Effect of diode laser cyclophotocoagulation in treatment of patients with refractory glaucoma

Background/Aim. Refractory glaucoma is glaucoma resistant to conventional management (maximally tolerated medical therapy, one or more glaucoma surgeries) and glaucoma in cases of neovascularisation after panretinal photocoagulation or cryoablation. The aim of the study was to determine the intraocular pressure (IOP) lowering efficacy of transscleral diode laser cyclophotocoagulation (DCPC) treatment in the management of pain and IOP in patients with refractory glaucoma. Methods. This nonrandomized, retrospective study, included 95 patients (95 eyes) with refractory glaucoma treated at the University Eye Clinic, Clinical Center of Vojvodina, Novi Sad, Serbia, between November 2007 and November 2012 in accordance with the established protocols (16–18 spots, 270°, up to 5J of energy). All the eyes were treated with transscleral DCPC (Iris Medical OcuLight SLx, Iridex Co, Mountain View, USA). Patient's symptoms, bests corrected visual acuity and IOP were recorded 7 days, and 1, 3 and 6 months after the DCPC treatment. Results. Out of 95 patients (95 eyes) enrolled in this study 24 (25.2%) were with primary (the group I), and 71 (74.5%) with secondary (the group II) glaucoma. The mean baseline IOP in these two groups was similar: 36.08 ± 8.39 mmHg for the first group and 37.36 ± 8.19 mmHg in the second group. Measurement of the mean IOP in the group I showed the following results: on the day 7 it was 13.96 ± 8.30 mmHg (62.1% decrease of the baseline value), on the day 30 it was 18.44 ± 8.85 mmHg (48.9% decrease regarding the baseline value), after 3 months it was 22.44 ± 7.36 mmHg (37.8% decrease regarding the baseline value), and after 6 months it was 25.92 ± 7.65 mmHg (28.2% decrease regarding the baseline value). Measurement of IOP in the group II showed the following results: on the day 7 it was 15.77 ± 9.73 mmHg (57.8% decrease of the baseline value), on the day 30 it was 20.14 ± 10.20 mmHg (46.1% decrease regarding the baseline value), after 3 months it was 23.46 ± 9.83 mmHg (37.2% decrease regarding the baseline value) and after 6 months it was 27.23 ± 9.87 mmHg (27.2% decrease regarding the baseline value). Pain was the main symptom in 70 (73.6%) patients before the treatment and it persisted in only 4 (4.2%) of our patients. Other complaints (burning, stinging, foreign body sensation) were experienced by 39 (41%) of the patients, postoperatively. A total of 52 (54.7%) patients had no complaints after the treatment. Conclusion. Our study confirmed that transscleral DCPC is a useful, effective and safe procedure with predictable amount of IOP decrease, which makes it the treatment of choice for refractory glaucoma.


