|Year : 2020 | Volume
| Issue : 2 | Page : 540-545
Changes in macular thickness after trabeculectomy with or without adjunctive mitomycin C
Hoda M. K El Sobky1, Ahmed A AL Masry2, Moataz F El Sawey1, Basma A. Moustafa3
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Damnhour Ophthalmology Hospital, Damnhour, Albehaira, Egypt
|Date of Submission||17-Dec-2018|
|Date of Decision||17-Feb-2018|
|Date of Acceptance||18-Feb-2018|
|Date of Web Publication||27-Jun-2020|
Basma A. Moustafa
Source of Support: None, Conflict of Interest: None
To assess macular thickness changes posttrabeculectomy with and without mitomycin C (MMC) and to find the association between these postoperative changes and intraocular pressure (IOP).
Patients and methods
This study included 40 eyes of 31 patients who underwent trabeculectomy. It was done at a private eye center in Alexandria from December 2017 to September 2018. Study patients were stratified into two groups (20 each): trabeculectomy with MMC and trabeculectomy without MMC.
The mean (±SD) (IOP) reduced from 29.48 (±3.57) mmHg before trabeculectomy to 19.05 (±2.86) mmHg 1 week (P < 0.001) and to 15.38 (±3.05) mmHg 6 months (P < 0.001) after the operation. One week postoperatively, the mean macular thickness increased from 289.98 (±18.11) μm to 296.81 (±17.15) μm (P < 0.001); macular thickening was significant in all macular subfields. Mean macular thickness correlated positively with postoperative IOP reduction (P < 0.005). Significant correlation was found at central (P < 0.001), superior inner (P = 0.014), inferior outer (P = 0.001), and nasal outer (P = 0.023) macular subfields. Six months later, macular thickening remained significant only at the central and inner nasal macular subfields (P2=0.007, P2 <0.001), respectively, and there was no significant correlation between IOP reduction and macular thickness at the same time. MMC had no effect on these changes.
Trabeculectomy may increase macular thickness in the early postoperative period. However, MMC has no effect despite its possible toxic effects on the retina.
Keywords: intraocular pressure, macula, mitomycin C, retinal thickness, trabeculectomy
|How to cite this article:|
El Sobky HM, AL Masry AA, El Sawey MF, Moustafa BA. Changes in macular thickness after trabeculectomy with or without adjunctive mitomycin C. Menoufia Med J 2020;33:540-5
|How to cite this URL:|
El Sobky HM, AL Masry AA, El Sawey MF, Moustafa BA. Changes in macular thickness after trabeculectomy with or without adjunctive mitomycin C. Menoufia Med J [serial online] 2020 [cited 2020 Jul 14];33:540-5. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/540/287802
| Introduction|| |
Trabeculectomy is a filtering surgery where an ostium is created into the anterior chamber from underneath a partial thickness scleral flap to allow for aqueous flow out of the eye into the subconjunctival space. While the goal of trabeculectomy is to establish a subconjunctival filtration bleb that lowers the intraocular pressure (IOP) sufficiently, the bleb itself can cause many late-onset complications. Bleb can leak, become infected and induce endophthalmitis, or cause chronic discomfort. Antimetabolites offer a more successful long-term IOP lowering in patients who are at high risk of filtration failure and in primary trabeculectomy,. Target IOP at the normal end of the normal range (around 12 mmHg) is required to arrest progression of glaucoma over a decade. The healing response is one of the major determinants of long-term IOP levels after glaucoma surgery, and prospective studies demonstrate that application of antimetabolites improve trabeculectomy survival outcomes.
Certain patient characteristics increase the risk of failure after glaucoma surgery which include previous failed trabeculectomy, previous cataract surgery through a conjunctival incision, neovascular glaucoma, African origin, recent intraocular surgery, young age, and chronic topical medication. Patients with any of these should have some form of antimetabolite treatment.
Structural changes in ocular posterior pole such as shortening of axial length, anterior displacement of lamina cribrosa, reversal of the optic nerve cupping, and thickening of macular and parapapillary choroid have been reported after acute reduction in IOP following glaucoma filtration surgery.
