Continuing Education Activity

Cyclodiode laser has traditionally been used to treat high intraocular pressures and refractory cases of glaucoma not amenable to medical or other surgical options. The cyclodiode laser ablates the ciliary processes reducing aqueous humor formation and lowering the intraocular pressure. The development and advancement in cyclodiode laser delivery devices have led to an expansion in treatment options for varying subtypes of glaucoma. This activity reviews the background of cyclodiode laser as a treatment for glaucoma, its mechanism of action, indications, contraindications, surgical techniques available, potential complications, and highlights the role of the interprofessional team in evaluating and managing patients undergoing this treatment.

Objectives:

• Summarize cyclodiode laser devices available and their mechanism of action in glaucoma.
• Outline the indications for cyclodiode laser therapy.
• Describe the various surgical techniques available for cyclodiode treatment.
• Review the complications and risk factors for poor ocular outcomes.

Introduction

Glaucoma represents a spectrum of diseases that culminates in a progressive optic neuropathy characterized by optic disc excavation, loss of the retinal ganglion cells, and eventual visual field loss.[1][2] Intraocular pressure (IOP) is a significant primary risk factor and is the only modifiable risk factor for which treatment can be directed to slow or halt progression.[3] In glaucomatous disease, the main treatment sites to lower IOP are targeted to improve the facility of aqueous outflow from the eye or reduce aqueous production at the ciliary processes.  

Destruction of the ciliary body secretory epithelium to lower aqueous humor production and treat refractory or uncontrolled glaucoma has been advocated since the early 1930s.[4] Cyclodestruction has been performed by various methods, including diathermy, surgical excision, cryotherapy, ultrasound, and laser. Cyclodiode laser has now become the mainstay treatment of ciliary body destruction using an 810 nm laser.[2][5] Various subtypes of cyclodiode laser now exist, from Trans-scleral cyclophotocoagulation (TCP) to Micropulse (MP-TCP) and Endocyclophotocoagulation (ECP).[6]

Anatomy and Physiology

Aqueous humor is produced from the ciliary processes and predominantly drains via the pressure-dependent trabecular meshwork with the residual component of aqueous humor draining via the pressure-independent uveal scleral pathway.

There are approximately 80 ciliary processes, which are projections arising from the ciliary body, an encircling ring of smooth muscle lining the inner wall of the sclera. These ciliary processes consist of a double-layer of epithelium protruding into the anterior chamber overlying a core of stroma and fenestrated capillaries. From the external surface of the eyeball, these ciliary processes are located approximately 1.5 mm posterior to the corneoscleral limbus.[7][8]

The continuous-wave TCP diode laser emits laser energy at a wavelength of 810 nm. When directed at the ciliary processes, it causes ablation of the ciliary epithelium resulting in homogenous blanching and shrinking of the ciliary processes. Histopathologic studies have demonstrated significant damage to the pars plicata and surrounding tissues, including the sclera, pars plana, and iris root. Adjacent damage to the pars plana provides another mechanism by which cyclodiode acts by enhancing uveoscleral outflow.[5] 

Unlike the continuous-wave TCP, MP-TCP delivers a series of short, pulsed repetitive bursts of laser energy in on/off phases, in which the 'off-phase' allows time for surrounding tissues to cool, therefore lessening propagation of thermal damage while still lowering IOP.[5][9] In contrast to TCP, ECP laser is performed under direct visualization of the ciliary processes resulting in localized shrinkage of the ciliary processes and reduced thermal damage to surrounding tissues.[5][8]

Indications

Cyclodiode laser has traditionally been reserved for patients who have failed previous drainage surgery or suffer from refractory glaucomatous conditions, including neovascular, traumatic, aphakic, silicone-oil induced, inflammatory, and congenital/developmental glaucoma. Furthermore, blind painful eyes or eyes with poor visual potential are also candidates. Cyclodiode laser is also recommended in eyes with significant conjunctival scarring from previous surgery, trauma, or inflammation.[2][5] 

Cyclodiode has also been described in cases of acute angle-closure glaucoma unresponsive to conventional medical and laser treatment allowing the IOP to stabilize and inflammation to subdue before more definitive surgical procedures are undertaken.[10]

Cyclodiode can also be utilized in those non-surgical candidates and in those who display poor compliance to treatment.

