One-year outcomes of selective laser trabeculoplasty for open-angle glaucoma in Indian eyes

Abstract

Purpose:

To assess the effectiveness of selective laser trabeculoplasty (SLT) in Indian eyes with open-angle glaucoma (OAG).

Settings and Design:

Single-center, prospective, interventional study.

Methods:

Patients undergoing SLT from January 2014 to June 2018 for OAG were included in the study. Treatment-naive naive as well as patients on antiglaucoma medications (AGM) with suboptimal intraocular pressure (IOP) control were included. The main outcome measure was the percentage reduction in IOP. Complete success was defined as IOP reduction > 20% from baseline after 12 months or reduction in the number of AGM. Qualified success was defined as > 20% IOP reduction at 12 months with AGM. Secondary outcomes were occurrence of adverse events and factors predicting treatment outcomes.

Results:

A total of 104 eyes of 62 Indian patients underwent SLT for OAG. Eighty-three (79.81%) eyes were treatment-naïve, and 21 (20.19%) eyes were on AGM. The median (IQR) baseline IOP was 20 (16–26) mmHg. At 12 months, the median IOP was 16 (4–19) mmHg, the median decrease in IOP was 4 (0–6.5) mmHg, and the percentage reduction in IOP was 17.42% (0%–30.76%). Maximum IOP reduction was noted at 12 months. Overall, success was achieved in 48 (46.15%) patients. Five eyes (4.8%) experienced minor SLT-related complications. Age, gender, prior use of AGM, type of OAG, and higher baseline IOP were not found to be predictive factors for treatment outcome.

Conclusion:

SLT was found to be a relatively safe and effective procedure in Indian eyes with OAG.

Glaucoma is a multifactorial progressive optic degenerative neuropathy and is the leading cause of irreversible blindness worldwide.[1] The global prevalence of the disease is estimated to be 3.54% in populations aged 40–80 years and 3.05% for primary open-angle glaucoma (POAG).[1] The disease is expected to afflict over 100 million individuals by 2040.[1] In India, the issue of missed diagnosis and over-treatment/under-treatment adds to the ever-increasing disease burden.[2]

Treatment options for open-angle glaucoma (OAG) include topical antiglaucoma medications (AGM), laser trabeculoplasty, and surgery. Topical medications are usually the first line of treatment; however, they require good patient compliance, may have side effects, and may cost more than other treatment options in the long run.[3] In a recent study done in India to assess patient compliance to AGM, it was found that 50.5% of patients reported missing medication in the past month and cost was high for income in 28.7%.[4]

Selective laser trabeculoplasty (SLT) was introduced in 1995 and has become an established modality for lowering intraocular pressure (IOP) with the advantage of not requiring extensive patient compliance.[5,6] SLT may be used as primary monotherapy, as an alternative to failed monotherapy, or as an adjunctive treatment.[7] The results from the “LiGHT” study supported the use of SLT as primary treatment for OAG and ocular hypertension.[8]

Most of the studies on SLT have reported a high success rate of 6.9%–35.9% reduction in IOP for OAG.[9] However, the predictability of SLT has been reported to be variable in some studies, and hence it is not widely and unanimously accepted as the first line of treatment in OAG.[10] SLT has been well studied in the West; however, literature is sparse on the response of Indian eyes to SLT. One study found that SLT produced clinically significant IOP reduction among South African adults but was significantly less effective in socioeconomically comparable patients of Indian ancestry.[11] Another study conducted in India to analyze the effect of SLT in patients with primary angle closure disease showed that SLT is a safe, cost-effective modality for reducing IOP in primary angle-closure disease.[12] The aim of the current study was to assess the effectiveness of SLT (as primary as well as adjunctive treatment) in Indian eyes with OAG.

Methods

This was a hospital-based, prospective, interventional study. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Ethics and Scientific Committee. Patients who underwent SLT from January 2014 to June 2018 for any OAG were included in the study. Written informed consent was obtained from all the patients before enrollment.

Selection criteria - Patients (either treatment-naive or on AGM but not achieved target IOP) above 18 years of age with POAG/juvenile open-angle glaucoma (JOAG)/normal tension glaucoma (NTG)/ocular hypertension (OHT)/pseudoexfoliation glaucoma (XFG)/pigment dispersion glaucoma (PDS)/silicone oil (Si)-induced glaucoma or angle recession (AR) glaucoma were included in the study. Patients with angle closure glaucoma, patients undergoing retinal surgery/cataract surgery, or intravitreal steroid injection after SLT were excluded from the study.

