Risk Of Nonarteritic Anterior Ischemic Optic Neuropathy Research Articles

Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

ObjectiveTo investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population. DesignThis retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. ParticipantsThis study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists. MethodsPatient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Main Outcome MeasuresThe occurrence of NAION. ResultsThe final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60–8.97; 2 years: HR, 2.31; 95% CI, 0.86–6.17; 3 years: HR, 1.51; 95% CI, 0.71–3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03–2.28; 2 years: HR, 0.44; 95% CI, 0.09–2.21; 3 years: HR, 0.44; 95% CI, 0.09–2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42–1.57; 2 years: HR, 1.2; 95% CI, 0.74–1.94; 3 years: HR, 1.19; 95% CI, 0.78–1.82). ConclusionsThe findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.

Does Inter-Eye Asymmetry of Disc Area Explain Differences in Onset of Nonarteritic Anterior Ischemic Optic Neuropathy?

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals over the age of 50 years. It is associated with conventional vascular risk factors and structural vulnerabilities including "disc-at-risk." We aim to ascertain if a correlation exists between optic nerve head size and the onset of NAION. We performed a retrospective chart review of patients with an ICD-10 diagnosis of unilateral or bilateral NAION who underwent optical coherence tomography (OCT) and visual field testing. The primary outcome measure was the disc area as measured on OCT at a follow-up (minimum 6 months after acute vision loss) of the involved (or first involved for bilateral cases) vs fellow eye. The secondary outcome was the cup-to-disc ratio (CDR) of the first vs fellow eye. Seventy-three patients were included, of which 58 (79%) had unilateral and 15 (21%) had bilateral NAION, with a median follow-up of 23 months. Between the first eye involved and the fellow eye, there were no statistically significant differences in the mean disc area (1.69 ± 0.29 vs 1.71 ± 0.29, P = 0.7). However, average CDR (0.41 ± 0.20 vs 0.28 ± 0.18, P < 0.001) and vertical CDR (0.42 ± 0.20 vs 0.28 ± 0.19, P < 0.0001) were significantly larger in the involved eye. Despite no statistically significant differences in the disc area between the affected eye and the fellow eye, CDR was larger in eyes with a history of NAION compared with fellow eyes. Further research is required to elucidate local factors that may increase the risk of NAION in one eye relative to the other.

Nonadherence to Cardiovascular Drugs Predicts Risk for Non-Arthritic Anterior Ischemic Optic Neuropathy: A Large-Scale National Study.

Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03-1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89-21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23-1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide

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). To investigate whether there is an association between semaglutide and risk of NAION. 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. Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Cumulative incidence and hazard ratio of NAION. 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). This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Hormone Replacement Therapy and the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: a Nationwide Population-Based Study (2009-2018).

This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population. The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference. Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001). Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.

Nonarteritic Anterior Ischemic Optic Neuropathy After Cataract Surgery: A Systematic Review and Meta-Analysis.

Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur after cataract surgery. It is not clearly established whether cataract surgery increases the risk of NAION over baseline. Medline, PubMed, Embase, and Cochrane Central registers were systematically searched for eligible studies reporting on postcataract surgery NAION (psNAION) within 1 year. All peer-reviewed publications with events n ≥ 10 were included. Pooled incidence and odds/hazard ratios and 95% confidence intervals (CIs) were extracted and calculated using random effect models for early and delayed psNAION. Time to event data were pooled for temporal analysis of psNAION events within the first year. This systematic review was registered (PROSPERO CRD42021274383). Nine articles met the selection criteria with five studies suitable for meta-analysis. A total of 320 psNAION cases, 1,307 spontaneous NAION (sNAION) cases, 1,587,691 cataract surgeries, and 1,538,897 noncataract surgery controls were included. Pooling of 63,823 cataract surgeries and 161,643 controls showed a hazard ratio of 4.6 (95% CI 2.7-7.8) of psNAION within 1 year of surgery. Pooled unadjusted incidence of psNAION within 2 months was 99.92 (95% CI 38.64-161.19) per 100,000/year, psNAION within 1 year was 32.36 (95% CI 9.38-55.34) per 100,000/year, and sNAION was 8.87 (95% CI 2.12-15.62) per 100,000/year. psNAION cases were older by a mean of 7.6 years; otherwise, pooled odds ratios for baseline risk factors in psNAION vs. sNAION cases were not statistically significant. psNAION within the first year peaked within 72 hrs and at 6 weeks after the surgery with 73% of cases occurring within 6 months. The risk of NAION after cataract surgery is four times greater within the first year and usually occurs within 6 months. However, the absolute risk remains low at 1 in 1,000-3,100 surgeries and is unlikely to warrant extra mention for consenting.

