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Laser Management of Glaucoma in Exfoliation Syndrome

Sandhu, Simrenjeet, MD; Damji, Karim F., MBA, MD, FRCSC

doi: 10.1097/IJG.0000000000000909
Exfoliation Syndrome

Argon laser trabeculoplasty as well as selective laser trabeculoplasty can be used in patients with exfoliation syndrome with similar safety and efficacy. However, treatment effect may abruptly reverse and patients need to be followed regularly to monitor intraocular pressure control. Newer laser treatment modalities including micropulse laser trabeculoplasty, titanium sapphire laser trabeculoplasty and pattern scanning trabeculoplasty show promising results but need to be studied in exfoliation patients. For exfoliation patients with angle closure, peripheral iridectomy, iridoplasty or cataract extraction can be very helpful. For refractory exfoliation glaucoma, transscleral diode laser cyclophotocoagulation offers a reasonable option to lower intraocular pressure. Other approaches to cyclophotocoagulation such as micropulse transcleral diode laser need to be studied further in exfoliation patients.

Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada

Disclosure: The authors declare no conflict of interest.

Reprints: Karim F. Damji, MBA, MD, FRCSC, Royal Alexandra Hospital, 2317, 10240 Kingsway Avenue, Edmonton, AB, Canada T5H 3V9 (e-mail: kdamji@ualberta.ca).

Received January 26, 2018

Accepted January 28, 2018

Laser trabeculoplasty is a suitable option for patients with exfoliation syndrome (XFS) who are on maximal medical management, are intolerant or unable to comply with drops, wish to reduce the number of medications, or as an alternative initial treatment. This chapter will discuss various laser treatment modalities applicable to open-angle glaucoma associated with XFS including argon laser trabeculoplasty (ALT), selective laser trabeculoplasty (SLT) (Fig. 1), and micropulse laser trabeculoplasty (MLT). When angle closure is present, laser peripheral iridectomy (PI) may be helpful and when glaucoma is refractory to other treatment modalities, cyclophotocoagulation (CPC) may also be indicated. PI and CPC are thus also briefly covered in this article.

FIGURE 1

FIGURE 1

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ALT

ALT to lower intraocular pressure (IOP) was first applied by Ticho and Zauberman1 in 1976. Positive predictors for ALT success in lowering IOP include age older than 65 years, moderate to marked trabecular meshwork pigmentation, and XFS.2 The mechanism of action is thought to be one or more of the following: mechanical opening of the trabecular meshwork, opening of Schlemm canal, and changes in extracellular matrix within the trabecular meshwork.3,4

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Efficacy and Safety

In a study comparing ALT to SLT in exfoliation patients by Kent et al,5 31 eyes received ALT therapy. Baseline IOP before ALT treatment was 25.2 mm Hg and IOP was reduced to 18.2 mm Hg at 6 months.5 Results revealed a 7.7 mm Hg reduction at 6 months, with 73% of ALT patients having at least a 20% reduction in IOP and no change in number of glaucoma medications compared with baseline.5 Psilas et al6 examined 41 eyes with exfoliation glaucoma (XFG), with a 13.4 mm Hg reduction after ALT. Studies have shown XFG patients having a greater IOP reduction compared with primary open-angle glaucoma (POAG).7 A retrospective ALT study by Threlkeld et al7 compared 29 patients with XFG to 66 eyes with POAG. The XFG group had a significantly greater drop in IOP at 12 months compared with POAG, with an IOP reduction from baseline of 38% and 19%, respectively.7

Long-term follow-up has also been reported. The Glaucoma Laser Trial Follow-up Study investigated 203 patients with POAG that included XFG patients undergoing ALT, with a median duration follow-up of 7 years.8 Compared with eyes treated initially with medication, ALT treated eyes had 1.2 mm Hg greater IOP reduction and 0.6 dB greater improvement in the visual field.8 Many studies have shown that repeat ALT procedures may not be effective for XFG.9,10

The most common complications from ALT procedures in both POAG and XFG were IOP spikes occurring in 3% to 5% of patients using alpha-adrenergic prophylaxis before treatment.11 Without prophylaxis, a major study has shown IOP spikes occurring in 23% of study patients.12 Other complications from ALT may include corneal burns, peripheral anterior synechiae and low grade iritis.

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General Techniques and Treatment Guidelines

Laser settings are commonly a 50 μm spot size, 0.1 second duration and between 200 and 800 mW depending on tissue response (ideally aiming for blanching of tissue and occasional bubble formation).

