Ophthalmology: Line of sight

Douglas Clarkson looks at the use of selective laser trabeculoplasty (SLT) and how it compares with other forms of treatment for the effective management of glaucoma.

Image: wikipedia.org

The pressure within the eye is a fine balance between values that are sufficiently high to maintain the rigidity of the eye but not so high that it results in glaucoma, a condition that can cause irreversible damage to the nerve fibre layer and associated structures in the eye. In its normal state the inflow of clear fluid in the eye, the aqueous humour, is balanced by the outflow of fluid through the trabecular meshwork. Where the effectiveness of this meshwork to release fluid is impaired, then the pressure in the eye increases’ a condition known as primary open angle glaucoma. Currently more than half a million people in the UK have glaucoma of various types and more than 200,000 people have lost their sight through this condition.

Conventional surgery has always included a surgical procedure called trabeculotomy to open up the trabecular meshwork where other interventions including topical medication have failed to reduce pressure levels. During the 1970s the technique of using lasers to try to open up the meshwork and hence reduce the intraocular pressure (IOP) was developed using argon lasers’ a technique called argon laser trabeculoplasty (ALT). At the same time a range of specific laser types including krypton, continuous Nd:YAG and diode lasers were also investigated.

The mode of interaction of the argon laser with the trabecular meshwork and adjacent tissue can result in coagulative damage to associated structures as a consequence of the relatively high levels of energy delivered during the treatment process. The specific tissues within the trabecular meshwork are a mixture of pigmented and nonpigmented cells and with the argon treatment producing nonselective cell damage.

It was subsequently determined by Anderson and Parish1, however, that optical radiation could be tailored to selectively target pigmented tissue structures. This led Latina and Park2to develop a selective laser trabeculoplasty (SLT) technique where effects at the cellular level could be triggered using pulses of shorter duration and lower energy, with the benefit of much reduced collateral damage.

Selective laser trabeculoplasty has centred on the use of a wavelength of 532nm (green light) at a pulse duration of three nanoseconds. The beam diameter used is 400 microns. A mechanism known as frequency doubling is used to convert optical radiation at 1064nm produced by a Nd:YAG laser to the 532nm wavelength. In the delivery technique a special lens is used to reflect light through the pupil to target the trabecular meshwork above the rim of the iris. Most treatments involve a 180 nasal section of the trabecular meshwork, though other studies have involved both 90 and 360 sections. Current theory suggests that a key factor in effectiveness of the SLT technique is the release of macrophages within treated cells which results in the restoration of function of the meshwork.

Clinical studies

There have been a range of clinical studies comparing the effectiveness of different treatments for glaucoma, including argon laser trabeculoplasty, selective laser trabeculoplasty and a range of conventional topical medications. A comparative study carried out by Martinez-de-la-Casa3, for example, looked at both the SLT and the ALT techniques (see table). Similar to other studies, it found a greater mean percentage decrease in IOP six months after treatment with SLT treatment. There is a trend for the decrease of IOP to continue beyond the six-month post-treatment period as if the metabolism of the trabecular meshwork continues to recover some time after initial treatment.

SLT appears to be a low energy technique for the restoration of the function of the trabecular meshwork in a majority of patients presenting with raised levels of intraocular pressure.

The study by Martinez-de-la-Casa is novel in the sense that it determines an objective measurement of inflammation as a result of treatment  determined by the level of light scatter within the aqueous humour. The SLT technique was noted to also give rise to a smaller IOP spike’s after treatment compared with ALT.

Usually the level of post-treatment IOP elevation with SLT is not significant. However, a review by Harasymowycz4 of patients presenting with IOP elevation after SLT indicates that patients may be at higher risk of this complication in cases where the trabecular meshwork is deeply pigmented, previous ALT procedures have been undertaken or multiple topical medications have been applied.

One of the few studies to compare longer-term outcomes was undertaken by Juzych5. Patients receiving SLT (41 eyes) and ALT (154 eyes) were compared over a five-year period. Success was defined using two separate criteria. The first was a decrease in intraocular pressure of 3mm Hg or more with no additional medications, laser or glaucoma surgery. The second was the same but an IOP reduction of 20% or more was required for success. For the first criterion, 31% of patients treated by SLT were considered a success compared with 21% for those who had had ALT. For the second, the comparable figures were 31% with SLT and 13% with ALT. However, overall the long-term success rate between the two groups was not significantly different. But the authors noted that in the longer term many of the patients treated with ALT and SLT required further medical or surgical interventions to manage the levels of intraocular pressure.

In some ways, the conclusions drawn by Juzych exercise caution regarding the effectiveness of SLT in IOP management. The indication, however, that a single SLT treatment can manage IOP levels over a five-year period for a significant number of patients is not without an obvious health economic benefit. The topical application of drugs, is not without identified side effect’s  although the latest types of anti-glaucoma medication, such as prostaglandin analogues, are once daily and produce fewer side effects than, for example, beta-blockers. It is a common feature, however, of clinical studies into glaucoma medication that a significant percentage of patients may discontinue their medication. In addition, patients may not respond favourably to topical drug management.

A useful current review of SLT studies was recently published in Opththalmology Clinical North America by Latina6. To date in the UK, the National Institute of Health and Clinical Excellence (NICE) does not appear to be considering the evaluation of SLT technology. The only current work in hand in connection with glaucoma is evaluation of lerdelimumab  one of a series human anti-TGF beta 2 antibodies, with the potential to prevent post-operative scarring in patients undergoing conventional surgical trabulectomy. In the US, where physicians are paid at specific rates for delivering SLT treatments, around 1000 laser SLT systems have been installed and are in regular use. In addition, the SLT mode is actively promoted as an upgrade path to an existing Nd:YAG system.

Market availability

Current offerings in the marketplace include the Selecta II Glaucoma Laser System from Lumenis with the Selecta Duet also providing conventional Nd:YAG capsulotomy treatments. The Solo model (SLT only) and Tango model (SLT with Nd:YAG) are also available from Laserex.

Clinical studies show the value of SLT as an intervention to lower intraocular pressure, although an appropriate level of follow-up is required for effective longer-term patient management which may require additional interventions. As the management of glaucoma has a significant impact on the health economy, and current levels of population screening are not sufficient to detect the disease in its early stages, there are also sound economic arguments to adopt SLT as the primary means for lowering intraocular pressure. Choosing the appropriate technique to manage treatment can help to prevent vision loss, benefiting the patient and improving their quality of life.