The prognostic value of the wuerzburg bleb classification score for the outcome of trabeculectomy

Original Paper

Ophthalmologica

Ophthalmologica 2011;225:55–60 DOI: 10.1159/000314717

Received: October 23, 2009 Accepted after revision: April 2, 2010 Published online: August 14, 2010

The Prognostic Value of the Wuerzburg Bleb Classification Score for the Outcome of Trabeculectomy Thomas Klink Gunda Kann Patrick Ellinger Janine Klink Franz Grehn Rainer Guthoff Department of Ophthalmology, Julius Maximilian University, Wuerzburg, Germany

Key Words Bleb grading ⴢ Bleb classification ⴢ Glaucoma surgery ⴢ Filtering bleb ⴢ Trabeculectomy

Abstract Background: The Wuerzburg bleb classification score (WBCS) aims at an objective and standardized assessment of the developing filtering bleb after trabeculectomy, in order to detect and treat bleb scarring at the earliest possible stage of development. The purpose of this retrospective study was to evaluate the prognostic value of the early postoperative WBCS for the long-term outcome of trabeculectomy. Methods: The WBCS is a grading system for clinical bleb morphology. It evaluates the following parameters: vascularization, corkscrew vessels, encapsulation and microcysts. The WBCS of 113 eyes of 113 consecutive patients after trabeculectomy was determined 1 day, 1 and 2 weeks, 3, 6 and 12 months after surgery. Complete success was defined as an intra-ocular pressure (IOP) !21 mm Hg and 120% pressure reduction without glaucoma medication after 1 year. Results: A complete success rate of 73.9% and a qualified success rate of 82.4% were achieved 1 year after surgery. The average total bleb score during follow-up in the success group was always higher than in the failure group, but there was no statistically significant difference at any time. The bleb average

© 2010 S. Karger AG, Basel 0030–3755/11/2251–0055$38.00/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com

Accessible online at: www.karger.com/oph

score for eyes with an IOP of ^12 mm Hg after 2 weeks was significantly higher (p = 0.005) than for eyes with an IOP 613 mm Hg at the end of follow-up. Conclusion: Patients with a higher early WBCS postoperatively had a significantly lower IOP 1 year after surgery. However, the study could not reveal a certain prognostic value of the early total bleb score using the WBCS for the long-term complete success of trabeculectomy.

Copyright © 2010 S. Karger AG, Basel

Introduction

Scarring of the filtering bleb is the main reason for failure of penetrating glaucoma surgery. Postoperative application of wound-modulating drugs is meanwhile routinely included in postsurgical management and has led to an increase in success rates after filtering procedures [1, 2]. In clinical practice, thorough slit-lamp examination is essential to assess filtering bleb development in order to start wound modulation when needed. Several scoring systems offer a framework for structured patient examination and facilitate the interpretation of clinical findings [3–6]. The Wuerzburg bleb classification score (WBCS) aims at an objective and standardized assessment of the developing filtering bleb after trabeculecPriv.-Doz. Dr. Thomas Klink Universitäts-Augenklinik Würzburg, Josef-Schneider-Strasse 11 DE–97080 Würzburg (Germany) Tel. +49 931 201 20610, Fax +49 931 201 20490 E-Mail klink_t @ klinik.uni-wuerzburg.de

Table 1. Parameters and scoring of the WBCS [4]

Vascularity

3 = avascular 2 = similar to adjacent conjunctiva 1 = increased 0 = massive

Corkscrew vessels

3 = none 2 = in one third 1 = in two thirds 0 = entire bleb

Microcysts

3 = entire bleb 2 = lateral or medial of the flap 1 = over the scleral flap 0 = none

Encapsulation

3 = none 2 = in one third 1 = in two thirds 0 = entire bleb

tomy, in order to detect and treat bleb scarring at the earliest stage [4]. Since 1998, the WBCS has been used in clinical studies and clinical routine, as a basis for intensified postoperative care [7–10]. The WBCS has a low interobserver variability and provides a good basis for consistent clinical decisions [11]. The purpose of this retrospective study was to evaluate the prognostic value of the early postoperative WBCS for the outcome of trabeculectomy after 1 year.

