Modified Trabeculectomy Using Ologen® Collagen Matrix with Or

Modified Trabeculectomy Using Ologen® Collagen Matrix with or without A Cyclodestructive Procedure for Canine Glaucoma: A Retrospective Review of 14 Cases Sung-Jun Lee1 Joon-Young Kim2,† Soon-wuk Jeong1

1Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Korea 2Veterinary Medical Teaching Hospital, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Korea †Corresponding author: Joon-Young Kim Veterinary Medical Teaching Hospital, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea Tel.: 82-2-444-6150 Fax: 82-2-444-4396 E-mail: [email protected]

KEY WORDS: canine glaucoma, photocoagulation (TSCP); and group 3 (four cyclodestructive procedure, filtering eyes), MTO with endocyclophotocoagula- surgery, intraocular pressure, ologen® CM, tion (ECP). Data pertaining to signalment, trabeculectomy pre- and postoperative intraocular pressure ABSTRACT (IOP) and visual acuity, preoperative management, detailed surgical procedures, post- Trabeculectomy in the dogs has not generally used because of filtering bleb failure operative treatments, follow-up duration, due to episcleral fibrosis and subconjuncti- surgical outcomes, and complications were val scarring for glaucoma. To overcome this retrospectively reviewed. The outcomes of filtering bleb failure, we applied a modified trabeculectomy and bleb formation were trabeculectomy using ologen® Collagen evaluated using ultrasound biomicroscopy Matrix (CM) with or without a cyclode- (UBM). IOP was successfully stabilized at structive procedure for dogs with medically < 25 mmHg at different time points in 12 uncontrolled glaucoma. This study was of the 14 (85.7%) eyes. Six of nine eyes performed as retrospective case series. 14 (66.7%) maintained vision after surgery, and eyes of 12 dogs with medically uncontrolled two of five (40.0%) eyes with preoperative glaucoma was evaluated from 2015 through vision loss regained vision after surgery. All 2016. The dogs were divided into three eyes except two exhibited successful filter- groups: group 1 (six eyes), modified trabecu- ing bleb formation without major complica- lectomy using ologen® CM (MTO); group 2 tions. IOP showed no significant differences (four eyes), MTO with transscleral cyclo- among groups (P > 0.05). Modified trabecu-

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 47 lectomy using ologen® CM is easy to per- of bleb-related complications such as bleb form and demonstrates successful outcomes leakage, subconjunctival tissue necrosis, with minimal postoperative complications. hypotony maculopathy, blebitis, and endo- This new surgical technique may be an ef- phthalmitis.2,7 Recently, tissue-engineered fective alternative procedure for IOP control implants were developed as alternatives to in canine glaucoma. MMC and 5-FU, with lesser adverse effects. One of these is the ologen® Collagen Matrix INTRODUCTION (ologen® CM, Aeon, Astron, Leiden, the Glaucoma is one of the common causes of 1, 2 Netherlands), which consists of lyophilized vision loss in humans and animals. Cur- porcine atelocollagen and glycosaminogly- rently, transscleral cyclophotocoagulation can with a 10- to 300-μm pore size. It is (TSCP), and endocyclophotocoagulation biodegradable and an implantable extra- (ECP) and are considered effective methods 3,4 cellular matrix (ECM) mimic specifically for lowering IOP in animals. But ECP is configured to support and modulate tissue generally performed at the time of phaco- repair processes in connective and epithelial emulsification with intraocular lens implan- ocular tissues.14 According to recently re- tation to prevent postoperative secondary 5 ported studies on glaucoma filtering surger- cataract formation. And TSCP can cause ies performed in animal models and humans, short- and long-term complications, such ologen® CM is effective in promoting bleb as postoperative intraocular hypertension, formation by modulating fibroblast migra- hyphema, uveitis, secondary cataract, and 4 tion and proliferation into the pore struc- ulcerative keratitis. In the field of veterinary tures and normalizing secreted collagen ophthalmology, the most common filter- and another extracellular matrix deposition, ing procedures involve the use of anterior 15,16 6 resulting in reduced scar formation. In chamber shunts or gonioimplantation. the present study, we aimed to determine Several reports have described gonioimplan- a surgical technique that is easier and less tation as an effective procedure for normal- complicated than gonioimplantation, which izing IOP and maintaining vision in dogs 2,7,8,9 is the most commonly used method, and in with medically uncontrolled glaucoma. our opinion, the use of ologen® CM for tra- However, it is associated with early and late beculectomy may be an effective alternative complications, including hypotony, ante- for the surgical treatment of canine glau- rior uveitis, tube obstruction, conjunctival coma. Although, to the best of our knowl- erosion, tube migration, corneal endothelial edge, no previous study has documented the decompensation, and filtering bleb failure, in 6,10 outcomes of modified trabeculectomy using humans and dogs. Trabeculectomy which ologen® CM with or without a cyclode- is another filtering surgery has not generally structive procedure for the treatment of used because of filtering bleb failure due canine glaucoma. The aim of the present to episcleral fibrosis and subconjunctival 4,6 study was to describe the surgical techniques scarring for glaucoma in the dogs. Exces- and clinical outcomes associated with modi- sive fibrosis of the filtering bleb may lead fied trabeculectomy using ologen® CM with to bleb failure and lower the success rate of or without a cyclodestructive procedure for filtering surgeries, including trabeculectomy medically uncontrolled glaucoma in 12 dogs and gonioimplantation, in both humans and (14 eyes). animals.11,12 To prevent bleb scarring, several adjunctive antimetabolies, including mito- MATERIALS AND METHODS mycin C (MMC) and 5-fluorouracil (5-FU), Review of medical records are commonly used.2,11,13 Although the use of The medical records at Veterinary Medi- antimetabolites during or following surgery cal Teaching Hospital (VMTH), Konkuk has improved the long-term success rate for University were reviewed to identify 14 filtering surgeries,2,8 it has increased the rate eyes of 12 dogs with medically uncontrolled

