This is the first real-world study in Latin America to report success outcomes from SLT and also to evaluate possible risk factors for failure in a large sample of patients with glaucoma and ocular hypertension followed for a relatively long period of time. Several studies have showed previously that SLT can be offered as a first-line treatment for glaucoma and ocular hypertension patients, supporting a change of paradigm in clinical practice.9, 12, 25 This is particular important, specially, in a developing country like Brazil, where access to public health services is scarce and the cost of treatment of the eyedrops may represent a barrier to adequate treatment adherence.17, 26 Thus, we believe that the findings of the present study, as derived from real-world data in a developing country, provides significant information regarding patients’ clinical course following SLT and may add clinicians to identify the best candidates for laser treatment, increasing the chances of successful management.
In the current study we divided the patients according to the SLT indication in clinical practice. Thus, 3 different scenarios were considered: First, patients with uncontrolled IOP without the use of medication, which is in line with that we currently offer to our patients as first line therapy. Second patients with uncontrolled IOP in which medications did not achieve the target pressure and SLT would be an option to reduce IOP or in some cases even delay a glaucoma surgery (if the patient was under maximum tolerated topical therapy). The third and last scenario is also common in clinical practice and consists of a group of patients that have IOP under control (either a glaucoma without progression with adequate target IOP with medication or a patient with ocular hypertension that achieved adequate IOP control with medication). This group of patients was submitted to SLT in an attempt to reduce or eliminate eyedrops. In fact, in our sample the majority of patients (55% or 456 eyes) were in this third group. Within this group of 456 eyes, 222 of them (49%) had a successful treatment at the end of follow-up. Additionally, 170 of them (37%) remained free of eyedrops during follow-up, showing that SLT is a good option to reduce the number of medications, improving adherence for the remaining bottles or even eliminating the need of eye drops, possibly leading to a better quality of life.27
There was a low prevalence of naïve to topical medication treatment patients in our sample (16%). This may have occurred due to our retrospective design, including patients since 2011 and at that time, offering SLT before introducing an eyedrop was not a consensus among glaucoma specialists. With the publication of several randomized clinical trials in recent years, such as the LIGHT study, scientific evidence has reinforced the concept and benefit of using SLT as a first line therapy and we expect that a higher number of patients will receive SLT before topical medication in Brazil.9, 28
The current study showed an estimated probability of treatment success rate of 88% at 12 months, 70% at 24 months and 54% at 36 months after the SLT using the Kaplan-Meier survival analysis. This is the first study to show outcome results in a large sample in a Brazilian population. We should be careful when comparing these results with other real-world data studies, since the success rates will depend directly on the characteristics of the sample and also the criteria adopted to define failure or success. Khawaja et al found significant reductions in IOP with treatment success in 70% and 45%, of eyes at 6, and 12 months post-SLT, respectively. However, the majority failed treatment by 2 years (27% success at 24 months) due to an inadequate reduction in IOP (>21 mmHg or <20% reduction), or an increase in number of glaucoma medications, or by undergoing a subsequent glaucoma procedure. Kuley et al in a study with 997 eyes from 677 patients found that that only 227 eyes (22.8%) achieved treatment success after 12 month follow-up.14 These differences on success outcomes might have occurred due to the fact that the majority of our patients (55% or 456 eyes) were submitted to initial SLT with an attempt to reduce or eliminate the use of eyedrops. It is important to highlight that even though for this specific group, we considered success the reduction of eyedrops, we still consider that the definition of success established were stringent since we still kept the other criteria for failure such as, the need for a glaucoma surgery, or new SLT to achieve target IOP or an increase in IOP values between baseline and last visit.
The investigation of predictors of success for SLT is important to guide the clinician into obtaining better outcomes and also to provide patients with information regarding risks of failure and procedure outcomes. Despite previous studies have described baseline IOP as predictor of success, in our univariable and multivariable analyses, baseline IOP did not achieve statistical significance.14, 29 We found that patients with less advanced functional damage had better chances of obtaining success after SLT in the univariable analysis. This finding reinforces the concept that SLT is a good option for initial treatment, especially for those with mild glaucoma comparing to patients with moderate and advanced glaucoma that might require a lower target pressure. We also found that patients who underwent 360 degrees of SLT treatment presented lower failure risk comparing to 180 degrees of treatment. In fact, previous authors have already reported that performing 360 degrees is more effective than180 degreess.30, 31
The influence of angle pigmentation in the outcomes of SLT is controversial. In the present study, the multivariable model showed that patients with denser angle pigmentation presented higher chances of treatment success, corroborating findings from previous studies.14, 32 However, Garg et al, investigating success predictors in the LIGHT trial, found that angle pigmentation was not directly correlated to absolute IOP reduction.28 Latina et al have described that coagulation of the TM is not an important component to the mechanism of IOP lowering after SLT.5 In fact, disruption of pigmented TM cells appears to induce a response that results in a reduction of IOP probably by inducing trabecular cells hyperplasia with formation of healthy trabecular tissue and enhance outflow capacity.33 Unfortunately, data from total energy used during SLT sessions was not available for most patients in our study. Therefore, a correlation between angle pigmentation and amount of energy was not performed.
