SLT’s Successful Clinical Implementation Will Rank Among Ophthalmology’s Milestones
SLT’s leading proponents share their preliminary and long-term findings.
SLT is a non-thermal laser treatment that uses short pulses of low energy light (532 nm) to target selectively and irradiate only the pigmented cells in the trabecular meshwork (TM). In contrast to argon laser trabeculoplasty (ALT), there is neither collateral damage to adjacent tissue nor direct damage to the underlying structure of the TM. Macrophage recruitment takes place to remove damaged cells, and TM cells divide to replace the lost cells. Finally, a healthier, more ‘porous’ TM restores balanced aqueous outflow.
Dr Madhu Nagar, a consultant ophthalmologist and lead clinician, specialising in glaucoma management, is a strong advocate of the treatment: “Selective laser trebeculoplasty embodies the qualities and capabilities that the literature and my clinical experience ascribe to ideal glaucoma treatment. It can be used early enough to enable patients to avoid vision loss, is effective and repeatable and it eliminates or reduces compliance issues because it eliminates or reduces dependence on glaucoma drugs.
“These factors and others were addressed at the annual meeting of the European Society of Cataract and Refractive Surgery (ESCRS) by me,” continued Dr Nagar, “and other glaucoma specialists including Prof. Jens Funk, MD, Lawrence F. Jindra, MD, and Karin Hornykewycz, MD. Prof. Funk, of Zurich, moderated the event and shared his preliminary SLT research findings, while Dr Jindra, a U.S. glaucoma specialist and longtime SLT proponent, presented long-term outcomes. Dr Hornykewycz, of Austria, and I reported our SLT findings, as well, adding to a growing body of data substantiating the therapy’s efficacy as a primary glaucoma treatment.”
Dr Lawrence Jindra, has said that he suspects that SLT’s successful clinical implementation will rank among ophthalmology milestones, such as the development of phacoemulsification and the invention of the IOL. Dr Nagar agrees: “It was just a matter of time before phacoemulsification for cataract surgery took root as the gold standard even among its staunchest critics, and now, as Dr Jindra’s theory goes, it is just a matter of time until evolution elevates SLT to the head of the glaucoma treatment paradigm.”
In short...
Selective laser trabeculoplasty (SLT) can undoubtedly stake its claim as an effective primary treatment for glaucoma as mounting evidence from the Glaucoma Laser Trial, the Ocular Hypertension Treatment Study and the Early Manifest Glaucoma Trail have demonstrated. Here Professor Jens Funk, Dr Lawrence Jindra, Dr Karin Hornykewycz and Dr Madhu Nagar share their research findings.
Efficacy of SLT in patients with insufficient control of IOP under max drug therapy
Professor J. Funk, Dr Cornelia Hirn, Dr Sandrine Zweifel Universitätsspital Zurich, eye clinic, Switzerland
Professor Funk’s study addresses the efficacy of SLT in patients with insufficient IOP control under maximally tolerated medication. “We are investigating whether additional IOP reduction occurs when SLT is applied and if yes, how long it is maintained. Since our follow-up covers a postoperative period of one year, we are also examining the option and effectiveness of possible retreatment,” he said.
Inclusions & exclusions
Patients with primary open-angle glaucoma (including normal tension glaucoma), pseudoexfoliation glaucoma (PEX) and ocular hypertension were enrolled in our open, prospective, noncontrolled study. A previous Argon laser trabeculoplasty (ALT) is not considered an exclusion criterion. The standard exclusion criteria apply. Follow-up examinations were performed after 2 hours, 1, 30, 90, 180 and 360 days postoperative.
Patient assurance and information
There were 30 patients enrolled in the study (20 women, 10 men). Fifteen right and 15 left eyes were treated with an SLT. Our patient collective consisted of 20 patients with primary open-angle glaucoma (4 of these with normaltention glaucoma), 7 patients with PEX, 2 with ocular hypertension and one patient with juvenile glaucoma.