Macular edema following intraocular surgery including trabeculectomy can result in visual impairment,,,. The use of antimetabolite including mitomycin C (MMC) in glaucoma surgery increases the risk of postoperative complications such as bleb leakage, hypotonic maculopathy, uveitis, and infectious endophthalmitis,,,. The anti-fibrotic agents used in glaucoma surgery could lead to enhancement of the postoperative structural changes in macula because they are associated with a marked IOP reduction, postoperative inflammation, and a possible subclinical cytotoxic effect on the retina,,,. Hence the aim of this study is to evaluate macular changes after trabeculectomy with or without application of MMC and its relation with IOP changes.
| Patients and Methods|| |
The present study included 40 eyes of 31 patients who underwent glaucoma filtration surgery (trabeculectomy). They were divided into two equal groups (20) each. In the first group A, the operation was done with MMC and in the second group B, the operation was done without MMC. The study was carried out at a private eye center in Alexandria from December 2017 to September 2018. A written informed consent was obtained from all study participants after the nature and possible consequences of the study, the procedures involved, the expected duration, the potential risks, benefits involved, and any discomfort that may be caused were explained to them. Before initiating this study, all procedures were reviewed and approved by the Ethics Committee of the Menoufia University Hospital.
Each patient was informed that participation is voluntary, that he or she may withdraw from the study at any time and without giving reasons. The withdrawal did not affect the subsequent medical treatment or relationship with the treating surgeon.
Presence of glaucoma with uncontrolled IOP requiring trabeculectomy.
Prior intraocular surgery except phacoemulsification with intraocular lens implantation; refractive error beyond –6.0 D and +6.0 D of sphere and ±3.0 D of cylinder; poor image quality because of opaque ocular media; age-related macular degeneration of Age-Related Eye Disease Study category 4; uveitis, cystoid macular edema, and hypotony maculopathy.
After detailed history taking and full thorough ophthalmic evaluation, an optical coherence tomography (OCT) scan of the macula was performed using the Spectralis (Heidelberg GmbH69121, SN: TR-KT-2077, manufactured: 02/13; Heidelberg, Germany) to map the nine standard subfields (central, inner superior, inner nasal, inner inferior, inner temporal, outer superior, outer nasal, outer inferior, and outer temporal sectors) and document the mean and sectoral macular thickness.
A standard trabeculectomy was then performed on all study eyes. A traction suture (placed partial thickness through the peripheral clear cornea) is used for adequate exposure of the surgical site (superior quadrants of the eye). A conjunctival peritomy is created to expose the superior bare sclera. Gentle cautery is used to achieve hemostasis. A partial thickness scleral flap is created in the superior sclera, hinged at the limbus. The scleral flap is dissected forward until the bluish gray zone at the limbus is exposed. Dissection of the subconjunctival space is then performed. A paracentesis is created in the peripheral clear cornea prior to creating an ostomy into the anterior chamber from underneath the scleral flap. Viscoelastic material may be injected to stabilize the IOP. Then, a peripheral iridectomy is created. Sutures (usually 9-0 or 10-0 nylon) are then used to close the scleral flap. The conjunctival peritomy is then closed using absorbable or nylon sutures. MMC can be applied to the surgical site by soaking a surgical sponge and placing it onto the surgical site prior to creation of the ostomy, before or after creation of a scleral flap. The sponge is removed after 30 s to 5 min followed by irrigation of the subconjunctival space. Alternatively, the MMC may be injected preoperatively into the subconjunctival space and then irrigated.
Follow-up visits were scheduled before surgery and 1 week and 6 months postoperatively.
