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Neodymium:YAG Laser Trabeculopuncture in Open-angle Glaucoma
Neodymium:YAG Laser Trabeculopuncture in Open-angle Glaucoma DAVID L. EPSTEIN, MD, SHLOMO MELAMED, MD, CARMEN A. PULIAFTO, MD, ROGER F. STEINERT, MD
Abstract: Ten eyes of eight patients with open-angle glaucoma (OAG) had neodymium (Nd):YAG trabeculopuncture performed in an investigational protocol as an alternative to surgical intervention. In each, at four to six sites in the mid-trabecular meshwork, three to six superimposed applications were made (2 to 6 mJ). In four of six patients with adult OAG, a small decrease in intraocular pressure (lOP) was noted (from a mean of 25.5 to 20.0 mmHg after 3-4 weeks in the treated eyes, compared to no change at 21 mmHg in the fellow eyes). There appeared to be further attenuation of this lOP effect over the subsequent 2 to 11 months, and all patients demonstrated gonioscopic closure of all the puncture sites with time. One patient demonstrated an acute lOP elevation to 58 mmHg after the procedure, necessitating emergency filtration surgery. In contrast, in four eyes of two patients with juvenile open angle glaucoma, a dramatic lowering of lOP and improvement in tonographic outflow facility was demonstrated, although the effects were only temporary in one patient. YAG laser treatment to the trabecular meshwork may have its greatest potential usefulness when abnormalities in the uveal meshwork are involved, such as in certain cases of juvenile or congenital glaucoma, and may help identify the need for a surgical goniotomy. With more usual forms of OAG, however, widespread use of this technique should be avoided until greater efficacy can be achieved. [Key words: glaucoma, laser, juvenile glaucoma, open-angle glaucoma, trabecular meshwork, trabeculopuncture, YAG laser goniotomy.) Ophthalmology 92:931-937, 1985
Since the trabecular meshwork is believed to be the locus of abnormal resistance to aqueous humor outflow in open angle glaucoma, 1 an appealing, potentially simple treatment involves the placement of one or more "holes" through this tissue by means of laser energy in order to bypass this site of abnormality.Z- 14 We have recently
From the Glaucoma Consultation Service and Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. Presented at the Eighty-ninth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Supported in part by National Glaucoma Research, a program of the American Health Assistance Foundation. Reprint requests to David L. Epstein, MD, 243 Charles St., Boston, MA 02114.
utilized the Nd:YAG laser to so puncture the trabecular meshwork in living monkeys. 15 By superimposition of a few applications, one can very readily penetrate through the trabecular meshwork into Schlemm's canal and obtain blood reflux from the canal into the anterior chamber. Acutely, there is substantial intraocular pressure (lOP) reduction associated with a measured increase in aqueous humor outflow facility. However, after eight days, lOP and outflow facility return to baseline levels and gonioscopically one observes "filling in" of the puncture sites with a tissue that consists morphologically of fibrous "scar" tissue covered by a focal downgrowth of a Descemet's-like membrane. 15 Thus, it would seem that the normal biological response of the trabecular meshwork to such laser application would preclude its clinical applicability in human glaucoma. There is a potential flaw, however, in this reasoning which involves the comparison of young, normal mon931
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keys with that of adult, abnormal glaucoma patients. It is known that argon laser trabeculoplasty, an increasingly utilized clinical treatment for open-angle glaucoma, is ineffective in improving outflow facility in normal monkeys. 16 It is possible that the "healing" properties of glaucomatous trabecular tissue may be different from that of the normal monkey. In addition, there are anatomical differences between the monkey and human. For example, Schlemm's canal is more anterior in the monkey and it would seem very difficult in the monkey to avoid some energy absorption by the peripheral corneal endothelium during trabeculopuncture. Likewise, blood reflux from Schlemm's canal would not be expected with trabeculopuncture in a usual human glaucomatous eye and it is possible that blood elements might be involved somehow in the trabecular healing process in the monkey. For these various reasons, it seemed important to gain further knowledge of the potential efficacy of Nd:YAG trabeculopuncture in a few carefully selected patients with open-angle glaucoma. Our preliminary experience with this treatment forms the basis of this report.
MATERIALS AND METHODS Informed consent was obtained from all patients who realized that this was an investigational protocol. The protocol was approved by the Investigational Review Board, Massachusetts Eye & Ear Infirmary. In all cases, trabeculopuncture was utilized only as an alternative to glaucoma surgery in the involved or fellow eye (in case 5 the blind eye was treated in order to guide treatment of the fellow eye). An American Medical Optics YAG100 Q-switched Neodymium:YAG laser was utilized with a coated 3-mirror Goldmann contact lens (Ocular Instruments). I% methylcellulose without preservative was utilized for gonioscopic fluid. In each patient four to six sites in the mid portion of the trabecular meshwork evenly spaced around the circumference of the angle were selected for Nd:YAG application (our unpublished calculations [Johnson MC et al] indicated that with four evenly spaced penetrations through the trabecular meshwork, resistance to circumferential flow around Schlemm's canal would thereby be insignificant). At each site, three to six superimposed applications were made (2-6 mJ) until it was judged that the meshwork was fully penetrated. Except for cases 4 and 5, where blood reflux occurred (similar to the monkey), it was difficult to be sure that one had fully penetrated at each of the sites. The "whiteness" of the viewed outer wall of Schlemm's canal was however a useful guide and in all eyes it was believed that the majority of the penetrations at least were, in fact, full thickness. No more than six applications at any one site were made, however, even· if there .was uncertainty about the depth of the penetration. In cases 7 and 8 (juvenile open-angle glaucoma), initial laser punctures were performed similarly. However, ~or the repeat treatment of case 7 and the 932
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right eye of case 8, attempts were made to primarily disrupt the uveal and superficial trabecular meshwork rather than necessarily achieve full thickness penetration (although this was also usually obtained at many of the sites). Patients were treated with topical steroids three to four times a day for seven to ten days after the procedure.