Introduction
Refractory glaucoma is glaucoma resistant to conventional management (maximally tolerated medical therapy, one or more glaucoma surgeries) and glaucoma in cases of neovascularisation after panretinal photocoagulation or cryoablation 1 .
Beside refractory primary open and angle closure glaucoma indications for cyclodestructive procedures are: neovascular, post-traumatic, aphakic/pseudophakic glaucoma especially with anterior chamber intraocular lenses (IOL), severe congenital glaucoma with multiple failed surgeries, post-penetrating keratoplasty glaucoma, post-retinal detachment surgery glaucoma, silicone oil induced glaucoma, inflammatory glaucoma.
Mechanism of action of cyclophotocoagulation includes decrease of aqueous production and increase of aqueous outflow 3 . Destruction of the ciliary epithelium combined with destruction of ciliary blood vessels and coagulative necrosis, leads to decrease in aqueous production 4 . In many cases inflammation after the treatment leads to short-term hypotension 5 . Neuroepithelial defects created after laser treatment, and creation of transscleral flow similar to cyclodialysis, are responsible for increase of aqueous outflow which is related to the extent of treatment 6 . Diode laser causes destruction of the pigmented and nonpigmented ciliary epithelium and capillaries in the ciliary processes with pigment clumping, coagulative necrosis, and extensive destruction of ciliary muscle with a moderate reduction in vascularity 7 . Some histopathologic studies have shown that diode laser produces most of its coagulative effect on the ciliary body stroma 8 .
Even though it is not completely understood, it seems that there is an increase of uveoscleral outflow through the enlarged extracellular spaces from the anterior chamber into the suprachoroidal space 9 .
Diode and Nd:YAG lasers require the presence of ciliary body pigment epithelium for the absorption of laser energy 10 . A diode laser (810 nm) has a greater melanin ab-sorption compared to a Nd:YAG laser (532 nm), requiring lesser energy per spot 11 . Data about dosage and laser treatment protocol-related response vary in available literature 1,12,13 . A totally delivered energy, the number of laser burns per session and pulse power and duration were analyzed in numerous studies, but the results were inconclusive and contradictory. However, most of the results confirmed that refractory glaucoma can be successfully managed on a longterm basis with single or repeated diode laser cyclophotocoagulation 14 .
Recently, contact diode laser cryoablation has emerged as the preferred treatment because cryoablation and Nd:YAG laser cyclophotocoagulation are associated with a greater risk of hypotony and phthisis due to excessive ciliary body destruction [15][16][17][18][19] .
The aim of the study was to determine the intraocular pressure (IOP) lowering efficacy of transscleral DCPC treatment in the management of pain and IOP in patients with refractory glaucoma. of wavelength. The average power used was 2.5 W, with 1.5 seconds of duration. Contact tip of G-probe was positioned 1.2 mm behind surgical limbus and 16-18 spots spread over 270° per session were made. The sound of "pop" or "snap" at the treatment site was used as indicator for tissue disruption within the ciliary body. To prevent potential inflammatory reactions topical 1% dexamethasone, every one to two hours while awake, and atropine sulfate 1%, twice a day for the first seven days, were applied in all the patients.

Methods
When the patients required repeated treatment due to insufficient reduction in IOP, spots were made in untreated quadrants behind limbus.
The patient's symptoms, BCVA and IOP were recorded 7 days, and 1, 3 and 6 months after the DCPC treatment.
For statistical analyses we used Microsoft Excel software with standard statistical parameters and methods -numerical data were presented using minimum, maximum and average values) standard deviation (SD) and 95% confidence interval (CI). Student's t-test was used to make comparison between the groups and to compare IOP values.

Results
A total of 95 patients (95 eyes) were enrolled in this study, of whom 24 (25.2%) were with primary (the group I) and 71 (74.5%) with secondary (the group II) glaucoma. In the group I, there were 20 (21%) patients with POAG and 4 (4.2%) patients with PACG. In the group II 53 (55.7%) patients had neovascular glaucoma, 11 (11.5%) patients had glaucoma after pars plana vitrectomy and 7 (7.3%) patients had traumatic glaucoma.
There was a predominance of males in both groups (55.7% vs 44.3%). The mean age of patients was 61.5 years (SD ± 15.4; range 13-86 years). Forty-five (47.3%) patients were with no light perception (L-). BCVA ≤ 0.1 was found in 50 (52.7%) patients. There was no significant difference between the treatment groups in the mean age, gender and visual acuity. Pain was the chief complaint and the main reason for treatment in 70 (73.6%) patients (20 patients in the group I and 4 patients in the group II), while other complaints (burning, stinging, foreign body sensation) were the main reason for treatment in 25 (26.4%) patients (4 patients in the group I and 21 in the group II). The mean baseline IOP in the two groups was similar: 36.08 ± 8.39 mmHg for the group I and 37.36 ± 8.19 mmHg in the group II. The demographic characteristics and the baseline IOP values are shown in Table 1.
Mean IOP measurement in the group I showed the following results: on the day 7 it was 13.96 ± 8.30 mmHg (62.1% decrease regarding the baseline volume), on the day 30 it was 18.44 ± 8.85 mmHg (48.9% decrease regarding the baseline value), after 3 months it was 22.44 ± 7.36 mmHg (37.8% decrease from the baseline value), and after 6 months it was25.92 ± 7.65 mmHg (28.2% decrease regarding the baseline value) (Figure 1).

