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Micropulse laser treatment has application for severe edema in uveitis
The therapy can be used as a first-line treatment and as an adjunct to steroids and anti-VEGF drugs.
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Retinal laser photocoagulation aims to cause coagulation necrosis and denaturation of cellular proteins. It is known to be an effective treatment for a number of diseases including diabetic retinopathy, macular edema, branch retinal vein occlusion and microvascular abnormalities. The accepted treatment endpoint for effective laser therapy has been clinically visible retinal burns based on the Early Treatment of Diabetic Retinopathy Study and then modified ETDRS, which produces a less intense treatment but still induces retinal burns. While laser photocoagulation remains the standard of care, anti-VEGF has emerged as a promising alternative for reducing macular edema, with some studies even showing it to be more effective than conventional laser treatment.
As part of the natural progression to find therapies that are more effective and cause fewer side effects, scientists and clinicians have been testing alternative protocols for laser photocoagulation. Micropulse laser therapy (MPLT) is a treatment modality whereby the continuous-wave laser beam is “chopped” into a train of repetitive short pulses, separated by longer intervals that allow the tissue to cool, preventing thermal buildup. For nearly 25 years, the method of applying micropulse laser has been tested and retested. Research at the cellular level combined with clinical experience is broadening the scientific understanding of the resulting therapeutic effect despite the lack of a visible laser burn. Contrary to the previous understanding that edema was reduced via the destruction of tissue, it has been discovered that the retinal pigment epithelium (RPE) mediates diabetic macular edema, and micropulse laser may stimulate physiologic alteration of RPE cytokine expression.
Treatment protocols
I first began performing MPLT with the IQ 577 (Iridex) on my patients with mild macular edema in the foveal region because there is less risk of damage. Patient response has been so positive, I have expanded my use to include patients with more severe edema as well as uveitis and other pathologies with macular edema as an endpoint. I also use intravitreal injections of anti-VEGF agents on these patients. I have found that combination therapy reduces the necessary frequency of injections, thereby ameliorating this significant patient burden.
The determination to use MPLT or medical therapy first depends entirely on the patient. A patient who had cytomegalovirus retinitis, HIV and a history of tuberculosis also developed immune recovery uveitis. Steroids were ruled out because they could activate infectious agents in the eye; thus, I decided to use MPLT first. I followed laser treatment with intraocular Avastin (bevacizumab, Genentech), and this regimen appears to be working well.
In my experience, MPLT is effective at getting rid of subretinal fluid, while bevacizumab tends to help more with intraretinal fluid. In certain cases, delivery of drugs to the back of the eye is not sufficient to treat the pathology, whereas MPLT is able to effectively deliver therapy to the retina and the RPE.
In addition to being an effective treatment, MPLT also manifests a lower risk profile for my uveitis patients. Intraocular steroids can induce cataract progression or steroid-response glaucoma. They also reduce the body’s natural immune system, making them relatively contraindicated in cases of infectious uveitis. Anti-VEGF injections are effective, but repeated injections present a burden to the patient and every injection has a small risk of retinal detachment or endophthalmitis. MPLT creates no obvious thermal injury to the retina and can be repeated if necessary without sequela.
Case example
A 63-year-old man was referred to me with recalcitrant uveitis. He had diabetes and high blood pressure and required regular monitoring. I observed neuroretinitis in his right eye and a similar but less severe presentation in his left eye. His visual acuity in the left eye was 20/50, with the macula flat and dry as viewed by optical coherence tomography. Infectious disease was ruled out, and he was lost to follow-up. Two years later, the patient returned reporting flashing lights and floaters in his right eye for 5 months, with visual acuity of 20/400 and central subfield thickness of 681 µm on OCT. He was given an injection of bevacizumab, and further testing identified a diagnosis of sarcoidosis.
Over the next year, the patient received three additional bevacizumab injections along with two periocular steroid injections and one intravitreal steroid injection. Macular edema decreased at times but recurred frequently and often became more severe, at one point exceeding 1,000 µm. Similar fluctuations were seen with visual acuity, which was 20/150 at best and counting fingers at worst. During this time, the macular edema in the patient’s left eye also became more severe. Four weeks after the final intravitreal steroid injection, the patient’s right eye manifested large amounts of fluid, hard exudates and a full-appearing optic nerve with blurred margins. Central subretinal thickness was 727 µm, visual acuity was 20/200, and the patient developed central serous chorioretinopathy, likely due to the steroid therapy.
The patient agreed to undergo MPLT. I performed a test burn outside of the vascular arcades on the flat retina using the IQ 577 laser in continuous-wave mode and observed a barely visible tissue reaction at 100 mW with 100 ms exposure duration. I then switched the laser to micropulse mode at a 5% duty cycle, increased the power to 400 mW, increased the duration to 200 ms and then delivered a high-density application of 1,500 confluent spots over the edematous area. Approximately 2 weeks later, the patient’s central subretinal thickness was reduced to 334 µm. Follow-up 1 month later showed continued improvement in central subretinal thickness at 164 µm and the resolution of fluid in the eye. Unfortunately, the patient’s visual acuity remained 20/400 due to a disruption of the IS/OS junction resulting from the prolonged edema.
Summary
MPLT has revolutionized my use of laser therapy in my patients. I have found it effective in cases of mild and severe edema, and it has provided an option for infectious uveitis patients who previously did not have a good treatment option. I use it effectively as a first-line therapy as well as in combination with steroids and anti-VEGF drugs. If it had been used sooner in the patient above, he may have improved visual acuity. I am glad I now have this tool in my armamentarium.
References:
Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1985;doi:10.1001/archopht.1985.01050120030015.Luttrull JK, et al. Curr Diabetes Rev. 2012;doi:10.2174/157339912800840523.
Rajendram R, et al. Arch Ophthalmol. 2012;doi:10.1001/archophthalmol.2012.393.
For more information:
Jeevan R. Mathura, MD, can be reached at George Washington University, 2150 Pennsylvania Ave. NW, Floor 2A, Washington, DC 20037; 202-741-2800; email: jmathura@mfa.gwu.edu.Disclosure: Mathura has no relevant financial disclosures.