Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

Figure 41.2 Transscleral diode cyclophotocoagulation, showing use of G-Probe to position fiberoptic 1.2 mm from surgical limbus and to space adjacent laser applications.

An ophthalmic laser microendoscope (Endo Optiks Inc., Little Silver, NJ) has also been developed which houses fiberoptics for a video monitor, diode laser endophotocoagulation, and illumination in a 20-gauge probe (31) (Fig. 41.3). The diode laser has 1.2 W of power output and is focused visually by means of a 670 nm (2.0 mW) laser aiming beam. Optimal focal distance for the laser is 0.75 mm from the tip of the probe. Depth of focus while viewing is from 0 to 20 mm, and the camera lens has a 70degree field of view.

Krypton Lasers

Transscleral cyclophotocoagulation has also been performed with a retinal krypton laser, delivered by a

contact probe. The shorter wavelength results in poorer scleral transmission but better uveal pigment absorption than with the Nd:YAG laser, and histologic lesions in rabbits were similar with the two lasers (32). Successful clinical results were reported, using 4 to 5 J of energy, 10-second exposures, and firm compression with the probe (33, 34).

Figure 41.3 A: An ECP unit (Uram E2, Endo Optiks, Little Silver, NJ), including laser, monitor, and foot pedal. B: An ECP probe (20 gauge). A 27-gauge cannula tip is shown above for size comparison. (From Lin SC. Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma. 2008;17:238-247.)

Theories of Mechanism

The mechanism by which transscleral cyclophotocoagulation reduces IOP is not fully understood. The prevailing theory is that it reduces aqueous production by damaging the pars plicata, although it is unclear whether this is due to direct destruction of the ciliary epithelium or reduced vascular perfusion. Still other investigators suggest that the primary mechanism may be increased outflow through an effect on the pars plana.

Evidence for Reduced Aqueous Production

Rabbit studies have demonstrated that transscleral application of Nd:YAG laser energy results in coagulative necrosis of the ciliary epithelium, including destruction of ciliary vessels in the overlying area (35).

Studies of human autopsy eyes revealed structural changes of the ciliary body similar to those seen in rabbits. The gross appearance of lesions created by the noncontact, free-running Nd:YAG laser was a white elevation of the ciliary epithelium (36). The histologic correlate was a blister-like elevation of the epithelial layers from the adjacent stroma, with marked disruption primarily of the pigmented epithelium but minimal change in the ciliary muscle and sclera in the path of the laser beam (37, 38) (Fig. 41.4). In contrast, the histologic appearance of lesions created by the contact, continuous-wave Nd:YAG laser was a smaller, more coagulative effect on the epithelium with less of the blister-like elevation (38, 39). One study showed a more full-thickness thermal effect, including sclera (38), while another showed no scleral alteration (39). A videographic study of human autopsy eyes also showed that shorter-duration Nd:YAG laser exposures caused greater tissue disruption, whereas the more prolonged, continuouswave exposures produced a more coagulative, shrinkage-like lesion (40).

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Figure 41.4 Light microscopic view of human autopsy eye treated with transscleral thermal, pulsed Nd:YAG cyclophotocoagulation showing blister-like elevation of disrupted ciliary epithelium (arrows) with minimal ciliary muscle and scleral damage. Defect on scleral surface was created by needle with India ink to mark center of laser track after laser application.

Histologic studies have also been performed on human eyes that were enucleated at some point after transscleral Nd:YAG cyclophotocoagulation. In one series of eyes treated with the noncontact, freerunning Nd:YAG laser a few days before scheduled enucleation, the structural changes were the same as those seen in human autopsy eyes with the addition of fibrin and scant inflammatory cells between the disrupted epithelial layers and stroma (41). No changes in ciliary body vasculature were observed. A clinicopathologic study of three eyes enucleated 2 weeks, 8 weeks, and 17 months after noncontact Nd:YAG cyclophotocoagulation revealed destruction of the nonpigmented and pigmented ciliary epithelium, occlusion of capillaries, and stromal necrosis, with subsequent hyperplasia of the epithelial layers, fibrosis, and near-total atrophy of the ciliary processes (42). Histologic evaluation of another eye, which had received the same laser treatment 70 days before enucleation for hypotony and pain, revealed pigment disruption and granulomatous inflammation of the ciliary body (43). Two eyes treated with contact, continuous-wave Nd:YAG transscleral cyclophotocoagulation 1 day before enucleation for melanomas revealed epithelial necrosis and partial capillary thrombosis of the ciliary body with slight scleral damage (44).

