Lowering the intraocular pressure (IOP) currently remains the only clinically proven method to prevent or slow progressive glaucomatous visual loss. When medical therapy does not achieve the desired aim, or results in intolerable side effects, laser or surgical procedures can be used as adjuvants or on their own for IOP lowering.

In recent years the management of glaucoma, be that with laser or surgery, has undergone innovation and many changes, with continuing improvements to current methods as well as an array of newer evolving technologies which will be discussed.

Laser

Laser trabeculoplasty

Laser trabeculoplasty has been primarily used to treat open-angle glaucoma. The two commonest types of laser trabeculoplasty used are: argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT).

ALT involves the application of argon laser burns to the trabecular meshwork (TM), enhancing aqueous flow, and thus lowering the IOP. ALT’s mechanism of action is believed to result from the mechanical tightening of trabecular tissue, thereby opening adjacent untreated trabecular spaces (Figure 1).

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It is also thought to induce cell division and migration of macrophages to clear the TM of debris. It is applied with the help of a goniolens, with the aiming beam focused at the junction of the pigmented and non-pigmented TM. The area of treatment can vary between half (180°) or the whole circumference (360°) of the anterior chamber angle. ALT has been largely superseded by SLT (Figure 2).

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SLT utilises a Nd:YAG laser which selectively targets the melanin pigment in the TM cells, sparing non-pigmented structures. It provides easier targeting compared to the ALT apparatus, is reported to have a lower side effect profile due to the lower amount of laser energy used in treatment and has been shown to be as effective as ALT.1

MicroPulse laser trabeculoplasty (MLT) is a more recent method using the IRIDEX IQ 532 and is reported to be equivalent to ALT and SLT in lowering IOP.2

Iridotomy

The Nd:YAG laser can be used to ‘open’ a ‘narrow’ or ‘occludable’ angle. Since the angle forms the part of the eye that aqueous fluid passes through, iridotrabecular apposition of the angle is a risk for angle-closure glaucoma. A peripheral iridotomy can be performed to reduce the risk of angle-closure glaucoma from pupillary block mechanisms.

Iridoplasty

In certain circumstances an iridotomy by itself may be insufficient to prevent appositional angle closure. This may be encountered in patients with non-pupillary block mechanisms such as plateau iris. Argon laser iridoplasty can be performed to the peripheral iris to cause contraction of the peripheral iris stroma away from the angle structures resulting in deepening of the angle recess. It can also be performed in an acute primary angle-closure crisis with significantly raised IOPs refractory to medical lowering.

Cycloablation

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Diode laser cycloablation (cyclodiode) lowers IOP by ablating small areas of the ciliary body which is responsible for producing aqueous humour. With the help of a focused laser beam it can be performed either trans-sclerally or endoscopically (Figures 3 and 4). Several clinical trials are currently being conducted by companies such as EyeSonix and EyeTechCare developing ultrasound emitting devices with the aim of improving outflow by reducing aqueous outflow resistance.3

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Surgery

Trabeculectomy

Trabeculectomy is currently the most commonly performed glaucoma filtration operation. The procedure aims to create a filtration channel via a scleral flap to allow aqueous outflow from the anterior chamber to the subconjunctival space. This creates, a filtration ‘bleb’ which appears as a raised ‘blister’ above the sclera, covered by the upper eyelid (Figure 5).

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Trabeculectomy surgery can be ‘augmented’ with the use of anti-fibrotics, such as mitomycin-C and 5-fluorouracil, to limit postoperative fibrosis and scarring, thereby improving the potential for longer term filtration and control of IOP. Filtration surgery is not without potential risks that may result in visual loss, such as over filtration leading to low IOP (hypotony), bleb leaks and infection, and (rarely) bleb-related endophthalmitis.

Non-penetrating glaucoma surgery

Techniques such as deep sclerectomy, viscocanalostomy and canaloplasty attempt to avoid or limit the production of a filtration bleb by improving aqueous outflow via Schlemm’s canal. Following a similar concept, trabeculotomy ab interno (with the Trabectome from NeoMedix) is designed to re-establish access to the eye’s internal drainage pathway. The surgery is performed under direct visualisation with a gonioscopy lens and uses electrocautery to remove a 60-120° strip of TM and the inner wall of Schlemm’s canal. The goal is to achieve direct flow of aqueous into Schlemm’s canal and then into the collector channels (Figure 6).

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Aqueous drainage implants

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Most drainage implant procedures involve inserting a small tube into the anterior chamber of the eye, in front of the iris. Aqueous drains through the tube, to a plate making up the posterior end of the implant which is placed under the conjunctiva. Drainage implant shunts are more commonly performed in individuals with secondary glaucoma, or when other glaucoma treatments or operations have previously been unsuccessful. Drainage shunts may be subdivided into ‘valved’ (Ahmed) (Figure 7) and ‘non-valved’ (Baerveldt and Molteno) implants (Figure 8), depending on whether or not a valve mechanism is present that acts to limit flow through the tube to the plate to reduce the risk of IOP being too low postoperatively.

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Similar postoperative issues seen in trabeculectomy and non-penetrating surgery can also be encountered with drainage implants whereby postoperative fibrosis and scarring can occur leading to inadequate IOP control. Other complications from drainage tube implants may include diplopia due to restriction of the extraocular muscles by the end plate, and corneal oedema as a result of contact between the tube in the anterior chamber and the corneal endothelium.

