Cyclodestructive Procedures

■The main advantages of transscleral cyclodestructive procedures compared to other glaucoma surgical procedures are (a) ease of performance and (b) possibility of retreatments.

■Both transscleral cyclocryocoagulation and cyclophotocoagulation using either Nd:YAG or diode laser are characterized by (a) a comparable success rate and (b) no linear dosage–efficacy relationship.

■Because transscleral cyclophotocoagulation acts more selectively (by melanin absorption) than cyclocryocoagulation, (a) postoperative inflammatory reaction is less intense and (b) the risk of further scleral damage, such as scleral atrophy from scleritis, is lower.

■There is a strong age-dependent probability of success for all cyclodestructive procedures, which is independent of the underlying type of glaucoma.

■Transscleral cyclophotocoagulation has not only a lower risk profile, but also a lower success rate than other surgical procedures in pediatric glaucoma, including secondary glaucoma in pediatric uveitis. It remains a surgical procedure of last choice in children.

■Transscleral cyclophotocoagulation offers a good therapeutic opportunity in older patients with uveitic glaucoma after other glaucoma surgery has failed. Probably it has the best benefit–risk ratio in scleritis-associated glaucoma if parameters of application are reduced.

■Endoscopic cyclophotocoagulation is an intraocular procedure, which allows more precise diode laser application under direct visualization of the ciliary processes. Whereas the results in refractory glaucoma are encouraging, success rate is much lower in pediatric glaucoma. More experience is needed with this treatment modality concerning inflammatory glaucoma.

17.1 Introduction

Secondary glaucoma is a common, frequently serious complication of inflammatory ocular disease. Glaucoma in inflammatory eye disease is characterized by its heterogeneity in etiology, pathogenesis, and a wide range of different clinical pictures and circumstances, such as scleritis, episcleritis, uveitis, keratouveitis, previous surgical intervention, response to steroids, and others. Surgical procedures such as trabeculectomy are associated with the risk of failure or activation of the inflammatory process.

Cyclodestructive procedures are typically indicated in patients with advanced and refractory glaucoma as a treatment option of second or last choice and are one way of treating severe glaucoma as a result of an underlying, usually persistent, inflammatory eye disease. Different transscleral procedures have been developed, including cyclocryocoagulation and contact and noncontact laser procedures using the diode laser, Nd:YAG, or ruby laser. Today, clinically relevant transscleral cyclodestructive procedures are:

–Contact diode laser cyclophotocoagulation

–Contact Nd:YAG laser cyclophotocoagulation

–Cyclocryocoagulation

Transscleral cyclocryocoagulation still remains a widely used cyclodestructive procedure since its introduction 17 in clinical practice by Bietti in 1950 [19]. The principal mechanism is destruction of epithelial as well as vascular and stromal components with hemorrhagic microcirculatory infarction of the ciliary body resulting in

ciliary body atrophy [15].

Nd:YAG and diode laser are the energy sources of choice for transscleral cyclophotocoagulation. Cyclodestruction is achieved by transscleral application of infrared light (wavelength diode laser 805–810 nm, Nd:YAG 1,064 nm), which is mainly absorbed by the pigmented epithelium of the ciliary body, resulting in destruction of the ciliary epithelium and coagulative necrosis of the ciliary body stroma [27]. Hemorrhagic infarction by photothrombosis and rarefication of the ciliary body microvasculature is probably a strong synergistic mechanism in the decrease of intraocular pressure (IOP) [24].

A relatively new way of cyclodestruction is endoscopic cyclophotocoagulation under direct visualization of the ciliary processes by fiber-optic systems. The diode laser is the energy source of choice for fiber-optic systems.

17.2Effectivity and Safety of Transscleral Cyclocryocoagulation in Advanced Glaucoma

Transscleral cyclocryocoagulation has been an established clinical method for lowering the IOP in advanced, mostly secondary glaucoma for more than 50 years. In heterogeneous glaucoma populations, a success rate between 30% and 100% (depending on different success criteria, study criteria, glaucoma subtypes, follow-up periods, and so on) has been reported in the literature [4, 6]. The retreatment rate is between 17% and 43%. In different types of pediatric glaucoma, a success rate of 66% was reported. However, an average number of 4 treatment sessions per eye was needed to obtain this result [30]. Most of the serious complications (hypotonia, phthisis bulbi, anterior segment ischemia) were found after 360° cyclocryotherapy. After 180° cyclocryotherapy, bulbus hypotonia has been reported in up to 10%, phthisis bulbi between 3% and 12%.

