Contact Transscleral Continuous Wave Neodymium:YAG Laser Cyciophotocoaguiation JOEL s. SCHUMAN, MD, CARMEN A. PULIAFITO, MD, R. RAND ALLINGHAM, MD, C. DAVIS BELCHER, MD, A. ROBERT BELLOWS, MD, MARK A. LATINA, MD, BRADFORD J. SHINGLETON, MD Abstract: Advanced glaucoma in 140 eyes of 136 patients was treated with contact transscleral continuous wave neodymium:YAG (Nd:YAG) laser cyclophotocoagulation (eyC) with a sapphire-tipped probe. The anterior edge of the probe was placed 0.5 to 1.5 mm posterior to the limbus, using 7 to 9 W of power for 0.7 seconds with 32 to 40 applications, sparing the 3 and 9 o'clock meridians. Patients were studied prospectively. The mean preoperative intraocular pressure (lOP) of 36.7 ± 0.97 mmHg decreased to 21.2 ± 0.99 mmHg (P = 0.004) after treatment (mean follow-up, 3.2 ± 0.35 months) for a mean decrease in lOP of 15.5 ± 1.21 mmHg and a mean percent decrease of 39%. Forty-one eyes were followed 6 or more months (mean, 6.7 ± 0.25 months). The eye reduced lOP to 25 mmHg or less in 71 % of eyes, to 22 mmHg or less in 62% of eyes, and to 19 mmHg or less in 49% of eyes. Maximum lowering of lOP occurred 1 week to 1 month after treatment and remained at that level through 6 months of follow-up. Retreatment was required in 11 % of patients; only one patient was retreated more than once. Four patients treated with 9 W of power developed lOPs below 5 mmHg; two of these patients had an lOP of mmHg. Other complications of therapy were minimal, and patients had little pain. There was no significant change in visual acuity. Early results of this newly available therapy are encouraging. Ophthalmology 1990; 97:571-580

o

The use of light to ablate the ciliary body was first proposed by Weekers and co-workers! in 1961 using xenon arc photocoagulation. Although they showed no advanOriginally received: September 26,1989. Revision accepted: January 3, 1990. From the Morse Laser Center, Glaucoma Consultation Service, Massachusetts Eye and Ear Infirmary, Boston. Presented at the American Academy of Ophthalmology Annual Meeting, New Orleans, Ocl/Nov 1989. Supported in part by a grant from the Heed Ophthalmic Foundation (Dr. SChuman). The authors have no proprietary interest in the development or marketing of the instrument used in this study. Reprint requests to Joel S. Schuman, MO, Glaucoma Consultation Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114.

tage over penetrating diathermy, investigation into transscleral cyclophotocoagulation continued, and in 1972, Beckman and co-authors2 reported transscleral cyclodestruction with a ruby laser. Cyclocryotherapy (CCT) has remained the cyclodestructive treatment of choice in patients with glaucoma refractory to medical and surgical treatment, in part because of the limited availability of the ruby laser. Neodymium:YAG laser (Nd:YAG) cyclophotocoagulation has now been shown to be another effective means of lowering intaocular pressure (lOP) by ciliodestruction. The Nd:YAG laser energy for transscleral cyclophotocoagulation can be delivered by the non contact or contact method. Several studies showed the efficacy of noncontact transscleral continuous wave Nd:YAG laser cyclophotocoagulation (NCYC) in rabbitsY autopsy human eyes,3,5 and in human clinical studies. 6 - 9 Contact transscleral continuous wave Nd:YAG laser cyclophotocoagu571

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Table 1. Treatment Technique: Contact Neodymium:YAG

Fig 1. Treatment pattern: contact transscleral continuous wave neodymium:YAG laser cyclophotocoagulation.

0.5 TO 1 MM

(1) Continue all preoperative glaucoma medications before laser treatment (2) Obtain informed consent (3) Confirm satisfactory operation of laser and fiberoptic delivery system (4) Administer retrobulbar or peri bulbar anesthesia (5) Lie patient supine (6) Surgeon and assistants wear protective eye gear (7) Lid speculum for treated eye, patch opposite eye (8) Moisten cornea with balanced saline solution between quadrants (9) Laser settings Power, 7 W Duration, 0.7 second (10) Treatment parameters No. of applications, 32 Treatment pattern, 8 spots per quadrant Spare 3 and 9 o'clock Spot location Anterior edge of probe 0.5-1.0 mm from limbus, i.e., center probe 1.5-2.0 mm posterior to limbus Measure with calipers Treatment technique Press gently with the probe, keeping the handpiece perpendicular to the sclera Maintain contact throughout energy delivery (11) Document power, duration, no. of spots, distance from limbus and total energy delivered, and diagram treatment (12) Postoperative medications Patch eye postoperatively 4-6 hrs Atropine 1% twice daily, taper as inflammation subsides Prednisolone acetate 1% 4 times daily, taper as inflammation subsides Continue all preoperative glaucoma medications except miotics May resume miotics if needed when inflammation subsides (13) Check lOP at 1 hr, 1 day, and 1 wk after treatment; follow-up and medications thereafter depend on clinical response (14) Patient may require retreatment if lOP is not adequate at 1-mo check. lOP

=

intraocular pressure.

