• Comprehensive Ophthalmology

    The March issue of the Archives of Ophthalmology focuses on the expanding area of genomics in ophthalmology and includes four original research articles and two editorials. The editorials discuss the promise of personalized medicine in ophthalmology and the work being conducted by the National Eye Institute's National Ophthalmic Disease Genotyping Network (eyeGENE). The research articles advance our knowledge of the effects of genetics on ophthalmic disease and emphasize the holistic nature of disease development - an amalgam that includes not only genetics but possibly environmental and other factors. Some of the research concludes that even though genetics doesn't always tell the whole story of an individual's disease status, it can play an important role when clinical and histopathologic information is not able to accurately diagnose.

    The editorial on personalized medicine in ophthalmology discusses how the strategy could greatly expand the use of genomic information to determine treatments and doses most likely to be effective and without significant side effects. An increased emphasis on personalized medicine could help minimize morbidity and costs related to inappropriate treatment and spur the development of gene-directed therapies and the investigation during clinical trials into how genomic factors affect drug effectiveness. Additionally, the growing understanding that environmental factors may interact with genetics in determining disease development holds the potential for clinicians to be able to identify individuals genetically at risk for particular conditions and advise them on environmental conditions to avoid.

    The other editorial provides an overview of the role of eyeGENE, which became operational in 2006, as a repository for DNA, blood, and phenotype information that is being used to conduct research on mendelian disorders that affect vision. On the NEI Web site you can find a list of the genes and diseases currently being tested by the eyeGENE Network, as well as instructions on how to send samples from your patients to eyeGENE.

    The authors of a study on discordant phenotypes of retinitis pigmentosa and cone-rod dystrophy resulting from the same genetic mutation of the retinitis pigmentosa GTPase regulator gene in fraternal twin brothers argue that their results provide strong evidence that modifier genes can produce diverse disease phenotypes in people with these mutations. The researchers recommended additional genetic analysis in families in which intrafamilial retinal disease phentopyic variation is caused by similar genetic mutations. They also noted that environmental factors could play a role in modulating disease phenotype.

    Another study examines five Chinese families with congenital fibrosis of the extraocular muscles (CFEOM) and lends further support to the conclusion that multiple phenotypes of some ocular diseases can arise from the same mutation. The researchers looked for mutations by sequencing the kinesin family member 21A gene (KIF21A) in the subjects. The study's conclusions stressed that clinical and genetic findings can complement each other in determining the most appropriate diagnosis, prognosis, and treatment for CFEOM patients.

    One study used genetic, clinical, and histopathologic examinations to investigate a novel mutation in the transforming growth factor β-induced gene (TGFBI), p.Met619Lys, and its associated variant of combined granular-lattice corneal dystrophy in affected and unaffected relatives of one family. The researchers concluded that the phenotypic expression of this atypical TGFBI dystrophy was likely determined by a combination of the mutation's effects on the structure and function of the encoded protein, an individual's genetic background, and environmental factors. They asserted that molecular genetic information about TGFBI dystrophies was key in understanding and classifying corneal dystrophies, since neither clinical nor histopathologic features could accurately diagnose and classify them.

    A study on a novel mutation of the GUCY2D gene responsible for autosomal dominant cone degeneration in an African-American family-thought by the authors to be the first clinical and genetic report of cone degeneration in an African-American family and of this particular GUCY2D mutation-reported that cone degeneration was incomplete and age-dependent in the members of the family with the genetic mutation. The researchers designated the autosomal dominant cone degeneration they described as cone degeneration 2 to distinguish it from cone degeneration 1, previously reported X-linked cone degeneration.