INITIAL EXPERIENCE WITH A NEW METHOD OF LASER TRANSSCLERAL CYCLOPHOTOCOAGULATION FOR CILIARY ABLATION IN SEVERE GLAUCOMA*

Transcription

1 INITIAL EXPERIENCE WITH A NEW METHOD OF LASER TRANSSCLERAL CYCLOPHOTOCOAGULATION FOR CILIARY ABLATION IN SEVERE GLAUCOMA* BY Douglas E. Gaasterland, MD AND Irvin P. Pollack, MD INTRODUCTION OPHTHALMOLOGISTS HAVE USED CILIARY ABLATION TO REDUCE PRESSURE in eyes with severe glaucoma for more than five decades. Bietti' has provided an early review and the first report of studies of cyclocryotherapy. Ciliary ablation has been done with nearly every imaginable method of energy delivery to the eye, including coagulation with chemicals,1 diathermy,2 freezing,' xenon light,3 laser light delivered directly to the ciliary processes4 or across the sclera,5,6 and ultrasound.7 Usually, ciliary ablation has been reserved as a treatment for eyes with poor vision and a difficult, severe glaucoma uncontrolled with medications despite numerous previous surgeries. The goal of ciliary ablation is to slow the formation of aqueous humor, bringing inflow into better balance with outflow resistance, which is usually severely impeded in these eyes. The many problems and complications after cyclocryotherapy8 have generated interest in laser methods of ciliary ablation; this has grown since commercial neodymium:yttrium-aluminum-garnet (Nd:YAG) ophthalmic laser systems with continuous or free-running ("long-pulse") output have become available.9-1" In a number of studies, the complications and problems after laser ciliary ablation have not been as severe or as harmful to the eye as observed after cyclocryotherapy. In 1972 Beckman and co-workers5 using a free-running ruby laser, were first to report a laser method for transscleral cyclophotocoagulation (TSCPC) for ciliary ablation in humans. A long-pulsed neodymium-glass laser sys- *From the Center for Sight, Georgetown University Medical Center, Washington, DC, and Krieger Eye Institute, Sinai Hospital, Baltimore. Both authors have had a propriatary interest in IRIS Medical Instruments. TR. AM. OPHTH. Soc. vol. LXXXX, 1992

2 226 Gaasterland & Pollack tem caused similar effects to the ruby laser system.6 The approach was based on the high transmission through the sclera of longer wavelength light (the red and near-infrared wavelengths) coupled with high absorbance of these wavelengths by pigmented ciliary tissue Favorable 1- year results of studies of ruby laser TSCPC were reported in 1984,15 but there was little popularity of TSCPC until commercial laser systems were available (Lasag, Microruptor; Surgical Laser Technologies [SLT]). The Lasag Nd/YAG laser system delivers 2-msec pulses of light to the eye through the air from a slit-lamp biomicroscope for noncontact treatment. The SLT system delivers continuous-wave light to the eye through fiberoptics to a hand-held, sapphire optic-tipped probe for contact treatment. The tips of the fibers used with this system for TSCPC are designed to enhance treatment. Numerous laboratory and clinical studies of effects of these systems on the ciliary body have been reported, and the methods have become an accepted alternative for ciliary ablation in severe glaucoma. Recently, semiconductor diode laser technology has advanced and continuous-wave systems with power output exceeding 2 W have become commercially available for eye treatment. These systems produce light in the near-infrared wavelength (typically around 8 nm). They are attractive compared with Nd:YAG systems because of small size, high efficiency of converting electric to laser energy, high reliability, low cost, and ease of fiberoptic delivery of laser energy. Laboratory studies have indicated that diode laser light at 81 nm wavelength is nearly two times more effective for TSCPC than is Nd:YAG laser light at 164 nm At 164 nm, light from the Nd:YAG systems traverse sclera with less absorption and scatter than 81-nm light, but absorption by uveal melanin is greater at 81 nm than at 164 nm, and this effect predominates. We have worked with a clinical diode laser system (IRIS Medical Instruments, Oculight SLx) that provides light energy to the eye through a specially designed quartz glass, fiberoptic "G-Probe." Its use for TSCPC is based on studies in autopsy eyes. 16 A multicenter pilot clinical study of short-term effects on glaucomatous eyes has been completed.17 While participating in this work, we accumulated prospective information and follow-up results after treatment of a number of eyes. About half the eyes were enrolled in the multicenter pilot study. The purpose of this paper is to report our initial experience with diode laser TSCPC. We include the characteristics of the treated patients and their glaucoma, the technique, the problems associated with treatment, and outcome information; and we compare the diode laser method with the Nd:YAG method of TSCPC.

3 Laser Transcleral Cyclophotocoagulation 227 METHODS The Institutional Review Boards at our centers approved a plan for a pilot study and the informed consent document. The boards gave compassionate approval for treatment of some of our patients after pilot study enrollment ended. ELIGIBILITY AND EXCLUSION CRITERIA Patients had to be at least 18 years of age and have primary or secondary, open- or closed-angle, chronic glaucoma for which they were using maximal tolerable and effective medications. The eligibility intraocular pressure (IOP) requirement was 23 mm Hg, or higher, on at least two occasions, despite medical treatment. After determining eligibility, we determined a baseline IOP. We limited study to patients with glaucomatous optic nerve damage, but required vision to be at least perception of light. The first several eyes treated at our centers were required by the protocol to be aphakic or pseudophakic; thereafter this restriction was removed, allowing treatment of phakic eyes. Additional criteria were high risk of failure of a conventional filtering operation, inablility of patient to receive additional filtering surgery, ability to cooperate and have local retrobulbar anesthesia, treatable with TSCPC, and ability to cooperate with study examinations. Patients had to be willing to participate, demonstrated by signing the consent document. Patients were excluded from eligibility if the eye could receive laser trabeculoplasty and there was reason to believe it would relieve the glaucoma. Also, patients were excluded if the eye had surgery of any type within 2 months of the eligibility examination or for concurrent active disease that might confuse interpretation of effects of the TSCPC (eg, active uveitis or infection, central corneal scars, macular edema, active proliferative retinopathy). Patients were not invited to enroll an eye if the fellow eye had previously been enrolled, if they had active kidney disease for which they were receiving dialysis, or if the eye had no perception of light. BASELINE INFORMATION Before surgery, we collected information on each patient's age, sex, race, and systemic problems. We determined the ocular history and diagnosis for the eye with uncontrolled glaucoma (Table I). Regarding the glaucomatous eye, we evaluated iris coloration as an indicator of ocular pigmentation, amount of the anterior chamber angle covered by peripheral anterior synechiae (PAS), best-corrected visual acuity, number of medications taken for glaucoma, intraocular pressure on at least two

