
==== Front
Int J Appl Basic Med Res
Int J Appl Basic Med Res
IJABMR
Int J App Basic Med Res
International Journal of Applied and Basic Medical Research
2229-516X
2248-9606
Wolters Kluwer - Medknow India

IJABMR-14-156
10.4103/ijabmr.ijabmr_154_24
Original Article
Safety and Efficacy of Mitomycin C: Augmented Trabeculectomy: Subtenon’s Injection versus Sponge Application
Sedani Kanan Vimal
Bhagat Purvi Raj 1
Chauhan Abhishek Suryakant
Department of Ophthalmology, M and J Western Regional Institute of Ophthalmology, B.J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
1 Department of Ophthalmology, Glaucoma Unit, M and J Western Regional Institute of Ophthalmology, B.J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
Address for correspondence: Dr. Kanan Vimal Sedani, 201, Vinit Apartment, Opp. SNK School, University Road, Rajkot - 360 005, Gujarat, India. E-mail: kvs199@gmail.com
Jul-Sep 2024
24 8 2024
14 3 156161
04 4 2024
09 7 2024
15 7 2024
Copyright: © 2024 International Journal of Applied and Basic Medical Research
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Objective:

The objective of the study was to study the safety and efficacy of subtenon injection of mitomycin C (MMC) versus sponge application of MMC during trabeculectomy.

Materials and Methods:

Thirty-seven patients having primary glaucoma warranting trabeculectomy were enrolled in the study and their forty eyes were alternately allocated into either of the two groups: subtenon injection (ST) of 0.1 mL of 0.01% of MMC or sponge application (SP) of 0.02% of MMC and were operated by a single surgeon and followed for 3 months. The outcome was analyzed primarily based on reduction in intraocular pressure (IOP) and bleb morphology.

Results:

Similar outcome in terms of complete success (ST – 90% and SP – 85%), qualified success (ST – 5% and SP – 5%), and failure rate (ST – 5% and SP – 10%) was seen at the end of 3 months. The absolute reduction in IOP from the baseline was −10.00 ± 3.67 mmHg (−41.2% ± 12.30) in ST versus −8.90 ± 5.56 mmHg (−35.9% ± 16.1) in the SP group at the end of 3 months. At the end of 3 months, blebs in the ST group had low-to-medium height and in the SP group had low height. Blebs in both the groups were diffuse with mild vascularity. Antiglaucoma medications required postoperatively were 0.20 ± 0.62 versus 0.40 ± 1.10 in the ST and SP group, respectively. The duration of surgery was 19.85 ± 0.75 min in the ST group versus 22.50 ± 0.51 min in the SP group.

Conclusion:

Subtenon injection of MMC is as efficacious and safe as the conventional sponge application technique.

Bleb morphology
intraocular pressure
mitomycin C
subtenon’s injection
trabeculectomy
==== Body
pmcIntroduction

Untreated glaucoma is the second leading cause of irreversible blindness globally, with intraocular pressure (IOP) being the only modifiable factor.[1] Failure to reduce the IOP, despite maximum medical therapy, requires surgical intervention, the mainstay being trabeculectomy.[2] The use of antifibrotic agents, the most common being mitomycin C (MMC), has increased the rate of success by preventing subconjunctival scarring, which is the most common cause of surgical failure.[3]

Factors influencing the efficacy of MMC include its concentration, volume, duration of exposure, dose delivered to the tissues, preparation method, administration, and other local tissue-related factors.[4] The method of MMC application to the tissue has been found to determine the morphology of the filtering bleb and its long-term survival.[5] Most surgeons place sponges soaked in MMC in the subconjunctival or subtenon’s space before scleral flap dissection while others place the sponges under the scleral flap.[6] Application of MMC over a larger surface area achieves a significantly lower incidence of bleb scarring and a higher short-term decrease in IOP compared to the eyes with smaller area of contact.[7] Other variables affecting the outcome of MMC application include thickness of tenon’s capsule, degree of tissue vascularity, bleeding, and different receptor responses to MMC.[8] Further, the sponges can be nonuniform in size, and hence, the effective dose delivered is not always precisely known and the maximum area of contact is almost always not there. There is a risk of conjunctival damage during manipulation, sponge fragmentation, or retention and a longer surgical time.

