Nonarteritic Anterior Ischemic Optic Neuropathy Patients Research Articles

Optic nerve head circulation in nonarteritic anterior ischemic optic neuropathy and optic neuritis

Purpose To quantify optic nerve head circulatory abnormalities in patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) or optic neuritis (ON), and to assess the potential of such measurements to differentiate NAION from ON. Design Prospective, cross-sectional, observational study. Participants Thirty consecutive patients with unilateral NAION, 22 consecutive patients with unilateral ON, and 50 healthy control subjects. Methods All subjects underwent a complete neuro-ophthalmologic evaluation. The widths of Doppler-broadened frequency spectra, which are directly proportional to the speed of blood cells flowing through the capillaries of the optic nerve head, were measured at multiple sites in both eyes of each subject. The variation of Doppler broadening (DB) with age was determined in the control subjects. Doppler broadening values in the patients were compared between similar sites in affected and contralateral eyes, and between both affected and contralateral eyes and the age-adjusted values determined in the control subjects. Main outcome measures The differences in DB between (1) the affected and contralateral eyes of the patients, (2) the patients and the control subjects, and (3) the patients with NAION and those with ON. Results In NAION, DB was decreased at both temporal (−20.2% and −18.5%) and nasal (−12.8% and −12.4%) sites of the nerve head in affected eyes compared with contralateral eyes or eyes of control subjects. In ON, DB was also decreased at temporal sites (−11.3% and −9.2%) in affected eyes compared with contralateral or control eyes. At nasal sites, there were no significant differences in DB in affected eyes of ON patients compared with contralateral or control eyes. The DB decreases were significantly greater in NAION patients than in ON patients. Conclusions Optic nerve head circulatory abnormalities are present in patients with NAION or ON. This is the first demonstration of such abnormalities in ON, a finding consistent with the recent attention given to the phenomenon of axonal loss in this disease. Although there are differences in the circulatory abnormalities between the 2 diseases that provide insights into the pathophysiological mechanisms at play, they are not large enough to enable the clinician to distinguish between ON and NAION in an individual patient.

Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation

The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction–complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 ± 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P = .009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an α value of .05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (χ 2 = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy ( n = 4) or during pregnancy ( n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its preven tion and treatment and help protect against thrombi in other vascular beds.

Use of magnetic resonance imaging to differentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy

Objective To determine if magnetic resonance imaging (MRI) of the optic nerves obtained during the acute phase can distinguish patients with optic neuritis (ON) from those with nonarteritic anterior ischemic optic neuropathy (NAION). Design Retrospective, neuroradiologic, observational study. Participants Sixty-four patients diagnosed as having either ON or NAION who were diagnosed by clinical criteria and imaged by MRI. Methods Demographic information on the MRI scans was masked and the patients were presented randomly and in a blinded fashion to a neuroradiologist (JDR) for determination of abnormalities. Reproducibility was assessed by presenting 10 of the scans a second time to the same neuroradiologist. Main outcome measures The presence or absence and location of abnormal MRI signals of the optic nerve. Results Evaluation of reproducibility revealed identical interpretations of the ten scans submitted a second time. The optic nerve was abnormal in the clinically affected eye in 31 of the 32 ON patients but in only 5 of the 32 NAION patients. Thirty of the 31 ON patients who received gadolinium had enhancement, and 27 of the 32 ON patients had increased short T 1 inversion recovery signal in the clinically affected optic nerve. The five NAION patients with abnormal scans in the clinically affected eye had increased short T 1 inversion recovery signal, and in two of these, there also was enhancement of the optic nerve. For the ON patients, enhancement involved the entire length of the intraorbital optic nerve in 18 cases and the intracranial segment of the optic nerve in 19 cases. Conclusions Our study shows that MRI scanning of the optic nerve shows significantly different results between patients clinically diagnosed with either ON or NAION.

ACE and angiotensin II and nonarteritic anterior ischemic optic neuropathy: Author reply

Dr. Donahue’s letter expresses concerns that in our article, “The Role of Angiotensin Converting Enzyme and Angiotensin II Type 1 Receptor Gene Polymorphisms in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy (NAION),” further statistical analysis are required to support our conclusion that angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) have no role in the pathogenesis of the disease. The insignificant P values in our study could result from true lack of effect or from small sample sizes and, consequently, low power. We have carried out the power calculations requested by Dr. Donahue with respect to a 20% absolute difference in the allele frequencies of the presumed risks (D allele in the case of ACE and C allele in the case of AT1R). The calculations were based on the use of a two-sided 5% test. The power to detect a 20% difference in ACE and AT1R was 98.7% and 95.2%, respectively. More cogent is a computation of the 95% confidence intervals (CI) for the differences in the D and C allele frequencies (NAION patients minus controls). The 95% CI for the D allele of ACE was −14.9, 6.5 and for the C allele of AT1R, was −3.3, 16.4. For both polymorphisms, the 95% CI indicated small differences; and it ruled out a 20% increment among NAION patients over the controls. Thus, additional calculations support our conclusion that ACE and AT1R polymorphisms have no role in the pathogenesis of NAION.

Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion

Objective This study aimed to determine the prevalence of hyperhomocystinemia among patients with nonarteritic anterior ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), or central retinal vein occlusion (CRVO). Design Retrospective, case-control study. Participants The study cohort consisted of 74 consecutive patients with NAION, CRAO, or CRVO who were examined at the Retina or Neuro-ophthalmological Unit of the Tel-Aviv Sourasky Medical Center from 1998 through 1999. The control group consisted of 81 consecutive patients of similar gender and age with no history of these pathologic conditions. Main outcome measures Plasma homocystine levels of all study participants were obtained. Results Eighteen of 40 patients (45%) with NAION and eight of 13 patients (61.5%) with CRAO had hyperhomocystinemia compared with three of 21 (14.3%) in the CRVO group ( P < 0.001) and eight (9.8%) in the control group ( P < 0.0001). Hypertension and ischemic heart disease were significantly more prevalent in the NAION patients with elevated plasma homocystine. Conclusions Our findings suggest that hyperhomocystinemia is a risk factor for NAION and CRAO.