Genetic polymorphisms of apolipoprotein E in nonarteritic anterior ischemic optic neuropathy.

To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.

Association Study of MTHFR Polymorphisms with Nonarteritic Anterior Ischemic Optic Neuropathy in a Spanish Population

Introduction: Nonarteritic anterior ischemic optic neuropathy (NAION), painless loss of central and/or peripheral vision, is a multifactorial disease caused by insufficient blood flow through the posterior ciliary arteries to the optic nerve head. Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene, triggering hyperhomocysteinemia as a consequence of a decreased activity of the codified enzyme, have been considered to be among the risk factors of NAION. Objective: The main aim was to study the association of the most common MTHFR genetic polymorphisms C677T and A1298C with NAION in a Spanish population. Methods: In this case-control study, the association of the most common MTHFR polymorphisms was investigated in 94 unrelated native Spanish patients diagnosed with NAION and 204 healthy controls. Two single nucleotide polymorphisms located in the MTHFR gene, C677T (rs1801133) and A1298C (rs1801131), were analyzed by DNA sequencing and TaqMan assays. Results: The allelic and genotypic frequencies of the MTHFR variants obtained in the NAION group were not significantly different when compared with the control group. A higher frequency of the C677T/A1298C genotype, codifying the nonmutated MTHFR form, was obtained in control subjects (11.27%) compared to NAION patients (4.26%), suggesting a protective effect of the wild-type protein, although this result was not conclusive considering the obtained confidence interval (CI) (95% CI: 0.13–1.06). Study of additional clinical factors including hypertension, diabetes mellitus, and dyslipidemia showed no association with a higher risk of NAION. Conversely, the clinical history of heart or cerebrovascular diseases was significantly higher in NAION patients compared to controls. Over the world, risk variants of the MTHFR gene are highly frequent, excluding African black populations, indicating a racial influence. Conclusions: The MTHFR variants did not significantly increase the risk of suffering from NAION. However, considering that individuals with at least one of the risk variants have the MTHFR enzyme with decreased activity, it cannot be ruled out that these mutations are relevant for the development of NAION in a subgroup of the population with other specific characteristics. These may include high plasma levels of homocysteine along with nutritional deficiencies including low folate or vitamin B12 and the combination of systemic and local risk factors.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy After Cataract Surgery

To determine whether the development of nonarteritic anterior ischemic optic neuropathy (NAION) is increased after receiving cataract surgery in a large general population. Nationwide, population-based, retrospective cohort study. Setting: A 12-year nationwide, population-based, retrospective cohort study including 1,025,340 beneficiaries in the 2002-2013 Korean National Health Insurance Service database. We identified 40,356 patients who had undergone cataract surgery and matched non-cataract surgery controls (1:2) using estimated propensity scores in reference to age, sex, demographics, comorbidities, and co-medications. Kaplan-Meier curves and Cox proportional hazard models were generated to determine the risk of developing NAION in the cataract surgery group compared to the non-cataract surgery group. Effect (hazard ratio [HR]) of cataract surgery on NAION development. The 10-year incidence probability of NAION was 0.70% (95% confidence interval [CI], 0.55%-0.86%) in the cataract surgery group and 0.27% (95% CI, 0.25%-0.29%) in the non-cataract surgery group (P < .0001, log-rank test). The cataract surgery group had an increased risk of developing NAION compared to the non-cataract surgery group (HR=1.80; 95% CIs, 1.46-2.21) even after adjusting for demographics, comorbidities, Charlson comorbidity index, and co-medications. Our results suggest that patients undergoing cataract surgery have an increased risk of NAION.

