Acute Nonarteritic Ischemic Optic Neuropathy Research Articles

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy

BackgroundAn effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®).MethodsWe conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 106cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year.ResultsIn this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up.ConclusionsBesides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION.Trial registration: Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638.

Macular Edema as Unusual Presentation of Non-Arteritic Ischemic Optic Neuropathy (NAION)

Introduction: Non-arteritic Ischemic Optic Neuropathy is the most common type of ischemic optic neuropathy. Nearly half of NAION patients presented with 20/30 or better visual acuity. Central vision is often preserved relative to the visual field loss. Macular edema in NAION patient is rare, and its occurrence may confuse to other disease and lead to unnecessary treatment.
 Case Report: We identified three NAION patients presented with macular edema. The patients' age was above 40 and had diabetes mellitus (DM). Our patients had clinical findings consistent with NAION with poor visual acuity at the early presentation. Optical coherence tomography examination was performed, and all patients had prominent subretinal fluid. Intravitreal anti-VEGF injection was done on our first patient and no treatment was given to our second and third patient. All patients showed a significant improvement of macular edema.
 Discussion: Macular edema is a rare clinical manifestation that may contribute a visual deterioration in NAION. The incidence of macular edema in NAION patients is difficult to measure since OCT of macula is not routinely performed. In our report, we encountered three cases of NAION complicated by macular edema that underwent a different approach in therapy. Spontaneous regression of subretinal fluid was seen during observation without any treatment given. Our patients achieved a stable visual acuity and visual field defect. This finding is under the literature that spontaneous recovery will be observed during the natural course of acute NAION.
 Conclusion: Macular edema is an unusual but self-limiting presentation of NAION. Therefore, a comprehensive examination is needed to prevent any unnecessary treatment.

Follow-up of Nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography.

Peripapillary and macular microvasculature alterations after nonarteritic ischemic optic neuropathy (NAION) have been investigated in several studies. We aimed to explore the vascular changes from acute NAION (aNAION) to chronic NAION (cNAION). This prospective observational study composed of 16 eyes with aNAION and 40 healthy age-matched controls. Eyes with NAION were followed up for more than 6 months after acute event. Optical coherence tomography angiography (OCTA) was used to evaluate peripapillary and macular vessel densities (VDs). The customized software was used for calculating deep retinal VD to attenuate the large superficial vessel projection effect. The mean age of patients with NAION and controls was 56.13 ± 13.2 and 54.46 ± 15.5 years, respectively (P = 0.195). Radial peripapillary capillary density was significantly lower in both eyes with aNAION and eyes with cNAION than healthy eyes. Peripapillary capillary density decreased significantly from the acute to the chronic phase of NAION with values of 41.77 ± 4.05% and 34.35 ± 7.30%, respectively (P < 0.001). The mean superficial macular VD was 46.83 ± 3.47% in aNAION and 44.49 ± 4.50% in cNAION eyes with no significant difference between them (P = 0.252), but both were lower than control eyes. Deep macular VD was not affected in aNAION and cNAION eyes compared with control eyes. Correlation analysis in eyes with cNAION revealed that there were significant correlations between peripapillary nerve fiber layer and the capillary density (r = 0.772, P < 0.001) and between ganglion cell complex thickness and corresponding superficial macular VD. Although a decrease in peripapillary capillary density in aNAION eyes with active disc edema progressed when evaluated in the cNAION state, progressive VD loss was not observed in the macular area, suggesting a nonprogressive nature of macular vessel involvement in NAION.

Macular Evaluation wıth Spectral Domain Type Optic Coherence Tomography in Eyes with Acute Nonarteritic Ischemic Optic Neuropathy at the Presentation Visit.