RESULTS GONIOSCOPY
In all six cases of adult glaucoma, 24 hours after the YAG treatment, one could easily identify the sites of YAG puncture, but only rarely was one certain that the penetrations were full thickness to the outer wall of Schlemm's canal. Most often, there appeared to be some gray tissue deep in the base of the lesion. Regardless, at all sites in all patients, over the next several weeks the puncture sites filled in with tissue that appeared to have a similar appearance to trabecular meshwork. No white "scars" in the meshwork were seen, unlike the monkey. 15 Often only a shallow depression in the surface of the trabecular meshwork, sometimes containing a few pigment specks, or alteration of the uveal meshwork remained to identify the lesion. Sometimes the site of the laser application could no longer be identified. In contrast, in both cases of juvenile open angle glaucoma (cases 7, 8), the abnormalities in the adjacent uveal meshwork allowed easy identification of the laser site and 24 hours after treatment the lesions were observed to extend deeply into the trabecular meshwork, to which was believed to be the outer wall ofSchlemm's canal. In case 7 over several weeks subsequent to treatment there appeared to be deep tissue that filled in the laser lesions. Although depressions in the surface of the meshwork persisted, there appeared to be condensation of the superficial tissue. The defects in the meshwork appeared "filled in." In contrast, in case 8, although the deep holes likewise seemed to disappear in several weeks, the disruptions in the uveal meshwork persisted and the surface of the lesions appeared to have a consistency like "normal" meshwork without any condensed tissue. INTRAOCULAR PRESSURE (TABLE 1)
In cases 1 to 3, there was noticeable reduction in lOP 24 hours after Y AG puncture. The treated eyes demonstrated a small amount of inflammation and since tonography was not routinely performed at this time period, it is uncertain whether the change in lOP truly represented an increase in aqueous humor outflow or, at least partially reflected a change in secretion of aqueous humor due to the inflammation. In cases 4 and 5, there was frank blood reflux into the trabecular meshwork and/or anterior chamber, and lOP was unaltered 24 hours after treatment. In case 6, lOP was also acutely unaltered and despite no detectable inflammation
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lOP increased dramatically within a week, necessitating, after insufficient medical maneuvers, emergency filtration surgery. Treatment of case 6 was thus a dramatic and noteworthy failure. In case 5 there seemed to be no real effects from the Y AG puncture despite the observed blood reflux into the anterior chamber. In cases 1 through 4, we observed a tendency for a small decrease in lOP following the procedure (lOP decreasing from a mean of 25.5 to 20 mmHg after 3-4 weeks, compared to no change at 21 mmHg in the fellow eye), although this was of only marginal clinical significance. In cases 1 through 3 there appeared to be further lessening of any pressure lowering effect of the laser procedure, beginning several months after treatment. With such small changes in lOP, it is difficult to interpret the tonographic data which unfortunately was not obtained as a baseline in all cases. Nevertheless, by comparison between eyes of a patient it seems reasonable, except in case 1, to attribute the small changes in lOP observed after YAG to small changes in outflow facility. Case 4 may represent a substantial lOP effect from the Y AG procedure, since with a measured episcleral venous pressure elevation to 18 mmHg, lOP below approximately 20 mmHg would not be expected from any trabecular resistance-altering procedure. In contrast to the six adult cases of open-angle glaucoma, the two patients with juvenile open angle glaucoma demonstrated dramatic lOP lowering following the YAG trabecular treatment. Case 7 is sufficiently noteworthy to justify a detailed presentation.
CASE REPORT Case 7. A 13-year-old girl saw her local ophthalmologist with a complaint of "burning and tearing" for the past several months. Corrected visual acuity was 20/50 in the right eye and 20/25 in the left eye not improveable with pinhole. Applanation pressures were 52 mmHg in the right eye and 51 mmHg in the left eye. There was an equivocal Marcus Gunn pupillary phenomenon in the right eye. Both corneae were clear without epithelial edema. Schwalbe's line was moderately prominent (posterior embryotoxon). The anterior chambers of both eyes were clear and deep. Gonioscopy revealed that both angles were wide open to the ciliary body band. The trabecular meshwork appeared blank in appearance without any pigment. The right disc showed almost total cupping. There was a very large cup in the left eye with only thin rim tissue above and below. Both lenses were clear. Indirect ophthalmoscopy was unremarkable. Goldmann visual fields revealed a dense superonasal paracentral defect in the right eye and a small defect in the left eye. There was a strong family history for open-angle glaucoma, with both parents and several other relatives affected. The patient was placed on timolol and pilocarpine ocusert therapy but pressures for both eyes remained between 30 and 40 mmHg. On March 30, 1983 she underwent a laser trabeculoplasty procedure with the argon laser to the nasal half of the right angle. Two weeks after this procedure pressures were 35 mmHg in the right eye and 40 mmHg in the left eye, and
one month after the procedure pressures were 36 mmHg in the right eye and 40 mmHg in the left eye. With full informed consent the patient underwent Nd:YAG trabeculopuncture to the right eye. Four sites were treated using 2 to 4 mJ. When the opening was made through the trabecular meshwork to the scleral wall of Schlemm's canal, it became apparent that the most superficial uveal meshwork adjacent to the opening had a homogenous translucent thick texture without apparent fenestrations. This "solid" appearance to the uveal meshwork had not been detected upon direct gonioscopic view. Immediately following the laser procedure applanation pressures were observed to be 52 mmHg in the right eye and 48 mmHg in the left eye. There was a moderate cellular reaction in the anterior chamber. The following day applanation pressures were 18 mmHg in the right eye and 43 mmHg in the left eye. The right eye was white and quiet. The holes through the trabecular meshwork were apparent in the right eye. Two weeks later, a similar Y AG trabeculopuncture was performed in the left eye. A small amount of blood reflux into the anterior chamber from the meshwork was apparent at the end of the procedure. Two days later, on May 26th, applanation pressures were 19 mmHg in the right eye and 20 mmHg in the left eye. Gonioscopy in both eyes revealed definite openings in the uveal meshwork with the underlying sclera (presumably the outer wall ofSchlemm's canal) visible through the opening. Three weeks after the trabeculopuncture in the left eye (on June 13th) applanation pressures were 16 mmHg in the right eye and 26 mmHg in the left eye. Gonioscopy in the left eye indicated that the trabeculopuncture openings appeared to be "filling in." Also in the right eye, despite the good lOP, there appeared to be some tissue in the trabeculopuncture openings in front of the scleral wall of the canal. On July 25th applanation pressures were 32 mmHg in the right eye and 35 mmHg in the left eye, and gonioscopy had revealed further filling in of the openings in the trabecular meshwork in both eyes. Tonography revealed the following: right eye, Po = 20; C55 = 0.06; Po/C55 = 333; left eye, Po = 22; C55 = 0.01; Po/C55 = 2200. On July 27th with full informed consent the patient underwent repeat Y AG trabeculopuncture to the right eye. Six sites were treated using 4 to 6 mJ. Immediately after the procedure applanation pressures were 44 mmHg in the right eye and 30 mmHg in the left eye. The next day (July 28, 1983) applanation pressures were 14 mmHg in the right eye and 36 mmHg in the left eye. Gonioscopy in the right eye revealed three definite areas of deep opening into the uveal meshwork but, unlike the first treatment, there did appear still to be some deep tissue present in the base of the openings. Tonography revealed the following: right eye, Po = 15; C55 = 0.15; Po/C55 = 100; left eye, Po = 40; C55 = 0.04; Po/ C55 = 1000. On August 4th, applanation pressures were 15 mmHg in the right eye and 38 mmHg in the left eye. Tonography revealed the following: right eye, Po = 16; C55 = 0.11; Po/ C55 = 145; left eye, Po = 43; C55 = 0.04; Po/C55 = 1075. Gonioscopy was unchanged. However, right eye pressures returned to previous levels and gonioscopically there was further filling in of the YAG treatment sites. Therefore repeat Y AG trabeculopuncture was performed in the right eye on August 24th, but similarly there was pressure reduction of only short duration. The patient ultimately underwent a surgical goniotomy in the right eye. The left eye underwent argon laser trabeculoplasty and six weeks later, repeat YAG trabeculopuncture. Two months after this lOP remained in the low teens in the left eye, although there
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Table 1.