A novel technique was described for subtenon MMC application by Lee et al. in 2008.[6] In the subtenon injection method, the dose and volume of MMC injected are fixed and predetermined, whereas in sponge application, the amount and concentration delivered to the tissue are difficult to assess.[9] With subtenon injection, MMC can spread more diffusely leading to a final bleb morphology that is mildly elevated and diffuse and not focal, thin, avascular, and cystic as with the sponge application.[9] There have been a few comparative studies between the two techniques in different countries, with fewer studies in India. The aim of our study was therefore to assess the safety and efficacy of subtenon injection versus sponge application of MMC.

Materials and Methods

This prospective, interventional, open-label, controlled study was conducted from July 2021 to December 2022 among patients attending the glaucoma clinic of our tertiary care center. The patients aged above 18 years, diagnosed with primary glaucoma and warranting the need for primary trabeculectomy with MMC, and willing to give consent for the study were included in the study. The patients unwilling for surgery or follow-up as advised, pregnant and lactating women, having extreme thinning of the sclera and/or conjunctiva prohibiting the use of MMC, previously operated for other ocular conditions, undergoing resurgery or combined surgery, having secondary or childhood glaucoma and having systemic comorbidities, or using drugs likely to influence wound healing were excluded from the study. Ethical clearance was obtained from the Institutional Ethical Committee vide letter no 15/2021 Dated: February 3, 2021, and informed written consent was taken from each patient before the surgery.

Forty eyes of 37 patients were included. Forty eyes were alternately allocated into one of the two groups: subtenon injection of MMC (ST group) and sponge-soaked application of MMC (SP group) resulting into 20 eyes in each group. For each patient, the demographic parameters were recorded. A thorough clinical evaluation was done preoperatively in the form of best-corrected visual acuity recorded using Snellen’s distance visual acuity chart, IOP measurement using Goldmann’s applanation tonometer, anterior segment evaluation on slit lamp, gonioscopy using 4-mirror Goldmann gonioscope, fundus evaluation by direct ophthalmoscopy and 90 D lens, visual field examination on Octopus 900 perimeter, ultrasonic pachymetry and ultrasonography, and ultrabiomicroscopy if required.

All patients were operated by a single surgeon under local peribulbar anesthesia. A fixed concentration of 0.1 mL of 0.01% MMC for subtenon injection and 0.02% for sponge application was used. The eye operated, date of surgery, method of application of MMC, surgical time (from the point of taking corneal fixation suture to the subconjunctival injection of steroid – antibiotic at the end of surgery), and surgeon’s self-perception rating for the technique (using the Likert scale [score 1 – very poor to score 5 – excellent]) were recorded for every patient.

Surgical technique

After routine aseptic precautions and insertion of a wire speculum, a corneal fixation suture was applied superiorly using 6-0 vicryl suture.

For the ST group, MMC vial having 2 mg of the drug was diluted with 20 ml of sterile water creating a concentration of 0.01%. Subtenon injection (0.1 mL of 0.01% MMC) was given about 7 mm away from the area of the planned bleb using a tuberculin syringe and 26-gauge needle, as shown in Figure 1. Using sterile cotton buds, the injected MMC was spread diffusely around the area, following which a superior fornix-based conjunctival peritomy was done using corneoscleral scissors. Hemostasis was achieved using bipolar cautery without damaging the conjunctiva.

Figure 1 Subtenon injection of mitomycin C

For the SP group, MMC vial having 2 mg of the drug was diluted with 10 mL of sterile water giving a concentration of 0.02% which was used to soak few cotton sponges/pledgets 1 mm by 1 mm in size. Superior fornix-based conjunctival peritomy was done using corneoscleral scissors. Hemostasis was achieved using bipolar cautery without damaging the conjunctiva. Two pledgets dipped in MMC were put under the conjunctiva for 2 min, then removed carefully followed by a thorough wash with 20 cc of balanced salt solution.

