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CLINICAL NEWS OF SATURDAY,
NOVEMBER 11, 2006

Editor-in-Chief: H.Dunbar Hoskins Jr., MD
Chief Medical Editors: Richard P. Mills, MD, MPH and Andrew G. Iwach, MD
Executive Editor: Patty Ames | Managing Editor: Susanne Medeiros
Senior Editors: Denny Smithand Chris McDonagh
Advisory Panel:
Terry L. Forrest, MD, Jean E. Ramsey, MD, Franco M. Recchia, MD,
James C. Tsai, MD and Helen K. Wu, MD
Guest Medical Editor: David DeRose, MD



Eyes on the frontier
In “Science Frontiers,” several physicians peeked behind the optic disc to find other phenomena contributing to glaucoma. Yeni H. Yücel, MD, PhD, described damage that may begin familiarly with the optic nerve but does not stop there. Dr. Yücel’s histologic evidence from a human case—consistent with experimental monkey models of glaucoma—shows how transsynaptic degeneration can pass neuronal injury, relay-style, along the visual pathway as far as the lateral geniculate nucleus (LGN). The LGN, of course, is arranged in well-known layers that correspond to various functions of motion and color processing, and they convey information to the visual cortex and associative cortices. Neuronal loss in Dr. Yücel’s slides can clearly be seen in the magno- and parvocellular LGN layers, and some changes can be noted in the koniocellular layer. The net effect of transsynaptic degeneration is a serious pathologic loss and/or atrophy of optic nerve fiber. Dr. Yücel added that the drug memantine may be useful in mitigating neuron shrinkage in the LGN.

Claude F. Burgoyne, MD, tackled the biomechanics of the optic nerve head (ONH) to illuminate causes of glaucomatous damage. His model is predicated on a more dynamic model of mechanics than the older, simple axonal-damage one. In his model, vascular and mechanical considerations are integrated, and stresses (forces), and strains (microdeformations) act upon neural and connective tissue architecture in predictable ways, independent of the origins of the stress and strain, and independent even of IOP. The resulting ischemia affects the volume of blood flow and nutrient diffusion in the peripapillary sclera and laminar beams, making them the principal sites of vascular and connective tissue interaction and resulting glaucoma injury. In addition, Dr. Burgoyne said, the more rigid connective tissues of an aged ONH will produce a shallower cupping profile than that typical of younger eyes. Consequent ly, visual field loss in older patients may be in progress before disc changes are obvious to the physician.

The fascinating hypothesis that glaucoma has an immunologic component was surveyed by Gülgün Tezel, MD. The activation of glial cells is apparent in the ONH and retina of glaucomatous eyes, Dr. Tezel said. She went on to profile a host of immunologic suspects in glaucoma progression: abnormal T-cell subsets, heightened monoclonal gammopathy, elevated optic nerve autoantibodies and retinal antigens, deposition of retinal immune globulin and up-regulation of retinal complement. Dr. Tezel pointed out that some of this activity may actually be neuroprotective as much as neurodegenerative. But clearly the aberrant immune activity is capable of facilitating degenerative processes. She hoped that continuing research would explain the immunogenic circumstances of glaucoma, and perhaps create new treatment opportunities.

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Growing worldwide diabetes epidemic likened to the global AIDS pandemic
David W. Parke, II, MD, speaking today at Retina Subspecialty Day reported that by 2010 the worldwide prevalence of diabetes is expected to increase by 46 percent, and by 2030, 370 million people worldwide are expected to have diabetes. “This growing epidemic should be considered in the same context as AIDS. It’s global, it’s at least partially preventable, the economic costs are quantifiable and the human cost is incalculable,” Dr. Parke said.  

Dr. Parke noted that the challenges are many: There is no routine population screening, diagnostic rates are inadequate, not all available therapies arrest disease progression, secondary treatment failure rates are rampant, treatment responder rates vary between 40 percent and 70 percent, and side effects of current treatments are significant and compliance suffers. Prevention has a particular attraction because tight glycemic control is difficult to achieve once type 2 diabetes has developed. He noted that the Finnish Study, the Diabetes Prevention Program, was stopped one year early due to clear results demonstrating that diet and moderate exercise reduced the risk of developing diabetes by 58 percent. He mentioned other studies that have demonstrated tight blood glucose control and tight blood pressure control provide sustained protection against diabetes progression. “We have our work cut out for us as physicians and members of the global community. You, as ophthalmologists, have a vital role in the education of your patients. You need to stress the importance of tight blood glucose control and tight blood pressure control,” Dr. Parke said.

