Comparison between contrast-enhanced fat-suppressed 3D FLAIR brain MR images and T2-weighted orbital MR images at 3 Tesla for the diagnosis of acute optic neuritis.

PURPOSE: The purpose of this study was to compare the capabilities of contrast-enhanced fat-suppressed (CE FS) three-dimensional fluid-attenuated inversion recovery (3D FLAIR) brain magnetic resonance imaging (MRI) with those of coronal T2-weighted orbital MRI obtained at 3 Tesla for the diagnosis of optic neuritis (ON). MATERIALS AND METHODS: Patients who presented to our center with acute visual loss and underwent MRI examination of the orbits and the brain between November 2014 and February 2020 were retrospectively included. Three radiologists independently and blindly analyzed CE FS 3D FLAIR and coronal T2-weighted images. Disagreements in image interpretation were resolved by consensus with an independent neuroradiologist who was not involved in the initial reading sessions. The primary adjudication criterion for the diagnosis of ON was the presence of an optic nerve hypersignal. Sensitivity, specificity, and accuracy of CE 3D FLAIR brain images were compared with those of coronal T2-weighted orbital images using McNemar test. Artifacts were classified into three categories and compared between the two image sets. RESULTS: A total of 1023 patients were included. There were 638 women and 385 men with a mean age of 42 ± 18.3 (standard deviation) years (age range: 6-92 years). Optic nerve hyperintensities were identified in 375/400 (94%) patients with ON using both 3D FLAIR and coronal T2-weighted images. Sensitivity, specificity, and accuracy of both sequences were 94% (95% CI: 91.3-96.1), 79% (95% CI: 75.5-82.2), and 89% (95% CI: 86.8-90.7), respectively. Optic disc hypersignal was detected in 120/400 patients (30%) using 3D FLAIR compared to 3/400 (0.75%) using coronal T2-weighted images (P < 0.001). Optic radiation hypersignal was observed in 2/400 (0.5%) patients using 3D FLAIR images. Significantly more artifacts (moderate or severe) were observed on coronal T2-weighted images (801/1023; 78%) by comparison with 3D FLAIR images (448/1023; 44%) (P < 0.001). CONCLUSION: The performance of 3D FLAIR brain MRI for the diagnosis of ON is not different from that of coronal T2-weighted orbital MRI and its use for optic nerve analysis may be beneficial.

Are PHOMS (Peri papillary hyperreflective ovoid mass-like structures ) with an elevated optic disc still a diagnosis dilemma?

OBJECTIVE: To identify clinical characteristics that would help make or rule out the diagnosis of Idiopathic intracranial hypertension (IIH) in patients referred for papilledema (PE) with peripapillary hyperreflective ovoid mass-like structures (PHOMS) DESIGN: A retrospective cohort study SUBJECTS: All patient referred for PE excluding PE with Frisén grade ≥ 3, optic neuritis, ischemic optic neuropathy, compressive optic neuropathy. Patients were divided into 2 groups: Group1= isolated PHOMS Group2= PHOMS associated with IIH METHODS: We analyzed the location of PHOMS based on OCT-EDI and calculated their volume MAIN OUTCOME MEASURES: P RNFL,GCC, PHOMS' volume RESULTS: 154 patients (308 eyes) were included, mean age was 29 with female predominance (78%). PHOMS were associated to these etiologies : IIH(38.3%) isolated (35.7%), posterior uveitis (11%),optic disc drusen (ODD)(10%), and tilted optic disc (5%). An MRI was obtained in 83.1% of cases. More than half of the MRIs were interpreted as consistent with IIH. However, only 39.7% of these patients had confirmed IIH with 44.5% of sensitivity and 55.5% of sensibility. PHOMS were overrepresented in the nasal region (95.5%).The location of PHOMS in the superior and/ or inferior quadrant was significantly associated to IIH or optic dusc drusen, while their presence in the temporal or nasal sector was strongly associated to isolated lesions. PHOMS mean and median volume were 1.66 µm3 and 1.50 µm3 respectively. There was a significant difference in PHOMS volume with higher volume in IIH patients (p=0.0037). Follow up of these patients at 3 and 6 months demonstrated no significant changes in visual function, as per visual field mean deviation, and visual acuity measurements as well as Ganglion cell layer (GCL).Mean pRNFL, showed a decrease of -4.225 µm at 3 months and of -6.489 µm at 6 months, when compared to initial measurement independing of the etiology. CONCLUSION: Isolated PHOMS should be considered as a distinct entity. In asymptomatic patients, PHOMS should be carefully studied. Nasal or temporal location, small volume, stable aspect over the course of weeks or months, are so suggestive of this entity. This strategy would considerably reduce the impact on patients' anxiety and morbidity.