The rest of the surgical steps as for a conventional trabeculectomy were followed for both the groups. The scleral flap was sutured using one apical suture. Watertight conjunctival closure was done using 2 wing sutures. Subconjunctival dexamethasone and gentamicin injection was given followed by the instillation of atropine 1% eye ointment at the end of the surgery and patching.

Postoperatively, the patients were instructed to omit all prior antiglaucoma agents. From 1st postoperative day, they were advised to start moxifloxacin 0.5% eye drops 4 times a day, prednisolone 1% eye drops 6 times a day (which were tapered gradually as per the healing and inflammatory response), and atropine 1% eye ointment 3 times a day.

Follow-up assessment was done at postoperative day 1, week 1, 1 month, and 3 months for unaided and aided visual acuity, IOP, anterior segment, and bleb grading using the Indiana Bleb Appearance Grading System (IBAGS).[10] Any complications related to the bleb or surgery were noted on all visits. Antiglaucoma medications were restarted whenever required to achieve the target IOP and were documented.

Complete success was defined as more than 20% reduction from the baseline IOP without the use of any antiglaucoma medications at 3 months.[11] Qualified success was defined as more than 20% reduction from the baseline IOP with the use of additional antiglaucoma medications at 3 months.[11] Failure of surgery was defined as <20% reduction from the baseline IOP or IOP more than 21 mmHg at 3 months.[11] Postoperative hypotony was defined as IOP <6.5 mmHg without the use of antiglaucoma medications.[12]

Statistical analysis

Results were entered into a Microsoft Excel sheet for analysis. The data were analyzed using mean ± standard deviation/median for continuous variables and frequency along with percentage for categorical variables. The baseline and other surgical data were compared using Independent t-test/Mann–Whitney U test (depending on normality) for continuous variables among the ST versus SP group, and the Chi-squared test was used wherever required for association.

The difference in the postoperative IOP between the two groups and the bleb changes were compared at day 1, 1 week, 1 month, and 3 months postoperatively using Wilcoxon–Mann–Whitney U test or independent t-test wherever required and change with time was compared using generalized estimating equations. The outcome in terms of complete and qualified success was analyzed using Fisher’s exact test. The number of antiglaucoma medications used pre- and postoperatively among the two groups were compared using Wilcoxon–Mann–Whitney U test.

Results

The 40 eyes were alternatively allocated into two groups: ST and SP with 20 eyes in each group. There was no significant difference between the baseline demographic and clinical characteristics between the two groups as represented in Table 1.

Table 1 Baseline characteristics of the patients

Parameters	Group	P	
	
ST (n=20), n (%)	SP (n=20), n (%)	
Age (years)	52.00±16.86	50.10±17.53	0.729a	
Gender				
 Male	9 (45.0)	12 (60.0)	0.342b	
 Female	11 (55.0)	8 (40.0)		
Diagnosis				
 POAG	14 (70.0)	13 (65.0)	0.736b	
 PACG	6 (30.0)	7 (35.0)		
Preoperative BCVA				
 6/6–6/18	15 (75)	14 (70)		
 <6/18–6/60	4 (20)	3 (15)		
 <6/60–PL +	1 (5)	3 (15)		
IOP (mmHg) (preoperative)	23.80±3.49	23.60±5.34	0.493c	
Indication for trabeculectomy				
 Progressive field changes	9 (45.0)	7 (35.0)	0.765b	
 Uncontrolled IOP	6 (30.0)	8 (40.0)		
 Poor compliance to multiple medications	5 (25.0)	5 (25.0)		
Number of antiglaucoma drugs preoperatively	5.60±0.94	5.40±0.88	0.449c	
at-test; bChi-squared test; cWilcoxon–Mann–Whitney U-test. ST: Subtenon injection group; SP: Sponge application group; POAG: Primary open-angle glaucoma; PACG: Primary angle-closure glaucoma; BCVA: Best-corrected visual acuity; IOP: Intraocular pressure; PL: Perception of light

At the end of 3 months, one Snellen line drop in visual acuity was seen in 37.5% in the ST group versus in 35.3% in the SP group. More than 1 Snellen line drop in visual acuity was seen in 6.2% in the ST group versus 11.8% in the SP group [Table 2]. This difference was not statistically significant. The data of seven patients were not included in this analysis as vision of these patients was very low and could not be taken on Snellen chart. Of these 7, 1 in each group had choroidal detachment and 1 in the ST group had cystoid macular edema.

