inherited retinal degeneration: genetics, disease...

EditorialInherited Retinal Degeneration: Genetics, DiseaseCharacterization, and Outcome Measures

Naheed W. Khan,1 Benedetto Falsini,2 Mineo Kondo,3 and Anthony G. Robson4,5

1Department of Ophthalmology & Visual Science, University of Michigan, Ann Arbor, MI 48105, USA2Department of Ophthalmology, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del S. Cuore, Rome, Italy3Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan4Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK5Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK

Correspondence should be addressed to Naheed W. Khan; [email protected]

Received 13 September 2017; Accepted 14 September 2017; Published 25 September 2017

Copyright © 2017 Naheed W. Khan et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly cited.

Inherited retinal degenerations (IRDs) lead to incurablevision loss and affect 1 in 2000 to 3000 individuals. Thesedisorders may cause blindness associated with dysfunctionor death of photoreceptor cells, but prognosis is difficult todetermine due to variable disease expression. There havebeen significant advances in understanding the pathogenesisand genetics of IRDs with more than 250 genes being impli-cated to date. This has led to the development of treatmentsaimed at restoring function or delaying progression.

The design of therapeutic interventions depends on thephenotype and the molecular characteristics of the IRD.With advances in genetic testing methodology, there is anincreased detection of variants in multiple genes in the samefamily or even in the same individual, which makes the deter-mination of the primary genetic cause of disease more diffi-cult to assess. Using next generation sequencing, Menget al. show in a multigeneration Chinese family that PRPF3-associated autosomal dominant retinitis pigmentosa coexistswith CYP4V2-associated Bietti’s crystalline corneoretinaldystrophy. This further complicates the characterization ofphenotypes of an autosomal dominant condition with anautosomal recessive condition which results in a more severedisease phenotype.

Due to genetic heterogeneity of these retinal conditions,patients may have very similar clinical phenotypes but differ-ent genetic diagnoses, requiring for example gene-specifictherapy or gene-editing treatments to address the underlying

cause of disease. Development of effective treatment strate-gies requires robust clinical characterization to establishgenotype-phenotype correlations and to determine the ther-apeutic window and optimal stage for intervention. Katagiriand colleagues demonstrate in 20 patients with angioidstreaks that ABCC6 variants play a significant role in affectedJapanese individuals. Retinal degenerations may expressvariability in phenotype even within the same family. Iarossiet al. report genetic heterogeneity and associated variablephenotypes in familial exudative vitreoretinopathy (FEVR)which is a complex disorder characterized by incompletedevelopment of the retinal vasculature. The phenotypic vari-ability in such disorders adds a further degree of complexitywhen establishing study protocols.

Another major consideration is the development of teststo monitor the natural history of the disease to best measureoutcomes and to evaluate therapeutic efficacy in human clin-ical trials. Newer imaging technologies have made it possibleto study microstructural details of the retina. Quantitativeassessment of the structural and functional integrity of theretina and the correlation between the functional and struc-tural measures will improve our understanding of the diseaseand help in the design of appropriate outcome measures andtherefore in determining which patients might be the bestcandidates for treatments. There is a battery of methods totest visual function and retinal function, which poses achallenge when deciding which test or which combination

HindawiJournal of OphthalmologyVolume 2017, Article ID 2109014, 2 pageshttps://doi.org/10.1155/2017/2109014

https://doi.org/10.1155/2017/2109014

of tests to choose for a particular phenotype. Abed and col-leagues evaluate the relationship between cone photoreceptorfunction assessed by visual acuity and the focal electroretino-gram (FERG) and the integrity and structure of photorecep-tors using optical coherence tomography in Stargardt disease.Their study demonstrates that FERG amplitude can be reli-ably used to monitor macular cone function and that visualacuity is a useful indicator of foveal function.

Neuroprotection is a largely nonspecific strategy toprovide a protective environment for slowing the process ofphotoreceptor degeneration, thus extending the therapeuticwindow to later stages of disease. Exercise has been shownto have neuroprotective effects on photoreceptors in mousemodels of retinal degeneration. Levinson et al. did a retro-spective case-control study to report baseline physical activ-ity levels in individuals with retinitis pigmentosa. They usedthree quality of life questionnaires to determine the relation-ship between physical activity and visual function andshowed that increased physical activity is associated withgreater self-reported visual function and quality of life.

Naheed W. KhanBenedetto Falsini

Mineo KondoAnthony G. Robson

2 Journal of Ophthalmology

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