A Deep Learning Approach for Accurate Discrimination Between Optic Disc Drusen and Papilledema on Fundus Photographs.

BACKGROUND: Optic disc drusen (ODD) represent an important differential diagnosis of papilledema caused by intracranial hypertension, but their distinction may be difficult in clinical practice. The aim of this study was to train, validate, and test a dedicated deep learning system (DLS) for binary classification of ODD vs papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs collected in a large international multiethnic population. METHODS: This retrospective study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External testing was performed on an independent data set (221 patients), including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study. RESULTS: The DLS could accurately distinguish between all ODD and papilledema (all severities included): area under the receiver operating characteristic curve (AUC) 0.97 (95% confidence interval [CI], 0.96-0.98), accuracy 90.5% (95% CI, 88.0%-92.9%), sensitivity 86.0% (95% CI, 82.1%-90.1%), and specificity 94.9% (95% CI, 92.3%-97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90-0.96), accuracy 84.2% (95% CI, 80.2%-88.6%), sensitivity 78.4% (95% CI, 72.2%-84.7%), and specificity 91.3% (95% CI, 87.0%-96.4%). CONCLUSIONS: A dedicated DLS can accurately distinguish between ODD and papilledema caused by intracranial hypertension, even when considering buried ODD vs mild-to-moderate papilledema.

Comparison of a Whole-Brain Contrast-Enhanced 3D TSE T1WI versus Orbits Contrast-Enhanced 2D Coronal T1WI at 3T MRI for the Detection of Optic Nerve Enhancement in Patients with Acute Loss of Visual Acuity.

BACKGROUND AND PURPOSE: MR imaging is the technique of choice for patients presenting with acute loss of visual acuity with no obvious ophthalmologic cause. The goal of our study was to compare orbits contrast-enhanced 2D coronal T1WI with a whole-brain contrast-enhanced 3D (WBCE-3D) TSE T1WI at 3T for the detection of optic nerve enhancement. MATERIALS AND METHODS: This institutional review board-approved retrospective single-center study included patients presenting with acute loss of vision who underwent 3T MR imaging from November 2014 to February 2020. Two radiologists, blinded to all data, individually assessed the presence of enhancement of the optic nerve on orbits contrast-enhanced 2D T1WI and WBCE-3D T1WI separately and in random order. A McNemar test and a Cohen κ method were used for comparing the 2 MR imaging sequences. RESULTS: One thousand twenty-three patients (638 women and 385 men; mean age, 42 [SD, 18.3] years) were included. There was a strong concordance between WBCE-3D T1WI and orbits contrast-enhanced 2D T1WI when detecting enhancement of the optic nerve: κ = 0.87 (95% CI, 0.84-0.90). WBCE-3D T1WI was significantly more likely to detect canalicular enhancement compared with orbits contrast-enhanced 2D T1WI: 178/1023 (17.4%) versus 138/1023 (13.5%) (P < .001) and 108/1023 (10.6%) versus 90/1023 (8.8%) (P = .04), respectively. The WBCE-3D T1WI sequence detected 27/1023 (3%) instances of optic disc enhancement versus 0/1023 (0%) on orbits contrast-enhanced 2D T1WI. There were significantly fewer severe artifacts on WBCE-3D T1WI compared with orbits contrast-enhanced 2D T1WI: 68/1023 (6.6%) versus 101/1023 (9.8%) (P < .001). The median reader-reported confidence was significantly higher with coronal T1WI compared with 3D TSE T1WI: 5 (95% CI, 4-5) versus 3 (95% CI, 1-4; P < .001). CONCLUSIONS: Our study showed that there was a strong concordance between WBCE-3D T1WI and orbits contrast-enhanced 2D T1WI when detecting enhancement of the optic nerve in patients with acute loss of visual acuity with no obvious ophthalmologic cause. WBCE-3D T1WI demonstrated higher sensitivity and specificity in diagnosing optic neuritis, particularly in cases involving the canalicular segments.

Method to Quickly Map Multifocal Pupillary Response Fields (mPRF) Using Frequency Tagging.

