Seminars in Ophthalmology
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface Rajen Tailor, Ruchika Batra & Shabbir Mohamed To cite this article: Rajen Tailor, Ruchika Batra & Shabbir Mohamed (2014): A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.986585 To link to this article: http://dx.doi.org/10.3109/08820538.2014.986585
Published online: 09 Dec 2014.
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Date: 06 November 2015, At: 01:03
Seminars in Ophthalmology, Early Online, 1–7, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.986585
ORIGINAL ARTICLE
A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface* Rajen Tailor, Ruchika Batra, and Shabbir Mohamed
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Department of Ophthalmology, University Hospitals, Birmingham, UK
ABSTRACT Background: Preserved anti-glaucoma drops cause ocular surface disease (OSD), which is increasingly being recognized as a likely cause of trabeculectomy failure. Aim: To determine the routine pre-trabeculectomy management of the ocular surface by glaucoma specialists. Methods: A questionnaire consisting of 11 questions was posted to 146 UK glaucoma specialists. Results: The first-time response rate was 43.8%. Regarding routine pre-operative management, 40.6% of specialists use preservative-free drops, 29.7% commence a drop holiday, and 53% advise lid hygiene. 42.1% prescribe lubricants, 50% prescribe topical steroids, 7.8% topical NSAIDs, and 34.4% systemic tetracyclines. 84.4% of specialists change their routine management if OSD is present. Preoperative optimization of the ocular surface is viewed ‘‘necessary’’ by 48.4% and ‘‘beneficial’’ by 85.9%. Conclusion: A wide variation exists in the routine pre-operative management of the ocular surface. Research to determine the impact of different pre-operative interventions upon trabeculectomy outcomes is required. Keywords: Glaucoma, ocular surface disease, ocular surface inflammation, preservative, trabeculectomy
INTRODUCTION
information is based on short-term studies on selected groups of patients, and patients with pre-existing OSD are usually excluded from these studies. We do know, however, that non-selective beta blockers may cause hyperaemia, decreased ocular blood flow, decreased corneal sensation, and a significant reduction in the tear break-up time.4–6 Alpha–agonists, carbonic anhydrase inhibitors, and prostaglandin analogues cause hyperaemia and conjunctival inflammation. In our experience, prostaglandins tend to have a significant effect on Meibomian gland function with subsequent ocular surface inflammation. Prostaglandins are also known to cause peri-orbital fat atrophy as well as lid changes that can become significant. Impression cytology studies have demonstrated various degrees of squamous cell metaplasia and decreased goblet cell density with all four groups of glaucoma medications described. Surprisingly, the studies demonstrated no
The term ‘‘ocular surface disease’’ (OSD) encompasses dry eye, lid disease, conjunctivitis, and keratitis. OSD is highly prevalent in patients with glaucoma and ocular hypertension, with 59% of patients reporting symptoms in at least one eye and 65% of patients having a severe decrease in tear quality in at least one eye.1 It is recognized that the condition is exacerbated by topical anti-glaucoma medications.2 This has been attributed primarily to the use of benzalkonium chloride (BAK), the common preservative in such medications.3 The various classes of glaucoma medications and the individual formulation have different effects on the ocular surface, but the information on the ocular surface effects of glaucoma medications is far from comprehensive. Much of the pre-marketing
Received 18 March 2014; revised 29 September 2014; accepted 3 November 2014; published online 9 December 2014 *Research from this article was presented at the following meetings: 6th International Congress on Glaucoma Surgery, Glasgow, September 2012; Midlands Ophthalmological Society Meeting, October 2012—awarded prize for the ‘‘Best Poster Presentation.’’ Correspondence: Ruchika Batra, Speciality Registrar in Ophthalmology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, West Midlands, UK. E-mail: [email protected]
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statistically significant difference in the impression cytology scores between different groups of medications.6 For all topical glaucoma treatments, the preservatives as well as the individual formulation of buffers and stabilizers in combination with the active agent appear to be significant contributing factors in the development of OSD.6 As these agents are used for long periods, the cumulative effects on the ocular surface over time are also a significant consideration in treating these patients. OSD is increasingly being recognized as a likely cause of trabeculectomy failure in patients with glaucoma. Furthermore, as the number of pre-operative topical anti-glaucoma medications increases, the success rate of trabeculectomy surgery has been found to decrease.7 A higher rate of inflammatory cell infiltrates and fibroblasts has been found in conjunctival and trabecular tissue samples from patients undergoing trabeculectomy who have been exposed to multiple preserved glaucoma medications compared with patients exposed to monotherapy.8 Breusegem et al. found that the pre-operative use of a topical steroid or a topical non-steroidal anti-inflammatory (NSAID) drug reduced the need for post-operative bleb needling. They also reported a significantly reduced need for additional post-operative intraocular pressure (IOP) lowering medication in patients receiving topical steroid for one month prior to surgery.9 In light of the emerging importance of OSD as a possible risk factor for trabeculectomy failure and evidence that pre-operative optimization reduces post-operative interventions, we undertook a national (United Kingdom) survey of glaucoma specialists to determine current practice regarding the routine pre-trabeculectomy management of the ocular surface. To our knowledge, this is the first survey on this subject.
by the RCOphth. The names and addresses were obtained from the RCOphth database. A total of 146 questionnaires were posted. Figure 1 is the questionnaire distributed nationally and comprises three main questions with several stems. The first question was to determine the grade of the clinicians who routinely list the patients for trabeculectomy surgery. The second question included multiple components to assess whether specialists take any pre-operative steps to routinely assess and optimize the ocular surface; examine the ocular surface; use preservative-free (PF) intraocular pressure (IOP) lowering drops; commence a drop holiday and, if so, the duration of this; advise lid hygiene for blepharitis; prescribe ocular lubricants, topical steroids, topical NSAID, or oral doxycycline. If any of the latter medications were prescribed, further questions were asked to determine their name, frequency, and dose as appropriate. The next stem of this question was to ascertain if routine management is altered when signs of OSD are present and how this is done. The final question was to determine if the respondents felt that pre-operative optimization of the ocular surface was necessary or beneficial. Replies were collected over three months. Anonymity of all respondents was maintained. Reponses were tabulated into a Microsoft Excel spreadsheet. This study was reviewed by the internal review board, who deemed that ethical approval was not required. The main outcome measures were the percentage of respondents who gave consideration to the ocular surface when listing patients for trabeculectomy surgery and examine it routinely as part of the preoperative assessment, the percentage who replace the existing glaucoma drops with preservative-free preparations, and the percentage who prescribe one or more appropriate treatments for OSD.
