|Year : 2017 | Volume
| Issue : 2 | Page : 51-58
A prospective comparative study between trabeculectomy versus trabeculectomy with Ologen for patients with primary open-angle glaucoma at 3-year follow-up
Ahmed G Elmahdy MD
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||15-Feb-2017|
|Date of Acceptance||30-Mar-2017|
|Date of Web Publication||20-Jul-2017|
Ahmed G Elmahdy
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, 11563, Cairo
Source of Support: None, Conflict of Interest: None
The aim of this study was to compare the outcomes of trabeculectomy with collagen implant versus conventional trabeculectomy for uncontrolled intraocular pressure (IOP).
Patients and methods
Sixty-eight eyes of 58 patients were randomly selected for trabeculectomy either with Ologen implant (the study group) or without implant (the control group). Preoperative history taking and examinations were carried out. Data including age, sex, glaucoma type, IOP, and numbers of postoperative glaucoma medications were collected. Postoperative IOP, number of postoperative glaucoma medications, and postoperative complications were recorded. Each patient was followed up for 3 years.
No significant differences were observed between the two groups in terms of preoperative IOP and number of preoperative antiglaucoma medications. Postoperative IOP in the Ologen group was significantly lower than that in the control group at all follow-up visits; the mean IOP in the Ologen group was 12.88±2.37 mmHg and that in the control group was 17.26±2.72 mmHg (P=0.006). The mean number of antiglaucoma medications (0.61±0.15) in the Ologen group was significantly lower than that in the control group (1.48±0.19) at last visit (P<0.001). There were no statistically significant differences between the two groups as regards postoperative complications as observed in this study.
Trabeculectomy with Ologen showed significant advantages over trabeculectomy alone in terms of IOP. Large sample size is needed to confirm the safety and long-term outcome of trabeculectomy with Ologen.
Keywords: bleb, glaucoma, intraocular pressure, Ologen, trabeculectomy
|How to cite this article:|
Elmahdy AG. A prospective comparative study between trabeculectomy versus trabeculectomy with Ologen for patients with primary open-angle glaucoma at 3-year follow-up. J Egypt Ophthalmol Soc 2017;110:51-8
|How to cite this URL:|
Elmahdy AG. A prospective comparative study between trabeculectomy versus trabeculectomy with Ologen for patients with primary open-angle glaucoma at 3-year follow-up. J Egypt Ophthalmol Soc [serial online] 2017 [cited 2018 Mar 22];110:51-8. Available from: http://www.jeos.eg.net/text.asp?2017/110/2/51/211142
| Introduction|| |
Glaucoma is a common cause of blindness. It is characterized by the progressive loss of ganglion cells of the retina and their axons ,. Reduction of intraocular pressure (IOP) is the main target of treatment. Generally, vision and visual field are preserved in glaucomatous eyes when IOP is kept at a lower level than that causes optic nerve damage .
Although medical treatment for glaucoma with antiglaucoma drugs is the first choice, surgical intervention is necessary in certain situations such as poor compliance of the patient and disease progression . Glaucoma filtration surgery lowers IOP by creating an opening between the anterior chamber and the subconjunctival space for the drainage of aqueous humor . Trabeculectomy has been used since 1968 and still is the standard surgery for glaucoma . The outcome of trabeculectomy is affected by many factors such as history of previous incisional surgery involving the superior conjunctiva, prolonged use of topical antiglaucoma medication ,, black race, and young age ,. Conjunctival scaring and fibrosis are the main causes of failure in trabeculectomy that cause blockage of aqueous outflow by creating adhesions between conjunctiva and episclera, and between scleral flap and underlying tissues .
Modified surgical techniques using 5-fluorouracil (5-FU) and mitomycin C (MMC) have improved the success rate of trabeculectomy results by preventing intraoperative or postoperative scarring through the inhibition of fibroblast proliferation in wound healing process, and thus preventing scar formation and bleb failure ,,. However, the use of antimetabolites increases the risk for bleb leakage , hypotony maculopathy , endophthalmitis , and many other dangerous ophthalmic complications ,. Tendency to increase the success rate of surgery and reduce the complications led to the search for an effective method for preventing postoperative fibrosis.