Risk Factors for Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic Neuropathy.

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals older than 50 years. Demographic, ocular, and systemic risk factors for NAION have been identified, and we sought to determine which, if any, of these factors also increase risk of NAION in the fellow eye. We performed a retrospective chart review of patients with "ischemic optic neuropathy" (based on International Classification of Disease [ICD] codes) seen at a single eye center between 2007 and 2017. Patients who met diagnostic criteria for unilateral NAION without fellow eye optic neuropathy at diagnosis were included. Demographic information, ocular comorbidities, and systemic diagnoses were recorded, in addition to whether the fellow eye developed NAION during the follow-up period. Univariate and multivariate Cox proportional hazard regression were used to calculate hazard ratios (HRs) for fellow eye involvement. Three hundred eighteen patients were identified by ICD codes, and 119 were included in the study. Twenty-nine (24%) patients developed NAION in the fellow eye over the mean follow-up period of 3.6 years (range: 1 month-11 years). Significant risk factors for fellow eye NAION included the presence of bilateral optic disc drusen (ODD, HR 2.78, 95% confidence interval [CI] 1.12-6.90, P = 0.02) and noncompliance with continuous positive airway pressure (CPAP) in patients with moderate-to-severe obstructive sleep apnea (HR 4.50, 95% CI 1.79-11.3, P = 0.0015). Bilateral ODD and noncompliance with CPAP when indicated are associated with increased risk of NAION in the fellow eye. Patients with these risk factors should be counseled on the potentially devastating visual consequences of bilateral NAION, and compliance with CPAP should be stressed when appropriate.

Obstructive sleep apnoea and increased risk of non-arteritic anterior ischaemic optic neuropathy

Background/aimsTo determine whether the development of non-arteritic anterior ischaemic optic neuropathy (NAION) is increased among patients newly diagnosed with obstructive sleep apnoea (OSA) in a large general population.MethodsA 12-year nationwide,...

Nonarteritic anterior ischaemic optic neuropathy and its association with obstructive sleep apnoea: a health insurance database study.

Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in old age. Although there are several known risk factors, the influence of obstructive sleep apnoea (OSA) has not been completely elucidated. The aim of this study was to evaluate the association between NAION and OSA. This retrospective, longitudinal cohort study used the national health insurance database of Taiwan covering the period 1996-2013. Patients without NAION at the diagnosis of OSA or who developed NAION 1year after the diagnosis of OSA were enrolled. The patients were followed until death or the last day of the study. Cox proportional hazard regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) to investigate the association between OSA and NAION. There were 8488 patients in the OSA group and 33952 in the control group (without OSA), for a ratio of approximately 1:4. The percentages of NAION were 0.36% and 0.2% in the OSA and control groups, respectively, with a statistically significant difference (p<0.01; chi-square test), and this significant difference remained in multivariate analysis (p=0.019) with a significantly higher HR (1.66; 95% CI: 1.08-2.55). There was significant difference in the 30-39years age group in multivariate analysis (p<0.01, HR: 6.30; 95% CI: 2.28-17.40). There was a strong association between NAION and OSA, and the patients with OSA had a higher risk of NAION. Further large-scale, prospective studies are warranted to evaluate the effect of OSA on developing NAION.

The Association Between Phosphodiesterase Type 5 Inhibitor Use and Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