The assessment included detailed history (age, gender, type of glaucoma, number of AGM), visual acuity, refraction, and slit lamp evaluation. IOP was measured by Goldmann applanation tonometry at each visit. Gonioscopy was performed using Sussman 4 mirror goniolens (Ocular Instruments Inc, USA). Additional evaluation included ultrasound pachymetry (Tomey-SP 100, Tomey Corp, Japan), optic disc evaluation using +78D (Volk, USA) lens on slit lamp, Optical coherence tomography (OCT)- Retinal nerve fiber layer (RNFL) thickness (Spectral OCT SLO, OPKO Health, Inc., Florida, USA) and Humphrey visual field (Humphrey field analyzer, the Swedish Interactive Threshold Algorithm 24-2; Carl Zeiss Meditec, Dublin, CA, USA).

SLT was performed by a single trained glaucoma specialist using a Selecta duet SLT machine (Selecta II Glaucoma Laser System, Lumenis, USA) and Latina lens (Ocular Instruments Inc, USA) with methylcellulose as a coupling agent. This machine has a 532-nm, Q-switched, frequency-doubled Nd: YAG laser. The laser energy was delivered to the posterior trabecular meshwork (PTM). The starting energy per shot was usually 0.8 mJ; the endpoint was the appearance of “champagne bubbles.” Once this was visualized, the energy was progressively lowered until the maximum energy at which this bubble was not visualized was noted. This was the energy per shot for the rest of the procedure, for one angle. Energy was titrated similarly for each angle. Contiguous spots were delivered to 360° of the PTM. If there was a post-procedural IOP rise of more than 5 mmHg from baseline at 1 hour, it was treated with a short course of oral acetazolamide. If the anterior chamber reaction was more than 2+ as per the Standardization of Uveitis Nomenclature classification, a 1-week course of topical non-steroidal anti-inflammatory drugs (NSAIDs) was used (Flurbiprofen 0.03% 4 times/day). Patients were evaluated at 1 hour, 1 week, 1 month, 3 months, 6 months, and 12 months after performing SLT.

If the IOP at 1 month post SLT was lower than or equal to the target IOP, we stopped/reduced the AGM in patients who were on AGM. If the target IOP was not achieved at the end of 1 month, AGM was continued/added. Complete success was defined as IOP reduction > 20% from baseline after 12 months or reduction in the number of AGM. Qualified success was defined as > 20% IOP reduction at 12 months with AGM.

Statistical analysis

Taking previously published data as reference,[13] the minimum required sample size with 10% margin of error and 5% level of significance was calculated as 92 eyes. Taking the attrition rate as 10%, the total sample size to be taken was 104 eyes. The presentation of categorical variables was done in the form of numbers and percentages (%). Quantitative data with non-normal distribution were presented as medians with 25^th and 75^th percentiles (interquartile range (IQR)). The data normality was checked by using the Shapiro-Wilk test. In the cases in which the data were not normal, we used non-parametric tests. The following statistical tests were employed for the results:

1. Friedman test followed by post-hoc comparison was used for the comparison of IOP across follow-up. Wilcoxon signed-rank test was used for comparison between IOP at baseline and at 12 months across different diagnoses, and the Kruskal-Wallis test was used for comparison of IOP reduction across different diagnoses.

2. Univariate logistic regression was used to find out significant risk factors of treatment failure.

3. The association of the variables which were qualitative in nature was analyzed using Fisher’s exact test as at least one cell had an expected value of less than 5.

Data entry was done in a Microsoft EXCEL spreadsheet, and the final analysis was done with the use of Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, version 25.0. For statistical significance, P < 0.05 was considered statistically significant.