Technologies, Inc., Malvern, PA). The probe tip was 2.2 mm in diameter, constructed of synthetic sapphire. PATIENT SELECfION AND PROTOCOL Fig 2. Distance of contact probe from limbus.

lation (CYC) has been effective in rabbits lO- 14 and autopsy human eyes (R. Rand Allingham, MD, personal communication); one clinical study of23 patients showed lOP lowering with CYC. 15 We report on a clinical trial of 160 treatments with this new technology for transscleral Nd: YAG laser cyclophotocoagulation.

MATERIALS AND METHODS LASER AND DELIVERY SYSTEM

A continuous-wave Nd:YAG laser with a 600-JI,m quartz fiberoptic contact probe was used (Surgical Laser

572

We treated 140 eyes (160 treatments) of 136 patients (average age, 61 ± 1.7 years; range, 2-90) with transscleral photocoagulation of the ciliary body (Figs 1,2; Table 1). All were treated by the authors and 14 additional surgeons in accordance with the protocol discussed below; patients were followed prospectively. Patients undergoing CYC had glaucoma refractory to conventional treatment and were using maximum-tolerated medical therapy. There were no entry criteria regarding absolute lOP or visual acuity. The treatment protocol was reviewed and approved by the Human Studies Committee of the Institutional Review Board of the Massachusetts Eye and Ear Infirmary. Two groups of patients were studied. The first group (group 1: 52 of 160 procedures [33%]) was treated with

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CONTACT ND:YAG CYCLOPHOTOCOAGULATION

the following parameters: the anterior edge of the probe was positioned 1.5 mm posterior to the limbus with 40 applications of 7 W for 0.7 seconds each. The second group (group 2: 108 of 160 procedures [67%]) was treated with the following parameters: anterior edge of the probe 0.5 to 1.0 mm posterior to the limbus with 32 applications of9 W for 0.7 seconds. In each group the 3 and 9 o'clock meridians were not treated to avoid injury to the long posterior ciliary arteries. The surgeons were permitted to vary the treatment power, number of applications, or the distance of the probe from the limbus at their discretion. Nineteen eyes, therefore, fit the strict criteria for group 1, and 50 eyes fit the strict criteria for group 2. Sixty-four eyes (40%) were treated with 7 W, 91 eyes (57%) with 9 W, two eyes (1%) with 5 W, and three eyes (2%) with 6 W. The eyes were compared (and the results were reported) with respect to treatment group and each separate parameter, i.e., treatment power, distance of the probe from the limbus, and number of applications. Patients were followed at 1 hour, 1 day, 1 week, 1 month, 3 months, 6 months, and as needed thereafter. Data collected at each visit are shown in Table 2. RETREATMENT

Sixteen patients had one eye retreated with CYC once each; one patient had one eye retreated four times. Retreated eyes were analyzed with the rest of the study population and were considered continuations of the first treatment for statistical analysis. Four patients had two eyes treated.

Table 2. Information Collected Preoperatively and at Follow-up Name Date of treatment Physician Primary diagnosis* Type of glaucoma* Previous laser or surgical procedures' Current medications Visual acuity Intraocular pressure Slit-lamp examination Conjunctival injection (0-4+) Cells (0-4+) Flare (0-4+) Cataract (0-4+) Fundus examination' Postoperative paint , Collected only preoperatively. t Postoperative pain assessed on postoperative day 1. Table 3. Glaucoma Diagnosis in 136 Eyes Primary Diagnosis

No. of Eyes (%)

Primary open-angle glaucoma Neovascular glaucoma Chronic angle-closure glaucoma Mixed mechanism glaucoma Secondary open-angle glaucoma Angle recession glaucoma

46 (34) 45 (33) 23 (17) 9 (7) 12 (9) 1 (1)

Table 4. Previous Laser and Surgical Treatment in 136 Eyes

GLAUCOMA TYPE AND PREVIOUS TREATMENTS

Six types of glaucoma were represented in the population (Table 3): neovascular (NVG), primary open-angle (POAG), chronic angle-closure (CACG), mixed mechanism, secondary open-angle, and angle-recession. Differences between these groups were studied as were differences between NVG and non-NVG and between POAG and non-POAG. Various laser and surgical treatments had been done before CYC in many patients (Table 4). Of the 137 eyes, there were 49 phakic eyes and 45 eyes with NVG; 29 of the phakic eyes had NVG. RACE

Seventeen of the patients were not white (black, Hispanic, or Oriental). There was no significant correlation between race and treatment group. DROPOUTS

Fourteen patients were dropped from the study prematurely. Nine were treated with CCT for lOP control. One patient moved out of state, one left the country, and one underwent surgery with Molteno plate implantation. One patient refused to return for follow-up after treatment. All patients were included in the data analysis until the time of failure or loss to follow-up. Three patients with no posttreatment follow-up were excluded from the data analysis.

