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 Table of Contents  
Year : 2021  |  Volume : 11  |  Issue : 3  |  Page : 205-206

Management and treatment of inherited retinal dystrophies

1 Department of Ophthalmology, Pathology and Cell Biology, Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Columbia Stem Cell Initiative, Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
2 Department of Ophthalmology, Pathology and Cell Biology, Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Columbia Stem Cell Initiative, Institute of Human Nutrition, Vagelos College of Physicians and Surgeons; Edward S. Harkness Eye Institute, New York-Presbyterian Hospital; Department of Pathology and Cell Biology, The Herbert Irving Comprehensive Cancer Center, Institute of Human Nutrition, Columbia University, New York, NY, USA

Date of Submission04-Aug-2021
Date of Acceptance04-Aug-2021
Date of Web Publication11-Sep-2021

Correspondence Address:
Dr. Stephen H Tsang
Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, 635 West 165th Street, Box 112, New York, NY 10032
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjo.tjo_32_21

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How to cite this article:
Levi SR, Jenny LA, Tsang SH. Management and treatment of inherited retinal dystrophies. Taiwan J Ophthalmol 2021;11:205-6

How to cite this URL:
Levi SR, Jenny LA, Tsang SH. Management and treatment of inherited retinal dystrophies. Taiwan J Ophthalmol [serial online] 2021 [cited 2021 Dec 5];11:205-6. Available from: https://www.e-tjo.org/text.asp?2021/11/3/205/325853

Inherited retinal dystrophies (IRDs) are a rare group of hereditary diseases that lead to progressive degeneration of retinal cells.[1] While there are currently several ongoing clinical trials utilizing pharmacological agents and adeno-associated virus (AAV) vector-mediated gene augmentation therapeutics, only one Food and Drug Administration approved therapy currently exists that is merely capable of treating a small fraction of the population: those afflicted by mutations in the RPE65 gene.[2],[3],[4],[5],[6],[7] At this point in time, countless physicians and scientists are poised to address this unmet need for a treatment or cure for IRDs, however, given that most therapies are mutation specific, this task is both highly cost- and time-inefficient.[8] Moreover, we must overcome several crucial obstacles, including on- and off-targeting in genome editing techniques,[9] delivery of genes with a payload too large for that of an AAV vector delivery system,[10] the complexity of removing the gain-of-function allele to repair autosomal dominant genes, and a system of ensuring long-term efficacy of gene augmentation.[11]

Treatment options that circumvent the production of each therapy specified to the individual's genetic variant are promising solutions to this scientific and medical challenge.[12] Ryu et al. describe alternative pathways common to several IRDs that may hold the key to slowing retinal degeneration. Specifically, the authors' work highlights the damaging role that reactive oxygen species play in IRDs, leading to oxidative stress and subsequent cellular death. One pathway, the nuclear factor erythroid-2-related factor-Kelch-like ECH-associated protein 1 pathway presents a system whereby oxidative stress is neutralized. Similar work was reviewed by Nolan et al. in this series, addressing the role of metabolic coupling in healthy and atrophic retinal cells. Ultimately, investigations such as these have the potential to not only uncover the underlying pathology of each dystrophy but also identify points for therapeutic intervention capable of slowing progression, common to countless retinal degenerative processes. At present, metabolic reprogramming is making great strides in the field, buying time for genome surgery and stem cell transplantation techniques to excel and pave the way toward a long-term cure for IRDs.