4 228 Gaasterland & Pollack PATIENT NO TABLE I: DEMOGRAPHICS OF PATIENTS PARTICIPATING IN STUDY OF DIODE LASER TSCPC AGE (YR) SEX RACE OCULAR DIAGNOSIS PERTINENT SYSTEMIC DIAGNOSES GU 1 6 F W 1981: POAG filter; 1986: None PKP/ECCE; 1989: secondary AC IOL GU 2 77 M B 199: ECCE with AC IOL; None 199: Vitreous hemorrhage; vitrectomy, IOL removal, secondary PC IOL GU 3 67 F B 1988: Cataract extraction; IDDM/ I and hyperten- ABK; 1991: PKP, vitrec- sion 3 yr; asthma tomy, 2 PC IOL GU 4 69 M B POAG OU x2 yr; ALT IDDM/ I and hyperten- OU; trabeculectomy OU, sion, prostatic CA to x2 luniis GU 5 68 F B POAG OU x 15 yr; ALT None OU; ECCE with PC IOL ou GU 6 67 M W POAG OU x 8 yr; 1985: None ECCE with PC IOL; 1986: ALT GU 7 32 F W Rieger's anomaly; "numer- None ous" trabeculectomies; cataract removal; PKP X4; cyclocryotherapy x 2 GU 8 69 M W POAG x 1 yr; 1989, None 199: ALT x2; 199: Gl triple; 199: trabeculectomy SH 1 7 F W 2 OAG, apakia None SH 2 82 F W 2 OAG, apakia None SH 3 54 F W Rieger's syndrome; 1985: None ECCE/trabeculectomy; 1988: trabeculectomy #2 SH 4 75 F B POAG, pseudophakia None SH 5 32 F B Aphakia; CNAG None SH 6 68 M W Aphakia; 2 OAG None SH 7 8 F W 197: CE; 199: PKP/IOL None SH 8 66 M W Aphakia None SH 9 74 M W 2 angle closure Gl None SH 1 61 M W Congenital glaucoma; None trabeculotomy x 2; cyclocryotherapy x 1 SH 1 91 F W POAG None SH F W POAG None SH F B POAG None POAG, primary open angle glaucoma; PKP, penetrating keratoplasty; ECCE, extracapsular cataract extraction; AC IOL, anterior chamber intraocular lens; PC IOL, posterior chamber intraocular lens; ABK, aphakic bullous keratopathy; OU, both eyes; ALT, argon laser trabeculectomy; Gl, glaucoma; CNAG, chronic narrow angle glaucoma; CE, cataract extraction.

5 Laser Transcleral Cyclophotocoagulation 229 occasions (the first to determine eligiblity and the last to serve as a baseline for data analysis), whether there existed a glaucomatous visual field defect (in eyes that could be tested), and the vertical cup-to-disk ratio determined during stereoscopic slit-lamp biomicroscopic examination of the posterior pole of the eye (Table II). ) If) o))o if Z )s )O ) s at 5))a 66o-Ho6o-66o o o o Q) U) 4.) Q) ) ) ) =4 V v: C)) kl bc- C)- a H z C) H C)) C) H a. z ;e oc)) to LO c 't O C CD 'r f CJ CCO^ IS )OOt 't cn ) _f C))C1 i ) ' 1' 1) to cq It CQtV co CtO U) co C Cq ic stc oc s C) a F CU.U S) " 26 CZ) C)) W C)) W ( O in ' :. : ^- to11 1 1o "p> o o J6 _ o_ 5' o o 6o ~ o; ~ u 6 = o o > cli c' cli cq cl ci cli cli cs O] cs c ).F ~ - z Cl)Cl)ncn ccl) C)cn~ )1~c / 1 O. :.- -e!,-4pl ) PL PA Z) )C - a.o CU CU & HI U) I~ H C) z M "r ~C t- co t cq c CV V V V V V c ) cn '= cl cn cn

6 23 Gaasterland & Pollack SURGICAL TECHNIQUE Participating patients came to the outpatient facility for treatment. Local anesthesia was accomplished with a retrobulbar or peribulbar injection of 2 to 4 ml of 2% lidocaine HCI (Elkins-Sinn Inc, Cherry Hill, NJ) alone or in combination with.5% bupivacaine HCI (Astra Pharmaceutical Products Inc, Westborough, MA), or equivalent. The semiconductor diode laser system (IRIS Medical Instruments, Oculight SLx, Fig 1) had maximum power output of 2.5 W and maximum duration of 9.9 seconds. The laser delivery quartz fiberoptic diameter was 6,um; its planar polished end protruded.7 mm from a handpiece (G-Probe, IRIS Medical Instruments, Fig 2) fabricated in a shape to encourage accurate fiberoptic location centered 1.2 mm behind the surgical limbus and oriented parallel to the visual axis. Subsequent laser applications were spaced one-half the width of the probe tip (ie, 2 mm) by aligning the lateral edge of the probe on the center of the last application. This produced confluent burns of the ciliary processes in autopsy eye studies.'6..i... FIGURE 1 Diode laser system used for this study. Console is set at 175 mw (1.75 W) of power and 2 msec (2. seconds) of duration and indicates 18 laser applications have been made. Quartz glass fiberoptic G-Probe attached (arrow) to output port.