Table 2 Drop in visual acuity, postoperative intraocular pressure, and outcome of surgery

Parameters	Group	P	
	
ST (n=20), n (%)	SP (n=20), n (%)	
Drop in visual acuity (Snellen line)				
 None	9 (56.2)	9 (52.9)	1.000a	
 1	6 (37.5)	6 (35.3)		
 >1	1 (6.2)	2 (11.8)		
IOP (mmHg), mean±SD				
 Day 1	9.95±2.98	11.35±3.82	0.204b	
 1 week	11.70±2.27	12.10±2.86	0.597c	
 1 month	13.00±2.87	14.00±3.43	0.581c	
 3 months	13.80±2.75	14.70±3.91	0.375c	
Outcome				
 Complete success	18 (90.0)	17 (85.0)	1.000a	
 Qualified success	1 (5.0)	1 (5.0)		
 Failure	1 (5.0)	2 (10.0)		
aFisher’s exact test; bt-test; cWilcoxon–Mann–Whitney U-test. ST: Subtenon injection group; SP: Sponge application group; SD: Standard deviation; IOP: Intraocular pressure

IOP change postoperatively at each follow-up is also represented in Table 2. The mean preoperative IOP in the ST group was 23.80 ± 3.49 mmHg and SP group was 23.60 ± 5.34 mmHg, which reduced to 13.80 ± 2.75 mmHg and 14.70 ± 3.91 mmHg, respectively, at final visit with P < 0.001 in both the groups. The absolute reduction in IOP from the baseline was −10.00 ± 3.67 mmHg (−41.2% ±12.30%) in the subtenon versus −8.90 ± 5.56 mmHg (−35.9% ±16.1%) in the sponge-applied group at the end of 3 months. In terms of IOP, at every visit, the mean IOP for the subtenon group was lower than the sponge group, but the difference was not statistically significant. Progressive change in IOP over time in both the groups showed a similar trend.

Complete success was more in the ST group, qualified success was same in both, and failure was more in the SP group. These results were not statistically significant [Table 2].

On an average, 5–6 antiglaucoma [Table 1] medications were required for IOP control preoperatively in both the groups; however, postoperatively, only 10%, i.e., 2 of 20 patients in the ST group and 15%, i.e., 3 of 20 patients in the SP group required additional medications for IOP control. The number of additional topical antiglaucoma medications required were 0.20 ± 0.62 versus 0.40 ± 1.10 in the ST and SP group, respectively.

As shown in Table 3, blebs in the ST group had low height, were diffuse, with mild-to-moderate vascularity with no bleb leak at postoperative day 1 and 1 week. In the SP group, blebs had low height, were diffuse, with mild-to-moderate vascularity with one patient having a wound leak at postoperative day 1 and low height, were diffuse, with mild vascularity with no bleb leak at 1 week. At postoperative 1 month and 3 months, blebs in the ST group had low-to-medium height, were diffuse, with mild vascularity with no bleb leak and in the SP group had low height, were diffuse, with mild vascularity and no bleb leak. At 3 months, blebs had more height 1.85 ± 0.49 in the ST group versus 1.20 ± 0.52 in the SP group. The extent at 3 months was 2.55 ± 0.51 in the subtenon group versus 2.10 ± 0.45 in the sponge group with P = 0.007. Mild vascularity of 2.10 ± 0.45 in the ST group versus 1.90 ± 0.64 in the SP group was observed. The rate of complications was similar in both the groups which was in 6 of 20 patients in each. Early postoperative hypotony was more in the subtenon group (15%, i.e., three patients) as compared to the sponge-applied group (10%, i.e., two patients). Rate of choroidal detachment and blocked sclerostomy were same in both with one patient in each group. One patient in subtenon group had cystoid macular edema, and in sponge-applied group, 1 had bleb leak and 1 had bleb failure. However, the difference was not statistically significant [Table 4].