“We place great value on good, thorough and open patient information prior to the SLT procedure,” explained Professor Funk. “We emphasize that laser treatment is, overall, completely harmless and painless. However, we are at pains to explain that the patient may be blinded after the SLT due to the illumination during the procedure and not be able to see for up to 30 minutes after the procedure, that positioning of the contact glass may cause mild mechanical irritation (a scratchy feeling in the eye), and that the eye may become somewhat reddened after the procedure.
“After performing the SLT, we point out to our patients that they must continue to take their glaucoma medication for the time being. The original topical glaucoma therapy is continued especially since the SLT effect may be delayed and must first be checked. After about six months, we check whether the medication can be discontinued (in our study, this applies so far to one patient who no longer needs medication six months after the procedure).”
Technical prerequisites & mechanism of action
Due to the different parameters in a SLT, a separate laser with specific settings is necessary for this procedure. The required short impulse duration is not attained with the usual retinal laser, although it is identical in appearance.
The SLT is performed with a frequency-doubled, Q switched Nd: YAG laser, which functions with a wavelength of 532 nm. The laser beam diameter is 400 microns, the pulse duration is 3 nanoseconds.
Unlike the ALT, the SLT is a nonthermal laser treatment. Its mechanism of action is probably based on the stimulation of endothelial cells. The energy flow density, which is smaller by a factor 100, explains the lower thermic effect. In SLT, there is selective absorption of the laser energy by the pigment cells of the trabecular meshwork.1,2 The SLT treatment can be repeated without any great risk or damage.3
The SLT procedure
“All study participants received Brimonidine eyedrops immediately preoperative. Then a contact glass was positioned, we used the Latina SLT lens from Ocular Instruments,” confirmed Professor Funk. “During the clinical study, we performed a circular 360° treatment with 100 continuous, nonoverlapping laser spots as standard. The focus during treatment must lie on the pigment cells to be treated and not on the laser spots.
“The energy is adapted to the degree of pigmentation of the trabecular network (energy between 0.3 - 1.6 mJ). The corresponding selected initial energy is increased stepwise by 0.1 mJ until champagne bubbles form. Then the energy level is decreased in steps of 0.1 mJ below this threshold.”
Postoperative drug therapy
The preoperative drug glaucoma therapy remained unchanged during the initial postoperative period.
Professor Funk confirms: “All SLT procedures performed during the study were without complications. The treatment time itself was very short and lasted for less than 10 minutes.
“Despite preoperative administration of Brimonidine,” he continued. “We observed a paradox IOP increase (IOP > 26 mmHg) in 3 patients (10%) 2 hours after the procedure. These patients were treated additionally with Azetazolamide (Diamox) 250 mg per os.
“Eleven patients developed mild inflammatory reactions in the anterior chamber after the SLT. These healed spontaneously, i.e. we did not administer any additional antiinflammatory drops. There was no formation of synechia in the anterior chamber angle in any of the patients.”
Results
Initial findings showed that an IOP reduction of 20% to 25% is possible without severe complications or side effects, even in patients on maximum medical therapy. “In our patient collective,” explains Professor Funk, “The mean IOP was 15.5 mmHg (-20.3%, p=0.001) after 30 days and 15.5 mmHg (-24.3, p=0.005) after 90 days. “Expressed in absolute figures, we used the laser successfully for the classical indication i.e. in patients who need additional IOP reduction of about 4 mmHg to achieve the target pressure.”
In the not too distant future
Professor Funk envisions a future where repeating SLT every one to two years instead of administering daily eye drops is not out of the realms of possibility. “The selective laser trabeculoplasty is a non-thermic laser treatment which, unlike ALT, does not cause coagulative cell damage. Its use could enable lower treatment costs, since less topical therapy is required or local therapy might even be totally unnecessary.”
References
1. K.F. Damji et al., Br J Ophthalmol 1999;83;718-722.
2. M.A. Latina & C. Park Eye Res. (1995) 60, 359-372.
3. J.D. Stein & P. Challa Ophthalmol 18;140-145.
Special Contributor Professor Jens Funk is a glaucoma specialist at the Universitätsspital Zurich, Eye clinic, Switzerland. He can be reached by Email: jens.funk@usz.ch
Long-term outcomes of SLT
Dr Jindra’s presentation, focused on the long term efficacy of SLT. He reviewed five years of retrospective data on 2,056 eyes undergoing SLT as primary, secondary or repeat treatment from January 2002 to February 2007 and reported that treatment with SLT in this clinical series resulted in a significantly lowered IOP, significantly fewer medications and a reduced repeat rate in comparison to ALT.