Statistical analysis was performed using the Statistical Package for Social Sciences, version 20 (SPSS Inc., Chicago, Illinois, USA). Pearson's correlation was used to show the correlation between two continuous normally distributed variables while Spearman's correlation was used for not normally distributed ones. Repeated measurements analysis of the variants test was used for comparison of the mean value of preoperative and postoperative measurements. P value was adjusted for multiple comparisons using Bonferroni correction. The correlation and univariate regression analysis were performed. A P value less than 0.005 was considered statistically significant.
| Results|| |
The study was conducted on 40 eyes (18 right) of 31 (21 men) patients. The mean age ± SD (range) of the study participants was 53.35 (±17.77) years (9–81 years). Distribution of the studied cases according to demographic data are described in [Table 1].
|Table 1: Distribution of the studied cases according to demographic data|
Click here to view
The mean preoperative IOP was 29.48 (±3.57) mmHg and was reduced significantly to 19.05 (±2.86) (P1 <0.001) after 1 week and significantly to 15.38 (±3.05) (P2 <0.001) after 6 months [Figure 1]. The IOP reduction did not differ significantly between the patients with or without adjunctive MMC. No major sight-threatening complications were encountered during the study period.
|Figure 1: Comparison between the two groups according to IOP. IOP, intraocular pressure.|
Click here to view
The mean macular thickness at all measured early treatment diabetic retinopathy study (ETDRs) sectors increased 1 week after trabeculectomy (P < 0.001) [Table 2]. One week postoperatively, the mean macular thickness change was 6.83 (±6.02) μm (P < 0.001). Six months following surgery a significant macular thickening was observed in central (P2 =0.007) and inner nasal macular (P2 <0.001) subfields only [Table 3].
|Table 2: Central retinal thickness measurements at baseline and after operation|
Click here to view
|Table 3: Comparison between the three periods according to the central and inner nasal macular areas|
Click here to view
There was positive correlation between the magnitude of the mean macular thickening and the IOP reduction 1 week postoperatively (P = 0.005) [Figure 2]. It was significant in central (P = 0.001), superior inner (P = 0.014), inferior outer (P = 0.001), and nasal outer (P = 0.023) macular subfields.
|Figure 2: Correlation between IOP and mean macular thickening 1 week after trabeculectomy. IOP, intraocular pressure.|
Click here to view
However, at the later follow-up there was no significant correlation between IOP reduction and macular thickening.
| Discussion|| |
In this study, we evaluated the effect of uncomplicated trabeculectomy with or without MMC on macular thickness in the short-term and long-term postoperative periods and the correlation between IOP reduction and change in macular thickness at this time using SD-OCT. There was thickening of all macular subfields one week postsurgery. Six months after trabeculectomy this thickening stayed significant in central and inner nasal macular subfields, but was less pronounced.
In agreement with our early postoperative results, Sesar et al. reported a thicker central macula 1 week after trabeculectomy in 34 glaucomatous eyes.
Additionally, Karasheva et al. have reported significant IOP reduction and macular thickness increase after filtering surgical procedures in all visits within a month of surgery. It was considered that the IOP reduction after filtration surgery results in a moderate increase in macular thickness. They showed in their prospective study using OCT that increase in macular thickness over about 1 month returns to normal preoperative levels after 3 months and coincides with visual acuity reestablishment.
This is in contradistinction to the finding of the current study in which we found that the slight macular thickening remained significant 6 months after surgery at the central and inner nasal macular subfields.
These results agree with Pitale et al., who reported a total macular thickness increase as a result of a surgical IOP reduction after an average of 10.8 ± 5.3 months follow-up, with Drukteiniene et al., who found that there was a reduction in mean ± SD IOP up to 12 months after filtering surgery and with Lima et al., who reported that macular thickness increased in eight of the 14 studied patients with prolonged postoperative hypotonia and without clinically visible maculopathy.
Nevertheless, Németh and Horóczi, by using ultrasound, revealed increased thickness and volume of the ocular wall after trabeculectomy explaining that these changes might be caused by ocular hypotonia and postoperative inflammation.
Klink et al. found that measurements by OCT showed a reduction in macular thickness when IOP returns to normal levels in the eyes with hypotonia after the filtering procedure.
Regarding the relationship between IOP and retinal changes after trabeculectomy, our results showed a positive correlation between the mean macular thickness and IOP reduction. It was significant in central, superior inner, nasal inner, and inferior outer macular subfields 1 week postoperatively, yet we did not find significant correlation between IOP reduction and macular thickness change 6 months following the operation.