Figure 41.5 A: Histopathology of rabbit ciliary processes 1 month after contact transscleral diode cyclophotocoagulation. Note coagulative necrosis of the ciliary tissue with cyclitic membrane formation (X40). B: Histopathology of rabbit ciliary processes 1 month after diode laser ECP. Disruption of ciliary architecture is shown but a relatively normal process with patent vessel is seen to the left (×40). C, cornea; CP, ciliary processes; I iris. (From Lin SC. Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma. 2008;17:238-247.)

Histologic observations with both light microscopy and scanning electron microscopy reveal that tissue treated with transscleral diode cyclophotocoagulation shows pronounced tissue disruption of the ciliary body muscle and stroma, ciliary processes, and both pigmented and nonpigmented ciliary epithelium.

ECP-treated tissue, however, only exhibits pronounced contraction of the ciliary processes with disruption of the ciliary body epithelium, sparing of the ciliary body muscle with less architectural disorganization (Fig. 41.5) (45). A study of vascular effects of transscleral compared with ECP in rabbits demonstrated immediate and severely reduced or nonexistent blood flow in the areas of treatment after both types of procedures (46). After 1 week and 1 month, however, transscleral-treated processes remained nonperfused, whereas ECP processes showed some reperfusion that increased over time. The authors concluded that chronic poor perfusion of the ciliary after transscleral diode cyclophotocoagulation may partly account for its efficacy and the significant complications, including hypotony and phthisis. Late reperfusion of this region after ECP may provide some insight into the differences in efficacy and complication rates, compared with transscleral diode cyclophotocoagulation. Evidence for Increased Aqueous Outflow

Although the aforementioned studies confirm that transscleral cyclophotocoagulation can destroy tissues of the pars plicata, most likely by a direct effect on the ciliary epithelium, this does not prove that direct destruction of the pars plicata is an essential element in the mechanism of IOP reduction. Other studies have shown that more posteriorly placed lesions over the pars plana or even peripheral retina also decrease the IOP (47, 48, 49 and 50). The explanation for this observation could be reduced aqueous production due to the inflammatory response (47), although it is unlikely that this would be a sustained effect. An alternative explanation is enhanced aqueous outflow, either by transscleral filtration or uveoscleral outflow (48, 49, 50, 51 and 52). In a monkey study of contact, continuous-wave Nd:YAG cyclophotocoagulation, in which right eyes were treated over the pars plicata, 1 mm behind

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the limbus, and left eyes were treated over the pars plana, 3 mm behind the limbus, IOP reduction occurred in both eyes but returned to baseline by 8 weeks in the former group, whereas the latter group maintained IOP reduction for the 6-month observation period (51). Histology of the latter eyes suggested enhanced uveoscleral outflow by showing tracer elements in enlarged extracellular spaces of the ciliary stroma from the anterior chamber to the suprachoroidal space. In a similar clinical trial in which laser applications were placed either 1.5 mm or 3.0 to 4.0 mm behind the limbus, the latter group had a higher percentage of eyes with sustained IOP reduction, although they also had received more than twice as many laser applications (52). In another clinical trial using noncontact Nd:YAG

cyclophotocoagulation in which all treatment parameters were kept constant except for laser placement 1.5 or 3.0 mm posterior to the limbus, the former group had significantly lower IOP and required fewer repeated treatments during 6-month follow-up (53).