Microinvasive glaucoma surgery (MIGS)

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Techniques and devices are continually being developed in an attempt to further improve the safety profile of glaucoma surgery and there has been increasing interest in MIGS. Initial reported results are encouraging. These newer devices utilise one of four broad outflow strategies as indicated in Figure 9:

(1) Via Schlemm’s canal

(2) Into the suprachorioidal/ciliary space

(3) Subconjunctival outflow

(4) Cilio-ablative.

Schlemm’s canal

iStent: a trans-trabecular titanium stent coated with heparin which can be placed in the angle, directly through a small clear corneal incision during cataract surgery. It works by directly draining aqueous fluid from the anterior chamber into Schlemm’s canal (Figure 10). A NICE appraisal [IPG396] on the iStent raised no major safety concerns. Several studies have shown promising IOP lowering results when compared to cataract surgery alone.4-5

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Hydrus Microstent: developed by Ivantis Inc and currently in phase IV clinical trials. The microstent is made from an elastic, biocompatible, nickel-titanium alloy (nitinol) and is inserted into Schlemm’s canal as an ‘intracanalicular scaffold’ to increase outflow by dilating and stabilising the canal structure and targeting multiple collector channels.

Suprachoroidal space

Devices such as the Solx Gold Shunt, iStent Supra and CyPass Micro-Stent are designed to be placed into the suprachoroidal space increasing uveoscleral outflow (Figure 11).

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Non-FDA studies of the CyPass microstent appear to show a 35 per cent reduction in IOP at 24 months when used with phacoemulsification and slightly less when used alone. STARflo is a silicone device with 27-µm pores designed by iSTAR Medical. The head of the device extends into the anterior chamber with the body curving through the sclera to the suprachoroidal space. The company is currently working with the FDA on an investigational device exemption (IDE) study which allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data.3

Sub-conjunctiva

Ex-Press Mini Shunt is made from stainless steel and is inserted under a scleral flap during a modified trabeculectomy procedure (Figure 12). It can be argued that when compared to other MIGS devices the Ex-Press is not a true MIGS procedure as the patient would still undergo a trabeculectomy. The belief is that the fixed small lumen from the Ex-Press provides for a more controlled IOP outcome and lower risk of post-operative hypotony.

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The Xen implant (from Aquesys) is a soft, compressible and tissue-conforming gel stent (Figure 13). The device and its pre-loaded injector can be used combined with cataract surgery, or as a standalone procedure. The stent is an ab interno 6mm medical device with a 45µm bore which bypasses the TM, permitting aqueous outflow from the anterior chamber to the subconjunctival space. It is CE marked and currently undergoing phase IV FDA approval.

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The InnFocus MicroShunt works on a similar principle to the Xen implant. It has a 70-µm lumen and is about 8.5mm in length.

Conclusion

The decision to perform glaucoma surgery, and the choice of procedure should be taken on a case-by-case basis after a comprehensive risk-benefit analysis and discussion with the patient. Modern trabeculectomy techniques can minimise potential early and late complications. Glaucoma drainage devices are more commonly used in refractory secondary glaucomas, when other filtering procedures such as trabeculectomy or non-penetrating surgery are less likely to be successful, or have previously failed. MIGS offer alternative therapeutic options. Many of the newer MIGS procedures have yet to be validated in robust randomised controlled trials, but hold significant promise in their scope and safety profile in a rapidly developing and exciting field.

Model answers

Which of the following statements about selective laser trabeculoplasty is true?

B It requires lower laser energy

Which of the following is appropriate in managing pupillary block?

A Iridotomy

Which of the following directly reduces aqueous production?

B Cycloablation

To which of the following is aqueous diverted after trabeculectomy?

D Subconjunctival space

For which of thee following is an aqueous drainage implany most likely appropriate?

D Secondary glaucoma

The iStent is coated with heparin. Why?

D Reduces the risk of blood coagultion around the wound site

References

1 Damji Karim F, et al. ‘Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial.’ British Journal of Ophthalmology, 1999; 83: 718-722.

2 Fudemberg, SJ, Myers, JS, Katz, LJ Trabecular meshwork tissue examination with scanning electron microscopy: a comparison of micropulse diode laser (MLT), selective laser (SLT), and argon laser (ALT) trabeculoplasty in human cadaver tissue. Invest Ophthalmol Vis Sci, 2008;49.

3 Gebhart F. New glaucoma devices bring new dimension treatment OphthalmologyTimes. Jun 2015.

4 Samuelson Thomas W, et al. ‘Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract.’ Ophthalmology, 2011; 118: 459-467.

5 Arriola-Villalobos Pedro, et al. ‘Combined iStent trabecular micro-bypass stent implantation and phacoemulsification for coexistent open-angle glaucoma and cataract: a long-term study.’ British Journal of Ophthalmology,  2012 96: 645-649.

Dr A Khan and Dr N Hickley are specialist trainees in ophthalmology. Mr Dan Nguyen is a consultant ophthalmologist and the lead clinician for glaucoma at Mid-Cheshire Hospitals NHS Foundation Trust. He is a consultant ophthalmologist at Optegra Eye Hospital Manchester where he also collaborates with Optegra’s Eye Sciences associates