In contrast, no significant correlation was shown between the retinal thickness changes and the surgery-induced IOP reduction in the studies of Sesar et al., and Karasheva et al..
Potentially, a greater reduction of IOP after surgery and a bigger sample size in comparison with the previous studies permitted us to find a significant association between IOP reduction and mild early macular changes.
Sigal et al. agreed that several mechanisms may result in central retinal thickening after trabeculectomy such as an acute IOP reduction may increase macular thickness directly since the inner force of the IOP on the retina is reduced allowing to regain its original shape and the indirect effect of the IOP lowering via subsequent scleral deformations transmitted to compliant adjacent intraocular tissues appears to play a role.
Additionally, Sesar et al. and Guyton and Hall concluded that IOP lowering leads to a decrease in retinal interstitial pressure and an increase in the gradient of the capillary/intercellular pressure leading to enhanced filtration and fluid accumulation in the intracellular retinal space. The above-mentioned pattern of 'Starling forces' (capillary pressure/interstitial fluid pressure) could play a very important role in reducing macular volume in glaucomatous eyes compared with normal eyes.
Lederer et al. have shown that the progression of glaucoma with higher values of IOP leads to a decrease in the macular volume.
Moreover, Barisić et al. have reported decreased values of macular volume and average macular thickness in glaucoma patients in comparison to healthy individuals.
It has been suggested by Zeimar et al. that loss of retinal ganglion cells in advanced glaucomatous disease could be responsible for a reduction in retinal thickness and, contrarily, higher IOP leads to an increase in interstitial fluid pressure, lowering the net filtration pressure and increasing fluid absorption from the intercellular space into the capillaries, leading to thinning of the retina.
Finally, Ursell et al., Miyake et al., and Costa and Arcieri, agreed that inflammation have a role in macular edema, because the inflammatory mediators released from the anterior chamber reach the posterior pole of the eye and increase the permeability of the blood–aqueous barrier associated with vascular leakage,,.
In the current study, we also investigated the effect of MMC on macular thickness.
We found no significant impact of the use of MMC on the change in macular thickness. This is in agreement with Sesar et al. and Karasheva et al., who reported no significant difference in the change of macular thickness with the use of MMC.
The strengths of the current study were the prospective design, long follow-up, and the wide macular area measured. The limitations are the small number of patients, no method of randomization, and lack of visual field data.
| Conclusion|| |
In our study, we conclude that trabeculectomy may induce a slight increase in macular thickness which is more obvious in the early period after operation.
The IOP reduction has an important role in this process and is associated with the thicker postoperative macula; still, the inflammatory mechanism may be considered. Despite the possible inflammatory, hypotonic, and cytotoxic effects on the eye, the adjunctive antimetabolite MMC has no effect on the central retinal thickness after glaucoma surgery.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jinza K, Saika S, Kin K, Ohnishi Y. Relationship between formation of a filtering bleb and an intrascleral aqueous drainage route after trabeculectomy: evaluation using ultrasound biomicroscopy. Ophthalmic Res 2000; 32
Miller MH, Rice NS. Trabeculectomy combined with beta-irradiation for congenital glaucoma. Br J Ophthalmol 1991; 75
Kirwan JF, Cousens S, Venter L, Cook C, Stulting A, Roux P, et al
. Effect of beta radiation on success of glaucoma drainage surgery in South Africa: randomized controlled trial. BMJ 2006; 333
Sihota R, Angmo D, Ramaswamy D, Dada T. Simplifying 'target' intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J Ophthalmol 2018; 66
The Fluorouracil Filtering Surgery Study Group. Five year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1996; 121
The European Glaucoma Society. Terminology and guidelines for glaucoma
ed. Savona, Italy; 2003. 1441.