MATERIALS AND METHODS
RESULTS
A pilot study was initially undertaken. A doublesided postal sample questionnaire regarding the routine preoperative (pre-trabeculectomy) management of the ocular surface was sent to five consultant ophthalmologists with a special interest in glaucoma in the United Kingdom National Health Service. The questionnaire was distributed with a cover letter and a self-addressed, pre-paid envelope. Following this pilot study, a few modifications were made to the questionnaire before it was posted to all UK consultant glaucoma specialists. The survey was limited to consultant members of the Royal College of Ophthalmologists (RCOphth) who had self-declared that they were glaucoma subspecialists. These are fully trained independent practitioners who are recognized as meeting national standards set
The response rate from UK glaucoma specialists was 43.8% (n = 64). No further reminders or questionnaires were sent. When assessing a patient preoperatively, 95.3% of specialists stated they would routinely examine the ocular surface. With respect to the routine pre-operative management of the ocular surface (Figure 2), 40.6% of specialists would replace existing glaucoma drops with preservative-free drops (6.2% routinely, 34.4% only if there was clinical evidence of conjunctival inflammation or of allergy or intolerance); 29.7% would commence a drop holiday (1.6% routinely and 28.1% only if there was significant OSD); 53% would advise lid hygiene (21.9% routinely and 31.2% if there were signs of blepharitis). Seminars in Ophthalmology
Survey of Management of Ocular Surface 1.
Which members of your team lists patients for trabeculectomy (please tick)? Only listed by consultant
Staff/Assoc Specialist Doctors
Glaucoma fellow
Others (Please specify)
Trainee (Specify Grade) 2.
As part of your routine pre-trabeculectomy management do you (please tick):
a)
Examine the ocular surface?
b)
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c)
Yes
No
Sometimes
- under what circumstances?
Replace existing glaucoma drops with preservative-free preparations? Yes
No
Sometimes
- under what circumstances?
Commence a drop holiday? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, for how long? d)
Advise daily lid hygiene? Yes
No
Sometimes e)
- under what circumstances?
Prescribe ocular lubricants? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which lubricants and frequency? Lubricant______________________ f)
Frequency ________times per day
Prescribe topical steroids? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which steroids and frequency? Steroid______________________
preserved / non-preserved (please delete)
Frequency ________times per day
g)
Prescribe topical NSAIDs? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which NSAID and frequency? NSAID______________________ h)
Frequency ___________ times per day
Prescribe oral doxycycline? Yes Sometimes
No - under what circumstances?
If yes/sometimes, which dose and for how long? _________mg i)
Pre-operatively if there are signs of ocular surface disease (e.g. meibomian gland dysfunction, atopy etc), would your pre-operative management change? Yes
3.
_______weeks/months (delete as appropriate)
No
If yes, how would it change?
Do you feel that pre-operative optimisation of the ocular surface in patients undergoing trabeculectomy is a. Necessary Yes/No b.
Beneficial
Yes/No
Thank you for your time.
FIGURE 1. Trabeculectomy and ocular surface questionnaire.
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Percentage of respondents
50.0%
40.0%
30.0%
20.0%
10.0%
0.0% Preservative Drop holiday Lid hygiene Lubricants Topical free glaucoma steroids drops Intervention to manage the ocular surface
Topical NSAID
Doxycyccline
FIGURE 2. Percentage of respondents using each of the pre-operative interventions to manage the ocular surface, both routinely and in the presence of ocular surface disease.
With regards to the use of lubricants, 42.1% would prescribe lubricants (10.9% routinely, 31.2% if there were signs and/or symptoms of dry eyes). Lubricants stated in order of decreasing frequency included: carmellose sodium (Celluvisc, Allergan, CA, USA), hyaluronic acid, carmellose sodium and glycerol (Optive, Allergan, CA, USA), and polyethylene and propylene glycol (Systane, Alcon, TX, USA). The frequency of administration ranged from four to eight times a day. With regards to the preoperative use of antiinflammatory treatment, 7.8% would prescribe topical NSAID (1.6% routinely, 6.2% only if a patient was a known steroid responder) and 50% of specialists would prescribe topical steroids (10.9% routinely, 39.1% if there were signs of blepharoconjunctivitis, conjunctival inflammation, or a history of uveitis or previous failed trabeculectomy). The commonest topical steroids prescribed in decreasing frequency of use were: dexamethasone (44.4%, of which 75% of specialists would prescribe PF dexamethasone and 25% would prescribe preserved dexamethasone), PF prednisolone (29.6%), fluorometholone (FML, 18.5%), prednisolone acetate 1% (3.7%), and betnesol (3.7%). The vast majority of specialists would prescribe topical steroids four times a day (70.3%), with a smaller number (22.2%) preferring to prescribe three times a day. The commonest prescribed NSAIDs were ketorolac and preserved and PF diclofenac.