Time Interval Between Argon LTP & YAG
Medications
Diagnosis
Age
Race
Sex
OAG OU
68
w
M
10 Mo
2
OAG OU
73
w
M
6 Wk
3
Exfoliation Glaucoma OU OAG OU Increased episcleral venous pressure OD (18 mmHg) ?dural shunt Exfoliation OU
72
M
10 Mo
55
w w
F
10 Mo
Timolol 0.5% E-pilo 4% Methazolamide 100 mg
65
w
M
No Argon
OAG OU History of Iritis
67
w
F
7 Wk
7
Juvenile OAG OU
13
w
F
6 Wk
8
Juvenile OAG OU with prominent iris processes (onset age 15)
22
w
F
No Argon
Timolol 0.5% Pilocarpine 4% Methazolamide 50 mg Timolol 0.5% Carbachol 3% Methazolamide 200 mg Timolol 0.5% Pilo 40 Ocusert Timolol 0.5% Propine 0.1% Pilo 40 Ocusert
Case
4
5
6
ou
Timolol 0.5% Pilocarpine 4% Propine 0.1% Timolol 0.5% Pilocarpine 4% Pro pine 0.1% Methazolamide 50 mg Timolol 0.5%
Baseline Tonography
Visual Acuity
Po
20/20 20/80
20 26
0.16 0.13
125 200
Fair Fair
20/30 20/100
17 19
0.08 0.08 11
213 238
Good Good
15
0.07** 0.06**
214 450
Good Good
C55
Po/C55
Curve
HM 20/60 20/40 20/20
20/25 NLP
20/60 20/300 20/50 20/25 20/15 20/20
27
W = white; B = black; M = male; F = female; Wk = weeks; Mo = months; OAG = open-angle glaucoma; OU = both eyes; 00 = right eye; LTP = laser trabeculoplasty; HM = hand movements; NLP = no light perception. *For all lOP, right eye listed on top of left eye. t YAG trabeculopuncture subsequently performed. t Baseline = last visit prior to YAG. § 00 had filtration surgery in interval; methazolamide discontinued; on prednisone. II Performed prior to Argon LTP. #Argon LTP performed in interval. ** 20 months prior to YAG. tt 6 weeks after YAG. H 11 months after YAG. () C55. ## Continued on next line.
appeared to be some filling in of the deep tissues in the puncture sites. When last seen four months later, applanation pressures were II mmHg in the right eye and 12 mmHg in the left eye. However, both the surgical goniotomy site in the right eye and the YAG puncture sites in the left eye appeared to contain deep tissue that was partially filling in the lesions.
anything, improvement in the lOP effect with time (at least in the initial treated eye with 11 months followup), which was associated with the absence of such a trabecular tissue response.
Thus, in case 7 there is good documentation for a substantial short-term lOP reduction associated with an improvement in tonographic outflow facility. Unfortunately, these effects diminished with time and. this was associated with the described "filling in" of the puncture site. In contrast, in case 8 there appeared to be, if
DISCUSSION
934
The results of Nd:YAG trabeculopuncture in our adult patients with open-angle glaucoma are disappointing. In four patients, only a small decrease in lOP was
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Intraocular Pressure lOP (mmHg)* Visit Prior Baseto Baseline:j: line
1 Day after YAG (C55)
3-4 Wk after YAG
3 Mo after YAG
6 M after YAG
21 25
18 26t
18 15
20 19
20 22
18 22
23 19
26 20t
23 (0.09) 16 (0.10)
24 17
21 17
23 18
30 16 29 22
29t 18 27t 22
16 (0.07) 16 (0.04) 28 22
22 22 22 17
24t 15# 20 19
20 (.07) 13 (.10) 20 18
38 53
41 52t
41 53
39 44
20§ 50§
32 19
36t 13
36 21
8-12 Mo after YAG
Follow-up Tonography (1-3 Months) Po
C55
Po/C55 Curve
19 18
0.11 0.08
173 225
Good Good
18# 19
18 15
0.07 0.11
257 136
Fair Fair
22 (.06) 17 (.08) 20 18
22 15 18 16
0.08 0.09# 0.13 0.16
275 166 136 100
Fair Fair Good Good
36t 40
18 43t
16 26
30 34
26 26t
26 (0.09) 13 (0.11) 13 22
26 (0.09) 26 (0.06) 20 18
Blood reflux into anterior chamber at YAG; persisted on meshwork for several weeks. Blood reflux at time of YAG; 20% hyphema persisted for two weeks. 1 week-emergency filter performed
58 (1 week) 15
35 41
Comments
00.
See text See text 30 22
32 18
obtained (mean decrease from 25.5 to 20 mmHg after 3-4 weeks with no change in the fellow eye), which is at the threshold of clinical significance. Also, in three of these cases there appeared to be further attenuation of this small effect with time. In addition, one patient had a dramatic increase in lOP to dangerous levels that did not respond to medical therapy and required emergency filtration surgery. The potential for such an adverse effect must be kept in mind for any future studies which may attempt to augment the small lOP lowering achieved with such a procedure. The reason for the failure of this procedure is not
27t** 15**
17 11
0.14tt 0.15:j::j:
121 73
Good Good
YAG disrupted uveal meshwork, which did not fill in
necessarily certain. Since, already at 24 hours posttreatment it is rare to observe a full thickness "hole" into Schlemm's canal, but rather there seems to be some deep gray tissue in the base of the lesion, and with time there is progressive obliteration of the YAG lesion with "filled in" tissue, it is reasonable to suppose that it is the healing process in the glaucomatous human trabecular meshwork that, as in the monkey, closes the penetrating channel created through the meshwork. If so, then further investigations of this procedure should include attempts to alter the biological response of the trabecular tissue to the laser application. On the other 935
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hand, one should not rule out the possibility that in the glaucomatous condition abnormalities also occur in Schlemm's canal, itself, or more distally, in which case simple penetration of the trabecular meshwork, by itself, might not fully bypass the abnormality in outflow resistance. Tonographic studies performed shortly after trabeculopuncture might provide important information in this regard. Since the trabecular punctures were observed to invariably close in the adults in this study, one might also reasonably question why there should even be a small lOP effect in any patient. An explanation for this is also not certain. It is possible that a small perforation, at least to the deeper portions of the meshwork, may still persist but be too small for gonioscopic detection. Alternatively, it is possible that the "healing process" to the Y AG laser injury in the meshwork results in mechanical or biological changes in the adjacent meshwork tissue that can alter outflow resistance. Similar considerations apply to possible mechanisms of action of argon laser trabeculoplasty. In contrast to the adults, the two patients with juvenile open angle glaucoma demonstrated dramatic reductions in lOP that were clearly associated with improvements in tonographic outflow facility. In case 7, unfortunately, this effect was only temporary (at least in one eye) and failure was associated with gonioscopic "filling in" of the deeper portions of the laser sites with gray tissue. The short-term beneficial effect, however, identified the possibility, at least, that surgical goniotomy might be effective (as an alternative to filtration surgery) and this was performed with at least temporary lOP control. However, similar to the fellow eye's YAG puncture sites, when the patient was last seen there appeared to be tissue similarly "filling in" the goniotomy site and it is not certain that this surgical procedure will be effective long