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   Table of Contents      
Year : 2018  |  Volume : 66  |  Issue : 10  |  Page : 1389-1390

Precision medicine and clinical ophthalmology

Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Date of Web Publication24-Sep-2018

Correspondence Address:
Dr. Bradley R Straatsma
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1459_18

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How to cite this article:
Straatsma BR. Precision medicine and clinical ophthalmology. Indian J Ophthalmol 2018;66:1389-90

How to cite this URL:
Straatsma BR. Precision medicine and clinical ophthalmology. Indian J Ophthalmol [serial online] 2018 [cited 2020 Sep 21];66:1389-90. Available from: http://www.ijo.in/text.asp?2018/66/10/1389/241997

The Precision Medicine Initiative gained prominence in the United States when announced in the 2015 State of the Union Address by President Barak Obama.[1] In the following year, the U.S. National Institutes of Health commenced recruitment of 1 million or more people to participate in longitudinal studies to determine the ways in which genomic, health history/behavior, and lifestyle/environmental factors interact to cause disease. Participants in the precision medicine cohort contribute blood samples for genomic analysis and storage, electronic medical records, lifestyle/environmental information, and longitudinal data to a federal “biobank.”[2]

This U.S. biobank and other large medical data repositories will be analyzed to reveal previously unknown and unsuspected relationships among genomic findings, health history/behavior, lifestyle/environmental factors, and the risk of or onset of disease.

Ophthalmology has been at the forefront of genomic research with discovery of more than 260 genes causing inherited retinal disease and extensive studies of many other eye and vision-related diseases.[3] The several ways in which genomic research affects clinical ophthalmology may be illustrated by considering inherited retinal disease therapy, the important applications of genomic research in ophthalmic oncology, and the major gene-related insights concerning multifactorial diseases such as age-related macular degeneration (AMD).

For the inherited retinal disease of Leber congenital amaurosis caused by mutations in both copies of the RPE65 gene, extensive research and favorable 3-year results of a controlled clinical trial of therapy led the U.S. Federal Drug Administration (FDA) to approve treatment with Luxturna (voretigene neparvovec-rzyl; Spark Therapeutics, Inc.).[4] Approved in 2017, this is the first FDA-approved gene therapy for an inherited disease.[3],[4],[5] In patients with RPE65-related Leber congenital amaurosis, early-stage diagnosis and treatment are essential for preservation of vision.

Clinical trials for a number of single-gene inherited retinal diseases are in progress, including trials for X-linked retinoschisis, Stargardt disease, Usher syndrome, choroideremia, and retinitis pigmentosa.[5] Investigations using CRISPR systems for genetic modification of inherited retinal disease are underway.[6] In mid-2018, the FDA approved the first “gene-silencing” drug, Onpattro (patisiran; Alnylam Pharmaceuticals, Inc.), for treatment of hereditary transthyretin-mediated amyloidosis.[7] Additional therapies for genomic disease are expected.

In ophthalmic oncology, comprehensive knowledge of the genomic alterations responsible for the cancer is the foundation for understanding tumor biology, developing diagnostics, assessing prognosis, and formulating targeted therapeutics.[8],[9],[10] For ciliochoroidal melanoma, ophthalmic oncologists have, for more than a decade, used genomic studies of tumor biopsy, performed at the time of definitive treatment, to confirm the diagnosis and assess the DNA and RNA factors associated with high risk or low risk of metastasis. Moreover, genetic mutation of BAP1 in the melanoma biopsy may be associated with germline mutation and predisposition for other forms of cancer. Further studies of tumor genomics using genome-wide, single-nucleotide polymorphism mapping arrays have been used to identify significant targets for molecular therapy.[9] In overview, genetic information obtained from the melanoma is combined with tumor pathology, patient family history, medical history/behavior, and lifestyle/environmental factors to assess metastatic risk and provide the best possible care for the patient.

For the complex, multifactorial disease of AMD, research has identified approximately 36 causative genetic loci.[10] Although genetic testing is not currently useful for management of patients with AMD, research involving two cohorts totaling 835 persons with two or more AMD risk alleles of CFH or ARMS2 and photographic evidence of early-stage AMD were followed for more than 10 years.[11] Study participants showed AMD progression associated with three modifiable risk factors (smoking, infrequent consumption of fish, and low lutein–zeaxanthin intake). This study illustrates the advantage of research on patients with genetically defined risk factors and comprehensive medical health/behavior and lifestyle/environmental information to demonstrate modifiable factors that may be used in clinical practice to defer progression of disease.

Precision medicine recognizes the increasing importance of patient-specific genetics and genomic studies in medical care and the practice of ophthalmology. For ophthalmology, genomics may affect clinical practice in several ways. Patient genomics may lead to a specific diagnosis (e.g., inherited retinal disease) or therapy (e.g., RPE65-related Leber congenital amaurosis) and genomic studies of a tumor (e.g., ciliochoroidal melanoma) provide prognostic information that enables more effective follow-up. Furthermore, research on a genetically defined cohort with a multifactorial disease (e.g., AMD) may lead to discovery of significant treatment options.

Adopting the principles of precision medicine, ophthalmologists are encouraged to obtain patient genomic studies when appropriate and to combine genetic information with overall evaluation of family history, health history/behavior, lifestyle/environmental factors, eye health/vision history, and ophthalmology examination. The goal is to determine significant risk factors for disease, enable early-stage diagnosis, and provide the most effective therapy to improve, preserve, and restore vision.

  References Top

The Precision Medicine Initiative. Available from: http://www.whitehouse.gov/precision-medicine. [Last accessed on 2018 Aug 13].  Back to cited text no. 1
Precision Medicine Initiative Cohort Program. Available from: http://www.nih.gov/precision-medicine-initiative-cohort-program. [Last accessed 2018 Aug 13].  Back to cited text no. 2
Leroy BP, Pennesi ME, Ohnsman CM. Brave New World: Gene Therapy for Inherited Retinal Disease. American Academy of Ophthalmology EyeNet; Supp 2018. p. 1-16.  Back to cited text no. 3
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. 4
Tuart A. Inherited Retinal Disease. American Academy of Ophthalmology EyeNet; May 2018. p. 42-8.  Back to cited text no. 5
Tsang SH. Precision Medicine, CRISPR, and Genome Engineering. Switzerland: Springer Publishing; 2017. p. 1-178.  Back to cited text no. 6
Loftus P. FDA approves first “gene silencing” drug. Wall St J 2018;B2:11-2.  Back to cited text no. 7
Young TA, Burgess BL, Rao NP, Glasgow BJ, Straatsma BR. Transscleral fine-needle aspiration biopsy of macular choroidal melanoma. Am J Ophthalmol 2008;145:297-302.  Back to cited text no. 8
McCannel TA, Burgess BL, Nelson SF, Eskin A, Straatsma BR. Genomic identification of significant targets in ciliochoroidal melanoma. Invest Ophthalmol Vis Sci 2011;52:3018-22.  Back to cited text no. 9
Roach L. Precision medicine. American Academy of Ophthalmology EyeNet; 2017. p. 45-9.  Back to cited text no. 10
Jaochim N, Kifley A, Colijn JM, Lee KE, Buitendijk GHS, Klein BEK, et al. Joint contribution of genetic susceptibility and modifiable factors to progression of age-related macular degeneration over 10 years. Ophthalmol Retina 2018;2:684-93.  Back to cited text no. 11


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