Systemic tetracycline use (doxycycline) varied amongst specialists (34.4%). Of these, 3.2% would routinely prescribe a tetracycline and 31.2% only if a patient had blepharitis. The duration of treatment ranged from 2 to 12 weeks, with the majority of specialists prescribing the treatment for two to eight weeks (52%). The dose of doxycycline ranged from 50–100 mg per day, with the duration ranging from four weeks pre-operatively to 12 weeks postoperatively. A total of 65.6% (N = 42) of respondents did not use any of the mentioned pre-operative interventions routinely. A total of 23.4% (N = 15) respondents used at least one form of treatment routinely and 34.6% used one or more forms of treatment routinely. A total of 7 (10.9%) respondents combined two or more treatments (Figure 3). Pre-operatively, if there were signs of OSD, 84.4% of specialists expressed that they would change their routine management, with the majority simply stating that they would ‘‘treat the OSD’’. Only 14 respondents (33%) expressed specific management strategies. These comprised primarily using lid hygiene (11/14 respondents) combined with either PF anti-glaucoma drops or lubricants. The use of topical steroids, doxycycline, and a drop holiday were suggested by three separate respondents. Pre-operative optimization of the ocular surface was seen as ‘‘necessary’’ by 48.4% of specialists and ‘‘beneficial’’ by 85.9% of specialists. Seminars in Ophthalmology
Survey of Management of Ocular Surface No. of treatment combinations used
No. of respondents using combinations
5
Combinations used (number of respondents)
2
3
hygiene & lubricants (2) hygiene & topical steroids (1)
3
2
Preservative free(PF) drops, hygiene & lubricants (1) Hygiene, lubricants & topical steroids (1)
4
2
PF drops, hygiene, lubricants and topical steroids (1) PF drops, hygiene, topical steroids and NSAID’s (1)
FIGURE 3. Number of respondents using two or more combinations of interventions to routinely treat the ocular surface pre-operatively.
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DISCUSSION Our survey demonstrates a wide variation in strategies for the pre-operative optimization of the ocular surface amongst glaucoma specialists in the UK. The majority of specialists expressed that they routinely examined the ocular surface pre-operatively and, if there were signs of OSD, they would change their management. Furthermore, the majority of specialists expressed pre-operative optimization of the ocular surface to be beneficial. However, less than 50% believed it was necessary. The interventions used to optimize the ocular surface varied considerably amongst specialists, with the majority only implementing interventions if there were signs of OSD or in the case of topical steroids, a previous history of uveitis, or failed trabeculectomy. Ocular surface disease (OSD) is common amongst patient with glaucoma1 and the prevalence of symptomatic OSD has been shown to increase with the duration of treatment and the number of anti-glaucoma drops.10 It is now well-established that preservatives (of which BAK has been most widely studied) cause inflammation of the conjunctiva and tenon’s capsule. Indeed, histological studies have demonstrated that the conjunctiva and tenon’s capsule of patients treated with BAK containing anti-glaucoma drops has an increased number of macrophages, lymphocytes, mast cells, and fibroblasts and a significant decrease in the number of epithelial goblet cells.11,12 This evidence is supported by immunological studies using conjunctival impression cytology and conjunctival biopsies in patients treated with preserved anti-glaucoma drops, where there was an increased expression of proinflammatory markers: HLA-DR antigens (one of the main inflammatory markers of the conjunctiva); adhesion molecules (ICAM-1 and 3 and beta-2 integrins); CD45RO (membrane phosphatase expressed by immune cells); CD23 (low affinity IgE receptor).8,13 Furthermore, the overexpression of HLA-DR and CD23 has also been demonstrated in patients treated with preserved anti-glaucoma drops with no signs of ocular surface disease. By contrast, HLA-DR expression was not significantly increased in !
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patients receiving PF timolol compared to healthy controls.14 Studies have shown that reducing the BAK load resulted in an improvement in the signs and symptoms of OSD, a reduction in IOP, a reduction in the expression of conjunctival inflammatory markers, and an increase in MUC5AC production (a mucin produced by human conjunctival goblet cells).15,16 Hence, it appears that some of the effects of BAK on the human conjunctiva are reversible. Furthermore, our group (Batra et al.),17 in a retrospective case series, demonstrated that interventions to improve the ocular surface (lid hygiene, PF lubricants, doxycycline, and PF anti-glaucoma drops where appropriate) resulted in a significant and sustained reduction in the IOP. The authors proposed a spiralling disease process whereby preserved antiglaucoma drops induced OSD, which in turn resulted in aqueous outflow resistance, which resulted in an increase in the IOP. By treatment of the OSD, this spiralling process could be interrupted and partially reversed. This process was termed ‘‘OSD exacerbated glaucoma’’. The long-term use of topical anti-glaucoma medications causes ocular surface disease with overexpression of inflammatory markers and a predisposition to scarring. The latter effect can compromise trabeculectomy surgery.7 Broadway et al.12 reported a success rate of 90% in patients who had undergone a primary trabeculectomy, 93% in patients treated with a single anti-glaucoma drop (B blocker), 72% in patients taking two drops, and 45% in patients on three drops. In addition, the success rate was significantly lower in the patients treated with topical anti-glaucoma drops for more than three years (55%) compared to those patients treated for less than three years (94% p50.001). A retrospective study by Lavin et al.18 showed that patients who underwent a primary trabeculectomy had a higher success rate (97.9%) compared to patients who had been treated with antiglaucoma drops for at least 12 months prior to surgery (79.1%, p50.001). These studies suggest that the duration and number of anti-glaucoma treatments are directly linked to the success of trabeculectomy.