No. of Eyes (%) Previous Treatment Prior cyclophotocoagulation Contact Noncontact Laser trabeculoplasty Once Twice Three or more times Laser iridotomy Goniophotocoagulation Panretinal photocoagulation

20 (15) 12 (9) 18 (13) 20 (15) 3 (2) 12 (9) 3 (2) 20 (15)

Previous surgery Glaucoma surgery Filtration surgery Cyclodialysis Cyclocryotherapy Penetrating keratoplasty Cataract extraction Vitreoretinal surgery

47 (35) 6 (4) 24 (18) 18 (13) 84 (63) 28 (21)

STATISTICAL ANALYSIS

All data were coded and entered into a commercial spreadsheet (Lotus 1-2-3 Release 2.01, 1987, Lotus Development Corporation, Cambridge, MA) and analyzed 573

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using a commercial statistical software package (CSS Complete Statistical System, 1988, StatSoft, Tulsa, OK). Tests for significance included analysis of variance, multiple regression, two-tailed t test, and chi-square test; These are listed with their P values. Means are listed with standard errors of the mean; P values are for two-tailed t tests unless otherwise indicated. Retreatments were considered as continuations of initial treatments; that is, each eye was considered a single case whether it had one treatment or several.

RESULTS INTRAOCULAR PRESSURE

The mean pretreatment lOP for those patients followed 6 months or more was 35.2 ± 1.59 mmHg (range, 1958). Six months or more after treatment the mean lOP was 18.4 ± 1.16 mmHg (range, 5-38; N = 41) (Fig 3). This difference was statistically significant (P < 0.001). The mean reduction in lOP at the most recent postoperative visit compared with pretreatment was 16.8 ± 1.95 mmHg, a mean percent decrease of 44%. The mean follow-up for the 41 patients followed 6 or more months was 6.7 ± 0.25 months. For all patients at their most recent follow-up visit (average follow-up, 3.2 ± 0.35 months), the mean pretreatment lOP was 36.7 ± 0.97 mmHg, and the mean posttreatment lOP was 21.2 ± 0.99 mmHg (range, 0-57; P = 0.004). This represents a mean lOP reduction of 15.5 ± 1.21 mmHg, a mean percent decrease of 39%. The procedure reduced lOP to 5 to 25 mmHg in 68% of patients, 5 to 22 mmHg in 59%, and 5 to 19 mmHg in 46% (Table 5). Success rates at the lOP levels most commonly used as criteria for success in the literature are provided for the purpose of comparison between studies. The lOP appears to reach its nadir at 1 week to 1 month and remains at 574



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that level through atleast the 6-month follow-up (Fig 4). An lOP rise after treatment was uncommon, with an 8mmHg or greater lOP elevation 1 hour postoperatively in 12 of 130 treatments (9%) and 1 day postoperatively in seven of 125 eyes (6%). Three eyes had lOP elevations of 8 mmHg or greater at both 1 hour and 1 day. For those with a final lOP between 5 and 19 mmHg, the average pretreatment lOP was 34.7 ± 1.45 mmHg, compared with 38.4 ± 1.28 mmHg for those without a "successful" final lOP. This difference was not statistically significant. The average final lOP for "successes" was 12.8 ± 0.50 mmHg and for "failures" was 28.5 ± 1.31 mmHg (P < 0.001). Patients who would be successful could be identified by the first week postoperatively; successful patients had a mean lOP at 1 week of 15.0 ± 0.98 mmHg, and failures had an average lOP at 1 week of24.7 ± 1.70 mmHg (P < 0.001) (Fig 5). Similar findings were seen whether success was defined as lOPs between 5 to 22, 5 to 25, 3 to 19, 3 to 22, or 3 to 25 mmHg. Over half of the patients who failed did so within the first week (Fig 6). A higher initial lOP correlated significantly with a higher final lOP by regression analysis (beta = 0.243, P = 0.004), and there was a significant correlation between higher initial lOP and failure (final lOP < 5 or > 25 mmHg, beta = 0.242, P = 0.004). However, there was a greater change and percent change in lOP (change in lOP: beta = 0.600, P < 0.001; percent change in lOP: beta = 0.234, P < 0.001). The NVG patients had a greater absolute decrease in lOP than non-NVG patients, but the percent decrease in lOP was not significantly different between the two groups (decrease in lOP = 20.0 mmHg in NVG, 13.2 mmHg in non-NVG, P = 0.008; percent decrease in lOP = 42.5% in NVG, 37.4% in non-NVG, P = 0.362). Mean pretreatment lOP was higher in the NVG than in the non-NVG group, but there was no significant difference between the groups for lOP at the last follow-up visit (mean pretreatment lOP = 44.0 mmHg in NVG, 33.1 mmHg in nonNVG, P < 0.001; mean final lOP = 24.0 mmHg in NVG, 19.9 mmHg in non-NVG, P = 0.052). The non-POAG patients had a significantly greater magnitude of reduction and percent decrease in lOP than the POAG patients (reduction in lOP = 10.7 mmHg in POAG, 17.9 mmHg in non-POAG, P = 0.005; percent decrease in lOP = 31.2% in POAG, 43.0% in non-POAG, P = 0.033). Patients who had had a penetrating keratoplasty (PK) had a significantly greater reduction in lOP and percent change in lOP than those who had not undergone PK (decrease in lOP = 22.0 mmHg in PK, 14.6 mmHg in non-PK, P = 0.039; percent decrease in lOP = 53.8% in PK, 37.1% in non-PK, P = 0.031). A history ofPK was significantly correlated with a final lOP between 5 and 22 mmHg (beta = 0.233, P = 0.006). There was a greater percent decrease in lOP at 1 day and 1 week after the first CYC treatment than after retreatment; after 1 week there was no significant difference between these groups (percent decrease lOP at 1 day = 26.7% for first treatment, 6.4% for retreatment, P

SCHUMAN et al



CONTACT ND:YAG CYCLOPHOTOCOAGULATION

= 0.012; at I week = 43.6% for first treatment, 25.9% for retreatment, P = 0.027).