XFG following ALT may have an unpredictable course and closer follow-up is recommended for this group.13

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SLT

In 1998, Latina et al14 used a q-switched 532 nm Nd:YAG laser selectively targeting the pigmented trabecular meshwork in 53 patients with uncontrolled open-angle glaucoma. Minimal damage is apparent on imaging using scanning and transmission electron microscopy compared with ALT.15 The mechanism of action is thought to be release of cytokines post selective photothermolysis that improves outflow facility.4

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Efficacy and Safety

Patients with XFG treated with SLT seem to do as well or perhaps slightly better than POAG patients treated with SLT.16,17 Kara et al16 showed a significant IOP difference 1 year following SLT between patients with POAG and XFG, with an IOP reduction of 4.4±2.1 and 6.1±3.6 mm Hg, respectively. Similarly, Lindegger et al17 also showed a significant IOP reduction in patients with XFG compared with those with POAG, 1 year after SLT treatment. In a study by Kent et al,5 45 exfoliation eyes received SLT therapy. Baseline IOP before SLT treatment was 23.1 mm Hg and IOP was reduced to 18.2 mm Hg at 6 months.5 There was a 6.8 mm Hg IOP reduction at 6 months with 73% of SLT patients having at least a 20% reduction in IOP; there was also a reduction in glaucoma medications by 0.16.5 Gracner18 found that 10 patients with XFG had a 31.4% IOP reduction at 18 months. Goldenefeld et al19 studied 57 patients with uncontrolled XFG undergoing SLT. Mean IOP after 1-year follow-up demonstrated a decrease from baseline of 26.0 to 17.8 mm Hg and medications deceased from 2.8 to 2.3.19 Shazly et al20 investigated the long-term safety and efficacy of SLT in 18 eyes with XFG. At 30 months, the mean IOP was 18.3 mm Hg with a reduction of 5.3 mm Hg from baseline.20

If IOP is well controlled with the initial 180 degrees of treatment, the remaining 180 degrees can also be treated if IOP rises over time. Given less damage to the trabecular meshwork and surrounding structures with SLT versus ALT, studies have also examined IOP lowering with retreatment. Golez et al21 retrospectively reviewed 79 eyes with XFG, of which 21 underwent repeated SLT. Of those with repeat treatment, 11 eyes maintained IOP control after a second treatment of SLT and 2 eyes maintained IOP after a third treatment of SLT.21 Retreatment of SLT may be beneficial, but further studies are needed to confirm long-term efficacy.

The most common complications from SLT procedures include early postoperative IOP spikes, anterior chamber reactions, redness, pain, and blurred vision.22,23 Corneal burns, peripheral anterior synechiae, and low grade iritis have also been reported.22,23 Most are transient and minor, resolving without any major sequelae, although persistent spikes in IOP associated with endothelial failure have been reported.24 Cellini et al25 proposed a possible mechanism for IOP spikes after SLT, attributing to a failure to decrease the tissue inhibitor of metalloproteinases/metalloproteinases ratio.

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General Techniques and Treatment Guidelines

Patient preparation is the same as described earlier for ALT. Laser spots are a fixed 400 μm size and are centered on the trabecular meshwork. The duration is a fixed 3 ns and the power is typically between 0.8 and 1.1 mJ/pulse. Settings should be adjusted to reach an endpoint of occasional bubble formation. If there is heavy meshwork pigmentation, which is often the case with exfoliation patients, then the energy setting will need to be reduced, typically between 0.4 and 0.6 mJ/pulse.

Treatment can span 180 to 360 degrees, with 50 spots for every 180 degrees. Our practice is to treat 180 degrees when SLT is used as adjunctive therapy in patients on medication, and to treat 360 degrees if used as initial treatment. Patient follow-up is similar to ALT above, but nonsteroidal anti-inflammatory medication can be prescribed instead of prednisolone acetate.

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MLT

MLT uses intermittent pauses between microsecond pulses to reduce the coagulative damage attributed to consistent thermal energy.26,27 Similar to SLT, a biochemical theory proposes that MLT treatments cause cytokine release increasing outflow with less tissue destruction compared with ALT.28

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Efficacy and Safety

Studies have shown promising IOP reductions with minimal complications in eyes with POAG after being treated with MLT.29,30 To our knowledge, MLT has not been investigated in XFG. Although MLT may be a promising treatment modality, studies focusing on this subgroup are needed.