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To date, there is only one publication on the preoperative treatment of the ocular surface. In a prospective, randomized, double-blinded placebo control trial comparing pre-operative (trabeculectomy) treatment of the ocular surface for one month prior with either artificial tears, a NSAID (Aculare), or a topical steroid (fluorometholone, FML 0.1%), Breusegem et al.9 showed a 35% and 36% reduction in the incidence of needling in the NSAID and topical steroid treated group, respectively, at 12 months compared to the placebo group (p = 0.006), and a significant reduction in the need for IOP-lowering medication to achieve a target IOP in the steroid-treated group. There was no difference in the success rate of trabeculectomy at 12 months. Despite the evidence, our survey suggests that only a minority of specialists prescribe topical NSAIDs or steroids preoperatively. The objective of this survey was to determine current practice on pre-operative management of the ocular surface. The findings highlight that the majority of glaucoma specialists regard pre-operative examination of the ocular surface as necessary and optimization as beneficial. However, there appears to be significant variation in the interventions used to optimize the ocular surface pre-operatively. The latter may partly explain the wide variation in surgical outcomes following trabeculectomy. Further research in this area is warranted to determine how these different interventions might be beneficial and which interventions are optimal in this setting. In our practice, we routinely examine and optimize the ocular surface using many of the stated interventions, depending on the needs of the individual patient. We have found this approach beneficial in terms of surgical outcomes following trabeculectomy and would recommend it for all cases. In our practice, prostaglandin agonists are discontinued and topical steroids are prescribed for all patients one month prior to surgery. It is important to individualize treatment for each patient. Treatment is dependent on continuity of care, with ideally the same clinician monitoring the ocular surface. In patients with mild OSD, preservative-free lubricants such as Carmellose sodium are prescribed 4–6 times per day, twice-daily lid hygiene is taught, topical treatments are changed to preservative-free alternatives, and doxycycline 50 mg OD for three months is prescribed. The management of moderate OSD is as for mild OSD; however, with the addition of a discussion about nutrition accompanied by blood tests for nutritional deficiencies which may impact upon ocular surface health, such as full blood count, urea and electrolytes, vitamin B12 and folate levels, and vitamin D and calcium levels. Deficiencies can therefore be treated as appropriate. The management of severe ocular surface disease includes the above with the addition of an autoimmune screen. All of these patients are referred
to a cornea specialist for the management of their ocular surface and possibly to a general physician if the autoimmune screen highlights any abnormalities. The principal limitations of this survey are that the response rate was low, the responses may not reflect true clinical practice, and the respondents are likely to be a self-selected group of specialists with an interest in ocular surface disease. In retrospect, we feel it may have been useful to send a reminder letter in order to try and increase the response rate. Furthermore, as the number of respondents using combination treatments was small, we were unable to determine any patterns of routine pre-operative interventions. Due to constraints on the size of the questionnaire, the section about whether the pre-operative optimization of the ocular surface was (1) necessary of (2) beneficial comprised two closed questions only (requesting either yes or no answers in both instances). Further elaboration was not sought and therefore we cannot deduce whether the groups in favor of pre-operative optimization treated the OSD more aggressively. This survey nevertheless highlights the wide variations in interventions used to optimize the ocular surface pre-operatively, even amongst these motivated specialists. There is significant evidence in the literature that suggests that topical anti-glaucoma drops cause ocular surface disease, which may or may not be clinically evident. Furthermore, the longer patients are on topical treatment, the lower the risk of success following a trabeculectomy. The question then arises: Can we modify the pre-operative management of our patients to improve the outcome of trabeculectomy? To date, only one well-constructed, randomized control trial has shown that use of pre-operative topical steroids and NSAIDs significantly reduces the postoperative needling rate and the use of topical steroids reduces the need for topical glaucoma therapy to achieve target IOP.9 To increase awareness and uptake of pre-operative management strategies, a randomized control trial using pre-operative interventions to treat the ocular surface is required.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors have received no funding for this work, and they alone are responsible for the content and writing of the paper.
REFERENCES 1. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma 2008;17: 350–355. Seminars in Ophthalmology
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Survey of Management of Ocular Surface 2. Chang L, Crowston JG, Cordeiro MF, et al. The role of the immune system in conjunctival wound healing after glaucoma surgery. Surv Ophthalmol 2000;45:49–68. 3. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol 2002;86:418–423. 4. Kuppens EVMJ, de Jong CA, Stolwijk TR, et al. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol 1995;79(4):339–342. 5. Kastelan S, Tomic M, Metez SK, Salopek-Rabatic J. How ocular surface disease impacts the glaucoma treatment outcome. Biomed Res Int 2013 Oct 9. [Epub ahead of print]. 6. Asbell PA, Potapova N. Effects of topical antiglaucoma medications on the ocular surface. Ocul Surf 2005; 3(1):27–40. 7. Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication II. The outcome of filtration surgery. Arch Ophthalmol 1994; 112:1446–1454. 8. Baudouin C, Pisella PJ, Fillacier K, et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: Human and animal studies. Ophthalmol 1999;106: 556–563. 9. Breusegem C, Spielberg L, Van Ginderdeuren R, et al. Preoperative nonsteroidal anti-inflammatory drug or steroid and outcomes after trabeculectomy: A randomized controlled trial. Ophthalmol 2010;117:1324–1330. 10. Garcia-Feijoo J, Sampaolesi JR. A multicenter evaluation of ocular surface disease prevalence in patients with glaucoma. Clin Ophthalmol 2012;6:441–446.
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11. Sherwood MB, Grierson I, Millar L. Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon’s capsule in glaucomatous patients. Ophthalmol 1989; 96:327–335. 12. Broadway DC, Grierson I, O’Brien C. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol 1994;112:1437–1445. 13. Baudouin C, Garcher C, Haouat N, et al. Expression of inflammatory membrane markers by conjunctival cells in chronically treated patients with glaucoma. Ophthalmol 1994;101:454–460. 14. Pisella PJ, Debbasch C, Hamard P, et al. Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: An ex vivo and in vitro study. Invest Ophthalmol Vis Sci 2004;45: 1360–1368. 15. Uusitalo H, Chen E, Pfeiffer N. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol 2010;88: 329–336. 16. Hommer A, Kimmich F. Switching patients from preserved prostaglandin-analog monotherapy to preservative-free tafluprost. Clin Ophthalmol 2011;5:623–631. 17. Batra R, Tailor R, Mohamed S. Ocular surface disease exacerbated glaucoma: Optimizing the ocular surface improves intraocular pressure control. J Glaucoma 2014; 23(1):56–60. 18. Lavin MJ, Wormald RP, Migdal CS, Hitchings RA. The influence of prior therapy on the success of trabeculectomy. Arch Ophthalmol 1990;108:1543–1548.