term. The curious, only temporary, effectiveness of surgical goniotomy in adult open angle glaucoma, in contrast to congenital glaucoma, is brought to mind. In surgical goniotomy for adult glaucoma, the meshwork incision has been observed to heal with time, whereas in congenital glaucoma such "filling in" is uncommon (Grant WM, personal communication). The reason for this difference is obscure. In case 7, although initially undetected, once the meshwork had been penetrated by the YAG laser, it appeared that the adjacent uveal meshwork had an "abnormal" homogenous texture without apparent fenestrations. It thus seemed that, although the initial objective was in fact to puncture through the meshwork, in this patient the procedure might have worked by disrupting this abnormal uveal meshwork. (Repeat treatt;nents were therefore performed with the aim of disrupting this tissue, as in a goniotomy, without necessarily fully penetrating the meshwork. However, similar only temporary effects were produced.) Perhaps, however, in this patient with such a strong family history of adult open angle glaucoma, deeper abnormalities in the trabecular meshwork (as presumably account for goniotomy failure in adults) were additionally involved. 936
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In contrast, in case 8 disruption of the uveal meshwork without full thickness hole formation seemed to have more long lasting effects. In contrast to case 7, in this case of juvenile open angle glaucoma recondensation and apparent "fibrosis" of the surface of the trabecular meshwork after Y AG therapy did not occur. Perhaps this relates to the response. of congenital forms of glaucoma to surgical goniotomy noted above. Although longer term observations are clearly required, the response of this patient suggests that YAG treatment to the uveal meshwork may be an appropriate consideration for cases of congenital glaucoma (where slit-lamp treatment is feasible) or juvenile open angle glaucoma where surgical goniotomy might be contemplated, ie. cases of trabeculodysgenesis. 17 At the very least, a favorable, although even temporary, change in lOP after YAG therapy might indicate that surgical goniotomy rather. than filtration surgery be performed. Further studies should provide information as to whether surgical goniotomy is any more effective than Y AG treatment. What is the future of YAG therapy to the trabecular meshwork? Certainly, from the above, it seems that where abnormalities in the uveal meshwork are suspected to be involved in the glaucoma mechanism, as in certain cases of congenital and juvenile glaucoma, cautious YAG treatment can be reasonably contemplated. Perhaps even in certain secondary glaucomas in adults where surface abnormalities on the meshwork are suspected, consideration to YAG treatment can be made, although the propensity of adult trabecular meshwork to "heal" and the potential for severe lOP elevation demonstrated by case 6 must be carefully weighed. For the patients with the "usual" forms of adult open angle glaucoma, it would seem that further investigations of methods to improve the efficacy of this procedure are clearly justified. Until this can be accomplished, however, widespread use of this treatment should be avoided. At the best, the lOP lowering effects of the current method for Y AG trabeculopuncture are quite small, and may be short-term. One must always remember the morphological observations of trabecular scar formation and focal Descemet's downgrowth demonstrated in monkeys so treated. 15 On the other hand, the potential advantage of such a technique is that, if current assumptions about the locus of abnormal resistance in glaucoma are correct, the method if successful, would allow a "bypass" of the site of the abnormality by means of a focal treatment that involves only a small portion of the trabecular meshwork. Clearly, it is important to work further towards this goal. It is possible that some small modification of technique or equipment in the future may allow enhanced effectiveness of this procedure. (It should be mentioned that it is possible there may be some flaw in the method used in this study although it was simply and effectively utilized for trabecular puncture in monkeys). More likely, however, the true efficacy of such a laser method will only be realized when there is much more knowledge about the basic biological responses of the trabecular meshwork tissue to such laser energy absorption.
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ACKNOWLEDGMENTS The authors thank David Greenseid, MD, Henry Mosher, MD, John Regan, MD, Kenneth Stampfer, MD, and Charles Wingate, MD for referring patients for this study.
REFERENCES 1. Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol 1963; 69:783-801. 2. Krasnov MM. Q-switched laser iridectomy and Q-switched laser goniopuncture. Adv Ophthalmol 1977; 34:192-6. 3. Krasnov MM. Q-switched laser goniopuncture. Arch Ophthalmol 1974; 92:37-41. 4. Krasnov MM. Laseropuncture of anterior chamber angle in glaucoma. Am J Ophthalmol 1973; 75:674-8. 5. Bonney CH, Gaasterland DE, Rodrigues MM, et al. Short-term effects of Q-switched ruby laser on monkey anterior chamber angle. Invest Ophthalmol Vis Sci 1982; 22:310-8. 6. Ticho U. Laser application to the angle structures in animals and in human glaucomatous eyes. Adv Ophthalmol 1977; 34:201-10. 7. Witschel B, Dannheim F, Rassow B. Experimental studies on laser trabeculo-puncture. Adv Ophthalmol 1977; 34:197-200.
8. Ticho U, Cadet JC, Mahler J, et al. Argon laser trabeculotomies in primates: evaluation by histological and perfusion studies. Invest Ophthalmol Vis Sci 1978; 17:667-74. 9. Wickham MG, Worthen DM. Argon laser trabeculotomy: long-term follow-up. Ophthalmology 1979; 86:495-503. 10. Worthen DM, Wickham MG. Laser trabeculotomy in monkeys. Invest Ophthalmol 1973; 12:707-11. 11. Ticho U, Zauberman H. Argon laser application to the angle structures in the glaucomas. Arch Ophthalmol 1976; 94:61-4. 12. Vander Zypen E, Fankhauser F. Lasers in the treatment of chronic simple glaucoma. Trans Ophthalmol Soc UK 1982; 102:147-53. 13. Vander Zypen E, Fankhauser F. The ultrastructural features of laser trabeculopuncture and cyclodialysis; problems related to successful treatment of chronic simple glaucoma. Ophthalmologica 1979; 179: 189-200. 14. Van der Zypen E, Bebie H, Fankhauser F. Morphological studies about the efficiency of laser beams upon the structures of the angle of the anterior chamber; facts and concepts related to the treatment of the chronic simple glaucoma. lnt Ophthalmol 1979; 1:109-22. 15. Melamed S, Pei J, Puliafito CA, Epstein DL. Q-switched neodymium YAG laser trabeculopuncture in monkeys. Arch Ophthalmol 1985; 103:129-33. 16. Gaasterland, DE, Kuwabara T. Effects on monkey eyes of argon laser glaucoma treatment. ARVO Abstracts. Invest Ophthalmol Vis Sci 1980; 19(Suppl):83-4. 17. Hoskins HD Jr, Shaffer RN, Hetherington J. Anatomical classification of the developmental glaucomas. Arch Ophthalmol 1984; 102:1331-6.