Purpose:To evaluate the macula with spectral domain type optic coherence tomography (OCT) in eyes with acute nonarteritic anterior ischemic optic neuropathy (NAION) at the presentation visit.Methods:Medical charts of the 133 patients who received the diagnosis of acute NAION between January 2008 and July 2014 at the Neuro-ophthalmology unit of Dokuz Eylul University were reviewed retrospectively. Sixtythree patients within 30 days of symptom onset with available baseline spectral domain type macular OCT were included in this study. Clinical and macular characteristics of the affected eye were assessed and compared to the fellow eyes.Results:Sixty-three eyes of 63 patients comprised the study group. Twenty one study eyes (33.3%) had normal posterior pole, 22 (34.9%) some evidence of subretinal fluid, 10 (15.8%) vitreomacular adhesion, five (7%) age-related macular degeneration related changes, four (6%) epiretinal membrane and one (1%) previous grid laser scars. On the other hand, 41 of 63 the fellow eyes (65%) had normal posterior pole, ten (15.8%), vitreomacular adhesion, seven (10.7%), age-related macular degeneration related changes, three (4%) epiretinal membrane and two (3%) other type of changes. OCT scan passing through the fovea exhibited 10 or more hyperreflective dots in 10 (15%) of the study eyes whereas two of the fellow eyes (3.2%) had 10 or more hyperreflective dots.Conclusion:Macular OCT can be a part of the routine neuroophthalmologic examination in patients with acute NAION not only to show the NAION related changes such as the subretinal fluid accumulation but also to identify the other coexistent macular abnormalities.

Is There A Role for Intravitreal Pharmacotherapy in the Treatment of Acute Nonarteritic Ischemic Optic Neuropathy?

Is There A Role for Intravitreal Pharmacotherapy in the Treatment of Acute Nonarteritic Ischemic Optic Neuropathy?

Single intravitreal aflibercept injection for unilateral acute nonarteritic ischemic optic neuropathy.

Acute nonarteritic ischemic optic neuropathy (ANAION) is the most common optic neuropathy in the elderly population without a well-established treatment. A 67-year-old man with a sudden painless visual loss in his left eye of one-day duration was diagnosed to have left ANAION. Next day, 2 mg aflibercept injection was injected intravitreally in OS. Visual acuity improved to 7/10 from 1/10 a week after the injection. Mean retinal nerve fiber layer thickness (RNFLT) was reduced to 159,7 μm from 182,4 μm at the first week. Visual fields improved dramatically during the follow-up of three months. The aim of this study is to present a case having ANAION treated with a single intravitreal aflibercept injection and discuss the place of intravitreal anti-VEGF injections in the treatment of armamentarium of ANAION.

Efficacy of Intravitreal Ranibizumab Injection in Acute Nonarteritic Ischemic Optic Neuropathy: A Long-Term Follow Up§

Background: To evaluate the effect of a single intravitreal ranibizumab injection in eyes with acute nonarteritic ischemic optic neuropathy (NAION).Subjects and Methods: In this retrospective clinical data analysis, 17 eyes of sixteen patients who experienced a visual loss with duration of 15 days or less comprised the study group. In addition to standard ophthalmic examination, retinal nerve fiber layer thickness (RNFLT) analysis with spectral domain OCT was also performed prior to 0.5 mg Ranibizumab injection, one week, one, three, six months and one year after the injection.Results: The mean time between visual loss and intravitreal injection was 7.5 days (Range, 2-15 days). Mean age of patients was 59 years (Range, 41-90 years). Male to female ratio was 6:10. After a single dose of ranibizumab injection, visual gain was noted in 14 of 17 study eyes. In two eyes, visual acuity was minimally reduced and no change was noted in the remaining eye with an initial visual acuity of hand motions. While pre-injection mean best-corrected visual acuity (BCVA) was 1.45 ±0.88 log Mar unit, post-injection mean BCVA was 1.00±0.68, 0.86 ±0.70, 0.80 ±0.71, 0.77 ±0.70, 0.77 ±0.70 log Mar unit respectively at the first week, first month, third month, sixth month and first year. In all patients, the mean RNFLT dramatically decreased after the injection during the follow- up. While pre-injection mean RNFLT was 210 ±38 µm, post-injection mean RNFLT was 162.11±40.2, 94±27, 71.23±22.5, 63 ±19 and 57 ±18 µm respectively at the first week, first month, third month, sixth month and first year. No injection related complication was noted during the follow-up period.Conclusion: Intravitreal ranibizumab injection can be a treatment modality in eyes with acute NAION.