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface Rajen Tailor, Ruchika Batra & Shabbir Mohamed To cite this article: Rajen Tailor, Ruchika Batra & Shabbir Mohamed (2014): A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.986585 To link to this article: http://dx.doi.org/10.3109/08820538.2014.986585
Published online: 09 Dec 2014.
Submit your article to this journal
Article views: 24
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [University of Pennsylvania]
Date: 06 November 2015, At: 01:03
Seminars in Ophthalmology, Early Online, 1–7, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.986585
ORIGINAL ARTICLE
A National Survey of Glaucoma Specialists on the Preoperative (Trabeculectomy) Management of the Ocular Surface* Rajen Tailor, Ruchika Batra, and Shabbir Mohamed
Downloaded by [University of Pennsylvania] at 01:03 06 November 2015
Department of Ophthalmology, University Hospitals, Birmingham, UK
ABSTRACT Background: Preserved anti-glaucoma drops cause ocular surface disease (OSD), which is increasingly being recognized as a likely cause of trabeculectomy failure. Aim: To determine the routine pre-trabeculectomy management of the ocular surface by glaucoma specialists. Methods: A questionnaire consisting of 11 questions was posted to 146 UK glaucoma specialists. Results: The first-time response rate was 43.8%. Regarding routine pre-operative management, 40.6% of specialists use preservative-free drops, 29.7% commence a drop holiday, and 53% advise lid hygiene. 42.1% prescribe lubricants, 50% prescribe topical steroids, 7.8% topical NSAIDs, and 34.4% systemic tetracyclines. 84.4% of specialists change their routine management if OSD is present. Preoperative optimization of the ocular surface is viewed ‘‘necessary’’ by 48.4% and ‘‘beneficial’’ by 85.9%. Conclusion: A wide variation exists in the routine pre-operative management of the ocular surface. Research to determine the impact of different pre-operative interventions upon trabeculectomy outcomes is required. Keywords: Glaucoma, ocular surface disease, ocular surface inflammation, preservative, trabeculectomy
INTRODUCTION
information is based on short-term studies on selected groups of patients, and patients with pre-existing OSD are usually excluded from these studies. We do know, however, that non-selective beta blockers may cause hyperaemia, decreased ocular blood flow, decreased corneal sensation, and a significant reduction in the tear break-up time.4–6 Alpha–agonists, carbonic anhydrase inhibitors, and prostaglandin analogues cause hyperaemia and conjunctival inflammation. In our experience, prostaglandins tend to have a significant effect on Meibomian gland function with subsequent ocular surface inflammation. Prostaglandins are also known to cause peri-orbital fat atrophy as well as lid changes that can become significant. Impression cytology studies have demonstrated various degrees of squamous cell metaplasia and decreased goblet cell density with all four groups of glaucoma medications described. Surprisingly, the studies demonstrated no
The term ‘‘ocular surface disease’’ (OSD) encompasses dry eye, lid disease, conjunctivitis, and keratitis. OSD is highly prevalent in patients with glaucoma and ocular hypertension, with 59% of patients reporting symptoms in at least one eye and 65% of patients having a severe decrease in tear quality in at least one eye.1 It is recognized that the condition is exacerbated by topical anti-glaucoma medications.2 This has been attributed primarily to the use of benzalkonium chloride (BAK), the common preservative in such medications.3 The various classes of glaucoma medications and the individual formulation have different effects on the ocular surface, but the information on the ocular surface effects of glaucoma medications is far from comprehensive. Much of the pre-marketing
Received 18 March 2014; revised 29 September 2014; accepted 3 November 2014; published online 9 December 2014 *Research from this article was presented at the following meetings: 6th International Congress on Glaucoma Surgery, Glasgow, September 2012; Midlands Ophthalmological Society Meeting, October 2012—awarded prize for the ‘‘Best Poster Presentation.’’ Correspondence: Ruchika Batra, Speciality Registrar in Ophthalmology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, West Midlands, UK. E-mail: [email protected]
1
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statistically significant difference in the impression cytology scores between different groups of medications.6 For all topical glaucoma treatments, the preservatives as well as the individual formulation of buffers and stabilizers in combination with the active agent appear to be significant contributing factors in the development of OSD.6 As these agents are used for long periods, the cumulative effects on the ocular surface over time are also a significant consideration in treating these patients. OSD is increasingly being recognized as a likely cause of trabeculectomy failure in patients with glaucoma. Furthermore, as the number of pre-operative topical anti-glaucoma medications increases, the success rate of trabeculectomy surgery has been found to decrease.7 A higher rate of inflammatory cell infiltrates and fibroblasts has been found in conjunctival and trabecular tissue samples from patients undergoing trabeculectomy who have been exposed to multiple preserved glaucoma medications compared with patients exposed to monotherapy.8 Breusegem et al. found that the pre-operative use of a topical steroid or a topical non-steroidal anti-inflammatory (NSAID) drug reduced the need for post-operative bleb needling. They also reported a significantly reduced need for additional post-operative intraocular pressure (IOP) lowering medication in patients receiving topical steroid for one month prior to surgery.9 In light of the emerging importance of OSD as a possible risk factor for trabeculectomy failure and evidence that pre-operative optimization reduces post-operative interventions, we undertook a national (United Kingdom) survey of glaucoma specialists to determine current practice regarding the routine pre-trabeculectomy management of the ocular surface. To our knowledge, this is the first survey on this subject.
