A Comparison of Neodymium:Yttrium Aluminum Garnet and Diode Laser Transscleral Cyclophotocoagulation and Cyclocryotherapy

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1 Investigative Ophthalmology & Visual Science, Vol. 32, No. 10, September 1991 Copyright Association for Research in Vision and Ophthalmology A Comparison of Neodymium:Yttrium Aluminum Garnet and Diode Laser Transscleral Cyclophotocoagulation and Cyclocryotherapy Ehud I. Assia, Hugh L. Hennis, William C. Stewart, Ulrich F. C. Legler, Alan N. Carlson, and David J. Apple The cyclodestructive effects of cyclocryotherapy and of the neodymium:yttrium aluminum garnet (Nd:YAG) and diode laser transscleral cyclophotocoagulation were investigated in phakic and pseudophakic cadaver eyes using a modified Miyake posterior-view technique and light microscopy. Cyclocryotherapy to -80 C was applied with a 2.5-mm diameter tip, 1 and 2 mm from the limbus. Freezing at the ciliary processes was evident after sec and reached a diameter of 3-4 mm by 30 sec. No visible changes were evident grossly in the ciliary processes, crystalline lens, or intraocular lens. Histologically increased separation of cells was observed. Effective noncontact Nd:YAG and diode laser applications to the ciliary processes were observed grossly as tissue blanching and shrinking and pigment dispersion. This effect was obtained by aiming mm behind the limbus at a 1-mm defocus using 4 J of energy for the NdrYAG and 1.2 J for the diode laser. The diode laser spot size did not affect the tissue response. No damage was observed in the crystalline or intraocular lens with either type of laser. Histologic changes using both lasers were coagulation necrosis with fragmentation and detachment of the ciliary body epithelium. This study suggested that the gross and histologic thermal effects produced by the diode and Nd:YAG laser were similar in the ciliary body. Also, at the time of surgery, these cyclodestructive procedures potentially cause little alteration of the crystalline or intraocular lens. Invest Ophthalmol Vis Sci 32: ,1991 Cyclodestructive procedures are done in selected patients in whom conventional filtering surgery either previously failed or was not indicated. Over the past several decades, cyclocryotherapy was the cyclodestructive procedure most commonly performed. However, several laser cyclodestructive techniques recently were described, using either the neodymium:yttrium aluminum garnet (Nd:YAG) or semiconductor diode laser energy. In this study, we compared the gross and histologic changes in the ciliary body, crystalline lens, intraocular lens, and capsular bag of cadaver eyes, using various treatment parameters of these cyclodestructive techniques. Our results were evaluated using a modified Miyake posterior photographic technique and light microscopy. From the Glaucoma Service in the Department of Ophthalmology at the Medical University of South Carolina, Charleston, South Carolina. Supported in part by a grant from Research to Prevent Blindness, Inc. The authors have no proprietary interest in the Frigitronics, Keeler Instruments, or Lasag Corporation. Submitted for publication: February 15, 1991; accepted May 15, Reprint requests: Dr. William C. Stewart, Storm Eye Institute, 171 Ashley Avenue, Charleston, SC Materials and Methods Eight eyes, obtained within 36 hr of death, were prepared according to the Miyake posterior photographic technique by transsecting the globe anterior to the equator and filling it with 1% hyaluronic acid. 1 This technique was modified from the method used in previous reports to allow real-time posterior photographic imaging of transscleral cyclodestructive laser applications from a slit-lamp apparatus. In four of the eyes evaluated in this study, the lens nucleus was removed by manual extraction, followed by aspiration of cortical material. A one-piece polymethylmethacrylate posterior chamber intraocular lens 12.5 mm in length with a 6-mm diameter optic was implanted in the capsular bag. Cyclocryotherapy was applied to -80 C with nitrous oxide gas (Frigitronics, Coral Gables, Florida) 1 and 2 mm posterior to the surgical limbus with slight pressure on a 2.5-mm diameter probe tip. Separate applications were done for 1, 2, 4, and 8 min. A Microrupter 2 (Lasag, Eden Prairie, Minnesota) was used for the Nd: YAG transscleral cyclophotocoagulation. This laser has a wavelength of 1064 nm and was used in the thermal mode with a maximum defocus. Laser applications were evaluated that were aimed 0.5, 1, and 2 mm posterior to the surgical lim-

2 No. 10 COMPARISON OF CYCLODE5TRUCTIVE PROCEDURES / Assio er ol 2775 bus as measured by Castroviejo calipers. Also, energy levels of 2, 4, 6, and 8 J were studied. Applications were made with the eye perpendicular to the laser beam without a contact probe or contact lens. The Microlase (Keeler, Broomall, Pennsylvania) was used for semiconductor diode laser transscleral cyclophotocoagulation. This is a portable photocoagulator with two infrared laser diodes with wavelengths of 780 to 830 nm. We applied laser burns 0.5, 1.0, and 2 mm from the surgical limbus as measured by Castroviejo calipers. In addition, we varied the depth of focus by first placing burns aimed at the scleral surface, then 1 and 2 mm posteriorly, by moving the slit-lamp apparatus toward the cadaver eye as measured with a millimeter rule. Spot sizes of 100, 200, and 500 Mm were evaluated. Power settings of 1000 and 1200 mw were studied as were pulse durations of 0.2, 0.4,0.5,0.6,0.7, and 1 sec. The laser was applied with the eye perpendicular to the laser light without using a contact lens or contact probe. Cyclodestructive lesions were evaluated grossly by three independent observers (EIA, HLH, and UFCL) using 35-mm transparencies and videotape. For laser transscleral cyclophotocoagulation, ciliary process blanching and shrinking and pigment dispersion were believed to represent effective laser burns because they probably indicated destruction of the ciliary body epithelium and stroma. With cyclocryotherapy, ice-ball formation at the ciliary processes was considered to represent effective destruction of the ciliary body epithelium. 