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Enzymatic Sclerostomy
Pilot Human Study
Jacob A. Dan, MD, PhD;
Santosh G. Honavar, MD;
David A. Belyea, MD;
Anil K. Mandal, MD;
Chandrasekhar Garudadri, MD;
Brian Levy, OD, MSc;
Rengappa Ramakrishnan, MD;
Ramasamy Krishnadas, MD;
Marc F. Lieberman, MD;
Robert L. Stamper, MD;
Arieh Yaron, PhD
Arch Ophthalmol. 2002;120:548-553.
ABSTRACT
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Objective To evaluate the feasibility and safety of enzymatic sclerostomy as a
new modality to lower intraocular pressure in patients with open-angle glaucoma.
Methods This single-center, prospective, noncomparative, interventional case
series included 15 blind symptomatic eyes of 15 patients with primary open-angle
glaucoma. Enzymatic sclerostomy was performed with the patient under topical
or peribulbar anesthesia. A specially designed polymethylmethacrylate enzyme
applicator filled with a mean ± SD of 123 ± 13 µg of collagenase
was introduced through a 5-mm peritomy, and affixed to the limbus by means
of cyanoacrylate tissue glue. After 22 to 24 hours, the applicators were removed
and the patients were followed up for 1 year. Intraocular pressure changes
from baseline and complications related to the procedure were the main outcome
measures.
Results Controlled thinning of the treated sclera associated with aqueous percolation
and shallow filtration bleb was seen in all eyes in the immediate postoperative
period. The mean ± SD intraocular pressure decreased from 43.5 ±
9.8 mm Hg (while the patients were receiving a mean ± SD of 1.75 ±
0.75 antiglaucoma medications) preoperatively to 24.8 ± 10.6 mm Hg
(a 43.0% decrease from baseline with no antiglaucoma medication) on the first
postoperative day and to 34.8 ± 10.5 mm Hg (a 20.0% decrease from baseline
with no antiglaucoma medication) at the end of 1 year. Ophthalmic adverse
effects were limited to the treated area and included immediate postoperative
transient conjunctival reaction ranging from mild chemosis to conjunctival
maceration. Immediate full-thickness perforation developed in 1 eye; the patient
was treated and excluded from data analysis. Two eyes developed symptoms related
to increase in intraocular pressure after 9 months; the patients were treated
and excluded from further data analysis. No systemic complications were noted.
Conclusions Enzymatic sclerostomy demonstrated immediate and sustained intraocular
pressure reduction and provided symptomatic relief in blind eyes with primary
open-angle glaucoma. The procedure, however, needs further technical refinement.
INTRODUCTION
TRABECULECTOMY is an established surgical modality in the treatment
of glaucoma. However, it has a long learning curve and is associated with
several sight-threatening complications. Imaginative procedures such as microtrabeculectomy,1 holmium and erbium laser sclerostomy,2-4
ultrasonic insonification,5 excimer laser filtration
surgery,6 deep sclerectomy,7
and viscocanalostomy8 have been proposed as
minimally invasive alternatives to conventional trabeculectomy.
Clostridial collagenase has been used in humans for discolysis in cases
of prolapsed intervertebral disk,9 for removal
of the cheloid plaques in Peyronie disease,10
and as an adjunct in vitrectomy.11 The potential
of collagenase to act as a "biological knife" to selectively digest collagen
inspired us to develop a treatment modality for glaucoma that we named enzymatic sclerostomy, wherein highly purified collagenase
is used to create deep focal scleral digestion, possibly enabling micropercolation
of aqueous humor. Our group has studied the directional selectivity of propagation
of collagenase through the scleral collagen lamellae and has demonstrated
the efficacy of this method in reducing the intraocular pressure in a rabbit
model.12 We have established the optimal duration
of exposure to collagenase in humans by evaluating variable periods of application
with constant enzyme concentration and placement location and have demonstrated
ocular and systemic safety.13 Preliminary human
studies performed at the Beilinson Hospital, Petah-Tikva, Israel; Aravind
Eye Hospital, Madurai, India; and California Pacific Medical Center, San Francisco,
included 16 blind eyes of 16 patients. Placement of the enzyme delivery system
at the anatomic limbus and a mean ± SD enzyme exposure time of 22 ±
2 hours were found most effective in reducing intraocular pressure without
causing full-thickness scleral digestion or ocular and systemic toxicity.