Table 3 Postoperative bleb morphology (Indiana Bleb Appearance Grading System)[10]

Parameters	Group	P	
	
ST (n=20)	SP (n=20)	
Bleb grading: Day 1				
 Height***	1.25±0.72	0.75±0.55	0.021a	
 Extent***	2.60±0.50	2.10±0.45	0.003a	
 Vascularity	2.60±0.50	2.45±0.60	0.465a	
 Seidel	0.00±0.00	0.05±0.22	0.342a	
Bleb grading: 1 week				
 Height***	1.40±0.68	0.90±0.55	0.014a	
 Extent***	2.60±0.50	2.10±0.45	0.003a	
 Vascularity	2.50±0.51	2.45±0.60	0.890a	
 Seidel	0.00±0.00	0.00±0.00	-	
Bleb grading: 1 month				
 Height***	1.85±0.49	1.20±0.52	<0.001a	
 Extent***	2.60±0.50	2.10±0.45	0.003a	
 Vascularity	2.25±0.44	2.10±0.64	0.469a	
 Seidel	0.00±0.00	0.00±0.00	-	
Bleb grading: 3 months				
 Height***	1.85±0.49	1.20±0.52	<0.001a	
 Extent***	2.55±0.51	2.10±0.45	0.007a	
 Vascularity	2.10±0.45	1.90±0.64	0.326a	
 Seidel	0.00±0.00	0.00±0.00	-	
***Significant at P<0.05; aWilcoxon–Mann–Whitney U-test. ST: Subtenon injection group; SP: Sponge application group

Table 4 Postoperative complications

Parameters	Group	P	
	
ST (n=20), n (%)	SP (n=20), n (%)	
Any postoperative complication (yes)	6 (30.0)	6 (30.0)	1.000a	
Postoperative complications				
 None	14 (70.0)	14 (70.0)	1.000b	
 Early postoperative hypotony	3 (15.0)	2 (10.0)		
 Blocked sclerostomy	1 (5.0)	1 (5.0)		
 Choroidal detachment	1 (5.0)	1 (5.0)		
 Bleb failure	0	1 (5.0)		
 Bleb leak	0	1 (5.0)		
 Cystoid macular edema	1 (5.0)	0		
aChi-squared test; bFisher’s exact test. ST: Subtenon injection group; SP: Sponge application group

There was a significant difference between the two groups in terms of duration of surgery (P ≤ 0.001), with the duration being 19.85 ± 0.75 min in the ST group which was lesser as compared to 22.50 ± 0.51 min in the SP group.

There was a significant difference (P ≤ 0.001) between the two groups in terms of surgeon’s self-perception scoring of the technique, with the scoring being 4.50 ± 0.51: very good to excellent in the ST group as compared to 2.50 ± 0.51: poor to good in SP group.

Discussion

Trabeculectomy is the gold standard for the surgical management of glaucoma till date. Judicious use of antimetabolites helps to prevent reactive tissue scarring, resulting in an efficient filtering bleb.[13] Sponge application of MMC does not deliver a uniform dose resulting in avascular, thin, and cystic blebs postoperatively, with an additional risk of fragmentation or loss of sponge in the orbit intraoperatively. The desired bleb morphology can be achieved with the novel method of standardized dose delivery using the subtenon’s injection route.

Pakravan et al.[14] conducted a short-term trial for 6 months where 80 open-angle glaucoma cases were randomized into two groups: Group 1 receiving subtenon’s injection of 0.1 mL of 0.01% MMC, whereas Group 2 received 0.02% MMC-soaked sponge application. The complete as well as qualified success in both the groups was 82.5%.[14] Pakravan et al.[14] also showed an absolute reduction in IOP from the baseline of −12.2 ± 5.9 mmHg in the subtenon versus −11.5 ± 6.2 mmHg in the sponge group at the end of 3 months.[14] In our study, results were similar to these with both the groups being similar in terms of complete success (ST – 90% and SP – 85%), qualified success (ST – 5% and SP – 5%), and failure rate (ST – 5% and SP – 10%).

