Departments of *Ophthalmology and Visual Science
†Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
Presented at the World Ophthalmology Congress 2010 Berlin, Germany, held from June 5 to 9, 2010 (poster presentation).
Disclosure: The authors declare no conflict of interest.
Reprints: Satoshi Okimoto, MD, Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan (e-mail: firstname.lastname@example.org).
Received July 31, 2011
Accepted January 2, 2013
Purpose: The goal of this study was to identify the early postoperative intraocular pressure (IOP) that predicts low pressure control after a trabeculectomy with mitomycin C.
Materials and Methods: This study retrospectively analyzed the medical records of the initial trabeculectomy with mitomycin C in patients with primary open-angle glaucoma. We established 2 target postoperative IOPs, ≤11 and ≤15 mm Hg. The preoperative and early postoperative factors contributing to the success and failure of postoperative IOP control were studied by multiple regression analyses. These factors included the sex and age of patients, record of cataract surgery, number of preoperative medications, preoperative IOP, IOP recorded 2 weeks after surgery, laser suture lysis after surgery, and the presence of a shallow anterior chamber and choroidal detachment during the first month after surgery. The optimal IOP levels 2 weeks after surgery for long-term IOP control were examined using the Kaplan-Meier survival analyses.
Results: Sixty-six patients (66 eyes) with open-angle glaucoma participated in the study. The age and IOP 2 weeks after surgery were selected as the confounding factors affecting the probability of successfully satisfying both target IOPs;≤11 and≤15 mmHg postoperatively. An IOP under 8 mm Hg at 2 weeks after surgery was found to be associated with maintaining the postoperative IOP at either ≤11 and ≤15 mm Hg for an extended period.
Conclusions: An IOP of 8 mm Hg was associated with successful outcomes in patients undergoing trabeculectomy. Also, younger age was found to be a risk factor for surgical failure.
The use of mitomycin C (MMC) and laser suture lysis (LSL) have improved the outcome of trabeculectomy. In particular, the intraocular pressure (IOP) control after trabeculectomy has been improved remarkably by the intraoperative use of MMC.1–4 A combination of tight scleral flap trabeculectomy with subsequent postoperative LSL is a safe and effective method for low-level IOP control, and minimizes the incidence of complications caused by excessive aqueous filtration.5,6 However, there have so far been few studies that have examined the relationship between the IOP at an early stage after trabeculectomy and the final outcome of the surgery. There is currently no definite cut-off IOP level to indicate when LSL should not be used to maintain long-term low IOP. Hara et al7 showed that the IOP could be stabilized 9 to 14 days after trabeculectomy using LSL, and suggested that the IOP 2 weeks postoperatively is a predictor of the long-term outcome of trabeculectomy. They also reported that a mean IOP of 8 mm Hg on postoperative days 9 to 14 would give the most reasonable balance for late IOP control of ≤15 mm Hg, and a lower incidence of postoperative complications.7
In this retrospective study, we set the target IOPs after the trabeculectomy at 2 levels, namely ≤11 and ≤15 mm Hg. We tried to identify the prognostic factors associated with good long-term IOP control after trabeculectomy and to determine the optimum IOP level at the early stage after surgery to achieve long-term IOP control.
MATERIALS AND METHODS
We retrospectively studied patients with primary open-angle glaucoma (POAG) who underwent initial trabeculectomy with MMC at Hiroshima University between January 2007 and March 2008 and were followed up for ≥4 months after surgery. This study complied with the Declaration of Helsinki. The research protocol was approved by the Institutional Review Board and University Hospital Medical Information Network (registration number; 2816). The main goal of this study was to identify the IOP at 2 weeks postoperation which predicted late IOP control at ≤11 and ≤15 mm Hg. The secondary purpose of this research was to identify the prognostic factors associated with long-term good IOP control. When both eyes underwent trabeculectomy during the above period, we selected the data for the eye that was treated first. In all the eyes, a trabeculectomy was indicated after pharmacological therapy in our clinic because of poor IOP control or progressive visual field damage despite receiving the maximum tolerated dose of glaucoma medications.
The trabeculectomy was carried out according to the modification of Cairns using a fornix-based conjunctival flap.8 After a square-shaped (3.0×3.0 mm) scleral flap was prepared, surgical absorbent sponge pieces soaked in a 0.04% MMC solution prepared just before use were placed between the episclera and conjunctival flap for 5 minutes. After removal of the sponge pieces, the site was rinsed with 100 mL of balanced salt solution. Following resection of a 1×2.5 mm sclerocorneal block and peripheral iridectomy, the flap was closed with 5 sutures of 10-0 nylon. The sutures were adjusted so that a little leakage around the margin of the flap was seen without being associated with the development of a shallow anterior chamber. Postoperatively, topical steroids and antibiotics were given and then were gradually tapered off over 2 months. When the postoperative IOP exceeded the target IOP and the formation of a bleb indicated poor filtration, LSL was carried out. Examinations including IOP measurements, biomicroscopy, and indirect ophthalmoscopy were carried out daily during the first 1 to 2 weeks after trabeculectomy and once a month thereafter. Afterwards, the patients were observed at intervals of <3 months. When the IOP exceeded the target IOP, appropriate medical treatment was administered.