On the basis of the results of our earlier experimental and preliminary human
studies, we planned a controlled interventional noncomparative case series
to evaluate the efficacy and safety of enzymatic sclerostomy in human subjects.
PATIENTS AND METHODS
The study was performed at the VST Center for Glaucoma Care, LV Prasad
Eye Institute, Hyderabad, India, with approval from the institutional review
board. Fifteen consecutive patients (15 eyes) with primary open-angle glaucoma
who met the inclusion criteria and agreed to participate in the study were
enrolled. All the eyes were legally blind and symptomatic because of elevated
intraocular pressure, and had had no previous ocular surgery. Each patient
had functional vision in the fellow eye. To minimize variations due to differences
in the collagen structure, patients selected were uniformly Asian-Indian in
race, and the age range was restricted (45-75 years). The patients signed
an informed consent and agreed to adhere to the follow-up protocol.
Preoperative evaluation (by J.A.D. and S.G.H.) included slitlamp biomicroscopy
of the ocular surface and the anterior segment, intraocular pressure measurement
by Goldmann applanation tonometry, evaluation of the anterior chamber angle
by Goldmann 2-mirror gonioscope, and optic disc examination with a +60 diopter
lens. In patients who were taking topical antiglaucoma medications, the drugs
were discontinued at least 1 day before the enzymatic sclerostomy was scheduled.
When required, however, the use of topical antiglaucoma medications in the
fellow eye continued. An internist performed systemic evaluation to rule out
conditions associated with abnormal collagen structure.
Highly purified collagenase (nucleolysine, approved as investigational
drug 1491410), lot 60901, containing 5150 U/vial,14 was supplied as lyophilized powder (BioSpecifics
Technologies Corp; Lynbrook, NY). Cyanoacrylate tissue glue was acquired commercially
(Braun; Melsungen, Germany). The forceps used for grasping the enzyme applicator
were designed and manufactured at the Tools Laboratory of the Weizmann Institute
of Science (Rehovot, Israel). Polymethylmethacrylate enzyme applicators were
manufactured (ASCON; Madras, India) in conformance with the design previously
used.9 The applicators were manually filled
with lyophilized collagenase powder in the range of 100 to 152 µg (mean
± SD, 123 ± 13 µg), stored at -4°C, and used
within 72 hours.
The surgery was performed in the operating room under an operating microscope
by 1 of 3 surgeons (J.A.D., S.G.H., and A.K.M.). Topical anesthesia (4% lidocaine
drops) was used in 8 eyes and peribulbar anesthesia (1:1 mixture of 2% lidocaine
and 0.5% bupivacaine, 5 mL) in 7 eyes. A lid speculum was introduced and a
5-mm peritomy was performed at the superior limbus. Wet-field cautery was
applied to achieve hemostasis. The exposed sclera at the intended site of
application was thoroughly dried with a cellulose sponge. A drop of tissue
adhesive was placed on the ventral surface of the applicator in the trough
encircling the well containing the enzyme (Figure 1). The applicator was grasped during the procedure by means
of specially designed forceps. It was then firmly applied to the sclera with
its anterior edge corresponding to the anterior edge of the anatomic limbus
(Figure 2). Fixation of the applicator
to the sclera was verified by attempting to mechanically displace it over
the scleral surface. Fixation was deemed good when there was no movement of
the applicator over the sclera. Fixation was graded fair when there was minimal
movement, and poor when there was edge lift or significant movement. Where
the applicator fixation was poor, a new applicator with fresh glue was applied
to ensure satisfactory fixation. The conjunctiva was repositioned to completely
cover the applicator (Figure 3), and it was held in position with an 8-0 polyglactin suture or a drop of cyanoacrylate
tissue glue. Ciprofloxacin, 0.3% ointment, was applied and the eye was patched.