In summary, the most likely mechanism of IOP lowering by transscleral cyclophotocoagulation is reduced aqueous production through destruction of ciliary epithelium. However, alternative possibilities, including reduced inflow due to ciliary vascular disruption or chronic inflammation, or increased outflow due to pars plana-transscleral outflow or enhanced uveoscleral outflow, have not been ruled out. Techniques

Preoperative and Postoperative Management

Unlike most other glaucoma laser procedures, the intraoperative pain associated with transscleral cyclophotocoagulation is such that retrobulbar anesthesia is required, although this has been omitted by some surgeons with the contact, continuouswave technique (44). Also, unlike most other laser procedures and other transscleral cyclodestructive procedures, postoperative IOP rise is not a frequent problem, and special preoperative and postoperative measures, such as the use of topical apraclonidine, are usually unnecessary. For ECP, peribulbar, topical, or intracameral anesthesia may be selected. Postoperative inflammation can be a significant problem, requiring special prophylactic measures. One approach is to give a subconjunctival injection of a short-acting steroid at the end of the procedure and to prescribe topical atropine and steroid for approximately 10 days (54). Use of preoperative glaucoma medications is continued, except for miotics, until IOP reduction allows discontinuation. Postoperative pain is typically mild, and a weak analgesic is usually sufficient. IOP is usually checked a few hours after the procedure, the following day, and then thereafter as required.

Laser Settings and Protocols

The histologic studies with human eyes, as previously described, have been used to establish protocols for clinical trials. However, preferred settings differ among surgeons, and the optimum protocols have yet to be established.

Nd:YAG Noncontact, Thermal Mode, and Continuous Wave. These instruments are no longer available but appear to have a similar mechanism of action as contact, thermal mode lasers.

Semiconductor Diode, Continuous Wave. With the Oculight SLx, the G-Probe footplate is placed on conjunctiva with the short side adjacent to the limbus, which positions the fiberoptic tip 1.2 mm behind the limbus. Initial settings are 1750 mW and 2 seconds (30). If a popping sound is heard with the initial application, the power is reduced by increments of 250 mW until no pop is heard. If no pop is heard with the initial application, the power is increased by the same increments until the sound is heard, and then it is reduced by one increment. Videographic studies of human autopsy eyes have shown that this audible indicator represents excessive tissue destruction, whereas a power setting one increment below this level is believed to provide optimum tissue damage (55). Some surgeons prefer lower power and longer duration burns, such as 1250 mW at 4 seconds in heavily pigmented eyes and 1500 mW at 3.5 seconds in lightly pigmented eyes (56). The laser applications are spaced circumferentially by placing the side of the G-Probe footplate adjacent to the indentation mark of the previous fiberoptic placement. The original protocol involved 17 to 19 applications for 270 degrees (30), although 24 applications for 360 degrees may provide more effective IOP reduction. We suggest avoiding the 3- and 9-o'clock positions because this may reduce the chances of occluding the long posterior ciliary vessels and thus reduce the chance of anterior segment ischemia. This procedure can be performed with the patient supine or reclining in an examination chair or positioned at a standard slitlamp.

The G-probe used with transscleral diode cyclophotocoagulation can be reused several times without loss of power, even if cleaned by alcohol each time (57). More research is needed, however, to determine the best sterilization methods for this probe.

For ECP, a limbal or pars plana approach can be used. In the limbal approach, a paracentesis is created (about 2 mm), usually at the temporal side initially, and the anterior chamber is filled with viscoelastic agent (typically a cohesive viscoelastic such as sodium hyaluronate), which is further used to expand the space between the iris and the intraocular lens. This viscoelastic expansion of the posterior chamber allows for easier approach to the pars plicata with the ECP probe. A pars plana approach is preferred if

there is an anterior chamber IOL or if the anterior segment structures are disrupted or the view is not good (e.g., with a failed penetrating keratoplasty graft). The pars plan approach can be used if eyes have received a previous complete vitrectomy, or where simultaneous vitrectomy can be done.

After orientation of the probe image outside of the eye (with black lettering on a ruler, suture pack, or label), the ECP probe is inserted through the incision and into the posterior chamber. At this time, the ciliary processes are viewed on the monitor and the surgeon's attention can be turned to the monitor (Fig. 41.6). Usually, about five to six processes are viewed and the aiming beam is directed on the apex of the processes. It is important to have the probe oriented as flat as possible (otherwise the aiming beam will focus further posteriorly on the pars plana or ora serrata).