Laser speckle flowgraphy for differentiating between nonarteritic ischemic optic neuropathy and anterior optic neuritis

The aim of this study was to investigate the usefulness of laser speckle flowgraphy (LSFG) for the differentiation of acute nonarteritic ischemic optic neuropathy (NAION) from anterior optic neuritis (ON). To investigate blood flow in the optic disc under normal conditions, NAION, and anterior ON, we compared the tissue blood flow of the right eye with that of the left eye in the control group, and that of the affected eye with that of the unaffected eye in the NAION and anterior ON groups. In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had decreased optic disc blood flow in the NAION eye when compared with the unaffected eye. By contrast, in the anterior ON group, all 6 patients had increased optic disc blood flow in the anterior ON eye when compared with the unaffected eye. In the NAION group, the mean blur rate (MBR) of the affected eyes was 29.5 % lower than that of the unaffected eyes. In the anterior ON group, the MBR of the affected eyes was 15.9 % higher than that of the unaffected eyes. LSFG could be useful in differentiating between NAION and anterior ON. In addition, this imaging technique saves time and is noninvasive.

Visual Fields at Follow-up in the Ischemic Optic Neuropathy Decompression Trial: Evaluation of Change in Pattern Defect and Severity Over Time

Purpose To evaluate change from baseline to 12 months follow-up in study and nonstudy (fellow) eye visual fields from the Ischemic Optic Neuropathy Decompression Trial (IONDT). Design Randomized controlled trial and observational study. Participants The IONDT enrolled patients ≥50 years with acute nonarteritic ischemic optic neuropathy (NAION). Randomized patients (n = 258) had visual acuity ≤20/64; nonrandomized patients (n = 160) had visual acuity >20/64 or refused randomization. Interventions Optic nerve decompression surgery (n = 127) or careful follow-up (n = 131). Main Outcome Measures We measured visual fields at baseline and at 6 and 12 months follow-up. Using a computerized system, we classified visual field defects by pattern, location, and severity. We examined changes over time by treatment group, age, baseline comorbidities, and change in visual acuity. In fellow (nonstudy) eyes, we assessed change by whether NAION was present at baseline and also incidence of NAION by whether a visual field defect was present at baseline. Results We analyzed 245 study eye visual field pairs (179 and 66, randomized and nonrandomized, respectively) for change from baseline to 12 months. We observed significant changes in defect distribution within the central field (P = 0.02) for randomized eyes. Superior and inferior altitudinal defects were less severe at follow-up in both randomized and nonrandomized eyes. We observed an association between change in central field severity and change in visual acuity from baseline (P<0.001 at 6 months; P = 0.01 at 12 months; Kendall's tau-b), but no association between visual field change and treatment group, age, or baseline comorbidities. Superior and inferior visual field defects present at baseline in nonstudy eyes improved at follow-up. Fellow (nonstudy) eyes with normal fields did not have an increased risk of developing NAION compared with eyes with ≥1 defects. Conclusions Visual fields of NAION patients enrolled in the IONDT were relatively stable from baseline to follow-up. A visual field defect in the nonstudy eye at baseline was not associated with development of NAION during follow-up compared with eyes with normal fields. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article. To evaluate change from baseline to 12 months follow-up in study and nonstudy (fellow) eye visual fields from the Ischemic Optic Neuropathy Decompression Trial (IONDT). Randomized controlled trial and observational study. The IONDT enrolled patients ≥50 years with acute nonarteritic ischemic optic neuropathy (NAION). Randomized patients (n = 258) had visual acuity ≤20/64; nonrandomized patients (n = 160) had visual acuity >20/64 or refused randomization. Optic nerve decompression surgery (n = 127) or careful follow-up (n = 131). We measured visual fields at baseline and at 6 and 12 months follow-up. Using a computerized system, we classified visual field defects by pattern, location, and severity. We examined changes over time by treatment group, age, baseline comorbidities, and change in visual acuity. In fellow (nonstudy) eyes, we assessed change by whether NAION was present at baseline and also incidence of NAION by whether a visual field defect was present at baseline. We analyzed 245 study eye visual field pairs (179 and 66, randomized and nonrandomized, respectively) for change from baseline to 12 months. We observed significant changes in defect distribution within the central field (P = 0.02) for randomized eyes. Superior and inferior altitudinal defects were less severe at follow-up in both randomized and nonrandomized eyes. We observed an association between change in central field severity and change in visual acuity from baseline (P<0.001 at 6 months; P = 0.01 at 12 months; Kendall's tau-b), but no association between visual field change and treatment group, age, or baseline comorbidities. Superior and inferior visual field defects present at baseline in nonstudy eyes improved at follow-up. Fellow (nonstudy) eyes with normal fields did not have an increased risk of developing NAION compared with eyes with ≥1 defects. Visual fields of NAION patients enrolled in the IONDT were relatively stable from baseline to follow-up. A visual field defect in the nonstudy eye at baseline was not associated with development of NAION during follow-up compared with eyes with normal fields.