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 48 Figure 1. Modified trabeculectomy with ologen® glaucoma treated by modified Collagen Matrix (CM) for medically uncontrolled trabeculectomy using ologen® CM glaucoma in dogs. (a) A fornix-based conjunctival/ with or without a cyclodestructive Tenon’s flap is prepared at the 12 o’clock position, 0.5 procedure (TSCP or ECP) from mm behind the superior limbus. (b) A rectangular 2.0 x 2015 through 2016. Data pertain- 2.0-mm2 wide, 300-μm thick limbal-based scleral flap ing to signalment, pre- and post- is dissected using a crescent knife. operative IOP and visual acuity, (c) A 1 to 1.5-mm trabeculectomy window is created preoperative management, detailed using a corneoscleral punch for glaucoma after the surgical procedures, postoperative placement of a stab incision using a No. 11 blade. (d) treatment, follow-up duration, sur- The scleral flap is repositioned with ologen® CM (8.0 gical outcomes, and postoperative × 2.0 × 2.0 mm) implanted beneath it. (e) Flap closure complications were collected. The is achieved with two interrupted sutures, one tight and outcomes of trabeculectomy and one loose, using 10-0 nylon on the bilateral edges of bleb formation were also evaluated the flap. (f) Another ologen® CM (10.0 × 8.0 × 2.0 using ultrasound biomicroscopy mm) implant is positioned over the scleral flap without (UBM). All eyes were divided the use of sutures. (g) The conjunctiva is closed with a into three groups according to the simple continuous suture pattern using 9-0 polyglactin surgical procedure. Six eyes (cases 910. 1–6, group 1) underwent modified trabeculectomy using ologen® CM (MTO), four eyes (cases 7–10, group 2) underwent MTO with TSCP, and four eyes (cases 11–14, group 3) underwent MTO with ECP. Pre- and postoperative IOP was evaluated using applanta- tion tonometry (Tonopen VetTM, Reichert. INC., Depew, NY, USA). All data were statistically analyzed using SPSS statistics 24.0 for Win- dows (IBM, Armonk, NY, USA). The normality of data distribution was evaluated using the Shapiro– Wilk test. One-way ANOVA and the Kruskal–Wallis test were performed to compare differences in mean IOP values at different time points (before surgery; 5 h, 1 day, and 1, 2, 3, 4, 5, 6, and 12 months after surgery) among the three groups. A P-value of <0.05 was considered statistically significant. Modified trabeculectomy using ologen® CM General anesthesia was induced with intravenous propofol (6 mg/ kg; Provive 1%, Myungmoon Pharm. Co., Ltd, Korea) and maintained with 1.5%–2.0 % isoflurane