2 For each cyclodestructive procedure, the effect on the crystalline lens, intraocular lens, and capsular bag also was noted. Histologic evaluation was done by first fixing the cadaver eyes with 10% buffered neutral formalin. Fig. 1. Gross photograph of a posterior view of an eye after the lens material was removed and a posterior chamber intraocular lens was implanted in the capsular bag. Ice-ball formation occurred after 3 min of cyclocryotherapy from a cryoprobe placed 2 mm from the limbus (left). The ciliary processes and the lens capsular equator are involved in the ice-ball. Fig. 2. Photomicrograph shows the ciliary body after cyclocryotherapy treatment for 8 min. The stromal matrix appears looser with marked separation of cells compared with the untreated area of the same eye (periodic acid-schiff, original magnification X40). After processing and sectioning, the eyes were stained with hematoxylin and eosin and periodic acid-schiff and examined for thermal or cryogenic destruction in the ciliary body stroma and epithelium. Tissue specimens for areas treated with different cyclodestructive techniques were examined by three independent observers (EIA, UFCL, and DJA) and compared with normal untreated areas of the same eye. Cyclocryotherapy Results Ice-ball formation was observed grossly in the pars plana and ciliary processes sec after freezing was begun. The ice ball reached 3-4 mm in diameter by 30 sec. Applications 2 mm from the surgical limbus caused ice-ball formation over the pars plana and posterior ciliary processes. Those 1 mm from the surgical limbus caused ice-ball formation in the anterior and posterior ciliary processes and the crystalline lens, intraocular lens haptic, and capsular bag (Fig. 1). After thawing no gross visible structural alterations were observed. Histologically, compared with untreated areas of the same eye, an increased separation of cells in the ciliary body stroma and epithelium was observed after 8 min of cyclocryotherapy but not after shorter times (Fig. 2). Nd:YAG Transscleral Cyclophotocoagulation A thermal reaction in the ciliary body processes was observed with applications aimed mm behind the surgical limbus using 4-6 J of energy (Fig. 3). Excessive damage (hole formation) was created with 8 J of energy; 2 J caused no thermal effect at the ciliary processes. Applications 2 mm behind the limbus

3 2776 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / September 1991 Vol. 02 Fig. 3. Gross photograph of the ciliary body region of a pseudophakic eye after Nd:YAG cyclophotocoagulation using 4 J of energy placed I mm from the limbus. Blanching and tissue disruption is seen at the junction of the pars plana and pars plicata, and involves the anterior portion of the ciliary processes. No damage to the lens capsule was seen adjacent to the involved area of the pars plicata. Fig. 5. Photomicrograph of the ciliary body after an application from a Nd:YAG laser of 8 J of power focused 2 mm posterior to the limbus. Both layers of epithelium of the pars plicata and most of the pars plana show coagulation necrosis with cystic separation forming a large schisis cavity. No capsular damage exists despite massive disruption of the adjacent pars plicata (periodic acid-schiff, original magnification X25). showed a thermal effect in the pars plana and posterior ciliary processes only (Figs. 4-6). Historically the ciliary body stroma showed coagulation necrosis and fragmentation along with separation of the epithelial layers (Figs. 5-7). No gross effects were observed on the crystalline lens, intraocular lens, or capsular bag for any parameter studied (Figs. 3, 4). Semiconductor Diode Transscleral Cyclophotocoagulation A thermal reaction at the ciliary body processes was observed with applications aimed mm from the limbus using J of energy (Fig. 8). Spot size had little effect on the quality of the lesion produced. Applications 2 mm behind the surgical limbus showed a thermal reaction in the pars plana only. Histologically, the ciliary body stroma showed coagulation necrosis and fragmentation along with separation of the epithelial layers (Fig. 9). No gross effects were observed on the crystalline lens, intraocular lens, or capsular bag for any parameter studied (Fig. 8). Discussion Cyclodestructive procedures are used in selected glaucoma patients who need a reduction in their intraocular pressure and in whom filtering surgery failed or was not indicated. In the past several decades, cyclo- H- x Fig. 4. Gross photograph of Nd:YAG cyclophotocoagulation using 8 J of energy applied 2 mm from the limbus. Extensive damage to the pars plana was seen, including hole formation. However, the anterior tips of the ciliary processes, which are the most active in aqueous production, are only minimally affected {upper left). Fig. 6. Photomicrograph of the ciliary body after an Nd:YAG laser treatment of 4 J, 2 mm posterior to the limbus. The changes are similar to those seen in Figure 5, although less intense (periodic acid-schiff, original magnification X25).