IntroductionPhosphodiesterase type 5 inhibitors (PDE5-Is) are first-line drugs for erectile dysfunction. Non-arteritic anterior ischemic optic neuropathy (NAION) has been linked with PDE5-I use. However, no meta-analysis or conclusive review has explored the association between NAION and PDE5-I use.AimTo investigate the association between PDE5-I use and risk of NAION.MethodsA comprehensive literature search was conducted using online databases in October 2017 to obtain studies researching the association between PDE5-I application and occurrence of NAION. Summarized unadjusted risk ratios (RRs) with 95% CIs were calculated for the strength of this association. This study was conducted in accordance to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and registered in PROSPERO under number CRD42017080865.Main Outcome MeasuresThe strength of association between PDE5-I use and risk of NAION was assessed through pooled unadjusted RRs and 95% CIs.Results5 original articles with 6 clinical observations were included in the meta-analysis. No significant higher risk of NAION was observed after the use of PDE5-Is within a 1-month period (RR = 1.16, 95% CI = 0.98-1.39, P = .09). Subgroup analyses indicated 2 PDE5-Is were significantly related to NAION (tadalafil: RR = 2.14, 95% CI = 1.20–3.84, P = .01; sildenafil: RR = 2.25, 95% CI = 1.29–3.94, P = .004).ConclusionsAlthough we found no association between NAION and PDE5-I use, our results should be interpreted cautiously because we included only observational studies and could not control for potential confounders. Because NAION is a rare ocular disease and difficult to diagnose, this association should be confirmed in prospective comparative studies with larger samples and more rigorous designs.Liu B, Zhu L, Zhong J, et al. The Association Between Phosphodiesterase Type 5 Inhibitor Use and Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis. Sex Med 2018;6:185−192.

The polymorphisms of ATOH 7, ET-1 and ACE in non-arteritic anterior ischemic optic neuropathy

Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic neuropathy in the elderly. The role of the genetic polymorphisms of Atonal Homolog 7 (ATOH7), Endothelin-1 (ET-1) and Angiotensin Converting Enzyme (ACE) in NAION and the combined effects of the gene-gene and gene-medical comorbidities on NAION were not clear. We conducted a perspective, case-control study. 71 NAION patients and 142 age and sex-matched healthy controls were enrolled. Single nucleotide polymorphisms of ATOH7 (rs1900004), ET-1 (rs5370) and ACE (rs1799752) were identified by polymerase chain reaction (PCR) method and all PCR products were screened with Sanger sequencing. The prevalence of genetic factors in NAION patients were compared to normal people, and assessed in conditional logistic regression models. The modified effects of gene-gene or gene-medical comorbidities on NAION development were assessed with a multiplicative model. A significant high risk was found in the T allele of ATOH7 in NAION, with an odds ratio (OR) of 1.55 (P = 0.04). Conditional logistic regression analysis, including diabetes and hypertension, revealed that ATOH7 TT genotype carriers conferred a significantly increased risk of NAION (TT/CC + CT, OR = 3.32, 95% confidence interval (CI) = 1.16–9.53, P = 0.03). Interaction analysis showed that ET-1 (P = 0.01), ACE (P = 0.046) and hypertension (P = 0.02) have modified effects on NAION development. Our results showed that the polymorphism of optic disc associated gene-ATOH7 conferred a significant risk of NAION. Combination of ATOH7 and ET-1, ATOH7 and ACE, as well as ATOH7 and hypertension, increased the susceptibility of NAION. Our data may be useful for NAION predicting.

Prospective Case-crossover Study Investigating the Possible Association Between Nonarteritic Anterior Ischemic Optic Neuropathy and Phosphodiesterase Type 5 Inhibitor Exposure

To evaluate the association between intermittent phosphodiesterase type 5 inhibitor (PDE5i) exposure and risk of acute nonarteritic anterior ischemic optic neuropathy (NAION) using a case-crossover design. Male adults with suspected NAION were enrolled at 41 US ophthalmology sites from 2010 to 2015 and were interviewed regarding risk factors for NAION, medical history, and PDE5i use before NAION onset (index date of onset [IDO]). An adjudication committee confirmed the NAION cases. The primary analysis, using the person-time method, examined the rate of PDE5i exposure within 5 half-lives of NAION onset relative to PDE5i exposure over a 30-day study period preceding the IDO in men exposed to PDE5i intermittently as a measure of NAION risk associated with PDE5i exposure. Rate ratios were estimated using the Mantel-Haenszel estimator. Secondary analyses included person-time analyses over the 12-months preceding the IDO and matched-interval analyses over 42 days preceding the IDO. Of 279 men with confirmed NAION, 22 were exposed to PDE5i intermittently within 30 days of IDO. The Mantel-Haenszel rate ratio for risk of NAION associated with PDE5i exposure within 5 half-lives of IDO was 2.27 (95% confidence interval [CI]: 0.99-5.20) over the 30-day period (n = 22) and 3.52 (95% CI: 1.59-7.79) over the 12-month period (n = 26). Sensitivity analyses showed similar results and were statistically significant. The matched-interval method found no association (hazard ratio = 1.64 [95% CI: 0.60-4.51]). Overall, the study suggests an increased risk of NAION associated with PDE5i use. Patients and health-care providers should continue to weigh the risks and benefits of PDE5i use, including the potential for NAION.