We present a method for mapping multifocal Pupillary Response Fields in a short amount of time using a visual stimulus covering 40° of the visual angle divided into nine contiguous sectors simultaneously modulated in luminance at specific, incommensurate, temporal frequencies. We test this multifocal Pupillary Frequency Tagging (mPFT) approach with young healthy participants (N = 36) and show that the spectral power of the sustained pupillary response elicited by 45 s of fixation of this multipartite stimulus reflects the relative contribution of each sector/frequency to the overall pupillary response. We further analyze the phase lag for each temporal frequency as well as several global features related to pupil state. Test/retest performed on a subset of participants indicates good repeatability. We also investigate the existence of structural (RNFL)/functional (mPFT) relationships. We then summarize the results of clinical studies conducted with mPFT on patients with neuropathies and retinopathies and show that the features derived from pupillary signal analyses, the distribution of spectral power in particular, are homologous to disease characteristics and allow for sorting patients from healthy participants with excellent sensitivity and specificity. This method thus appears as a convenient, objective, and fast tool for assessing the integrity of retino-pupillary circuits as well as idiosyncrasies and permits to objectively assess and follow-up retinopathies or neuropathies in a short amount of time.

Incidence and Outcomes of Eye Trauma Associated With Recreative Use of Nonpowder Toy Guns: A 12-Year Retrospective Study.

PURPOSE: Nonpowder toy guns (NPTGs) are responsible for many ocular traumas. This study aims to detail the outcomes of these injuries depending on the causative NPTG. DESIGN: Retrospective, observational case series. METHODS: Cases of NPTG-associated ocular trauma managed in a Parisian eye emergency department between August 1, 2010, and January 1, 2023, were reviewed. The date of trauma, causative NPTG, patient demographics, initial and follow-up eye examinations, any surgical procedure, and visual outcomes for each ocular trauma were analyzed. RESULTS: Over 12 years, NPTGs were responsible for 324 eye injuries and 980 visits. Patients were mostly male (77.5%), and mean age at trauma was 16.2 years. Foam bullets or foam dart blasters accounted for 54.9% of traumas and were mainly responsible for corneal injuries and hyphema (30.9% and 27%, respectively). BB guns and airsoft guns were frequently responsible for anterior segment lesions, as well as intravitreal hemorrhages (14.7%) and commotio retinae (21.1%). Paintball guns accounted for the largest proportion of posterior segment lesions (eg, intraretinal or subretinal hemorrhages leading to macular atrophy/contusion maculopathy), and one-third of casualties had undergone ocular surgery. Among all traumas, final visual acuity was lower than 20/200 in 6.5% of cases. Phthisis occurred in 8 cases: Two were related to foam bullets or foam dart blaster injuries (1 contusion and 1 rupture), 2 other cases followed a rupture due to BB guns/airsoft guns, 1 case occurred after a rupture related to a paintball gunshot, and 3 others were due to other types of compressed air guns (1 rupture, 1 intraocular foreign body, and 1 total retinal detachment). CONCLUSIONS: NPTG-related ocular trauma outcomes differ according to the causative toy. Paintball guns and BB guns/airsoft gun-related traumas were more likely to be associated with severe lesions, but an increasing number of ocular injuries related to the use of foam bullets or foam dart blasters are reported in younger and younger children. Public health policies should promote the use of protective eyewear.

Characteristics and Prognosis of Binocular Diplopia in Patients With Giant Cell Arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a large vessel vasculitis associated with a risk of permanent ophthalmologic complications. Data about diplopia prognosis in GCA are scarce. This study was designed to better characterize diplopia in newly diagnosed GCA patients. METHODS: All consecutive patients diagnosed with GCA from January 2015 to April 2021 in a French tertiary ophthalmologic center were retrospectively reviewed. GCA diagnosis relied on a positive temporal artery biopsy or high-definition MRI. RESULTS: Among 111 patients diagnosed with GCA, 30 patients (27%) had diplopia. Characteristics of patients with diplopia were similar to other GCA patients. Diplopia resolved spontaneously in 6 patients (20%). Diplopia was attributed to cranial nerve palsy in 21/24 patients (88%), especially third (46%) and sixth cranial nerve (42%). Ocular ischemic lesions occurred in 11 of the 30 patients with diplopia (37%); 2 patients developed vision loss after initiation of corticosteroids. In the remaining 13 patients, diplopia resolved after treatment onset in 12 patients (92%) with a median delay of 10 days. Patients treated intravenously tended to have a quicker improvement than those treated orally, but with a similar resolution rate of diplopia at 1 month. Two patients had relapse of diplopia at 4 and 6 weeks after an initial treatment course of 24 and 18 months, respectively. CONCLUSIONS: Diplopia is a rare feature at GCA diagnosis, but should raise clinician suspicion for GCA when associated with cephalic symptoms and prompt the initiation of corticosteroids to prevent ocular ischemic complications.