The patients were classified as experiencing treatment failure when they exceeded the target IOP of >11 or >15 mm Hg, on 3 successive occasions from 1 month postoperatively. The patients were also classified as having treatment failure when the pressure dropped <5 mm Hg after 1 month postoperatively or when their visual acuity decreased. The patients who required further glaucoma or cataract surgery were also classified as failures, and observation was discontinued. The patients in whom the target IOP was able to be maintained without medication were defined as complete successes, and the patients who were able to maintain their target IOP using medication were defined as qualified successes.
We conducted a multivariate logistic regression analysis using a stepwise selection method in which the terms were retained if they reached the 0.25 level of significance. The factors studied were the sex, age, history of cataract surgery, number of preoperative medications, preoperative IOP, the IOP level recorded 2 weeks after trabeculectomy, the presence of a shallow anterior chamber, the presence of choroidal detachment during the first month after the surgery, and the use of LSL after the surgery. We examined the incidence of complications during the early phase after surgery. The complications included choroidal detachment, a shallow anterior chamber, bleb leakage, anterior chamber bleeding, formation of fibrin, and vitreous hemorrhage. A shallow anterior chamber was defined as an axial anterior chamber depth of less than half of the preoperative value as estimated by biomicroscopy, and the extent of choroidal detachment was monitored by indirect ophthalmoscopy through the dilated pupil. We divided the patients into 2 groups based on the IOP at 2 weeks postoperatively, which we referred to as the boundary IOP in this study. We examined the survival curves of 2 groups (<boundary IOP, ≥ boundary IOP) using a Kaplan-Meier analysis and compared the cumulative survival rates between the 2 groups by a log-rank test. In this study, we set 4 boundary IOPs, which were 7, 8, 9, and 10 mm Hg.
We used the JMP 9.0 and Stat View Ver. 5.0 statistical software package (SAS Institute Inc., CA) for the analysis, and a P value of <0.05 was considered to indicate a significant difference.
The patient characteristics and ocular data are shown in Table 1. The average preoperative IOP was 18.5±5.5 mm Hg. Medication was used on 29 eyes (44%) after the operation. The number of glaucoma medications being applied at the final consultation was 0.7±0.9. Reoperation for glaucoma was performed for 9 eyes. The results of the Kaplan-Meier analysis with surgical success defined according to the target IOP≤11 mm Hg and IOP≤15 mm Hg are shown in Figure 1.
The results of the multivariate logistic regression analysis are presented in Tables 2 and 3. The patient age and the IOP at 2 weeks postoperatively made a significant contribution to the probability of success for both an IOP control of ≤11 mm Hg and of ≤15 mm Hg. These results suggest that the IOP at 2 weeks after the operation can be used as an early postoperative indicator for late IOP control (Tables 2 and 3). The history of cataract surgery, preoperative IOP, choroidal detachment, and LSL were important factors associated with IOP control of ≤15 mm Hg (Table 3).
Table 4 shows the results of the comparison of the cumulative survival rates between the groups divided by the boundary IOP. The group with an IOP<8 mm Hg at 2 weeks after the operation demonstrated a significantly better IOP control than the group with IOP≥8 mm Hg, regardless of the use of medication after surgery. When the boundary IOP was set at 9 and 10 mm Hg, there were no significant differences in survival curves between the groups for the target IOP≤11 mm Hg and IOP ≤15 mm Hg (Table 4).
The incidence of complications during the early postoperative phase is summarized in Table 5. Complications related to excessive filtration were observed in 7 eyes that developed choroid detachment, and 5 eyes with a shallow anterior chamber. The group with an IOP≤7 mm Hg 2 weeks after the operation had a higher incidence of hypotonic complications than the group with an IOP≥8 mm Hg; however, these differences were not significant.
