Erbium: Yag Laser Trabecular Ablation with a Sapphire Optical Fiber

Exp. Eye Res. (1997) 65, 151–155

Erbium : Yag Laser Trabecular Ablation with a Sapphire Optical Fiber M. L I S A M  H A M, D A N L. E I S E N B E R G, J O E L S. S C H U M A N* a n d N A N W A N G New England Eye Center, New England Medical Center, Tufts University School of Medicine, Boston, MA, U.S.A. (Received Columbia 14 July 1996 and accepted in revised form 13 December 1996) The purpose of the study was to evaluate the effect of erbium (Er) : yttrium aluminum garnet (YAG) laser trabecular ablation with a sapphire optical fiber on outflow facility. After obtaining baseline outflow facility using a computerized differential pressure perfusion system, human cadaver eyes were subjected to Er : YAG laser trabecular ablation using a sapphire optical fiber. Single pulses at varying energy levels (10 to 20 mJ pulse−") were applied in a nearly contiguous fashion over four clock hours of meshwork. Post-laser outflow facility was then determined utilizing the same perfusion system and histopathologic analysis performed. Of the ten eyes, nine were perfused to steady baseline facility. One eye was excluded from the study because of a leak in our system during the initial perfusion. The mean baseline facility was 0±283³0±08 µl min−" mmHg−". There was a significant increase in outflow facility after trabecular ablation, with a mean post-laser facility of 0±62³0±15 µl min−" mmHg−" (P ¯ 0±01). Eyes which received a sham treatment showed no increase or a minimal increase in facility. Histopathologic analysis revealed ablation into Schlemm’s canal with some thermal damage to the outer wall at all energy levels. Er : YAG laser trabecular ablation with a sapphire fiber is capable of increasing outflow facility in human cadaver eyes. # 1997 Academic Press Limited Key words : laser ; glaucoma ; erbium : YAG, filtration surgery ; trabecular meshwork.

1. Introduction Although the exact characteristics of aqueous outflow are still controversial, the bulk of the evidence accumulated over the past several decades indicates that the primary site of resistance to outflow lies within the trabecular meshwork and the inner wall of Schlemm’s canal (Grant, 1955a, 1955b, 1958, 1963 ; Ellingsen and Grant, 1972 ; Bill and Svedbergh, 1972). Surgery to create a direct passage from the anterior chamber into Schlemm’s canal, thereby bypassing the primary site of resistance, has many theoretic advantages over conventional glaucoma filtration surgery. This approach utilizes the physiologic pathways for the passage of aqueous and would avoid the complications associated with filtering blebs such as endophthalmitis, leaks, and Dellen formation. Surgery which mechanically incises the trabecular meshwork into Schlemm’s canal, such as goniotomy and trabeculotomy, has met with some success in congenital and juvenile glaucoma patients but results in primary open angle glaucoma have been discouraging (Luntz and Livingston, 1977), presumably because of rapid filling in and scarring of the incised area (Nesterov, 1970). The Nd : YAG laser has been used to create small holes (spot size 20 µm), with both focal and linear confluent applications, in the trabecular meshwork (Krasnov, * Address correspondence to Joel S. Schuman, New England Eye Center, Tufts University School of Medicine, 750 Washington St, Box 450, Boston, MA 02111, U.S.A.

0014-4835}97}080151­05 $25.00}0}ey960274

1974 ; Epstein et al., 1985 ; Melamed, Latina and Epstein, 1987), but the IOP lowering effect has been limited by rapid closure of the openings (Epstein et al., 1985 ; Melamed et al., 1957 ; Robin and Pollack, 1985). Histology in monkey eyes has revealed extensive blast effects to surrounding trabecular meshwork and the walls of Schlemm’s canal, with exposure of scleral collagen, followed by hypertrophic scar formation (Melamed et al., 1985). The greatest success with this technique has been in juvenile open angle glaucoma, where there may be a primary angle abnormality (Epstein et al., 1985 ; Melamed, 1987). The Er : YAG laser with a wavelength of 2±94 µm has characteristics which may be favorable for the creation of longer-lived openings. This laser is capable of removing tissue to produce large, contiguous 200–300 µm openings through trabecular meshwork into Schlemm’s canal, a process known as laser trabecular ablation (Hill, 1991). Because this wavelength is strongly absorbed by water, energy in tissue is confined to a small volume, allowing lower total energy expenditure for ablation. The result is a significant decrease in thermal damage to contiguous structures, which theoretically might minimize inflammation and the scarring response. The combination of larger openings with less thermal damage could promote patency of the direct passages into Schlemm’s canal. In this pilot study, we evaluated the effect of Er : YAG laser trabecular ablation (LTA) on outflow facility in human cadaver eyes. As lack of an effective and # 1997 Academic Press Limited

