Review
Biochemistry & Molecular Biology
Sheng-Chu Chi, Hui-Chen Cheng, An-Guor Wang
Summary: This review article discusses the molecular pathophysiology of LHON and provides an update on the current status of gene therapy for LHON.
Review
Ophthalmology
Pamela Davila-Siliezar, Michael Carter, Dan Milea, Andrew G. Lee
Summary: This review examines recent therapeutic advancements in the treatment of Leber hereditary optic neuropathy (LHON), including the use of synthetic antioxidants and gene therapy.
CURRENT OPINION IN OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Byron L. Lam, William J. Feuer, Janet L. Davis, Vittorio Porciatti, Hong Yu, Robert B. Levy, Elizabeth Vanner, John Guy
Summary: This study evaluated the safety of gene therapy for G11778A Leber hereditary optic neuropathy (LHON) and found that the only vector-related adverse event was uveitis, which did not result in significant vision sequelae. Improvements in visual acuity of >15 letters were observed in some treated eyes and fellow eyes, as well as in some surrogate study eyes and fellow eyes of natural history subjects. However, all study eyes in group 3 (BCVA > 20/40) lost > 15 letters of visual acuity within the first year despite treatment.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Review
Cell Biology
Hoda Shamsnajafabadi, Robert E. MacLaren, Jasmina Cehajic-Kapetanovic
Summary: Leber hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease that causes blindness in young adults. Three specific variations in the mitochondrial DNA are responsible for over 95% of LHON cases. Treatment options for LHON remain limited, but gene therapy and other alternative strategies are being explored. This study examines the complexity and challenges of LHON treatment, with a focus on recent advances in gene therapy using adeno-associated viral vectors.
Article
Oncology
Catherine Vignal-Clermont, Jean-Francois Girmens, Isabelle Audo, Saddek Mohand Said, Marie-Helene Errera, Lise Plaine, Denis O'Shaughnessy, Magali Taiel, Jose-Alain Sahel
Summary: This study evaluated the safety and tolerability of lenadogene nolparvovec in treating LHON, showing good tolerability and clinically relevant and durable improvements in vision during the 5-year follow-up.
Review
Clinical Neurology
Benson S. Chen, Patrick Yu-Wai-Man, Nancy J. Newman
Summary: This review outlines the current landscape of treatments for Leber hereditary optic neuropathy (LHON). The treatments can be classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation, while mutation-independent therapies aim to improve mitochondrial function. Currently, only one drug is approved for LHON treatment. However, innovations in gene therapy and editing are driving the expansion of therapeutic options.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2022)
Article
Neurosciences
Sindhu Velmurugan, Tsung-Han Chou, Jeremy D. Eastwood, Vittorio Porciatti, Yuan Liu, William W. Hauswirth, John Guy, Hong Yu
Summary: This study developed two gene therapy strategies, mitochondrial-targeted and allotopic expressed, and compared their efficacy in a LHON mouse model. The results suggest that mitochondrial-targeted gene therapy is more efficient in rescuing the LHON phenotype compared to allotopic gene therapy.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Clinical Neurology
Rabih Hage, Catherine Vignal-Clermont
Summary: Leber hereditary optic neuropathy is a maternally inherited mitochondrial disease that affects retinal ganglion cells, leading to vision loss. While various treatments have been evaluated and some progress made, there is currently no effective treatment to restore vision in patients with chronic disease lasting over 1 year.
FRONTIERS IN NEUROLOGY
(2021)
Review
Clinical Neurology
Nancy J. Newman, Patrick Yu-Wai-Man, Valerio Carelli, Valerie Biousse, Mark L. Moster, Catherine Vignal-Clermont, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Jean-Francois Girmens, Chiara La Morgia, Adam A. DeBusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, Francois Montestruc, Michel Roux, Magali Taiel, Jose-Alain Sahel
Summary: The study compared the evolution of visual outcomes in LHON patients treated with gene therapy with the natural history of NH studies, showing that patients treated with gene therapy exhibited significant improvement in visual acuity over time.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Ling Wang, Hao Ding, Bihong T. Chen, Ke Fan, Qin Tian, Miaomiao Long, Meng Liang, Dapeng Shi, Chunshui Yu, Wen Qin
Summary: LHON patients show occult brain white matter impairment, which may not be correlated with disease duration or retinal nerve fiber layer thickness.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Darius W. Lambiri, Leonard A. Levin
Summary: This study models and explores the influence of H2O2 on axonal degeneration in Leber hereditary optic neuropathy (LHON). It finds that zonal oxidative stress correlated with H2O2 gradients is associated with the observed injury patterns in LHON. Small injuries may trigger cascading failures of neighboring axons. These findings are consistent with clinical observations of LHON.