The treated eye was evaluated 18 to 20 hours after application (while the
enzyme applicator was still in place) by slitlamp biomicroscopy and Goldmann
applanation tonometry. Special note was made of the position of the conjunctival
flap, conjunctival reaction, position of the enzyme applicator, presence of
aqueous leak, anterior chamber depth, anterior chamber inflammation, and position
of the lens. The conjunctival reaction was graded on a scale of 1 to 5 as
follows: grade 1, localized chemosis over the applicator; grade 2, as in grade
1 combined with conjunctival hemorrhage over or around the applicator; grade
3, diffuse hemorrhage surrounding the applicator and/or thinning of the conjunctiva
over the applicator; grade 4, thinning of the conjunctiva around the applicator
and/or localized melt over the applicator; and grade 5, conjunctival maceration
over and around the applicator.
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Figure 1. Appearance of the ventral surface
of the applicator, showing the central well containing the enzyme, encircled
by a trough containing the glue. Inset A, A droplet of adhesive glue filling
the trough. Inset B, A computer-designed drawing of the microapplicator (original
magnification x15).
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Figure 2. Intraoperative photograph showing
the applicator being firmly affixed to the sclera by means of application
forceps (arrow). Note that the anterior edge of the enzyme applicator is positioned
at the anatomic limbus.
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Figure 3. Slitlamp photograph 22 hours after
application showing the conjunctiva completely covering the applicator (arrow).
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Enzyme applicators were removed with the patient under topical anesthesia
(4% lidocaine drops) a mean ± SD of 22 ± 2 hours after application.
The applicator was removed along with the glue in 1 piece. It was examined
under an operating microscope to evaluate the adequacy of the glue in the
trough and to check if there was accidental spread of the glue to the well
containing the enzyme. The area of scleral application was wiped with a cellulose
sponge and then thoroughly irrigated with Ringer lactate solution to remove
enzyme residue. The position and depth of scleral digestion and the presence
of aqueous micropercolation were carefully noted. The depth of scleral digestion
was graded as follows: none, no perceptible effect on sclera; fair, concave
crater with brownish or bluish hue at the base and minimal aqueous percolation;
good, deep concave crater with brownish or bluish hue at the base with continuous
and diffuse aqueous percolation; excessive, marked scleral thinning with uveal
tissue shining through but with no frank uveal prolapse; and perforation,
full-thickness scleral melt and uveal prolapse. The conjunctiva was repositioned
to fully cover the treated area, and it was fixed in place with an 8-0 polyglactin
suture or with a drop of cyanoacrylate tissue glue. The eye was not patched
after removal of the enzyme applicator.
Each surgical procedure of enzyme application was analyzed for the position,
fixation, and conjunctival coverage of the applicator. Factors evaluated at
the time of removal of the applicator included conjunctival reaction, position
and fixation of the applicator, adequacy and distribution of glue, shape and
depth of scleral digestion, and the presence of aqueous percolation from the
treated site (Figure 4).
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Figure 4. Appearance of the treated site
22 hours after enzyme application. The arrow points to the scleral crater
formed by the enzymatic digestion.
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All patients received topical 0.3% gentamicin sulfate eyedrops 4 times
a day for 1 week and topical 0.1% betamethasone phosphate eyedrops 4 to 6
times a day, tapered over a period of 4 weeks. Patients were examined on postoperative
days 1, 2, and 3; at weeks 1, 2, and 4; and every 3 months thereafter. Specific
inquiries were made regarding patient comfort during the procedure and at
each follow-up visit. Change in intraocular pressure compared with the baseline
and the occurrence of complications were the main outcome measures. The statistical
significance of the change in intraocular pressure was determined with the
2-tailed paired t test. All data are presented as
mean ± SD unless otherwise specified.
RESULTS
Of the 15 patients, 11 were men and 4 were women, ranging in age from
45 to 75 years. Three patients were newly diagnosed with primary open-angle
glaucoma and were previously untreated. Twelve patients were taking 1.75 ±
0.75 (range, 1-3) types of antiglaucoma medication for symptomatic relief
at enrollment. Use of topical antiglaucoma medication was discontinued at
least 1 day before surgery. The baseline intraocular pressure was 43.5 ±
9.8 mm Hg. Three patients were excluded from further data analysis, 1 because
of full-thickness scleral perforation requiring scleral grafting and 2 because
of an elevation of intraocular pressure after 9 months requiring additional
treatment (transscleral cyclophotocoagulation in 1 eye and topical timolol
maleate 2 times a day in 1 eye). The final follow-up was at 12 months after
enzymatic sclerostomy.