7 Laser Transcleral Cyclophotocoagulation 231 z -I..., ll 1~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~... _N.^,,X'X ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~... B...} FIGURE 2 Close-up view ofdelivery end of G-Probe showing curved surface for mating with perilimbal sclera and.7-mm protrusion of 6,um diameter fiberoptic tip (arrow).

8 232 Gaasterland & Pollack Seventeen to 19 laser applications, each with a 2-second duration, were delivered to three quarters of the circumference of the ciliary body. In the first TSCPC for an enrolled eye, we omitted treatment of the temporal 9 degrees of the circumference and made evenly spaced laser applications to the remaining 27 degrees. Applications started with power of 1.75 W If there was no tissue-disruption reaction (a "pop" or "snap" sound from within the eye) during the first two applications, power was increased to 2 W If there was a "pop" or "snap" during more than one subsequent laser application, power was reduced back to 1.75 W If a "pop" or "snap" sound occurred at 1.75 W during more than one laser application, we reduced power to 1.5 W, and completed treatment at this power. After treatment, we gave topical atropine and topical steroid medications. The IOP was monitored for several hours. A monocular patch was applied to the anesthetized eye. We prescribed acetaminophen or acetaminophen with codeine to be taken as needed for ocular pain. Repeat TSCPC was done for three of our patients when clinically indicated. OBSERVATIONS DURING AND AFTER SURGERY Patients returned for examination 24 to 48 hours after TSCPC; at 1, 3, and 6 weeks; at 3 and 6 months; and at other times as needed. The sequence was modified for a few because they had to return to distant homes; for these patients, some observations were available from their referring ophthalmologists. The variables for this report include the number of laser applications, the number of "pops" (presumably intraocular tissue disruption)15 during treatment, and occurrence and number of surface burns of the eye. We recorded the patients' reports about postoperative pain (characterized as "none," "mild," or "more than mild"), and observations about inflammation (characterized as "none," "mild," or "more than mild"), formation of a protein clot in the anterior chamber, hypopyon, bleeding, change of IOP from baseline during the first 48 hours, and other problems occurring during or soon after treatment (Table III). At their last examination, we recorded elapsed time (months) since TSCPC, additional surgery during the interval, number of medications being used, best corrected visual acuity, and IOP (Table IV). RESULTS The series consists of 21 eyes of 21 consecutively eligible and treated patients at our two centers, 8 at the Georgetown University Medical Center, and 13 at the Sinai Hospital in Baltimore. Longer-term follow-up

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10 234 Gaasterland & Pollack TABLE IV: STATUS OF EYES AT END OF FOLLOW-UP TIME SINCE PATIENT TREATMENT ADDITIONAL VISUAL NO. OF NO. (MO) SURGERY ACUITY MEDICATIONS IOP GU 1 GU 2 GU 3 GU 4 GU 5 GU 6 GU 7 GU 8 SH 1 SH 2 SH 3 SH 4 SH 5 SH 6 SH 7 SH 8 SH 9 SH 1 SH 11 SH 12 SH mo: IOP 37; second diode TSCPC wk: IOP elevated; VA fell to NLP d: IOP 29; second diode TSCPC 4 2 mo: 5th PKP 6 1 mo: IOP 53; second diode TSCPC 3 mo: IOP 53; LT trabeculectomy + MMC 4 mo: IOP 4; Molteno implant wk 6 wk 6 6 Immediately: suture closure of leak 2t5 2/2 NLP 2/1 2/4 2/6 2/2 2/3 2/8 2/4 LP CF LP CF 2/4 2/4 2/4 2/1 HM 2/1 2/ NLP, no light perception; PKP, penetrating keratoplasty; LT, lower temporal; MMC, mitomycin C; LP, light perception; CF, count fingers; HM, hand motion. has been inhibited for two patients in the Georgetown University series and three in the Sinai Hospital series, because the patients departed to their homes in other parts of the world. Measurements for these patients were available from their local ophthalmologist and have been included. Fifteen of the 21 eyes in this report were aphakic or pseudophakic (Table I). All had previous glaucoma surgeries. Three had glaucoma due to congenital anomalies of the anterior chamber angle. Two had previous penetrating keratoplasties. None of the eyes had neovascular glaucoma.

11 Laser Transcleral Cyclophotocoagulation 235 Our group included 11 right eyes and 1 left eyes (Table II). Eight eyes had blue or green iris color; five eyes had light brown iris color; and eight eyes had dark brown iris color. Preoperative visual acuity ranged from 2/25 to light perception; the median preoperative visual acuity was 2/2. Nine eyes had preoperative vision better than 2/1. Nine eyes had preoperative vision of counting fingers, hand motions, or light perception. Twelve of the 19 eyes (63%) in which the anterior chamber angle could be evaluated had some peripheral anterior synechiae (PAS); the amount varied from 3 degrees (1 eye) to 36 degrees (9 eyes). Seven eyes had an open anterior chamber angle, with no PAS. The patients had been using from two to five glaucoma medications, with the average being three. The average baseline IOP for this group, measured after eligibility was established, was 32.6 mm Hg ( SD) (range, 16 to 7 mm Hg). In the 16 eyes with sufficiently clear media to see the optic nervehead, the average vertical cup-to-disk ratio was.9 (+.15 SD), reflecting the severe glaucoma damage. The number of laser applications during treatment ranged from 2 to 18, with most eyes having 16, 17, or 18 (Table III). We treated two eyes with a reduced number of laser applications. One (GU 7) previously had four penetrating keratoplasties and two cyclocryotherapies; it had only 11 remaining ciliary processes on preoperative transillumination and gonioscopic examination of the surgically aniridic eye. After application of topical 4% cocaine to induce anesthesia, this eye had TSCPC limited to two laser applications. The second of these eyes (SH 1) received 11 laser applications. No tissue disruption ("pops") occurred during treatment of 4 of the 21 eyes. These included two with blue-green irides, one with a light brown iris, and one with a dark brown iris. Ten eyes (5 blue-green, 3 light brown, and 2 dark brown) had one or two "pops." Five eyes (1 blue-green, 1 light brown, and 3 dark brown) had three to six "pops." One eye had 7 and one eye had 12 "pops"; both were dark brown eyes in black patients. The last (SH 5), with 12 "pops," received a total of 18 laser applications. Overall, one or more "pops" occurred in 6 of 8 eyes (75%) with blue-green irides, 4 of 5 eyes (8%) with light brown irides, and 7 of 8 eyes (88%) with dark brown irides. Eyes with brown irides, when they had "pops" during treatment, tended to have more "pops" than eyes with blue-green irides. There were no surface burns in 13 eyes; 6 of these had blue-green irides, 3 had light brown irides, and 4 had dark brown irides. Thus 6 of 8 (75%) blue-green eyes, 3 of 5 (6%) light brown eyes, and 4 of 8 (5%) dark brown eyes had no surface burns during treatment. Mild surface burns occurred in seven eyes, one with a blue-green iris, two with light brown

