Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial.

PURPOSE: We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Prospective, randomized controlled clinical trial. PARTICIPANTS: Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries. MAIN OUTCOME MEASURES: Ophthalmic features of NAION and cardiovascular risk factors. METHODS: We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables. RESULTS: The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53-84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was -16.5 dB (IQR, -22.2 to -12.6 dB) for stimulus III and -15.7 dB (IQR, -20.8 to -10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1-0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features. CONCLUSIONS: The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visualization of Optic Nerve Structural Patterns in Papilledema Using Deep Learning Variational Autoencoders.

Purpose: To visualize and quantify structural patterns of optic nerve edema encountered in papilledema during treatment. Methods: A novel bi-channel deep-learning variational autoencoder (biVAE) model was trained using 1498 optical coherence tomography (OCT) scans of 125 subjects over time from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and 791 OCT scans of 96 control subjects from the University of Iowa. An independent test dataset of 70 eyes from 70 papilledema subjects was used to evaluate the ability of the biVAE model to quantify and reconstruct the papilledema spatial patterns from input OCT scans using only two variables. Results: The montage color maps of the retinal nerve fiber layer (RNFL) and total retinal thickness (TRT) produced by the biVAE model provided an organized visualization of the variety of morphological patterns of optic disc edema (including differing patterns at similar thickness levels). Treatment effects of acetazolamide versus placebo in the IIHTT were also demonstrated in the latent space. In image reconstruction, the mean signed peripapillary retinal nerve fiber layer thickness (pRNFLT) difference ± SD was -0.12 ± 17.34 µm, the absolute pRNFLT difference was 13.68 ± 10.65 µm, and the RNFL structural similarity index reached 0.91 ± 0.05. Conclusions: A wide array of structural patterns of papilledema, integrating the magnitude of disc edema with underlying disc and retinal morphology, can be quantified by just two latent variables. Translational Relevance: A biVAE model encodes structural patterns, as well as the correlation between channels, and may be applied to visualize individuals or populations with papilledema throughout treatment.

Attitudes and Beliefs Toward Thymectomy in the Myasthenia Gravis Patient Registry.

OBJECTIVES: To evaluate patient attitudes and beliefs toward thymectomy for myasthenia gravis (MG). METHODS: The Myasthenia Gravis Foundation of America administered a questionnaire to the MG Patient Registry, an ongoing longitudinal survey of adult MG patients. Questions assessed reasons for or against thymectomy and how hypothetical scenarios would have affected their decision. RESULTS: Of 621 respondents, 190 (31%) reported a history of thymectomy. Of those who underwent thymectomy for nonthymomatous MG, 97 (51.6%) ranked symptom improvement as most important and 100 (53.2%) ranked reducing medication as least important. Among 431 nonthymectomy patients, the most frequent reason for not undergoing thymectomy was that their doctor did not discuss it (152 of 431 = 35.2%) and 235 (56.8%) said that they would have considered it more strongly if their doctor spent more time discussing it. CONCLUSIONS: Thymectomies are motivated more by symptoms than by medication, and a lack of neurologist discussion is the most common barrier to thymectomy.

Archetypal analysis of longitudinal visual fields for idiopathic intracranial hypertension patients presenting in a clinic setting.