To date there is no consensus on the optimal anti-inflammatory treatment regimen to be used after a SLT procedure. Comparing to ALT, SLT causes less inflammation since there is no thermal coagulation damage to adjacent cells of the TM.4 Thus, in theory there is no need to use intensive anti-inflammatory drugs. In the present study, patients that received corticosteroid eyedrops after SLT treatment presented lower risk for failures (HR 0.59; 95% CI: 0.39 – 0.91, P=0.018) in the multivariable model. Unfortunately, we were not able to discriminate which specific type of steroid was used (prednisolone acetate or fluorometholone). Kim et al evaluated the effect of anti-inflammatory treatment on the long-term (4.6 +/- 3.4 years) outcome of ALT, comparing 0.25% fluorometholone versus placebo eyedrops four times daily before and after ALT.34 They found no statistically significant differences in the success rate between groups. More recently, Jinapriya et al, performed a randomized, double-masked, placebo-controlled trial to compare prednisolone acetate 1%, ketorolac tromethamine 0.5% and placebo eye drops. They concluded that anti-inflammatory eyedrops after SLT does not seem to influence the IOP lowering effect of SLT compared to placebo.35 However, a double-masked, randomized, placebo-controlled trial by Groth et al showed that both NSAID and steroid treatment showed a statistically significantly greater IOP reduction compared with the placebo group after 12 weeks.36 However, no difference was found between both anti-inflammatory agents. One could have hypothesized that in an uncontrolled setting such as this real-world study, patients with denser trabecular meshwork pigmentation undergoing SLT treatment would be more prone to receive an anti-inflammatory regimen with steroids eye-drops post-SLT, which could in part explain the fact that eye that received steroids had better outcomes as eyes with denser angle pigmentation also had higher success rates. However, as we performed a multivariable analysis, the use of steroids was independently associated with success treatment since the analysis was adjusted for angle pigmentation (Table 5). It is important to highlight that even though we found that eyes that received corticosteroid eyedrops regimen after SLT treatment presented lower risk for failures, more studies are necessary to evaluate the true effects of steroids and NSAID on SLT outcomes.
Even though the BCVA presented statistically significant decrease during follow-up and VF showed MD worsening with marginal statistically significance (Table 2), we believe that these changes might not be attributed specifically to SLT treatment. In fact, we have to remember that glaucoma progression can occur even under regular treatment and patients might have developed media opacities, such as cataract during the follow-up. In addition, we do not believe that the amount of MD decrease could be considered clinically significant in the context of the length of the follow-up.
This study has several limitations. First, the findings from a retrospective study offers an inferior level of evidence comparing to randomized controlled trials. Second, data collection based on chart reviews often lead to missing information. For instance, in Table 4 we discriminate the number of patients included in each analysis and our final multivariate model included 767 patients (Table 5), which still represents the majority of our total sample. Nevertheless, this should be taken into consideration while interpreting our findings. On the other hand, it should be noted that the current study has a large sample size, from 5 centers in different regions of Brazil, being more representative of the general population and likely reducing the risk of selection bias. Third, the relatively low incidence of IOP spikes might be explained by the fact that we included the first IOP measurement only seven days after SLT treatment. Even though some centers included IOP measurements one day after the procedure, not all centers followed the same clinical routine. On the other hand, it should be noted that despite being derived from retrospective data, our rates of IOP spikes (1.5%) is very similar to the LIGHT trial findings (1.7%), as described by Garg et al.28
This real-world study reported relatively high success rates without sight-threating complications following SLT in more than 800 Brazilian patients with glaucoma and ocular hypertension, followed for 30 months on average. We found that patients with denser angle pigmentation and those that received anti-inflammatory treatment with steroids after SLT had lower failure risk. Our real-world data not only corroborate previous findings regarding SLT outcomes, but also provides significant information regarding patients’ clinical course and may aid clinicians to identify the best candidates for laser treatment, reinforcing the change of paradigm in clinical practice in developing countries such as Brazil.