Int Ophthalmol DOI 10.1007/s10792-013-9868-6
ORIGINAL PAPER
Intraocular pressure control with Ahmed glaucoma drainage device in patients with cicatricial ocular surface disease-associated or aniridia-related glaucoma Radwan Almousa • Damian B. Lake
Received: 16 June 2013 / Accepted: 7 October 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract To analyze the control of intraocular pressure (IOP) with an Ahmed glaucoma drainage device (AGDD) in two groups of glaucoma patients— one with cicatricial ocular surface disease (COSD) and one with aniridia. This is a retrospective comparative case series of nine patients (11 eyes) with COSD and six patients (8 eyes) with aniridia who underwent AGDD surgery to control IOP. The main outcome measure in both groups was stability of IOP between 6 and 21 mmHg. Mean IOP decreased significantly in both groups after AGDD surgery (29.6 ± 8.7 vs 14.7 ± 2.5, p = 0.008 in the COSD group; 26.3 ± 8.2 vs 15.3 ± 5.8, p = 0.008 in the aniridia group). Over a mean post-surgery follow-up of 37.1 months in the COSD group, we managed to control IOP in nine eyes; IOP control was successful in 87 % of eyes at 12 months and 58 % of eyes at 26 months. Over a mean post-surgery follow-up of 37.4 months in the aniridia group, we managed to control the IOP in seven eyes; IOP control was successful in 87 % of eyes at 12 months. AGDD surgery had no significant deleterious effect on visual acuity in either group. A severe complication occurred R. Almousa D. B. Lake Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, UK R. Almousa (&) Ophthalmology Department, University Hospitals Coventry and Warwickshire, Coventry CV2 2DX, UK e-mail: [email protected]
in one eye (1/8) in the aniridia group (lost vision due to retinal detachment) and in one eye (1/11) in the COSD group (tube exposure). AGDD surgery is effective in controlling IOP and has a low complication rate in COSD and aniridia patients; however, some of the complications are severe and prompt management is needed to prevent deleterious results. Keywords Ahmed glaucoma device Intraocular pressure Cicatricial pemphigoid Aniridia
Introduction Glaucoma is a frequent complication in the clinical course of patients with severe cicatricial ocular surface disease (COSD) [1–3]. The etiology of the refractory increased intraocular pressure (IOP) in this group of ocular surface diseases is related to impaired outflow facility due to raised episcleral and scleral venous pressure and trabeculitis [1–4]. The prevalence of glaucoma in ocular cicatricial pemphigoid (OCP) patients has been reported to be in the range of 26–42.8 % [1, 2]; 46 % in patients with Stevens–Johnson syndrome (SJS) [2], and 37.7–55 % in patients with severe chemical injury [2, 3]. Medical treatment for IOP associated with COSD is usually poor [1]; furthermore, topical medication could induce
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or increase ocular surface cicatrization, further complicating IOP management [5, 6]. Conventional trabeculectomy surgery has low efficacy in IOP control in COSD, presumably related to hyperproliferation of fibroblasts in a thin, scarred and inflamed conjunctiva [1]. Unlike COSD, aniridia-related ocular surface disease is not characterized with cicatrization changes [1]. Glaucoma drainage devices (GDDs) such as the Ahmed glaucoma drainage device (AGDD) (New World Medical, Inc., Rancho Cucamonga, CA, USA) have become an important method for IOP control in difficult cases [7, 8]. We report our results of AGDD implantation in patients with COSD-associated glaucoma and in patients with aniridia-related glaucoma. The results of the two groups were compared and the risk factors affecting AGDD survival in both groups were analyzed.