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 49

IOP IOP

None

Fibrin Fibrin

Uveitis Uveitis

Uveitis,

Hyphema

deposition

ulceration, ulceration,

Uncontrolled Uncontrolled

Complications

Corneal edema Corneal

Uveitis, Corneal Corneal Uveitis,

○

Maintenance of IOP below 20 20 below IOP of Maintenance

mmHg during the follow-up period follow-up the during mmHg

gery because of severe uveitis and corneal ulceration, bBlindness was observed 1 day after after day 1 observed was bBlindness ulceration, corneal and uveitis severe of because gery

Follow-up Follow-up

duration (weeks) duration

Post-OP Post-OP

visual status visual

Blind

Vision Vision

Post-OP Post-OP

maintained

visual status visual

Blind

Vision Vision

Pre-OP Pre-OP

maintained

visual status visual

ECP

MTO

TSCP

MTO, MTO,

Surgery

IOP

Pre-OP Pre-OP

PACG

uveitis

surgery

surgery surgery

Chronic Chronic

Cataract Cataract

Cause of of Cause

glaucoma

Age

ECS

ACS

Breed

Samoyed

No.

Case Case

Summary of signalment and clinical data of surgical procedures performed in each case. case. each in performed procedures surgical of data clinical and signalment of Summary 1. Table

surgery because of persistently elevated IOP, cBlindness was observed at 33 weeks after surgery because of a transient IOP increase IOP transient a of because surgery after weeks 33 at observed was cBlindness IOP, elevated persistently of because surgery

tomy using ologen® CM, ECP: endoscopic cyclophotocoagulation, TSCP: transscleral cyclophotocoagulation, aBlindness was observed at 3 weeks after sur after weeks 3 at observed was aBlindness cyclophotocoagulation, transscleral TSCP: cyclophotocoagulation, endoscopic ECP: CM, ologen® using tomy Pre-OP: preoperative, Post-OP: postoperative, IOP: intraocular pressure, ACS: American Cocker Spaniel, ECS: English Cocker Spaniel, ST: Shih Tzu, MP: Miniature Poodle, PACG: primary angle-closure glaucoma, MTO: modified trabeculec modified MTO: glaucoma, angle-closure primary PACG: Poodle, Miniature MP: Tzu, Shih ST: Spaniel, Cocker English ECS: Spaniel, Cocker American ACS: pressure, intraocular IOP: postoperative, Post-OP: preoperative, Pre-OP:

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 50 (Isoflurane; Choongwae Co., Ltd, Korea). trabeculectomy. Normal saline 0.9% was used for intraop- ECP using a diode laser (Diovet, Iris erative fluid management. The dog was Medical Instruments, Mountain View, CA, positioned in dorsal recumbency, and the USA) with the E4 Ophthalmic Laser Endos- affected eye was clipped and prepared for copy system (Endo Optiks Little Silver, New surgery using 0.2% povidone–iodine solu- Jersey, USA) was performed before trab- tion for sterilization of the ocular surface. eculectomy in four dogs with pseudophakia. For adequate globe positioning, intravenous Ciliary process ablation using 250 mV was atracurium besylate (0.2 mg/kg; Atra®, performed within a range of 180° to 270°. Hana pharm Co., Ltd., Seoul, Korea) was Whitening and contraction of each treated administered just before surgery. All 14 eyes ciliary process were identified. underwent trabeculectomy using the same Postoperative management procedure. A fornix-based conjunctival/ After the surgery in each animal, predniso- Tenon’s flap positioned at 12 o’clock was lone acetate 1% (Pred Forte®, Allergan, prepared by dissection of the conjunctiva Inc., Irvine, CA) and ofloxacin (Tarivid®, and Tenon’s capsule 0.5 mm behind the su- Santen Pharm., Ltd, Korea) were topically perior limbus using Westcott tenotomy scis- applied on the operated eye every 6 h. Over sors (Fig. 1a). A rectangular 2.0 × 2.0-mm2, a duration of 2 to 4 weeks, ofloxacin was 300-μm thick limbal-based scleral flap was discontinued if there was no evidence of dissected using a crescent knife (Fig. 1b), infectious disease. The frequency of pred- and a 1 to 1.5-mm trabeculectomy window nisolone acetate 1% was gradually tapered, was created using a corneoscleral punch with a maintenance frequency of once a day. for glaucoma after the placement of a stab The frequency and number of antiglaucoma incision using a No. 11 blade (Fig. 1c). The medications were gradually decreased with a scleral flap was repositioned with ologen® decrease in or normalization of IOP. CM (8.0 × 2.0 × 2.0 mm) implanted beneath it (Fig. 1d). Flap closure was achieved with RESULTS two interrupted sutures, one tight and one In total, there were three English Cocker loose, using 10-0 nylon (ALCON® Closure Spaniels (three eyes), three American Systems, Alcon Laboratories, Inc. Texas, Cocker Spaniels (four eyes), three Shih USA) on the bilateral edges of the flap (Fig. Tzus (four eyes), two Miniature Poodles 1e). Another ologen® CM (10.0 × 8.0 × (two eyes), and a Samoyed (one eye). The 2.0 mm) implant was positioned over the mean age was 8.5 years (range, 3–14 years). scleral flap without the use of sutures (Fig. All eyes were diagnosed with glaucoma: 1f). Finally, the conjunctiva was closed with five with glaucoma secondary to chronic a simple continuous suture pattern using uveitis, seven with glaucoma as a compli- 9-0 polyglactin 910 (Vicryl*, Ethicon LLC, cation of cataract surgery, and two with USA) (Fig. 1g). An intracameral injection primary angle-closure glaucoma (PACG). of tissue plasminogen activator (tPA, 25 mg; All eyes exhibited intraocular hyperten- Actilase®, Beringer Ingelheim, Germany) sion (IOP > 25 mmHg) before surgery was administered after surgery. despite antiglaucoma medications such as Cyclodestructive procedure β-adrenoceptor blockers, α2-adrenoceptor TSCP using a diode laser (Diovet, Iris Medi- agonist, carbonic anhydrase inhibitor, and cal Instruments, Mountain View, CA, USA) prostaglandin analogs. The clinical data for was performed before trabeculectomy in all eyes are shown in Table 1. Following four dogs. Energy was delivered to 20 sites surgery, IOP was successfully stabilized at by 600-mm spots with a power setting of <20 mmHg at different time points in 12 of 1000 mV for a duration of 5000 ms. The 12 the 14 eyes (cases 1-7, 9-11, 13, 14; 85.7%). o’clock site was avoided in order to perform The antiglaucoma medications for these 12 eyes were gradually tapered or discontinued

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 51 Table 2. Evaluation of IOP (mean ± SD) values during the follow-up period for each group. Group 1 Group 2 Group 3 Day P-value (n-6) (n = 4) (n = 4) Pre-OP 39.00 ± 3.16 45.75 ± 8.73 40.50 ± 6.14 0.629a Post-OP 12.17 ± 2.48 26.50 ± 13.03 23.00 ± 11.23 0.063a 1 day 13.67 ± 1.97 20.00 ± 7.26 29.50 ± 15.42 0.130a 1 month 15.17 ± 7.60 17.75 ± 7.27 24.00 ± 11.97 0.235a 19.67 ± 13.32 2 months 16.17 ± 6.61 13.50 ± 4.04 0.608b (n = 3) 15.00 ± 3.74 14.00 ± 1.00 3 months 14.50 ± 4.80 0.935b (n = 5) (n = 3) 14.50 ± 3.70 14.00 ± 1.00 4 months 14.50 ± 3.70 0.919b (n = 4) (n = 3) 13.75 ± 1.89 14.00 ± 1.73 5 months 16.00 ± 5.03 0.717a (n = 4) (n = 3) 12.75 ± 2.22 15.33 ± 5.77 13.67 ± 2.08 6 months 0.841a (n = 4) (n = 3) (n = 3) 12.50 ± 3.54 17.50 ± 10.60 15.50 ± 2.12 12 months c (n = 2) (n = 2) (n = 2) Group 1: modified trabeculectomy using ologen® CM (MTO), Group 2: MTO with trans-scleral cyclophotocoagulation, Goup 3: MTO with endocyclophotocoagulation, Pre-OP: preoperative, Post-OP: 5 h after surgery, aKruskal– Wallis test, bOne-way ANOVA, cStatistical verification not possible because of small sample size on the basis of IOP normalization. Although cerated. Case 8 exhibited an elevated IOP IOP exhibited a transient increase (>25 at 1 week after surgery. Slit-lamp examina- mmHg) in seven (cases 1, 4, 5, 6, 11, 13, 14) tion revealed deep corneal ulceration with of the 12 eyes between 1 day and 41 weeks severe uveitis, and the eye lost vision despite (mean, 9.9 weeks; median, 6 weeks) after medical treatment. The corneal ulcer and surgery, it normalized immediately or within uveitis recovered after 1 month of intensive a few days after the temporary administra- medical treatment, although severe fluctua- tion of antiglaucoma and anti-inflammatory tions in IOP were observed (from 10 mmHg medications with or without tPA injections to 41 mmHg). At the time of glaucoma in the anterior chamber. The number of anti- surgery, nine eyes (cases 1, 3, 5-8, 11, 12, glaucoma medications required by these 12 14) exhibited intact visual function; this was eyes was smaller after surgery than before maintained in six eyes (cases 1, 3, 5- 7, 11; surgery. Postoperative hypotony was not 66.7%) after surgery. The remaining three observed in any eye. In the remaining 2 eyes eyes (cases 8, 12, 14) lost vision within 1 (cases 8 and 12), however, IOP could not day to 231 days (mean, 80 days) after sur- be effectively controlled after surgery. Case gery. Cases 8 and 12 lost vision because of 12 demonstrated intraocular hypertension uncontrolled high IOP, as explained above. immediately after surgery, and IOP could Case 14 exhibited a transient IOP increase not be controlled despite intensive medical and vision loss at 41 weeks after surgery. treatment and anterior chamber paracente- Before this, the condition of the eyes was sis. This eye lost vision within a day after very good with no other side effects and surgery and exhibited a persistently elevated well-maintained vision, which was lost IOP for 14 weeks. Eventually, it was evis- despite IOP normalization. This dog died 3