A difference in reduction of lOP was not statistically significant in the following groups: white versus nonwhite patients, aphakic versus phakic patients, group I versus group 2, or patients over 60 years of age versus those less than 60 years of age. Varying the distance of the probe from the limbus or the number of applications of the laser had no statistically significant effect on pressure reduction. There was no significant difference in lOP reduction for patients treated with 7 W of power compared with those treated with 9 W.Covariate analysis by analysis of variance and multiple regression showed no effect on lOP of changes in power, distance of the probe from the limbus, or number of applications. There was no significant correlation between posttreatment pain and reduction ofIOP or postoperative inflammation and lOP reduction. There was no significant difference among the treatment results of the various surgeons.

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Fifty-one percent of patients developed mild (I +) postoperative anterior chamber inflammation, 66% had I to 2+ flare and cells, and 25% had 3 to 4+ inflammation at I to 7 days. Inflammation generally resolved by I week.

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Nine of 122 eyes (7%) lost two or more lines of vision (two or more lines below pretreatment levels on two or more consecutive postoperative visits). All such eyes had initial visual acuity of 20/200 or worse. Eyes that lost vision had a significantly greater increase in cataract I week postoperatively and thereafter (P < 0.004). Six of the nine eyes with visual loss had NVG (P = 0.017), and seven of the nine eyes were phakic (P = 0.014). There was more cellular reaction in eyes that lost vision than those that did not at I hour and I day (P < 0.019) and more flare at I month and 6 months (P < 0.020). No statistically significant differences were found for race, amount of treatment power, number of applications, or distance of the probe from the limbus. There was no significant change in visual acuity in any group (success versus failure, white versus nonwhite, NVG versus non-NVG, POAG versus non-POAG, greater or less than 60 years of age, phakic versus aphakic, number of applications, 7 versus 9 W of power, probe placement, treatment groups I or 2, history of PK or no PK, or first treatment versus retreatment). The NVG group did not have a statistically significant loss of visual acuity over the course of the study. Three patients progressed to no light perception (NLP): one with NVG progressed from hand motions to NLP at an lOP of 22 mmHg, one with NVG progressed from light perception (LP) to NLP at an rop of 44 mmHg, and one with CACG progressed from LP to NLP at an lOP of 34 mmHg. All had reduced lOP, and there were no documented pressure spikes.

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Twenty-one percent of patients had trace to 1+ cells preoperatively. Mild to moderate flare was apparent in 79% of patients after treatment, and mild to moderate conjunctival injection was present in 80% of patients postoperatively. There was no statistically significant difference between cellular reaction, aqueous flare, or conjunctival injection before treatment and that at 3 or 6 months after treatment; however, cellular reaction, flare, and conjunctival injection were each significantly greater from 1 hour after treatment through 1 month after treatment than before CYe. Mean conjunctival injection was "trace" pretreatment, increased to 1 to 2+ at 1 hour postoperatively, was 1+ at 1 day and 1 week, and at 1, 3 and 6 months, was again "trace." Nonwhite patients had a significantly greater increase in cellular reaction and flare at 1 hour to 1 week than white patients (P < 0.03). They also had a greater increase in conjunctival injection at 1 hour and 1 week (P < 0.05). The NVG group, compared with the non-NVG group, had significantly greater cellular reaction at 1 day and 1 week (P < 0.02) and a greater increase in flare at 3 months (P < 0.01). There was no significant difference in conjunctival injection between NVG and non-NVG patients. Aphakic patients had statistically less inflammation at 1 hour postoperatively, flare (P = 0.020) at 1 hour and 1 day, and cellular reaction (P < 0.03); however, this difference in inflammation was not present when the NVG eyes were eliminated from the analysis. There was no significant difference for conjunctival injection in aphakic patients compared with phakic patients. Probe placement with the anterior edge of the probe at 0.5 and 0.75 mm posterior to the limbus caused less cellular reaction than placement of the probe more posteriorly at 1 hour through I week (P < 0.05), less increase in flare at I week (P = 0.004), and less conjunctival injection at I hour (P = 0.041). Placement at 0.5 to 1.0 mm posterior to the limbus gave less flare at I week than more posterior placement (P = 0.044). There was no significant difference in inflammatory reaction with regard to cellular reaction, increased flare, or conjunctival injection after treatment for the following groups: success versus failure, POAG or non-POAG, treatment groups I or 2, initial treatment or retreatment, age greater or less than 60 years old, history of PK or no PK, number of applications, and 7 or 9 W of power. CATARACT

Cataract was rated on a scale of 0 to 4+. The NVG patients had a greater increase in lens changes than the non-NVG patients at 1 week, 1 month, and 6 months (P < 0.03). There were more lens changes at I day and I month in patients treated with 9 W of power compared with those treated with 7 W, although changes in lens opacities were small (P < 0.04).

0.4 0.2 0.0

6.0 Time (Months)

Fig 6. Kaplan-Meier survival curve for contact transscleral continuous wave neodymium:Y AG laser cyclophotocoagulation. Notice that over half of the failures occurred within the first week after treatment.