Materials and Methods Patient Selection and Trial Protocol Data of 152 consecutive patients, who had undergone fornixbased trabeculectomy for medically uncontrolled primary or secondary open-angle glaucoma or chronic angle closure glaucoma between 2003 and 2005, were retrospectively analysed at the Department of Ophthalmology of the University Hospital Wuerzburg. 39 patients were excluded due to incomplete data (absence of bleb score during follow-up) or follow-up (no further appearance after 1 week of follow-up). Finally, 113 eyes of 113 patients were included. The data acquisition included age, gender, diagnosis, previous surgery, intra-operative and postoperative antimetabolites, intra-ocular pressure (IOP) measured with Goldmann applanation tonometry, medication and bleb morphology using the WBCS. The last 3 parameters were assessed at 7 specific dates postoperatively: 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months and 12 months after surgery.

Wuerzburg Bleb Classification Score The WBCS evaluates vascularization, corkscrew vessels, encapsulation and microcysts (table 1) [4, 11]. Following the WBCS, most parameters were scored from 0 to 3 as compared to standard

56

Ophthalmologica 2011;225:55–60

photographs [11]. The presence of microcysts was scored from 0 to 3 according to thirds of bleb area bearing microcysts, and bleb height was estimated as multiples of corneal thickness. The total bleb score was calculated as the sum of the scores of vascularization, corkscrew vessels, encapsulation and microcysts. The classification of the bleb morphology was performed under supervision of a glaucoma specialist.

Surgery Four eyes underwent fornix-based trabeculectomy without antimetabolites and 109 underwent surgery with antimetabolites (17 eyes 5-fluorouracil, 5-FU, 50 mg/ml, 57 eyes mitomycin C 0.1 mg/ml, 34 eyes mitomycin C 0.2 mg/ml and 1 eye mitomycin C 0.5 mg/ml) under general anaesthesia. 5-FU and mitomycin C 0.1 mg/ml were chosen when there were no risk factors for scarring, mitomycin C 0.2 mg/ml was used when there were risk factors like allergies to topical treatment or previous surgery, and mitomycin C 0.5 mg/ml was applied when the eye had had previous surgery involving the conjunctiva combined with massive early bleb scarring.

Postoperative Treatment Postoperative topical medication consisted of prednisolone acetate 1% 6 times per day that was tapered off during at least 4 weeks and gentamicin 3 times per day for 5 days. Topical steroids were increased when postoperative bleb assessment revealed corkscrew vessels or increased vascularization. If signs of encapsulation appeared, according to the WBCS 5-FU was injected subconjunctivally [4, 8, 12]. The regimen was equal for all patients, independently of the individual risk of scarring. All patients were kept as inpatients for 10–14 days postoperatively. After discharge the follow-up intervals were twice weekly (1 visit at the Glaucoma Service of the University Eye Hospital Wuerzburg and 1 visit at the referring ophthalmologist in the same week). The patients were seen weekly for at least 4 weeks postoperatively. If increased scarring occurred, the follow-up was extended individually.

Success Criteria Complete success was defined as a 20% pressure reduction with reference to the treated IOP level (mean of 3 values) and an upper limit of IOP ^21 mm Hg without glaucoma medication after 1 year of follow-up (European Glaucoma Society Guidelines, www.eugs.org/eng/EGS_guidelines.asp). Qualified success used the same criteria allowing for glaucoma medication.

Statistical Analysis Statistical analysis was performed using Excel for Windows (Microsoft, USA) and MEDAS (Grund EDV, Margetshoechheim, Germany). p values of !0.05 were considered statistically significant.

Results

Demographic Data The study included 113 eyes of 113 patients (45 females and 68 males) at a mean age of 62.6 8 11.3 years. 79 patients (69.91%) suffered from primary open-angle glauKlink/Kann/Ellinger/Klink/Grehn/ Guthoff

Previous Surgery 58 patients had no previous surgery, 40 patients had one, 12 two, 1 three, 1 four and 1 five previous interventions. Most frequently an argon laser trabeculoplasty had been performed prior to trabeculectomy (38 eyes). Other previous surgeries were: 9 filtering procedures, 8 cyclodestructive procedures, 4 needling or revision of the bleb, 3 non-penetrating surgeries and 13 previous cataract surgeries.

Postoperative Antimetabolites 35.4% (40) of the eyes were not treated with 5-FU during follow-up. 5-FU injections were given starting in 39.8% (45) eyes during the first week postoperatively, in 14.2% (16) during the second week, in 8.9% (10) after 1 month, in 0.9% (1) after 3 months and in 0.9% (1) after 1 year. The mean number of 5-FU injections during followup was 6.5 8 4.6 (range 0–21). The patients who were treated with 5-FU after 1 week were significantly younger (59.5 years) than those who were not (64.4 years; p = 0.0072).