We previously applied archetypal analysis (AA) using visual fields (VF) from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) to derive a model, which quantified patterns (or archetypes [ATs] of VF loss), anticipated recovery, and identified residual VF deficits. We hypothesized that AA could produce similar results using IIH VFs collected in clinical practice. We applied AA to 803 VFs from 235 eyes with IIH from an outpatient neuro-ophthalmology clinic and created a clinic-derived model of ATs, with the relative weight (RW) and average total deviation (TD) for each AT. We also created a combined-derived model from an input dataset containing the clinic VFs and 2862 VFs from the IIHTT. We used both models to decompose clinic VF into ATs of varying percent weight (PW), correlated presentation AT PW with mean deviation (MD), and evaluated final visit VFs considered "normal" by MD ≥ -2.00 dB for residual abnormal ATs. The 14-AT clinic-derived and combined-derived models revealed similar patterns of VF loss previously identified in the IIHTT model. AT1 (a normal pattern) was most prevalent in both models (RW = 51.8% for clinic-derived; 35.4% for combined-derived). Presentation AT1 PW correlated with final visit MD (r = 0.82, p < 0.001 for the clinic-derived model; r = 0.59, p < 0.001 for the combined-derived model). Both models showed ATs with similar patterns of regional VF loss. The most common patterns of VF loss in "normal" final visit VFs using each model were clinic-derived AT2 (mild global depression with enlarged blind spot; 44/125 VFs; 34%) and combined-derived AT2 (near-normal; 93/149 VFs; 62%). AA provides quantitative values for IIH-related patterns of VF loss that can be used to monitor VF changes in a clinic setting. Presentation AT1 PW is associated with the degree of VF recovery. AA identifies residual VF deficits not otherwise indicated by MD.

Specific recommendations to improve the design and conduct of clinical trials.

There are many reasons why the majority of clinical trials fail or have limited applicability to patient care. These include restrictive entry criteria, short duration studies, unrecognized adverse drug effects, and reporting of therapy assignment preferential to actual use. Frequently, experimental animal models are used sparingly and do not accurately simulate human disease. We suggest two approaches to improve the conduct, increase the success, and applicability of clinical trials. Studies can apply dosing of the investigational therapeutics and outcomes, determined from animal models that more closely simulate human disease. More extensive identification of known and potential risk factors and confounding issues, gleaned from recently organized "big data," should be utilized to create models for trials. The risk factors in each model are then accounted for and managed during each study.

Unsupervised Machine Learning Shows Change in Visual Field Loss in the Idiopathic Intracranial Hypertension Treatment Trial.

PURPOSE: We previously reported that archetypal analysis (AA), a type of unsupervised machine learning, identified and quantified patterns of visual field (VF) loss in idiopathic intracranial hypertension (IIH), referred to as archetypes (ATs). We assessed whether AT weight changes over time are consistent with changes in conventional global indices, whether visual outcome or treatment effects are associated with select AT, and whether AA reveals residual VF defects in eyes deemed normal after treatment. DESIGN: Analysis of data collected from a randomized controlled trial. PARTICIPANTS: Two thousand eight hundred sixty-two VFs obtained from 165 participants during the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: We applied a 14-AT model derived from IIHTT VFs. We examined changes in individual AT weights over time for all study eyes and evaluated differences between treatment groups. We created an AT change score to assess overall VF change from baseline. We tested threshold baseline AT weights for association with VF outcome and treatment effect at 6 months. We determined the abnormal ATs with meaningful weight at outcome for VFs with a mean deviation (MD) of -2.00 dB or more. MAIN OUTCOME MEASURES: Individual AT weighting coefficients and MD. RESULTS: Archetype 1 (a normal VF pattern) showed the greatest weight change for all study eyes, increasing from 11.9% (interquartile range [IQR], 0.44%-24.1%) at baseline to 31.2% (IQR, 16.0%-45.5%) at outcome (P < 0.001). Archetype 1 weight change (r = 0.795; P < 0.001) and a global score of AT change (r = 0.988; P < 0.001) correlated strongly with MD change. Study eyes with baseline AT2 (a mild diffuse VF loss pattern) weight of 44% or more (≥ 1 standard deviation more than the mean) showed higher AT2 weights at outcome than those with AT2 weight of < 44% at baseline (P < 0.001). Only the latter group showed a significant acetazolamide treatment effect. Archetypal analysis revealed residual VF loss patterns, most frequently representing mild diffuse loss and an enlarged blind spot in 64 of 66 study eyes with MD of -2.00 dB or more at outcome. CONCLUSIONS: Archetypal analysis provides a quantitative approach to monitoring VF changes in IIH. Baseline AT features may be associated with treatment response and VF outcome. Archetypal analysis uncovers residual VF defects not otherwise revealed by MD.