In this regard, recently the idea of using biodegradable implants derived from tissue engineering as an alternative to antifibrotic agents in trabeculectomy surgery has been proposed. The biodegradable collagen matrix implant (≥90% collagen and ≤10% glycosaminoglycan), marketed initially as OculusGen and currently as Ologen and iGen, is a novel bioengineered implant designed to be used at the time of trabeculectomy . It consists of a collagen-based scaffold containing thousands of microscopic pores . The implant is placed directly over the scleral flap and influences the healing process by forcing fibroblasts and myofibroblasts to grow into the pores and secrete connective tissue in the form of a loose matrix .
This implant aims to regulate aqueous flow by keeping pressure gradient on top of the scleral flap and by acting as a reservoir, as aqueous is absorbed into its porous structure. This implant, also, prevents the collapse of the subconjunctival space and creates microcysts with collagen deposition .
The aim of this study was to compare between surgical outcomes of trabeculectomy versus trabeculectomy with Ologen as regards IOP, postoperative medications, bleb function, and postoperative complications.
| Patients and methods|| |
A prospective randomized clinical study was conducted at a public hospital, at Al-Azhar University Hospitals (El-Hussein and Bab-Elsheryia Hospitals). Sixty-eight eyes of 58 patients who presented with primary open-angle glaucoma were included in this study.
Thirty-four eyes were treated with trabeculectomy alone (the control group) and the other 34 eyes were treated with trabeculectomy with subconjuctival implant of Ologen (Ologen group) under the Tenon and over the scleral flap. Ologen is a collagen matrix of 1% collagen/C-6-S copolymer (OculusGen Biomedical Inc., Taipei, Taiwan). The selected size is the recommended size by the company, which is 7 mm length, rounded disc-shaped with 4 mm thickness for all cases.
Written consent for participation in the study was taken from all patients after explaining the purpose of the study based on the Helsinki Declaration of tents, and the approval of the Ethics Committee of Al-Azhar University Hospitals and Faculty of medicine of Al-Azhar University was obtained.
Inclusion criteria were as follows: age more than 40 years and primary open-angle glaucoma that was not controlled and/or tolerated the medication. Exclusion criteria were as follows: history of prior ocular surgery, pregnancy or breastfeeding, age less than 40 years, normal tension glaucoma, secondary open-angle glaucoma, and ocular surface disease.
Preoperatively, the following data were collected, such as age, sex, and numbers of medications. All patients underwent a comprehensive ophthalmic evaluation, including best-corrected visual acuity testing, IOP measurement with a Goldmann applanation tonometer, slit-lamp biomicroscopy, visual field testing, gonioscopy, and funduscopy.
Statistical analysis was performed using Microsoft excel (Microsoft Redmond, Washington, USA) and Student’s t-test programs.
All surgeries were performed using the same identical techniques using the standard method with Fornix-based conjunctival flap. After peribulbar anesthesia and proper draping, a bridle suture was inserted into peripheral clear cornea superiorly; fornix-based conjunctival flap dissection with good dissection of Tenon capsule was performed in a separate layer. Rectangular, half-thickness scleral flap (3.5×4 mm) was created; paracentesis, 2×1 mm deep sclerectomy, and a peripheral iridectomy were performed thereafter. Scleral flap was closed with two sutures (10/0 nylon). Ologen was placed over the edge of the scleral flap beneath the conjunctiva, making the operation area dry for 34 eyes of the study. Conjunctiva was closed like a wing with two sutures using 10/0 nylon.
Treatments after surgery were the same in the two groups, including the use of topical antibiotic for a week and topical steroids for 2–3 weeks and cycloplegic drops for 2 weeks. Follow-up was scheduled for all eyes for 3 years as follows: first postoperative day, 1 week, 1, 3, and 6 months, and 1, 2 and 3 years.
On the first postoperative day, the anterior chamber, amount of inflammation, bleb status and its function, bleb leakage, and IOP were recorded. At each postoperative visit, examinations included the following: measurement of vision, measurement of IOP using applanation tonometer, examination with silt lamp (bleb condition), and recording the number of antiglaucoma medications. The presence of postoperative complications, including hyphema, choroidal effusion, hypotony and high filtration and endophthalmitis after surgery, and late bleb leaks were evaluated and recorded if present.
