|Year : 2019 | Volume
| Issue : 2 | Page : 63-67
Corneal endothelial changes after subscleral trabeculectomy with mitomycin-C
Faried M Wagdy1, Adel G Zaky1, Sara N.A Gohar2
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Student Hospital, Menoufia University, Menoufia, Egypt
|Date of Submission||19-Dec-2018|
|Date of Acceptance||28-Feb-2019|
|Date of Web Publication||24-Jul-2019|
Sara N.A Gohar
Department of Ophthalmology, Student Hospital, Menoufia University, El-Shohada, Menoufia 32717
Source of Support: None, Conflict of Interest: None
Background Antimetabolites have been proposed to increase the success rate and reduce fibrosis associated with filtering surgery. However, they have cytotoxic effect on corneal endothelial cells. Noncontact specular microscopy was used for measuring the endothelial cell changes after subscleral trabeculectomy (Trab) with antimetabolites.
Purpose The aim of this study was to evaluate the changes that occur in corneal endothelial cells after subscleral Trab with mitomycin-C (MMC).
Patients and methods This is a prospective interventional study that was carried out on 30 eyes of 26 patients attending the Ophthalmology Department of Menoufia University Hospitals. They were prepared for subscleral Trab with MMC in the period between April 2017 and April 2018. Follow-up for those patients was done by specular microscopy preoperatively and 1 week, 3, and 6 months postoperatively to evaluate corneal endothelial changes. Specular microscopy was performed at the Memorial Institute of Ophthalmology in Giza.
Results There was a significant decrease in cell density but nonsignificant difference in central corneal thickness and cell size 6 months after surgery compared with preoperative values. Intraocular pressure was controlled after surgery and remained low during the follow-up period.
Conclusion Subscleral Trab with MMC caused a significant but nonclinically remarkable loss of endothelial cells which occurred only intraoperatively or at the early postoperative period. However, prolonged toxic effect of MMC and progressive cell loss were not a major concern.
Keywords: changes, corneal, endothelial, mitomycin-C, subscleral trabeculectomy
|How to cite this article:|
Wagdy FM, Zaky AG, Gohar SN. Corneal endothelial changes after subscleral trabeculectomy with mitomycin-C. Delta J Ophthalmol 2019;20:63-7
|How to cite this URL:|
Wagdy FM, Zaky AG, Gohar SN. Corneal endothelial changes after subscleral trabeculectomy with mitomycin-C. Delta J Ophthalmol [serial online] 2019 [cited 2020 Feb 27];20:63-7. Available from: http://www.djo.eg.net/text.asp?2019/20/2/63/263416
| Introduction|| |
Trabeculectomy (Trab) is performed as a treatment for many types of glaucoma in an attempt to lower the intraocular pressure (IOP). Antimetabolites such as 5-fluorouracil are used to inhibit wound healing to prevent the conjunctiva scarring down onto the sclera . In Trab, mitomycin-C (MMC) may penetrate into adjacent ocular tissues, beyond its application site .
As corneal endothelial cells lack division capacity, possible insults are irreparable, and cell density diminishes gradually . Noncontact specular microscopy provides a noninvasive method of morphological analysis of the corneal endothelial cell layer. It makes the measurement of mean cell density, measurement of coefficient of variation (CV) in the cell size as well as the hexagonal appearance of the cells. These parameters provide an index of the functional status of corneal endothelial layer .
The aim of the study was to evaluate the changes that occur in corneal endothelial cells after subscleral Trab with MMC.
| Patients and methods|| |
This prospective interventional study was carried out on 30 eyes of 26 patients attending the Ophthalmology Department of Menoufia University Hospitals. They were prepared for subscleral Trab with MMC in the period between April 2017 and April 2018. Follow-up for those patients was done by specular microscopy preoperatively and 1 week, 3, and 6 months postoperatively to evaluate the corneal endothelial changes. Specular microscopy was done at the Memorial Institute of Ophthalmology in Giza.
All study procedures were carried out and approved by the Ethical Committee of Menoufia Faculty of Medicine and in accordance with the Declaration of Helsinki. Participant’s names were kept on a password-protected database and linked only with a study identification number for this research. Written informed consent was obtained from each patient before enrollment in the study.
Inclusion criteria of selected cases included uncontrolled glaucoma despite maximal tolerated medical therapy, primary open or closed angle glaucoma, and poor compliance with medications. Patients were excluded from the study if they had congenital glaucoma, secondary glaucoma, post-traumatic glaucoma, pre-existing corneal abnormality, performing cataract surgery simultaneously or during the follow-up period, and comorbidity with glaucoma except mild cataract.
Each patient underwent a standard subscleral Trab with antimetabolite in the usual way. Antimetabolite (MMC: 0.02%=0.2 mg/ml, Mitomycin-C Kyowa; Biochem Industries, Daman, India) was applied using multiple thin sponges under the scleral flap and between the sclera and Tenon’s capsule for 3 min.