Unsupervised Machine Learning Identifies Quantifiable Patterns of Visual Field Loss in Idiopathic Intracranial Hypertension.

Purpose: Archetypal analysis, a form of unsupervised machine learning, identifies archetypal patterns within a visual field (VF) dataset such that any VF is described as a weighted sum of its archetypes (ATs) and has been used to quantify VF defects in glaucoma. We applied archetypal analysis to VFs affected by nonglaucomatous optic neuropathy caused by idiopathic intracranial hypertension (IIH). Methods: We created an AT model from 2862 VFs prospectively collected from 330 eyes in the IIH Treatment Trial (IIHTT). We compared baseline IIH AT patterns with their descriptive VF classifications from the IIHTT. Results: The optimum IIH AT model yielded 14 ATs resembling VF patterns reported in the IIHTT. Baseline VFs contained four or fewer meaningful ATs in 147 (89%) of study eyes. AT2 (mild general VF depression pattern) demonstrated the greatest number of study eyes with meaningful AT weight at baseline (n = 114), followed by AT1 (n = 91). Other ATs captured patterns of blind spot enlargement, hemianopia, arcuate, nasal defects, and more nonspecific patterns of general VF depression. Of all ATs, AT1 (normal pattern) had the strongest correlation with mean deviation (r = 0.69, P < 0.001). For 65 of the 93 VFs with a dominant AT, this AT matched the expert classification. Conclusions: Archetypal analysis identifies quantifiable, archetypal VF defects that resemble those commonly seen in IIH. Translational Relevance: Archetypal analysis provides a quantitative, objective method of measuring and monitoring disease-specific regional VF defects in IIH.

Ocular myasthenia gravis - How effective is low dose prednisone long term?

INTRODUCTION: Controversy persists on the best treatment to control ocular myasthenia gravis (OMG) and reduce conversion to generalized myasthenia gravis (GMG). We hypothesized that low dose prednisone could accomplish both in a cohort of OMG patients followed after three years. METHODS: We reviewed the records of 168 patients who presented with OMG. Our study included 103 of the OMG patients who met inclusion criteria, requiring follow up for a minimum of 3 years without disease generalization. Low dose prednisone was defined as ≤7.5 mg per day. The main outcome was having single vision without ptosis blocking vision, measured by binocular single vision (BSV) and upper lid position. We also analyzed late progression to GMG. RESULTS: Of 87 patients treated with prednisone, chronic low dose prednisone alone restored BSV in 47 patients (46% of all patients) without GMG. Pyridostigmine monotherapy restored BSV in 11/14 patients (11% of all patients). Other immunomodulatory therapy (OIT) was needed in 38 patients (37%). Medical therapy maintained BSV at last evaluation (mean follow up 8.2 ± 5.0 years) in 93 patients (90%). GMG developed in 10 patients (10%) during the follow-up period. CONCLUSION: In OMG patients who do not generalize before 3 years, chronic long term prednisone at lower doses is moderately effective in maintaining optimum BSV. However, OIT are commonly required in these patients. In these OMG patients receiving prednisone and/or OIT, conversion to GMG after three years of disease is uncommon.

Retinal and Optic Nerve Deformations Due to Orbital Versus Intracranial Venous Hypertension.

