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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 16  |  Issue : 2  |  Page : 58-64

Efficacy and safety of the use of freeze-dried (lyophilized) amniotic membrane transplantation with combined trabeculotomy-trabeculectomy for congenital glaucoma


Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission18-Feb-2015
Date of Acceptance30-May-2015
Date of Web Publication28-Oct-2015

Correspondence Address:
Salah M Al-Mosallamy
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-9173.165060

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  Abstract 

Purpose
The aim of the study was to evaluate the outcome of the surgical technique that utilizes freeze-dried (lyophilized) amniotic membrane transplantation (AMT) with combined trabeculotomy-trabeculectomy in cases of primary congenital glaucoma with respect to its efficacy and complications.
Patients and methods
This was a prospective controlled study that included 25 eyes of 19 patients with primary congenital glaucoma. The patients were categorized into two groups: group I included 14 eyes that were treated with combined trabeculotomy-trabeculectomy with AMT and group II included 11 eyes that were treated with combined trabeculotomy-trabeculectomy without adjunctive (control group).
Results
Nineteen patients were included in the study: 13 were male and six were female. The mean age was 6.2 ± 3.5 months and 5.7 ± 2.9 months in groups I and II, respectively; there were no statistically significant differences between groups I and II regarding the patient demographics and preoperative characteristics. The surgical outcome of the two groups showed that absolute success was achieved in 71.4% and qualified success in 14.3% in group I, and in group II absolute success was achieved in 45.5% and qualified success in 27.2%. This difference was highly significant in terms of absolute success and significant in terms of total success between the two groups. The mean intraocular pressure (IOP) in this study was markedly decreased from preoperative values in both groups during postoperative follow-up visits, with statistically significantly lower IOP in group I than in group II at all postoperative visits. The complications encountered were hyphema in 28.6% of patients in group I and in 27.3% of patients in group II. Shallow anterior chamber associated with hypotony occurred in 21.4 and 18.2% of patients in groups I and II, respectively. One case in each group developed serous choroidal detachment. Flat nonfunctioning bleb with high IOP occurred in 14.3% of patients in group I and in 27.3% in group II. The complication rates were statistically insignificant between the two groups.
Conclusion
AMT-enhanced combined trabeculotomy-trabeculectomy appears to be an effective procedure for the treatment of primary congenital glaucoma with better long-term control of IOP and without added complications.

Keywords: amniotic membrane, congenital glaucoma, trabeculectomy, trabeculotomy


How to cite this article:
Al-Mosallamy SM. Efficacy and safety of the use of freeze-dried (lyophilized) amniotic membrane transplantation with combined trabeculotomy-trabeculectomy for congenital glaucoma . Delta J Ophthalmol 2015;16:58-64

How to cite this URL:
Al-Mosallamy SM. Efficacy and safety of the use of freeze-dried (lyophilized) amniotic membrane transplantation with combined trabeculotomy-trabeculectomy for congenital glaucoma . Delta J Ophthalmol [serial online] 2015 [cited 2017 Oct 20];16:58-64. Available from: http://www.djo.eg.net/text.asp?2015/16/2/58/165060


  Introduction Top


Pediatric glaucoma is one of the chief causes of blindness in the childhood population. Congenital glaucoma represents 5.1% of the congenital ocular disorders [1] and is responsible for 10.8% of all causes of visual impairment [2] . Surgical intervention is the main option for management of congenital glaucoma, planned to eliminate the outflow resistance by shifting the aqueous pathway from the anterior chamber angle [3] .

Trabeculectomy, trabeculotomy, and combined trabeculotomy-trabeculectomy are the three major surgical modalities used for the management of congenital glaucoma; goniotomy in early cases and glaucoma drainage tube shunts in advanced cases have also been applied [4],[5],[6] . Combined trabeculotomy-trabeculectomy, also called trabeculo-trabeculectomy, was described by Belmonte and Ladislao-Pérez [7] for primary congenital glaucoma (PCG) in 1979, which offered a potentially double pathway for the aqueous drainage: namely, the direct access to the canal of Schlemm and to the subconjunctival space. This combined technique has raised the success rate from 72% for trabeculectomy alone to 93% when the combined technique was used in primary congenital glaucoma after 2 years' follow-up [8] .

Fibrosis and scarring occurring at the subconjunctival space is the main cause of failure of the most established glaucoma filtration surgery, especially in recurrent cases. Widespread use of antiproliferative agents affecting fibroblast proliferation and apoptosis, such as mitomycin-C and 5-fluorouracil, have improved the surgical outcomes, but their well-known complications such as thin bleb and endophthalmitis imply that safer alternatives for fibrosis control are still needed [9],[10],[11] .

