September 2015




World Cornea Congress highlights

New approaches for managing corneal opacities and dystrophies

by Lauren Lipuma EyeWorld Staff Writer


Subtle corneal opacities in an individual with granular corneal dystrophy type II (GCD type II, a TGFBI corneal dystrophy). As the opacities are not characteristic of GCD type II, genetic analysis is the only means of making an accurate diagnosis to determine candidacy for refractive surgery.

Failure to identify and exclude individuals with GCD type II as candidates for refractive surgery may result in a significant exacerbation of the corneal deposits, as seen here.

Source: Anthony Aldave, MD

Specialists present alternatives to traditional ways of classifying, diagnosing, and treating corneal disease

Physicians have historically described congenital corneal opacities and corneal dystrophies in terms of the patients clinical presentation. But recently, as new methods such as anterior segment imaging and DNA sequencing have deepened our understanding of these conditions, they have shown that traditional classification systems are woefully inadequate. During the Dystrophies, Degenerations, and Genetics session at World Cornea Congress VII, several cornea specialists described how they have used new technologies to create superior classification systems for corneal disease that could lead to better diagnostic testing, more effective treatments, and improved visual outcomes.

Getting rid of outdated terminology

Ken Nischal, MD, FRCOphth, professor of ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, highlighted the shortcomings of the terms physicians use to describe congenital corneal opacities. Corneal opacities in newborns that are not due to glaucoma are often lumped together under the headings of Peters anomaly or sclerocornea, but these terms dont really make sense, Dr. Nischal said, because they dont communicate a specific sign or a disease. In addition, with the advent of anterior segment imaging, it became apparent that Peters anomaly and sclerocornea were describing many types of opacities that dont originate in the cornea. One example is primary aphakia, where the lens fails to form and this causes corneal opacification secondary to a primary lens failure. It doesnt make any sense to call it sclerocornea because the problem is not the sclera or the cornea, Dr. Nischal said in his presentation. To label this as sclerocornea doesnt impart the gravity of the intraocular complications youre about to deal with. Dr. Nischal suggests naming congenital opacities as primary and secondary corneal diseases, where primary corneal diseases are developmental anomalies of the cornea itself and secondary corneal diseases are those that originate elsewhere but have corneal symptoms. He and other ophthalmologists who treat these conditions hope to establish an international consensus on this classification system in the near future.

Choosing the best treatment for each child

Congenital corneal opacities are usually treated with penetrating keratoplasty, but if the opacity doesnt affect the entire cornea, there is another option. If the opacity is central or eccentric, you can do an optical iridectomy by cutting out the iris in the area of the clear cornea, Dr. Nischal said in an interview with EyeWorld. If, however, the cornea is completely opaque, there is no other option than a corneal transplant. Determining whether the opacity is primary or secondary could help physicians predict how successful a transplant will be. Patients with secondary corneal opacities often have a poor prognosis and their grafts frequently failbecause the problem is not the cornea. If you have congenital glaucoma and a corneal opacity, if I said to you that the way to treat that was to do a corneal graft, you would think I was mad, and you would be right, Dr. Nischal said in his presentation. But there are conditions inside the eye affecting the lens that give you a corneal opacity, and we do a corneal transplant and expect it to work. That is equally mad. Physicians usually measure a transplants success by graft clarity, but in children with congenital opacities, graft clarity does not necessarily translate into functional vision. A better measure of success, Dr. Nischal said, is how well postop vision allows a child to continue developing. We know in pediatrics that if you give children vision that goes from hand movements to counting fingers in the first year of life, you exponentially improve their global development rather than just their visual development, he said. Rather than treating these opacities as if they were in adult corneas, Dr. Nischal urged physicians to recognize that these infants and children are still developing biologically and their brains have huge potential for compensation. Even if a graft is rejected, poor vision is better than none. The brain is a blank canvas, Dr. Nischal said. If you leave it blank, its not going to do very well. But if you give it some information, it will utilize that information to its maximum potential.