Review
Ophthalmology
Srilekha Sundaramurthy, Ambika SelvaKumar, Jared Ching, Vidhya Dharani, Sripriya Sarangapani, Patrick Yu-Wai-Man
Summary: Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA disorder, characterized by bilateral subacute vision loss and optic nerve degeneration. While treatment options are limited, ongoing clinical trials, including gene therapy, are investigating potential treatments for this mitochondrial disorder.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2021)
Article
Clinical Neurology
Yufang Cheng, Lu He, Qingmei Miao, Wenyu Wang, Jiajia Yuan, Changzheng Chen
Summary: This study characterizes features of retinal never fiber in Leber Hereditary Optic Neuropathy (LHON) using multicolor (MC) imaging and color fundus photography (CFP). The results suggest that green reflectance (GR) and green-blue-enhanced (BG) imaging in MC can effectively delineate retinal never fiber, providing a potentially inexpensive and rapid method for detecting and monitoring never fiber bundle defects. These imaging techniques can also help identify patients with a high suspicion of LHON.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Nancy J. Newman, Patrick Yu-Wai-Man, Prem S. Subramanian, Mark L. Moster, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Michel Roux, Eric D. Cox, Magali Taiel, Jose-Alain Sahel
Summary: Leber hereditary optic neuropathy (LHON) is a mitochondrial blindness caused by the m.11778G>A mutation. The REFLECT phase 3 study investigated the efficacy and safety of lenadogene nolparvovec gene therapy in LHON patients. It showed improvement in visual acuity, with better results in patients who received bilateral treatment. The trial demonstrated a favorable benefit/risk profile for bilateral injections compared to unilateral injections.
Article
Medicine, General & Internal
Katarzyna Nowomiejska, Patrycja Lesiuk, Agnieszka Brzozowska, Katarzyna Tonska, Robert Rejdak
Summary: The vasculature and thickness of the macula were assessed using OCT-A in patients with LHON or NA-AION. The superficial vessel density and retinal thickness were more affected in LHON eyes, especially in the nasal and temporal sectors.
Article
Ophthalmology
Jonathan F. Russell, Victor M. Villegas, Stephen G. Schwartz, Christina Y. Weng, Janet L. Davis, Harry W. Flynn, J. William Harbour
Summary: The study examined 12 patients diagnosed with exophytic JRCH at Bascom Palmer Eye Institute and Baylor College of Medicine. Multimodal imaging is valuable in the diagnosis of JRCH, aiding in ruling out other conditions.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Editorial Material
Ophthalmology
Hasenin Al-khersan, Guillermo Amescua, Janet L. Davis
Summary: A 50-year-old woman presents with left eye redness and headaches, with examination showing scleral nodules and surrounding hyperemia, along with elevated levels of antibodies in laboratory tests. Further investigation is needed to determine the cause of the condition and develop a treatment plan.
JAMA OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Leticia S. C. da Silva, Luciana P. S. Finamor, Gabriel C. Andrade, Luiz H. Lima, Claudio Zett, Cristina Muccioli, Eduardo P. Sarraf, Paula M. Marinho, Julia Peruchi, Raiza D. de L. Oliveira, Lena Giralt, Ivonne Charcan, Alex Fonollosa, Jose D. Diaz, Janet L. Davis, Heloisa Nascimento, Rubens Belfort
Summary: This study aimed to investigate vascular retinal findings related to COVID-19 vaccination, and it found that such events are rare. Further research is needed to understand the relationship between these retinal events and vaccination.