Increasingly, cyclodiode is seen as a primary treatment option even in eyes with good visual potential. This is particularly more evident in developing countries as a viable long-term treatment option.[11][12][13]

MP-TCP should be considered if available, especially in eyes at higher risk of post-operative complications due to its more favorable safety profile.[9]

ECP is commonly combined with cataract extraction but can equally be used as a primary intraocular procedure.[7]

Contraindications

Cyclodiode laser is generally not recommended in phthisical eyes with disorganized internal structures or where other alternative and more effective treatment modalities are available, especially in eyes with good vision or at risk of macular edema.[1]

ECP is not recommended in patients with advanced pseudoexfoliation due to the material obstructing energy uptake.

Uveitic patients or neovascular glaucoma cases must also be considered carefully due to their risk of severe inflammation and hypotony post-operatively.[7]

Equipment

The TCP unit is a portable compact device that consists of a semiconductor solid-state diode laser system that emits laser energy at 810 nm. This device is connected to a handpiece in the shape of a curved footplate, matching the spherical curvature of the sclera and enabling laser energy delivery.[14][15] 

The laser energy is transmitted through a 600 um diameter quartz fiber oriented within the handpiece 1.2mm posterior to the limbus. A tip protrudes 0.7mm beyond the probe to provide indentation on the ocular surface, thereby improving laser energy effectiveness. The continuous-wave laser energy is administered with the handpiece aligned to the visual axis on the conjunctiva surface for the duration of the desired burn.[15][16]

The MP-TCP is also a portable device connected to a handpiece that, on contact with the conjunctiva, similarly delivers laser energy to TCP.  Unlike the continuous-wave TCP, the MP-TCP device is set on micropulse delivery and with specific on-off times.[9]

The ECP probe is inserted intraocularly on an 18-20G handpiece and consists of an 810 nm diode laser, 175 W xenon light source, a helium-neon laser aiming beam, and a video imaging camera. The endoscope provides a 110 to 160-degree field of view. This probe can be used in a pulsed or continuous-wave mode. ECP requires the addition of an operating microscope and intraocular instrument set up.[5][7][8]

Personnel

This procedure is routinely performed in the operating theatres or dedicated minor operating rooms due to the hazards of laser scatter. The health care professionals undertaking this procedure include the primary ophthalmic surgeon with the assistance of a scrub nurse and/or theatre team. The ophthalmic surgeon may administer a peri/retrobulbar block, or this may be performed by a supporting anesthetist if available.[17]

Preparation

Appropriate patient selection and discussion regarding potential benefits, risks, recovery expectations, and complications are mandatory. Similar to incisional glaucoma procedures workups, the surgeon should take into account the patient's general health, including the status of the other eye. The patient must be assessed as to their anesthetic suitability, whether they are a candidate for local anesthesia under peribulbar/retrobulbar block or whether they require a general anesthetic assessment.[16]

A complete ocular examination and subsequent biometry measurements for IOL selection are required if performing ECP with combined cataract surgery. 

This assessment should consider any concurrent ocular inflammation and preoperatively control this as necessary. Along with factoring in any potential future interventional surgical operations the patient may later undertake and consider sparing the superotemporal quadrant of conjunctiva if deemed a possibility.

Technique or Treatment

During the laser procedure, protective safety wear must be worn by all participants in the room to avoid inadvertent laser scatter. 

TCP

If performed under local anesthesia, a peribulbar block or retrobulbar block is administered preoperatively. The patient may also receive sedation or, in rare cases, a general anesthetic.[5] The diode laser unit is calibrated to the user's desired settings, typically 1000 to 2000 mW for 1500 to 2000 ms duration.[17]

The patient remains supine on the bed, and a speculum may be inserted to obtain adequate exposure of the eye.[4]

It is recommended the ciliary body be identified with a handheld transilluminator before treatment to visualize the dark band of the ciliary processes, and this is particularly important in congenital cases where there may be distorted limbal anatomy.[15][16][17] Avoiding the 3 and 9 o'clock positions, representing the long ciliary artery and nerve, the handpiece is aligned with the heel of the footplate adjacent to the limbus with the probe directed vertically in line with the visual axis.[4][5] The laser burns are applied around the limbus spaced half the width of the handpiece apart from one another by approximately 2 mm. This typically represents six burns per quadrant.[14][18]