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AREDS supplements appear to have long-term protective effects
On Friday, Emily Chew, MD presented 10-year follow-up results of the Age-Related Eye Disease Study (AREDS). AREDS study participants treated with antioxidants alone or with antioxidants plus zinc for a median of 6.5 years appeared to continue to benefit from the supplements 10 years later. Dr. Chew said it’s unclear why the benefits persisted, but it is clear that the combination treatment of high-dose antioxidants and zinc remains the most effective of the treatment options in reducing the risk of progression to advanced AMD.  For progression to neovascular AMD, treatment effects were stronger in the full follow-up than in the clinical trial. These results support the recommendation to consider combination treatment of antioxidant vitamins and zinc with copper for patients with extensive intermediate drusen or large drusen in both eyes and patients with advanced AMD in one eye. The AREDS formulation will be further refined in the current AREDS 2 stud y which will evaluate the possible deletion of beta carotene and lowering the zinc levels to 25 mg from the original formulation.

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Implantable miniature telescope improves visual acuity and quality of life in patients with end-stage AMD
Paul Sternberg Jr., MD, Friday presented 24-month data that showed mean distance BCVA improved 3.2 lines and mean near BCVA improved 2.9 lines in patients with bilateral moderate to profound central vision impairment due to end-stage AMD. A gain of three or more lines of distance BCVA occurred in 59.2 percent of implanted eyes compared to 10.3 percent of fellow control eyes. NEI VFQ scores show relevant VFQ subscales improved seven to 14 points after one year. A loss of three or more lines of distance BCVA occurred in 0.6 percent of implanted eyes compared with 7.5 percent of fellow eyes. The implantable miniature telescope is a prosthetic telescope developed for monocular implantation to reduce visual impairment due to advanced AMD. Dr. Sternberg noted that, if approved for use, this device could provide the first treatment option that offers quality of life and sustained long-term visual acuity improvements in this subgroup of AMD patients with bilateral severe vision loss. But vitreoretinal specialists should be aware that these patients will require multidisciplinary patient management. Patients will need to be referred to appropriate anterior segment surgeons for device implantation and to visual rehabilitation specialists to help them use their new vision in everyday activities.

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Poor compliance with glaucoma therapy is more common than you think
Steven L. Mansberger, MD, speaking at the Glaucoma Subspecialty Day, said that at least 10 percent of visual field loss in glaucoma patients is related to noncompliance with medical therapy. “Noncompliance may be the modifiable risk factor most likely to reduce vision loss,” said Dr. Mansberger. According to studies he has been involved with, patients who said they used their medication 100 percent of the time, were actually only using it 76 percent of the time. He said he has been “shocked” by some of the study results. He has also found that 40 percent of patients are not using their drops 90 percent of the time. “And you get the same thing too in your practice,” he told the audience. “One patient who said he was pretty compliant, actually missed three days in a row. And he was well-informed about glaucoma, so I was shocked.”

So, how do you determine patient compliance? Ask them. If they say they aren’t compliant, they probably aren’t. But if they say they never miss a drop, they may still be noncompliant. Other ways to determine compliance include looking at the patients’ refill history, and electronic drop monitors in medication bottles. Because it has been shown that medication compliance improves just before a visit, those having a hard time with compliance should be seen more often. Other advice on improving compliance: educate the patient about the benefits of treatment, show them photos of their optic disc and visual field compared with normal photos, work with them, ask them if they want to use the medication first thing in the morning or at night, praise them when they do well, talk about subjects other than glaucoma, consider once-a-day dosing and refrigerate the drops. Borrowing a tip fr om potty training can also work well, Dr. Mansberger said. Just as his wife finds that a little peer pressure can help induce toddlers into potty training, he has found that inviting friends and family into the exam room helps glaucoma compliance. “My wife hates it when I use this photo,” describing a photo of a row of toddlers in the act, “but it works.”

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Combination of ReZoom/ReStor multifocal IOLs appears to mitigate problems with intermediate vision
Frank Bucci Jr., MD, today reported on his findings comparing the near and intermediate visual function in bilateral cataract and refractive lensectomy patients receiving either ReZoom/ReStor or the ReStor/ReStor multifocal IOLs. There was no significant difference observed when comparing bilateral near vision, but there was a statistically significant difference when comparing bilateral intermediate vision (RS/RS=J 3.81 vs. RZ/RS= J 2.39). A comparison between unilateral RZ and RS eyes revealed significantly better intermediate vision with the ReZoom (RZ = J 3.03 vs. RS = J 4.21). There was no difference observed between the two lenses in near vision. Most significantly, said Dr. Bucci, is that 15 of the 55 patients in the RS/RS group volunteered complaints regarding intermediate vision, while no patient in the RZ/RS group offered such complaints. When he replaced one of the ReStor lenses with a ReZoom lens in these 15 patients, they no longer complained about their intermediate vision.  

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