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Newer treatments for vitreoretinal diseases show promise
Several experimental and recently introduced treatments are showing potential for treating formerly untreatable diseases.
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A number of innovative vitreoretinal surgery techniques are described in our Spotlight on Vitreoretinal Surgery in this issue. The diversity of these approaches demonstrate that posterior segment surgeons and researchers continue to search for ways to arrest and reverse vision loss that was once thought to be unavoidable.
The variety of recently developed approaches to age-related macular degeneration, to take one example, shows the degree of innovation being applied to this disease. Photodynamic therapy, transpupillary thermotherapy, blood filtration — and on the horizon, the possibility of retinal implants — all may eventually have a role in restoring the vision of patients with AMD or preventing its loss in the first place.
Diabetic eye disease and other less common retinal disorders may also benefit from recently developed approaches to treatment.
Ocular Surgery News features in this special section a review of several studies of innovative vitreoretinal techniques in use or under investigation to treat macular disease.
Novel approaches to AMD
Few treatments are available for age-related macular degeneration (AMD), one of the most common causes of vision loss in people older than 60 years. Harvey Fishman, MD, PhD, and colleagues at Stanford University are among those working at the leading edge of the visual prosthetics field, hoping their work will eventually benefit these patients. They are developing a microchip called the Artificial Synapse Chip that has the potential to replace photoreceptor cells lost to AMD. They are simultaneously working on regeneration of healthy retinal nerve cells.
Using nanotechnology originally designed for the microprocessing of computer chips, the Stanford researchers have created a microchip they hope can replicate biological processes. Their device stands out in the field of visual prosthetics because it uses neurotransmitting chemicals instead of an electrical stimulus to fire nerve impulses. The chip dispenses the neurotransmitter glutamate in minute amounts to stimulate the nerve cells.
So far, the researchers have demonstrated the ability to re-grow cells and direct their growth onto specific areas of their microchip. Studies have been done on animals and in vitro specimens of human tissue. Clinical studies are expected to be done in the next 5 to 10 years.
The application of nanotechnology to the field of visual prosthetics may be applicable to other areas of medicine, the researchers say. If the technology is successful for AMD, it may also find applications in glaucoma, and outside of ophthalmology in spinal cord and bladder injuries, musculoskeletal disorders and neurodegenerative diseases of the brain, Dr. Fishman said.
Another approach to treating AMD is the more familiar technique of photodynamic therapy (PDT) with the drug verteporfin. PDT can benefit AMD patients with subfoveal, predominantly classic choroidal neovascularization (CNV). However, some patients still lose vision after initial treatment with verteporfin. Continued treatment at 3-month can improve vision in some of these patients, but investigators have been interested in trying earlier re-treatment schedules.
In a study discussed in this issue by Vanessa Cruz-Villegas, MD, 31% of a subset of AMD patients who received early re-treatment with PDT gained visual acuity. Researchers are now conducting a study to learn more about the effects of early re-treatment in AMD and CNV.
Extracorporeal blood filtration for AMD, also called rheopheresis, has been controversial, but as more data emerges there appears to be a benefit from the procedure. Repeated extracorporeal procedures have a positive influence on the natural course of the dry form of AMD, according to Randolf A. Widder, MD. Patients with dry AMD had their blood filtered, cleaned of proteins and lipids, and then returned to their bodies.
Results of the procedure show that on average, patients gained two lines of ETDRS acuity after 2 years of treatment. Patients were treated 6 times a year for 3 to 4 years.
Transpupillary thermotherapy (TTT) has been found to successfully close retinal leaks in AMD, but the mechanism of action is unclear. Paolo Lanzetta, MD, and colleagues performed a retrospective study to evaluate TTT in patients with subfoveal CNV in AMD. They assessed the eyes using fluorescein and ICG angiography and found that 1 week after TTT, leaking had ceased. There was increased leakage immediately after treatment, however.
Researchers theorize that closure of the retinal leaks begins with the damaged endothelial cells in the target tissue. They believe the damage triggers a series of responses including leukocyte adhesion and increased vascular permeability. The mechanism of TTT is closely related to the mechanism of PDT, they theorized.
Treatments for diabetic retinopathy
Like AMD, diabetic retinopathy has historically had few treatments available. Though laser treatment is still the standard, vitrectomy or corticosteroids can be helpful in some patients, and agents to inhibit vascular endothelial growth factor (VEGF) are in development.
Gary Abrams, MD, discusses these alternative treatments for diabetic retinopathy and diabetic macular edema in this issue.
He said one study showed that vitrectomy can serve as an effective secondary treatment in patients with diabetic macular edema in which laser has not improved vision. Vitrectomy with separation of the hyaloid proved effective for most of the patients in the study, he said.
Injectable steroids may be effective for uveitic macular edema and choroidal neovascularization in patients with age-related macular degeneration, Dr. Abrams said. Animal studies have shown promise, although there is a risk of causing cataract and glaucoma with these injections, he said.
Also in development for use in diabetes-related eye disease are sustained-release implants of intravitreal fluocinolone. Similar to the ganciclovir implant used for patients with cytomegalovirus retinitis, the fluocinolone implant is slightly smaller and diffuses the drug slowly into the vitreous.
Agents to inhibit VEGF can also be administered via intravitreal implants. Although injections have had success, repeat injections increase the risk for problems. Anti-VEGF agents, such as oral protein kinase C, will hopefully eliminate the need for injections.
Gamma knife effects
The gamma knife has recently been discussed as a treatment modality for intraocular tumors. Now it seems that radiation retinopathy, commonly found after ophthalmologic radiotherapy, has been associated with gamma knife use in treating choroidal melanoma.
Anton Haas, MD, said that a single-fraction high-dose of the Leskell gamma knife is highly associated with early radiation retinopathy. He said eyes with large basal cell tumors were more likely to be affected, but there were no clear risk factors prior to the therapy.
Radiation retinopathy is extremely damaging to the eye and involves damage to the retinal vasculature. A variety of conditions, most commonly intraretinal hemorrhages, are indicative of radiation-induced complications.
In a study, Dr. Haas found that using the gamma knife in patients with choroidal melanoma led to radiation retinopathy in 84% of patients, and 47% developed neovascular glaucoma.
Atrophic maculopathy treatment
Macular translocation, a treatment better known for use in subfoveal CNV, may also be used in selected patients with atrophic maculopathy. The technique involves placing the fovea over healthy retinal pigment epithelium to maintain foveal function, said Janet S. Sunness, MD.
In this issue she discusses the results of the procedure in a single case. A patient with rapid progressive loss in one eye elected to have the procedure. Preoperative examination showed a central blocked hypofluorescence surrounded by a rim of transmission hyperfluorescence within the macula of the right eye. In her left eye, her best corrected visual acuity (BCVA) had dropped to 20/400.
A pars plana vitrectomy was done. The temporal retina was detached through infusion of fluid through a 39-gauge needle into the subretinal space. The retina was reattached, completing the translocation of the macula.
Initially, the patient’s visual acuity improved; however, there was a significant amount of astigmatism, so astigmatic keratotomy was performed. Six months later, the patient developed a blind spot, poor night vision and BCVA had decreased. Dr. Sunness performed limited macular translocation in the affected left eye. This third treatment finally improved the patient’s vision, Dr. Sunness said.