937
Abstract: Ten eyes of eight patients with open-angle glaucoma (OAG) had neodymium (Nd):YAG trabeculopuncture performed in an investigational protocol as an alternative to surgical intervention. In each, at four to six sites in the mid-trabecular meshwork, three to six superimposed applications were made (2 to 6 mJ). In four of six patients with adult OAG, a small decrease in intraocular pressure (lOP) was noted (from a mean of 25.5 to 20.0 mmHg after 3-4 weeks in the treated eyes, compared to no change at 21 mmHg in the fellow eyes). There appeared to be further attenuation of this lOP effect over the subsequent 2 to 11 months, and all patients demonstrated gonioscopic closure of all the puncture sites with time. One patient demonstrated an acute lOP elevation to 58 mmHg after the procedure, necessitating emergency filtration surgery. In contrast, in four eyes of two patients with juvenile open angle glaucoma, a dramatic lowering of lOP and improvement in tonographic outflow facility was demonstrated, although the effects were only temporary in one patient. YAG laser treatment to the trabecular meshwork may have its greatest potential usefulness when abnormalities in the uveal meshwork are involved, such as in certain cases of juvenile or congenital glaucoma, and may help identify the need for a surgical goniotomy. With more usual forms of OAG, however, widespread use of this technique should be avoided until greater efficacy can be achieved. [Key words: glaucoma, laser, juvenile glaucoma, open-angle glaucoma, trabecular meshwork, trabeculopuncture, YAG laser goniotomy.) Ophthalmology 92:931-937, 1985
Since the trabecular meshwork is believed to be the locus of abnormal resistance to aqueous humor outflow in open angle glaucoma, 1 an appealing, potentially simple treatment involves the placement of one or more "holes" through this tissue by means of laser energy in order to bypass this site of abnormality.Z- 14 We have recently
From the Glaucoma Consultation Service and Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. Presented at the Eighty-ninth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Supported in part by National Glaucoma Research, a program of the American Health Assistance Foundation. Reprint requests to David L. Epstein, MD, 243 Charles St., Boston, MA 02114.
utilized the Nd:YAG laser to so puncture the trabecular meshwork in living monkeys. 15 By superimposition of a few applications, one can very readily penetrate through the trabecular meshwork into Schlemm's canal and obtain blood reflux from the canal into the anterior chamber. Acutely, there is substantial intraocular pressure (lOP) reduction associated with a measured increase in aqueous humor outflow facility. However, after eight days, lOP and outflow facility return to baseline levels and gonioscopically one observes "filling in" of the puncture sites with a tissue that consists morphologically of fibrous "scar" tissue covered by a focal downgrowth of a Descemet's-like membrane. 15 Thus, it would seem that the normal biological response of the trabecular meshwork to such laser application would preclude its clinical applicability in human glaucoma. There is a potential flaw, however, in this reasoning which involves the comparison of young, normal mon931
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keys with that of adult, abnormal glaucoma patients. It is known that argon laser trabeculoplasty, an increasingly utilized clinical treatment for open-angle glaucoma, is ineffective in improving outflow facility in normal monkeys. 16 It is possible that the "healing" properties of glaucomatous trabecular tissue may be different from that of the normal monkey. In addition, there are anatomical differences between the monkey and human. For example, Schlemm's canal is more anterior in the monkey and it would seem very difficult in the monkey to avoid some energy absorption by the peripheral corneal endothelium during trabeculopuncture. Likewise, blood reflux from Schlemm's canal would not be expected with trabeculopuncture in a usual human glaucomatous eye and it is possible that blood elements might be involved somehow in the trabecular healing process in the monkey. For these various reasons, it seemed important to gain further knowledge of the potential efficacy of Nd:YAG trabeculopuncture in a few carefully selected patients with open-angle glaucoma. Our preliminary experience with this treatment forms the basis of this report.
MATERIALS AND METHODS Informed consent was obtained from all patients who realized that this was an investigational protocol. The protocol was approved by the Investigational Review Board, Massachusetts Eye & Ear Infirmary. In all cases, trabeculopuncture was utilized only as an alternative to glaucoma surgery in the involved or fellow eye (in case 5 the blind eye was treated in order to guide treatment of the fellow eye). An American Medical Optics YAG100 Q-switched Neodymium:YAG laser was utilized with a coated 3-mirror Goldmann contact lens (Ocular Instruments). I% methylcellulose without preservative was utilized for gonioscopic fluid. In each patient four to six sites in the mid portion of the trabecular meshwork evenly spaced around the circumference of the angle were selected for Nd:YAG application (our unpublished calculations [Johnson MC et al] indicated that with four evenly spaced penetrations through the trabecular meshwork, resistance to circumferential flow around Schlemm's canal would thereby be insignificant). At each site, three to six superimposed applications were made (2-6 mJ) until it was judged that the meshwork was fully penetrated. Except for cases 4 and 5, where blood reflux occurred (similar to the monkey), it was difficult to be sure that one had fully penetrated at each of the sites. The "whiteness" of the viewed outer wall of Schlemm's canal was however a useful guide and in all eyes it was believed that the majority of the penetrations at least were, in fact, full thickness. No more than six applications at any one site were made, however, even· if there .was uncertainty about the depth of the penetration. In cases 7 and 8 (juvenile open-angle glaucoma), initial laser punctures were performed similarly. However, ~or the repeat treatment of case 7 and the 932
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right eye of case 8, attempts were made to primarily disrupt the uveal and superficial trabecular meshwork rather than necessarily achieve full thickness penetration (although this was also usually obtained at many of the sites). Patients were treated with topical steroids three to four times a day for seven to ten days after the procedure.