Materials and methods We performed a retrospective chart review of all patients who had AGDD surgery between May 24, 2000 and September 9, 2009. The study was conducted in a corneal tertiary referral center in the south-east of England. Inclusion criteria were AGDD surgery for IOP control in aniridia or COSD, IOP [21 mmHg, and age [21 years. Exclusion criteria were AGDD surgery for IOP control not related to aniridia or COSD, extensive missing data (e.g., no documentation of IOP), and no follow-up. The study was approved by the institutional review board and followed the tenets of the 1995 Helsinki Declaration (Edinburgh revision 2000). Informed consent was obtained from all patients. One surgeon performed all surgeries. The AGDD surgery involved forming a fornix-based conjunctival flap. In cases of severe subconjunctival cicatricial changes, the conjunctival flap was made posterior to the surgical limbus, where the conjunctiva and tenon could be separated from the underlying sclera and dissected posteriorly past the equator. The plate of the AGDD implant (model FP-7) was passed under the conjunctival flap and secured C9 mm posterior to the surgical limbus with 9-0 nylon sutures. In the majority of cases this was in the superior temporal quadrant; however, in cases with underlying pathology in the superior temporal quadrant, the plate was inserted in the superior nasal or the inferior temporal quadrant. The
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tube was irrigated with balanced salt solution and was cut to the appropriate length before insertion into the anterior chamber through a 23-gauge needle track. The tube was covered with a superficial rectangular scleral flap and secured with a 9-0 nylon suture. In cases of severe cicatricial changes, the scleral flap was extended from the surgical limbus to the limit of the severe scleral/episcleral adhesion to cover the tube. All eyes received subconjunctival steroid and antibiotic injections at the end of the procedure. Routine postoperative medications included topical antibiotics and steroids. The main outcome variable was IOP control. Successful control was defined as IOP[5 and\22 mmHg with or without ocular hypotensive medication at last followup and without loss of light perception and no other subsequent glaucoma surgical procedure. Secondary outcomes were risk factors associated with AGDD failure in both groups. IOP was assessed by Reichert Tono-penÒ XL (Reichert Inc., Depew, NY, USA) at 1 month before AGDD insertion and at 1, 3, 6, 12, 18, and 24 months and at last follow-up. Data were collected on visual acuity preoperatively and at 1, 3, 6 and 12 months post-insertion. If an eye was noted to have reduced vision post-insertion then the potential cause was also documented. We stratified the severity of the COSD as mild (subconjunctival fibrosis), moderate (fornix shortening), or severe (symblepharon, limbal stem cell deficiency, and corneal conjunctivalization). Statistical analysis For statistical analysis, p values \0.05 were considered to be statistically significant. Kaplan–Meier survival method was used to estimate the success of IOP control. We compared the AGDD survival rate between the COSD and the aniridia group with life table analysis. We used the univariate Cox proportional hazards model to determine the effect on AGDD survival of the following variables—age, use of subconjunctival antimetabolites during the procedure, position of the AGDD plate (superior temporal, superior nasal), associated surgeries, lens status (phakic, pseudophakic, aphakic), number of previous penetrating keratoplasty, number of preoperative glaucoma medications, the mean IOP of the 2 months before AGDD surgery, number of preoperative intraocular surgeries, number of postoperative intraocular surgeries, complications, and severity of COSD.
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The distribution of data was examined using the Shapiro–Wilk test of normality. Comparison between pre- and postoperative (at the last follow-up) medical treatment and IOP was performed using t test and Wilcoxon signed-rank test where appropriate. Comparison of IOP at last follow-up between the two groups was performed with two-sample t test. Visual acuity data were converted to the logarithm of minimum angle of resolution (logMAR). The following conversion to logMAR was used for vision worse than 20/400—counting fingers = 1.6, hand movements = 2.0, light perception = 2.5, and no light perception = 3.0 [9]. Friedman’s test was applied to the comparisons of visual acuity between the different follow-ups.
Results The case notes of 24 patients who had undergone AGDD surgery for COSD or aniridia were reviewed.