Medication Pre-operatively, the mean number of compounds (topical medication) of all 113 eyes was 1.95 8 1.14. Thirtytwo patients received additional pre-operative systemic medication for IOP lowering (acetazolamide). One year after trabeculectomy, 6 patients were treated with topical medication (1 substance each), and none of the patients needed systemic medication. The mean topical medication of all eyes (71) decreased to 0.08 8 0.26 after 1 year.

Intra-Ocular Pressure The mean pre-operative IOP of all eyes (113) was 23.88 8 7.77 mm Hg, and the mean maximum IOP according to chart history was 35.21 8 10.69 mm Hg. The mean IOP at the end of follow-up in all 113 eyes was 12.43 8 4.29 mm Hg. After 12 months the mean IOP was 12.4 8 4.4 mm Hg in the 71 eyes that completed the 1-year follow-up. Four patients had an IOP of 5 mm Hg and 2 patients had an IOP below 5 mm Hg after 12 months. Compared to the pre-operative and maximum IOP, the reduction of IOP was 43 and 61.8%, respectively.

Prognostic Value of the WBCS in Trabeculectomy

n = 109

Score of single parameter

coma, 30 patients (26.55%) had secondary open-angle glaucoma and 4 (3.54%) had chronic angle closure glaucoma. The mean follow-up was 444.2 8 382.6 days (median 361 days) for all eyes (113) and 359.5 8 78.1 days (median 340 days) for 71 eyes of patients that completed the 1-year follow-up.

111

109

104

97

73

71

3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8

Corkscrew vessels Encapsulation Microcysts Vascularization 1 day

1 week

2 weeks

1 3 6 12 month months months months Follow-up

Fig. 1. Development of the single bleb parameters vascularity,

corkscrew vessels, microcysts and encapsulation during followup for all patients.

Outcome after 12 Months 51 (71.8%) of the patients who completed the 1-year follow-up achieved complete success (patients fulfilled success criteria without medication) and 57 (80.3%) were classified as qualified success (patients fulfilled success criteria with or without medication). In 14 (19.7%) patients, the success criteria were not achievable. The complete success for all 113 eyes was 84 (74.3%), 93 (82.3%) achieved qualified success and 20 (17.7%) failed to reach the success criteria.

Bleb Classification (WBCS) The total bleb score increased (all eyes) from 7.6 8 1.3 (first postoperative day) to 9.6 8 1.3 (after 1 year). Figure 1 shows the development of the 4 single parameters (vascularization, corkscrew vessels, microcysts and encapsulation) during follow-up. All parameters showed a significant change over time (p ! 0.000005). The bleb height did not show a significant difference between the early phase (1–2 weeks) and 12 months after surgery (p = 0.91) and between the complete success and the failure group (p = 0.27), respectively. There was no significant correlation between bleb score (total or single parameters) and age, diagnosis, maximum IOP, pre-operative IOP, previous surgery and number of pre-operative medications, after 12 months. Patients who received mitomycin C intra-operatively had a significantly lower total bleb score Ophthalmologica 2011;225:55–60

57

n=

81 28

84 27

82 27

77 26

76 21

56 17

48 22

n=

56 53

55 56

55 54

50 53

46 51

37 36

36 34

10.5 10.0 10.0 Total bleb score

Total bleb score

9.5 9.0 8.5 8.0 7.5 Complete success Failure

7.0 1 day

1 week

2 weeks

1 3 6 12 month months months months Follow-up

9.5 9.0 8.5 8.0 7.5

IOP ≤12 mm Hg IOP ≥13 mm Hg

7.0 1 day

1 week

2 weeks

1 3 6 12 month months months months Follow-up

Fig. 2. Complete success and development of bleb score after trabeculectomy. Mean values and standard deviation.

Fig. 3. IOP ^12 mm Hg at last follow-up and development of total

after 1 week (p = 0.019; significantly more vascularization and corkscrew vessels), as compared to patients who received 5-FU during trabeculectomy. During further follow-up, no significant difference between the two types of antimetabolites was detectable.

According to the WBCS, the patients who had a significantly lower total bleb score after 1 week (significantly more vascularization and corkscrew vessels), had 5-FU treatment postoperatively (p = 0.00064).

For evaluation of the prognostic value of the WBCS, the correlation between the bleb score (total bleb score and single parameters) and the surgical outcome (complete and qualified success) and different postoperative IOP levels, respectively, were analysed. The total bleb score after 1 week was 7.3 8 1.7 (84), after 2 weeks 7.9 8 1.7 (82), after 1 month 8.6 8 1.9 (77), after 3 months 9.4 8 1.9 (76), after 6 months 10.1 8 1.5 (56) and after 1 year 9.8 8 1.3 (48) in the success group and 7.1 8 1.1 (27), 7.2 8 1.6 (27), 8.3 8 2.1 (26), 9.0 8 1.8 (21), 9.9 8 1.6 (17) and 9.3 8 1.4 (21) in the failure group, respectively (fig. 2).