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POSTTREATMENT PAIN

Average postoperative pain was "minimal" (none = 0 to severe = 4). Nonwhite patients had significantly more postoperative pain than white patients (mean, "mild to

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CONTACT ND:YAG CYCLOPHOTOCOAGULATION

moderate" for whites and "moderate to severe" for nonwhites, P = 0.014). There were no significant differences in posttreatment pain between the following groups: success or failure, aphakic or phakic, POAG or non-POAG, treatment groups 1 or 2, primary treatment or retreatment, age greater or less than 60 years old, and history of PK or no PK. There was no correlation between posttreatment cellular reaction, flare, or conjunctival injection and posttreatment pain. No effect was found for type of glaucoma overall and posttreatment pain. There was no effect of varying probe placement on posttreatment pain. MEDICAnONS

Preoperatively, 69% of patients were receiving carbonic anhydrase inhibitors, 89% beta blockers, 59% miotics, 41 % epinephrine or its prodrug, 25% cycloplegics, and 51 % topical corticosteroids. There was no significant change in the number of patients receiving oral or topical glaucoma medications during the 6 months after treatment compared with pretreatment medications. Ninety percent of patients were treated with cycloplegics and 95% with topical steroids for some time after laser therapy. At 3 months 46% of patients continued to receive cycloplegics, but only 39% were still receiving topical steroids. COMPLICAnONS

One white aphakic patient with NVG treated with 33 spots at 9 W of power had an lOP of 0 mmHg at 3 months. Visual acuity was unchanged at counting fingers. One nonwhite aphakic patient with CACG, treated with 32 spots at 9 W, had an lOP of 0 mmHg at 3 months. Visual acuity did not decrease from pretreatment LP. Neither patient had had any prior cyclodestructive treatment. One nonwhite aphakic patient with CACG treated with 32 spots at 9 W had an lOP of 4 mmHg at 3 months. There was no change in visual acuity (hand motions preoperatively). The patient had no history of cycloablative procedures. One white aphakic patient with NVG and proliferative diabetic retinopathy (POR) treated with 16 spots at 9 W, then retreated at 1 week with 24 spots at 9 W, had an lOP of 4 mmHg at 6 weeks. There was an increase in vision from LP to hand motions at 1 week. The patient had a history of CCT and NCYC. One nonwhite phakic patient with POR and NVG had a traction retinal detachment within 2 weeks of treatment with 9 Wand 32 spots. It is not clear if the cyclophotocoagulation and the retinal detachment were related; however, the patient had severe postoperative inflammation which may have contributed to the detachment. One white phakic patient with NVG and POR underwent vitrectomy with a fluid-gas exchange for a preexisting vitreous hemorrhage between 1 and 4 weeks after treatment with 9 Wand 24 spots. One nonwhite phakic patient with suspected tuberculous uveitis had an anterior chamber washout and vitreous aspirate 1 day af,er CYC treatment with 9 Wand 24 spots. One nonwhite aphakic patient with POAG treated with 9 Wand 16 applications had severe inflammation and choroidal effusions requiring

drainage postoperatively. Visual acuity decreased from 20/50 to 20/400 but then improved to 20/80. One nonwhite aphakic patient with POAG, treated with 9 Wand 16 spots, and one white aphakic patient with NVG, treated with 9 Wand 20 spots, each developed severe inflammation after treatment. Two eyes were enucleated, both from white patients: one from a patient with NVG 2 weeks posttreatment with an lOP of 44 mmHg and pain, the other from a patient with CACG and an lOP of 11 mmHg, but with persistent pain at 1 year post-CYC.

DISCUSSION Cyclocryotherapy, proposed by Bietti 16 in 1950 and first reported in rabbits and humans in 1964 by Polack and de Roetth 17 and McLean and Lincoff, 18 has been the standard means of ciliary body destruction in cases of glaucoma refractory to other therapies. Although Bellows and Grant showed that CCT provides effective lOP reduction in advanced inadequately controlled glaucoma, especially in aphakic eyes,19,20 severe complications, including phthisis bulbi in 0 to 12% of patients and visual loss in over two thirds of patients may occur. 19- 23 In addition, severe postoperative inflammation, pain, chronic hypotony, macular edema, and vitreous hemorrhage combine to make CCT a treatment oflast resort in the management of advanced glaucoma. The emergence of transscleral continuous wave Nd: Y AG laser cyclophotocoagulation as a treatment method for refractory glaucoma presents new options. The two delivery methods, CYC and NCYC, differ in several ways. The NCYC is done at a slit lamp with the patient sitting, but CYC may be done with the patient in the supine position. The contact laser is portable and may therefore be moved to the operating room for treating patients under general anesthesia. The NCYC generally uses 5 to 8 J of energy delivered over 20 ms (250-400 W) in 32 applications. 3,5-9 We did CYC using 4.9 to 6.3 J over 0.7 seconds (7-9 W) in 32 to 40 applications. Optimum location for beam placement in NCYC is 1.5 mm posterior to the limbus;3,5 optimum placement for the anterior edge of the contact probe in CYC is 0.5 to 1.0 mm posterior to the limbus, thus centering the 2.2-mm diameter probe at approximately 1.5 mm posterior to the limbus, as shown by Allingham and co-workers (personal communication), The differences in power settings and exposure time, resulting in a similar total energy delivery, cause distinct types of histopathologic tissue changes after treatment; these may relate to variations in postoperative inflammation, pain, and decreased vision after treatment, Fankhauser and co-workers3 and England and associates4 showed that NCYC in rabbits resulted in the destruction of the ciliary epithelium and associated vessels acutely, with atrophy of the ciliary processes 4 to 8 weeks after the injury. 3,4 Hampton and Shields5 examined lesions in the human autopsy eyes treated with NCYC. The most consistent histopathologic finding was destruction of the