Magnetic Resonance Imaging of the Brain in Nonarteritic Ischemic Optic Neuropathy

We wished to determine whether the number of central nervous system (CNS) white matter lesions on magnetic resonance imaging (MRI) is increased in patients with nonarteritic ischemic optic neuropathy (NAION). T2-Weighted axial images of the brain in 13 patients with acute NAION and 16 age-matched controls were used to tabulate the number of subcortical and periventricular white matter lesions. Groups were compared by t test for means, the Wilcoxon-Mann-Whitney rank-sum test, and chi-square test for proportions with at least one lesion. The mean number of CNS white matter ischemic lesions in the NAION group was 4.0 (range 0-20) as compared to 1.4 (range 0-7) in the control group. The difference in these samples suggested a significant increase in NAION (p = 0.069, rank-sum test). The proportions of patients with at least one lesion were not significantly different (53.8% NAION vs. 56.3% controls). The data suggest an increased number of CNS white matter lesions in patients with NAION.

Use of pattern electroretinography to differentiate acute optic neuritis from acute anterior ischemic optic neuropathy

The transient pattern electroretinogram (PERG) was recorded from 16 patients with acute neuritis and from 13 patients with acute non-arteritic ischemic optic neuropathy (AION). All patients were tested within 35 days from the the onset of visual symptoms and all had significant central visual field abnormalities in their affected eyes as quantified by automated perimetry. Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally reduced for each eye affected with AION while it remained normal in optic neuritis. No significant alteration in P50 amplitude was observed in either condition. The loss of N95 amplitude in AION was highly correlated with the average depth of visual field loss (in decibels) within a radius of 10° of fixation. These results suggest that PERG could be used early in the course of optic neuropathy to distinguish optic neuritis from AION in those cases for which the diagnosis is still uncertain after the clinical examination.

Optic Nerve Sheath Decompression May Improve Blood Flow in Anterior Ischemic Optic Neuropathy

The purposes of this study are to evaluate the retrobulbar circulation in progressive nonarteritic ischemic optic neuropathy (NAION) and to assess changes in blood flow after optic nerve sheath decompression (ONSD). Twenty-five patients with progressive NAION were studied using color Doppler imaging (CDI) before and after ONSD. Blood flow velocities and vascular resistance were calculated for the ophthalmic artery, central retinal artery, and posterior ciliary arteries in each eye. Contralateral eyes served as the control group. Preoperatively, the study group demonstrated significantly lower blood flow velocities in the central retinal artery (P < 0.002) and posterior ciliary arteries (P < 0.02) when compared with the contralateral control group. Postoperatively, there was a significant increase in blood flow velocity in the ophthalmic artery (P < 0.04) and the central retinal artery (P < 0.05) as well as a significant decrease in vascular resistance in the posterior ciliary arteries (P < 0.02) in the study group. There were no significant changes in blood flow velocity or vascular resistance in the contralateral control group. Long-term follow-up on eight patients suggests a persistence of this trend. Seventeen of the 25 operated eyes demonstrated a postoperative improvement in visual function, defined as a gain of two lines or more in Snellen visual acuity or at least 20 degrees of visual field expansion. These data demonstrate that eyes with acute NAION have impaired blood flow when compared with the contralateral control group. Furthermore, they suggest that ONSD may improve blood flow to the ischemic optic nerve halting the progression of visual loss and in some cases improving visual function.