INTRODUCTION: Abnormal forces around the optic nerve head (ONH) due to orbital diseases, intracranial hypertension (IH), glaucoma, and space travel, are associated with alterations of the ONH shape. Elevated cerebral and ophthalmic venous pressure can contribute to stress and strain on the ONH and peripapillary retina. We hypothesize that IH and elevated ophthalmic venous pressure without IH cause different ONH and retinal changes. METHODS: We compared MRI and spectral domain optical coherence tomography (SDOCT) findings in patients with cavernous sinus arteriovenous shunts (CSAVSs), where orbital venous pressure is known to be elevated, with patients with intracranial dural venous sinus thrombosis and secondary IH. We also compared the results to those obtained in the Idiopathic IH (IIH) Treatment Trial. RESULTS: Among 18 patients with dural venous sinus thrombosis, the MRI/magnetic resonance venography displayed partial empty sella (61%) and optic nerve sheath distension (67%). None exhibited ophthalmic vein dilation or signs of orbital congestion. SDOCT of these eyes and IIH eyes showed a similar frequency of abnormal thickening of the mean retinal nerve fiber layer, anterior displacement of the basement membrane opening, peripapillary wrinkles, retinal folds (RF), and choroidal folds (CF). Among 21 patients with CSAVSs, MRI showed ipsilateral dilated superior ophthalmic vein (76%) and orbital congestion (52%) without distension of the optic nerve sheath or globe distortion. SDOCT showed CF (19%), one with overlying RF, and no ONH deformations. CONCLUSIONS: SDOCT findings for dural venous sinus thrombosis are similar to those seen with IIH but distinct from changes due to local ophthalmic venous hypertension. These data support the concept that IH even if due to a vascular cause and local orbital venous hypertension cause different stresses and strains on the ONH.

Optical Coherence Tomography Neuro-Toolbox for the Diagnosis and Management of Papilledema, Optic Disc Edema, and Pseudopapilledema.

BACKGROUND: Distinguishing optic disc edema from pseudopapilledema is a common, sometimes challenging clinical problem. Advances in spectral-domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) has proven to be a cost effective, noninvasive, outpatient procedure that may help. At its core are tools that quantify the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL). The SD-OCT also provides a set of tools that may be qualitatively interpreted in the same way that we read an MRI. They include the transverse axial, en face, and circular tomogram. Our goal is to describe a practical office-based set of tools using SD-OCT in the diagnosis and monitoring of papilledema, optic disc edema, and pseudopapilledema. EVIDENCE ACQUISITION: Searches on PubMed were performed using combinations of the following key words: OCT, papilledema, pseudopapilledema, optic disc drusen, retinal folds (RF), and choroidal folds (CF). RESULTS: The principal elements of SD-OCT analysis of the ONH are the RNFL and GC-IPL thickness; however, these metrics have limitations when swelling is severe. Qualitative interpretation of the transverse axial SD-OCT aids in assessing peripapillary shape that may help distinguish papilledema from pseudopapilledema, evaluate atypical optic neuropathies, diagnose shunt failures, and identify outer RF and CF. There is a consensus that the SD-OCT is the most sensitive way of identifying buried optic disc drusen. En face SD-OCT is especially effective at detecting peripapillary wrinkles and outer retinal creases, both of which are common and distinctive signs of optic disc edema that rule out pseudopapilledema. Mechanically stressing the ONH in the adducted eye position, in patients with papilledema, may expose folds and peripapillary deformations that may not be evident in primary position. We also discuss how to optimize the acquisition and registration of SD-OCT images. CONCLUSIONS: The SD-OCT is not a substitute for a complete history and a careful examination. It is, however, a convenient ancillary test that aids in the diagnosis and management of papilledema, optic disc edema, and pseudopapilledema. It is particularly helpful in monitoring changes over the course of time and distinguishing low-grade papilledema from buried drusen. The application of the SD-OCT toolbox depends on optimizing the acquisition of images, understanding its limitations, recognizing common artifacts, and accurately interpreting images in the context of both history and clinical findings.

Assessment of Pediatric Optic Neuritis Visual Acuity Outcomes at 6 Months.

Importance: Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis. Objective: To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively. Design, Setting, and Participants: This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON. Main Outcomes and Measures: Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein. Results: A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA. Conclusions and Relevance: The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.

The Effect of Acetazolamide and Weight Loss on Intraocular Pressure in Idiopathic Intracranial Hypertension Patients.