12 236 Gaasterland & Pollack irides, and four with dark brown irides. Thus 4 of 8 dark brown eyes (5%) and 2 of 5 light brown eyes (4%) had mild surface burns. One aphakic eye (SH 6) with a blue-green iris in a white patient had a severe burn of the conjunctiva and sclera during treatment, with perforation of the thin superior sclera. This eye received a total of 15 laser applications. The perforation involved the recess of the anterior chamber. The resultant leak of aqueous humor was repaired surgically by suturing across the defect. Eight patients reported no discomfort during the first 24 hours after treatment, and ten reported mild pain. Three patients had more than mild discomfort. In all cases discomfort was relieved with oral analgesics. Two treated eyes had no inflammation when the patient was examined 24 to 48 hours after treatment (Table III). Fifteen eyes had mild inflammation. Four eyes had more than mild inflammation, with a protein clot developing in the anterior chamber in three and a sterile hypopyon in one. All cleared uneventfully with topical steroid treatment. No eyes had bleeding in response to treatment. The IOP at 24 to 48 hours after treatment (Table III) averaged 12.3 mm Hg below baseline (± SD). The change of IOP ranged from -39 to + 8 mm Hg. Three eyes had IOP + 6, + 7, or + 8 above baseline at 24 to 48 hours; the other 18 eyes had IOP below baseline. The length of follow-up in this study ranges from.5 to 11 months (Table IV). At the end of follow-up, IOP (Fig 3) was 19 mm Hg, or less, in 12 eyes without additional glaucoma surgery. One of these 12 eyes (GU 5) had IOP of 1 mm Hg at the last examination, 11 months after laser treatment. This hypotony continued after suppressants of aqueous humor formation (timolol and methazolamide) were discontinued. Two additional eyes had IOP of 19 mm Hg and 15 mm Hg at the end of follow-up, but both had undergone a second diode laser TSCPC. The second operation was done at 1 week for one eye (GU 6) with persistent IOP elevation, and it was done at 9 months for the other eye (GU 3), which had recurrent IOP elevation. Fourteen of the 21 eyes (66%) had IOP of 19 mm Hg or less at the end of follow-up accomplished solely with diode laser TSCPC and continued medical treatment. One additional eye (GU 4) had IOP of 21 mm Hg while using four glaucoma medications at the end of follow-up, 6 months after a single diode laser TSCPC. The IOP of this eye was in the 4s before laser treatment. At the end of follow-up, five eyes had IOP ranging from 25 to 39 mm Hg despite continued medical treatment; these eyes were 1.5 to 7 months after laser treatment and are regarded as failures of a single diode laser TSCPC to reduce IOP adequately. Another eye (GU 8) was also a treat-

13 7 Final IOP 6 5 Laser Transcleral Cyclophotocoagulation HIGHER identity / * ~ ~~~~~ LOWER Baseline IOP FIGURE 3 Scattergram showing intraocular pressure at baseline (abscissa) and at end of follow-up (ordinate) for 21 glaucomatous eyes treated with diode laser transscleral cyclophotocoagulation. Oblique line of identity divides plot into two areas representing lower and higher intraocular pressure. ment failure; it had minimal effect on IOP from the initial diode laser TSCPC or from a repeat treatment 1 month later. This eye subsequently failed a lower temporal quadrant trabeculectomy with adjunctive mitomycin-c therapy. The glaucoma in this eye was eventually controlled by a single-plate Molteno implant operation, but not before considerable deterioration of visual acuity. Overall, in this study, there were eight failures of the initial diode laser TSCPC to reduce IOP to 21 mm Hg or less. All occurred within the first 6 months of follow-up. Additionally, one eye had hypotony, which may have been iatrogenic. The patients were using from none up to four glaucoma medications for the eyes in the study at the end of follow-up. When the eye that had a Molteno implant (GU 8) is excluded, the patients were using an average of 1.9 (+ 1.2 SD) medications. Best corrected visual acuity improved two or more lines on the Snellen chart in three eyes during this study (Fig 4). Five eyes had deterioration of visual acuity of two or more lines. The IOP in all five was 19 mm Hg or less at the end of follow-up. One of these five (GU 2) had a second diode laser TSCPC (at 9 months) and another (GU 8) had three additional