RESULTS GONIOSCOPY
In all six cases of adult glaucoma, 24 hours after the YAG treatment, one could easily identify the sites of YAG puncture, but only rarely was one certain that the penetrations were full thickness to the outer wall of Schlemm's canal. Most often, there appeared to be some gray tissue deep in the base of the lesion. Regardless, at all sites in all patients, over the next several weeks the puncture sites filled in with tissue that appeared to have a similar appearance to trabecular meshwork. No white "scars" in the meshwork were seen, unlike the monkey. 15 Often only a shallow depression in the surface of the trabecular meshwork, sometimes containing a few pigment specks, or alteration of the uveal meshwork remained to identify the lesion. Sometimes the site of the laser application could no longer be identified. In contrast, in both cases of juvenile open angle glaucoma (cases 7, 8), the abnormalities in the adjacent uveal meshwork allowed easy identification of the laser site and 24 hours after treatment the lesions were observed to extend deeply into the trabecular meshwork, to which was believed to be the outer wall ofSchlemm's canal. In case 7 over several weeks subsequent to treatment there appeared to be deep tissue that filled in the laser lesions. Although depressions in the surface of the meshwork persisted, there appeared to be condensation of the superficial tissue. The defects in the meshwork appeared "filled in." In contrast, in case 8, although the deep holes likewise seemed to disappear in several weeks, the disruptions in the uveal meshwork persisted and the surface of the lesions appeared to have a consistency like "normal" meshwork without any condensed tissue. INTRAOCULAR PRESSURE (TABLE 1)
In cases 1 to 3, there was noticeable reduction in lOP 24 hours after Y AG puncture. The treated eyes demonstrated a small amount of inflammation and since tonography was not routinely performed at this time period, it is uncertain whether the change in lOP truly represented an increase in aqueous humor outflow or, at least partially reflected a change in secretion of aqueous humor due to the inflammation. In cases 4 and 5, there was frank blood reflux into the trabecular meshwork and/or anterior chamber, and lOP was unaltered 24 hours after treatment. In case 6, lOP was also acutely unaltered and despite no detectable inflammation
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lOP increased dramatically within a week, necessitating, after insufficient medical maneuvers, emergency filtration surgery. Treatment of case 6 was thus a dramatic and noteworthy failure. In case 5 there seemed to be no real effects from the Y AG puncture despite the observed blood reflux into the anterior chamber. In cases 1 through 4, we observed a tendency for a small decrease in lOP following the procedure (lOP decreasing from a mean of 25.5 to 20 mmHg after 3-4 weeks, compared to no change at 21 mmHg in the fellow eye), although this was of only marginal clinical significance. In cases 1 through 3 there appeared to be further lessening of any pressure lowering effect of the laser procedure, beginning several months after treatment. With such small changes in lOP, it is difficult to interpret the tonographic data which unfortunately was not obtained as a baseline in all cases. Nevertheless, by comparison between eyes of a patient it seems reasonable, except in case 1, to attribute the small changes in lOP observed after YAG to small changes in outflow facility. Case 4 may represent a substantial lOP effect from the Y AG procedure, since with a measured episcleral venous pressure elevation to 18 mmHg, lOP below approximately 20 mmHg would not be expected from any trabecular resistance-altering procedure. In contrast to the six adult cases of open-angle glaucoma, the two patients with juvenile open angle glaucoma demonstrated dramatic lOP lowering following the YAG trabecular treatment. Case 7 is sufficiently noteworthy to justify a detailed presentation.
CASE REPORT Case 7. A 13-year-old girl saw her local ophthalmologist with a complaint of "burning and tearing" for the past several months. Corrected visual acuity was 20/50 in the right eye and 20/25 in the left eye not improveable with pinhole. Applanation pressures were 52 mmHg in the right eye and 51 mmHg in the left eye. There was an equivocal Marcus Gunn pupillary phenomenon in the right eye. Both corneae were clear without epithelial edema. Schwalbe's line was moderately prominent (posterior embryotoxon). The anterior chambers of both eyes were clear and deep. Gonioscopy revealed that both angles were wide open to the ciliary body band. The trabecular meshwork appeared blank in appearance without any pigment. The right disc showed almost total cupping. There was a very large cup in the left eye with only thin rim tissue above and below. Both lenses were clear. Indirect ophthalmoscopy was unremarkable. Goldmann visual fields revealed a dense superonasal paracentral defect in the right eye and a small defect in the left eye. There was a strong family history for open-angle glaucoma, with both parents and several other relatives affected. The patient was placed on timolol and pilocarpine ocusert therapy but pressures for both eyes remained between 30 and 40 mmHg. On March 30, 1983 she underwent a laser trabeculoplasty procedure with the argon laser to the nasal half of the right angle. Two weeks after this procedure pressures were 35 mmHg in the right eye and 40 mmHg in the left eye, and
one month after the procedure pressures were 36 mmHg in the right eye and 40 mmHg in the left eye. With full informed consent the patient underwent Nd:YAG trabeculopuncture to the right eye. Four sites were treated using 2 to 4 mJ. When the opening was made through the trabecular meshwork to the scleral wall of Schlemm's canal, it became apparent that the most superficial uveal meshwork adjacent to the opening had a homogenous translucent thick texture without apparent fenestrations. This "solid" appearance to the uveal meshwork had not been detected upon direct gonioscopic view. Immediately following the laser procedure applanation pressures were observed to be 52 mmHg in the right eye and 48 mmHg in the left eye. There was a moderate cellular reaction in the anterior chamber. The following day applanation pressures were 18 mmHg in the right eye and 43 mmHg in the left eye. The right eye was white and quiet. The holes through the trabecular meshwork were apparent in the right eye. Two weeks later, a similar Y AG trabeculopuncture was performed in the left eye. A small amount of blood reflux into the anterior chamber from the meshwork was apparent at the end of the procedure. Two days later, on May 26th, applanation pressures were 19 mmHg in the right eye and 20 mmHg in the left eye. Gonioscopy in both eyes revealed definite openings in the uveal meshwork with the underlying sclera (presumably the outer wall ofSchlemm's canal) visible through the opening. Three weeks after the trabeculopuncture in the left eye (on June 13th) applanation pressures were 16 mmHg in the right eye and 26 mmHg in the left eye. Gonioscopy in the left eye indicated that the trabeculopuncture openings appeared to be "filling in." Also in the right eye, despite the good lOP, there appeared to be some tissue in the trabeculopuncture openings in front of the scleral wall of the canal. On July 25th applanation pressures were 32 mmHg in the right eye and 35 mmHg in the left eye, and gonioscopy had revealed further filling in of the openings in the trabecular meshwork in both eyes. Tonography revealed the following: right eye, Po = 20; C55 = 0.06; Po/C55 = 333; left eye, Po = 22; C55 = 0.01; Po/C55 = 2200. On July 27th with full informed consent the patient underwent repeat Y AG trabeculopuncture to the right eye. Six sites were treated using 4 to 6 mJ. Immediately after the procedure applanation pressures were 44 mmHg in the right eye and 30 mmHg in the left eye. The next day (July 28, 1983) applanation pressures were 14 mmHg in the right eye and 36 mmHg in the left eye. Gonioscopy in the right eye revealed three definite areas of deep opening into the uveal meshwork but, unlike the first treatment, there did appear still to be some deep tissue present in the base of the openings. Tonography revealed the following: right eye, Po = 15; C55 = 0.15; Po/C55 = 100; left eye, Po = 40; C55 = 0.04; Po/ C55 = 1000. On August 4th, applanation pressures were 15 mmHg in the right eye and 38 mmHg in the left eye. Tonography revealed the following: right eye, Po = 16; C55 = 0.11; Po/ C55 = 145; left eye, Po = 43; C55 = 0.04; Po/C55 = 1075. Gonioscopy was unchanged. However, right eye pressures returned to previous levels and gonioscopically there was further filling in of the YAG treatment sites. Therefore repeat Y AG trabeculopuncture was performed in the right eye on August 24th, but similarly there was pressure reduction of only short duration. The patient ultimately underwent a surgical goniotomy in the right eye. The left eye underwent argon laser trabeculoplasty and six weeks later, repeat YAG trabeculopuncture. Two months after this lOP remained in the low teens in the left eye, although there
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Table 1.