The Relationship Between Phosphodiesterase-5 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy

A cause and effect relationship between phosphodiesterase-5 inhibitor (PDE5I) use and nonarteritic anterior ischemic optic neuropathy (NAION) has been hypothesized based on case reports. Review of literature. Thirty-nine case reports in the peer-reviewed medical literature have documented a possible relationship between PDE5I consumption and NAION. However, pertinent details, such as the dose and frequency of PDE5I use, and elapsed time between ingestion and onset of vision loss, are lacking from many of these reports. Investigations regarding alterations in ocular perfusion in research subjects who ingested sildenafil have been inconclusive because they have not been performed on subjects with "disc at risk" or risk factors for NAION. One case-crossover study demonstrated a 2-fold increase in risk of NAION after ingestion of PDE5I. When a diagnosis of NAION is made, an inquiry should be made as to whether any PDE5I was ingested before the onset of vision loss. If so, the patient should be counseled regarding the possibility that continued PDE5I use may increase the risk of NAION in the fellow eye. Patients with a known history of previous NAION should be cautioned regarding the use of PDE5I for erectile dysfunction or pulmonary hypertension because of the potential increased risk of fellow eye involvement.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy Following End-Stage Renal Disease.

To investigate the risk of nonarteritic anterior ischemic optic neuropathy (NAION) following end-stage renal disease (ESRD).A retrospective, nationwide, matched cohort study.ESRD patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 585.The study cohort included 93,804 ESRD patients registered with the Taiwan National Health Insurance Research Database between January 2000 and December 2009. An age- and sex-matched control group comprised 93,804 patients (case:control = 1:1) selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. The incidence and risk of NAION were compared between the ESRD and control groups. The adjusted hazard ratio (HR) for NAION after adjustment for potential confounders was obtained by a Cox proportional hazard regression analysis. A Kaplan–Meier analysis was used to calculate the cumulative incidence rate of NAION.The incidence of NAION following ESRD.In total, 133 ESRD patients (0.14%) and 51 controls (0.05%) had NAION (P < 0.001) during the follow-up period, leading to a significantly elevated risk of NAION in the ESRD patients compared with the controls (incidence rate ratio = 3.14, 95% confidence interval [CI] = 2.11–4.67). After adjustment for potential confounders including diabetes mellitus, hypertension, hypotension, hyperlipidemia, and 2-way interaction terms between any 2 factors, ESRD patients were 3.12 times more likely to develop NAION than non-ESRD patients in the full cohort (adjusted HR = 3.12, 95% CI = 2.10–4.64). Additionally, patients with hypertension and hyperlipidemia showed higher incidence rates of NAION in the ESRD group compared with the controls: 2.31 (95% CI = 1.40–3.82) for hypertension and 2.72 (95% CI = 1.14–6.50) for hyperlipidemia.ESRD increased the risk of NAION, which is an interdisciplinary emergency. Close collaboration between nephrologists and ophthalmologists is important in NAION management following ESRD to prevent fellow eye involvement.