Results

A total of 104 eyes of 62 Indian patients underwent SLT for OAG. The mean age was 63.06 ± 12.3 (25–86) years. The distribution of male eyes: female eyes was 64 (61.54%):40 (38.46%). With regards to prior use of AGM, 83 (79.81%) eyes were treatment-naive and 21 (20.19%) had prior use of AGM. The number of eyes with POAG, NTG, and XFG was 44 (42.31%), 37 (35.58%), and 13 (12.50%), respectively. We also included a subgroup “Others” (n = 10, 9.62%), which included eyes with JOAG (n = 4), silicone oil-induced glaucoma (n = 2), PDS (n = 2), AR glaucoma (n = 1), and OHT (n = 1). SLT was performed using the frequency-doubled Nd:YAG laser with a mean energy of 0.7 mJ (0.2–1.9 mJ) and a mean of 80 (20–140) pulses per eye. The mean total energy delivered to each eye was 62 mJ (26–170 mJ). Post procedure, one eye had grade 3 aqueous cells, requiring the use of topical NSAIDs for 1 week. Two eyes developed peripheral synechiae (PAS) in one quadrant after 3 months. A transient spike in IOP (>5 mmHg) was seen in three eyes, which resolved by 1 week with the use of oral acetazolamide.

Tables 1 and 2 show the median IOP at each visit and the change in IOP compared to baseline. The median (IQR) baseline IOP was 20 (16–26) mmHg. At 12 months, the median IOP was 16 (4–19) mmHg, the median decrease in IOP was 4 (0–6.5) mmHg, and the percentage reduction in IOP was 17.42% (0%–30.76%). The IOP reduction post SLT treatment was statistically significant at 1 month, 3 months, 6 months, and at the end of the 12-month follow-up period. Maximum IOP reduction was noted at 12 months post SLT (P < 0.0001).

Table 1.

IOP reduction over 12 months

	Median IOP in mmHg (IQR)	Range	Median reduction of IOP from baseline	Median percentage reduction of IOP from baseline	P
Baseline IOP	20 (16–26)	10–42	-	-	<0.0001*
1-hour IOP	20 (16–24)	10–42	0 (−2–2)	0 (−12.5–10.278)
1-week IOP	18 (16–22)	10–52	0 (−2–4)	0 (−9.028–20)
1-month IOP	18 (14–20.5)	10–48	2 (−2–6)	12.5 (−7.853–28.571)
3-month IOP	18 (14–22)	8–40	2 (0–4)	11.1 (0–20.77)
6-month IOP	16 (14–21.25)	8–46	2 (0–6)	12.5 (0–27.273)
12-month IOP	16 (14–19)	8–44	4 (0–6.5)	17.42 (0–30.769)

*Friedman test, IOP=Intraocular pressure

Table 2.

Post-hoc comparison

P	Baseline IOP	1-hour IOP	1-week IOP	1-month IOP	3-month IOP	6-month IOP	12-month IOP
Baseline IOP	1	1	0.336	<0.0001	0.003	<0.0001	<0.0001
1-hour IOP	1	1	0.455	0.0001	0.007	<0.0001	<0.0001
1-week IOP	0.336	0.455	1	0.112	0.637	0.058	0.001
1-month IOP	<0.0001	0.0001	0.112	1	0.955	1.000	0.700
3-month IOP	0.003	0.007	0.637	0.955	1	0.873	0.141
6-month IOP	<0.0001	<0.0001	0.058	1.000	0.873	1	0.844
12-month IOP	<0.0001	<0.0001	0.001	0.700	0.141	0.844	1

Table 3 shows the IOP reduction at various points of time among different subgroups of OAG. The reduction in IOP at the 12-month follow-up visit was statistically significant among all the subgroups of glaucoma. Maximum IOP reduction was noted in the XFG subgroup (27.27%).

Table 3.