152

M. L I S A M  H A M E T A L.

reliable delivery system for the 2±94 µm wavelength has been a problem limiting use of the Er : YAG laser, we utilized a new synthetic sapphire optical fiber for contact trabecular ablation. This fiber has improved transmission characteristics and is stable in aqueous media. 2. Materials and Methods A total of ten adult human eyes, all less than 48 hr post mortem with enucleation less than 4 hr post mortem, were obtained from the National Disease Research Institute or the New England Eye Bank. Only eyes without a history of ocular disease or ocular surgery were utilized in the study. A 5 mm central corneal trephination was performed, followed by a peripheral iridectomy. A stainless steel Grant fitting (Grant, 1958, 1963) was then attached to the cornea of each globe and tested for leaks. A computerized differential pressure perfusion system (Eisenberg, Schuman and Wang, 1994) was used to perform anterior chamber whole eye perfusions with Barany’s solution (Barany, 1964) at a constant pressure of 10 mmHg. The perfusion system is similar to the one reported by Ethier (Ethier, Ajersch and Pirog, 1993). A computer calculates perfusate inflow by comparing the pressure differential across a stainless steel tube of known resistance. A gauge pressure transducer is used to monitor the line pressure just before it enters the eye. This pressure is the IOP. A motorized fluid reservoir is moved by the computer to maintain constant pressure at the gauge transducer. By dividing instantaneous flow by instantaneous IOP, the facility of inflow is obtained. If there are no leaks in the system, then this must also be the facility of outflow. The computer calculates this value every 15 seconds and records all data in a running data log for the entire experiment. Baseline outflow facility was measured for 20 minutes after a steady-state intraocular pressure of 10 mmHg had been reached. After obtaining a baseline facility, the Grant fitting was removed and laser trabecular ablation performed. A pulsed (250 µs) Er : YAG laser (Candela Laser Corporation, Wayland, MA, U.S.A.) was employed in this study. Energy was emitted at 2±94 µm and measured with a joulemeter. The eye was positioned under the operating microscope such that the angle structures were well visualized through the central corneal trephination. The eye was bathed with drops of Barany’s solution throughout the procedure. The synthetic sapphire fiber (Sapphikon Inc., Milford, NH, U.S.A.) was placed through the trephination into direct contact with the trabecular meshwork. The prototype delivery system consisted of a trunk fiber, 1±5 meters in length, coupled to a handpiece fiber, 5 cm in length. Only the handpiece fiber was clad with plastic, and the fiber tip had been polished with diamond lapping paper. Fiber diameter was 300 µm. Single Er : YAG pulses at varying energy levels (10 mJ,

Fiber optic

F. 1. Laser trabecular ablation. A fiber optic is placed in contact with the trabecular meshwork and a pulse of erbium : YAG laser energy ablates the tissue, forming a direct communication with Schlemm’s canal.

15 mJ and 20 mJ) were then delivered to the tissue in a nearly contiguous fashion to treat 4 clock hours of trabecular meshwork (Fig. 1). At all times during firing, the fiber tip was immersed in Barany’s solution, which pooled in the chamber angle. The Grant fitting was reattached and a post-laser outflow facility obtained in the same manner as the baseline (Fig. 2). Because of a lack of treatment effect in the first 10 mJ treated eye and an unsuccessful perfusion secondary to leakage on the second 10 mJ eye, the remaining eyes were utilized for sham treatment and the higher energy 15 and 20 mJ ablations. Sham treatment eyes underwent the identical procedure, except that when the fiber tip was applied to the trabecular meshwork, no laser energy was delivered. Individual facility data were transferred to an Excel spreadsheet (Microsoft Corporation, Redmond, WA, U.S.A.) and exported to MathCad 5±0 for Windows (Mathsoft, Inc., Cambridge, MA, U.S.A.) for analysis. Linear regression analysis was used to test baseline stability and a paired t test used to compare treatment effect. Following the post-laser perfusion, the eyes were immersion fixed in 10 % formaline and prepared for histologic analysis. Four micron sections were examined and photographed using an Olympus photo-

