scholarly journals Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013084
Author(s):  
Blake Fortes ◽  
John J Chen ◽  
M. Tariq Bhatti
Keyword(s):  
Vision Loss ◽  
Systemic Corticosteroid ◽  
White Male ◽  
Clinical Suspicion ◽  
Whole Genome ◽  
Leber Hereditary Optic Neuropathy ◽  
Nutritional Conditions ◽  
Laboratory Investigations ◽  
Systemic Corticosteroid Therapy ◽  
Hereditary Optic Neuropathy

A 31-year-old healthy white male experienced painless sequential vision loss. Brain imaging and laboratory investigations for infectious, inflammatory, and nutritional conditions, in addition to targeted genetic testing for Leber hereditary optic neuropathy (LHON), were all normal or negative. Despite systemic corticosteroid therapy and plasma exchange, vision continued to worsen. Eventually, mitochondrial whole genome sequencing was performed, which demonstrated a mutation at the 13513G>A position confirming the diagnosis of LHON. Three primary mutations (11778G>A, 14484T>C and 3460G>A) account for 90% of LHON cases, therefore it is important to consider whole genome mitochondrial sequencing in cases with a high index of clinical suspicion.

scholarly journals A Typical Case Presentation with Spontaneous Visual Recovery in Patient Diagnosed with Leber Hereditary Optic Neuropathy due to Rare Point Mutation in MT-ND4 Gene (m.11253T>C) and Literature Review

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 202
Author(s):  
Rasa Liutkeviciene ◽  
Agne Sidaraite ◽  
Lina Kuliaviene ◽  
Brigita Glebauskiene ◽  
Neringa Jurkute ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Vision Loss ◽  
European Medicines Agency ◽  
Visual Recovery ◽  
Leber Hereditary Optic Neuropathy ◽  
Diagnostic Features ◽  
Mitochondrial Respiratory Chain Complex ◽  
Male Predominance ◽  
Mtdna Mutations ◽  
Hereditary Optic Neuropathy

Leber hereditary optic neuropathy (LHON) is one of the most common inherited mitochondrial optic neuropathies, caused by mitochondrial DNA (mtDNA) mutations. Three most common mutations, namely m.11778G>A, m.14484T>G and m.3460G>A, account for the majority of LHON cases. These mutations lead to mitochondrial respiratory chain complex I damage. Typically, LHON presents at the 15–35 years of age with male predominance. LHON is associated with severe, subacute, painless bilateral vision loss and account for one of the most common causes of legal blindness in young individuals. Spontaneous visual acuity recovery is rare and has been reported in patients harbouring m.14484T>C mutation. Up to date LHON treatment is limited. Idebenone has been approved by European Medicines Agency (EMA) to treat LHON. However better understanding of disease mechanisms and ongoing treatment trials are promising and brings hope for patients. In this article we report on a patient diagnosed with LHON harbouring rare m.11253T>C mutation in MT-ND4 gene, who experienced spontaneous visual recovery. In addition, we summarise clinical presentation, diagnostic features, and treatment.

scholarly journals Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison

2021 ◽  
Vol 12 ◽  
Author(s):  
Nancy J. Newman ◽  
Patrick Yu-Wai-Man ◽  
Valerio Carelli ◽  
Valerie Biousse ◽  
Mark L. Moster ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Visual Acuity ◽  
Natural History ◽  
Optic Neuropathy ◽  
Linear Mixed Model ◽  
Vision Loss ◽  
Indirect Comparison ◽  
External Control ◽  
Leber Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Objective: 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.Design: 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-ND4 vs. 11 pooled NH studies used as an external control.Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss.Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences.Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4.Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p < 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes (p < 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (−0.32 LogMAR, p < 0.0001).Conclusions: The m.11778G>A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies.Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071.

scholarly journals Natural history of patients with Leber hereditary optic neuropathy—results from the REALITY study

Eye ◽  
2021 ◽  
Author(s):  
Patrick Yu-Wai-Man ◽  
◽  
Nancy J. Newman ◽  
Valerio Carelli ◽  
Chiara La Morgia ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Vision Loss ◽  
The United States ◽  
Local Regression ◽  
Leber Hereditary Optic Neuropathy ◽  
Visual Outcomes ◽  
Mtdna Mutations ◽  
Presymptomatic Stage ◽  
One Year ◽  
Hereditary Optic Neuropathy

Abstract 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. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time. Results 44 LHON patients were included; 27 (61%) carried the m.11778G>A ND4 mutation, 8 (18%) carried the m.3460G>A ND1 mutation, and 9 (20%) carried the m.14484T>C ND6 mutation. Fourteen (32%) patients were under 18 years old at onset of vision loss and 5 (11%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4 patients, 1.52 LogMAR in ND1 patients, and 0.97 LogMAR in ND6 patients. The worst visual outcomes were reported in ND4 patients aged at least 15 years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA. Conclusions Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G>A ND4 mutation had the worst visual outcomes, consistent with prior reports.

scholarly journals Establishing risk of vision loss in Leber hereditary optic neuropathy

2021 ◽  
Author(s):  
M. Isabel G. Lopez Sanchez ◽  
Lisa S. Kearns ◽  
Sandra E. Staffieri ◽  
Linda Clarke ◽  
Myra B. McGuinness ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Vision Loss ◽  
Leber Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Leber Hereditary Optic Neuropathy

