Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy.

Importance: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

Objective: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

Design, Setting, And Participants: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the MT-ND4 Mutation).

The TsiogkaSpaeth grid for detection of neurological visual field defects: a validation study.

Background: The TsiogkaSpaeth (TS) grid is a new, low-cost, and easy to access portable test for visual field (VF) screening which could be used by clinicians in everyday clinical practice. Our study aimed to determine the validity of an innovative screening grid test for identifying neurological disease-associated VF defects.

Methods: We enrolled two groups of participants: We assessed the one eye of ten consecutive adult patients with different types of neurological disease associated VF defects and ten eyes of controls in each group.

Instances of ocular findings in transgender patients undergoing hormonal therapy.

Purpose: To describe the ophthalmological manifestations in transgender patients on gender-affirming hormone therapy.

Methods: A retrospective chart review study was conducted. Female-to-male (FTM) and male-to-female (MTF) transgenders on gender-affirming hormone therapy evaluated at a single center were included.

Comparing Gene Panels for Non-Retinal Indications: A Systematic Review.

Importance: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD).

Objective: To describe gene panel testing options for inherited eye disease phenotypes and their differences.

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.

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.

Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States.

Background/objective: To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites.

Methods: The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov.

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study.

Background: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

Methods: In RESCUE and REVERSE, 76 subjects with LHON because of the m.

Lumbar Puncture for Diagnosis of Idiopathic Intracranial Hypertension in Typical Patients.

Background: Patients with typical features of pseudotumor cerebri syndrome (PTCS) must undergo lumbar puncture (LP) to demonstrate elevated opening pressure and cerebrospinal fluid (CSF) analysis to rule out alternative diagnoses. As LP may be associated with significant morbidity, this study aims to determine its necessity in diagnosing typical PTCS.

Methods: Retrospective chart review at 3 university-based neuro-ophthalmology practices included women aged 18-45 years with body mass index >25, papilledema, negative neuroimaging, and who met criteria for PTCS or probable PTCS.

Cross-Sectional Analysis of Baseline Visual Parameters in Subjects Recruited Into the RESCUE and REVERSE ND4-LHON Gene Therapy Studies.

Objective: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

Methods: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE.

Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A Mutation: Systematic Review and Indirect Comparison.

This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies. A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2- vs. 11 pooled NH studies used as an external control.

Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study.

Background/objectives: REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON).

Subjects/methods: Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States of America and Europe.

Mismatch in Supply and Demand for Neuro-Ophthalmic Care.

Background: Previous research suggests the number of neuro-ophthalmologists in the United States may be below a level that provides sufficient access to neuro-ophthalmic care in much of the United States. However, national estimates of the amount of clinical time spent on neuro-ophthalmology are lacking.

Methods: The North American Neuro-Ophthalmology Society administered a survey on professional time allocation to its active members.

Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset.

Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).

Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.

Participants: Subjects with the m.

Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy.

REVERSE is a randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial that evaluated the efficacy of a single intravitreal injection of rAAV2/2- in subjects with visual loss from Leber hereditary optic neuropathy (LHON). A total of 37 subjects carrying the m.11778G>A () mutation and with duration of vision loss between 6 to 12 months were treated.

Posterior Cortical Atrophy: Characteristics From a Clinical Data Registry.

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that presents with higher-order visual dysfunction with relative sparing of memory and other cognitive domains, and it is most commonly associated with Alzheimer's disease pathology. There is a lack of data regarding the presentation of PCA to non-cognitive specialists. Therefore, we collected clinical data from neuro-ophthalmologists regarding the presentation of PCA to their practices and compared data to published cohorts and a published survey of cognitive specialists.

Papilloedema from Dural Venous Sinus Compression by Meningiomas.

Intracranial mass lesions may cause intracranial hypertension secondary to venous hypertension when they compress the dural venous sinuses (DVS) and may present with isolated papilloedema, mimicking idiopathic intracranial hypertension. We report a series of 16 patients with isolated papilloedema related to meningiomas compressing the DVS seen from 2012 to 2016 at three institutions. Correct diagnosis was delayed in 10/16 patients and treatment required a multidisciplinary approach, often with multiple sequential interventions, including combinations of acetazolamide, cerebrospinal fluid-shunt, optic nerve sheath fenestration, surgical resection of the meningioma, radiation therapy, and endovascular venous stenting.

One-sided triangle: A case of double vision.

A 51-year-old woman presented with acute diplopia and was found to have ptosis and complete bilateral external and internal ophthalmoplegia. She had normal reflexes and gait. Serological testing showed elevated levels of GQ1b ganglioside autoantibodies, making the diagnosis of Miller Fisher syndrome.

Gene therapy in optic nerve disease.

Purpose Of Review: Highlight some of the recent advances in gene therapy and gene modification for optic nerve disease to promote axon regeneration, neuroprotection, and increased visual functioning.

Recent Findings: Visual loss secondary to optic nerve damage occurs in numerous ophthalmologic and neurologic conditions. Damaged retinal ganglion cells (RGCs) do not regenerate once they undergo apoptosis after injury.

Herpes Zoster Optic Neuropathy.

Background: Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON.

Methods: A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome.

Efficacy of Orbital Color Doppler Imaging and Neuroimaging in the Diagnosis of Carotid Cavernous Fistulas.

Purpose: To evaluate the diagnostic sensitivity and specificity of orbital color Doppler imaging (CDI) and conventional neuroimaging (CT/MRI) compared with cerebral angiography in patients with carotid-cavernous fistulas (CCFs).

Methods: The study design was a retrospective patient chart and imaging review. The authors reviewed 655 charts of all patients who underwent CDI and neuroimaging (CT/MRI) between 2006 and 2015 at one institution.