Amniotic membrane transplantation (AMT) was initially used in the treatment of ocular surface disorders because it possesses the properties of promoting epithelialization by serving as a scaffold and a suitable basement membrane for epithelial cells to grow upon as well as inhibiting fibrosis by downregulating transforming growth factor-β signaling and myofibroblast differentiation [12] .

According to these properties, AMT has been used in glaucoma-filtering surgery to prevent subconjunctival fibrosis and in reconstruction of the filtering bleb [13] . A number of studies have noted that intraocular pressure (IOP) is better controlled with trabeculectomy when combined with amniotic membrane (AM) [14],[15] , but no studies were conducted to evaluate the use of AMT with combined trabeculotomy-trabeculectomy in congenital glaucoma. This study was designed to investigate the efficacy and safety of this new surgical technique that utilizes freeze-dried (lyophilized) AMT with combined trabeculotomy-trabeculectomy in primary congenital glaucoma cases [Figure 1].
Figure 1: Dried amniotic membrane (AM) used in the study

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  Patients and methods Top


This is a prospective controlled study that included a total of 25 eyes of 19 patients selected from those attending the Outpatient Clinic of Zagazig University Hospital and diagnosed with primary congenital glaucoma (and operated upon between January 2013 and December 2013). All presurgical and postsurgical data and follow-up examination results were assessed. Initial examination of all children was performed in the outpatient clinic to make a preliminary diagnosis of congenital glaucoma. Diagnosis was confirmed under general anesthesia using 1-1.5% halothane. Both eyes were examined under general anesthesia but surgery was performed in one eye. If both eyes were affected surgery was performed in the fellow eye after 1 week.

The child's condition was explained to the parents and consent was obtained for the examination under general anesthesia and for the surgery according to the declaration of Helsinki (1983) for research involving human subjects. Preoperative evaluation was carried out noting the age at onset of symptoms (months), age at presentation (months), sex, and the preoperative medications used. During examination under general anesthesia, horizontal corneal diameter (in mm) was measured using calipers, corneal clarity was assessed at presentation, and preoperative IOP (in mmHg) was determined using the applanation method (Perkins tonometer; Keeler UK, United Kingdom). Evaluation of the rest of the eyes including anterior segment and fundoscopy with preoperative optic disc evaluation was carried out when corneal clarity permitted.

Exclusion criteria

Patients with a history of previous surgery, secondary glaucoma,  Axenfeld-Rieger syndrome More Details, aniridia, Sturge-Weber, or Peter's anomaly were excluded from this study.

Patients were categorized into group I, which included 14 eyes that were treated with combined trabeculotomy-trabeculectomy augmented with AMT, and group II, which included 11 eyes that were treated with combined trabeculotomy-trabeculectomy without adjunctives; group II served as the control group.

Surgical technique

The combined technique was performed in group I in which surgery was performed by a single surgeon. Under general anesthesia and aseptic conditions, a superior rectus bridal suture using 4-0 silk or a corneal traction using an 8-0 virgin silk suture was placed, a fornix-based conjunctival flap was raised, and hemostasis was secured with cautery. A 3 × 3 mm partial thickness scleral flap was dissected into about 1 mm of clear cornea. A radial incision was then performed in the scleral bed, 2 mm long, with a No. 15 superblade at the junction between the white and the bluish transitional zone of the sclera (this marks externally the site of Schlemm's canal). The incision was deepened gradually and dried frequently with a microsponge until Schlemm's canal was identified, evidenced by gradual leak of aqueous humor and/or blood. Trabeculotomy was then performed by introducing one arm of the double-armed trabeculotome (right and left Sourdille-Paufique, Moria) [Figure 2]. There should be no obstacle during the introduction of the trabeculotome into the canal. A controlled rotation was then performed toward the anterior chamber, thereby crossing the internal side of Schlemm's canal, breaking the trabecular meshwork and the abnormal angle tissue, with great care to avoid damage to other intraocular structures [Figure 3].
Figure 2: Trabeculotome in Schlem m's canal

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Figure 3: Rotation of trabeculot ome to anterior chamber