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Table 6. Transscleral Neodymium:YAG Laser Cyclophotocoagulation Studies No. of Patients

Follow-up (mos)

No. of Spots

136

Average, 3.2

32-40

23

Average, 8.6

Laser Settings

Spot Locations

Final lOP (mmHg)

7-9W, 0.7 second

Anterior edge of probe, 0.5-1.5 mm posterior to limbus

16

4W, 0.5 second

Probe centered 1.5 mm posterior to limbus

:;:;25 (71%) :;:;22 (62%) :;:;19 (49%) 30

24

Mean, 8.8

40

Klapper et al ,8 1988

30

Average, 6

32

Trope and Ma, 1989t

29 eyes

Average, 22

100 eyes

Minimum, 6

Hampton et al,9 1989

29

32

Not provided

3 mm posterior to limbus, maximum defocusing 1.8-3.0 J, 2-3 mm posterior to 20 msecond limbus, maximum defocusing 3.5-4.5 J, 2-3 mm posterior to 20 msecond limbus, maximum defocusing Parameters not provided

8 J, 20 msecond

1.5 mm posterior to limbus, maximum defocusing

:;:;22 (69%) 1 Questionable phthisis; 41 % required retreatment :;:;21 (45.8%) 46% required multiple treatments :;:;22 (86%) 23% required retreatment :;:;21 (55%) Phthisis in 10.3%, visual loss in 20.6% despite lOP control; mean no. of treatments, 1.8 21%, transient lOP rise; 13.5%, severe pain; 28%, severe inflammation; 50% of patients lost vision; 25% required retreatment

lOP = intraocular pressure. * Presented at the Annual Meeting of the Association for Research in ViSion and Ophthalmology, 1985. t Presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, 1989.

ciliary epithelium with the creation ofa blister-like space. No coagulative necrosis was noted. Lesions in rabbit ciliary bodies using CYC were reported by Brancato and co-workers lO in 1987, Federman and associates 11 in 1987, Schubert and Federman l2 •13 in 1989, and Latina and co-authors l4 in 1989. The CYC lesions were well demarcated, white I-mm spots seen grossly I day after treatment. 1O•14 There was coagulative necrosis in the pigmented and nonpigmented epithelium, with extensive thermal damage in the ciliary body stroma. There was no significant scleral damage. 10. 14 Three weeks after treatment the ciliary body processes were flattened and covered by a fibrous membrane. 12 There was atrophy and disorganization of the ciliary body and iris stroma. The ciliary epithelium was abnormal where present. The sclera showed areas of compression with hypercellularity. 12 Latina and co-workers '4 demonstrated fusion and shortening of the ciliary processes with pigment epithelial pro-

578

liferation and focal epithelial interruptions and necrosis 4 weeks after CYC. Allingham and co-workers conducted human autopsy eye studies to determine the optimum probe placement and power levels for CYC. Their studies revealed coagulative necrosis of the ciliary body with disruption of the ciliary nonpigmented and pigmented epithelia at prime power levels with proper probe placement (personal communication). The coagUlative necrosis of the ciliary processes seen with CYC as opposed to the blister formation noted with NCYC 5,12 are probably related to the longer exposure time and lower power settings used with CYC; these may be associated with the greater postoperative inflammation, pain, and visual loss reported with NCYC. 6 •9 In reducing lOP in a number of studies (Table 6), NCYC has been shown to be clinically effective. 6- 8 Success rates range from 45 to 86% of patients with a final lOP