14 238 Gaasterland & Pollack Final VA HM WORSE iden 2/4 2/8 2/4 ~~~~ BETTER 2/2 I. 2/2 2/4 2/8 2/4 HM LP Baseline VA FIGURE 4 Scattergram showing best-corrected visual acuity at baseline (abscissa) and at end of followup (ordinate) for 21 glaucomatous eyes shown in Fig 3 treated with diode laser transscleral cyclophotocoagulation. Oblique line of identity divides plot into two areas representing better and worse visual acuity; lines above and below identity located at two Snellen lines of vision better and worse than baseline. surgical interventions. Fluorescein angiography-proved cystoid macular edema developed in one (SH 2), and vision decreased from 2/5 at baseline to 2/4 1 months later. This aphakic eye with circumferential PAS had an IOP of 26 mm Hg while the patient was using-two glaucoma medications on entry to the study. No additional surgery for glaucoma was done. Ten months later IOP was 12 mm Hg and one glaucoma medication had been stopped. The five eyes that lost vision entered the study with acuity of 2/7 or better, and the three that improved entered the study with acuity of 2/2 or worse. Thirteen (62%) of 21 eyes had vision at the end of follow-up within one line of baseline, but one of these had deteriorated from light perception to no light perception (regarded as a "oneline" loss). The eye with scleral perforation induced by laser treatment (SH 8) retained vision of finger counting at 3 feet throughout the study; the IOP was 25 mm Hg at the end of follow-up, 6 months after TSCPC. One eye (GU 3) had deterioration of vision from light perception to no light perception during the fourth month after diode laser TSCPC. Even though baseline IOP was 7 mm Hg in this eye, medications had been

15 Laser Transcleral Cyclophotocoagulation 239 reduced because IOP had fallen to 11 mm Hg. Vision was lost during the interval between examinations, during which the IOP again became elevated. DISCUSSION This study indicates that fiberoptic contact diode laser TSCPC of three quarters of the ciliary body circumference causes a durable reduction of IOP in about two thirds of eyes with severe, medically uncontrolled glaucoma. We also have found a reduced need for medical glaucoma treatment after diode laser TSCPC. Nearly two thirds of eyes retain the same visual acuity during early follow-up, and a few more improve. About one fourth of the eyes in this study have had a falloff of two or more lines of visual acuity on the Snellen chart during follow-up. Eyes with better acuity at the time of treatment are at more risk of deterioration of vision, and those with poorer acuity have a better chance of improvement. We have not included eyes with neovascular glaucoma in this study. The proportion of eyes with IOP of 19 mm Hg or less at the end of follow-up (66%) in the present study after one or two diode laser TSCPC treatments is slightly larger than the 51% reported with IOP of 2 mm Hg or less by Hampton and co-workers18 6 months after noncontact Nd:YAG laser TSCPC. Schuman and co-workers19 have found 49% of eyes with IOP of 19 mm Hg or less 3 months or more after contact Nd:YAG TSCPC. Other investigators have found similar rates of success at reduction of IOP to 2 mm Hg or less after both contact and noncontact Nd:YAG TSCPC with follow-up for as long as several years.2-23 We have found deterioration of visual acuity in 5 of 21 eyes (24%). Hampton and co-workers18 found a larger rate of deterioration (47%) of visual acuity after successful noncontact Nd:YAG TSCPC. This is not explained by the different definitions of deterioration used in the two studies. Others have reported deterioration of vision in 2% to 31% of eyes after noncontact Nd:YAG TSCPC Schuman and co-workers19 have reported a low proportion of eyes with vision deterioration (7%) during a short follow-up after contact Nd:YAG TSCPC. This increased substantially (to 47%) when follow-up lengthened to 12 months or more (Schuman and associates, October Unpublished data). With one exception, the problems and complications we have found associated with diode laser TSCPC have been mild. Intraocular tissue disruption at the treatment site ("pops") occurred in 81% of our series, but 66% of the eyes had disruption limited to two or fewer laser applications of an average of 17 applications. Two eyes in our series had disrup-

16 24 Gaasterland & Pollack tion with more than half the laser applications during TSCPC. Whether or not disruption occurred was not correlated with iris color, but a larger percentage of laser applications caused "pops" in eyes with darker colored irides than in eyes with blue or green irides. Microexplosions during TSCPC have been described by others. They are thought to be related to the amount of ocular pigmentation24'25 and to the laser power during treatment. 26 The amount of tissue disruption (number of "pops") during TSCPC in our study does not correlate with inflammation or accumulation of an anterior chamber protein clot or hypopyon at 24 to 48 hours after treatment. The latter has occurred in 3 of 21 eyes (14%). None of the eyes in our series have had bleeding as a result of TSCPC. Wright and coworkers2 report inflammation and bleeding to be more likely in eyes after 27 J of Nd:YAG energy is applied during noncontact treatment. We have used a maximum of 76 J for eyes in the present study. Others have also noted inflammation and chemosis.23'27'28 These have occurred more frequently after noncontact laser TSCPC. While laser TSCPC does not appear to cause as much discomfort as cyclocryotherapy, most reports indicate that mild to severe pain occurs in 2% to 1% of patients after both contact and noncontact TSCPC. 19,21,23,27,28 In our study, 3 of 21 patients (14%) have reported more than mild discomfort during the first 24 hours after treatment; all were more comfortable after treatment with topical cycloplegics and mild oral analgesics. Mild burns of the ocular surface occur during noncontact and contact laser TSCPC.29,3 Most investigators do not mention this as a problem. In the present study seven eyes (33%) had mild surface burns during treatment. These healed quickly. Another eye had an important surface burn problem that we have not found reported as a complication of TSCPC in glaucoma patients. The sclera was thin in this eye at the site of previous cataract surgery. The quartz glass fiberoptic tip, protruding.7 mm (Fig 2) from the surface of the delivery probe, burned the surface tissue during one laser application. It was cleaned. During the next application the fiberoptic perforated the sclera, creating a sclerostomy that leaked aqueous humor. Treatment for this consisted of suturing the defect, which successfully closed the leak, and administering topical antibiotics, steroids, and cycloplegics. No additional problems occurred in this eye, although the final IOP is 25 mm Hg; the baseline IOP for this eye was 26 mm Hg. This episode has led to redesign of the fiberoptic of the G-Probe; the tip now has a chamfer to reduce the chance of a sharp edge of the fiber cutting conjunctival vessels and causing bleeding. Blood and debris on the