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In the same manner, the trabeculotome was then introduced through the other end of the incision. The internal wall of Schlemm's canal was opened in ~120° of its circumference. After trabeculotomy was performed a small portion of trabecular tissue was removed from the corneoscleral bed, which was rectangular in shape, with an approximate size of 1 × 1.5 mm, including some trabecular meshwork tissue and a portion of the roof of Schlemm's canal (trabeculectomy), followed by a peripheral iridectomy, after which a dried-freezed (lyophilized) AM was used [manufactured by National Center for Radiation Research and Technology (NCRRT), sterilized by g ray and distributed by Matrex Health Care S.A.E]. Lyophilized AM was used after wetting the dry form in balanced salt solution for 3-5 min; a 4 × 4 mm part was then cut from the AM and placed on the scleral bed and extended to the adjacent subconjunctival area. The membrane was placed with its epithelium surface facing up [Figure 4]. The two corners of the scleral flap were sutured over it with two interrupted stitches with a 10-0 nylon suture onto the corners, and the stitches' knots were buried [Figure 5]. The conjunctiva was closed using interrupted 8-0 virgin silk sutures [Figure 6].
Figure 4: Manipulation of amniotic membrane (AM) before its implantation

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Figure 5: Amniotic membrane (AM) implantation and suturing of the scleral flap over it

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Figure 6: Conjunctival closure over scleral flap and amniotic memb rane (AM)

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In group II, patients were subjected to a combined trabeculotomy-trabeculectomy without AM use. At the conclusion of surgery in both groups dexamethasone (1 mg) and gentamicin (20 mg/ml) were injected subconjunctivally. Topical cyclopentolate 1% and moxifloxacin eyedrops were instilled, in addition to combined dexamethasone-tobramycin eye ointment. An eye patch was applied.

Preparation of amniotic membrane

The AM was obtained under sterile conditions after elective cesarean delivery from a seronegative donor. Donors at risk of having HIV, hepatitis B virus, hepatitis C virus, or  Creutzfeldt-Jakob disease More Details were excluded. The placenta was first irrigated free of blood with balanced salt saline containing 50 μg/ml penicillin, 50 μg/ml streptomycin, 100 μg/ml neomycin, and 2.5 μg/ml amphotericin B. The internal AM was separated from the rest of the chorion by blunt dissection through the potential spaces between these tissues. The membrane was then flattened onto a nitrocellulose paper, with the epithelium basement membrane surface up. The membrane with the paper was cut into 5 × 5 cm pieces and placed in a sterile vial containing Dulbecco's modified Eagle's medium and glycerol at a ratio of 1 : 1. The vials were frozen at −80°C. The membrane was preserved either in wet form to be defrosted immediately before use or in dry form to be wetted 3-5 min before use [15] .

Postoperative management

Children were examined postoperatively at 1 day, 1 week, 2 weeks, 1 month, and then 3 monthly for 1 year. During each visit patients were examined under general anesthesia as described before with special attention to the following parameters: corneal clarity, bleb characteristics, IOP, and corneal diameter.

Success criteria

Because the reduction of IOP in congenital glaucoma is the most important surgical endpoint, more important than optic disc or visual changes [8] , IOP was taken as a sole parameter for success. Absolute success was defined as an IOP of 21 mmHg or less and 6 mmHg or more without additional glaucoma surgery and without devastating complications as endophthalmitis or phthisis bulbi. Qualified success was established when the above criteria were fulfilled but with antiglaucoma topical medications.

Statistical analysis

Data were collected, tabulated, and statistically analyzed using EPI info statistical package software for the χ2 -test and probability (P value) and Microsoft Excel 2010 version 16 (USA) for the F-test.


  Results Top


Of the 19 patients included in the study,13 were male and six were female with a mean age of 6.2 ± 3.5 months and 5.7 ± 2.9 months in groups I and II, respectively; there were no statistically significant differences between group I and group II regarding patient demographics and preoperative characteristics (P > 0.05) [Table 1].
Table 1 Demographics and patient characteristics of the two groups in the study

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The surgical outcome of the two groups showed 10 cases of absolute success (71.4%) and two cases of qualified success (14.3%) in group I and five cases of absolute success (45.5%) and three cases of qualified success (27.2%) in group II. There was a highly significant difference in absolute success (P < 0.001) and significant difference in total success (P < 0.05) between the two groups [Table 2].
Table 2 Surgical success of the two studied groups

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The mean IOP was markedly decreased from preoperative values in both groups during postoperative follow-up visits, with statistically significantly lower IOP in group I than in group II at all postoperative visits (P < 0.05) [Table 3] and [Figure 7].
Figure 7: Mean intraocular pressure (IOP) (mmHg) values preoperatively and during postoperative visits in the two studied groups

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Table 3 Mean intraocular pressure (mmHg) values preoperatively and during postoperative visits in the two studied groups