The laser is set at 2000 milliseconds or continuous wave and energy settings with the separate diode laser at 400 to 600 mW (which may need to be adjusted if using the built-in laser). Approximately 120 to 150 degrees of ciliary processes is photocoagulated

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(more can be done with a curved probe). Laser energy is applied to each process until shrinkage and whitening occurs (Fig. 41.7). Raised processes and valleys in between are treated (it is important to treat the entire process that is visible, not just the tip). If excessive energy is used, the ciliary process explodes (or “pops”) with bubble formation, and this should be avoided. Before closure of the wounds with suture material, viscoelastic is irrigated out with balanced salt solution (ideally by using a manual or automated irrigation and aspiration device), taking care to remove viscoelastic from the anterior and posterior chambers to prevent or minimize postoperative IOP spikes. If further treatment is required, an incision can be made superonasally to access the temporal ciliary processes. Usually, it is best to treat at least 270 to 300 degrees (particularly for high starting pressure) (58).

Figure 41.6 Surgeon performing ECP. A video monitor is used to view the ciliary processes during the procedure.

In the pars plana approach, the entry is made about 3.5 mm behind the limbus, avoiding the 3- and 9- o'clock positions so as not to interfere with the long posterior ciliary arteries. An optional infusion port can be created through the pars plana elsewhere or in the anterior chamber.

With ECP, depending on the degree of postoperative inflammation anticipated, subtenons dexamethasone, methylprednisolone (Depo-Medrol), or triamcinolone (Kenalog) is administered at the end of the procedure. Postoperatively, antibiotics, cycloplegics, and aqueous suppressants are given. The patient's eye can be patched overnight (e.g., after peribulbar anesthesia) or left unpatched (if topicalintracameral).

Figure 41.7 Endoscopic view of ciliary processes. A: Untreated processes. B: Treated processes, which are white andshrunken. (Courtesy of Martin Uram, MD, MPH. From Weiss HS, Schwartz KS, Schwartz AL. Laser surgery in glaucoma. In: Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology. Vol 6. Lippincott Williams & Wilkins; 2006:chap 19.)

Clinical Experience Indications and General Results

Transscleral cyclophotocoagulation, as with other cyclodestructive procedures, is typically reserved for patients with refractory forms of glaucoma, such as advanced aphakic or pseudophakic glaucoma, neovascular glaucoma, chronic angle-closure glaucoma, inflammatory glaucoma, tumorassociated glaucoma, and in patients with multiple failed filtering procedures or who have had penetrating keratoplasty (59, 60). It has also been evaluated—w ith inconclusive results—as a primary surgical treatment in developing countries where conventional glaucoma therapy is unavailable (61). Maximum pressure reduction is typically achieved in 1 month, and it is usually desirable to wait at least this long before retreating. Results differ somewhat according to the type of glaucoma. In general, patients with aphakic or pseudophakic eyes have more favorable results, and those with neovascular glaucoma tend to do less well. Patients with glaucoma after penetrating keratoplasty have good IOP response to Nd:YAG cyclophotocoagulation, although graft failure is a problem in some cases (62, 63). Long-term success with Nd:YAG cyclophotocoagulation appears to be about 50% at 10 years, with most failures (40%) in the first year of treatment (64).

Contact transscleral Nd:YAG and diode laser cyclophotocoagulation have also been shown to be beneficial in children with refractory glaucoma (65, 66). Patients with severe uveitis, silicone oil, or severe neovascular glaucoma, and children with glaucoma in an aphakic eye, appear not to do as well in terms of IOP lowering as patients with other indications; in addition, these patients have a higher risk of severe complications, such as inflammation or choroidal detachment (67).

ECP appears to be associated with a lower risk of hypotony, phthisis, and severe vision loss. Hence, it may be considered in eyes with reasonable vision potential where an intraocular procedure would be deemed safe. Some surgeons have advocated using ECP in conjunction with cataract surgery to reduce the burden of medications in patients with glaucoma; further longterm data on efficacy and safety are needed, however.

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Figure 41.8 An eye of a Patient who underwent noncontact transscleral cyclophotocoagulation. A: Slitlamp view at postoperative day 1, showing substantial hyperemia. B: Slitlamp view at postoperative day 7, by which time the hyperemia has improved considerably.