The collagenase-specific activity as determined by the manufacturer
showed no decay from the day of enzyme charging in the applicators until the
actual day of application.
Patients reported no pain or discomfort during application. Applicator
position and fixation were inadequate in 5 eyes, and new applicators were
applied (twice in 4 cases and 9 times in 1 case) until satisfactory position
and fixation were obtained. However, when evaluated after 22 ± 2 hours,
during the removal of the applicators, the position of the enzyme applicator
was good only in 12 eyes; in 2 eyes it was placed too far anterior and in
1 eye too far posterior. The fixation of the applicator to the sclera was
deemed good in 10 cases, fair in 3 cases, and poor in 2 cases. The glue was
adequately distributed in the applicator trough in 9 cases. In 2 cases, the
glue was excessive and partially obstructed the well that contained collagenase,
thereby possibly impeding the contact of the enzyme with sclera. In 4 cases,
the glue did not fully fill the trough, possibly inadequately limiting the
area of enzymatic effect. The surgical procedure lasted less than 5 minutes
in each of the 10 eyes where the first attempt at application was successful.
An examination 18 to 20 hours after enzyme application (before applicator
removal) disclosed in all the eyes a uniformly deep and quiet anterior chamber,
round and regular pupil, and undamaged lens. The intraocular pressure was
28.5 ± 12 mm Hg (range, 10-54 mm Hg), representing a decrease of 34.5%
from the baseline. All the applicators were in the original position and were
well covered by the conjunctiva. The conjunctival reaction was grade 1 in
3 cases, grade 2 in 3 cases, grade 3 in 2 cases, grade 4 in 5 cases, and grade
5 in 2 cases. This seemed to correlate with the degree of applicator fixation.
Applicators were removed 22 ± 2 hours after placement. The patients
reported no pain or discomfort. Applicators were removed in less than 3 minutes
in all cases. The applicator and the glue that bound the applicator to the
sclera could be dislodged in one piece by using the application forceps with
gentle force. No difficulties were encountered in the removal of the applicator
or repositioning of the conjunctiva to the limbus.
Morphologically, the scleral digestion appeared in the shape of a cup
with sharp borders, deepest at the center and sloping steeply at the periphery.
The depth of enzymatic scleral digestion was good in 7 eyes, fair in 3 eyes,
and poor in 3 eyes. In one case (patient 14), enzymatic digestion of the sclera
was excessively deep, progressing to the Descemet membrane. In this case,
the amount of collagenase used was 125 µg, the applicator was positioned
anterior to the limbus, application was successful in the second attempt,
and fixation was good with an adequate amount of glue. In another case (patient
15), a full-thickness sclerocorneal perforation (measuring 1 mm in diameter)
with uveal prolapse resulted. The amount of collagenase used in this case
was 116 µg, application was successful in the first attempt, fixation
was good, and amount of glue was adequate, but the position of the applicator
was anterior to the limbus. Slitlamp examination 3 hours before the applicator
was removed showed grade 1 conjunctival reaction, deep and quiet anterior
chamber, round and central pupil, and an intraocular pressure of 21 mm Hg.
The applicator was removed 24 hours after enzyme application, showing a full-thickness
focal perforation. The perforation was managed with a small scleral patch
graft and a peripheral iridectomy, and the patient was excluded from further
data analysis. The patient experienced pain in the operated-on eye, which
subsided in 2 weeks. Follow-up was continued, with careful attention given
to signs of continuous collagenase digestion of the sclera or other intraocular
collagenous tissues. One year after the initial surgery, the scleral patch
graft remained well positioned and no signs of collagen tissue digestion were
observed. Intraocular pressure ranged from 17 to 20 mm Hg with treatment with
0.5% timolol maleate twice a day for the duration of follow-up.