4 No. 10 COMPARISON OF CYCLODESTRUCTIVE PROCEDURES / Assio er ol 2777 Fig. 7. Photomicrograph of the ciliary body treated with 4 J of energy applied directly at the limbus. Cellular disruption and coagulation necrosis is seen at the pars plicata. Most of the pars plana (right) remains intact (hematoxylin and eosin, original magnification X25), Fig. 9. Photomicrograph of the ciliary body after diode laser application near the limbus. A large cavity is surrounded by dispersed pigment and coagulation necrosis of the ciliary epithelium and stroma (periodic acid-schiff, original magnification X100). cryotherapy was the most commonly used cyclodestructive procedure. 2 It causes hemorrhagic infarction of the ciliary body, resulting in disorganized ciliary body epithelium, flattened ciliary processes, capillary obliteration, and epithelial fibrosis. 3 ' 4 Clinically, cyclocryotherapy controls the intraocular pressure in 60-90% of patients, but serious complications, such as phthisis, hypotony, or visual loss may occur postoperatively. 2 Recently, Nd:YAG transscleral cyclophotocoagulation was introduced. It has a potential advantage over cyclocryotherapy of being able to focus thermal destruction on the ciliary body. In cadaver eyes, blanching of the ciliary processes has been observed grossly, and epithelial disruption with separation Fig. 8. Gross photograph of diode cyclophotocoagulation applied 2 mm from the limbus. Wide blanching, pigment dispersion, and gas-bubble formation are seen. However, the ciliary processes are involved only at the posterior edge. from the underlying ciliary body stroma has been seen by light microscopy. 5 ' 6 Clinically, this procedure controls the intraocular pressure to less than mm Hg in 65-86% of patients after one or more treatments; it has similar types of complications as does cyclocryotherapy. 7 " 12 Semiconductor diode laser transscleral cyclophotocoagulation has been shown to produce a short-term decrease in intraocular pressure in rabbits comparable to that of the Nd:YAG laser. 13 We compared directly the effects on the ciliary body and lens structures in cadaver eyes of cyclocryotherapy with Nd:YAG and diode laser transscleral cyclophotocoagulation using a modified Miyake posterior photographic technique and light microscopy. Our study showed that blanching of the ciliary processes was observed with Nd:YAG transscleral cyclophotocoagulation at similar energy levels used in previous reports. 56 A similar reaction also was observed with the diode laser at slightly lower energy levels; this may have resulted partially from the better melanin absorption associated with infrared wavelengths closer to the visible spectrum. 14 When viewed dynamically, both pigment dispersion and bubble formation were visualized using both types of lasers. The bubble formation we observed may account for the anterior chamber gas seen clinically after some cases of Nd:YAG transscleral cyclophotocoagulation. 11 ' 12 Both laser transscleral cyclodestructive procedures showed similar histologic features including coagulation necrosis and extensive shrinking of the ciliary processes, with fragmentation and detachment of the pigment epithelium. These effects were not observed grossly or histologically with cyclocryotherapy; this may be a result of the different cyclodestructive effects of this procedure compared with laser cyclophotocoagulation.