by the RCOphth. The names and addresses were obtained from the RCOphth database. A total of 146 questionnaires were posted. Figure 1 is the questionnaire distributed nationally and comprises three main questions with several stems. The first question was to determine the grade of the clinicians who routinely list the patients for trabeculectomy surgery. The second question included multiple components to assess whether specialists take any pre-operative steps to routinely assess and optimize the ocular surface; examine the ocular surface; use preservative-free (PF) intraocular pressure (IOP) lowering drops; commence a drop holiday and, if so, the duration of this; advise lid hygiene for blepharitis; prescribe ocular lubricants, topical steroids, topical NSAID, or oral doxycycline. If any of the latter medications were prescribed, further questions were asked to determine their name, frequency, and dose as appropriate. The next stem of this question was to ascertain if routine management is altered when signs of OSD are present and how this is done. The final question was to determine if the respondents felt that pre-operative optimization of the ocular surface was necessary or beneficial. Replies were collected over three months. Anonymity of all respondents was maintained. Reponses were tabulated into a Microsoft Excel spreadsheet. This study was reviewed by the internal review board, who deemed that ethical approval was not required. The main outcome measures were the percentage of respondents who gave consideration to the ocular surface when listing patients for trabeculectomy surgery and examine it routinely as part of the preoperative assessment, the percentage who replace the existing glaucoma drops with preservative-free preparations, and the percentage who prescribe one or more appropriate treatments for OSD.
MATERIALS AND METHODS
RESULTS
A pilot study was initially undertaken. A doublesided postal sample questionnaire regarding the routine preoperative (pre-trabeculectomy) management of the ocular surface was sent to five consultant ophthalmologists with a special interest in glaucoma in the United Kingdom National Health Service. The questionnaire was distributed with a cover letter and a self-addressed, pre-paid envelope. Following this pilot study, a few modifications were made to the questionnaire before it was posted to all UK consultant glaucoma specialists. The survey was limited to consultant members of the Royal College of Ophthalmologists (RCOphth) who had self-declared that they were glaucoma subspecialists. These are fully trained independent practitioners who are recognized as meeting national standards set
The response rate from UK glaucoma specialists was 43.8% (n = 64). No further reminders or questionnaires were sent. When assessing a patient preoperatively, 95.3% of specialists stated they would routinely examine the ocular surface. With respect to the routine pre-operative management of the ocular surface (Figure 2), 40.6% of specialists would replace existing glaucoma drops with preservative-free drops (6.2% routinely, 34.4% only if there was clinical evidence of conjunctival inflammation or of allergy or intolerance); 29.7% would commence a drop holiday (1.6% routinely and 28.1% only if there was significant OSD); 53% would advise lid hygiene (21.9% routinely and 31.2% if there were signs of blepharitis). Seminars in Ophthalmology
Survey of Management of Ocular Surface 1.
Which members of your team lists patients for trabeculectomy (please tick)? Only listed by consultant
Staff/Assoc Specialist Doctors
Glaucoma fellow
Others (Please specify)
Trainee (Specify Grade) 2.
As part of your routine pre-trabeculectomy management do you (please tick):
a)
Examine the ocular surface?
b)
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c)
Yes
No
Sometimes
- under what circumstances?
Replace existing glaucoma drops with preservative-free preparations? Yes
No
Sometimes
- under what circumstances?
Commence a drop holiday? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, for how long? d)
Advise daily lid hygiene? Yes
No
Sometimes e)
- under what circumstances?
Prescribe ocular lubricants? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which lubricants and frequency? Lubricant______________________ f)
Frequency ________times per day
Prescribe topical steroids? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which steroids and frequency? Steroid______________________
preserved / non-preserved (please delete)
Frequency ________times per day
g)
Prescribe topical NSAIDs? Yes
No
Sometimes
- under what circumstances?
If yes/sometimes, which NSAID and frequency? NSAID______________________ h)
Frequency ___________ times per day
Prescribe oral doxycycline? Yes Sometimes
No - under what circumstances?
If yes/sometimes, which dose and for how long? _________mg i)
Pre-operatively if there are signs of ocular surface disease (e.g. meibomian gland dysfunction, atopy etc), would your pre-operative management change? Yes
3.
_______weeks/months (delete as appropriate)
No
If yes, how would it change?
Do you feel that pre-operative optimisation of the ocular surface in patients undergoing trabeculectomy is a. Necessary Yes/No b.
Beneficial
Yes/No
Thank you for your time.
FIGURE 1. Trabeculectomy and ocular surface questionnaire.
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R. Tailor et al. 60.0% Only if signs of Ocular Surface Disease Routinely
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Percentage of respondents
50.0%
40.0%
30.0%
20.0%
10.0%
0.0% Preservative Drop holiday Lid hygiene Lubricants Topical free glaucoma steroids drops Intervention to manage the ocular surface
Topical NSAID
Doxycyccline
FIGURE 2. Percentage of respondents using each of the pre-operative interventions to manage the ocular surface, both routinely and in the presence of ocular surface disease.
With regards to the use of lubricants, 42.1% would prescribe lubricants (10.9% routinely, 31.2% if there were signs and/or symptoms of dry eyes). Lubricants stated in order of decreasing frequency included: carmellose sodium (Celluvisc, Allergan, CA, USA), hyaluronic acid, carmellose sodium and glycerol (Optive, Allergan, CA, USA), and polyethylene and propylene glycol (Systane, Alcon, TX, USA). The frequency of administration ranged from four to eight times a day. With regards to the preoperative use of antiinflammatory treatment, 7.8% would prescribe topical NSAID (1.6% routinely, 6.2% only if a patient was a known steroid responder) and 50% of specialists would prescribe topical steroids (10.9% routinely, 39.1% if there were signs of blepharoconjunctivitis, conjunctival inflammation, or a history of uveitis or previous failed trabeculectomy). The commonest topical steroids prescribed in decreasing frequency of use were: dexamethasone (44.4%, of which 75% of specialists would prescribe PF dexamethasone and 25% would prescribe preserved dexamethasone), PF prednisolone (29.6%), fluorometholone (FML, 18.5%), prednisolone acetate 1% (3.7%), and betnesol (3.7%). The vast majority of specialists would prescribe topical steroids four times a day (70.3%), with a smaller number (22.2%) preferring to prescribe three times a day. The commonest prescribed NSAIDs were ketorolac and preserved and PF diclofenac.