17 Laser Transcleral Cyclophotocoagulation 241 tip can become carbonized during contact coagulations with planar fiber tips.3 The temperature at the tip can rise to 3 C in the presence of adherent carbonized tissue debris; this temperature is sufficient for scleral penetration or for a sclerostomy. A small percentage of cases with hypotony or phthisis occurs after laser TSCPC. The rate has varied from % to 11% Hypotony developed in one patient (5%) during this study of the effect of diode laser TSCPC. Many reports indicate that nearly half of eyes have insufficient response or loss of response after initial Nd:YAG laser TSCPC. These eyes are usually managed with another treatment.18-23,27,31 Three eyes in our series underwent a second diode laser TSCPC; two of these were successful at reducing IOP below 2 mm Hg. Five additional eyes had an IOP above 24 mm Hg at the end of follow-up. These five eyes are candidates for additional treatment. In all, we have found failure of the initial diode laser treatment to reduce the IOP below 2 mm Hg in 8 of 21 eyes (38%) during the first 6 months after treatment (Table IV). Single cases of focal scleral thinning,32 malignant glaucoma,33 and sympathetic ophthalmia34 have been reported after Nd:YAG laser TSCPC. We have observed focal scleral thinning in other cases after noncontact Nd:YAG TSCPC. We have not found any of these problems in the patients in our diode laser series. Laboratory16,35,36 and glaucoma patient'7'37 studies have indicated that transscleral application of diode laser energy to the ciliary body can burn the target tissue. Both noncontact37 and contact17 methods reduce the IOP in medically uncontrolled glaucomatous eyes. In general, this is accomplished with no more than minor problems. The present report shows that this treatment has the potential for causing major problems. Transscleral diode laser TSCPC with a sharp-edged, planar-tipped fiberoptic resulted in a sclerostomy in one of our patients. This demonstrates, once again, the need to proceed cautiously in developing new treatment methods. Overall, our initial experience with the new method of contact diode laser TSCPC is favorable. The treatment reduces the IOP in as many eyes and as much as other laser methods of TSCPC. It has no more deleterious effect on vision than other laser methods of TSCPC. With the one exception previously emphasized, for most eyes the discomfort, inflammation, problems, and complications after diode laser TSCPC appear to be at least no more, and perhaps less, than after other laser methods oftscpc. The equipment is comparatively inexpensive, rugged, portable, and versatile.

18 242 Gaasterland & Pollack REFERENCES 1. Bietti G: Surgical interventions on the ciliary body. New trends for the relief of glaucoma. J Am Med Assoc 195; 142: Vogt A: Versuche zur intraokularen Druckherabsetzung mittelst Diathermieschadigung des Corpuscilaire (Zyklodiathermiestichelung). Klin Monatsbl Augenheilkd 1936; 97: Weekers R, Lavergne G, Watillon M, et al: Effects of photocoagulation of ciliary body upon ocular tension. Am J Ophthalmol 1961; 52: Lee PF, Pomerantzoff : Transpupillary cyclophotocoagulation of rabbits eyes: An experimental approach to glaucoma surgery. Am J Ophthalmol 1971; 71: Beckman H, Kinoshita A, Rota AN, et al: Transscleral ruby laser irradiation ofthe ciliary body in the treatment of intractable glaucoma. Trans Am Acad Ophthalmol Otolaryngol 1972; 76: Beckman H, Sugar HS: Neodymium laser cyclocoagulation. Arch Ophthalmol 1973; 9: Coleman DJ, Lizzi FL, Driller J, et al: Therapeutic ultrasound in the treatment of glaucoma: I. Experimental model. Ophthalmology 1985; 92: Caprioli J, Strang SL, Spaeth GL, et al: Cyclocryotherapy in the treatment of advanced glaucoma. Ophthalmology 1985; 92: Wilensky JT, Welch D, Mirolovich M: Transscleral cyclocoagulation using a neodymium:yag laser. Ophthalmic Surg 1985; 16: Fankhauser F, van der Zypen E, Kwasniewska S, et al: Transscleral cyclophotocoagulation using a neodymium:yag laser. Ophthalmic Surg 1986; 17: Federman JL, Ando F, Schubert HD, et al: Contact laser for transscleral photocoagulation. Ophthalmic Surg 1987; 18: Smith RS, Stein MN: Ocular hazards of transscleral laser radiation: I. Spectral reflection and transmission of the sclera, choroid and retina. Am J Ophthalmol 1968; 66: Rol P, Niederer P, Diirr U, et al: Experimental investigations on the light scattering properties of the human sclera. Lasers Light Ophthalmol 199; 3: Vogel A, Dlugos C, Nuffer R, et al: Optical properties of human sclera, and their consequences for transscleral laser applications. Lasers Surg Med 1991; 11: Beckman H, Waeltermann J: Transscleral ruby laser cyclocoagulation. AmJ Ophthalmol 1984; 98: Monsour M, Albrecht K, Gaasterland D: Contact semiconductor diode laser transscleral cyclophotocoagulation in human autopsy eyes (abstract 943). Invest Ophthal Vis Sci (Suppl) 1991; 32: Gaasterland DE, Abrams DA, Belcher CD, et al: A multicenter study of contact diode laser transscleral cyclophotocoagulation in glaucoma patients (abstract 1644). Invest Ophthalmol Vis Sci (Suppl) 1992; 33: Hampton C, Shields MB, Miller KN, et al: Evaluation of a protocol for transscleral neodymium:yag cyclophotocoagulation in one hundred patients. Ophthalnology 199; 97: Schuman JS, Puliafito CA, Allingham RR, et al: Contact transscleral continuous wave neodymium:yag laser cyclophotocoagulation. Ophthalmology 199; 97: Wright MM, Grakewslo AL, Feuer WJ: Nd:YAG cyclophotcoagulation: Outcome of treatment for uncontrolled glaucoma. Ophthalmic Surg 1991; 22: Noureddin BN, Wilson-Holt N, Lavin M, et al: Advanced uncontrolled glaucoma: Nd:YAG cyclophotocoagulation or tube surgery. Ophthalmology 1992; 99: Trope GE, Steven MA: Mid-term effects of neodymium:yag transscleral cyclocoagulation in glaucoma. Ophthalmology 199; 97: Balazsi G: Noncontact thermal mode Nd:YAG laser transscleral cyclocoagulation in the treatment of glaucoma: Intermediate follow-up. Ophthalmology 1991; 98: Schubert HD, Federman JL: A comparison of CW Nd:YAG contact transscleral cyclophotocoagulation with cyclocryopexy. Invest Ophthalmol Vis Sci 1989; 3:

19 Laser Transcleral Cyclophotocoagulation Cantor LB, Nichols DA, Katz LJ, et al: Neodymium-YAG transscleral cyclophotocoagulation: The role of pigmentation. Invest Ophthalmol Vis Sci 1989; 3: Fankhauser F: Contact neodymium:yag laser for cyclophotocoagulation. Ophthalmic Surg 1992; 23: Kalenak JW, Parkinson JM, Kass MA, et al: Transscleral neodymium:yag laser cyclocoagulation for uncontrolled glaucoma. Ophthalmic Surg 199; 21: Ando F, Miyake K, Federman JL: Nd:YAG laser transscleral contact cyclophotocoagulation in refractory glaucoma. Lasers Light Ophthalmol 199; 3: Shields MB, Blasini M, Simmons R, et al: A contact lens for transscleral Nd:YAG cyclophotocoagulation. Am J Ophthalmol 1989; 18: Stolzenburg S, Kresse S, Muller-Stolzenburg NW: Thermal side reactions during in vitro contact cyclophotocoagulation with the continuous wave Nd:YAG laser. Ophthalmic Surg 199; 21: Cohen EJ, Schwartz LW, Luskind RD, et al: Neodymium:YAG laser transscleral cyclophotocoagulation for glaucoma after penetrating keratoplasty. Ophthalmic Surg 1989; 2: Fiore PM, Melamed S, Krug JH Jr: Focal scleral thinning after transscleral Nd:YAG cyclophotocoagulation. Ophthalmic Surg 1989; 2: Hardten DR, Brown DJ: Malignant glaucoma after Nd:YAG cyclophotocoagulation. Am J Ophthalmol 1991; 111: Edward DP, Brown SVL, Higginbotham E, et al: Sympathetic ophthalmia following neodymium:yag cyclotherapy. Ophthalmic Surg 1989; 2: Brancato R, Leoni G, Trabucchi G, et al: Histopathology of continuous wave neodymium:yttrium aluminum garnet and diode laser contact transscleral lesions in rabbit ciliary body: A comparative study. Invest Ophthalmol Vis Sci 1991; 32: Assia EI, Hennis HL, Stewart WC, et al: A comparison of neodymium:yttrium aluminum garnet and diode laser transscleral cyclophotocoagulation and cyclocryotherapy. Invest Ophthalmol Vis Scd 1991; 32: Hennis HL, Stewart WC: Semiconductor diode laser transscleral cyclophotocoagulation in patients with glaucoma. Am J Ophthalmol 1992; 113: DISCUSSION DR GEORGE L. SPAETH. Doctors Gaasterland and Pollack have given us a carefully designed, implemented, and analyzed study of the effects of a relatively new method of reducing aqueous inflow. As Doctor Gaasterland mentioned at the start of his presentation, the basic mechanism of reducing aqueous inflow by damaging the ciliary body is an old one. Some of those still practicing today will remember the relative enthusiasm that some investigators expressed for penetrating cyclodiathermy. Two quite different issues will be covered in this discussion: first, Doctor Gaasterland's presentation, which really speaks for itself, and second, two more generic issues that relate directly to this study and to all others like it. The authors have shown that damaging the ciliary body with energy produced by a diode laser is probably roughly comparable to damaging the ciliary body with energy produced by a Nd:YAG laser. While there are some theoretical advantages of the contact versus the noncontact method ofapplication of laser energy, the end result does not appear to vary significantly between the two methods. It appears that there is not a significant difference in outcome between use ofa diode laser or the Nd:YAG laser. Both can, and do, produce significant lowering ofpressure with

20 244 Gaasterland & Pollack benefit to patients, and both can, and do, produce hypotony with damage to patients. Although the authors have not compared cyclophotocoagulation with other cyclodestructive procedures, such as cyclocryotherapy, the superiority of cyclophotocoagulation is reflected by greater control of the procedure, markedly less pain for the patient, and fewer devastating complications, such as phthisis bulbi. The Nd:YAG lasers used to perform cyclophotocoagulation, however, are expensive and cumbersome. The ability to have a similar effect with a much simpler, less expensive laser system represents a real step forward, and it is reassuring that this laser, which will soon be readily available, functions satisfactorily. The generic issues, however, are of more concern. The first of these relates to the entire problem of treating end-stage glaucoma with any technique, but especially with the technique that relies on producing a ciliary body destruction and decreasing inflow. In a normal eye there is a large amount of compensatory ability of the outflow system. As inflow increases or decreases, outflow increases or decreases relatively commensurately, maintaining stable IOP As glaucoma becomes more advanced, and as the outflow mechanisms become increasingly damaged, not only does the total amount of outflow decrease, but the adaptability of the outflow mechanism decreases. In end-stage glaucoma there is little outflow, and there is little ability of the outflow to change. This phenomenon partially explains why IOP becomes increasingly unstable in patients with increasingly poor outflow. A vitally important correlate, however, is that the effect of therapy is based on decreasing inflow that has increasingly variable effects as glaucoma becomes more advanced. If one assumes an inflow and an outflow of 24 arbitrary units of aqueous humor, and one assumes a decrease of outflow ability of around 9 U (around 37%) then decreasing inflow about 3% would result in no change in IOP, the pressure that was present before the outflow decreased. However, it is not only total outflow that decreases with glaucoma, it is also the adaptability of the outflow mechanisms; the ability of the eye to compensate in changes in inflow becomes increasingly poor as the eye becomes increasingly damaged by glaucoma. Thus, as the outflow mechanisms become less able to compensate, a change in inflow results in a larger change in IOP. Eventually, when the outflow mechanisms are almost totally obliterated with no compensatory ability, then even small changes in inflow result in dramatic changes in IOP An eye with an outflow capacity of 1 U could have a "normal" IOP if the amount of inflow were at 1 U. But if the eye had even a slight increase in inflow, say 3 U, the IOP would increase markedly, and if the eye had even a slight decrease in inflow, say 1 U, then the pressure would become seriously hypotonus. The entire concept of trying to regulate IOP by altering inflow in an eye in which the outflow is extraordinarily damaged to start with is, thus, a faulty one. The phenomenon of serious hypotony in association with the use of medical agents that reduce inflow is well described. When the mechanism of reducing inflow is more likely to be permanent, as it is with the cyclodestructive procedures, then the seriousness of this complication increases to such an extent as to cast serious doubt on the appropriateness of the procedure itself

