DEC 2013

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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64 EW MEETING REPORTER December 2013 continued from page 63 Reporting live from the 9th International Symposium of Ophthalmology (ISO) in Guangzhou, China to graft failure. CMV infection, said Dr. Tan, has always been common in solid organ transplant; however, its significance in corneal transplantation has only recently started to be recognized. Dr. Tan and his colleagues at the Singapore National Eye Centre recently came up against cases of recurrent, recalcitrant disease in graft patients that were mistaken for conditions such as Fuchs' heterochromic cyclitis. Definitive diagnosis was finally made through RT-PCR studies of aqueous fluid revealing CNV DNA. Cases are treated with high dose oral valganciclovir— 900 mg BID until aqueous taps are negative. Consulting their eye bank, Dr. Tan and his colleagues performed serologic testing of donor corneas and found that 25 out of 26 were positive for CMV serology— indicating a seroconversion rate of 96%. Fortunately, all were negative for CMV DNA, indicating that while exposure to CMV may be common, the donor tissue was unlikely to be the source of infection in their case. The question that naturally arises now is how many failed corneal transplants in the past were in fact due to CMV infection? The true extent and impact of CMV infection, said Dr. Tan, is yet to be determined. November 11, 2013 Targeting trabecular meshwork There are currently no drugs that act directly on the trabecular meshwork to affect aqueous flow. That may soon change with the elucidation of the structure's regulatory system. There are many regulatory systems in the anterior segment that relate to the anterior segment's configuration, said Paul Kaufman, MD, U.S. For instance, the contraction of ciliary muscle, regulated in response to stimulation of proprioceptive nerve terminals, leads to expansion of the Schlemm's canal—thus regulating outflow through secondary mechanisms. There is, it turns out, an analogous system that primarily regulates outflow within the trabec- ular meshwork. Contraction of the trabecular meshwork is effected by a rho kinase pathway; rho inhibition causes cellular relaxation and disruption of adhesions in the meshwork, leading to expansion of the aqueous network and widening of the canal. The trabecular meshwork is thus capable of finely tuned contraction and relaxation, actively modulating aqueous flow, indicating a "true trabecular outflow facility," said Dr. Kaufman. This facility, he said, represents the efferent arm of a reflex; various factors such as IOP and shear stress represent the afferent arm— the equivalent of the stimuli to which ciliary muscles respond with contraction. Between the efferent and afferent arms of the regulatory system, he said, there have to be some mediator molecules. In the case of the trabecular meshwork, the elevation of pressure is associated with the production of nitrous oxide and the upregulation of iNOS gene expression. "The meshwork is alive, aware of itself, its state of expansion and contraction, not at all a passive filter," said Dr. Kaufman. The elucidation of the meshwork's regulatory system, its pathways and mediators, even its regulatory genes, provides specific therapeutic targets, opening conditions like glaucoma up to treatments that, rather than destroying anterior segment structures, exploits physiological mechanisms to enhance outflow. "Since we know the pathway and that we can intervene genetically [...] we can dramatically increase the trabecular meshwork's outflow facility," said Dr. Kaufman. Editors' note: Dr. Kaufman has financial interests with various companies currently developing agents intended to act directly on the trabecular meshwork. Unresolved crosslinking issues While their work on accelerated collagen crosslinking adds to the growing pool of data indicating the procedure's ability to stabilize the cornea in patients with keratoconus (as well as its application in a growing number of other potential indi- cations such as symptomatic relief in patients with bullous keratopathy), Victoria Wong, MD, Hong Kong, noted that unresolved issues remain. These issues have to do with the variable individual response to the procedure and the paucity of prognostic factors for determining that individual response. Some patients' corneas, for instance, have been found to regress over six months after crosslinking; it remains to be determined whether these patients would benefit from retreatment. In the future, Dr. Wong said that customized graded protocols need to be established to allow clinicians to vary parameters such as soaking time, riboflavin concentration, total energy, illumination time and radiance intensity in response to individual patients' needs. Laser-cut corneas Having performed just over 100 cases, Shigeru Kinoshita, MD, Japan, noted some advantages to femtosecond laser-assisted corneal transplantation over manual penetrating keratoplasty (PKP). The femtosecond laser allows the creation of a zigzag cut, the specifications of which can be adjusted to include more or less endothelium as needed. Histologic examination shows that the femtosecond laser cuts the cornea beautifully, and Dr. Kinoshita said he is very satisfied with the laser's ability to create precise incisions In terms of the corneal endothelium, Dr. Kinoshita said that endothelial cell viability immediately after donor preparation did not differ significantly between the femtosecond laser and a manual trephine; neither did corneal endothelial cell density after transplantation. Measuring corneal hysteresis and corneal resistance factor, manual PKP resulted in weaker corneas; corneas that received the zigzag femto laser-cut donor tissues were comparable to both DSAEK and normal corneas. EW

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