PURPOSE: Acetazolamide (ACZ) lowers intraocular pressure (IOP), acutely in normal eyes and both acutely and chronically in eyes with glaucoma, and cerebrospinal fluid pressure (CSFp), chronically in patients with idiopathic intracranial hypertension (IIH). We hypothesize chronic daily ACZ would significantly reduce IOP and contribute to a translaminar pressure gradient change reflected by alteration in the CSFp-IOP difference and the deformation of the neural canal in patients with IIH and no glaucoma. PATIENTS AND METHODS: Before randomization to ACZ or placebo treatment for 6 months, 165 participants in the IIH Treatment Trial had evaluations that included Goldmann applanation, CSFp measurement, and optical coherence tomography determination of the neural canal deformation. These measures were repeated at the 6-month outcome. RESULTS: The IOP was not significantly decreased from baseline at 1, 3, or 6 months in eyes in both treatment groups. At month 6, the amount of ACZ or weight modification did not correlate with any IOP change. The 6-month mean change in neural canal deformation was 0.96 and -0.04 (P=0.001) and in CSFp was -128 and -38 mm H2O (P=0.001), but CSFp-IOP difference change was not significant, in the ACZ and placebo groups, respectively. CONCLUSIONS: ACZ does not reduce the IOP in eyes without glaucoma but does decrease the pathologic elevated CSFp, providing evidence that normal systems can compensate for chronic medication effects. The CSFp-IOP is not a direct marker of translaminar pressure gradient and the ACZ normalization of the neural canal deformation appears due to CSFp reduction alone.

Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure of unknown cause. IIH has been shown to be associated with female sex as well as obesity. This genome-wide association study was performed to determine whether genetic variants are associated with this condition. METHODS: We analyzed the chromosomal DNA of 95 patients with IIH enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and 95 controls matched on sex, body mass index, and self-reported ethnicity. The samples were genotyped using Illumina Infinium HumanCoreExome v1-0 array and analyzed using a generalized linear mixed model that accounted for population stratification using multidimensional scaling. RESULTS: A total of 301,908 single nucleotide polymorphisms (SNPs) were evaluated. The strongest associations observed were for rs2234671 on chromosome 2 (P = 4.93 × 10), rs79642714 on chromosome 6 (P = 2.12 × 10), and rs200288366 on chromosome 12 (P = 6.23 × 10). In addition, 3 candidate regions marked by multiple associated SNPs were identified on chromosome 5, 13, and 14. CONCLUSIONS: This is the first study to investigate the genetics of IIH in a rigorously characterized cohort. The study was limited by its modest size and thus would have only been able to demonstrate highly significant association on a genome-wide scale for relatively common alleles exerting large effects. However, several variants and loci were identified that might be strong candidates for follow-up studies in other well-phenotyped cohorts.

Long-term efficacy of fractionated conformal radiotherapy for the management of primary optic nerve sheath meningioma.

BACKGROUND/AIM: Fractionated conformal radiotherapy (FCRT) is now used to treat vision-threatening optic nerve sheath meningioma (ONSM), but long-term efficacy and safety data are lacking; the purpose of this study was to assess these key data. METHODS: This is a retrospective chart review with prospective follow-up of adult patients treated with FCRT for primary ONSM at four academic medical centres between 1995 and 2007 with ≥10 years of follow-up after treatment. RESULTS: 16 patients were identified with a mean post-treatment follow-up of 14.6 years (range: 10.5-20.7 years). The mean age at symptom onset was 47.6 years (range: 36-60 years). FCRT was performed at a mean of 2.3 years after symptom onset (range: 0.2-14.0 years). At last follow-up, visual acuity had improved or stabilised in 14 of the 16 (88%) patients, and 11 (69%) had retained or achieved ≥20/40. The mean deviation on automated perimetry remained stable (-14.5 dB pretreatment vs -12.2 dB at last follow-up; p=0.68, n=10). Two (11%) patients had persistent pain, proptosis or diplopia, compared with six (38%) pretreatment (p=0.11). Two (13%) patients developed radiation retinopathy more than 6 months after completion of therapy, one (50%) of whom had worse visual acuity compared with pretreatment. No patient developed tumour involvement or radiation damage in the fellow eye. CONCLUSION: FCRT stabilises or improves visual function in patients with primary ONSM and is associated with a low risk of significant ocular sequelae. This treatment should be considered instead of surgery in patients with primary ONSM who require intervention due to loss of visual sensory and/or ocular motor function.