21 Laser Transcleral Cyclophotocoagulation 245 The other generic issue has to do with the inevitable disadvantages of designing a study in a way that maximizes the safety and appropriateness of treatment. The method of the laser treatments in Doctor Gaasterland and Pollack's study was not entirely standard. Indeed, the method was purposely altered to ensure that the treatment would be most appropriate for the individuals being treated. And while this does result in more appropriate treatment for the individual, it makes analysis of the data extraordinarily difficult. The ethical dilemma is, of course, should studies be designed to be optimally safe, or to produce the optimal amount of valid information? That subject in itself could take up an entire series of meetings. DR D. JACKSON COLEMAN. I very much enjoyed your presentation and would like to comment and ask you a question that relates to your mention of corneoscleral perforations. We evaluated the records of 11 patients treated with the therapeutic ultrasound techniques which, like laser, also embodies a heat conversion method. We had four scleral perforations in that total series. Heat causes thinning of collagen, and is more marked in juvenile and/or regenerative collagen than adult collagen. Scar tissue as from previous surgery, is thus more easily thinned. This can be very useful in restoring failing filter blebs where regenerative collagen led to closure of the scleral opening. Your patients age 31 to 51 years would probably not have either juvenile or regenerative collagen but the fact that different collagens respond in different ways to heat, should be considered along with the pigment variations that you mentioned in choosing sites for treatment. You described popping noises that occur during the photodestructive process. As far a I am aware these relate to the cavitation phenomenon which has not been well described in the literature. My question is: Are you familiar with any data on the energy released during the laser thermal treatments you have described? DR JACOB T. WILENSKY. I would like to add my congratulations to the authors of this study. I was particularly interested in the reports of the conjunctival burns and the scleral perforation. We have spent a lot of time working with Nd:YAG lasers, and particularly the last couple of years have been using the contact mode. We have not seen scleral perforation as a problem in a much larger series. I was wondering whether you think that possibly the fact that you are using a 2-second burn could be contributing to this as opposed to the.7 to.8 seconds that most people are using with the Nd:YAG? Secondly, I would like to respond to Doctor Spaeth's comments. Again, within our series we really have not seen much phthisis at all. We have seen hypotony, not really phthisis. Perhaps we are being less than aggressive on some of these cases. But I also wonder if maybe there is the possibility that in addition to reduction of aqueous production is there a possibility that we are creating or enhancing somewhat uveoscleral outflow so that we are actually getting a beneficial affect on outflow from the eye. I don't know whether we are or not, but I would like hear the authors comments on that. DR DOUGLAS E. GAASTERLAND. Doctor Spaeth has emphasized that the patients treated with ciliary ablation are often at a late stage of glaucoma, with almost no

22 246 Gaasterland & Pollack outflow and in need of minimal inflow if the pressure is to be brought to balance. These eyes are precarious. They are difficult. A small flow of aqueous is potentially too much; and a lessening of it can result in hypotony. Typically, when we do laser ciliary ablation we discontinue medications that suppress aqueous formation. This leaves some room to achieve a new balance of inflow and outflow by using aqueous suppressing medications after the eye has healed. Doctor Coleman properly emphasizes the problem of scleral perforation (sclerostomy) that occurred in one of our patients. This isolated event was an aberration, though an important one. It has previously been reported that scleral perforation can be achieved with fiberoptics having planar tips if tissue debris becomes baked onto the glass at the tip. During laser irradiation the temperature at contaminated fiberoptic tips has been measured by Stolzenburg and co-workers in excess of3 C, sufficient to melt and burn through scleral tissue. This effect is not good ifwe are doing transscleral ciliary ablation, but it might provide a tool for laser filtering procedures if it could be achieved reproducibly. Doctor Wilensky has commented that the sapphire tip for the fiberoptic for one of the commercial Nd:YAG systems combined with the shorter exposure time (.7 seconds) typically used for ciliary ablation with that system might be more safe than our 2-second exposures. I disagree. Several years ago we did human autopsy eye studies using a rounded tip fiberoptic, an argon blue-green laser, and exposures of.1 second at 2.5 W We easily burned through the sclera after an average of six laser applications. In my view, the important variables affecting sclerostomy are absorption of light energy by the target tissue and temperature at the tip of the fiberoptic. Several discussants have raised the important issue of phthisis. This occurs frequently after cyclocryotherapy as shown in reports by Bellows and by Caprioli and co-workers. We share in the widely held impression that phthisis occurs less frequently after laser ciliary ablation. This impression deserves testing. Finally, following up on Doctor Spaeth's comments, I believe there is an appealing and clinically justified role for diode laser TSCPC earlier in the steps of surgical glaucoma intervention. Rather than save the treatment until the outflow is nearly zero, use it earlier in the glaucoma surgical sequence. At the earlier stage the precarious balance characteristic of late glaucoma is less a problem. This is a stage when ophthalmologists have patients use beta blockers and carbonic anhydrase inhibitors. Like these medications, laser ciliary ablation reduces the aqueous flow rate. We thank the discussants for their thoughtful comments.