Park HY, Shin HY, Jung KI, Park CK. Changes in the lamina and pre lamina after intraocular pressure reduction in patients with primary open-angle glaucoma and acute primary angle-closure. Invest Ophthalmol Vis Sci 2014; 55
Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. Curr Opin Ophthalmol 2012; 23
Vukicevic M, Gin T, Al-Qureshi S. Prevalence of optical coherence tomography diagnosed postoperative cystoid macular oedema in patients following uncomplicated phacoemulsification cataract surgery. Clin Exp Ophthalmol 2012; 40
Jampel HD, Musch DC, Gillespie BW, Lichter PR, Wright MM, Guire KE. Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS). Am J Ophthalmol 2005; 140
Gedde SJ, Schiffman JC, Feuer WJ. Three year follow-up of the tube versus trabeculectomy study. Am J Ophthalmol 2009; 148
Shields MB, Scroggs MW, Sloop CM, Simmons RB. Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C. Am J Ophthalmol 1993; 116
Greene DS, Parrish RK. Bleb rupture following filtering surgery with mitomycin-C: clinicopathologic correlations. Ophthalmic Surg Lasers1996; 27
Singh K, Mehta K, Shaikh NM, Tsai JC, Moster MR, Budenz DL, et al
. Trabeculectomy with intraoperative mitomycin C versus. Uorouracil. Prospective randomized clinical trial. Ophthalmology 2000; 107
Palanca-Capistrano AM, Hall J, Cantor LB, Morgan L, Hoop J, WuDunn D. Long-term outcomes of intraoperative 5- fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery. Ophthalmology 2009; 116
Sesar A, Cavar I, Sesar AP, Geber MZ, Sesar I, Laus KN, et al
. Macular thickness after glaucoma filtration surgery. Coll Antropol 2013; 37
Karasheva G, Goebel W, Klink T, Haigis W, Grehn F. Changes in macular thickness and depth of anterior chamber in patients after filtration surgery. Graefes Arch Clin Exp Ophthalmol 2003; 241
Pitale PM, Catha U, Patel V, Gupta L, Waisbourd M, Michael J. Changes in macular thickness following glaucoma surgery. Int J Ophthalmol 2016; 9
Drukteiniene E, Strelkauskaitė E, Kadziauskienė A, Ašoklis R,
Lesinskas E, Schmetterer L. Macular thickness after intraocular pressure reduction following trabeculectomy. Acta Ophthalmol 2017; 95
Lima MC, Paranhos A, Salim S, Honkanen R, Devgan L, Wand M, et al
. Visually significant cystoid macular edema in pseudophakic and aphakic patients with glaucoma receiving latanoprost. JGlaucoma2000; 9
Németh J, Horóczi Z. Changes in the ocular dimensions after trabeculectomy. Int Ophthalmol 1992; 16
Klink T, Lieb WE, Göbel W. Early and late findings with optical coherence tomography (OCT) in patients with postoperative hypotonia. Ophthalmologe 2000; 97
Sigal IA, Flanagan JG, Ethier CR. Factors influencing optic nerve head biomechanics. Invest Ophthalmol Vis Sci 2005; 46
Guyton AC, Hall JE. Medical physiology
. Philadelphia: Saunders Elsevier; 2012.
Lederer DE, Schuman JS, Hertzmark E, Heltzer J, Velazques LJ, Fujimoto JG, et al
. Analysis of macular volume in normal and glaucomatous eyes using optical coherence tomography. Am J Ophthalmol 2003; 135
Barisić F, Sicaja AJ, Ravlić MM, Mandić Z. Macular thickness and volume parameters measured using optical coherence tomography (OCT) for evaluation of glaucoma patients. Coll Antropol2012; 36
Zeimer R, Asrani S, Zou S, Quigley H, Jampel H. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping. A pilot study. Ophthalmology 1998; 105
Ursell PG, Spalton DJ, Whitcup SM, Nussenblatt RB. Cystoid macular edema after phacoemulsification: relationship to blood-aqueous barrier damage and visual acuity. J Cataract Refract Surg 1999; 25
Miyake K, Nishimura K, Harino S, Ota I, Asano S, Kondo N, et al
. The effect of topical diclofenac on choroidal blood flow in early postoperative pseudophakias with regard to cystoid macular edema formation. Invest Ophthalmol Vis Sci2007; 48
Costa VP, Arcieri ES. Hypotony maculopathy. Acta Ophthalmol Scand 2007; 85
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]