Postoperatively, all patients were treated with topical antibiotics (gatifloxacin administered four times per day) and topical corticosteroids (prednisolone acetate administered four times per day for 2 weeks that were tapered off slowly over 6–8 weeks.). Antiglaucoma medication was added if necessary based on the IOP.
Postoperatively, all patients were examined at the first postoperative day, 1 week, 1, 3, and 6 months by slit lamp and by measuring the IOP. Specular microscopy was performed at 1 week, 3, and 6 months postoperatively to evaluate the cell density and CV using TOPCON SP-2000P specular microscope (Topcon SP-2000P; Topcon Inc., Tokyo, Japan). Topcon SP-2000P is an automatic noncontact specular microscope, which automatically evaluates, calculates, and displays the cell density and CV. Cell density is a measurement of cell density in mm2 (cells/mm2), which varies in normal population from 2000 to 3200 cells/mm2. CV represents the coefficient or degree of variation in the size of the endothelial cells (polymegathism). A CV less than 40 is normal . Increase in CV means increased polymegathism and decreased hexagonality of the cells ([Figure 1]).
Data were described in terms of mean, SD, median, and range, or frequencies and percentages when appropriate. Preoperative and postoperative values were compared using paired t-test. SD is presented if relevant. P values less than 0.05 were considered statistically significant.
| Results|| |
This study was carried out on 30 eyes of 26 patients (15 patients were males, involving 14 eyes, and 12 patients were females, involving 16 eyes). Eight patients were unilateral (eight eyes), and four patients were bilateral (eight eyes).
The mean IOP before surgery was 31.10±3.48 mmHg, which decreased to 14.3±3.85 mmHg after 1 week, 13.90±3.11 mmHg after 1 month, 13.73±3.25 mmHg after 3 months, and 13.3±3.28 mmHg after 6 months. The decrease in IOP was significant at 1 week, 1, 3, and 6 months (P<0.001) when compared with the preoperative IOP, which reflects the efficacy of surgery in controlling the IOP. There was no statistically significant difference between postoperative IOP measured at 1 week, 1, 3, and 6 months (P=0.267; [Table 1]).
The mean central endothelial cell density was 2739.47±591.41 cells/mm2 preoperatively, which decreased to 2429.17±503.89 cells/mm2 after 1 week postoperatively, with cell loss of 11.3%, which was significant (P=0.024). The mean corneal endothelial cell density was 2424.80±502.64 cells/mm2 after 3 months (P=0.022) and 2418.30±501.23 cells/mm2 after 6 months (P=0.020), which represents a cell loss of 10.14 and 10.42%, respectively. The cell loss was significant at 1 week, 3, and 6 months compared with the preoperative value but insignificant from 1 week to 6 months (P=0.936; [Table 2]).
The CV was 50.07±15.8 before surgery and increased to 52.30±16.10 after 1 week, by ∼4%; 53.47±15.95 after 3 months, by ∼6.8%; and 53.93±15.89 after 6 months, by ∼7.71%. This variation was statistically insignificant in 1 week, 3, and 6 months (P=0.589, 0.411, and 0.350, respectively). It was also was not significant from 1 week to 6 months (P=0.692; [Table 3]).
The mean central corneal thickness was 527±32 µm before surgery and slightly increased to 531±44 µm at 1 week, 531±37 µm at 3 months, and 531±30 µm at 6 months after surgery, with no further increase. These differences were nonsignificant (P=0.403, 0.38, and 0.347, respectively; [Table 4]).
With regard to the safety of the surgery, there were minimal reported postoperative complications such as hyphema in three (10%) cases, which was seen in the first postoperative day and subsided 2 days later. Hypotony with shallow anterior chamber was observed in one (3.3%) case and was relieved after 7 days with decreasing frequency of topical steroids and fitting a bandage contact lens. Blebitis occurred in one (3.33%) case and subsided with combined antibiotic and steroid topical treatment. This reflected the fair safety of the surgery ([Table 5]).
| Discussion|| |
In this study, a significant decrease of IOP was noted early after surgery and remained low until the end of the follow-up period. This is compatible with many studies that reported the efficacy of MMC in subscleral Trab operation regarding IOP reduction .
In the present study, there was a decrease in endothelial cell density by 11.3% 1 week after antimetabolite-augmented subscleral Trab and slightly decreased to 10.14% after 3 months and 10.42% after 6 months. The change in endothelial cell density from 1 week to 6 months was not statistically significant and was close to the expected physiologic cell loss of ∼0.6%/year. This is slightly comparable with Dreyer et al.  who reported that after MMC-augmented subscleral Trab, there was an endothelial cell loss of 14% after 3 months and 6.8% after 1 year. In addition, Storr-Paulsen et al.  reported a corneal endothelial cell count (CECD) loss of 9.5% after 3 months of MMC-augmented subscleral Trab and a 10% cell loss after 12 months.