17.3Effectivity and Safety of Transscleral Cyclophotocoagulation in Advanced Glaucoma

In heterogeneous glaucoma populations, overall success rates of transscleral cyclophotocoagulation between 35% and 85% were reported on midterm follow-up periods [1, 5, 12, 25]. Both transscleral contact laser procedures (Nd:YAG or diode laser) seem comparable in efficacy and risk profile. Today, the risk of severe complications such as hypotonia and phthisis bulbi is probably less than 1% after initial transscleral cyclophotocoagulation using established parameters for application. Therefore the use of transscleral cyclophotocoagulation has been extended to various types of glaucoma, including eyes with good visual acuity or eyes with primary and secondary open-angle glaucoma even as a primary or secondary treatment [1, 12]. On the other hand, no linear dosage–efficacy relationship exists, although higher dosages are more effective, including a higher risk of overdosage/complications, than lower dosages [7].

In cases of refractory pediatric glaucoma, a useful reduction in IOP was reported in 72% of treated eyes after a mean of 2.3 treatment sessions in one study [16]. Taking all experiences together, transscleral cyclophotocoagulation shows a clear age-dependent component, resulting in a much lower success rate in children compared to adults (see Sects. 17.4 and 17.6).

Cyclocryocoagulation and cyclophotocoagulation probably are equally effective in decreasing the intraocular pressure in patients with refractory, uncontrolled

glaucoma [11]. The risk of side effects is significantly lower with transscleral laser cyclophotocoagulation than with cyclocryocoagulation (see Sect. 17.8).

Complications of transscleral cyclocryocoagulation and cyclophotocoagulation in advanced (mostly secondary) glaucoma include:

–Mild anterior uveitis (50–100%)

–Severe iridocyclitis (seldom)

–Conjunctival hyperemia/chemosis (cyclocr­ yocoagulation)

–Conjunctival burns (cyclophotocoagulation)

–Scleral atrophy/thinning

–Scleral perforation (seldom)

–Intraocular pressure rise

–Hypotonia

–Phthisis bulbi

–Decrease in visual acuity

–Intraocular hemorrhage

–Cystoid macular edema

–Corneal transplant decompensation/reaction

–Pupil distortion (cyclophotocoagulation)

–Choroidal detachment (with flat anterior chamber—malignant glaucoma)

–Exudative retinal detachment

–Anterior segment ischemia

–Neuroparalytic keratitis/corneal ulceration

–Sympathetic ophthalmia

17.4Transscleral Cyclophotocoagulation in Inflammatory Eye Disease

No large or long-term studies have investigated the efficacy and safety of transscleral cyclophotocoagulation in inflammatory glaucoma.

So far, only one prospective study has been published [23]. In this study, 22 eyes of 20 consecutive patients (9–77 years, mean age 50.3 ± 20.6 years) with inflammatory, medically uncontrollable glaucoma, secondary to chronic uveitis, chemical injury, episcleritis, and necrotizing scleritis with inflammation (see case report) were treated by diode laser cyclophotocoagulation and followed over one year after the initial treatment. Nearly 40% of the eyes had previous failed glaucoma surgery. Within 12 months after the first treatment, intraocular pressure was controlled in 77% of all eyes (72% in uveitic glaucoma). No serious side effects were observed. More than one treatment was necessary in 64% of the patients (mean of 2.0 treatments per eye). The proce-

dure failed in five eyes with uveitic glaucoma (mean of 3.0 treatments in these 5 eyes). Two of the five eyes were aphakic; three eyes had previous failed cyclocryocoagulation (including the child with JCA-associated uveitis) and two had a previous failed trabeculectomy.

In eyes with thin/atrophic sclera (e.g., after scleritis) parameters for application should be reduced to avoid further scleral damage and tissue disruption (see case report). Scleral perforation has been observed in only a few patients after cyclophotocoagulation [2, 10].

Case Report

A 60-year-old female patient developed a severe secondary glaucoma due to recurrent anterior necrotizing scleritis with inflammation in her right eye (Fig. 17.1) [22].