Redefining corneal dystrophies

Recent advances in DNA sequencing and improved histology and microscopy techniques have given physicians a better understanding of the genetic and cellular origins of corneal dystrophies. Using this information, cornea specialists have regrouped these conditions into a new classification system. The International Committee for Classification of Corneal Dystrophies (IC3D), Edition 2, was published in the February 2015 issue of the journal Cornea. Jayne S. Weiss, MD, chair of the Department of Ophthalmology, Louisiana State University Medical School, New Orleans, the papers lead author, presented the new IC3D to attendees during the session. We now recognize that some corneal dystrophies affect many cell layers, and this is reflected in the new anatomic classification, Dr. Weiss said. Dr. Weiss and her collaborators updated the IC3D to include the major clinical, histopathologic, and genetic information that has been learned since the first edition was published in 2008. They reclassified corneal dystrophies into 4 groups based on corneal anatomyepithelial and subepithelial dystrophies, epithelial-stromal dystrophies caused by mutations in the transforming growth factor, beta-induced gene (TGFBI), stromal dystrophies, and endothelial dystrophies. The IC3D Edition 2 is the first to group the TGFBI dystrophies together in a distinct anatomic category. TGFBI mutations affect multiple layers of the cornea, so these dystrophies had been grouped separately depending on the layer affected despite the fact that they come from the same gene. The authors also described a category of dystrophies that were previously not well recognized epithelial recurrent erosion dystrophies. The 3 variants of this disease are inherited as autosomal dominant disorders and present in the first decades of life with recurrent epithelial erosions. During the pain-free periods, corneal exams are normal, but by midlife, patients may have subepithelial corneal fibrosis or corneal keloid. These hereditary conditions can be an under recognized cause for recurrent corneal erosions, Dr. Weiss said. The IC3D Edition 2 is available for free online to be used as an easy reference for comprehensive ophthalmologists. The prior edition is available online at in English, Spanish, and German. Disease templates now include specifics about histopathology, OCT and/or confocal microscopy, in addition to inheritance patterns, gene involvement, and clinical signs and symptoms. Electron micrographs and histopathology images are also included to complement traditional clinical photographs.

Genetic testing is not just for pediatrics

As physicians gain a better understanding of the genetics of corneal disease, they have begun to ask the question: Is there any use in testing adults for genetic corneal disorders? While many ophthalmologists believe the answer is no, Anthony Aldave, MD, professor of ophthalmology and chief of the cornea service, Stein Eye Institute, Los Angeles, showed one situation where it is usefulduring preoperative testing for keratorefractive surgery. Some corneal dystrophies are contraindications for LASIK because the surgery can exacerbate symptoms and stimulate opacity formation in the cornea. But patients with corneal dystrophies that are associated with a later onset of the dystrophic deposits could decide to have refractive surgery before the corneal opacities appearor when present but so subtle they may be easily overlooked or misdiagnosed. Dr. Aldave presented several cases where patients with corneal opacities underwent refractive surgery. In one case, a patient presented with a few corneal opacities diagnosed as corneal scars during the preop exam. The patient had no known family history of corneal disease. Several years after surgery, however, the patient developed a significant exacerbation of the corneal opacities and reduced vision. Genetic testing confirmed that the patient had granular corneal dystrophy type II. Dr. Aldave described another refractive patient who had normal topography and corneal thickness at the preop exam. The patient had subtle endothelial changes in one eye that were suggestive of posterior polymorphous corneal dystrophy (PPCD). Genetic testing to confirm the diagnosis of PPCD, which has recently been associated with corneal ectasia, was not performed, however. Following surgery, the patient developed bilateral corneal ectasia. The take-home message from these cases is that it does make sense to do genetic testing on certain patients prior to refractive surgery. Dr. Aldave recommends testing patients who have unexplained corneal stromal or endothelial opacities, and individuals under 40 years of age with Korean or Japanese ancestry, a family history of a TGFBI dystrophy, or a family history of corneal transplantation for an unclear reason. Avellino Labs (Menlo Park, Calif.), Asper Biotech (Tartu, Estonia), and the Carver Lab at the University of Iowa (Iowa City) offer commercially available tests for corneal dystrophies that are easy to performa DNA sample from blood, saliva, or a cheek swab is all that is needed. If patients test positive for any of the TGFBI corneal dystrophies or PPCD, Dr. Aldave recommended avoiding LASIK.

Editors note: Dr. Aldave has financial interests with Avellino Labs. Drs. Nischal and Weiss have no financial interests related to this article.

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