However, this is in contradiction to some experimental studies, which have predicted that MMC-related endothelial cell loss in clinical settings is unlikely to happen ,. These discrepancies observed in clinical studies may be attributable to variations in study design, sample size, surgical technique, and follow-up period. Such discrepancies may also reflect that the effect of MMC on CECD is small. Although this small cell loss would probably cause no significant clinical problem, a low or borderline preoperative endothelial cell count could significantly be affected by the intraoperative use of MMC, leading to a clinically decompensated cornea, as reported by some authors ,.
The present study showed a significant postoperative CECD loss compared with the preoperative value, but it did not interfere with corneal clarity. However, patient selection is still an important issue, because as mentioned before, modest endothelial loss in these patients may result in corneal decompensation. In this subset of patients, use of ocular viscoelastic devices may be helpful in reducing MMC-related CECD loss, as recommended by some authors .
CECD loss at 1 week postoperatively was significantly higher than CECD loss from the first to 6 month after surgery. This suggests that MMC-related endothelial toxicity takes place intraoperatively or during the early postoperative period up to 1 month, and that progressive endothelial cell loss should not be a major concern. This is in accordance with Storr-Paulsen et al.  who found that significant cell loss occurs during or immediately after MMC-augmented subscleral Trab with no progressive cell loss from 3 to 12 months. In addition, Zarei et al.  reported cell loss of 3.4% in the control group without the use of MMC in the first month compared with loss of 7.2% in the MMC group.However, this study assessed the endothelium of the central cornea and did not evaluate the peripheral cornea. Thus, significant regional differences in cell density could have been missed. Endothelial cell toxicity may be local or more prominent adjacent to the site of application, and central corneal parameters may not actually reflect the whole effect ,.
| Conclusion|| |
Subscleral Trab with MMC caused a significant but also not clinically remarkable loss of endothelial cells, which occurred only intraoperatively or at the early postoperative period. However, prolonged toxic effect of MMC and progressive cell loss were not a major concern.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Green E, Wilkins M, Bunce C, Wormald R. 5-Fluorouracil for glaucoma surgery. Cochrane Database Sys Rev 2014; 19:CD001132.
Wu K, Hong S, Huang H, Lin C, Chen C. Toxic effects of mitomycin-C on cultured corneal keratocytes and endothelial cells. J Ocular pharmacol Therapeutics 1999; 5:401–411.
Joyce NC. Cell cycle status in human corneal endothelium. Exp Eye Res 2005; 81:629–638.
Huan S, Bullimore M. Factors affecting corneal endothelial morphology. Cornea 2007; 26:520–525.
Curto JD, Pinto JC. The coefficient of variation asymptotic distribution in the case of non-independent random variables. J Appl Stat 2009; 36:21–32.
Habash A, Leyla A, Owaidhah O, Deepak P. A review of the efficacy of mitomycin C in glaucoma filtration surgery. Clin Ophthalmol 2015; 9:1945–1951.
Dreyer E, Chaturvedi N, Zurakowski D. Effect of mitomycin C and fluorouracil-supplemented trabeculectomies on the anterior segment. Arch Ophthalmol 1995; 113:578–580.
Storr-Paulsen T, Norreguard J, Ahmed S, Storr-Paulsen A. Corneal endothelial cell loss after mitomycin C-augmented subscleral trabeculectomy. J Glaucoma 2008; 17:654–657.
McDermott M, Wang J, Shin D. Mitomycin and the human corneal endothelium. Arch Ophthalmol 1994; 112:533–537.
Nuyts R, Pels E, Greve E. The effects of 5-fluorouracil and mitomycin C on the corneal endothelium. Curr Eye Res 1992; 11:565–570.
Mietz H, Roters S, Krieglstein GK. Bullous keratopathy as a complication of Subscleral trabeculectomy with mitomycin C. Graefe’s Arch Clin Exp Ophthalmol 2005; 243:1284–1287.
Shin D, Lee S, Kim C. Effects of viscoelastic material on the corneal endothelial cells in Subscleral trabeculectomy with adjunctive mitomycin-C. Korean J Ophthalmol 2003; 17:83–90.
Sihota R, Sharma T, Agarwal H. Intraoperative mitomycin C and the corneal endothelium. Acta Ophthalmol Scand 1998; 76:80–82.
Zarei R, Zarei M, Fakhraie G, Eslami Y, Moghimi S, Mohammadi M et al.
Effect of mitomycin-C augmented subscleral trabeculectomy on corneal endothelial cells. J Ophthalmic Vis Res 2015; 10:257–262.
Pastor S, Williams R, Hetherington J, Hoskins HD, Goodman D. Corneal endothelial cell loss following subscleral trabeculectomy with mitomycin C. J Glaucoma 1993; 2:112–113.
Nassiri N, Nassiri N, Rahnavardi M, Rahmani L. A comparison of corneal endothelial cell changes after 1-site and 2-site phaco subscleral trabeculectomy. Cornea 2008; 27:889–894.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]