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Fuchs Dystrophy: From Genetics to App

Lester Briney is a successful engineer and entrepreneur. He has his own company and is Chief Technology Officer (CTO) of another. His work was getting harder because his vision steadily declined over a decade. The truth is that he has Fuchs Corneal dystrophy, a degeneration of the inner cell layer of the cornea (the clear tissue in the front of the eye). As the CTO of a company developing video technology, this made it difficult to see if the product was functioning well or not. Working in the mornings soon became impossible because this was the time when his eyesight was at its worst. He could not drive to work until noon. His failing eyesight was not only a difficulty in his work, but a detriment to his life. As if it was not bad enough, the additional progression of cataracts nearly put his eyes out of commission.


He decided it was time to get to the bottom of his vision decreasing. Being an engineer, he knew the importance of seeking expert advice. He took to the Internet in search of help. He soon found Natalie Afshari, M.D., known for her research in Fuchs endothelial corneal dystrophy and clinical care of patients afflicted with it. At the time of his research, Dr. Afshari had just been recruited to the UC San Diego Shiley Eye Center from Duke University where she was Professor of Ophthalmology. Soon after walking into her new Shiley Eye Center office last fall, she opened a letter already on her desk from Mr. Briney. Three days later, they were scheduling his first appointment.

Dr. Afshari, as the new Chief of Cornea and Refractive Surgery and Professor of Ophthalmology, checked his eyes during different times of the day and noted a significant difference. It was clearly time to plan for DSAEK (Descemet’s automated endothelial keratoplasty) surgery, which is a partial thickness corneal transplant surgery. Mr. Briney was unsure about having surgery but he had faith in Dr. Afshari. To his relief, the surgery was painless and successful. After his surgery, he opened his eyes to see the world as though it was in “high definition.” Mr. Briney admitted, “I was postponing this surgery because I didn’t know what to expect, but I was pleasantly surprised and very glad to finally see clearly.”

Fuchs endothelial corneal dystrophy is one of the leading reasons for ~ 40,000 corneal transplants that are performed annually in the United States. It causes decreased vision as a result of endothelial cell loss and corneal swelling. Cornea endothelial cells, comprising the innermost layer of the cornea, are cells that pump fluid out of the cornea and keep it clear. A significant reduction in the endothelial cell density results in insufficient pump function required for the cornea to stay clear and dehydrated. This causes the cornea to swell, compromising transparency, and leading to a decrease in visual acuity.

Future Therapy

Dr. Afshari has been studying the genetics of Fuchs Corneal Dystrophy for over a decade and has collected over 1500 patients’ DNA sample with this disease. With colleagues, great strides have been made in pinpointing areas of the genome responsible for this disease. They have also been developing new options for treatment of Fuchs Endothelial Dystrophy. Her colleagues Dr. Shigeru Kinoshita and Dr. Noriko Koizumi from Kyoto, Japan have worked on a type of molecule called ROCK inhibitor as a potential agent for division of the corneal endothelial cells. Dr. Afshari has also worked on developing eye drop medications as opposed to surgical treatment for Fuchs corneal dystrophy. Topical administration of ROCK inhibitors in animals has demonstrated marked reduction of corneal swelling in treated eyes. “For the future, my hope is to treat patients that have Fuchs with eye drops rather than surgery. I believe this is achievable very soon” says Dr. Afshari.

“Dr. Afshari’s research on Fuchs represents some of the most important opportunities to make advances both in our fundamental understanding of corneal diseases, as well as in bringing new treatments forward” says Jeffrey Goldberg, M.D., Ph.D., Director of Research and Professor of Ophthalmology at the Shiley Eye Center.


Fig 1: iPhone Application for Physicians

How does all of this relate to smartphones?

Most recently, Dr. Afshari and her team have developed a smartphone application to be utilized by physicians for predicting the refractive shift (correction needed with eye glasses or lens implant) in patients’ eyes after DSAEK. Although this surgery often produces excellent visual outcomes and rapid recovery, patients also commonly experience some change in refraction in the transplanted eye - usually becoming slightly more far-sighted. Recently, Dr. Afshari developed a mathematical model and formula for predicting this change in vision after DSAEK surgery based on measurements of the patient’s eye and the transplant tissue made before surgery. Because this formula is cumbersome to calculate manually, she and her team developed a smart phone application to allow corneal surgeons to select the optimal lens implant for clearest vision. Smartphones are everywhere, even in the operating room these days. “I hope that our smartphone App helps accuracy of surgical outcomes for patients around the world” says Dr. Afshari.

In each version of the application, the user will be asked to input the patient’s preoperative central corneal thickness in micrometers, the patient’s preoperative posterior radius of curvature in millimeters, the corneal transplant’s central graft thickness in micrometers, and finally the corneal transplant’s graft central-peripheral thickness ratio in order to calculate the post-DSAEK refractive shift.

Mathematical Algorithm for the smartphone Application to Predict Post-DSAEK Refraction Shift


Fig 2: Published in Investigative Ophthalmology and Visual Science (Refractive changes after descemet stripping endothelial keratoplasty: a simplified mathematical model. Hwang RY, Gauthier DJ, Wallace D and Afshari NA.)


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