Comparison of IOP reduction among various subgroups of glaucoma

	Median IOP at baseline in mmHg (IQR)	Median IOP at 12 months	Median reduction of IOP at 12 months	Percentage reduction of IOP at 12 months	P
Diagnosis
POAG (n=44)	22 (18–26.5)	18 (14–22)	4 (2–8.5)	22.22 (8.173–31.9)	0.0001§
NTG (n=37)	16 (14–18)	14 (12–16)	2 (−2–4)	12.5 (−14.286–20)	0.023§
XFG (n=13)	24 (20–28)	16 (14–22)	8 (4–10)	27.27 (15.385–40)	0.003§
Others (n=10)	24 (17.5–31.5)	20 (16–22)	3 (0.5–8.5)	12.92 (2.083–27.983)	0.024§
P	<.0001‡	0.002‡	0.001‡	0.018‡	-
Others
JOAG (n=4)	27 (23.5–30.5)	23 (21–24.5)	4 (3–5.5)	15.76 (10–21.449)	0.102§
Si oil (n=2)	33 (28.5–37.5)	16 (13–19)	17 (9.5–24.5)	42.26 (25.298–59.226)	0.180§
PDS (n=2)	16 (16–16)	15 (14.5–15.5)	1 (0.5–1.5)	6.25 (3.125–9.375)	0.317§
AR (n=1)	14 (14–14)	16 (16–16)	−2 (−2–−2)	−14.29 (−14.286–−14.286)	-
OHT (n=1)	32 (32–32)	22 (22–22)	10 (10–10)	31.25 (31.25–31.25)	-
P	0.157‡	0.268‡	0.291‡	0.341‡	-

^‡Kruskal-Wallis test, §Wilcoxon signed rank test, IOP=Intraocular pressure, POAG=primary open-angle glaucoma, NTG=normal tension glaucoma, XFG=pseudoexfoliation glaucoma, JOAG=juvenile open-angle glaucoma, Si oil=Silicone oil induced glaucoma, PDS=pigment dispersion glaucoma, AR=angle recession glaucoma, OHT=ocular hypertension

Complete success was noted in 29 (28%) patients and qualified success in 19 (18%) patients [Table 4]. Treatment-naive eyes had a higher success rate (48.19%) as compared to those with prior use of AGM (38.09%), the difference being statistically significant (P = 0.045). Overall, in 48 (46.15%) patients, SLT was effective (success + qualified success) in lowering IOP, either as primary or adjunctive treatment.

Table 4.

Outcomes of SLT

	Success	Qualified success	Total	Percentage	P
Treatment naive (SLT as primary treatment) (n=83)	n=27	n=13	n=40	48.19%	0.045†
Prior use of AGM (SLT as adjunctive treatment) (n=21)	n=2	n=6	n=8	38.09%
Total (n=104)	n=29	n=19	n=48	46.15%

^†Fisher’s exact text, n=number of eyes, SLT=Selective laser trabeculoplasty, AGM=antiglaucoma medication

Table 5 shows the analysis of various parameters with treatment failure at 12 months. On performing univariate regression, none of the variables was a significant predictive factor for treatment failure (P > 0.05).

Table 5.

Univariate analysis of predictors of treatment failure

Variable	Beta coefficient	Standard error	P	Odds ratio	Odds ratio Lower bound (95%)	Odds ratio Upper bound (95%)
Age (years)	−0.027	0.017	0.108	0.973	0.941	1.006
Gender
Female				1.000
Male	−0.559	0.411	0.174	0.572	0.255	1.279
Eye involved
Left eye				1.000
Right eye	−0.176	0.395	0.656	0.839	0.387	1.819
Prior use of AGM	0.634	0.510	0.214	1.885	0.694	5.122
POAG	−0.420	0.399	0.294	0.657	0.300	1.438
NTG	0.694	0.422	0.100	2.002	0.876	4.577
XFG	−1.099	0.637	0.085	0.333	0.096	1.162
Baseline IOP >21 mmHg	−0.659	0.404	0.102	0.517	0.235	1.141
Total energy used >70 mJ	0.025	0.416	0.952	1.026	0.453	2.319

AGM=antiglaucoma medication, POAG=primary open-angle glaucoma, NTG=normal tension glaucoma, XFG=pseudoexfoliation glaucoma, IOP=Intraocular pressure

Discussion

The primary goal of glaucoma treatment is to preserve visual function as per the expected lifetime of the patient, at a sustainable cost and with minimal side effects.[7] The efficacy of SLT in lowering IOP was first described by Latina et al.[5] and was echoed by numerous studies published thereafter. Over the past two decades, SLT has increasingly become an established treatment to lower IOP, either as primary or adjunctive treatment. Most studies describe SLT for POAG or ocular hypertension. In this study, we extended the spectrum to various types of OAG. Furthermore, we assessed the outcomes of SLT as primary treatment as well as adjunctive treatment. To the best of our knowledge, this is the first study to assess the outcome of SLT over 12 months for OAG in Indian eyes.