Success is defined as follows: complete success is defined as postoperative IOP of less than 21 mmHg without any antiglaucoma medications; qualified success is defined as postoperative IOP less than 21 mmHg with antiglaucoma medications (in patients with IOP >21 mmHg with the same treatment preoperatively); and failure is defined as an IOP of 21 mmHg or more with or without antiglaucoma medications. Hypotony was defined as IOP equal to or less than 6 mmHg.
| Results|| |
All patients included in this study completed the period of follow-up (3 years). There was no statistically significant difference between the two groups as regards demographic data ([Table 1]). As regards operative procedure ‘subscleral trabeculectomy’, there were no recorded intraoperative complications in both groups.
The average age of the trabeculectomy group was 65.00±1.76 (range: 48–71) years, and in the trabeculectomy group with Ologen it was 61.00±2.82 (range: 42–67). There was no significant difference between the two groups in terms of age distribution (P=0.215). In the trabeculectomy group, 50% were female (17 patients) and 50% male (17 patients). In the Ologen group, 53% were female (18 patients) and 47% were male (16 patients) and there were no statistically significant differences between the two groups in terms of sex distribution (P=0.463).
In this study, the mean preoperative IOP in the Ologen and control groups were 34.79±1.69 and 33.39±1.36 mmHg, respectively, with no statistically significant difference (P=0.187).
Postoperatively, mean IOP was calculated at all postoperative visits ([Figure 1]) and is reported in [Table 2], which shows a statistically significant difference between the two groups. It was found that the mean IOP in the Ologen group was 12.88±2.37 mmHg and in the control group the mean IOP was 17.26±2.72 mmHg (P=0.006). Moreover, the mean IOP at last visit for both groups was as follows: the Ologen group, 15.61±2.38 mmHg, and the control group, 19.43±2.27 mmHg (P=0.006).
|Table 2 The mean postoperative intraocular pressure values of two groups|
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In this study, postoperative complications were reported in both groups ([Table 3]), with no statistically differences. In the Ologen group two eyes (2/34, 5.9%) were complicated by severe hypotony with shallow anterior chamber. Surgical interference with injection of viscoelastic was made for both eyes, which responded with return of IOP to normal level. Moreover, hypotony was reported in two eyes (2/34, 5.9%) in the control group, and was managed by increasing the rate of topical postoperative corticosteroids eye drops and with ocular bandage.
Hyphema was recorded in five eyes (5/68, 7.35%), two and three eyes in the Ologen and control groups, respectively, which resolved in few days postoperatively. Transient shallowing of the anterior chamber was seen in 7/68 eyes (10.3%), four (11.8%) and three (8.8%) eyes in the Ologen and control groups, respectively, which improved within few days postoperatively. Two eyes (2/68) showed positive Seidel testing (early leak) (2.9%) in the Ologen group, which was treated conservatively with ocular bandage. No other major complications were seen, such as endophthalmitis or choroidal effusion.
Bleb encapsulation after first follow-up visit was reported in 6/68 (10.3%) eyes, one (3%) and five (14.7%) eyes in the Ologen and control groups, respectively, which lead to increased IOP and failed to return to normal levels despite needling with multiple 5-FU injection. Flat bleb with high IOP was reported in 5/68 (7.35%) eyes, one (3%) and four (11.8%) eyes in the Ologen and control groups, respectively, at the 6 and 12 months of follow-up visits, with return to antiglaucoma medications again.
The incidence of postoperative complications, including encapsulated bleb, flat bleb, and bleb revision was higher in the control group in comparison with the Ologen group ([Figure 2]).
|Figure 2 Comparison between the two groups as regards postop. complications and success rate|
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In this study, postoperative antiglaucoma medications were reported in both groups, as shown in [Table 4]. The mean number of postoperative antiglaucoma medications was 0.61±0.15 drugs in the Ologen group, whereas in the control group it was 1.48±0.19 drugs (P≤0.001), which was highly significant ([Figure 3]).