SCHUMAN et al



CONTACT ND:YAG CYCLOPHOTOCOAGULATION

of 22 mmHg or less. It is difficult to compare study results due to the differences in criteria for success and treatment parameters used by the different investigators. Limited follow-up for this new procedure also makes interpretation of the results and anticipation of the long-term complications difficult. Although phthisis did not develop before Devenyi's report (average follow-up, 8.8 months),6 Trope and Ma reported a 10.3% phthisis rate and a 20.6% rate of visual loss with NCYC in a group with a 22-month average follow-up (presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, FL, 1989). Our CYC results, with 68% (93 of 137) of our patients' eyes with a final lOP of 5 to 25 mmHg, 59% (81 of 137) with 5 to 22 mmHg, and 46% (63 of 137) with 5 to 19 mmHg, compare with the literature for NCYC (Table 6). We used 4.9 to 6.3 J per spot, for a total energy delivery of approximately 200 J (40 spots in group 1 and 32 spots in group 2), less energy than the 8-J and 32-spot treatments recommended for NCYC and less power per spot. 5 We had an 11 % retreatment rate, with only one patient requiring more than two treatments. Variations in power at the levels we used did not significantly affect the final lOP. There were, however, more inflammation and complications in the patients treated with 9 W of power than those treated with 7 W. This may represent the effect of treatment with a suprathreshold energy level. All patients with severe inflammation, and those with hypotony, were treated with 9 W of power. Three of the four patients with severe inflammation and 50% of those with hypotony were nonwhite; they were also in the higher power group. These combined factors may have produced more serious complications. In 1989, Brancato and co-workers l5 reported on 23 patients treated with CYC at 4 W of power for 0.5 seconds in 16 applications with the probe centered 1.5 mm posterior to the limbus (anterior edge approximately 0.5 mm posterior to the limbus; no sapphire tip was used). These settings delivered 2 J of energy per spot (32 J total), and 57% of patients required retreatment, with 21 % requiring three sessions (average follow-up, 8.6 months). On last follow-up visit, 66.6% had an lOP of 25 mmHg or less; three of the 23 patients had an lOP ofless than 20 mmHg. No cases of phthisis were reportedY Although it is difficult to compare the results of the Brancato group with ours (due to the use of a sapphire tip in our study, with a beam convergent at approximately 2 mm in air, whereas Brancato and associates used the bare quartz fiber, with a divergent beam), it is clear that the patients treated with 4.9 to 6.3 J per spot required fewer retreatments and that more patients treated with the higher energy levels had a lower final lOP, regardless of the number of treatments. Recent reports illustrate the differences in the incidence of severe inflammation and visual loss between CYC and NCYC. Trope and Ma's report was amplified by Hampton and co-authors,9 who followed 100 NCYC treatments for at least 6 months. They found severe pain in 13.5%, severe inflammation in 28%, a retreatment rate of approximately

25%, and visual loss in nearly 50%. We found less inflammation and pain with CYC than with NCYC,9 with only rare severe inflammation and a mean of minimal to mild postoperative pain. Visual loss was uncommon in our treatment group, occurring in only 7% of eyes. These differences between CYC and NCYC may be related to the type of histopathologic damage. 5,12 As with other forms of cyclodestruction, reduction in lOP and postoperative inflammatory response may depend on preexisting disease, with NVG patients responding poorly. 19,22 Krupin et al 22 found only a 45% response to CCT in NVG. Bellows and Grant l9 noted only 30% control in NVG with CCT. Worse still, despite seemingly adequate lOP control, many of these eyes continued to lose vision, probably due to retinopathy. Although we did not find a statistically different pressure-lowering effect in NVG versus non-NVG, NVG patients had higher lOPs and poorer visual acuity throughout the study. The NVG patients represented at least 50% of patients with severe complications, including those progressing to NLP (2 of 3) and those with severe inflammation (3 of 4), phthisis (1 of 2), and hypotony (1 of 2). These numbers are too small for statistical analysis, but NVG patients remain as difficult to treat with CYC as with other therapies. Although aphakic patients had a better pressure-lowering response to CCT than phakic individuals,2o we did not find this difference for CYc. The changes in lens opacities noted in phakic eyes during our study were minimal, especially with lower power settings; thus it appears reasonable to use CYC in phakic eyes with advanced glaucoma unresponsive to other medical and surgical therapies. Patients who had had PK had better pressure lowering than those who had not had PK. This is encouraging in light ofthe difficulty in treating post-PK eyes with CCT24,25 and the 41 % incidence of graft rejection after Molteno plate implantation reported by McDonnell and co-workers.26 The incidence of graft rejection is unknown in our patients. There appears to be a "pigment effect," with more pigmented eyes having a more intense reaction to treatment than less pigmented eyes. Our nonwhite patients had more posttreatment pain and inflammation than white patients; however, there was no significant difference between whites and nonwhites in lOP reduction. This has been discussed by de Roetth 27 about CCT, and by Cantor and co-workers28 and Schubert and Federman l2 ,13 with regard to cyclophotocoagulation. It may be that patients with more pigmentation have more local tissue damage due to increased energy absorption by the pigment with greater resultant tissue damage. Interestingly, Cantor and associates28 found laser effects in pigmented rabbits (Dutch-belted) treated with NCYC, but no histopathologic changes could be seen in albino rabbits. Our study suggests that treatments should be done with a 7-W power setting for 0.7 seconds, in 32 to 40 applications, with the anterior edge of the probe 0.5 to 1.0 mm posterior to the limbus. There seems to be no therapeutic advantage to treating with 9 W of power, and patients so 579

OPHTHALMOLOGY



MAY 1990

treated have more complications with a similar final pressure-lowering effect. The optimum treatment parameters have yet to be determined. Early results of CYC are encouraging. The lOP was reduced quickly, with maximum pressure lowering at 1 to 4 weeks. Successful patients had a mean final lOP of 12.8 ± 0.50 mmHg. Our results compared with those seen with NCYC, with less apparent inflammation, pain, and visual loss. Complications were rarer than with CCT, although there was also less success with CYC. It remains essential to determine the ideal power levels and number of applications for treatment, titrating the therapy to provide the best possible result with the fewest complications.

ACKNOWLEDGMENTS The authors thank Drs. Steven Depperman, Anthony Fraioli, Shlomo Melamed, Roger Steinert, John V. Thomas, Thomas R. Richardson, Michael Loebel, Claudia U. Richter, Nalini Madiwale, Mohandas Kini, John Sebestyen, C. Stephen Foster, Joseph Kim, and John Lowenstein for their cooperation in providing patient data.



9.

10.

11. 12.

13.

14.

15.

16. 17.

