• Triamcinolone Data Coming In
• Drug May Reduce Vision Loss in Retinopathy
• What’s Good for the Head May Be Good for the Eyes
• Portable Television Goes Hands Free
Triamcinolone Data Coming In
With a few years of intravitreal steroid injections under their belts, vitreoretinal specialists are beginning to understand how to make the technique work without
subjecting their patients to irreversible complications.
Papers published over the last year, presentations at summer 2005 research meetings and a report planned for Retina Subspecialty Day this month retain their caution. But the numbers of patients in the reports are larger, and the presenters have less tentativeness to their optimism.
“There are side effects from intravitreal triamcinolone that one needs to be aware of, and they need to be managed properly,” said Daniel B. Roth, MD, a New Jersey retina surgeon who presented a 1,000-patient study at two major research meetings last spring and summer. “But I think, all in all, these injections are very safe.”
Meanwhile, the August Archives of Ophthalmology describes a study that used a similarly large patient population to conclude that it is “uncommon” to experience one of the most feared complications of intravitreal injections, acute endophthalmitis. Out of 1,006 eyes injected, not a single case of culture-positive endophthalmitis occurred, they found. There was one case of sterile endophthalmitis, which resolved successfully.1
At the Academy’s Retina Subspecialty Day, European investigators will present positive results from combining photodynamic therapy and intravitreal triamcinolone. They found: fewer re-treatments, an effect through two years, and an 18.4 percent occurrence of transient IOP elevation. Only two cases required surgery.2
Dr. Roth presented his report on 1,540 injections at the 2005 meetings of the Association for Research in Vision and Ophthalmology and the American Society of Retina Specialists.3,4 Patients had a wide variety of diagnoses, including diabetic macular edema, choroidal neovascular membranes, retinal vein occlusion and postoperative cystoid macular edema.
Dr. Roth, assistant professor of ophthalmology at the University of Medicine and Dentistry of New Jersey, reported these complications:
Cataract: 40.8 percent of the 576 phakic patients had cataract progression by 12 months after injection, with half of those requiring surgery. “Patients have to be warned,” he said.
IOP rise: Levels above 21 mmHg were seen in 38.7 percent of the eyes, and in 21 percent IOP measured > 25. Only one patient required filtration surgery, however. IOP elevation was most common in the 21 patients with uveitis, 71.4 percent of whom had an IOP > 21 mmHg and 42.9 percent > 25.
Adverse events: One patient had a recurrence of a retinal detachment, three suffered corneal abrasions and one had anterior scleritis.
Endophthalmitis: There were six cases of sterile endophthalmitis with hypopyon and four cases of marked inflammation without hypopyon (1 percent of eyes and 0.6 percent of injections).
The data and experience show that sterile endophthalmitis is rare and its impact is minimal, Dr. Roth said. The eyes aren’t painful or red, and the condition resolves without treatment, he said.
“Even if a patient develops this severe inflammatory response, I wouldn’t get overly concerned,” Dr. Roth said. “The patients come in and say, ‘Hey, I can’t see.’ It typically presents without pain or conjunctival injection on the next day, but it may occur within hours. I’d just wait it out cautiously and watch very carefully for other issues, seeing them again within 12 to 24 hours.”
Such news surely is reassuring to ophthalmologists who worry about the profession being a little cavalier in its embrace of intravitreal steroids before the data are all in.
1 Westfall, A. C. et al. Arch Ophthalmol 2005;123:1075–1077.
2 Augustin, A. J. “PDT and Steroids: The European Trial,” to be presented at Retina Subspecialty Day, Friday, Oct. 14, 2005, at 11:04 a.m.
3 Paper #4733 “Complications Associated With Intravitreal Triamcinolone Acetonide Injection —A Study of 1000 Eyes,” presented at the Association for Research in Vision and Ophthalmology, Thursday, May 5, 2005.
4 Presentation at the American Society of Retina Specialists, Sunday, July 17, 2005.
Drug May Reduce Vision Loss in Retinopathy
An enzyme-blocking drug for which many had high hopes has failed its primary clinical test of stopping diabetic retinopathy from progressing. However, ruboxistaurin did reduce the patients’ visual loss over the course of three to four years, according to the much-anticipated first report from a large clinical trial.
The Protein Kinase C ß Inhibitor Diabetic Retinopathy Study (PKC-DRS) tested three different oral dosages of ruboxistaurin in 252 patients. PKC ß is the form of this kinase most closely linked to damage in the retinal microvasculature of diabetics, probably via its role in initiating the VEGF pathway toward leaky, proliferating vessels. In other studies, ruboxistaurin is being investigated to halt other diabetes complications, including nephropathy, peripheral neuropathy and cardiovascular conditions.