In all cases, the conjunctival reaction completely resolved in 1 to
2 weeks and the conjunctiva over the treated site resembled a shallow filtering
bleb in the early postoperative period. Nevertheless, the actual presence
of filtration blebs could not be ascertained because of the presence of conjunctival
chemosis and hemorrhage. A shallow filtering bleb was seen in 5 eyes at 1
week after the sclerostomy (Figure 5),
persisting in 4 eyes for 2 weeks and in 3 eyes for 1 month. No bleb was recognized
in any of the eyes 3 months after treatment.
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Figure 5. Appearance of an eye 1 week postoperatively.
The eye is quiet, and conjunctival reaction is minimal. Note the shallow filtering
bleb, indicated by the slit beam.
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Intraocular pressure dynamics after enzymatic sclerostomy are presented
in Figure 6. The baseline intraocular
pressure was 43.5 ± 9.8 mm Hg (range, 24-56 mm Hg). The mean intraocular
pressure on the day after removal of the enzyme applicator was 24.8 ±
10.6 mm Hg (range, 11-42 mm Hg), representing a 43.0% decrease from the baseline.
The mean intraocular pressure was 31.0 ± 11.4 mm Hg (range, 15-45 mm
Hg), a 28.7% decrease from the baseline, at 1 week; 32.4 ± 9.3 mm Hg
(range, 21-42 mm Hg), a 25.5% decrease from baseline, at 1 month; and 34.8
± 10.5 mm Hg (range, 21-50 mm Hg), a 20.0% decrease from baseline,
at 1 year. The reduction in intraocular pressure due to enzymatic sclerostomy
was statistically significant (P<.001 at 1 day,
at 1 week, at 1 month, and at 1 year). All patients were comfortable with
the treatment, required no antiglaucoma medication, and remained so until
9 months after enzymatic sclerostomy. Between the 9th and 12th months of follow-up,
2 patients (patients 4 and 12) reported symptoms related to elevated intraocular
pressure. Symptoms were controlled by topical 0.5% timolol maleate twice daily
in patient 12, and by semiconductor diode laser transscleral cyclophotocoagulation
in patient 4. These 2 patients were excluded from further data analysis. In
all, 12 (86%) of 14 patients had symptomatic relief after enzymatic sclerostomy.
Ten (91%) of 11 patients (excluding 1 patient who underwent transscleral cyclophotocoagulation)
who were taking antiglaucoma medication for symptomatic relief before enzymatic
sclerostomy did not need medication after the procedure.
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Figure 6. Intraocular pressure dynamics
after enzymatic sclerostomy. Bars represent the high and low values of each
point at each examination.
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COMMENT
By causing an overall decrease of 43.0% in the intraocular pressure
immediately after treatment and a sustained lowering effect of 20.0% at 1
year, as well as relieving symptoms in 86% of patients without antiglaucoma
medication, enzymatic sclerostomy, although still in its technical infancy,
has demonstrated its potential as a treatment for open-angle glaucoma.
Encouraged by the results of enzymatic sclerostomy in laboratory animals
and on the basis of preliminary experience in humans in several institutions,
we decided to evaluate 15 blind, previously unoperated-on eyes with primary
open-angle glaucoma and elevated intraocular pressure treated enzymatically
according to a uniform protocol and followed up for a year. The LV Prasad
Eye Institute in India was chosen as the study site because of the availability
of a patient population corresponding to the enrollment criteria, its reputation
for providing high-standard medical care, and the availability of infrastructure
for conducting standard clinical trials.
None of the patients reported pain or discomfort during and after the
procedure (hence, no attempt was made to quantify patient discomfort), and
patients were equally comfortable under topical anesthesia or with peribulbar
block, suggesting that this treatment could be performed as an office procedure.
Conjunctival reaction varied from none to local maceration and seemed
proportionate to the adequacy of the applicator's scleral fixation; this may
explain the absence of detectable blebs beyond 3 months after application
in cases where the reaction was excessive.