REFERENCES 1. Weekers R, Lavergne G, Watillion M, et al. Effects of photocoagulation of ciliary body upon ocular tension. Am J Ophthalmol1961; 52:15663. 2. Beckman H, Kinoshita A, Rota AN, Sugar HS. Transscleral ruby laser irradiation of the ciliary body in the treatment of intractable glaucoma. Trans Am Acad Ophthalmol Otolaryngol1972; 46:423-36. 3. Fankhauser F, van der Zypen E, Kwasniewska S, et al. Transscleral cyciophotocoagulation using a neodymium:YAG laser. Ophthalmic Surg 1986; 17:94-100. 4. England C, van der Zypen E, Fankhauser F, et al. Ultrastructure of the rabbit ciliary body following transscleral cyciophotocoagulation with the free-running Nd:YAG laser: preliminary findings. Lasers Ophthalmol1986; 1:61-72. 5. Hampton C, Shields MB. Transscieral neodymium-VAG cyclophotocoagulation. A histological study of human autopsy eyes. Arch Ophthalmol1988; 106:1121-3. 6. Devenyi RG, Trope GE, Hunter WH, Badeeb O. Neodymium:YAG transscieral cyciocoagulation in human eyes. Ophthalmology 1987; 94:1519-22. 7. Schwartz LW, Moster MR. Neodymium:YAG laser transscleral cyciodiathermy. Ophthalmic Laser Ther 1986; 1:135-41. 8. Klapper RM, Wandel T, Donnefeld E, Perry HD. Transscieral neodym-

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27. 28.

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ium:YAG thermal cyciophotocoagulation in refractory glaucoma: a preliminary report. Ophthalmology 1988; 95:719-22. Hampton C, Shields MB, Miller KN, Blasini M. Evaluation of a protocol for transscleral Nd:YAG photocoagulation in 100 patients. Ophthalmology (in press). Brancato R, Leoni G, Trabucchi G, Trabucchi E. Transscleral contact cyclophotocoagulation with Nd:YAG laser CW: experimental study on rabbit eyes. Int J Tissue React 1987; 9:493-8. Federman JL, Ando F, Schubert HD, Eagle RC. Contact laser for transscleral photocoagulation. Ophthalmic Surg 1987; 18:183-4. Schubert HD, Federman JL. A comparison of CW Nd:YAG contact transscleral cyclophotocoagulation with cyclocryopexy. Invest Ophthalmol Vis Sci 1989; 30:536-42. Schubert HD, Federman JL. The role of inflammation in CW Nd:YAG contact transscieral photocoagulation and cryopexy. Invest Ophthalmol Vis Sci 1989; 30:543-9. Latina MA, Patel S, de Kater AW, et al. Transscleral cyclophotocoagulalion using a contact laser probe: a histologic and clinical study in rabbits. Lasers Surg Med 1989; 9:465-70. Brancato R, Giovanni L, Trabucchi G, Pietroni C. Contact transscieral cyciophotocoagulation with Nd:YAG laser in uncontrolled glaucoma. Ophthalmic Surg 1989; 20:547-51. Bietti G. Surgical intervention on the ciliary body. New trends for the relief of glaucoma. JAMA 1950; 142:889-97. Polack FM, de Roetth A Jr. Effect of freezing on the ciliary body (cyciocryotherapy). Invest OphthalmoI1964; 3:164-70. McLean JM, Lincoff HA. Cryosurgery of the ciliary body. Trans Am Ophthalmol Soc 1964; 62:385-407. Bellows AR, Grant WM. Cyciocryotherapy in advanced inadequately controlled glaucoma. Am J Ophthalmol 1973; 75:679-84. Bellows AR, Grant WM. Cyciocryotherapy of chronic open-angle glaucoma in aphakic eyes. Am J Ophthalmol 1978; 85:615-21. Feibel RM, Bigger JF. Rubeosis iridis and neovascular glaucoma: evaluation of cyclocryotherapy. Am J Ophthalmol1972; 74:862-7. Krupin T, Mitchell KB, Becker B. Cyciocryotherapy in neovascular glaucoma. Am J Ophthalmol1978; 86:24-6. Brindley G, Shields MB. Values and limitations of cyciocryotherapy. Graefes Arch Clin Exp Ophthalmol1986; 224:545-8. Tragakis MP, Brown SI. The significance of anterior synechiae after comeal transplantation. Am J Ophthalmol1972; 74:532-3. Binder PS, Abel R Jr., Kaufman HE. Cyciocryotherapy for glaucoma after penetrating keratoplasty. Am J Ophthalmol 1975; 79:489-92. McDonnell PJ, Robin JB, Schanzlin OJ, et al. Molteno implant for control of glaucoma in eyes after penetrating keratoplasty. Ophthalmology 1988; 95:364-9. de Roetth A Jr. Cryosurgery for the treatment of advanced chronic simple glaucoma. Am J Ophthalmol 1968; 66: 1034-41 . Cantor LB, Nichols DA, Katz J, et al. Neodymium-YAG transscleral cyciophotocoagulation: the role of pigmentation. Invest Ophthalmol Vis Sci 1989; 30:1834-7.

Contact transscleral continuous wave neodymium:YAG laser cyclophotocoagulation.

Advanced glaucoma in 140 eyes of 136 patients was treated with contact transscleral continuous wave neodymium:YAG (Nd:YAG) laser cyclophotocoagulation...
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