The Association Between Obstructive Sleep Apnea and Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis

ABSTRACT Purpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is a multifactorial disease, and recently epidemiologic studies have investigated the association between obstructive sleep apnea (OSA) and NAION. A systematic review of the association of OSA and NAION has not been performed. Therefore, the current meta-analysis was performed to assess such potential association between OSA and risk of NAION. Methods: A systematic search of PubMed and EMBASE databases was performed for published studies evaluating the association between OSA and NAION. The summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for categorical risk estimates. Sensitivity analyses and subgroup analyses were also performed to assess the robustness of pooled outcomes. Results: A total of four prospective cohort studies and one case–control study met our inclusion criteria. The pooled OR of developing NAION in the subjects with OSA was 6.18 (95% CI, 2.00–19.11) versus non-OSA controls. Sensitivity analyses showed that no matter one study excluded, the pooled OR did not change significantly, which indicated that the evidence was robust. In subgroup analyses, a significant association was seen in studies matched systemic risk factors (OR, 5.00; 95% CI, 2.22–11.25), but not in those non-matched. The magnitude and direction of effects were also affected by methodological variability, including study design, and diagnosis of OSA. Conclusions: The findings from this meta-analysis supported the robust evidence that OSA was a strong independent risk factor of NAION. Relative to non-OSA controls, the subjects with OSA were found to have a more than sixfold risk of NAION. In future, more well-designed studies are needed to confirm these findings.

Glutathione-S-Transferase Deletions and Non-arteritic Anterior Ischemic Optic Neuropathy.

In this study, we aimed at investigating the association between glutathione-S-transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may contribute to the understanding NAION pathogenesis and provide some clues for the prevention and treatment of optic diseases. The NAION group contains 113 subjects (33 males and 80 females, mean age 55.3 ± 9.8). And 98 subjects were enrolled in the control group (32 males and 66 females, mean age 56.7 ± 10.2). The individuals involved in the study were matched by gender and age to obtain two homogenous groups. GSTM1- and GSTT1- genotype and the combined genotype were investigated. The genotype distributions in NAION patients were compared with those in the controls. Significantly altered intraocular pressure (IOP) and cup-to-disc ratio (CDR) was detected between NAION patients and controls. An increased risk of NAION was observed among individuals with GSTM1- (P < 0.001). No significant difference was confirmed for GSTT1- (P = 0.290). Individuals with GSTM1-/GSTT1- have a higher susceptibility to NAION (P < 0.001); the GSTM1-/GSTT1+ genotype also had a significantly higher frequency in patients than in controls (P = 0.004). But the genotype of GSTM1+/GSTT1- seems to have no connection with NAION (P = 0.476). In conclusion, in this study, we confirmed the connection between NAION and GSTM1- genotype. But no significant association was observed between GSTT1- genotype and NAION susceptibility. In further analysis regarding combined genotype, a trend of protective effect was detected for GSTT1+ genotype. It is indicated by our result that oxidative compounds might play an important part in the pathogenesis of NAION.

Nonarteritic anterior ischemic optic neuropathy in young patients

To determine and report the demographic and clinical features of patients younger than 50 years with nonarteritic anterior ischemic optic neuropathy (NAION). In this comparative study, we retrospectively reviewed the medical records of 120 patients with NAION. Patients were divided into two groups according to their age; in group I, 44 patients were younger than 50 years, and in group II, 76 patients were older than 50 years. The gender distribution was similar in both main groups. Involvement was bilateral in 50% and 26.3% of patients, respectively (P<0.0001). Diabetes mellitus was present in 63.6% of patients in group I and 47.3% of patients in group II (P=0.009). We found hypertension as a frequent risk factor in group II (P=0.019). There was no significant difference in the initial and final visual acuities of patients between the two groups. Both groups had a significantly thinner peripapillary nerve fiber layer (RNFL) in every quadrant. The relative loss was greatest in the superior quadrant in both groups. We generally observed inferior altitudinal defect and superior RNFL thinning in two groups. In group I, 30 eyes (68.1%) demonstrated angiographically diffuse optic disc filling delay of ≥5seconds after choroidal filling confirming ischemia, and 14 (31.8%) eyes with segmental optic disc filling delay. In group II, diffuse optic disc filling delay was seen in 56 of 76 (73.6%) eyes. Segmental optic disc filling delay was present in 20 eyes (26.3%). There was no significant difference in angiographic findings between the two groups (P=0.67). We observed that age did not play a significant role in prognosis of NAION. Diabetes is an increased risk for NAION in the young age group, and HT for NAION in the older group. Fellow eye involvement is more frequent in young patients. These patients should be followed closely.