The extent of the scleral digestion varied from none to full-thickness
perforation. Reasons for this variability could be patient related (difference
in the scleral structure), applicator related (variation in collagenase content),
or procedure related (adequacy of application). However, the enzyme concentration,
the contact area, and the period of application seemed adequate, since most
eyes displayed observable scleral digestion and had a meaningful intraocular
pressure–lowering effect.
Full-thickness scleral perforation, a potentially sight-threatening
complication that demonstrates the importance of proper positioning of the
applicator, occurred in 1 patient. In this patient, the enzyme applicator
was misplaced on the peripheral cornea, anterior to the anatomic limbus. There
are differences in the collagen architecture and the relative composition
of glycosaminoglycan between the cornea and the sclera; these differences
may explain the increased susceptibility of the cornea to collagenase, resulting
in its perforation. It is possible that collagenase enzyme gained access to
the anterior chamber in this eye after perforation. However, the patient continued
follow-up and there was no evidence of continued collagenolytic action on
the sclera or the cornea. Data from this patient and from the 2 patients who
developed symptoms related to increase in intraocular pressure at 9 months
and needed additional treatment for the relief of symptoms were excluded from
further analysis.
By the conventional definition of intraocular pressure control after
glaucoma filtering surgery (intraocular pressure,  21 mm Hg), only 2 patients
(13%) demonstrated success in our study. However, most patients (80% [12/15])
were taking antiglaucoma medication when enrolled for the study, and their
baseline intraocular pressure was measured without an adequate washout period.
Therefore, the achievable intraocular pressure–lowering effect of enzymatic
sclerostomy may actually be higher. Moreover, the enzymatic treatment was
performed entirely on an Asian-Indian population, and the bleb survival as
well as the intraocular pressure–lowering effect may be different in
other patient populations.15 Twelve (86%) of
14 patients had symptomatic relief after enzymatic sclerostomy, demonstrating
the efficacy of the procedure in symptomatic eyes and its potential as an
alternative to cyclodestructive procedures. Ten (91%) of 11 patients who were
taking antiglaucoma medication for symptomatic relief before enzymatic sclerostomy
did not need medication after the procedure.
Sustained lowering of the intraocular pressure was achieved despite
the absence of a detectable filtering bleb in most eyes beyond 1 month and
in all eyes beyond 3 months. The possibility of alteration in the trabecular
cell biological characteristics or augmentation of episcleral drainage in
response to collagenase application as a mechanism of intraocular pressure
lowering cannot be ruled out except by further studies. It is possible that
enzymatically induced alterations in the walls of Schlemm canal and the trabecular
architecture, as shown in our previous histologic and electron microscopic
animal studies,12 could contribute to the intraocular
pressure–lowering effect. Although the safety of small amounts of collagenase
has been previously proved,11-13
collagenase activity in the anterior chamber and alteration in histologic
profile of ocular tissues in response to collagenase exposure are among the
issues yet to be investigated.
Despite the encouraging intraocular pressure–lowering effect,
enzymatic sclerostomy suffers from several technical difficulties. Successful
application was achieved only after several attempts in 30% of patients, and
optimal positioning with good or fair fixation was achieved in only 67% of
patients.
In summary, enzymatic sclerostomy has demonstrated its potential as
a relatively simple surgical treatment for glaucoma. The result herein presented
justifies further studies to improve and standardize the procedure and to
determine its ultimate place in glaucoma treatment.
AUTHOR INFORMATION
Submitted for publication July 24, 2001; final revision received December
10, 2001; accepted December 21, 2001.
This study was supported by a grant from Bausch & Lomb Global Biological
& Clinical Research, Rochester, NY.
This study was presented in part as a poster at the annual meeting of
the Association for Research in Vision and Ophthalmology, Ft Lauderdale, Fla,
March 15, 1998, and in part as a poster at the annual meeting of the American
Academy of Ophthalmology, Orlando, Fla, October 26, 1999.
Corresponding author: Jacob A. Dan, MD, PhD, PO Box 38, Hod-Hasharon
45100, Israel (e-mail: jdan{at}netvision.net.il).