Complications

Cyclophotocoagulation is frequently associated with mild to moderate conjunctival hyperemia, which typically resolves in a few days (Fig. 41.8). Anterior chamber flare and cells are seen in all cases. This is usually mild to moderate, although some patients may develop fibrin clots or hypopyon. Hyphema may also be seen, especially in patients with neovascular glaucoma. The inflammatory response is transient and is routinely managed with postoperative subconjunctival and subsequent topical steroids. Many patients are left with a chronic flare due to a breakdown in the blood-aqueous barrier, but this does not require long-term treatment. A transient IOP rise occurs in a small proportion of patients and usually is clinically insignificant (68). Nevertheless, checking the pressure a few hours after the procedure and the next day is advisable. Postoperative pain also tends to be mild, with many patients requiring no analgesic, and rarely more than a mild pain reliever in the first 24 hours. Inflammation, transient IOP elevation, and pain are all significantly less with laser cyclophotocoagulation, compared with cyclocryotherapy.

Other reported complications have included hypotony with choroidal detachments and a flat anterior chamber (69), vitreous hemorrhages, and cataracts. Several cases of sympathetic ophthalmia have been reported in association with transscleral cyclophotocoagulation (70, 71, 72, 73 and 74). In most cases, the treated eyes had previously undergone incisional surgery, and the sympathizing eyes typically respond promptly to steroid therapy. Cases of malignant glaucoma after Nd:YAG cyclophotocoagulation have also been reported (75, 76). With use of transscleral diode laser, necrotizing scleritis and inadvertent sclerostomy with filtering bleb formation have been reported (77, 78).

The most significant complication associated with transscleral cyclophotocoagulation is loss of visual acuity. Some degree of visual loss may occur in as many as 50% of patients. In many cases, this appears to be associated with the underlying disorder, such as a retinopathy or keratopathy. However, at least one half of the cases of visual reduction are thought to occur as a direct result of the laser treatment (79). The precise mechanisms of the latter are not fully understood, but likely causes include macular edema associated with the inflammatory response and possibly a direct phototoxic effect. One histologic study demonstrated that about 3% of 5% of the energy from laser treatment reaches the macula (80). It is advisable to use transscleral cyclophotocoagulation with caution in eyes with good visual potential. When performing the procedure, it is wise to use the lowest power and exposure durations possible and to keep the probe perpendicular to the sclera so that excess energy is transmitted more anteriorly instead of being directed toward the macula.

With ECP, complications include fibrin exudates, postoperative IOP spikes, hyphema, cystoid macular edema, decreased vision, and choroidal detachment; rarely, serious complications, such as retinal detachment and hypotony, may occur, primarily in pediatric cases (81). Although not reported in the

literature, endophthalmitis and choroidal hemorrhage are potential severe complications, owing to the intraocular nature of the surgery. On occasion, early postoperative IOP spikes may be related to retained viscoelastic material. Iris hooks may provide a safe alternative for elevation of the iris during ECP treatment and may be particularly advantageous in eyes with aphakia or posterior capsule compromise, in which viscoelastic removal is made more difficult (58).

Influence of Treatment Variables

Exposure Duration. Histologic and in vitro videographic studies of transscleral Nd:YAG cyclophotocoagulation have revealed an influence of exposure duration on tissue responses of the ciliary body. The thermal mode (20 milliseconds) produces an explosive, blister-like lesion, whereas the continuous-wave mode (usually 0.5 to 2.0 seconds) produces a more gradual contraction and coagulation of the tissue (36, 37, 38, 39 and 40).

Nd:YAG versus Diode Wavelengths. As previously noted, semiconductor diode lasers have the physical advantages of being compact and portable with no special electric outlet or watercooling requirements and with solid-state construction that is relatively durable and requires minimal maintenance. The different wavelengths of the Nd:YAG (1064 nm) and diode (750 to 850 nm) lasers also impart variable biologic effects, with the latter having less effective scleral transmission and increased light scattering but greater absorption by melanin. In a videographic study of human autopsy eyes that compared contact transscleral

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continuous-wave Nd:YAG with diode cyclophotocoagulation, the former produced more prominent whitening and contraction of the ciliary epithelium, whereas the latter seemed to produce a deeper tissue contraction. The histologic correlate was predominant coagulation and disruption of the ciliary epithelium with the Nd:YAG laser, whereas the diode treatment was associated with less epithelial effect and more coagulative response in the ciliary muscle. These findings are consistent with results of other studies that revealed coagulative changes in the ciliary epithelium, stroma, and vasculature of human autopsy eyes in response to diode cyclophotocoagulation and deeper, more extensive tissue damage, compared with use of similar energy levels of Nd:YAG treatment in both rabbit eyes and preenucleation human eyes (82, 83 and 84). However, the study involving human eyes revealed similar lesions at lower energy levels (84), and another videographic study of human autopsy eyes revealed similar ciliary body responses to noncontact Nd:YAG and diode laser applications (85). Results of clinical trials suggest that visual loss may be less with transscleral diode cyclophotocoagulation than with the Nd:YAG procedures (86).