The disappointing results on retinopathy progression might have occurred because study subjects all had moderately severe to very severe retinopathy before they began taking the drug, the authors speculate in their paper in the July Diabetes.1
“PKC ß is activated very early in diabetes, well before clinically apparent retinopathy,” they write. “Thus, in our study participants, significant biochemical and pathologic retinal changes that are no longer amendable to PKC ß inhibition may have already occurred before enrollment.”
But the positive results on the secondary endpoint—degree of visual loss—still represent cause for a certain amount of optimism about ruboxistaurin, said Peter K. Kaiser, MD, a retina specialist at the Cleveland Clinic, who was an investigator in the trial for the drug.
“Although it’s a secondary endpoint, that’s a powerful endpoint. Vision matters tremendously,” Dr. Kaiser said. “To have an oral medication that stems not only diabetic retinopathy but also peripheral neuropathy and nephropathy, that would be beautiful. It would be ideal. So I think this story isn’t over yet.”
Indeed, even as this first study was being discussed, the PKC-DRS investigators were analyzing their data on subjects who had diabetic macular edema, the subset that demonstrated the strongest trend toward a reduction in vision loss when taking 32 milligrams of ruboxistaurin daily, the largest of three doses tested.
The 32-mg dosage of ruboxistaurin significantly reduced the risk of moderate visual loss (> 15 letters on the ETDRS chart) to 37 percent of what it otherwise would have been.
For sustained moderate visual loss (> 15 letters at two consecutive visits at least six months apart), the results trended in the same direction but without statistical significance.
Another positive result reported in the trial was the lack of liver toxicity or the adverse events that were seen in earlier tests of drugs inhibiting multiple variants of PKC, instead of just the single ß isoform on which ruboxistaurin acts. There were only nine adverse events in the ruboxistaurin trial.
“We also found that patients did much better with ruboxistaurin if they had better control of blood sugar,” Dr. Kaiser noted. That is being factored into other ongoing trials, he said.
“I really like the idea of ruboxistaurin,” he said. “It’s about more than just their vision, because protein kinase C ß is active in so many body systems affected by diabetes. And it’s a pill, the most benign thing you can give someone. I hope the follow-up study results will mirror these, so the drug actually would get approved.”
Dr. Kaiser receives research grant support as an investigator but otherwise has no financial interest.
1 Aiello, L. P. et al. Diabetes 2005; 54(7):2188–2197.
Eye on Research
What’s Good for the Head May Be Good for the Eyes
German researchers have found what might be a new line of defense against corneal pain caused by PRK: sumatriptan.
Their study, published in the Journal of Cataract and Refractive Surgery, found that nearly 90 percent of the PRK patients who took the migraine drug reported excellent pain relief during the 24 hours after surgery.1
Sumatriptan, sold in the United States under the brand name Imitrex (and sold as Imigran in Europe and Canada), is a highly selective serotonin agonist that stops migraine pain through vasoconstriction. Because sumatriptan is known to directly affect the trigeminal nerve, the Regensberg, Germany, researchers set out to determine whether it also would short-circuit pain signals transmitted by the trigeminal’s first branch, the ophthalmic nerve.
Fifteen PRK patients (18 eyes) agreed to take oral sumatriptan as their postoperative pain medication, and then only when their discomfort reached 4 on a scale of 0 to 6. Some of the patients were told to take a second 100 milligram dose four hours later; the remainder did so only if pain recurred.
In the first group, pain alleviation was reported in nine of 10 eyes. In the second group, patients said that pain was reduced in seven of eight eyes, though by less than in the first group.
David R. Hardten, MD, a Minneapolis refractive surgeon who coauthored a paper on triptans and LASIK earlier this year,2 said that confirmation of the sumatriptan study’s results would give ophthalmologists another therapeutic option. “Every patient responds differently to pain and may benefit from a different pain medication.”
But sumatriptan and related drugs might also have side effects, he added. “It has been thought that triptans may reduce epithelial adhesion, and case reports of recurrent erosion syndrome in patients on triptans have been noted,” he said.
1 Gamulescu, M. A. et al. J Cataract Refract Surg 2005;31: 1255–1256.
2 J Cataract Refract Surg 2005; 31:72–76.
Portable Television Goes Hands Free
And you thought there already were enough of us walking around paying more attention to our cell phones than to the world around us. Apparently not, because the next ripple in mobile communications just might be . . . cellevision.
“Video in the cellular handset is really the next killer application,” said Mark Spitzer, PhD, founder and CEO of MicroOptical, of Westwood, Mass., which makes a spectacles-like device that plugs into a cell phone for viewing TV, games and other multimedia features. “The problem our eyewear solves is that the cell phone screen is too small and not really very good outdoors.”
The headgear contains two full-color microdisplays that project two separate video images in front of the wearer’s eyes, which the brain fuses, yielding a “TV screen” that seems to be 12 inches wide and 3 feet away.
This version of MicroOptical’s video eyewear allows surroundings to be seen only around the edges, but refractive correction can be added. Indeed, a European eyeglass manufacturer is already trying to do that, Dr. Spitzer noted.