Fig. 1 -Mean intraocular pressure (IOP) by the treatment groups.
Measurement of IOP in the second group showed the following results: on day 7 it was 15.77 ± 9.73 mmHg (57.8% decrease regarding the baseline value), on day 30 it was 20.14 ± 10.20 mmHg (46.1% decrease regarding the baseline value), after 3 months it was 23.46 ± 9.83 mmHg (37.2% decrease regarding the baseline value), and after 6 months it was 27.23 ± 9.87 mmHg (27.2% decrease regarding the baseline regarding) (Figure 1). During a 6-month follow-up IOP was significantly lower regarding the baseline values in both groups (p < 0.001), but there was no significant difference between the two groups.

Discussion
Transscleral cyclophotocoagulation with a diode laser has gained popularity and has practically replaced the Nd:YAG laser and cryo method for treatment of refractory glaucoma due to comparable efficacy. However, some studies have found that the therapeutic effect can be lost over time and in some cases repeated treatment is necessary 20 .
There are two factors that determine the laser powerenergy and the duration of application. The energy per application should be kept under 5 J. A longer duration allows the thermal energy to spread through the tissue and reach the ciliary epithelium 12 .
We obtained good results with settings of 2,500 mW and 1.5 seconds of duration (3.75 J), reserving the higher energy levels for repeated procedures and lower settings for eyes with more heavily pigmented irises.
Long-term study of Ataullah et al. 21 in the Manchester Royal Eye Hospital used 1,500 mW with 2.5 seconds of duration. Six months after DCPC IOP reduction was 42% regarding the baseline value. We found a reduction in IOP six months after the treatment by 28.2% (the group I) and 27.2% (the group II) regarding the baseline values.
Noureddin et al. 13 showed an IOP decrease in 36 refractory glaucoma eyes from 35.8 mmHg to 19 mmHg (47% regarding the baseline values) which is a higher IOP decrease than our study presented. This difference can be explained by the fact that they performed a 360 degrees cyclophotocoagulation compared to 270 degrees of treatment in our study.
The other study of Hawkins and Stewart 22 showed an IOP decrease by 36% after DCPC, from 32.5 mmHg preoperative to 21.8 mmHg six months after the treatment. That is comparable to the results of our study.
Egbert et al. 23 showed a 20% of IOP decrease six months after DCPC in the treatment of refractory POAG. In that study 360 degrees of laser treatment was performed and the energy was 1,500 mW. Our study showed a decrease in IOP in the patients with primary glaucoma of 28.2% regarding the baseline value.
A retrospective analysis of Murphy et al. 14 including 263 eyes with refractory glaucoma after transscleral DCPC, showed that 89% of the patients reached 30% drop in IOP. This overall IOP decrease was similar to our study results. They had found 3% of patients with pain after the treatment. In our study 4.2% of the patients had persistent pain postoperatively due to IOP increase unresponsive to the repeated procedures.
In a multicenter study, 30 eyes of 30 patients with refractory glaucoma were followed for a median of 2 years after DCPC. Seventeen to 19 applications were made over 270 degrees, 2 seconds duration and 1,500-2,000 mW power. IOP fell from a mean baseline pressure of 36.1 mmHg to a mean of 21.6 mmHg and remained essentially unchanged for the duration of the study 24 . After a 6-month follow-up our study showed comparable results.

Conclusion
Our study confirmed that transscleral diode laser cyclophotocoagulation is a useful, effective and safe procedure with predictable amount of intraocular pressure decrease, which makes it the treatment of choice for refractory glaucoma.