Specificities of pediatric ocular emergencies before and during the COVID-19 era: A retrospective comparative study in an eye-related emergency department in Paris.

INTRODUCTION: Epidemiological data on the use of eye-related emergency services by children are limited. The objective of this study was to determine how COVID-19 affected the epidemiological trends of pediatric ocular emergencies. METHODS: We performed a retrospective chart review of children under the age of 18 years who visited our eye-related emergency department between March 17 and June 7, 2020 and between March 18 and June 9, 2019. This was a descriptive and comparative analysis of the two study periods based on the demographic characteristics of patients and the diagnosis reported by the ophthalmologist in the digital medical charts. One of the investigators performed a second reading of the files to homogenize the diagnosis classification based on the most frequently found items. RESULTS: In total, 754 children were seen in our eye-related emergency department during the 2020 study period versus 1399 in 2019, representing a 46% decrease. In 2019, the four main diagnoses were traumatic injury (30%), allergic conjunctivitis (15%), infectious conjunctivitis (12%), and chalazion/blepharitis (12%). In the 2020 study period there was a significant decrease in the proportion of patients presenting with traumatic injuries (p < 0.001), infectious conjunctivitis (p = 0.03), and chalazion/blepharitis (p < 0.001). Consultations for chalazion/blepharitis were the most affected by the pandemic, followed by traumatic injuries (-72% and -64%, respectively). The proportion of patients who required surgery after trauma was higher in 2020 than in 2019 (p < 0.01), but the absolute number of severe trauma cases remained stable. CONCLUSIONS: The COVID-19 pandemic was accompanied by a decrease in the overall use of a pediatric eye-related emergency services in Paris. Visits due to benign causes and ocular trauma also decreased, but visits for more severe pathologies were not affected. Longer-term epidemiological studies may confirm or refute a change in eye emergency department use habits.

Relevance of kappa free light chains index in patients with aquaporin-4 or myelin-oligodendrocyte-glycoprotein antibodies.

BACKGROUND: The kappa free light chains index (κ-index) is increasing in importance as a fast, easy, cost-effective, and quantitative biomarker in multiple sclerosis (MS), which can replace cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) detection. In previous studies, controls often included mixed patients with several inflammatory central nervous system disorders. The aim of the present study was to assess the κ-index in patients with serum aquaporin-4 (AQP4)-IgG or myelin-oligodendrocyte-glycoprotein (MOG)-IgG. METHODS: We analyzed CSF/serum samples of patients with AQP4-IgG or MOG-Ig and evaluated distinct κ-index cut-offs. We described clinical and magnetic resonance imaging (MRI) features of patients with the highest κ-index values. RESULTS: In 11 patients with AQP4-IgG, median κ-index was 16.8 (range 0.2; 63) and 6/11 (54.5%) had κ-index >12. Among 42 patients with MOG-IgG, 2 had low positive MOG-IgG titers, were ultimately diagnosed with MS, and had a markedly increased κ-index (54.1 and 102.5 respectively). For the remaining 40 MOG-IgG-positive patients the median κ-index was 0.3 (range 0.1; 15.5). Some 6/40 (15%) and 1/40 (2.5%) patients had a κ-index >6 and >12, respectively. None fulfilled MRI dissemination in space and dissemination in time (DIS/DIT) criteria and the final diagnosis was MOG-IgG-associated disease (MOGAD) for these 40 patients. Four of the 40 (10%) MOG-IgG-positive patients had OCB. CONCLUSION: While a marked increase in κ-index could discriminate MS from MOGAD, a low κ-index threshold could lead to confusion between MS and MOGAD or AQP4 antibody-positive neuromyelitis optica spectrum disorder.

Incidence of Eye Trauma in Children Associated With Foam Bullets or Foam Darts From Nonpowder Guns.

This case series estimates the annual incidence of pediatric eye injuries associated with recreational use of nonpowder guns at an ophthalmologic emergency department in France.

Retinal Nerve Fiber Layer Thickness/Minimum Rim Width Ratio Differentiates Glaucoma From Other Optic Neuropathies.