ERBIUM: YAG LASER TRABECULAR ABLATION WITH A SAPPHIRE OPTICAL FIBER 1.000

Facility (µl min–1 mmHg–1)

0.900

15 mJ Post-LTA

0.800 0.700 0.600 0.500 0.400

Pre-LTA

0.300 0.200 0.100 0

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 Hours

F. 2. Representative pre and post LTA computerized constant pressure perfusion curves. Recorded outflow facility (µl min−" mmHg−") was the mean facility measured over 20 minutes after steady-state.

microscope (Lake Success, NY, U.S.A.). Sections from all eyes were examined for effective ablation into Schlemm’s canal and for the extent of damage to the wall of the canal. 3. Results Of the ten eyes, nine were perfused to steady baseline facility. One eye was excluded from the study because of a leak in our system during the initial perfusion. The mean baseline facility was 0±283³0±08 µl min−" mmHg−". Eyes which received a sham treatment showed a minimal increase in facility after LTA. Two eyes, one treated with 10 mJ and one with 15 mJ, showed no significant change in facility. The 15 mJ treated eye actually had a minimal decrease in facility. However, the remaining five eyes treated at energies of 15 mJ and 20 mJ demonstrated a substantial facility increase (Fig. 3), with a mean post-laser outflow facility of

Facility (µl min–1 mmHg–1)

1.25 1

0.75 0.5

0.25 0 Sham Sham 10 mJ 15 mJ 15 mJ 15 mJ 20 mJ 20 mJ 20 mJ

F. 3. Comparison of pre and post laser outflow facilities. The change in the mean facility before and after Er : YAG laser trabecular ablation is significant (P ¯ 0±01). The number of eyes at each energy level is not sufficient to demonstrate a dose-response effect. *, before ; 8, after.

153

0±620³0±15 µl min−" mmHg−". Although the number of treated eyes was insufficient to demonstrate a meaningful dose response correlation on regression analysis, there was a statistically significant increase in outflow facility after LTA when the pre and postlaser mean facilities were compared (P ¯ 0±01) (Table I). There was ablation through trabecular meshwork into Schlemm’s canal in all eyes. A flap of remaining adjacent trabecular tissue was present in all eyes. Thermal damage was limited to the adjacent meshwork and the inner and outer walls of Schlemm’s canal (Fig. 4). The amount of thermal damage to the outer wall of Schlemm’s canal was greater in the 15 mJ and 20 mJ treatments as compared to the 10 mJ LTA. 4. Discussion Evaluation of the therapeutic potential of the Er : YAG laser for procedures such as laser trabecular ablation has been limited, in part, by the lack of an acceptable fiber optic delivery system. The readily available low hydroxyl-fused silica fiber optic has a very high attenuation rate for the 2±94 µm wavelength, which limits its useful length to an impractical level and may result in accelerated fiber aging (Ozlar et al., 1991). Zirconium fluoride fibers have a low attenuation rate but are fragile and soluble in aqueous media, and the potential toxicity of fluoride ions liberated into the eye is of concern (Ozlar et al., 1991). These fibers may be useful for delivering the 2±94 µm wavelength when coupled to a second fiber optic at the tip for the direct tissue interface. The sapphire fiber optics used in this study for transmission for the Er : YAG wavelength and attenuation rates in the range of 4±5 dB}meter (35 % transmission}meter), which, although less efficient than the zirconium fluoride fiber, is compatible with the proposed surgical use. Technological improvements in the fiber growth process are ongoing and have produced single crystal sapphire fibers with significantly lower attenuation rates than that used in this study (Fitzgibbon et al., 1994). In addition to the favorable transmission characteristics, the sapphire fiber optics are well suited to use in aqueous media. They do require end polishing and are less flexible than the silica or zirconium fluoride fiber optics, but not to an extent which limits their usefulness. In the overall assessment, single crystal sapphire fiber optics with the low attenuation rates now available are the most reliable and efficient means of delivering the Er : YAG wavelength for the performance of intraocular procedures. This pilot study shows that trabecular ablation with the Er : YAG laser can be effectively performed via a synthetic sapphire fiberoptic directly applied to the trabecular meshwork. In addition, we have shown that this procedure may increase outflow facility in human cadaver eyes. This is consistent with the