ARQUIVOS BRASILEIROS DE OFTALMOLOGIA
(2022)
Article
Ophthalmology
Byron L. Lam, William J. Feuer, Janet L. Davis, Vittorio Porciatti, Hong Yu, Robert B. Levy, Elizabeth Vanner, John Guy
Summary: This study evaluated the safety of gene therapy for G11778A Leber hereditary optic neuropathy (LHON) and found that the only vector-related adverse event was uveitis, which did not result in significant vision sequelae. Improvements in visual acuity of >15 letters were observed in some treated eyes and fellow eyes, as well as in some surrogate study eyes and fellow eyes of natural history subjects. However, all study eyes in group 3 (BCVA > 20/40) lost > 15 letters of visual acuity within the first year despite treatment.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Francesco Pichi, Rosa Dolz-marco, Jasmine H. Francis, Adrian Au, Janet L. Davis, Amani Fawzi, Sarra Gattousi, Debra A. Goldstein, Pearse A. Keane, Elisabetta Miserocchi, Alessandro Marchese, Kyoko Ohno-matsui, Mandeep S. Sagoo, Scott D. Smith, Ethan K. Sobol, Anastasia Tasiopoulou, Xiaolu Yang, Carol L. Shields, K. Bailey Freund, David Sarraf
Summary: This study aimed to analyze the OCT findings in patients with VRL and correlate these features with clinical parameters. The study found that tumor infiltration in different retinal layers can be identified on OCT, and three main regions of retinal infiltration were identified.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vittorio Porciatti, Tsung-Han Chou
Summary: Neuroprotection in optic neuropathies aims to preserve retinal ganglion cells and their function. The use of the Pattern Electroretinogram (PERG) for noninvasive evaluation of RGC function can provide diagnostic and prognostic value, as well as support early treatment recommendations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Pia Allegri, Luca Cimino, Janet L. Davis, Ilknur Tugal-Tutkun
Summary: This study investigated the effectiveness and safety of PHBC in reducing the number and intensity of HLA-B27-related AAU relapses. The results showed that compared to the placebo group, the PHBC group had fewer relapses and a higher proportion of responders, with comparable severity of attacks. Therefore, PHBC treatment may be beneficial.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Editorial Material
Ophthalmology
Jason Fan, Chris Y. Wu, Janet L. Davis
JAMA OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Vittorio Porciatti, Diego E. Alba, William J. Feuer, Janet Davis, John Guy, Byron L. Lam
Summary: This study compared the baseline SS-PERG of LHON patients with different stages of visual acuity loss and found that the reduction in SS-PERG amplitude did not distinguish between disease stages, but the shortening of SS-PERG latency occurred in both asymptomatic and symptomatic eyes and distinguished between disease stages.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Cell Biology
Rosario Amato, Maurizio Cammalleri, Alberto Melecchi, Paola Bagnoli, Vittorio Porciatti
Summary: Glaucoma is a chronic optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). The main causes of RGC death are traditionally attributed to elevated intraocular pressure (IOP) and resulting mechanical stress. However, glaucoma can occur independent of IOP, suggesting a multifactorial nature of the disease. The present study aimed to comprehensively evaluate the neuro-glial-vascular changes associated with glaucoma progression.
Article
Ophthalmology
Jesse D. Sengillo, Ninel Z. Gregori, Robert A. Sisk, Christina Y. Weng, Audina M. Berrocal, Janet L. Davis, Carlos E. Mendoza-Santiesteban, D. Diane Zheng, William J. Feuer, Byron L. Lam
Summary: This study aimed to investigate the impact of patients' age, baseline visual acuity, and intraoperative foveal detachment on the outcomes of subretinal voretigene neparvovec-rzyl therapy, as well as the patients' perceptions of the treatment effect. The results showed that there were no significant vision changes for adult patients, while there was a trend of improvement for pediatric patients. The decrease in foveal thickness was observed, but its long-term significance remains to be determined.
OPHTHALMOLOGY RETINA
(2022)
Article
Ophthalmology
Lauren C. Kiryakoza, J. Daniel Diaz, Joshua Priluck, Janet Davis, Nicolas A. Yannuzzi
Summary: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome that presents with gradual vision loss. This case report describes a 73-year-old man with metastatic urothelial carcinoma who developed visual symptoms. Ophthalmic examination revealed fluid accumulation, subretinal deposits, and irregular hyperpigmentation, consistent with the diagnosis of BDUMP. Despite undergoing multiple plasmapheresis sessions, the patient did not experience sustained clinical improvement.
OPHTHALMIC SURGERY LASERS & IMAGING RETINA
(2022)
Article
Ophthalmology
Jila Noori, Yingying Shi, Jin Yang, Giovanni Gregori, Thomas A. Albini, Philip J. Rosenfeld, Janet L. Davis
Summary: This study introduces a novel method for assessing retinal vasculitis using swept-source OCT angiography (SS-OCTA), which detects structural retinal thickening secondary to inflammatory retinal vascular leakage. Further studies are needed to confirm whether SS-OCTA may serve as a semi-quantitative alternative to fluorescein angiography for diagnosing and monitoring treatment response in patients with retinal vasculitis.
OPHTHALMOLOGY RETINA
(2021)
Meeting Abstract
Ophthalmology
Mark E. Pennesi, Paul Yang, Andreas Lauer, Robert A. Sisk, Jason M. Comander, Rachel M. Huckfeldt, Edward Averbuhk, Eyal Banin, Ninel Gregori, Janet L. Davis, Byron L. Lam, Christine Kay, Erin Leone, Deanine Halliman, Nnenna Ihekoromadu, Matthew Feinsod
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Meeting Abstract
Ophthalmology
Vittorio Porciatti, Diego Alba, William J. Feuer, Janet L. Davis, Byron L. Lam
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)