From Revivim-Zahala Medical Consultants, Tel Aviv, Israel (Dr Dan);
Department of Biophysics and Biochemistry, Weizmann Institute of Science,
Rehovot, Israel (Drs Dan and Yaron); VST Center for Glaucoma Care, LV Prasad
Eye Institute, Hyderabad, India (Drs Honavar, Mandal, and Garudadri); Department
of Ophthalmology, George Washington University, Washington, DC (Drs Dan and
Belyea); Department of Ophthalmology, University of Rochester School of Medicine
& Dentistry, Rochester, NY (Dr Levy); Aravind Eye Hospital, Madurai, India
(Drs Ramakrishnan and Krishnadas); and Department of Ophthalmology, University
of California, San Francisco (Drs Lieberman and Stamper). The Weizmann Institute
of Science, and Drs Dan and Yaron have a proprietary interest in the materials
and the methods used in this study.
REFERENCES
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1. Vernon SA, Gorman C, Zambarakji HJ. Medium to long-term intraocular pressure control following small flap
trabeculectomy (microtrabeculectomy) in relatively low risk eyes. Br J Ophthalmol. 1998;82:1383-1386.
FREE FULL TEXT
2. Hoskins HD Jr, Iwach AG, Vassiliadis A, Drake MV, Hennings DR. Subconjunctival THC:YAG laser thermal sclerostomy. Ophthalmology. 1991;98:1394-1399.
ISI
| PUBMED
3. Jacobi PC, Dietlein TS, Krieglstein GK. Prospective study of ab externo erbium:YAG laser sclerostomy in humans. Am J Ophthalmol. 1997;123:478-486.
ISI
| PUBMED
4. Coleman DJ, Lizzi FL, Driller J, et al. Therapeutic ultrasound in the treatment of glaucoma, II: clinical applications. Ophthalmology. 1985;92:347-353.
ISI
| PUBMED
5. Brooks AM, Samuel M, Carroll N, Downie N, Taylor HR. Excimer laser filtration surgery. Am J Ophthalmol. 1995;119:40-47.
ISI
| PUBMED
6. Mermoud A, Schnyder CC, Sickenberg M, Chiou AG, Hediguer SE, Faggioni R. Comparison of deep sclerectomy with collagen implant and trabeculectomy
in open-angle glaucoma. J Cataract Refract Surg. 1999;25:323-331.
FULL TEXT
|
ISI
| PUBMED
7. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-angle glaucoma in black African patients. J Cataract Refract Surg. 1999;25:316-322.
FULL TEXT
|
ISI
| PUBMED
8. Wong VK, Koenig SB, Fogel ES, Freedman MI. Late detachment of Desçemet's membrane after subconjunctival
THC:YAG (holmium) laser thermal sclerostomy ab externo. Am J Ophthalmol. 1993;116:514-515.
ISI
| PUBMED
9. Sussman BJ, Bromley JW, Gomez JC. Injection of collagenase in the treatment of herniated lumbar disk:
initial clinical report. JAMA. 1981;245:730-732.
ABSTRACT
10. Gelbard MK, Lindner A, Kaufman JJ. The use of collagenase in the treatment of Peyronie's disease. J Urol. 1985;134:280-283.
ISI
| PUBMED
11. Moorhead LC, Radtke N. Enzyme-assisted vitrectomy with bacterial collagenase: pilot human
studies. Retina. 1985;5:98-100.
FULL TEXT
|
ISI
| PUBMED
12. Dan JA, Yaron A. Focal scleral permeability enhanced by collagenase digestion: experimental
model of enzymatic sclerostomy. Ophthalmology. 1994;101:461-472.
ISI
| PUBMED
13. Dan JA, Honavar SG, Sekhar GC, et al. Enzymatic sclerostomy: human study [abstract]. Invest Ophthalmol Vis Sci. 1998;39(suppl):939.
14. Mandl I, Zipper H, Ferguson ZB. Clostridium hystolyticum collagenase: its
purification and properties. Arch Biochem Biophys. 1958;74:465-475.
FULL TEXT
|
ISI
15. Ramakrishnan R, Michon J, Robin AL, Krishnadas R. Safety and efficacy of mitomycin C trabeculectomy in southern India:
a short-term pilot study. Ophthalmology. 1993;100:1619-1623.
ISI
| PUBMED
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