The power is increased in increments from 150 to 250 mW/shot until an audible pop is heard, implying an excess of power resulting in an explosion of the ciliary processes and surrounding tissues. From here, the power level is titrated to just below the audible popping noise by similar increments. Depending on the desired IOP-lowering effect, 180 to 360 degrees can be administered to the eye, ranging from 12 to 40 spot burns.[5]

Postoperatively, topical corticosteroid drops are prescribed 4 to 8 times per day; depending on patient characteristics and clinician discretion, anti-ocular hypertensives are usually continued postoperatively initially and then tapered according to the postoperative IOP response.[11][14]

MP-TCP

Similar to TCP, this procedure is generally performed under local anesthesia, and the patient is positioned as per TCP.

The MP-TCP device is set to pulse with specified on/off time frames, typically 0.5 ms 'on' and 1.1 ms 'off,' with power ranging from 1600-2400 mW.

A viscous coupling gel is applied to the eye to enable sustained contact of the probe to the ocular surface. The probe is placed adjacent to the limbus on the sclera, and the handpiece is aligned perpendicularly to the globe. The probe is then moved in a smooth continuous back and forth painting motion with constant gentle pressure on the eye along the arc of the limbus coursing over each quadrant or hemisphere. This technique similarly spares the 3 and 9 o'clock regions. Unlike TCP, there is no audible pop heard to define an endpoint of maximal recommended power settings. Each quadrant receives 10 to 15 seconds of sweeping laser application and can undergo 3 to 5 repeat passes, with the total duration of laser application ranging from 80 to 360 seconds. Postoperative drops are prescribed as per TCP.[9][19][20]

ECP

Preoperatively, dilating drops are applied to enhance pupillary dilatation for improved access and visualization of the ciliary processes. Like TCP and MP-TCP, a peribulbar block is administered, or the procedure is performed under topical anesthetic with adjunct sedation or general anesthesia in rare cases.

ECP is commonly performed at the time of cataract surgery, post crystalline lens removal, and following IOL insertion to avoid inadvertent lens damage and enable deepening of the ciliary sulcus to further facilitate visualization and access.[5][7][8]

ECP is most commonly performed via a limbal approach, with a 2.2 to 3.2 mm temporally based corneal incision. A viscoelastic agent is then inserted into the anterior chamber and the ciliary sulcus to maintain anterior chamber stability and enlarge the space between the lens and posterior surface of the iris.[5][7][8] The endoscope probe is then inserted, and the video monitor view is orientated correctly; the probe is directed towards the ciliary sulcus to view the ciliary processes.

The laser energy can be applied in a painting or sweeping fashion or individually via direct shots upon visualization of the ciliary processes. It is recommended that up to 6 ciliary processes be in view to ascertain the correct working distance for effective laser application.[8] Starting power parameters range from 200 to 300m W, and this is titrated as necessary to produce a whitening effect and shrinkage of the ciliary processes without tissue explosion. Up to 270 degrees of ciliary body can be treated with one corneal incision. However, 360-degree treatment requires an extra nasal or superior corneal incision.  

Viscoelastic is then removed from the anterior chamber via irrigation and aspiration, and the corneal wounds are sealed.

Intracameral or subconjunctival antibiotics and corticosteroids are routinely given at the end of the procedure, followed by topical postoperative steroids and antibiotics.[7][8]

Complications

Complications following diode laser treatment vary depending on the type of diode laser employed, the underlying glaucomatous diagnosis, and the treatment protocol administered.[5]

Commonly observed complications following diode laser include transient mild-moderate discomfort, conjunctival hyperemia, conjunctival burns, conjunctival hyperpigmentation, transient pupillary ovalization, and transient anterior chamber inflammation.