Comparisons with Alternative Procedures

Comparisons of transscleral Nd:YAG cyclophotocoagulation with cyclocryotherapy in both rabbit and human eyes have revealed insignificant differences in IOP responses, but less tissue destruction and fewer complications with the laser treatments (87, 88). On the basis of these and other reports of the various cyclodestructive operations, transscleral cyclophotocoagulation is now believed to be the cyclodestructive procedure of choice.

A comparison of noncontact transscleral Nd:YAG cyclophotocoagulation with several glaucoma drainage devices revealed better IOP control with the latter techniques (89). Although the laser group had less visual loss in that study, the loss of visual acuity with all transscleral cyclophotocoagulation procedures remains an important concern. In general, filtering surgery with adjunctive antimetabolite therapy or glaucoma drainage-device surgery is preferred in patients with good visual potential, although transscleral cyclophotocoagulation offers a reasonable alternative in the high-risk glaucoma population, especially when the visual potential is poor.

In patients with neovascular glaucoma, ECP has fared well compared with trabeculectomy (90, 91 and 92). ECP has also fared well when compared with Ahmed valve implantation (93).

Intraocular Cyclophotocoagulation

An alternative to transscleral and transpupillary cyclophotocoagulation in patients with glaucoma in aphakic, or possibly pseudophakic, eyes is intraocular cyclophotocoagulation, by using an

endophotocoagulator through a limbal or pars plana incision. Visualization with this technique can usually be accomplished by an endoscope or via the transpupillary route.

Vitreoretinal surgeons have reported the use of argon laser endophotocoagulators via a pars plana incision for the treatment of retinal disorders under transpupillary visualization (94, 95 and 96). During the course of a vitrectomy in an aphakic eye, it is possible to lower the IOP and use scleral indentation to bring the ciliary processes into transpupillary view for the purpose of cyclophotocoagulation with the intraocular laser probe (97, 98 and 99).

Figure 41.9 Intraocular cyclophotocoagulation with transpupillary visualization. Ciliary processes are brought into view with a scleral depressor and treated with laser endophotocoagulator via a pars plana incision.

After performing the vitrectomy, the vitreous instrument is removed and the endophotocoagulator is inserted through the same opening. Scleral indentation in the opposite quadrants is then used to bring several ciliary processes into view, and the tip of the laser probe is positioned 2 to 3 mm from the processes (Fig. 41.9). With an exposure time of 0.1 to 0.2 second, laser therapy is applied to individual ciliary processes by using an energy level sufficient to produce a white reaction and a shallow tissue disruption (usually 1000 mW). Three to five laser exposures are then applied to each process in the two quadrants opposite the entry site.

In one large series with a mean follow-up of 13 months, three fourths of the eyes had an IOP of 21 mm Hg or less with or without use of medications after one or two treatments (99). The primary value of this procedure is as an adjunct to pars plana vitrectomy in eyes with refractory glaucoma.

Transpupillary Cyclophotocoagulation

In 1971, Lee and Pomerantzeff (100) introduced the concept of argon laser cyclophotocoagulation via a transpupillary approach. Histopathologic studies in rabbit and human eyes confirmed the ability of direct laser application to selectively destroy ciliary processes (100, 101).

Transpupillary cyclophotocoagulation is limited to eyes in which a sufficient number of ciliary processes can be visualized gonioscopically. This is not possible in most eyes, especially those in which long-term miotic therapy prevents wide dilatation. However, situations such as aniridia, a large iridectomy, or retraction of the iris, as in advanced neovascular glaucoma, may provide adequate visualization of ciliary processes. Special contact lenses with scleral depressors have been developed to