Pakravan et al.[14] found that blebs in the subtenon group were less elevated as compared to the sponge group at the end of 3 and 6 months.[14] In our study, blebs at 3-month follow-up had low-to-medium height with the height being higher in the subtenon group as compared to the sponge group (1.85 ± 0.49 vs. 1.20 ± 0.52). Pakravan et al.[14] observed that bleb extent at 3 months was 2.10 ± 0.5 versus 2.00 ± 0.40, in the subtenon versus the sponge-applied group, respectively.

Esfandiari et al.[11] similarly found that blebs were more diffuse in the subtenon group at 12 months (2.17 ± 0.51 vs. 1.94 ± 0.33) and 36 months (2.13 ± 0.42 vs. 1.81 ± 0.40).[11] In our study also, the mean bleb extent at all time points fell in E2 (>2–<4 clock hours) of IBAGS classification, although blebs in the subtenon group were more diffuse as compared to the sponge group at all follow-ups. The extent at 3 months was 2.55 ± 0.51 in the subtenon group versus 2.10 ± 0.45 in the sponge group with P = 0.007. Pakravan et al.[14] found that blebs in the subtenon group were less vascular as compared to the sponge group at the end of 3 and 6 months.[14] In our study though, blebs were mildly vascular in both groups at the end of 3 months, the subtenon versus the sponge group (2.10 ± 0.45 vs. 1.90 ± 0.64), which was not statistically significant.

Esfandiari et al.[11] conducted a long-term study where 82 patients with uncontrolled open-angle glaucoma were followed up for 3-year period and 73 eyes were finally included in the analysis. Failure rate was higher in their study which may be due to their longer follow-up. In our short-term study, no patient required a repeat glaucoma surgery.

Maheshwari et al.[15] conducted a prospective analysis of 42 patients, 21 in each group who underwent trabeculectomy with MMC and followed up for 1 year.[15] In their study, the number of preoperative antiglaucoma medications was 2.4 ± 0.87 in the subtenon injection group and 2.3 ± 0.96 in the sponge-applied group, which reduced to 0.38 ± 0.5 and 0.91 ± 0.85, respectively, postoperatively.[15] In our study, use of additional topical antiglaucoma medications was required only in two patients in the subtenon and three patients in the sponge-applied group. The mean preoperative number of antiglaucoma medications was 5.60 ± 0.94 in the subtenon group and 5.40 ± 0.88 in the sponge-applied group, which reduced to 0.20 ± 0.62 and 0.40 ± 1.10, respectively, comparable to the results of the study mentioned above. Khouri et al.[16] conducted a retrospective study where 60 cases, 30 in each arm (subtenon vs. sponge), were compared. There was no difference between the groups in postoperative complications including bleb leak, hypotony, shallow anterior chamber, infection, corneal edema, and cataract formation.[16] In our study, 15% patients (3 of 20) in the subtenon versus 10% patients (2 of 20) in the sponge-applied group had early postoperative hypotony. Rate of choroidal detachment and blocked sclerostomy were the same in both with one patient in each group. One patient in the subtenon group had cystoid macular edema, and in the sponge-applied group, 1 had bleb leak and 1 had bleb failure. Hence, there was no significant difference in complications between the two groups.

Apart from these parameters, we studied two more factors. The duration of surgery was significantly reduced in the ST as compared to the SP group (19.85 ± 0.75 vs. 22.50 ± 0.51). Subtenon injection technique was given a “very good to excellent” rating by the surgeon, as compared to “poor to good” rating for sponge application; as the former technique was less time-consuming, the dose delivery appeared more predictable without the concern of sponge remnants and need for lavage.