Time Interval Between Argon LTP & YAG
Medications
Diagnosis
Age
Race
Sex
OAG OU
68
w
M
10 Mo
2
OAG OU
73
w
M
6 Wk
3
Exfoliation Glaucoma OU OAG OU Increased episcleral venous pressure OD (18 mmHg) ?dural shunt Exfoliation OU
72
M
10 Mo
55
w w
F
10 Mo
Timolol 0.5% E-pilo 4% Methazolamide 100 mg
65
w
M
No Argon
OAG OU History of Iritis
67
w
F
7 Wk
7
Juvenile OAG OU
13
w
F
6 Wk
8
Juvenile OAG OU with prominent iris processes (onset age 15)
22
w
F
No Argon
Timolol 0.5% Pilocarpine 4% Methazolamide 50 mg Timolol 0.5% Carbachol 3% Methazolamide 200 mg Timolol 0.5% Pilo 40 Ocusert Timolol 0.5% Propine 0.1% Pilo 40 Ocusert
Case
4
5
6
ou
Timolol 0.5% Pilocarpine 4% Propine 0.1% Timolol 0.5% Pilocarpine 4% Pro pine 0.1% Methazolamide 50 mg Timolol 0.5%
Baseline Tonography
Visual Acuity
Po
20/20 20/80
20 26
0.16 0.13
125 200
Fair Fair
20/30 20/100
17 19
0.08 0.08 11
213 238
Good Good
15
0.07** 0.06**
214 450
Good Good
C55
Po/C55
Curve
HM 20/60 20/40 20/20
20/25 NLP
20/60 20/300 20/50 20/25 20/15 20/20
27
W = white; B = black; M = male; F = female; Wk = weeks; Mo = months; OAG = open-angle glaucoma; OU = both eyes; 00 = right eye; LTP = laser trabeculoplasty; HM = hand movements; NLP = no light perception. *For all lOP, right eye listed on top of left eye. t YAG trabeculopuncture subsequently performed. t Baseline = last visit prior to YAG. § 00 had filtration surgery in interval; methazolamide discontinued; on prednisone. II Performed prior to Argon LTP. #Argon LTP performed in interval. ** 20 months prior to YAG. tt 6 weeks after YAG. H 11 months after YAG. () C55. ## Continued on next line.
appeared to be some filling in of the deep tissues in the puncture sites. When last seen four months later, applanation pressures were II mmHg in the right eye and 12 mmHg in the left eye. However, both the surgical goniotomy site in the right eye and the YAG puncture sites in the left eye appeared to contain deep tissue that was partially filling in the lesions.
anything, improvement in the lOP effect with time (at least in the initial treated eye with 11 months followup), which was associated with the absence of such a trabecular tissue response.
Thus, in case 7 there is good documentation for a substantial short-term lOP reduction associated with an improvement in tonographic outflow facility. Unfortunately, these effects diminished with time and. this was associated with the described "filling in" of the puncture site. In contrast, in case 8 there appeared to be, if
DISCUSSION
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The results of Nd:YAG trabeculopuncture in our adult patients with open-angle glaucoma are disappointing. In four patients, only a small decrease in lOP was
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Intraocular Pressure lOP (mmHg)* Visit Prior Baseto Baseline:j: line
1 Day after YAG (C55)
3-4 Wk after YAG
3 Mo after YAG
6 M after YAG
21 25
18 26t
18 15
20 19
20 22
18 22
23 19
26 20t
23 (0.09) 16 (0.10)
24 17
21 17
23 18
30 16 29 22
29t 18 27t 22
16 (0.07) 16 (0.04) 28 22
22 22 22 17
24t 15# 20 19
20 (.07) 13 (.10) 20 18
38 53
41 52t
41 53
39 44
20§ 50§
32 19
36t 13
36 21
8-12 Mo after YAG
Follow-up Tonography (1-3 Months) Po
C55
Po/C55 Curve
19 18
0.11 0.08
173 225
Good Good
18# 19
18 15
0.07 0.11
257 136
Fair Fair
22 (.06) 17 (.08) 20 18
22 15 18 16
0.08 0.09# 0.13 0.16
275 166 136 100
Fair Fair Good Good
36t 40
18 43t
16 26
30 34
26 26t
26 (0.09) 13 (0.11) 13 22
26 (0.09) 26 (0.06) 20 18
Blood reflux into anterior chamber at YAG; persisted on meshwork for several weeks. Blood reflux at time of YAG; 20% hyphema persisted for two weeks. 1 week-emergency filter performed
58 (1 week) 15
35 41
Comments
00.
See text See text 30 22
32 18
obtained (mean decrease from 25.5 to 20 mmHg after 3-4 weeks with no change in the fellow eye), which is at the threshold of clinical significance. Also, in three of these cases there appeared to be further attenuation of this small effect with time. In addition, one patient had a dramatic increase in lOP to dangerous levels that did not respond to medical therapy and required emergency filtration surgery. The potential for such an adverse effect must be kept in mind for any future studies which may attempt to augment the small lOP lowering achieved with such a procedure. The reason for the failure of this procedure is not
27t** 15**
17 11
0.14tt 0.15:j::j:
121 73
Good Good
YAG disrupted uveal meshwork, which did not fill in
necessarily certain. Since, already at 24 hours posttreatment it is rare to observe a full thickness "hole" into Schlemm's canal, but rather there seems to be some deep gray tissue in the base of the lesion, and with time there is progressive obliteration of the YAG lesion with "filled in" tissue, it is reasonable to suppose that it is the healing process in the glaucomatous human trabecular meshwork that, as in the monkey, closes the penetrating channel created through the meshwork. If so, then further investigations of this procedure should include attempts to alter the biological response of the trabecular tissue to the laser application. On the other 935
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hand, one should not rule out the possibility that in the glaucomatous condition abnormalities also occur in Schlemm's canal, itself, or more distally, in which case simple penetration of the trabecular meshwork, by itself, might not fully bypass the abnormality in outflow resistance. Tonographic studies performed shortly after trabeculopuncture might provide important information in this regard. Since the trabecular punctures were observed to invariably close in the adults in this study, one might also reasonably question why there should even be a small lOP effect in any patient. An explanation for this is also not certain. It is possible that a small perforation, at least to the deeper portions of the meshwork, may still persist but be too small for gonioscopic detection. Alternatively, it is possible that the "healing process" to the Y AG laser injury in the meshwork results in mechanical or biological changes in the adjacent meshwork tissue that can alter outflow resistance. Similar considerations apply to possible mechanisms of action of argon laser trabeculoplasty. In contrast to the adults, the two patients with juvenile open angle glaucoma demonstrated dramatic reductions in lOP that were clearly associated with improvements in tonographic outflow facility. In case 7, unfortunately, this effect was only temporary (at least in one eye) and failure was associated with gonioscopic "filling in" of the deeper portions of the laser sites with gray tissue. The short-term beneficial effect, however, identified the possibility, at least, that surgical goniotomy might be effective (as an alternative to filtration surgery) and this was performed with at least temporary lOP control. However, similar to the fellow eye's YAG puncture sites, when the patient was last seen there appeared to be tissue similarly "filling in" the goniotomy site and it is not certain that this surgical procedure will be effective long term. The