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 52 months later because of diabetic complica- effective IOP control. Ologen® CM was tions. Finally, two (cases 2, 9; 40%) of five gradually resorbed, and a clear drainway for eyes (cases 2, 4, 9, 10, 13) with preoperative aqueous humor from the anterior chamber blindness regained vision within 1 day after was detected around the scleral flap on UBM surgery. examinations (Fig. 2). Mild conjunctival Slit-lamp biomicroscopy and UBM hyperemia around the bleb, which resolved examinations revealed the successful forma- with short-term anti-inflammatory treatment, tion of filtering blebs without major com- was occasionally observed in three eyes plications, including conjunctival necrosis (cases 1, 9, 11). IOP normalized immedi- or dehiscence and endophthalmitis, during ately after surgery and was satisfactorily the follow-up period for all eyes except maintained over the long-term follow-up two (cases 8, 12), which did not achieve period. There were no significant differences

Figure 2. Evaluation of bleb formation using ultrasound biomicroscopy after modified trabeculectomy using ologen® Collagen Matrix (CM) for medically uncontrolled glaucoma in dogs. Ologen® CM is gradually resorbed, and a clear drainway for aqueous humor from the anterior chamber is visible around the scleral flap. (A) Four days after surgery (case 2), (B) 10 days after surgery (case 7), (C) 26 days after surgery (case 6), (D) 90 days after surgery (case 4), (E) 100 days after surgery (case 1), (F) 150 days after surgery (case 11), H: 1–1.5- mm trabeculectomy window, SF: scleral flap, B: bleb, D: drainway under the scleral flap