The limitations of our study are a small sample size and short-term follow-up. Grading of bleb using imaging techniques could help to further assess the bleb morphology with each of these techniques. Nevertheless, we could establish the fact that subtenon’s injection of MMC in trabeculectomy can deliver a standard dose of the drug in a uniform, reproducible, predictable, and less time-consuming manner.

Conclusion

The subtenon technique has shown rate of complications and IOP control similar to the sponge-applied MMC with an added advantage of better bleb morphology and reduced surgical time. Hence, subtenon injection of MMC in trabeculectomy is a promising method which can help improve the success rate of trabeculectomy.

Ethical statement

The study was approved by the Institutional Ethics Committee of B. J. Medical College and Civil Hospital, Ahmedabad (Approval No.: EC/Approval/15/2021/03/02/2021).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
==== Refs
1 Weinreb RN Aung T Medeiros FA The pathophysiology and treatment of glaucoma: A review JAMA 2014 311 1901 11 24825645
2 Razeghinejad MR Fudemberg SJ Spaeth GL The changing conceptual basis of trabeculectomy: A review of past and current surgical techniques Surv Ophthalmol 2012 57 1 25 22137574
3 Crowston JG Akbar AN Constable PH Occleston NL Daniels JT Khaw PT Antimetabolite-induced apoptosis in Tenon's capsule fibroblasts Invest Ophthalmol Vis Sci 1998 39 449 54 9478007
4 Jampel HD Effect of brief exposure to Mitomycin C on viability and proliferation of cultured human Tenon's capsule fibroblasts Ophthalmology 1992 99 1471 6 1407982
5 You YA Gu YS Fang CT Ma XQ Long-term effects of simultaneous subconjunctival and subscleral Mitomycin C application in repeat trabeculectomy J Glaucoma 2002 11 110 8 11912358
6 Lee E Doyle E Jenkins C Trabeculectomy surgery augmented with intra-Tenon injection of Mitomycin C Acta Ophthalmol 2008 86 866 70 19086929
7 Matlach J Panidou E Grehn F Klink T Large-area versus small-area application of Mitomycin C during trabeculectomy Eur J Ophthalmol 2013 23 670 7 23640510
8 Lama PJ Fechtner RD Antifibrotics and wound healing in glaucoma surgery Surv Ophthalmol 2003 48 314 46 12745005
9 Lim MC Mitomycin-C: The Injection Alternative Calif Sacramento 2014 Available from:Glaucoma section of reviewofophthalmology.com Last accessed on 2024 Mar 06
10 Cantor LB Mantravadi A WuDunn D Swamynathan K Cortes A Morphologic classification of filtering blebs after glaucoma filtration surgery: The Indiana Bleb Appearance Grading Scale J Glaucoma 2003 12 266 71 12782847
11 Esfandiari H Pakravan M Yazdani S Doozandeh A Yaseri M Conner IP Treatment Outcomes of Mitomycin C-augmented trabeculectomy, Sub-Tenon injection versus soaked sponges, after 3 years of follow-up: A randomized clinical trial Ophthalmol Glaucoma 2018 1 66 74 32672635
12 Sudhakar P Menon MG Post trabeculectomy situations: Hypotony Kerala J Ophthalmol 2021 33 230 5
13 Khaw PT Doyle JW Sherwood MB Grierson I Schultz G McGorray S Prolonged localized tissue effects from 5-minute exposures to fluorouracil and Mitomycin C Arch Ophthalmol 1993 111 263 7 8431167
14 Pakravan M Esfandiari H Yazdani S Douzandeh A Amouhashemi N Yaseri M Mitomycin C-augmented trabeculectomy: Subtenon injection versus soaked sponges: A randomised clinical trial Br J Ophthalmol 2017 101 1275 80 28100482
15 Maheshwari D Kanduri S Rengappa R Kadar MA Intraoperative injection versus sponge-applied Mitomycin C during trabeculectomy: One-year study Indian J Ophthalmol 2020 68 615 9 32174581
16 Khouri AS Huang G Huang LY Intraoperative injection versus sponge-applied Mitomycin C during trabeculectomy: One-year study J Curr Glaucoma Pract 2017 11 101 6 29151685