154

M. L I S A M  H A M E T A L.

F. 4. Light microscopy of anterior chamber angle after Er : YAG laser trabecular ablation using 15 mJ pulses. There is a welldefined ablation into Schlemm’s canal. Areas of hyperintense staining indicate thermal damage and can be seen in adjacent trabecular meshwork and the walls of Schlemm’s canal. Note that the extension of the thermal damage zone into surrounding tissue is limited to approximately 10–20 µm (hematoxylineosin, original magnification¬9).

concept that the primary site of resistance to aqueous outflow lies within the trabecular meshwork and inner wall of Schlemm’s canal. The Er : YAG laser removes tissue to create large openings into Schlemm’s canal with less collateral thermal damage than occurs with other wavelengths. Although this limited thermal damage has not proven to be an advantage in the survival of Er : YAG sclerostomies in humans (Wetzel, 1995 ; 1994) or sclerostomies with an automated trephine (Brown et al., 1987 ; 1988), failure of this procedure in rabbits (Hill et al., 1992) and humans has been primarily due to episcleral fibrosis and to a lesser extent, iris incarceration. Although holmium laser sclerostomy (Schuman et al., 1993), with its much greater thermal effect, appears to have better long-term survival than erbium : YAG laser sclerostomy in humans, these observations can not be directly generalized to laser trabecular ablation. With ab-interno trabecular surgery, there is no exposure to the episcleral tissues. It is possible that the scarring response of the trabecular meshwork and Schlemm’s canal after laser trabecular ablation could be dampened by a decrease in collateral thermal damage. This, combined with the relatively large size of the openings which can be produced by Er : YAG laser trabecular ablation, might limit the closure of the openings, such

as occurs after Nd : YAG trabeculopuncture or mechanical trabeculotomy in adults. Only further work will reveal if minimizing thermal damage is an advantage or disadvantage in preserving the patency of openings through trabecular meshwork. If the Canal of Schlemm remains patent, and the openings through the meshwork persist, the increase in outflow facility after Er : YAG trabecular ablation could be a lasting effect. Other advantages of this procedure would be accessibility to all quadrants as well as the ability to preserve conjunctiva. In living animal or human eyes, the procedure could be performed via a paracentesis using a sapphire optical fiber for direct contact ablation of the trabecular meshwork under gonioscopic guidance, using viscoelastic if necessary to maintain anterior chamber depth. Possible risks include bleeding into the anterior chamber, damage to the lens in a phakic patient, worsening of glaucoma, and inability to titrate the pressure lowering response once ablation has been performed. Overall, this procedure is in the early stages of development, but further work is warranted to determine if it could add to our surgical armamentarium for the treatment of glaucoma. Animal studies will be important to determine the longevity of the pressure lowering effect as well as any other potential risks.

ERBIUM: YAG LASER TRABECULAR ABLATION WITH A SAPPHIRE OPTICAL FIBER

Acknowledgements Supported by National Institutes of Health grant u1R43 EY10474. The authors have no proprietary interest in the development or marketing of the instruments used in this study.