Scleral thinning with focal staphyloma was present circumferentially. At first, control of the inflammatory activity was achieved by immunosuppression using methotrexate. Persistently high IOP values up to 40 mmHg were observed despite maximal medical treatment. Diode laser cyclophotocoagulation (Oculight SLx 810 nm, Iris Med Instruments, CA, USA) was performed under general anesthesia using reduced laser parameters (12 applications, 1 s, 1.25 W per application). Postoperatively, IOP decreased to normal values between 14 and 18 mmHg within a few days and remained stable. No retreatment was needed. Mild anterior uveitis was seen for a few days. No serious complications, especially scleral perforation, occurred. No reactivation of scleritis was seen.

Fig. 17.1  Diode laser cyclophotocoagulation using reduced parameters of application in an eye with anterior, necrotizing scleritis with inflammation after control of inflammatory activity by immunosuppression

Recently, Heinz and coworkers first reported about the results of diode laser cyclophotocoagulation as a primary treatment in children with chronic anterior uveitis (pediatric glaucoma associated with chronic juvenile arthritis) and secondary open-angle glaucoma [14]. In this retrospective study, 19 eyes of 12 patients received diode laser cyclophotocoagulation (retreatment rate nearly 80%) and were followed for a mean time of 10 months. Qualified success was achieved in only 32% despite this high retreatment rate. However, no serious complications were observed. In conclusion, cyclophotocoagulation has a much lower success rate in children with uveitic glaucoma than in adults and has a much lower success rate as a primary surgical treatment compared to other surgical techniques (e.g.; goniotomy, trabeculectomy). On the other hand, a very low complication rate is seen.

In conclusion, cyclophotocoagulation seems to be a safe procedure for the treatment of refractory inflammatory glaucoma, but seems to be associated with a lower success rate—especially in children—than other surgical procedures. Therefore cyclophotocoagulation should be regarded as a surgical procedure of second choice in the management of uveitic glaucoma in younger patients with uveitis. It might be helpful to gain time before surgical treatment is performed. Diode laser cyclophotocoagulation may become the surgical procedure of choice in treating secondary glaucoma due to chemical injury and also in scleritis-associated glaucoma, using reduced parameters for application.

17 17.5 Endoscopic

Cyclophotocoagulation

The predictability of transscleral cyclophotocoagulation is limited by the surgeon’s inability to visualize the target tissue and to assess completeness of treatment. Endoscopic cyclophotocoagulation using a diode laser is an intraocular procedure to treat the ciliary processes under direct endoscopic visualization. Endoscopic cyclophotocoagulation can be performed through a limbal incision via the anterior chamber (in pseudophakic patients) or a pars plana incision.

Early results showed a successful outcome in more than 80% of the treated eyes within 2 years of follow-up in patients with refractory glaucoma of different origin [8].

Direct prospective comparison between endoscopic cyclophotocoagulation and the Ahmed glaucoma valve showed a comparable success rate of 74% and 71% respectively in patients with refractory glaucoma at 2 years of follow-up [18]. Endoscopic cyclophotocoagula-

tion is a moderately effective procedure in the treatment of pediatric glaucoma. Neely and Plager (2001) reported a success rate of only 43% in pediatric glaucoma of different origin [20]. All significant postoperative complications, including retinal detachment, occurred in aphakic patients.

No study has been performed concerning the efficacy/safety of the procedure in secondary glaucoma due to inflammatory eye disease.

17.6Risk Factors for Failure of Treatment

17.6.1 Age

It has been reported by several authors that patients with repeated cyclophotocoagulation or cyclocryocoagulation are significantly younger than those with only one successful treatment [6, 28]. Furthermore, a clear relationship between success of treatment using diode laser cyclophotocoagulation and age of patients has been demonstrated [25]. Success rate was significantly better in patients above the age of 50 years than in patients below the age of 50 years. This age-dependent success rate of cyclophotocoagulation is not confined to very young patients (children or adolescents) only. A recently published work by Heinz and coworkers demonstrated also poor results of diode laser cyclophotocoagulation in children with uveitis, which may be predominantly associated with age of these patients more than the type of secondary glaucoma [14].

The reason for the relationship between age and success of cyclodestruction is not clear. Age-dependent changes in structure and function of the ciliary body epithelium and stroma may explain why the ciliary epithelium seems to be more susceptible to cyclodestruction in the elderly. Additionally, longstanding increase of IOP in chronic glaucoma results in pronounced atrophy of ciliary body structures, which may predispose to further damage.