|Table 4 Number of preoperative and postoperative antiglaucoma medications|
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|Figure 3 Comparison between the two groups as regards postop. antiglaucoma medications|
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Complete and Qualified success results were 32/34 eyes (94.1%) in the Ologen group ([Figure 4]), where two eyes had IOP more than 21 mmHg inspite of usage of antiglaucoma medications. In comparison with control group ([Figure 5]), Complete and Qualified success results were 29/34 eyes (85.3%) (P = 0.049 which was statistically significant) as there are five eyes with IOP more than 21 mmHg that failed to be controlled with antiglaucoma medications, and further intervention was planned.
|Figure 4 Serial photos of the conjunctival bleb (Ologen group); 1 week, 1, 3, 6, 12, 24 and 36 months postoperative|
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|Figure 5 Serial photos of the conjunctival bleb (control group); 1 week, 1, 3, 6, 12, 24 and 36 months postoperative|
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| Discussion|| |
It is known that postoperative scarring is a major problem compromising postoperative surgery success in trabeculectomy operation . Wound healing process is effective in determining the final postoperative IOP and bleb function and with extensive scarring, fibrosis, and obstruction of aqueous outflow occur, which is one of the most common reasons for the failure of glaucoma surgery ,,.
Since 1980 antiscarring antimetabolites such as 5-FU and MMC have been widely used to augment the success of trabeculectomy by reducing fibroblast proliferation in the subconjunctival space as well as in the Tenon capsule ,. However, these agents can cause adverse effects such as hypotony with maculopathy, cystic thin avascular bleb, bleb infection, endophthalmitis, and late-onset leaks ,. Other antiscar agents such as growth-factor inhibition and amniotic membrane have been applied to enhance the success rate of glaucoma surgery with limited results .
The Ologen implant is a novel bioengineered implant designed to be used at the time of trabeculectomy as an alternative to antimetabolite use in trabeculectomy surgery because of its modulatory effect on wound healing. The aim of this porous collagen polymer is to allow random proliferation of fibroblasts through the collagen matrix, hence decreasing collagen deposition and scarring. A literature suggests that Ologen degradation time is about 30–60 days ,. However, Boey et al.  found Ologen implant residue to be still present in 40% of cases at 90 days.
The clinical applications of Ologen have been presented at conferences (European Congress of Ophthalmology, Vienna, June 2007, and World Glaucoma Congress, Singapore, July 2007) .
In this study it was found that the mean postoperative IOP was more controlled with trabeculectomy in the Ologen than in the control group. At the same time, mean postoperative antiglaucoma drugs and complications were lower in the Ologen group than in the control group, most probably due to a decrease in scar tissue formation. In the same way, Gunenc et al.  found that trabeculectomy with OculusGen implant lowers IOP effectively and safely in a short term (1–12 months) of follow-up.
Moreover, Chen et al.  found 58.3% reduction in mean IOP after 9 months of follow-up in 59 eyes with refractory glaucoma that had undergone trabeculectomy with OculusGen implantation. There was no reportable complication.
Moreover, Rosentreter et al.  reported that Ologen is well effective in reducing scar formation that led to increased success rate of trabeculectomy.
In comparison with this study, Papaconstantinou et al.  found that; All eyes in the study group (Ologen group) and 95% of the eyes in the control group were considered qualified successes. They showed that trabeculectomy with Ologen does not seem to offer any significant advantages compared with trabeculectomy alone regarding to mean postoperative IOP, mean of antiglaucoma drugs and postoperative complications.
In comparison with trabeculectomy with MMC, it was found that MMC is more effective on conjunctival healing, getting marked reduction of fibrosis, and transparent polycystic blebs, but with high incidence of complications . In this study, no case of endophthalmitis was reported. In another study  they reported one case of endophthalmitis, but after culture it was found that it was not due to Ologen.
Although further studies with large sample designs are necessary to evaluate the effectiveness of Ologen matrix with trabeculectomy operation, my study has demonstrated a high success rate in comparison with trabeculectomy alone for 3 years of follow-up.
In conclusion, this new degradable collagen implant (Ologen) is a safe and effective method in reducing IOP and reducing the number of antiglaucoma drug therapies compared with trabeculectomy without adjuvant by improving and normalizing filtering surgical wound healing with more loosely organized bleb tissue and healthy blebs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]