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The complications encountered were hyphema in four cases (28.6%) in group I and in three cases (27.3%) in group II, all of which occurred intraoperatively during rotation of the trabeculotome in the anterior chamber and were mild and resolved spontaneously within 2-3 days. Shallow anterior chamber associated with hypotony occurred in three cases (21.4%) and two cases (18.2%) in groups I and II, respectively, most of which reformed without interference, but one case in each group developed serous choroidal detachment, which required surgical reformation of the anterior chamber with air. Flat nonfunctioning bleb with high IOP was encountered in two cases (14.3%) in group I and in three cases (27.3%) in group II, with the time of occurrence ranging from 3 to 4 months postoperatively, all of which required reoperation to control IOP and were considered as failures because additional glaucoma surgeries were needed. The complication rates were statistically insignificant between the two groups (P > 0.05) [Table 4].
Table 4 Complications encountered in each group

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  Discussion Top


In primary congenital glaucoma the site of pathology is in the trabecular meshwork, which shows a developmental defect leading to elevated IOP [16] . The benefit of combined trabeculotomy-trabeculectomy is that it provides two major additional outflow pathways, the trabeculotomy site and the bleb site; therefore, the IOP is usually maintained within normal range if one or the other of the pathways fails. Only if both are obstructed would the IOP become elevated [17] . The AM has been proven to have characteristics such as anti-inflammatory, antifibrotic, antiangiogenic, as well as antimicrobial, which are in addition to lack of immunogenicity and the ability to provide an excellent substrate for tissue growth [18] . It has been used in glaucoma to prevent sticking of the scleral flap and conjunctival covering through reduction of scarring at the site of filtering surgery and also in the repair of early or late leaks; it also acts as an adjunctive for valve procedures [19] . This study was designed to evaluate the efficacy and safety of AMT as an adjunctive to combined trabeculotomy-trabeculectomy.

The results revealed that, of the 19 patients included in the study, 13 were male and six were female, with a mean age of 6.2 ± 3.5 and 5.7 ± 2.9 months in groups I and II, respectively; there were no statistically significant differences between groups I and II regarding the patient demographics and preoperative characteristics. The surgical outcome of the two groups showed that absolute success was achieved in 71.4% and qualified success in 14.3% of patients in group I, and in group II absolute success was achieved in 45.5% and qualified success in 27.2% of patients. The difference in absolute success was highly significant between the two groups and that in total success was significant, thus proving the efficacy of AMT in improving the surgical success of the surgery. This study showed the mean IOP to be markedly decreased from preoperative values in both groups during postoperative follow-up visits, with statistically significantly lower IOP in group I than in group II at all postoperative visits, denoting that AM use successfully maintained lower IOP throughout the follow-up than when AM was not used. The complications encountered were hyphema in 28.6% of patients in group I and in 27.3% in group II. Shallow anterior chamber associated with hypotony occurred in 21.4 and 18.2% of patients in groups I and II, respectively. One case in each group developed serous choroidal detachment. Flat nonfunctioning bleb with high IOP was encountered in 14.3% of patients in group I and in 27.3% in group II. No added complications were encountered with AM use because the complication rates were statistically insignificant between the two groups. Campos-Mollo et al. [20] found the success rate of combined trabeculotomy-trabeculectomy as the initial operative procedure for primary congenital glaucoma to be 95.5% after 12 months and 78.2% after 24 months and concluded that the procedure offers long-term high efficacy in the control of IOP; the mean age of their patients was 2.3 months, which was less than in the present study because of the delay in diagnosis in developing countries. In contrast to their study was the one by Essuman et al. [21] , who achieved an overall success of combined trabeculotomy-trabeculectomy in primary congenital glaucoma of 79% in a Ghanian population (44.4% success after 12 months' follow-up; the success rate declined to only 13.3% after 21 months of follow-up). Improved results were obtained by Munira et al. [22] when they used mitomycin-C (0.25 mg/ml for 2 min) with combined trabeculotomy-trabeculectomy; they achieved 80% success after a mean follow-up of 8.25 months and their mean final IOP was 13 ± 2.5 mmHg. Similar results were obtained when peribleb 5-fluorouracil injections were used with combined trabeculotomy-trabeculectomy (80% success) [23] . To the best of our knowledge no studies had been conducted to investigate the use of AMT with combined trabeculotomy-trabeculectomy in primary congenital glaucoma.


  Conclusion Top


AMT-enhanced combined trabeculotomy-trabeculectomy appears to be an effective procedure for the treatment of primary congenital glaucoma with better long-term control of IOP and without added complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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