17.6.2Aphakia and Other Previous Ocular Surgery

Previous ocular surgery may be a risk factor for failure of cyclophotocoagulation in primary as well as secondary glaucoma [12, 25]. Aphakia, especially, is a significant risk factor for failure of cyclodestruction.

Cyclodestructive Procedures

17.6.3 Secondary Angle-Closure Glaucoma

Subtotal or total secondary angle-closure glaucoma as a result of peripheral anterior synechiae is a special risk factor for failure, because of the overwhelming amount of subtotal destruction of the ciliary body epithelium that must be achieved to lower IOP efficiently. A higher failure rate that leads to retreatment may be ultimately associated with a higher risk of hypotonia and phthisis. Nevertheless, good clinical results using diode laser cyclophotocoagulation have been reported in chronic angle-closure glaucoma [17].

17.7 Practical Approach

17.7.1 Anesthesia

In cyclocryocoagulation, parabulbar or retrobulbar anesthesia is used, but subconjunctival anesthesia using cocaine, lidocaine 2%, or mepivacaine 2% is also effective.

In transscleral cyclophotocoagulation, subconjunctival anesthesia is a simple but effective and very safe method of anesthesia [26]. Oxybuprocaine (or another topical anesthetic eye drop), approximately 4–6 drops, is instilled in the eye. Then, 1–1.5 ml of 2% mepivacaine/2% lidocaine is placed beneath the conjunctiva (Fig. 17.2). The needle is carefully placed 6–8 mm from the limbus to avoid bleeding at the injection site. The eye is patched for 10 minutes with a low-pressure bandage. In general, no oral or intravenous sedation is needed.

Fig. 17.2  Subconjunctival anesthesia using scandicaine 2% before diode laser cyclophotocoagulation. Bleeding of conjunctiva should be avoided by careful application and a limbal distance of 6 mm or more (see Fig. 17.3)

General anesthesia may be needed in children or noncompliant adults, or eyes with high risk of perforation by parabulbar or subconjunctival anesthesia (e.g., scleral staphyloma).

17.7.2 Transscleral Cyclocryocoagulation

Usually, six applications lasting 60 s each at −80°C on the inferior or superior 180° of the globe are performed [21]. The anterior edge of a 2.5 mm probe tip should be placed at a distance of about 1 mm from the anterior border of the limbus inferiorly, temporally, and nasally and about 1.5 mm superiorly. At the end of the operation subconjunctival steroid injection should be given in all eyes with uveitis, and steroid ointment should be instilled. Acetazolamide and osmotic agents can be used to control early postoperative IOP peaks in sighted eyes. If no adequate IOP response is obtained 4 weeks after the first treatment, the procedure can be repeated.

17.7.3 Transscleral Cyclophotocoagulation

Transscleral contact Nd:YAG laser cyclophotocoagulation using the Microruptur 3 (Meridian, Bern, Switzerland) is performed with a laser power of 10 W, exposure duration of 0.2–0.4 s (corresponding to 2–4 J/pulse) and 10–20 applications per treatment session [9].

For transscleral cyclophotocoagulation using a diode laser, the laser energy is delivered through a contact fi- ber-optic G-probe (IRIS Endoprobe®) attached to the

Oculight SLx semiconductor diode laser (IRIS Medical Instruments, Inc., CA, USA) (Fig. 17.3).

Typical treatment consists of approximately 20 applications of 2.0 W energy applied for 2.0 s, for not more than 270° (not more than 180° in glaucoma secondary to chemical injury). Energy and duration (1.5 s, 1.5 W) should be reduced in cases of thinned sclera (e.g., necrotizing scleritis) and if audible pops are heard, indicating disruption of the ciliary body epithelium. After surgery, 0.5 ml of dexamethasone is applied subconjunctivally, and topical corticosteroids, rimexolone or prednisolone acetate 1%, are administered for at least 2 weeks. Antiglaucoma medication is continued and gradually withdrawn during the follow-up period, starting with oral carboanhydrase inhibitors. If inadequate IOP response is obtained 4 weeks after the first treatment, the procedure can be repeated.