Almost 900 of the eyes in this series underwent SLT as a primary glaucoma treatment. Among those 879 eyes, there was a 31% mean reduction in IOP, which decreased from a mean of 19.1 mmHg to 13.2 mmHg. Throughout the study, 93% of these eyes required no further treatment. This is clinically significant, with more than 9/10ths of these patients not requiring glaucoma medication of any kind nor requiring repeat SLT within five years.
While these primary data appear very good, Dr Jindra pointed out that practitioners must bear in mind that although these patients have been diagnosed with glaucoma or the risk of glaucoma, many of these were previously untreated eyes that were being exposed to their first glaucoma treatment.
A large portion of patients in Dr Jindra’s series had IOP that was not successfully controlled by medications or could not tolerate the systemic and/or local side effects of their glaucoma regimen. These patients were studied as a separate group. In this arm of the study, 760 eyes underwent SLT as secondary treatment for glaucoma. IOP decreased from a mean of 20 mmHg to 15.9 mmHg over the five year period, which represented a 21% mean reduction in IOP. After undergoing SLT, the number of medications for these eyes decreased from a mean of 2.3 to 1.3, which represented a 44% mean reduction in the number of medications required over the five year study.
This retrospective analysis shows that after SLT, over five years, 86% of eyes that had previously been on one medication no longer required medication and that among eyes that were on two medications, 62% required no medication. Among the eyes that underwent SLT as secondary treatment, one out of three patients (32%) that were on four medications (dorzolamide hydrochloride, timolol maleate, latanoprost, and brimonidine tartrate) prior to SLT were able to get off all medications and have IOP under control. Dr Jindra pointed out that it is noteworthy that the mean reduction of IOP was greater than 20%, and that more than three quarters (77%) of these eyes did not require medication to control IOP and keep it under control.
Risk : benefit ratio
"My own clinical experience has shown me that no glaucoma treatment has a better risk/benefit ratio than SLT,” explains Dr Nagar. “During the symposium, I shared a retrospective review of case notes of my SLT patients treated over five years starting in January 2000. Of those, 380 or 53% received SLT as primary treatment for glaucoma; while 342 or 47% received SLT as adjunctive or replacement treatment.”
Results from the primary treatment group, comprising patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT), showed that IOP decreased from a mean of 27.8 mmHg to 19 mmHg, which represents a 32% drop in IOP or a reduction of 8.8 mmHg over a follow-up period of 45 months.
Results from the secondary treatment group, i.e. eyes with IOP that was not successfully controlled by medications or could not tolerate the systemic and/or local side effects of their glaucoma regimen, indicated that IOP decreased from a mean of 26.5 mmHg to 16.8 mmHg, which represents a 33% reduction in IOP or 8.8 mmHg. The mean follow-up in this secondary treatment group was 51 months.
Common ground in both groups
What’s particularly noteworthy about both treatment groups, is that therapeutic medical treatment was washed off prior to SLT in as many patients as possible, according to European Glaucoma Society (EGS) guidelines. As a result, baseline IOP in both arms were very similar hence IOP reduction was also similar. The higher the baseline IOP, the greater the IOP reduction following treatment with SLT, ALT or medications.
Additional IOP reductions were achieved in the patients with enhancements and/or repeat treatments. Enhancement entails treating 180 degrees of virgin TM following an initial 180 degree SLT treatment, while retreatment or repeat treatment entails performing SLT again on the previously treated area of TM. In the study, 110 eyes in the entire SLT cohort required further SLT treatment. Of those, 56 eyes were ‘enchanced,’ and 54 eyes underwent retreatment. Among the enhanced eyes, a 23% reduction in IOP was achieved, represented by a decrease from 26 mmHg to 16 mmHg. Among the eyes that had retreatment, a 29% drop in IOP represented by a decrease of 25.3 mmHg to 17.8 mmHg was achieved. The mean follow-up for enhancements was 24.7 months, while the mean follow-up for repeat treatments was 19.4 months.