Macula lesions often result in vision loss. Spooner et al. investigate the use of aflibercept, an antivascular endothelial growth factor agent, for patients with persistent macular edema due to retinal vein occlusion despite regular treatment with bevacizumab or ranibizumab. Here, the investigators identify that aflibercept significantly improved patient's visual functions, and as a result, quality of life. Abouhussein et al. also present data supporting the successful application of aflibercept in patients with bevacizumab-resistant diabetic macular edema. In addition, Chiu et al.'s study demonstrates the use of ranibizumab monotherapy versus concurrent ranibizumab with posterior subtenon triamcinolone acetonide. Their work revealed that patients with diabetic macular edema responded significantly better to the combined therapy option. Additional research has been directed toward surgical intervention for structural abnormalities. Macular holes are most commonly idiopathic, however, in rare cases, they are linked to genetic causes, schisis in highly myopic eyes, or age-related macular degeneration (AMD).[13] In this edition, Marlow et al. outline the various surgical strategies in autologous retinal transplants to address macular holes of various sizes. Taken together, these projects highlight how metabolome reprogramming and antioxidant therapies can be used in combination with conventional therapies for dry AMD and monogenic disorders (voretigene neparvovec).

It is imperative to treat secondary diagnoses – such as cystoid macular edema – as well as further investigate the underlying pathophysiology and metabolic processes leading to retinal degeneration. This special issue includes investigations that are critical to managing and ultimately treating these devastating and blinding dystrophies.

We wish to thank all our authors for their excellent work and contributions to this edition of the Taiwan Journal of Ophthalmology.


We thank Nan-Kai Wang, MD, for sharing ideas and for critically reading the editorial.

Financial support and sponsorship

JCVC is supported by the National Institute of Health 5P30CA013696, U01EY030580, U54OD020351, R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437, the Schneeweiss Stem Cell Fund, New York State (SDHDOH01-C32590GG-3450000), the Foundation Fighting Blindness New York Regional Research Center Grant (TA-NMT-0116-0692-COLU), Nancy and Kobi Karp, the Crowley Family Funds, The Rosenbaum Family Foundation, Alcon Research Institute, the Gebroe Family Foundation, the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA.

Conflicts of interest

Stephen H. Tsang has received financial benefits from Spark Therapeutics and research support from Abeona Therapeutics, Inc and Emendo.

  References Top

Ayuso C, Millan JM. Retinitis pigmentosa and allied conditions today: A paradigm of translational research. Genome Med 2010;2:34.  Back to cited text no. 1
Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, Phase 3 trial. Lancet 2017;390:849-60.  Back to cited text no. 2
Bainbridge JW, Mehat MS, Sundaram V, Robbie SJ, Barker SE, Ripamonti C, et al. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med 2015;372:1887-97.  Back to cited text no. 3
Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med 2008;358:2231-9.  Back to cited text no. 4
Cideciyan AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S, et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A 2013;110:E517-25.  Back to cited text no. 5
Duncan JL, Pierce EA, Laster AM, Daiger SP, Birch DG, Ash JD, et al. Inherited retinal degenerations: Current landscape and knowledge gaps. Transl Vis Sci Technol 2018;7:6.  Back to cited text no. 6
Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr., Mingozzi F, Bennicelli J, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med 2008;358:2240-8.  Back to cited text no. 7
Maeder ML, Stefanidakis M, Wilson CJ, Baral R, Barrera LA, Bounoutas GS, et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat Med 2019;25:229-33.  Back to cited text no. 8
Li J, Hong S, Chen W, Zuo E, Yang H. Advances in detecting and reducing off-target effects generated by CRISPR-mediated genome editing. J Genet Genomics 2019;46:513-21.  Back to cited text no. 9
Bulcha JT, Wang Y, Ma H, Tai PW, Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther 2021;6:53.  Back to cited text no. 10
Gange WS, Sisk RA, Besirli CG, Lee TC, Havunjian M, Schwartz H, et al. Perifoveal chorioretinal atrophy after subretinal voretigene neparvovec-rzyl for RPE65-mediated Leber congenital amaurosis. Ophthalmol Retina 2021;21:S2468-8.  Back to cited text no. 11
Caruso S, Ryu J, Quinn PM, Tsang SH. Precision metabolome reprogramming for imprecision therapeutics in retinitis pigmentosa. J Clin Invest 2020;130:3971-3.  Back to cited text no. 12
Gass JD. Idiopathic senile macular hole. Its early stages and pathogenesis. Arch Ophthalmol 1988;106:629-39.  Back to cited text no. 13


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