In normal eyes the use of transillumination does not seem to be necessary for exact placement of the laser or cryo probe over the pars plicata. However, transillumi-

Fig. 17.3  The “G-probe” is placed parallel to the optical axis with the anterior edge of the probe at the anatomical limbus

nation may be used for better localization of the ciliary band in eyes with abnormal dimensions or pathological changes of the anterior segment of the eye [29]. In retreatments, transillumination helps identify atrophic areas from previous cyclodestruction and permits more focused application.

17.8 Complications and Management

Severe complications after cyclodestructive procedures are relatively rare, especially after transscleral cyclophotocoagulation. However, early complications such as 17 severe iridocyclitis and decompensated IOP may occur and cause pain (Figs. 17.4 and 17.5). Therefore, frequent

Fig. 17.4  Application of diode laser energy using the G-probe in an area of subconjunctival bleeding. Conjunctival burning occurred due to stronger absorption of laser energy by the conjunctiva

Fig. 17.5  Anterior displacement of laser energy to the iris root may result in irreversible pupil distortion and severe iritis

follow-up of all patients is mandatory in the early postoperative phase.

Early postoperative increase of IOP can be treated by short-term use of acetazolamide and, rarely, by administration of osmotic substances. A steroid-responsive effect does not occur within the first days of treatment, so reduction of topical corticosteroids is probably not helpful in managing an early increase in intraocular pressure.

Early iritis is seen in nearly 50–100% of all patients after cyclodestructive treatment within the first few days after treatment. It is most often a bland, transient inflammatory reaction and should be manageable with topical prednisolone acetate 1% three to five times daily for 1–2 weeks postoperatively. A severe iridocyclitis associated with fibrinous reaction and pain may occur, most often some days after the cyclodestructive treatment has been performed. A more intensive treatment using prednisolone acetate 1% every hour for some days and occasionally high-dose systemic steroid treatment may be necessary to control the inflammation.

Scleral perforation is a very rare complication after transscleral cyclodestruction and can be avoided by reduction of application parameters in patients with preoperative scleral thinning. If scleral perforation occurs, a scleral patch is indicated to avoid hypotonia and endophthalmitis.

Hypotonia and phthisis bulbi are late and rare complications after cyclophotocoagulation and cyclocryocoagulation. In severe cases of prolonged hypotonia, the therapeutic options are limited. An inapparent cyclodialysis cleft should be considered. Intensive topical steroid therapy, discontinuation of all IOP-reducing medication, and occasionally injection of viscoelastic substances into the anterior chamber may be helpful to induce recovery of IOP.

Cyclodestructive Procedures

Sympathetic ophthalmia, malignant glaucoma, and retinal detachment have been reported in some patients after cyclophotocoagulation as well as after cyclocryocoagulation [3, 13]. A causal relationship between cyclodestructive procedures and sympathetic ophthalmia is doubtful.

Take Home Pearls

■Cyclodestructive procedures remain import­ ant treatment options in advanced glaucoma of different origins after medical antiglaucoma therapy or surgical procedures have failed.

■In comparison to cyclocryotherapy, transsc­ leral cyclophotocoagulation (Nd:YAG or diode laser) shows comparable efficacy but a signifi­ cantly lower risk profile.

■Transscleral cyclophotocoagulation is a rela­ tively safe procedure in eyes without active in­ flammatory process. Cyclodestruction should only be performed in eyes with chronic intra­ ocular inflammation if an adequate anti-in­ flammatory regimen is in place.

■Transscleral cyclophotocoagulation may be the surgical procedure of choice in treating secondary glaucoma caused by chemical in­ jury and in scleritis-associated glaucoma.

■Factors which limit success of cyclophotoco­ agulation are: age < 50 years, aphakia, previ­ ous ocular surgery, and total or subtotal sec­ ondary angle-closure glaucoma.

■Since many patients with chronic intraocular inflammation and secondary glaucoma are younger, the effect of cyclodestruction is often transient with a high rate of retreatment. The hypotensive response to cyclodestruction is especially poor in children with persistent an­ terior uveitis. Cyclodestruction remains a pro­ cedure of second choice in younger patients with glaucoma.

■Moderate improvement of the surgical success rate can probably be achieved by endoscopic cyclophotocoagulation in adult refractory glaucoma because of the direct visual control of the location and intensity of the cyclode­ structive effect. More experience is needed with this procedure to refine the risk–benefit ratio. The procedure is probably only moder­ ately effective in pediatric glaucoma.

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