The values for the complete success group were higher than in the failure group at every follow-up. However, there was no statistically significant difference of the total bleb score between the two groups at any time. Evaluation of the single parameters for the complete success group showed a significantly higher score for vascularization after 1 week (p = 0.02) and for encapsulation after 2 weeks (p = 0.007). The bleb score for eyes with an IOP of ^12

mm Hg after 2 weeks (n = 54, bleb score = 8.1 8 1.5) was significantly higher (p = 0.005) than for eyes with an IOP 613 mm Hg (n = 55, bleb score = 7.3 8 1.7) at the end of follow-up (fig. 3). The analysis of the single parameters showed a weakly significant difference after 2 weeks for microcysts (p = 0.03) and encapsulation (p = 0.046). At all other time points, no significant difference was revealed.

58

Ophthalmologica 2011;225:55–60

bleb score. Mean values and standard deviation.

Discussion

Several risk factors for failure of trabeculectomy are known [13, 14], which may help to estimate the outcome prior to surgery. If there are few or no risk factors, it is difficult to give an individual prognosis for postoperative success. For these cases it would be helpful to have predictive factors in the early phase (approx. first 4 weeks) after surgery. One possibility is to use IOP as a predictive factor in the first month after trabeculectomy [15]. Bleb morphology is aimed at a more individual prognosis and allows for specific measures against bleb scarring. Sacu et al. [2] showed that corkscrew vessels and microcysts can help to predict the IOP development. Smith et al. [16] found a correlation between bleb height and IOP after phacotrabeculectomy. The purpose of this retrospective study was to evaluate the prognostic value of the early postoperative WBCS for the long-term outcome of trabeculectomy.

Klink/Kann/Ellinger/Klink/Grehn/ Guthoff

The baseline characteristics, the use of intra-operative antimetabolites, the frequency of postoperative 5-FU application, IOP, medication and outcome after 12 months of our study were similar to other studies [2, 17, 18]. The total bleb score increased continuously during follow-up as did the parameters vascularity, corkscrew vessels and microcysts. This can be explained by the natural course of conjunctival wound healing [7, 12]. The decrease in the encapsulation score might, however, be due to a slow long-term scarring process, resulting in an increase in non-functioning blebs. In an earlier study [7], a low total bleb score was found in blebs with increased scarring. In our present study patients with a high risk for bleb scarring (receiving mitomycin C) or intense postoperative scarring reaction (5-FU postoperatively) had a significantly lower total bleb score in the first week after trabeculectomy. According to the natural course of wound healing, the vascular reaction is more pronounced in those filtering blebs. After 12 months no statistically significant difference was found. When we looked for a correlation of the total bleb score and the outcome of the surgery, the complete success group was above the failure group during the complete follow-up, but there was no difference of statistical significance. There might be two explanations for the marginal difference between the two groups. One is that the WBCS is not of prognostic value for the long-term results after trabeculectomy. Another reason might be the close and intensive follow-up, leading to prompt treatment adaptation when the bleb morphology changed. According to the postoperative treatment regimen (intensified postoperative care) with close follow-up of the patients, the second explanation is more

likely. It has to be re-evaluated in a prospective randomized trial. The single parameters vascularization and encapsulation showed a significant difference in the early phase (first 2 weeks). A low score in the early postoperative phase for these parameters (vascularization !1, encapsulation !2) might show a tendency for long-term failure of trabeculectomy. In addition, the early WBCS seems to be useful for estimating the IOP 1 year after surgery.

Patients with a higher bleb score (total bleb score 18.0) 2 weeks postoperatively had a significantly lower IOP (!12 mm Hg) 1 year after surgery. A total bleb score of less than 7.0 in the first 2 weeks postoperatively (fig. 2) seems to be associated with a higher long-term IOP. Regarding the single parameters, the blebs of patients with a lower long-term IOP had significantly more microcysts and less encapsulation 2 weeks after surgery. Similar to the study of Sacu et al. [2], we found that microcysts were associated with a low long-term IOP. Concerning corkscrew vessels (no significant correlation) and encapsulation (significantly less in patients with low long-term IOP), our findings were different from those of Sacu et al. Compared to the findings of Smith et al. [16], we could not find a correlation between bleb height and complete success or IOP. The WBCS can be implemented as a quick tool for daily clinical practice and is likewise useful in clinical trials [7, 8]. It may have a predictive value for IOP development in the early postoperative course after filtering surgery. However, the study could not reveal any prognostic value of the early total bleb score using the WBCS for the long-term complete success of trabeculectomy.