References Barany, E. H. (1964). Simultaneous measurement of changing intraocular pressure and outflow facility in the vervet monkey by constant pressure perfusion. Invest. Ophthalmol. Vis. Sci. 3, 135–43. Bill, A. and Svedbergh, B. (1972). Scanning electron microscopic studies of the trabecular meshwork and the canal of Schlemm : an attempt to localize the main resistance to outflow of aqueous humor in men. Acta Ophthalmol. 50, 295–318. Brown, R. H., Denham, D. B., Bruner, W. E., Lynch, M. G., Quigley, H. A. and Parel, J. M. (1987). Internal sclerectomy for glaucoma filtering surgery with an automated trephine. Arch. Ophthalmol. 105, 133–6. Brown, R. H., Lynch, M. G., Denham, D. B., Parel, J. M., Palmberg, P. and Brown, D. D. (1995). Internal sclerectomy with an automated trephine for advanced glaucoma. Ophthalmology 95, 728–34. Eisenberg, D. L., Schuman, J. S. and Wang, N. (1994). An ultra-sensitive ocular perfusion system. ARVO abstracts 35(4), 1844. Ellingsen, B. A. and Grant, W. M. (1972). Trabeculotomy and sinusotomy in enucleated human eyes. Invest. Ophthalmol. 11, 21–8. Epstein, D. L., Melamed, S., Puliafito, C. A. and Steinert, R. F. (1985). Neodymium : YAG laser trabeculopuncture in open-angle glaucoma. Ophthalmology 92, 931–7. Ethier, C. R., Ajersch, P. and Pirog, R. (1993). An improved ocular perfusion system. Curr. Eye Res. 12(8), 765–70. Fitzgibbon, J. J., Bates, H. E., Pryshlak, A. P. and Phickbrick, M. J. (1994). Sapphire optical fibers for the delivery of Erbium : YAG laser energy. Proc Biomed. Opt. Soc., SPIE. 2131(5), 50–5. Grant, W. M. (1995a). Tonographic measurements in enucleated eyes. Arch Ophthalmol. 53, 191–200. Grant, W. M. (1955b). Facility of flow through the trabecular meshwork. Arch Ophthalmol. 53, 245–8.

155

Grant, W. M. (1958). Further studies on facility of flow through the trabecular meshwork. Arch Ophthalmol. 60, 523–33. Grant, W. M. (1963). Experimental aqueous perfusion in enucleated human eyes. Arch. Ophthalmol. 69, 783–801. Hill, R. A., Baerveldt, G., Ozler, S. A., Pickford, M., Profeta, G. A. and Berns, M. W. (1991). Laser trabecular ablation. Lasers Surg. Med. 11, 341–6. Hill, R. A., Ozler, S. A., Baerveldt, G., Viscardi, J. J., Keates, R. H., Lee, M., Harrington, J. A. and Berns, M. W. (1992). Ab-interno neodymium : YAG versus erbium : YAG laser sclerostomies in a rabbit model. Ophthalmic surgery 23(3), 192–7. Krasnow, M. M. (1974). Q-switched laser goniopuncture. Arch. Ophthalmol. 92, 37–41. Luntz, M. H. and Livingston, D. G. (1977). Trabeculotomy ab externo and trabeculectomy in congenital and adult onset glaucoma. Am. J. Ophthalmol. 83, 174–9. Melamed, S., Pei, J., Puliafito, C. A., Epstein, D. L. (1985). Qswitched Neodymium : YAG laser trabeculopuncture in monkeys. Arch Ophthalmol. 103, 129–33. Melamed, S., Latina, M. A. and Epstein, D. A. (1987). Neodymium : YAG laser trabeculopuncture in juvenile open-angle glaucoma. Ophthalmology 94, 163–70. Nesterov, A. P. (1970). Role of the blockade of Schlemm’s canal in pathogenesis of primary open angle glaucoma. Am. J. Ophthalmol. 70, 691–6. Ozler, S. A., Hill, R. A., Andrews, J. J., Baerveldt, G. and Berns, M. W. (1991). Infrared laser sclerostomies. Invest. Ophthalmol. Vis. Sci. 32, 2498–502. Robin, A. L. and Pollack, I. P. (1985). Q-switched neodymium : YAG laser angle surgery in open-angle glaucoma. Arch. Ophthalmol. 103, 793–5. Schuman, J. S., Stinson, W. G., Hutchinson, B. T., Bellows, A. R., Puliafito, C. A. and Lytle, R. (1993). Holmium laser sclerectomy : Success and complications. Ophthalmology 100, 1060–5. Wetzel, W., Schmidt-Erfurth, U., Haring, G., Roider, J., Droge, G. and Birngruber, R. (1995). Laser sclerostomy ab externo using two different infrared lasers : a clinical comparison. German J. Ophthalmol. 4(1), 1–6. Wetzel, W., Haring, G., Brinkmann, R. and Birngruber, R. (1994). Laser sclerostomy ab externo using the erbium : YAG laser : First results of a clinical study. German J. Ophthalmol. 3(2), 112–15.