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 53 in IOP values at different time points among term foreign body reaction due to nonbio- the three groups (P > 0.05; Table 2). degradable devices.20 Trabeculectomy is a surgical method for the stabilization of IOP DISCUSSION by draining aqueous humor from anterior In the present study, we demonstrated a new chamber to the space between the sclera and filtering surgery involving modified trabecu- the conjunctiva. After ocular tissue damage lectomy using ologen® CM with or without caused by surgical procedure, normal wound a cyclodestructive procedure (ECP or TSCP) healing reaction occurs in the body. The for IOP control and vision maintenance in wound healing process is a complex physi- dogs with medically uncontrolled glaucoma. ological mechanism for tissue repair includ- IOP was controlled in 12 of the 14 included ing coagulation, inflammation, fibroplasia, eyes (85.7%). Six of nine eyes (66.7%) with angiogenesis, epithelization, maturation, and intact vision before surgery maintained their remodeling. After the acute inflammatory vision after surgery, and two of five eyes response, fibroblasts migrate and prolifer- (40%) with preoperative blindness regained ate into the wound site by growth factors vision. Our success rates for IOP control included transforming growth factor-β and vision maintenance after surgery are (TGF-β) and platelet-derived growth factor comparable with those previously reported (PDGF) which are released by macrophages for glaucoma drainage device (GDD) im- and platelets. Fibroblasts, play a key role in plantation (75% and 66.7%, respectively),8 7 the formation of scar tissue, synthesize new gonioimplantation (76%/46%) with TSCP, collagen and other extracellular matrix that and trabeculectomy with or without TSCP 17 are important components of granulation (55.6%/66.7%) in studies with varying tissue. Deposition and organization of newly follow-up periods. Currently, the placement synthesized collagen in the parallel to the of an anterior chamber shunt, such as an fibroblasts which are oriented in the wound Ahmed valve, a Baerveldt drainage implant, bed. Unidirectional alignment of collagen and a Krupin-Denver valve, Cullen frontal provides tensile strength of the scar tissue, sinus valved glaucoma shunt, using gonio- and it is different from aligned randomly implantation has been considered the most collagen in normal connective tissue.21 Fil- common filtering procedure for medically 1,4,6,18 tering bleb failure due to episcleral fibrosis uncontrolled glaucoma in animals, and and subconjunctival scarring is the major several studies have reported successful cause of poor outcomes after filtering sur- outcomes of this procedure for medically 4,6 2,7,8,16 gery for glaucoma in animals. For the pre- uncontrolled glaucoma in dogs. How- vention of excessive scar tissue formation, ever, in humans, trabeculectomy is a com- antimetabolites, such as MMC and 5-FU, mon surgical procedure for the treatment of are widely used in human and dogs during uncontrolled glaucoma. According to many or after glaucoma filtering surgery. These studies focusing on a comparison of long- agents are useful in inhibition of fibroblast term outcomes between gonioimplantation growth and replication, however, they can and trabeculectomy for glaucoma, there is 19 cause severe complications associated with no difference between the two procedures. their widespread fibroblast cytotoxicity and However, Tran et al reported that trabeculec- apotosis, including conjunctival necrosis, tomy is more effective than gonioimplanta- thin-walled avascular bleb formation, bleb 20 The advantages of tion for lowering IOP. leakage, bleb-related infection, and endo- trabeculectomy include the lack of compli- phthalimits.6,21 Recently, as alternatives to cations caused by intraocular implants, such antimetabolites, biodegradable collagen ma- as tube occlusion and migration, irritation terials such as ologen® CM were introduced of the corneal endothelium, tissue necrosis for use in trabeculectomy and other glau- around the reservoir base, implant exposure, coma filtering procedures.16 This implant and chronic anterior uveitis with a long- is composed of three-dimensional, porous,

