VITREORETINAL SURGERY FEATURE STORY Laser Treatment Shows Promise for Diabetic Macular Edema A Q-switched Nd:YAG laser may allow treatment earlier and closer to the fovea than standard laser photocoagulation. BY JOHN MARSHALL, PHD, FRCPATH, FRCOPHTH(HON); LUCIA PELONSIS, MRCOPHTH; PETER HAMILTON, FRCS, FRCOPHTH; AND ROBIN HAMILTON, MBBS, MRCOPHTH s anyone in medical practice sees on a daily basis, there is an increase in the incidence of The history of this field has been diabetes and diabetes-related complications among our patients. This is due in part to a sequence of increasingly subtle Aearlier diagnosis and screening programs, but also to an treatments applied at earlier increase in obesity and life expectancy. So acute is the points in the disease process. problem that the World Health Organization added diabetic retinopathy to its priority list of diseases.1 Just 4 decades ago, most people diagnosed with dia- RETINA REGENERATION THERAPY betes would likely go blind if they lived long enough Nonthermal Retina Regeneration Therapy (2RT; Ellex, because there were no safe and effective treatments for Adelaide, Australia), is a short-pulsed laser treatment managing associated ocular diseases. Available treatments that is intended to treat diabetic maculopathy and were associated with risk of significant complications.2 macular edema at an earlier stage of the disease. The The advent of retinal photocoagulation heralded a therapy may also have application in the treatment of tremendous change in treatment; for the first time, early-stage age-related macular degeneration. (For more there was a way of at least managing the progression information, see 2RT in Treatment of Age-Related of retinal disease in patients with diabetes.3 Laser ther- Macular Degeneration.) apy combined with early screening and effective con- The laser used for 2RT is a Q-switched, green Nd:YAG trol of the disease led to a decrease in the number of laser with a wavelength of 532 nm. Its pulse duration is patients who required more severe treatments, such as 3 nanoseconds with energy of 1 µJ per pulse. The laser vitrectomy. treatment triggers what we describe as photoregenera- The history of this field has been a sequence of tion of the retinal pigment epithelium and Bruch’s increasingly subtle treatments applied at earlier points membrane—the areas responsible for keeping retinal in the disease process. Currently, retinal photocoagula- function optimized—without damaging peripheral tion remains an effective means of controlling the pro- areas. gression of diabetic retinopathy, maculopathy, and mac- The laser was developed as a result of preclinical ular edema; however, we are still unable to treat affect- proof-of-principle laboratory work at Saint Thomas’ ed areas located near the fovea. A research and clinical Hospital.4 Ellex has since received an Australian govern- study that we have embarked upon may lead to the ment grant to expand the laboratory and clinical development of a subtle laser treatment that may be research on the 2RT. used, even at the fovea, prior to the development of Not only can the laser treatment be placed closer to ischemia. the fovea; equally significant, the 2RT can be used earlier 74 IRETINA TODAYIJULY/AUGUST 2008 VITREORETINAL SURGERY FEATURE STORY in the disease process, offering the potential to preserve put significant limitations on the location and timing a greater degree of functional vision for a longer time. of laser photocoagulation—not too close to the fovea, not too early in the course of the disease. With CLINICAL RESULTS 2RT, there is potential to develop a laser treatment In the first clinical study of the procedure,4 29 eyes that affects only the RPE without damaging the pho- (18 patients) underwent 2RT for the treatment of dia- toreceptor cells, meaning that we can get closer to betic maculopathy and/or macular edema. Currently, the fovea without damaging central vision. For the patients are being followed for 1 year. Postoperative first time, there is the potential for a prophylactic testing includes optical coherence tomography and treatment approach in patients with diabetic macular microperimetry. edema or maculopathy. At 3 months, most patients showed improvement in Further clinical studies are under way in the United visual acuity and decrease in central macular thickness. Kingdom and Australia, with expansion to follow to Central macular thickness decreased in 55% of eyes and additional international sites throughout 2008. If these remained stable in 24%. The remaining 20% experienced additional clinical studies achieve the results seen in an increase in central macular thickness. There was a the London study, Ellex plans to move forward with mean improvement in logMAR visual acuity from commercial introduction of the technology. 0.3 to 0.1. Microperimetry demonstrated no laser dam- The promise of earlier therapeutic intervention for age to photoreceptor cells. diabetic maculopathy and macular edema is significant. The energy initially used in the 2RT treatment was The ability to treat the whole ischemic retina and pre- 120 mJ/cm2; however, it triggered a reaction in the reti- serve visual function for as long as possible is a long- nal pigment epithelium (RPE). The treatment was then sought goal whose time may soon arrive. ■ reduced by half to create the desired effect without causing a visible reaction in the RPE. Peter Hamilton, FRCS, FRCOphth, is an Honorary Consultant at Moorfields Eye Hospital DISCUSSION and Honorary Consultant at Saint Thomas’ Although this is a preliminary study, early results are Hospital. Dr. Hamilton states that he has no encouraging. Consider that in the past, preservation financial interest in the products or companies of central vision with laser photocoagulation mentioned. destroyed, to some extent, the peripheral vision. This Robin Hamilton, MBBS, MRCOphth, is a Fellow in Medical Retina at Moorfields Eye Hospital and an 2RT FOR TREATMENT OF AGE-RELATED Honorary Fellow at Saint Thomas’ Hospital. Dr. Hamilton MACULAR DEGENERATION states that he has no financial interest in the products or companies mentioned. In addition to showing promise for earlier treatment of dia- John Marshall, PhD, FRCPath, FRCOphth(Hon), betic eye disease, Retina Regeneration Therapy (2RT; Ellex, is the Frost Professor of Ophthalmology and Adelaide, Australia) may have similar potential in the treat- Chairman of the Academic Department of ment of early-stage age-related macular degeneration (AMD). Ophthalmology, Kings College London at Saint At the moment, therapies for AMD mainly address Thomas’ Hospital, and was Sembal Professor of Experimental Ophthalmology at the Institute of Ophthalmology newly formed vessels in the exudative stage of the disease. from 1982-1991. Professor Marshall states that he is a member It would be preferable to treat the underlying disease of the Ellex Board of Directors and is compensated in this role. processes, one of which is the problem of waste disposal in He may be reached at e-mail: [email protected]. the aging eye, particularly in the retinal pigment epithelium Lucia Pelonsis, MRCOphth, is a clinical fellow at Saint and Bruch’s membrane. The 2RT laser offers an interim Thomas’ Hospital. Dr. Pelonsis states that she has no finan- treatment potential that might rejuvenate these systems cial interest in the products or companies mentioned. concerned with waste disposal. 1. World Health Organization. Priority eye diseases: Diabetic retinopathy. WHO Web site. By slightly tweaking the retinal pigment epithelium with http://www.who.int/blindness/causes/priority/en/index6.html. Accessed May 15, 2008. the laser, surgeons may clean up and reset the aging 2. Pituitary ablation for diabetic retinopathy. Br Med J. 1970;3(5725):724. 3. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic process within the outer retina. This might delay the devel- macular edema: ETDRS report number 1. Arch Ophthalmol. 1985;103:1796-1806. opment of manifestations of the disease. 4. Hamilton P. Selective laser retinal pigment epithelium treatment for diabetic macular edema. Paper presented at: Retina Subspecialty Day, Annual Meeting of the American Academy of Ophthalmology; November 10, 2007; New Orleans, LA. JULY/AUGUST 2008 IRETINA TODAYI 75.