We retrospectively analyzed the results of initial trabeculectomy with MMC in 66 consecutive Japanese patients with POAG. A logistic regression analysis shown in Tables 2 and 3 revealed that older age and a low IOP at 2 weeks postoperatively were advantageous for satisfying both a target IOP≤11 and ≤15 mm Hg postoperatively. We found that the group with an IOP <8 mm Hg at 2 weeks postoperatively had a significantly better late IOP control than the group with an IOP≥8 mm Hg. The POAG patients in the present study included normal tension glaucoma (NTG) patients. In Japanese subjects with progressive NTG, an IOP reduction of at least 20% from baseline or an IOP of ≤10 mm Hg is recommended as the target postoperative IOP.9 The average IOP of Japanese POAG patients was 15.2±2.9 mm Hg.10 On the basis of the desired 20% to 30% IOP reduction, we set the target postoperative IOP at ≤11 and ≤15 mm Hg. Hara et al7 reported the IOP at 2 weeks postoperatively to generally be stable, and it could therefore be a predictive factor for late IOP control. They showed that a mean IOP of 8 mm Hg on postoperative days 9 to 14 would provide the most reasonable balance between late IOP control≤15 mm Hg and prevention of postoperative long-term hypotony.7 The present study also showed an IOP<8 mm Hg at 2 weeks postoperatively to be an important factor for the achievement of both target IOPs (≤11 and ≤15 mm Hg). Keeping the IOP<8 mm Hg at that time point might therefore be essential for the surgical success of initial trabeculectomy in eyes with POAG, regardless of the final target IOP.
According to the results of a logistic regression analysis, a younger age is a risk factor for bleb failure following trabeculectomy, besides the IOP at 2 weeks postoperatively under all conditions (complete success, qualified success, target IOP≤11 or ≤15 mm Hg). This result was compatible with previous findings.11–15 The likely cause is that the more vigorous wound healing response in younger patients might be associated with subconjunctival fibrosis after trabeculectomy.16
With regard to ensuring that the IOP is maintained at ≤15 mm Hg, other risk factors for failure are a history of cataract surgery, a high preoperative IOP, the occurrence of choroidal detachment, and LSL (Table 3). Previous reports showed that patients who had previously undergone cataract extraction had worse IOP control after trabeculectomy than those who had not.17 Takihara et al11 suggested 2 reasons for the poorer surgical outcomes in the pseudophakic eyes. The first explanation is the widespread increased number of conjunctival fibroblasts and inflammatory cells in the pseudophakic eyes after phacoemulsification. The second is that there are alterations in the nature of the aqueous humor because of breakdown of the blood-aqueous barrier after previous intraocular surgery.18
According to a multivariate analysis in our study, choroidal detachment was a risk factor for the failure to achieve long-term IOP control when the target IOP was set at ≤15 mm Hg to achieve complete success. The incidence of complications related to excessive filtration are shown in Table 5, and indicated that the group with an IOP≤7 mm Hg at 2 weeks after the operation had a higher incidence of hypotonous complications compared to the group with an IOP ≥8 mm Hg. Therefore, this study showed that an IOP of at least 8 mm Hg is recommended at 2 weeks postoperatively to minimize postoperative complications. Benson et al19 reported that early posttrabeculectomy hypotony, including choroidal detachment (within 1 mo), is associated with reduced bleb survival over a 5-year period. Hypotony is associated with an alteration in aqueous flow, likely it initiates an inflammatory response.20 This means that in the hypotonous eye, there will be a reduced flow of aqueous fluid through the sclerostomy and into the bleb. This reduction in flow and increase in inflammatory mediators are likely to be potent causes of subconjunctival scarring and subsequent failure.21
In this study, we found LSL to be a possible risk factor for failure after trabeculectomy, which is in agreement with previous studies.12,21 Fontana et al22 reported that postoperative LSL was associated with a higher rate of failure for criteria of an IOP of 15 mm Hg and an IOP reduction of 25%; and an IOP of 12 mm Hg and IOP reduction of 30%. Takihara et al11 also indicated that postoperative LSL was a prognostic factor for surgical failure for a target IOP of <15 mm Hg. The reason why LSL is a risk facture for surgical failure is unclear from the past reports. One of the possible reasons is that the need for postoperative LSL might reflect lower filtration through the scleral flap, and even when LSL is successful, the trabeculectomy may have already started scarring.22 The patient sex and preoperative medications were not significant factors predicting the surgical outcome, which is in agreement with previous studies.13,22
There are inherited weaknesses in our study based on the retrospective design. The number of cases was small, and this research was carroed out at a single facility. In the early postoperative phase, the appearance of a bleb probably represents 2 independent factors: a reaction to the surgical insult and the amount of filtration. The elevation and breadth of the bleb are generally correlated with the IOP in the early postoperative phase. However, unlike the IOP, they are difficult to grade quantitatively. For these reasons, the appearance of a bleb was not included in our study as a marker, but the IOP and the presence or absence of signs of excessive filtration were included as early postoperative factors.
In summary, the present study suggested that, in eyes with POAG that had received multiple preoperative medications and then were subjected to an initial trabeculectomy with the intraoperative use of MMC, an IOP of 8 mm Hg 2 weeks after the operation can therefore be a useful indicator for obtaining good long-term IOP control.
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