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 54 collagen-glycosaminoglycan copolymers edges of the scleral flap is considered an ef- that can encourage fibroblasts and myofi- fective method, and very loose or very tight broblasts to grow in to the matrix pores and sutures can cause postoperative hypotony secrete connective tissue in the form a loose or ocular hypertension, respectively. In the matrix. By guiding the pattern of cellular present study, we applied one tight and one migration, that should promote random loose suture on the bilateral edges of the orientation of collagen deposition similar scleral flap to restore it to its original posi- to normal connective tissue, it inhibited the tion. Postoperative transient IOP spikes can dense scar tissue formation and wound con- lead to adverse effects on long-term visual traction. And also, application of the implant outcomes because of ischemic damage to the in the space between episclera and conjunc- optic disc and retina. Early detection of re- tiva can form a mechanical barrier that may elevated IOP and efforts for normalization prevent adhesion between these two tissue with active treatments, including medica- layers during the early postoperative pe- tions and revision surgery, are important riod.16,22 In addition, according to a previous for successful outcomes.2,7,8 In this case experimental study in an animal model, im- series, a transient IOP spike, including early plant-induced pressure created by position- postoperative intraocular hypertension, was ing between the scleral flap and conjunctiva observed in seven eyes at different time contributes to the prevention of excessive points after surgery, and it resolved with ad- aqueous humor drainage.14 Excessive out- ditional anti-inflammatory and antiglaucoma flow of aqueous humor with inflammatory medications in all eyes. mediators into the subconjunctival space in We identified bleb and drainway forma- uveitic conditions can lead to increased bleb tion using UBM in our study. In most cases, fibrosis and, consequently, a poor progno- ologen® CM was completely resorbed at 90 sis.2 Therefore, the use of ologen® CM aids days after surgery. A drainway was de- in the maintenance of adequate bleb func- tected at approximately 2 weeks, while bleb tion. In the present study, functional blebs formation was detected at approximately were formed in 12 of the 14 eyes (85.7%) at 1 month after surgery. Postoperative IOP the last follow-up visit. In the present study, values showed no differences among the we implanted ologen® CM not only subcon- three groups in our study, which suggests junctivally, similar to its placement during that the outcomes of trabeculectomy alone conventional glaucoma filtering procedures and trabeculectomy with a cyclodestruc- in humans, but also subsclerally. We believe tive procedure are not different. However, that the subconjunctival implant aided in a transient IOP spike occurred more fre- the formation of an adequate filtering bleb, quently in the early postoperative period in while the subscleral implant maintained the dogs that underwent trabeculectomy with a surgical passage for aqueous humor out- cyclodestructive procedure. Several reports flow through the prevention of subscleral on cyclophotocoagulation documented fibrosis. Thus, ologen® CM implantation intraocular hypertension within 1 week after contributed to the successful control of IOP surgery as the most common early postop- in our patients. In addition, this technique erative complication.1,3 Trabeculectomy for can prevent early postoperative hypotony, secondary glaucoma, particularly that caused which causes hypotensive retinopathy with by uveitis, is more challenging compared multifocal retinal folds because of overfiltra- with that for primary glaucoma in humans.19 tion of aqueous humor. It is one of the most Chronic and recurrent intraocular inflam- common complications of glaucoma filtering mation can result in postoperative hypotony surgery in humans and animals.2,6,8 Several due to ciliary body impairment. Moreover, modified techniques for the prevention of active intraocular inflammation can promote hypotony immediately after trabeculectomy undesired and excessive scarring of the have been studied.23 Suturing the bilateral subconjunctival bleb and adherence of the