References 1 Marquardt D, Lieb WE, Grehn F: Intensified postoperative care versus conventional follow-up: a retrospective long-term analysis of 177 trabeculectomies. Graefes Arch Clin Exp Ophthalmol 2004;242:106–113.

2 Sacu S, Rainer G, Findl O, Georgopoulos M, Vass C: Correlation between the early morphological appearance of filtering blebs and outcome of trabeculectomy with mitomycin C. J Glaucoma 2003;12:430–435.

3 Cantor LB, Mantravadi A, Wu Dunn D, Swamynathan K, Cortes A: Morphologic classification of filtering blebs after glaucoma filtration surgery: the Indiana Bleb Appearance Grading Scale. J Glaucoma 2003;12:266–271.

Prognostic Value of the WBCS in Trabeculectomy

4 Picht G, Grehn F: Classification of filtering blebs in trabeculectomy: biomicroscopy and functionality. Curr Opin Ophthalmol 1998; 9:2–8.

5 Wells AP, Ashraff NN, Hall RC, Purdie G: Comparison of two clinical bleb grading systems. Ophthalmology 2006;113:77–83.

6 Wells AP, Crowston JG, Marks J, Kirwan JF, Smith G, Clarke JC, Shah R, Vieira J, Bunce C, Murdoch I, Khaw PT: A pilot study of a system for grading of drainage blebs after glaucoma surgery. J Glaucoma 2004;13:454– 460.

7 Guthoff R, Klink T, Schlunck G, Grehn F: In vivo confocal microscopy of failing and functioning filtering blebs: results and clinical correlations. J Glaucoma 2006; 15: 552– 558.

8 Klink J, Schmitz B, Lieb WE, Klink T, Grein HJ, Sold-Darseff J, Heinold A, Grehn F: Filtering bleb function after clear cornea phacoemulsification: a prospective study. Br J Ophthalmol 2005;89:597–601.

9 Picht G, Welge-Luessen U, Grehn F, LutjenDrecoll E: Transforming growth factor beta 2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development. Graefes Arch Clin Exp Ophthalmol 2001;239:199–207.

10 Wimmer I, Welge-Luessen U, Picht G, Grehn F: Influence of argon laser trabeculoplasty on transforming growth factor-beta 2 concentration and bleb scarring following trabeculectomy. Graefes Arch Clin Exp Ophthalmol 2003; 241:631–636.

Ophthalmologica 2011;225:55–60

59

11 Klink T, Schrey S, Elsesser U, Klink J, Schlunck G, Grehn F: Interobserver variability of the Wuerzburg Bleb Classification Score. Ophthalmologica 2008;222:408–413.

12 Klink T, Guthoff R, Grehn F, Schlunck G: Postoperative care after glaucoma filtration surgery. Ophthalmologe 2006; 103: 815–823, quiz 824–815.

13 The Advanced Glaucoma Intervention Study (AGIS). 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Am J Ophthalmol 2002;134:481–498.

60

14 Broadway DC, Chang LP: Trabeculectomy, risk factors for failure and the preoperative state of the conjunctiva. J Glaucoma 2001;10: 237–249.

15 Alwitry A, Moodie J, Rotchford A, Abedin A, Patel V, King AJ: Predictive value of early IOP in mitomycin-C augmented trabeculectomy. J Glaucoma 2007;16:616–621.

16 Smith M, Chipman ML, Trope GE, Buys YM: Correlation between the Indiana Bleb Appearance Grading Scale and intraocular pressure after phacotrabeculectomy. J Glaucoma 2009;18:217–219.

Ophthalmologica 2011;225:55–60

17 Klink T, Rauch N, Klink J, Grehn F: Influence of conjunctival suture removal on the outcome of trabeculectomy. Ophthalmologica 2009;223:116–123.

18 Mutsch YA, Grehn F: Success criteria and success rates in trabeculectomy with and without intraoperative antimetabolites using intensified postoperative care (IPC).

Graefes Arch Clin Exp Ophthalmol 2000; 238:884–891.

Klink/Kann/Ellinger/Klink/Grehn/ Guthoff

Copyright: S. Karger AG, Basel 2010. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.