Ischemic optic neuropathy is a rare adverse ocular secondary effect of COVID-19 vaccines. Further basic and clinical research is needed to elucidate the pathogenic mechanisms and better characterize the clinical picture of this entity.

The pathophysiology of Sumatriptan induced non-arteritic anterior ischemic optic neuropathy.

Objective: To report a case of a non-arteritic anterior ischemic optic neuropathy (NAAION) in a patient treated with Sumatriptan. Materials and methods: NAAION represents a severe affection that frequently determines irreversible visual acuity damage. The exact cause is yet to be identified, but is usually connected to the systemic status of the patient. We presented the case of a 53-year-old female patient who complained of visual acuity loss in her right eye, associated with inferior visual field (VF) damage. Patient history revealed migraine attacks, raised arterial blood pressure (BP), mitral valve insufficiency and dyslipidemia. Systemic treatment included Sumatriptan for migraine attacks and Bisoprolol for arterial hypertension. Results: A complete ophthalmologic examination was performed, including a visual field examination and optic coherence tomography. Interdisciplinary consults, along with inflammatory biomarkers, brain scan and cardiovascular Doppler echography were used to establish the final diagnosis. Considering the patient's history, systemic medication, clinical picture, paraclinical findings and interdisciplinary check-ups, NAAION was established as a diagnosis. Discussion: NAAION occurs more frequently after the age of 50 years old and may be associated with systemic factors such as nocturnal hypotension, diabetes, atherosclerosis, sleep apnea. In the present case, the association of medically induced nocturnal hypotension and vasoconstriction led to optic nerve ischemia. Conclusions: In a patient with multiple pathology, we must consider the systemic therapy when performing any clinical examination. Abbreviations: AAION = arteritic anterior ischemic optic neuropathy, AION = anterior ischemic optic neuropathy, BCVA = best corrected visual acuity, BP = blood pressure, CS = corticosteroid, IOP = intraocular pressure, LE = left eye, MRI = magnetic resonance imaging, NAAION = non-arteritic anterior ischemic optic neuropathy, OCT = optical coherence tomography, ON = optic nerve, OU = both eyes, RE = right eye.

NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY AFTER INTRAVITREAL AFLIBERCEPT FOR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after intravitreal injection in a patient with a history of fellow-eye NAION. METHODS: Observational case report. RESULTS: An 82-year-old woman with a history of fellow eye NAION developed an inferior visual field defect 1 day after an intravitreal aflibercept injection for neovascular age-related macular degeneration. She was found to have optic disk edema and an inferior altitudinal defect, consistent with NAION. The mechanism may have involved compromised perfusion to the optic nerve head related to elevated intraocular pressure or vasoconstriction because of antivascular endothelial growth factor activity. CONCLUSION: Nonarteritic anterior ischemic optic neuropathy is a rare complication of intravitreal injection and may be related to postinjection elevation in intraocular pressure. Monitoring of intraocular pressure postinjection with low-threshold for preinjection aqueous suppression or postinjection anterior chamber paracentesis for persistently elevated intraocular pressure is recommended in patients with a history of NAION.

Algae Oil Treatment Protects Retinal Ganglion Cells (RGCs) via ERK Signaling Pathway in Experimental Optic Nerve Ischemia.

BACKGROUND: We investigated the therapeutic effects and related mechanisms of algae oil (ALG) to protect retinal ganglion cells (RGCs) in a rat model of anterior ischemic optic neuropathy (rAION). METHODS: Rats were daily gavaged with ALG after rAION induction for seven days. The therapeutic effects of ALG on rAION were evaluated using flash visual evoked potentials (FVEPs), retrograde labeling of RGCs, TUNEL assay of the retina, and ED1 staining of optic nerves (ONs). The levels of inducible nitric oxide synthase (iNOS), IL-1ß, TNF-α, Cl-caspase-3, ciliary neurotrophic factor (CNTF), and p-ERK were analyzed by using western blots. RESULTS: Protection of visual function in FVEPs amplitude was noted, with a better preservation of the P1-N2 amplitude in the ALG-treated group (p = 0.032) than in the rAION group. The density of RGCs was 2.4-fold higher in the ALG-treated group compared to that in the rAION group (p < 0.0001). The number of ED1-positive cells in ONs was significantly reduced 4.1-fold in the ALG-treated group compared to those in the rAION group (p = 0.029). The number of apoptotic RGCs was 3.2-fold lower in number in the ALG-treated group (p = 0.001) than that in the rAION group. The ALG treatment inhibited ERK activation to reduce the levels of iNOS, IL-1ß, TNF-α, and Cl-caspase-3 and to increase the level of CNTF in the rAION model. CONCLUSION: The treatment with ALG after rAION induction inhibits ERK activation to provide both anti-inflammatory and antiapoptotic effects in rAION.

Risk of nonarteritic ischaemic optic neuropathy with phosphodiesterase type 5 inhibitors: a systematic review and meta-analysis.

The development of nonarteritic anterior ischaemic optic neuropathy has been described to phosphodiesterase type 5 inhibitors. The aim of this systematic review and meta-analysis was to assess the risk of nonarteritic anterior ischaemic optic neuropathy associated with phosphodiesterase type 5 inhibitors exposure. A literature search was performed at MEDLINE, EMBASE, Toxline and VigiBase. Randomized controlled trials, observational studies, case reports and spontaneous reports describing nonarteritic anterior ischaemic optic neuropathy associated with phosphodiesterase type 5 inhibitors exposure were included. The risk of bias was assessed according to Centre for Reviews and Dissemination's (CRD) guidance. Data were analysed using descriptive statistics and meta-analysis. Four observational studies, 50 case reports and 608 spontaneous reports were identified. All observational studies evaluated males treated for erectile dysfunction. Treatment with phosphodiesterase type 5 inhibitors is not associated with an increased risk of definitive nonarteritic anterior ischaemic optic neuropathy [odds ratio (OR) 1.16; 95% CI 0.89, 1.52, p = 0.046; I2  = 62.6%]. The methodological quality was assessed as good for three studies. Among case reports, 12 (23%) patients did not have risk factors to develop nonarteritic anterior ischaemic optic neuropathy. Thirty-nine (78%) patients were treated for erectile dysfunction. A regular administration of phosphodiesterase type 5 inhibitors was observed in 24 (48%) case reports. All case reports were assessed as higher risk of bias. According to the available evidence, the treatment with phosphodiesterase type 5 inhibitors was not found to be associated with nonarteritic anterior ischaemic optic neuropathy. Further research is needed to study such association, including possible confounding factors.

Posterior Ischemic Optic Neuropathy After Extensive Spine Surgery: A Case Report and Review of the Literature.

Postoperative vision loss (POVL) after spine surgery is a rare but devastating complication. Because of its rarity (incidence < 0.2%), POVL might not be considered for inclusion in an informed consent by surgeons and anesthesia providers. We present a case of POVL due to posterior ischemic optic neuropathy following prone spine surgery. Posterior ischemic optic neuropathy is characterized by acute painless vison loss that is progressive and irreversible. Our case is atypical because the patient experienced moderate improvement of visual acuity. Increased awareness and understanding of risk factors associated with POVL is an important and timely patient safety topic. In this report we review different pathophysiologies and risk factors for POVL following spine surgery along with recommendations for informed consent and strategies to reduce the incidence of POVL.

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Orbital and Ocular Ischemic Syndrome With Blindness After Facial Filler Injection.

The authors herein describe a case of orbital and ocular ischemic syndrome with blindness after cosmetic hyaluronic acid filler injection. Orbital function, but not visual function, returned after treatment with orbital hyaluronidase and corticosteroids.