“Like many other SLT proponents, I have made SLT my first-line glaucoma treatment. The clinical outcomes that I reported at the ESCRS Symposium, as well as those which I have gathered prior to and since my talk, suggests that SLT success is proportional to the treatment area, and that there is a dose/response relationship. In a prospective, randomized study that we performed several years ago comparing 90°, 180°, and 360° SLT treatments and latanoprost 0.005% for the control of IOP in open angle glaucoma, we found that treating 360 degrees results in better outcomes than treating 180 degrees and treating bilaterally results in a better response than treating unilaterally. Success rates were greater with 180° and 360° compared to 90° SLT. With 360° SLT, 82% of eyes achieved greater than 20% IOP reduction and 59% achieve greater than 30% reduction from baseline. Although success rates were better with 360° than 180° SLT treatments, differences did not reach statistical significance.”
Early findings
Dr Hornykewycz described the outcomes of a relatively modest SLT patient pool comprising 141 patients and 201 eyes over four years. Of those patients, 43% have undergone bilateral treatment and 57% have had unilateral treatment; 84% had 180 degrees of TM treated, while just 14% required 360 degrees of treatment.
The majority of patients – 66 – had primary open angle glaucoma (POAG), this was followed by ocular hypertension (OHT) and normal tension glaucoma (NTG) with 42 and 41 patients respectively. The remaining eyes had pseudoexfoliation glaucoma (PEX), pigment dispersion syndrome-OHT (PDS-OHT), pseudoexfoliation OHT (PEX-OHT) and pigmentary glaucoma (PG). Before SLT 53% of patients were on zero to two glaucoma medications and 47% were on three or more medications.
To be continued…
Dr Hornykewycz found that medications could be avoided or reduced in 63% of her SLT patients and that in her data, there was no correlation between SLT effect and TM pigmentation, gender, age or stage of disease. With more patient enrollment and a longer followup period Dr Hornykewycz’s work promises significant results in the future.
A powerful clinical tool
Dr Madhu Nagar FRCS Ophth, MS Ophth Clayton Eye Centre, Wakefield, West Yorkshire, UK
"The findings of Professor Funk and Drs Jindra and Hornykewycz, like my own,” concludes Dr Nagar, “highlight that SLT is a non-invasive and repeatable modality that is a reasonably successful therapy for patients with low tolerance to glaucoma medications and their side effects, as well as for patients who are physically unable to administer their own medications. Advantages inherent in minimizing or avoiding a complicated medication regimen include cost savings and a reduction in compliance concerns.
“While SLT can be used in conjunction with traditional drug therapy, there are none of the risks of scarring and synechiae formation that are commonly associated with ALT. Studies show that ALT done a second time has only a modest (11%) clinical efficacy rate, while SLT results remain clinically effective with successive use. Dr Jindra reported that he has performed SLT on a single patient up to five times, and I have treated one patient four times and 5 patients 3 times over the past three years. Theoretically SLT could be done indefinitely because there is minimal or no structural damage to the TM. However, in my experience I have found that IOP reduction is slightly less with subsequent treatments as compared to initial treatment. The effect is a biologic, rather than a thermal, process that works very much like a prostaglandin. It creates a low grade inflammation, remodels the TM and reduces intraocular pressure. Many SLT proponents find that their patients overwhelmingly opt to have a repeat SLT rather than maintain or add medications, and this is what I have found in my practice, as well.
“Ultimately, when you have an intervention, such as SLT, that takes the patient’s ability to understand and comply with medication out of the loop - and the intervention has almost no side effects – and it gets IOP down and keeps it down, it is a very powerful clinical tool.”
Special Contributor Madhu Nagar, FRCS Ophth, MS Ophth. is a consultant ophthalmologist and lead clinician, specializing in glaucoma management, at Clayton Eye Centre, Wakefield, West Yorkshire, UK. She may be reached by Email: madhunagar@hotmail.com