2019 ◽  
pp. 25-28
Author(s):  
Matthew J. Thurtell ◽  
Robert L. Tomsak
Keyword(s):  
Optic Neuropathy ◽  
Vision Loss ◽  
Treatment Options ◽  
Leber Hereditary Optic Neuropathy ◽  
Dna Mutations ◽  
History Of ◽  
Eye Involvement ◽  
Promising Treatment ◽  
Almost All ◽  
Hereditary Optic Neuropathy

Leber hereditary optic neuropathy in an important cause of acute painless monocular vision loss. It most often occurs in young men. Almost all patients develop fellow eye involvement within a few months, resulting in severe irreversible binocular vision loss. In this chapter, we begin by reviewing the differential diagnosis of acute optic neuropathy. We next discuss the genetic basis for Leber hereditary optic neuropathy and list the three common mitochondrial DNA mutations that cause it. We then review the clinical features and natural history of Leber hereditary optic neuropathy. Lastly, we discuss the treatment approach for this condition and review promising treatment options.

scholarly journals Relapsing Uveitis due to Human T-lymphotropic Virus Type 1 in a Patient Living With HIV Diagnosed by Metagenomic Deep Sequencing

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Varun K Phadke ◽  
Jessica G Shantha ◽  
Ghazala O’Keefe
Keyword(s):  
Virus Type ◽  
Deep Sequencing ◽  
Vision Loss ◽  
Systemic Corticosteroid ◽  
Emerging Technology ◽  
T Lymphotropic Virus ◽  
Clinical Syndromes ◽  
Living With Hiv ◽  
Systemic Corticosteroid Therapy

Abstract HIV infection can result in vision loss from different causes, including HIV retinopathy and uveitis secondary to other infections, such as toxoplasmosis and viral retinitis. It is imperative to identify any infectious causes of uveitis to successfully treat the condition and prevent further vision loss. Metagenomic deep sequencing (MDS) is an emerging technology that presents an unbiased approach to the evaluation of clinical syndromes, including uveitis, that have not been diagnosed by pathogen-specific testing. Herein we present a case of a woman living with HIV with 11 years of relapsing bilateral uveitis refractory to systemic corticosteroid therapy who was diagnosed with human T-lymphotropic virus type 1 (HTLV-1)–associated uveitis by this technology. We also briefly review the literature of MDS as a diagnostic tool and the epidemiology, pathogenesis, and diagnosis of HTLV-1-associated uveitis.

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

2020 ◽  
Vol 12 (573) ◽  
pp. eaaz7423
Author(s):  
Patrick Yu-Wai-Man ◽  
Nancy J. Newman ◽  
Valerio Carelli ◽  
Mark L. Moster ◽  
Valerie Biousse ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Vision Loss ◽  
Viral Vector ◽  
Anterior Segment ◽  
Mechanistic Explanation ◽  
Leber Hereditary Optic Neuropathy ◽  
Sham Injection ◽  
Visual Improvement ◽  
The Right ◽  
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-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). A total of 37 subjects carrying the m.11778G>A (MT-ND4) mutation and with duration of vision loss between 6 to 12 months were treated. Each subject’s right eye was randomly assigned in a 1:1 ratio to treatment with rAAV2/2-ND4 (GS010) or sham injection. The left eye received the treatment not allocated to the right eye. Unexpectedly, sustained visual improvement was observed in both eyes over the 96-week follow-up period. At week 96, rAAV2/2-ND4–treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) of −0.308 LogMAR (+15 ETDRS letters). A mean improvement of −0.259 LogMAR (+13 ETDRS letters) was observed in the sham-treated eyes. Consequently, the primary end point, defined as the difference in the change in BCVA from baseline to week 48 between the two treatment groups, was not met (P = 0.894). At week 96, 25 subjects (68%) had a clinically relevant recovery in BCVA from baseline in at least one eye, and 29 subjects (78%) had an improvement in vision in both eyes. A nonhuman primate study was conducted to investigate this bilateral improvement. Evidence of transfer of viral vector DNA from the injected eye to the anterior segment, retina, and optic nerve of the contralateral noninjected eye supports a plausible mechanistic explanation for the unexpected bilateral improvement in visual function after unilateral injection.

Ramsay Hunt syndrome

2012 ◽  
Vol 153 (32) ◽  
pp. 1281-1283
Author(s):  
Róbert Kui ◽  
Zsuzsanna Bata-Csörgő ◽  
Margit Zeher ◽  
Lajos Kemény
Keyword(s):  
Herpes Zoster ◽  
Multidisciplinary Approach ◽  
Systemic Corticosteroid ◽  
Complete Recovery ◽  
Typical Case ◽  
Early Administration ◽  
Ramsay Hunt Syndrome ◽  
Peripheral Facial Palsy ◽  
Hunt Syndrome ◽  
Systemic Corticosteroid Therapy

Ramsay Hunt syndrome is a special form of herpes zoster which is typically characterized by peripheral facial palsy and unilateral herpetic vesicles on the ear. These symptoms are often accompanied by vestibulocochlear dysfunction and other neurological and ophthalmological symptoms. The diagnosis and therapy requires a multidisciplinary approach. The authors present a typical case where the early administration of combined antiviral and systemic corticosteroid therapy led to complete recovery. The authors emphasize the importance of early diagnosis and adequate combination therapy, which improves the prognosis of this disease. Orv. Hetil., 2012, 153, 1281–1283.

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