Nonarteritic Anterior Ischemic Optic Neuropathy Induced Retinal Folds and Deformations.

Purpose: We hypothesized that the edema/swelling in the retina due to acute nonarteritic anterior ischemic optic neuropathy (NAION) can induce retinal folds (RF). We determined the pattern and frequency of folds in NAION at presentation and in follow-up, and the relationship between folds and a number of functional and structural parameters over time. Methods: We prospectively studied eyes with acute NAION by spectral-domain optic coherence tomography (SD-OCT). We used transaxial and en face views to evaluate the presence of peripapillary fluid (PPF), peripapillary wrinkles (PPW), RF, choroidal folds (CF), creases, macular edema, and vitreous traction on the optic disc. Retinal deformations were correlated with the retinal nerve fiber layer (RNFL) thickness, logMAR visual acuity (VA) and mean deviation (MD). Results: At presentation, 60 eyes had mean RNFL = 224 ± 75 µm, no vitreous traction, and similar VA and MD regardless of the retinal deformation or macular edema. There was PPF in 73%, PPW in 57%, RF in 38%, creases in 20%, and macular edema in 18% of eyes, and no CF. Eyes with retinal deformations had significantly greater RNFL thickness (P< 0.026). At 1 to 2 months, 49 eyes had reduction of the RNFL (112 ± 40 µm, P = 0.001) and unchanged VA and MD that did not correlate with fewer eyes having PPF (15%, P = 0.001), PPW (10%, P = 0.001), RF (10%, P = 0.001), creases (17%), and macular edema (0%, P = 0.007). Conclusions: RF in NAION reflect stresses and strains due to extracellular fluid without increased pressure in the retrolaminar tissue and subarachnoid space, seen with papilledema. In NAION, the deformations and their resolution do not correlate with vision loss.

Peripapillary Retinal Pigment Epithelium Layer Shape Changes From Acetazolamide Treatment in the Idiopathic Intracranial Hypertension Treatment Trial.

Purpose: Recent studies indicate that the amount of deformation of the peripapillary retinal pigment epithelium and Bruch's membrane (pRPE/BM) toward or away from the vitreous may reflect acute changes in cerebrospinal fluid pressure. The study purpose is to determine if changes in optic-nerve-head (ONH) shape reflect a treatment effect (acetazolamide/placebo + weight management) using the optical coherence tomography (OCT) substudy of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) at baseline, 3, and 6 months. Methods: The pRPE/BM shape deformation was quantified and compared with ONH volume, peripapillary retinal nerve fiber layer (pRNFL), and total retinal (pTR) thicknesses in the acetazolamide group (39 subjects) and placebo group (31 subjects) at baseline, 3, and 6 months. Results: Mean changes of the pRPE/BM shape measure were significant and in the positive direction (away from the vitreous) for the acetazolamide group (P < 0.01), but not for the placebo group. The three OCT measures reflecting the reduction of optic disc swelling were significant in both treatment groups but greater in the acetazolamide group (P < 0.01). Conclusions: Change in the pRPE/BM shape away from the vitreous reflects the effect of acetazolamide + weight management in reducing the pressure differential between the intraocular and retrobulbar arachnoid space. Weight management alone was also associated with a decrease in optic nerve volume/edema but without a significant change in the pRPE/BM shape, implying an alternative mechanism for improvement in papilledema and axoplasmic flow, independent of a reduction in the pressure differential. (ClinicalTrials.gov number, NCT01003639.).

Optical Coherence Tomography in Neuroretinitis: Epipapillary Infiltrates and Retinal Folds.

Neuroretinitis is a form of papillitis associated with the delayed onset of an exudative macular star among other inflammatory ocular findings. We describe 4 patients with neuroretinitis who displayed several distinctive and novel findings on spectral-domain optical coherence tomography (OCT) that include "epipapillary infiltrates" and an atypical pattern of inner retinal folds. The recognition of these findings on OCT may help in the early diagnosis of neuroretinitis.