Systemic tetracycline use (doxycycline) varied amongst specialists (34.4%). Of these, 3.2% would routinely prescribe a tetracycline and 31.2% only if a patient had blepharitis. The duration of treatment ranged from 2 to 12 weeks, with the majority of specialists prescribing the treatment for two to eight weeks (52%). The dose of doxycycline ranged from 50–100 mg per day, with the duration ranging from four weeks pre-operatively to 12 weeks postoperatively. A total of 65.6% (N = 42) of respondents did not use any of the mentioned pre-operative interventions routinely. A total of 23.4% (N = 15) respondents used at least one form of treatment routinely and 34.6% used one or more forms of treatment routinely. A total of 7 (10.9%) respondents combined two or more treatments (Figure 3). Pre-operatively, if there were signs of OSD, 84.4% of specialists expressed that they would change their routine management, with the majority simply stating that they would ‘‘treat the OSD’’. Only 14 respondents (33%) expressed specific management strategies. These comprised primarily using lid hygiene (11/14 respondents) combined with either PF anti-glaucoma drops or lubricants. The use of topical steroids, doxycycline, and a drop holiday were suggested by three separate respondents. Pre-operative optimization of the ocular surface was seen as ‘‘necessary’’ by 48.4% of specialists and ‘‘beneficial’’ by 85.9% of specialists. Seminars in Ophthalmology
Survey of Management of Ocular Surface No. of treatment combinations used
No. of respondents using combinations
5
Combinations used (number of respondents)
2
3
hygiene & lubricants (2) hygiene & topical steroids (1)
3
2
Preservative free(PF) drops, hygiene & lubricants (1) Hygiene, lubricants & topical steroids (1)
4
2
PF drops, hygiene, lubricants and topical steroids (1) PF drops, hygiene, topical steroids and NSAID’s (1)
FIGURE 3. Number of respondents using two or more combinations of interventions to routinely treat the ocular surface pre-operatively.
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DISCUSSION Our survey demonstrates a wide variation in strategies for the pre-operative optimization of the ocular surface amongst glaucoma specialists in the UK. The majority of specialists expressed that they routinely examined the ocular surface pre-operatively and, if there were signs of OSD, they would change their management. Furthermore, the majority of specialists expressed pre-operative optimization of the ocular surface to be beneficial. However, less than 50% believed it was necessary. The interventions used to optimize the ocular surface varied considerably amongst specialists, with the majority only implementing interventions if there were signs of OSD or in the case of topical steroids, a previous history of uveitis, or failed trabeculectomy. Ocular surface disease (OSD) is common amongst patient with glaucoma1 and the prevalence of symptomatic OSD has been shown to increase with the duration of treatment and the number of anti-glaucoma drops.10 It is now well-established that preservatives (of which BAK has been most widely studied) cause inflammation of the conjunctiva and tenon’s capsule. Indeed, histological studies have demonstrated that the conjunctiva and tenon’s capsule of patients treated with BAK containing anti-glaucoma drops has an increased number of macrophages, lymphocytes, mast cells, and fibroblasts and a significant decrease in the number of epithelial goblet cells.11,12 This evidence is supported by immunological studies using conjunctival impression cytology and conjunctival biopsies in patients treated with preserved anti-glaucoma drops, where there was an increased expression of proinflammatory markers: HLA-DR antigens (one of the main inflammatory markers of the conjunctiva); adhesion molecules (ICAM-1 and 3 and beta-2 integrins); CD45RO (membrane phosphatase expressed by immune cells); CD23 (low affinity IgE receptor).8,13 Furthermore, the overexpression of HLA-DR and CD23 has also been demonstrated in patients treated with preserved anti-glaucoma drops with no signs of ocular surface disease. By contrast, HLA-DR expression was not significantly increased in !
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patients receiving PF timolol compared to healthy controls.14 Studies have shown that reducing the BAK load resulted in an improvement in the signs and symptoms of OSD, a reduction in IOP, a reduction in the expression of conjunctival inflammatory markers, and an increase in MUC5AC production (a mucin produced by human conjunctival goblet cells).15,16 Hence, it appears that some of the effects of BAK on the human conjunctiva are reversible. Furthermore, our group (Batra et al.),17 in a retrospective case series, demonstrated that interventions to improve the ocular surface (lid hygiene, PF lubricants, doxycycline, and PF anti-glaucoma drops where appropriate) resulted in a significant and sustained reduction in the IOP. The authors proposed a spiralling disease process whereby preserved antiglaucoma drops induced OSD, which in turn resulted in aqueous outflow resistance, which resulted in an increase in the IOP. By treatment of the OSD, this spiralling process could be interrupted and partially reversed. This process was termed ‘‘OSD exacerbated glaucoma’’. The long-term use of topical anti-glaucoma medications causes ocular surface disease with overexpression of inflammatory markers and a predisposition to scarring. The latter effect can compromise trabeculectomy surgery.7 Broadway et al.12 reported a success rate of 90% in patients who had undergone a primary trabeculectomy, 93% in patients treated with a single anti-glaucoma drop (B blocker), 72% in patients taking two drops, and 45% in patients on three drops. In addition, the success rate was significantly lower in the patients treated with topical anti-glaucoma drops for more than three years (55%) compared to those patients treated for less than three years (94% p50.001). A retrospective study by Lavin et al.18 showed that patients who underwent a primary trabeculectomy had a higher success rate (97.9%) compared to patients who had been treated with antiglaucoma drops for at least 12 months prior to surgery (79.1%, p50.001). These studies suggest that the duration and number of anti-glaucoma treatments are directly linked to the success of trabeculectomy.