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 55 scleral flap. The recurrence of uveitis should 8. Graham KL, Donaldson D, Billson FA, Billson FM. be prevented by aggressive anti-inflammato- 2017. Use of a 350-mm2 Baerveldt glaucoma drainage device to maintain vision and control ry treatments, including intracameral injec- intraocular pressure in dogs with glaucoma: a tion of tPA and continuation of topical and/ retrospective study (2013–2016). Vet Ophthalmol or systemic steroid application, in order to 20:427-434. 9. García-Sánchez GA, Whitley RD, Brooks DE, Trigo improve the prognosis after trabeculectomy F, Piñón A. 2005. Ahmed valve implantation to for secondary glaucoma. control intractable glaucoma after phacoemulsifica- The findings of the present study demon- tion and intraocular lens implantation in a dog. Vet Ophthalmol 8:139-144. strate that modified trabeculectomy using 10. Wilson MR, Mendis U, Paliwal A, Haynatzka V. ologen® CM with or without a cyclodestruc- 2003. Long-term follow-up of primary glaucoma tive procedure can control IOP and maintain surgery with Ahmed glaucoma valve implant versus trabeculectomy. Am J Ophthalmol 136:464- vision in dogs with medically uncontrolled 470. glaucoma. This modified surgical technique 11. Ji Q, Qi B, Liu L, Guo X, Zhong J. 2015. Efficacy and additional collagen matrix implanta- and safety of Ologen implant versus mitomycin tion can result in successful outcomes with C in primary trabeculectomy: a meta-analysis of randomized clinical trials. J Glaucoma 24:e88-e94. minimal complications such as postoperative 12. Tinsley DM, Betts DM. 1994. Clinical experience hypotony and bleb fibrosis. However, further with a glaucoma drainage device in dogs. Vet studies on methods to control transient IOP Comp Ophthalmol 4:77-84. spikes after surgery and the optimal position 13. WuDunn D, Cantor LB, Palanca-Capistrano AM, Hoop J, Alvi NP, Finley C, Lakhani V, Burnstein of ologen® CM for minimizing bleb and A, Knotts SL. 2002. A prospective randomized drainway fibrosis are warranted. To the best trial comparing intraoperative 5-fluorouracil vs of our knowledge, this is the first study on mitomycin C in primary trabeculectomy. Am J the outcomes of modified trabeculectomy Ophthalmol 134:521-528. 14. Chen HS-L, Ritch R, Krupin T. Hsu W-C. 2006. using ologen® CM for medically uncon- Control of filtering bleb structure through tissue trolled glaucoma in dogs. bioengineering: an animal model. Invest Ophthal- mol ViSl Sci 47:5310-5314. REFERENCES 15. Angmo D, Wadhwani M, Upadhyay AD, Temkar 1. Plummer CE., Regnier A, Gelatt KN. 2013. The S, Dada T. 2017. Outcomes of trabeculectomy canine glaucomas, In: Gelatt KN, Gilger BC, Kern augmented with subconjunctival and subscleral TJ, eds. Veterinary Ophthalmology 5th ed. Iowa, Ologen implantation in primary advanced glau- USA: John Wiley & Sons, Inc; 1050-1145. coma. J glaucoma 26:8-14. 2. Westermeyer HD, Hendrix DV, Ward DA. 2011. 16. Park KH, Kim JY, Choo SW, Yoon HY, Jeong SW. Long-term evaluation of the use of Ahmed go- 2016. Ahmed glaucoma valve implantation with nioimplants in dogs with primary glaucoma: nine Ologen® Collagen Matrix for the surgical treat- cases (2000–2008). J Am Vet Med Assoc 238:610- ment of feline glaucoma. Vet Ophthalmol 96-100. 617. 17. Amagai Y, Karasawa K, Matsuda H, Tanaka A. 3. Bras D, Maggio F. 2015. Surgical treatment of 2014. Diode laser transscleral cyclophotocoagu- canine glaucoma: cyclodestructive techniques. Vet lation in combination with trabeculectomy for Clin North Am Small Anim Pract 45:1283-1305. surgical therapy of canine refractory glaucoma. J 4. Gelatt KN, Esson DW, Plummer CE. 2011. Surgi- Vet Med Res 1:1010. cal procedures for the glaucomas. In: Gelatt KN, 18. Cullen CL. 2044. Cullen frontal sinus valved Gelatt JP, eds. Veterinary Ophthalmic Surgery. glaucoma shunt: preliminary findings in dogs with China, Elsevier Saunders; 265-303. primary glaucoma. Vet Ophthalmol 7:311-318. 5. Bras ID, Robbin TE, Wyman, Rogers AL. 2005. 19. Kwon HJ, Kong YXG, Tao LW, Lim LL, Martin Diode endoscopic cyclophotocoagulation in canine KR, Green C, Ruddle J, Crowston JG. 2017. Surgi- and feline glaucoma [abastract]. Vet Ophthalmol cal outcomes of trabeculectomy and glaucoma 8:449. drainage implant for uveitic glaucoma and relation- 6. Maggio F, Bras D. 2015. Surgical treatment of ship with uveitis activity. Clinl Exp Ophthalmol canine glaucoma: Filtering and end-stage glaucoma 2017. procedures. Vet Clin North Am Small Anim Pract 20. Tran DH, Souza C, Ang MJ, Loman J, Law SK, 45:1261-1282. Coleman AL, Caprioli J. 2009. Comparison of 7. Sapienza JS, Van Der Woerdt A. 2005. Combined long-term surgical success of Ahmed valve implant transscleral diode laser cyclophotocoagulation and versus trabeculectomy in open-angle glaucoma. Br Ahmed gonioimplantation in dogs with primary J Ophthalmol 93:1504-1509. glaucoma: 51 cases (1996–2004). Vet Ophthalmol 8:121-127.

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 56 21. Lama PJ, Fechtner RD. 2003. Antifibrotics and 23. Laspas P, Culmann PD, Grus FH, Prokosch-Willing wound healing in glaucoma surgery. Surv Ophthal- V, Poplawksi A, Pfeiffer N, Hoffmann EM. 2016. mol 48:314-346. A new method for revision of encapsulated blebs 22. Hsu W-C, Spilker MH, Yannas IV, Rubin PA. 2000. after trabeculectomy: combination of standard bleb Inhibition of conjunctival scarring and contraction needling with transconjunctival scleral flap sutures by a porous collagen-glycosaminoglycan implant. prevents early postoperative hypotony. PloS One Invest Ophthalmol Vis Sci 41:2404-2411. 11:e0157320.

Intern J Appl Res Vet Med • Vol. 17, No. 2, 2019. 57