PRCIS: Global peripapillary retinal nerve fiber layer thickness (pRNFL)/Bruch membrane opening-minimum rim width (BMO-MRW) ratio is an objective and effective parameter to separate glaucomatous optic neuropathies (GONs) from nonGONs (NGONs). PURPOSE: This study was undertaken to evaluate the diagnostic capability of the pRNFL/ BMO-MRW ratio to differentiate GONs from NGONs. PATIENTS AND METHODS: This retrospective study included patients with an optic neuropathy (ON), visual loss for>6 months and a confirmed single etiology. pRNFL thickness and BMO-MRW were measured with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The diagnostic accuracies of pRNFL, BMO-MRW and the global pRNFL/BMO-MRW ratio were evaluated with the areas under receiver operating characteristics curves. RESULTS: One eye each from 171 patients was investigated: 50 primary open angle glaucomas, 15 normal pressure glaucomas, 50 optic neuritises, 15 nonarteritic anterior ischemic ONs, 24 compressive ONs, 10 dominant optic atrophies, and 7 nutritional ONs. The global pRNFL/BMO-MRW ratio had the highest area under receiver operating characteristics curve [0.97 vs. 0.92; P =0.01]. It was able to distinguish between GONs and NGONs with a cutoff value of 0.34. Increased mean deviation of the visual field-defect severity was associated with a higher ratio for GONs and a lower ratio for NGONs. CONCLUSION: Compared with NGONs and for the same degree of pRNFL thinning, lower BMO- MRW was found to be a specific marker of glaucoma, reflecting the neuroglial architecture changes within the optic nerve head typical of glaucoma and supporting fundamental pathophysiological differences.

Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy.

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation.

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY).

Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy.

PURPOSE: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. DESIGN: Pooled analysis of safety data from 5 clinical studies. METHODS: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2. RESULTS: Almost all patients (95.2%) received 9 × 1010 viral genomes and 87.8% had at least 2 years of follow-up. Most patients (75.1%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients; none were serious. Intraocular inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%), and were of mild (90.3%) or moderate (8.8%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.

Generalization of ocular myasthenia gravis 10 years after onset.

BACKGROUND: Generalization of ocular myasthenia gravis (OMG) represents a pejorative evolution, and no validated generalization-prevention strategy exists. The study aimed to determine the percentage of patients with OMG generalization and identify factors predictive of it to establish a prediction score. METHODS: This retrospective, observational study included 151 patients diagnosed with OMG after an initial work-up in our institution. The outcome measure was time to MG generalization. The explanatory variables were age at onset (> 55 years), sex, first-year anti-acetylcholine-receptor antibody-positivity, repetitive nerve stimulation showing electromyogram decrement and corticosteroid use. Kaplan-Meier estimations of the probability of risk of generalization, and descriptive and multivariate Cox model analyses were computed. A nomogram combining explanatory variables was used to establish a score to predict the probability of OMG generalization. RESULTS: Among 183 patients' charts identified, 151 had confirmed OMG. Their median follow-up was 5.7 years. Estimations (95% CI) of OMG-generalization risk at 1, 3 and 10 years post-symptom onset, respectively, were: 13.0% (7.3-18.2), 25.1% (17.5-32.0) and 37.8% (27.2-45.2). The p-value-based multivariate analysis associated generalization with female sex, electromyogram decrement and first-year anti-acetylcholine-receptor antibody positivity, and Akaike information criterion-based analysis retained those three parameters and corticosteroid use. A nomogram was built and validated with an optimism-corrected C-statistic of 0.68, and calibration plots showed good fit. CONCLUSIONS: Our population's percentage of OMG generalization is in line with recent publications. Using the identified prognostic factors, the nomogram provided a score to predict the probable risk of generalization in our cohort.

Prognosis Factors and Outcomes of Neuro-ophthalmologic Sarcoidosis.

BACKGROUND: Neuro-ophthalmologic manifestations are uncommon in sarcoidosis. We aim to assess the prognostic factors and outcome of neuro-ophthalmic sarcoidosis. METHODS: We conducted a multicenter retrospective study on patients with neuro-ophthalmic sarcoidosis. Response to therapy was based on visual acuity, visual field, and orbital MRI exam. Factors associated with remission and relapse were analyzed. RESULTS: Thirty-five patients [median (IQR) age of 37 years (26.5-53), 63% of women] were included. The diagnosis of sarcoidosis was concomitant of neuro-ophthalmologic symptoms in 63% of cases. Optic neuritis was the most common manifestation. All patients received corticosteroids and 34% had immunosuppressants. At 6 months, 61% improved, 30% were stable, and 9% worsened. Twenty percent of patients had severe visual deficiency at the end of follow-up. Nonresponders patients had significantly worse visual acuity at baseline (p = 0.01). Relapses were less frequent in patients with retro-bulbar optic neuropathy (p = 0.03). CONCLUSION: Prognosis of neuro-ophthalmic sarcoidosis is poor.