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To date, there is only one publication on the preoperative treatment of the ocular surface. In a prospective, randomized, double-blinded placebo control trial comparing pre-operative (trabeculectomy) treatment of the ocular surface for one month prior with either artificial tears, a NSAID (Aculare), or a topical steroid (fluorometholone, FML 0.1%), Breusegem et al.9 showed a 35% and 36% reduction in the incidence of needling in the NSAID and topical steroid treated group, respectively, at 12 months compared to the placebo group (p = 0.006), and a significant reduction in the need for IOP-lowering medication to achieve a target IOP in the steroid-treated group. There was no difference in the success rate of trabeculectomy at 12 months. Despite the evidence, our survey suggests that only a minority of specialists prescribe topical NSAIDs or steroids preoperatively. The objective of this survey was to determine current practice on pre-operative management of the ocular surface. The findings highlight that the majority of glaucoma specialists regard pre-operative examination of the ocular surface as necessary and optimization as beneficial. However, there appears to be significant variation in the interventions used to optimize the ocular surface pre-operatively. The latter may partly explain the wide variation in surgical outcomes following trabeculectomy. Further research in this area is warranted to determine how these different interventions might be beneficial and which interventions are optimal in this setting. In our practice, we routinely examine and optimize the ocular surface using many of the stated interventions, depending on the needs of the individual patient. We have found this approach beneficial in terms of surgical outcomes following trabeculectomy and would recommend it for all cases. In our practice, prostaglandin agonists are discontinued and topical steroids are prescribed for all patients one month prior to surgery. It is important to individualize treatment for each patient. Treatment is dependent on continuity of care, with ideally the same clinician monitoring the ocular surface. In patients with mild OSD, preservative-free lubricants such as Carmellose sodium are prescribed 4–6 times per day, twice-daily lid hygiene is taught, topical treatments are changed to preservative-free alternatives, and doxycycline 50 mg OD for three months is prescribed. The management of moderate OSD is as for mild OSD; however, with the addition of a discussion about nutrition accompanied by blood tests for nutritional deficiencies which may impact upon ocular surface health, such as full blood count, urea and electrolytes, vitamin B12 and folate levels, and vitamin D and calcium levels. Deficiencies can therefore be treated as appropriate. The management of severe ocular surface disease includes the above with the addition of an autoimmune screen. All of these patients are referred
to a cornea specialist for the management of their ocular surface and possibly to a general physician if the autoimmune screen highlights any abnormalities. The principal limitations of this survey are that the response rate was low, the responses may not reflect true clinical practice, and the respondents are likely to be a self-selected group of specialists with an interest in ocular surface disease. In retrospect, we feel it may have been useful to send a reminder letter in order to try and increase the response rate. Furthermore, as the number of respondents using combination treatments was small, we were unable to determine any patterns of routine pre-operative interventions. Due to constraints on the size of the questionnaire, the section about whether the pre-operative optimization of the ocular surface was (1) necessary of (2) beneficial comprised two closed questions only (requesting either yes or no answers in both instances). Further elaboration was not sought and therefore we cannot deduce whether the groups in favor of pre-operative optimization treated the OSD more aggressively. This survey nevertheless highlights the wide variations in interventions used to optimize the ocular surface pre-operatively, even amongst these motivated specialists. There is significant evidence in the literature that suggests that topical anti-glaucoma drops cause ocular surface disease, which may or may not be clinically evident. Furthermore, the longer patients are on topical treatment, the lower the risk of success following a trabeculectomy. The question then arises: Can we modify the pre-operative management of our patients to improve the outcome of trabeculectomy? To date, only one well-constructed, randomized control trial has shown that use of pre-operative topical steroids and NSAIDs significantly reduces the postoperative needling rate and the use of topical steroids reduces the need for topical glaucoma therapy to achieve target IOP.9 To increase awareness and uptake of pre-operative management strategies, a randomized control trial using pre-operative interventions to treat the ocular surface is required.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors have received no funding for this work, and they alone are responsible for the content and writing of the paper.
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Survey of Management of Ocular Surface 2. Chang L, Crowston JG, Cordeiro MF, et al. The role of the immune system in conjunctival wound healing after glaucoma surgery. Surv Ophthalmol 2000;45:49–68. 3. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol 2002;86:418–423. 4. Kuppens EVMJ, de Jong CA, Stolwijk TR, et al. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol 1995;79(4):339–342. 5. Kastelan S, Tomic M, Metez SK, Salopek-Rabatic J. How ocular surface disease impacts the glaucoma treatment outcome. Biomed Res Int 2013 Oct 9. [Epub ahead of print]. 6. Asbell PA, Potapova N. Effects of topical antiglaucoma medications on the ocular surface. Ocul Surf 2005; 3(1):27–40. 7. Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication II. The outcome of filtration surgery. Arch Ophthalmol 1994; 112:1446–1454. 8. Baudouin C, Pisella PJ, Fillacier K, et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: Human and animal studies. Ophthalmol 1999;106: 556–563. 9. Breusegem C, Spielberg L, Van Ginderdeuren R, et al. Preoperative nonsteroidal anti-inflammatory drug or steroid and outcomes after trabeculectomy: A randomized controlled trial. Ophthalmol 2010;117:1324–1330. 10. Garcia-Feijoo J, Sampaolesi JR. A multicenter evaluation of ocular surface disease prevalence in patients with glaucoma. Clin Ophthalmol 2012;6:441–446.
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