curious, only temporary, effectiveness of surgical goniotomy in adult open angle glaucoma, in contrast to congenital glaucoma, is brought to mind. In surgical goniotomy for adult glaucoma, the meshwork incision has been observed to heal with time, whereas in congenital glaucoma such "filling in" is uncommon (Grant WM, personal communication). The reason for this difference is obscure. In case 7, although initially undetected, once the meshwork had been penetrated by the YAG laser, it appeared that the adjacent uveal meshwork had an "abnormal" homogenous texture without apparent fenestrations. It thus seemed that, although the initial objective was in fact to puncture through the meshwork, in this patient the procedure might have worked by disrupting this abnormal uveal meshwork. (Repeat treatt;nents were therefore performed with the aim of disrupting this tissue, as in a goniotomy, without necessarily fully penetrating the meshwork. However, similar only temporary effects were produced.) Perhaps, however, in this patient with such a strong family history of adult open angle glaucoma, deeper abnormalities in the trabecular meshwork (as presumably account for goniotomy failure in adults) were additionally involved. 936
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In contrast, in case 8 disruption of the uveal meshwork without full thickness hole formation seemed to have more long lasting effects. In contrast to case 7, in this case of juvenile open angle glaucoma recondensation and apparent "fibrosis" of the surface of the trabecular meshwork after Y AG therapy did not occur. Perhaps this relates to the response. of congenital forms of glaucoma to surgical goniotomy noted above. Although longer term observations are clearly required, the response of this patient suggests that YAG treatment to the uveal meshwork may be an appropriate consideration for cases of congenital glaucoma (where slit-lamp treatment is feasible) or juvenile open angle glaucoma where surgical goniotomy might be contemplated, ie. cases of trabeculodysgenesis. 17 At the very least, a favorable, although even temporary, change in lOP after YAG therapy might indicate that surgical goniotomy rather. than filtration surgery be performed. Further studies should provide information as to whether surgical goniotomy is any more effective than Y AG treatment. What is the future of YAG therapy to the trabecular meshwork? Certainly, from the above, it seems that where abnormalities in the uveal meshwork are suspected to be involved in the glaucoma mechanism, as in certain cases of congenital and juvenile glaucoma, cautious YAG treatment can be reasonably contemplated. Perhaps even in certain secondary glaucomas in adults where surface abnormalities on the meshwork are suspected, consideration to YAG treatment can be made, although the propensity of adult trabecular meshwork to "heal" and the potential for severe lOP elevation demonstrated by case 6 must be carefully weighed. For the patients with the "usual" forms of adult open angle glaucoma, it would seem that further investigations of methods to improve the efficacy of this procedure are clearly justified. Until this can be accomplished, however, widespread use of this treatment should be avoided. At the best, the lOP lowering effects of the current method for Y AG trabeculopuncture are quite small, and may be short-term. One must always remember the morphological observations of trabecular scar formation and focal Descemet's downgrowth demonstrated in monkeys so treated. 15 On the other hand, the potential advantage of such a technique is that, if current assumptions about the locus of abnormal resistance in glaucoma are correct, the method if successful, would allow a "bypass" of the site of the abnormality by means of a focal treatment that involves only a small portion of the trabecular meshwork. Clearly, it is important to work further towards this goal. It is possible that some small modification of technique or equipment in the future may allow enhanced effectiveness of this procedure. (It should be mentioned that it is possible there may be some flaw in the method used in this study although it was simply and effectively utilized for trabecular puncture in monkeys). More likely, however, the true efficacy of such a laser method will only be realized when there is much more knowledge about the basic biological responses of the trabecular meshwork tissue to such laser energy absorption.
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ACKNOWLEDGMENTS The authors thank David Greenseid, MD, Henry Mosher, MD, John Regan, MD, Kenneth Stampfer, MD, and Charles Wingate, MD for referring patients for this study.
REFERENCES 1. Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol 1963; 69:783-801. 2. Krasnov MM. Q-switched laser iridectomy and Q-switched laser goniopuncture. Adv Ophthalmol 1977; 34:192-6. 3. Krasnov MM. Q-switched laser goniopuncture. Arch Ophthalmol 1974; 92:37-41. 4. Krasnov MM. Laseropuncture of anterior chamber angle in glaucoma. Am J Ophthalmol 1973; 75:674-8. 5. Bonney CH, Gaasterland DE, Rodrigues MM, et al. Short-term effects of Q-switched ruby laser on monkey anterior chamber angle. Invest Ophthalmol Vis Sci 1982; 22:310-8. 6. Ticho U. Laser application to the angle structures in animals and in human glaucomatous eyes. Adv Ophthalmol 1977; 34:201-10. 7. Witschel B, Dannheim F, Rassow B. Experimental studies on laser trabeculo-puncture. Adv Ophthalmol 1977; 34:197-200.
8. Ticho U, Cadet JC, Mahler J, et al. Argon laser trabeculotomies in primates: evaluation by histological and perfusion studies. Invest Ophthalmol Vis Sci 1978; 17:667-74. 9. Wickham MG, Worthen DM. Argon laser trabeculotomy: long-term follow-up. Ophthalmology 1979; 86:495-503. 10. Worthen DM, Wickham MG. Laser trabeculotomy in monkeys. Invest Ophthalmol 1973; 12:707-11. 11. Ticho U, Zauberman H. Argon laser application to the angle structures in the glaucomas. Arch Ophthalmol 1976; 94:61-4. 12. Vander Zypen E, Fankhauser F. Lasers in the treatment of chronic simple glaucoma. Trans Ophthalmol Soc UK 1982; 102:147-53. 13. Vander Zypen E, Fankhauser F. The ultrastructural features of laser trabeculopuncture and cyclodialysis; problems related to successful treatment of chronic simple glaucoma. Ophthalmologica 1979; 179: 189-200. 14. Van der Zypen E, Bebie H, Fankhauser F. Morphological studies about the efficiency of laser beams upon the structures of the angle of the anterior chamber; facts and concepts related to the treatment of the chronic simple glaucoma. lnt Ophthalmol 1979; 1:109-22. 15. Melamed S, Pei J, Puliafito CA, Epstein DL. Q-switched neodymium YAG laser trabeculopuncture in monkeys. Arch Ophthalmol 1985; 103:129-33. 16. Gaasterland, DE, Kuwabara T. Effects on monkey eyes of argon laser glaucoma treatment. ARVO Abstracts. Invest Ophthalmol Vis Sci 1980; 19(Suppl):83-4. 17. Hoskins HD Jr, Shaffer RN, Hetherington J. Anatomical classification of the developmental glaucomas. Arch Ophthalmol 1984; 102:1331-6.
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