The mean age of patients in this study was 63.06 ± 12.3 years (25–86 years). Age was not found to be a predictive factor for treatment outcome. This is consistent with the findings of most studies.[14,15,16] However, Xu et al.[17] found that younger POAG patients may obtain better results after low-energy SLT treatment, and Swain DL et al.[18] found that higher patient age at SLT was significantly associated with an increased risk of receiving a subsequent surgical procedure. In this study, there was a 2:1 ratio of males and females. The higher proportion of males as compared to females may be attributed to the fact that in rural Indian localities, female health is still neglected and females are less proactive to come to a hospital for their health needs. Gender is not known to affect the success of SLT, and the current study also found the same.[6] Similarly, laterality of eye was not found to be a risk factor for treatment outcome, which is in agreement with published literature.[18,19]

Various studies have shown SLT to be equally efficacious as primary and adjunctive therapy.[20,21,22] In the present cohort, close to 80% of the eyes were treatment-naive. The success rate in virgin eyes and those with prior use of AGM was 48% and 38%, respectively (P = 0.045). However, prior use of AGM was not found to be a predictive factor for treatment outcome. POAG was the most common subtype of glaucoma, followed by NTG. This is slightly different from most studies on OAG, where POAG was most common followed by OHT.[16,18,19] We did not find subtype of glaucoma to be a risk factor affecting treatment outcome, although some of the subgroups had very small numbers to be included for a comparative analysis.

The most consistently reported patient factor, which predicts SLT success is known to be elevated baseline IOP.[6] One study reported that higher baseline IOP was associated with an increased risk of re-treatment with 360° SLT within the 10-year follow-up period.[23] In the current series, the median baseline IOP was 20 mmHg (16–26 mmHg). High baseline IOP (>21 mmHg) was not found to be a predictive factor for treatment outcome. With regards to the total energy used, some studies have shown that higher energy was associated with a greater IOP lowering effect,[24,25] while most report that there is no definitive indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction.[26] In this study, we did not find higher energy (>70 mJ) to be a predictive factor for treatment outcome.

The median decrease in IOP at the end of 12 months was 4 mmHg (0–6.5 mmHg), and the percentage reduction in IOP was 17.42% (0%–30.76%). In a similar study done by Elahi S et al.[27] on 170 eyes of 126 patients, it was found that the average IOP reduction was 3.3 ± 4.3, and the percentage reduction was 17.6% at 1-year follow-up. The IOP reduction in the current series was found to be statistically significant at each visit, and the maximum IOP reduction was noted at 12 months (P < 0.0001). However, a study done by Khawaja et al.[16] to assess the real-world outcomes of SLT in the UK showed that most patients initially responded to SLT, but the majority failed within 1 year. The overall success rate in the current study was 46.15% at 12 months, which is similar to some studies,[16,27,28] and lesser than that reported by certain studies.[19,29,30] However, direct comparison of the IOP reduction across various studies is precluded by the differences in study design, population groups, stage of glaucoma, baseline IOP, and criteria for success. Some of the known complications of SLT are anterior chamber inflammation, transient spike in IOP, peripheral anterior synechiae, endothelial decompensation, foveal burn, and corneal haze.[7] Most studies have found SLT to be a relatively safe procedure, and our findings are in agreement, with only five eyes (4.8%) experiencing minor SLT-related complications.

The strength of this study lies in the inclusion of varied types of OAG and in being one of the few studies done on an Indian population. All the SLT procedures were performed by a single-trained glaucoma specialist. The limitations of this study include a small subgroup sample size and small duration of follow-up. For some patients, both eyes were included in the study, which may have led to clustering. We did not analyze the changes in visual field or nerve fiber layer thickness post SLT. Lastly, the criteria for success in this study were relatively less stringent.

Conclusion

In summary, SLT was able to achieve an IOP reduction of around 17% at 1 year in an Indian population with OAG. Maximum IOP reduction was noted at 12 months. The overall success rate was 46.15% at 12 months. Close to 80% of the eyes were virgin and in approximately half of them, SLT was successful. SLT was found to be a relatively safe procedure. Age, gender, prior use of AGM, type of OAG, and higher baseline IOP were not found to be predictive factors for treatment outcome.

Conflicts of interest:

There are no conflicts of interest.

Funding Statement

Nil.