More serious reported complications include hyphaema, vitreous hemorrhage, loss of visual acuity, cataract formation, lens subluxation, malignant glaucoma, choroidal hemorrhage, scleral perforation, hypotony, phthisis bulbi, and sympathetic ophthalmia.[21]

Energy levels in TCP greater than 60J per treatment session are generally found to be at higher risk of developing postoperative hypotony.  Similarly, the greater number of shots delivered in TCP is a significant risk factor for hypotony.[14][21] Other ocular risks factors associated with higher rates of hypotony include neovascular glaucoma and a higher pre-treatment IOP. Sympathetic ophthalmia is an infrequent complication from TCP, to which the exact rate of occurrence is estimated to range from 0.03 TO 0.17%.[21]

MP-TCP is noted to have an improved safety profile compared to traditional TCP regarding rates of hypotony and phthisis bulbi, presumably due to its improved control in reducing collateral thermal tissue damage. Longer treatment duration and higher power settings are associated with higher rates of complications.[19][20][22]

Potential risks from ECP include all of the above for transscleral cyclodiode except for conjunctival surface burns.  Most studies suggest a lower rate of severe postoperative complications compared to TCP, particularly when power levels less than 500mW are applied.[8][9] Given the intraocular nature of this procedure, other risks are present, including damage to the crystalline lens, zonular damage, iris damage, retinal detachment, and endophthalmitis. To date, no cases of sympathetic ophthalmia have been reported from ECP.[5]

Clinical Significance

Although the definitions of success vary, multiple long-term follow-up studies report TCP as having an effective IOP reduction in 34 to 94% of cases with a mean follow-up of 2 to 5 years. Hypotony is reported in up to 10% of cases, phthisical development in up to 5% of cases, and vision loss is reported in up to 28% of cases.[14][16][23] 

Rotchford et al. described refractory and non-refractory glaucoma with good vision treated with TCP. They reported an effective IOP reduction in 79.6%, with no cases of hypotony and median visual acuity loss of 2 lines or more in 30.6%, which was similar to the proportion of vision loss associated following trabeculectomy surgery and was predominantly attributed to glaucomatous progression rather than macular edema.[13] 

More standardized protocols of lower energy delivery display lower rates of serious complications compared to initial studies. Notably, this treatment can assist in reducing the medical burden of anti-ocular hypertensive treatment on patients, particularly in the cessation of oral acetazolamide.[11][14]

Various studies reviewing MP-TCP have reported a success rate between 52 to 74% with a final IOP less than 21 mmHg or with a 20% reduction in IOP.  Hypotony has been reported in 5 to 18% of cases, with vision loss of 2 lines or more occurring in 9-19% of cases. Of note, the higher rates of documented complications were associated with longer treatment duration.  MP-TCP has been documented to lower IOP and reduce treatment medication burden effectively but with lower rates of significant complications compared to TCP.[20][22][24]

Multiple comparative trials reviewing ECP in cases of adult refractory glaucoma describe a success rate between 74 to 90% with a final IOP of 21 mmHg or less. Hyptony has been reported in up to 8% of cases, phthisis bulbi in 3% of cases, and vision loss in up to 6% cases.[8] 

ECP appears to be an emerging treatment modality, with initial studies documenting its success in refractory glaucoma.[25] Recent studies have shown ECP  to be comparable to Ahmed drainage devices following previous failed tube surgery.[26] Notably, ECP can be combined with cataract surgery and other accessory outflow procedures to enhance IOP lowering effects.

Cyclodiode laser is an emerging and growing treatment in managing glaucoma not solely relegated to refractory cases. The expansion of diode laser delivery devices has further led to the development and refinement of cyclodiode laser as a primary procedure in the developing world and even in eyes with less advanced glaucoma and good visual potential.[27][28]

Enhancing Healthcare Team Outcomes

Cyclodiode is an evolving treatment in the management of glaucomatous disease, not solely resigned to managing refractory cases. A thorough preoperative workup and assessment must be completed to ensure patient suitability and attain satisfactory IOP reduction while minimizing potential postoperative complications. The patient is consented to and made aware of other treatment modalities that can be considered.

On the day of surgery, the interprofessional team consists of an ophthalmic surgeon, ophthalmic nurses, and operating room staff. The team is required to ensure consent is obtained and the eyes for surgery are appropriately marked. During the procedure, local laser safety protocols and procedures must be adhered to. Postoperatively, the nursing staff will ensure the patient's prescription is available, inform them of the drop regime, educate the patient on potential symptoms and complications, and arrange further follow-up in the eye clinic.