Visual Recovery with Iloprost Added to Corticosteroids in a Case of Giant Cell Arteritis.

INTRODUCTION: To date, corticosteroids remain the cornerstone treatment of ocular involvement of GCA, and no other treatment has proven to be effective in this setting. We herein report on a unique case of GCA with ocular involvement worsening despite high dose corticosteroids and recovering with intravenous iloprost. CASE REPORT: A 70-year-old man presented with acute vision loss in his left eye related to anterior ischemic optic neuropathy. The diagnosis of giant-cell arteritis was confirmed by a temporal artery biopsy. Despite intravenous pulse methylprednisolone for 3 days then oral prednisone at 60 mg/day, the patient developed from day 5 fluctuating vision loss in the right eye, related to ocular ischemia by occlusion of the ophthalmic artery, and responsive to hyperhydration. Iloprost, an analog of prostacyclin PGI2, was then administered intravenously for 5 days and resulted in a stable improvement in visual acuity in the right eye. CONCLUSION: This case highlights the potential role of vasodilatator agents in giant cell arteritis with ocular involvement.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN GIANT CELL ARTERITIS.

PURPOSE: To report the occurrence of paracentral acute middle maculopathy (PAMM) in giant cell arteritis (GCA), describe its features and outcomes, and identify risk factors associated with PAMM in patients with GCA. METHODS: Review of medical records of patients with GCA who were examined in the Rothschild Foundation Hospital. Patients were divided into three groups: GCA with PAMM (Group 1), GCA with ophthalmic involvement but without PAMM (Group 2), and GCA without ophthalmic involvement (Group 3). We analyzed the data for age, sex, medical history, laboratory testing, visual acuity, and posterior segment vascular involvement. RESULTS: Among the 96 patients who met the inclusion criteria, 52 had ophthalmic involvement, and 16 patients were included in Group 1 (GCA with PAMM). In this subgroup, the mean age was 81.6 years and was found to be older than other groups. The visual prognosis was similar between Groups 1 and 2. Of the 20 eyes with PAMM, 35% were also associated with homolateral anterior ischemic optic neuropathy. No statistical difference was found in initial symptoms, signs, and laboratory testing. CONCLUSION: Paracentral acute middle maculopathy is frequently observed lesions in ocular GCA. Patients can present with isolated findings of PAMM as the only indication of GCA. Optical coherence tomography of the macula should be routinely performed in patients with suspected GCA, specifically if they complain of visual changes, to look for signs of ischemia in the middle layers of the retina. Isolated PAMM should raise suspicion for GCA in patients at risk.

Tilted disc syndrome (TDS): New hypotheses for posterior segment complications and their implications in other retinal diseases.

Tilted disc syndrome (TDS) is considered a congenital anomaly due to a delayed closure of the embryonic fissure. It is characterized by an oblique orientation of the axis of the optic disc, associated with other posterior pole anomalies such as inferior crescent, situs inversus and inferior staphyloma. The aim of this review was to summarize the data supporting the current hypotheses for the pathogenesis of TDS, and its anatomical and functional clinical consequences. Recent imaging techniques, such as magnetic resonance imaging, wide-field fundus imaging, and 2- and 3-D optical coherence tomography have provided a new perspective on TDS and its complications. Different abnormalities have previously been reported, both in the anterior and posterior segments. The focus was on vision-threatening chorioretinal changes or complications, including choroidal neovascularization and serous retinal detachments and their therapeutic options. Based on clinical observations, assumptions were proposed to understand the occurrence of complications such as chorioretinal degenerative changes, choroidal neovascularization and polypoidal choroidal vasculopathy, macular serous retinal detachment, myopic foveoschisis and chorioretinal folds. These hypotheses could be referred to as the curvature "breaking point" hypothesis, the uneven growth "tractional" hypothesis, the "container-content" imbalance hypothesis, and the "choroidal funnel" hypothesis. Because these complications could also occur in other contexts, understanding the pathogenesis of TDS complications could help to understand their pathophysiology.