Newer laser treatments such as titanium sapphire laser trabeculoplasty and pattern scanning trabeculoplasty also show early promising results in open-angle glaucoma patients and could also be studied in exfoliation patients.

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PI

XFS patients may develop angle closure related to weakness of the zonules causing forward movement of the lens, a more rigid iris, and iridolenticular adhesion/synechaie formation (due to a weak blood aqueous barrier). Studies have shown that the prevalence of angle closure varies in populations but can be as high as 31%.31 When iridotrabecular contact exceeds 180 degrees and is appositional, laser PI is indicated. Other alternatives include iridoplasty, use of dilute pilocarpine and cataract extraction, all of which can serve to open the angle.

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General Techniques and Treatment Guidelines

We recommend a cholinergic agent, such as Pilocarpine 1%, to stretch the iris as well as pretreatment with an α2 adrenergic receptor agonist, such as apraclonidine or brimonidine, to avoid postoperative IOP spikes. Using an Nd:YAG Laser, the Q-switched mode is utilized with 3 to 6 mJ/pulse until the opening is made. For dark irides, an argon laser can be used to either pretreat (before YAG) or to go completely through the iris. Argon laser settings are typically 50 μm spot size, 0.02 to 0.05 seconds and 900 to 1000 mW/pulse.

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Safety

The most common complications following PI include IOP spikes, laser-induced inflammation, peripheral anterior synechiae, hyphema, and diplopia.2 Other complications reported include lens opacities, corneal injury, postlaser malignant glaucoma and retinal burns.2

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TRANSSCLERAL DIODE LASER CPC

A diode laser is most commonly used for transscleral CPC procedures to decrease IOP by targeting feeder vessels and the secretory ciliary epithelium, resulting in decreased production of aqueous humor.32 Endoscopic CPC is another form of CPC that uses fiber optics to coagulate ciliary tissue. However, exfoliation material on the zonules can hinder laser uptake in exfoliation patients.33 ECP can also be technically more challenging given that the ciliary processes are coated with whitish exfoliation material making the laser penetration more difficult. One of us has experienced a situation where the laser energy was turned up to obtain shrinkage of the ciliary processes and this resulted in a sudden profuse hemorrhage from a ciliary process tip likely related to rupture of a large vessel.

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General Techniques and Treatment Guidelines

For transscleral CPC a retrobulbar anesthetic is administered. Three quadrants are typically treated with ∼7 spots per quadrant (avoiding the 3 and 9 o’clock positions so as not to disrupt the long posterior ciliary arteries). Although there are varying techniques, we prefer to use a 2000 mW pulse for a 2.0 second duration initially.34 The power setting is adjusted by ±250 mW depending on whether tissue pops are heard.35 If a tissue pop is heard then we turn the energy down slightly and proceed with treatment at this energy setting. Postoperative care includes a steroid medication that needs to be tapered over 1 month as well as short term use of atropine and oral analgesics as appropriate.

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Efficacy and Safety

Grueb et al35 performed a retrospective chart review analyzing 24 eyes with XFG which underwent transscleral diode CPC as primary and secondary surgical treatment. 25% of patients were successful after 12 months, defined as a final IOP between 4 and 18 mm Hg, minimum IOP reduction of 20% and absence of major complications.35 In a long-term study by Lliev and Gerber36 examining transscleral CPC in refractory glaucoma, 5 of 11 eyes with XFG were considered failures. It should be noted, however, that most patients were advanced cases with limited visual acuity.

The most common postoperative complication is pain, occurring in 33% to 50% of patients undergoing transscleral CPC. Other complications may include inflammation, bleeding, visual acuity changes, sympathetic ophthalmia, and malignant glaucoma.34

Other approaches to CPC include micropulse transscleral diode laser CPC and ultrasound-medicated cyclomodification. To our knowledge, these approaches have not been studied in exfoliation patients.

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CONCLUSIONS

IOP can be lowered effectively following laser trabeculoplasty in exfoliation patients with open angles. However, treatment effects may abruptly reverse resulting in elevated pressures. The authors recommend continued postoperative follow-up every 4 to 6 months. Laser iridectomy and transscleral CPC also have a role to play in patients with occludable angles and refractory glaucoma, respectively.

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Keywords:

exfoliation syndrome; glaucoma; laser; ALT; SLT; MLT; peripheral iridectomy; diode laser cyclophotocoagulation

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