5 2778 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / September 1991 Vol. 02 The cyclodestructive procedures studied did not affect the crystalline lens, intraocular lens haptic, or capsular bag grossly. A previous study using 8.8 J of energy focused transsclerally in cadaver eyes caused thermal damage to the haptic. 15 Our results with cyclocryotherapy and Nd:YAG cyclophotocoagulation also differed from clinical experience where cataract formation was reported postoperatively. 2 This difference may have resulted because of the localized treatment we applied; more extensive treatment may have been done on patients evaluated in studies in which cataracts occurred. Also, clinically uveitis is produced after cyclodestructive procedures, which may promote cataract formation. The potential usefulness of a modified Miyake technique in studying cyclodestructive procedures also was demonstrated by this study. The energy level required to create a thermal lesion at the ciliary processes with the Nd:YAG laser was similar to earlier studies where cadaver eyes were treated without the Miyake technique. This indicates that 1 % hyaluronic acid probably has a minimum influence on the quality of ciliary body lesion produced, but it facilitates both real-time and still photographic imaging. Our study suggests that diode and Nd:YAG transscleral cyclophotocoagulation produce similar thermal lesions in the ciliary body in cadaver eyes; therefore, they have the potential to produce comparable clinical results. Also, cyclocryotherapy and laser transscleral cyclophotocoagulation may have a minimum acute effect on lens structures when done clinically with the usual parameters. However, laser transscleral cyclophotocoagulation should be approached cautiously in the region of an intraocular lens haptic, especially when sulcus fixation is suspected. Thermal damage to the intraocular lens haptic was found previously in cadaver eyes. 15 Our results have only theoretic clinical value and do not specify the effects of these procedures when done in patients. This may be true especially for cyclocryotherapy because our study did not reproduce the insulating effects of ciliary body temperature or uveitic blood flow that may limit ice-ball formation. In addition, the procedures studied were not compared with therapeutic ultrasound, which may produce different effects on the ciliary body and lens structures. Further comparative clinical studies are needed to clarify which of these procedures is most useful in reducing the intraocular pressure in patients with glaucoma. Key words: glaucoma, cyclodestructive procedure, cyclocryotherapy, neodymium:yag transscleral cyclophotocoagulation, semiconductor diode laser Acknowledgments The authors thank Lasag Corporation who provided the Microrupter-2 and Keeler Instruments who provided the Microlase used in this study. References 1. Apple DJ, Lim E, Morgan R, Tsai JC, Gwin TD, Brown SJ, Carlson AN: Preparation and study of human eyes obtained postmortem with the Miyake posterior photographic technique. Ophthalmology 97:810, Stewart WC: Clinical Practice of Glaucoma. Thorofare, NJ, Slack, 1990, pp Wilkes TDI and Fraunfelder FT: Principles of cryosurgery. Ophthalmic Surg 10:21, Smith RS, Boyle E, and Rudt LA: Cyclocryotherapy: A light and electron microscopic study. Arch Ophthalmol 95:284, Fankhauser F, van der Zypen E, Kwasniewska S, Rol P, England C: Transscleral cyclophotocoagulation using a neodymium YAG laser. Ophthalmic Surg 17:94, Hampton C and Shields MB: Transscleral neodymium-yag cyclophotocoagulation: A histologic study of human autopsy eyes. Arch Ophthalmol 106:1121, Schuman JS, Puliafito CA, Allingham RR, Belcher CD, Bellows AR, Latina MA, Shingleton BJ: Contact transscleral continuous wave neodymium:yag laser cyclophotocoagulation. Ophthalmology 97:571, Hampton C, Shields MB, Miller KN, and Blasini M: Evaluation of a protocol for transscleral neodymiunryag cyclophotocoagulation in one hundred patients. Ophthalmology 97:910, Cohen EJ, Schwartz LW, Luskind RD, Parker AV, Spaeth GL, Katz LJ, Arentsen JJ, Wilson RP, Moster MD, Laibson PR: NeodymiunrYAG laser transscleral cyclophotocoagulation for glaucoma after penetrating keratoplasty. Ophthalmic Surg 20:713, Brancato R, Giovanni L, Trabucchi G, and Pietroni C: Contact transscleral cyclophotocoagulation with Nd:YAG laser in uncontrolled glaucoma. Ophthalmic Surg 20:547, Klapper RM, Wandel T, Donnenfeld E, and Perry HD: Transscleral neodymiunryag thermal cyclophotocoagulation in refractory glaucoma: A preliminary report. Ophthalmology 95:719, Badeeb O, Trope GE, and Mortimer C: Short-term effects of neodymium-yag transscleral cyclocoagulation in patients with uncontrolled glaucoma. Br J Ophthalmol 72:615, Schuman JS, Jacobson JJ, Puliafito CA, Noecker RJ, Reidy WT: Experimental use of semiconductor diode laser in contact transscleral cyclophotocoagulation in rabbits. Arch Ophthalmol 108:1152, L'Esperance FA: Ophthalmic Lasers Photocoagulation, Photoradiation, and Surgery. St. Louis, CV Mosby, 1983, p Blomquist PH, Gross RL, and Koch DD: Effect of transscleral neodymiunryag cyclophotocoagulation on intraocular lenses. Ophthalmic Surg 21:223, 1990.