Five patients had extensive missing data, and two patients underwent follow-up at a different hospital. Eleven eyes (9 patients) were included in the COSD group, and eight eyes (6 patients) in the aniridia group. Patient characteristics and baseline data are summarized in Table 1. Mean follow-up was 41.1 ± 40.8 months (range 6–111) for the COSD group, and 37.4 ± 17.9 months (range 31.4–68.5) for the aniridia group. All patients were Caucasian with a median age of 69 years (range 37–80) in the COSD group and 49 years (range 12–60) in the aniridia group (p value 0.029, t test). The COSD group comprised five OCP eyes, five chemical injuries, and one patient with SJS. Six of the COSD eyes presented with severe ocular surface disease and five had moderate changes. The AGDD plate was placed in the superior temporal quadrant for most of the patients in both groups, unless there was a previous trabeculectomy bleb (n = 1), or to avoid a quadrant with previous living-related conjunctival limbal allograft (n = 1), or to avoid a previous Morcher lens insertion incision (n = 1), or to avoid an
Table 1 Patient characteristics and baseline data No. of eyes
Cicatricial ocular surface group no. (%)
Aniridia group no. (%)
p value
0.446
11 (100)
8 (100)
Male
5 (45.4)
1 (12.5)
Female
6 (54.5)
7 (87.5)
28.09 ± 8.7
26.3 ± 8.2
5FU/MMC
5 (45.4)
1 (12.5)
None
6 (54.5)
7 (87.5)
Superior temporal
8 (72.7)
5 (62.5)
Superior nasal
1 (9.09)
3 (37.5)
Inferior temporal
2 (18.1)
0
Yes
1 (9.09)
1 (12.5)
No
10 (90.9)
7 (87.5)
2 (18.1)
0
Baseline IOP mean ± SD Antimetabolites
AGDD position
Associated surgery
Lens status Phakic
MMC mitomycin, 5FU 5 fluorouracil, AGDD Ahmed glaucoma drainage device a
Mean ± standard deviation (range)
Pseudophakic
8 (72.7)
5 (62.5)
Aphakic
1 (9.09)
3 (37.5)
No. of intraocular surgeries before AGDD procedure
1.8 ± 1.8 (0–5)a
2.1 ± 1.2 (0–4)a
No. of intraocular surgeries post AGDD procedure
2.09 ± 3.1(0–9)a
0.8 ± 0.9(0–3)a
Topical steroid treatment before AGDD
10 (90.9)
2 (25 %)
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area of severe conjunctival cicatrization (n = 3), for which the plate was placed in the superior nasal quadrant (n = 4) and in the inferior temporal quadrant (n = 2). Tables 2 and 3 summarize the surgery that was performed before and during the study period, respectively. One patient with a severe shortening of the fornices secondary to OCP, suffered from exposed superior temporal AGDD tube at 1 month postoperatively, which was treated by scleral patch graft, conjunctival suturing, n-butyl cyanoacrylate glue, amniotic membrane transplant with autologous blood subconjunctival injection, buccal membrane graft, and tying of the Ahmed tube. The Ahmed valve was finally replaced with another one placed in the superior nasal quadrant to stop the leak.
In both groups, medical treatment of the glaucoma had reduced significantly at last follow-up compared to preoperatively (COSD 0.6 ± 1.02 vs 3.6 ± 1.12, p = 0.004, Wilcoxon signed-rank test; Aniridia 1.25 ± 1.3 vs 3.8 ± 1.6, p = 0.004, t test). IOP had also reduced
Table 2 Surgical procedures before the study period Cicatricial ocular surface disease no. of eyes (%)
Aniridia no. of eyes (%)
Phacoemulsification
3 (27.2)
1 (12.5)
ECCE
2 (18.1)
3 (37.5)
SFIOL
0
1 (12.5)
Morcher lens
0
2 (25)
Morcher ring Corneal surgery
0
1 (12.5)
Cataract surgery
Penetrating keratoplasty
4 (36.3)
3 (37.5)
DSEK
1 (9.09)
0
KLAL
1 (9.09)
0
LrCLAL
1 (9.09)
0
Amniotic membrane transplant Trabeculectomy
0
0
0
2 (25)
ECCE extracapsular cataract extraction, SFIOL scleral fixed intraocular lens, DSEK Descemet’s stripping and endothelial keratoplasty, KLAL keratolimbal allograft, LrCLAL livingrelated conjunctival limbal allograft
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Surgery
Cicatricial ocular surface disease no. of eyes (%)
Aniridia no. of eyes (%)
Cataract and related surgeries Phacoemulsification
1 (9.09)
0
ECCE
0
0
IOL exchange
1 (9.09)
0
Penetrating keratoplasty
3 (27.2)
0
KLAL
0
0
Keratoprosthesis
2 (18.1)
0
EXVSCAL
1 (9.09)
3 (37.5)
LrCLAL
1 (9.09)
0
Corneal graft resuturing
0
1 (12.5)
Corneal surgery
Glaucoma surgery
Glaucoma outcome
Procedure
Table 3 Surgeries performed during the study period
Scleral patch for exposed tube
1 (9.09)
1 (12.5)
Conjunctiva suturing of exposed plate
1 (9.09)
0
Buccal membrane graft for exposed plate
1 (9.09)
0
AGD replacement
1 (9.09)
1 (12.5)
PPV
1 (9.09)
0
Anterior vitrectomy
0
1 (12.5)
Vitreoretinal surgery
ECCE extracapsular cataract extraction, IOL intraocular lens implant, KLAL keratolimbal allograft, EXVSCAL ex vivo stem cell allograft, LrCLAL living-related conjunctival limbal allograft, PPV pars plana vitrectomy
significantly in both groups at the last follow-up (COSD 28.09 ± 8.6 vs 15.09 ± 3.1, p = 0.008, t test; Aniridia 26.3 ± 8.2 vs 15.3 ± 5.8, p = 0.008, t test), and there was no difference in the final IOP measurement between both groups (p value 0.78, t test). Over a mean follow-up of 41 ± 40.8 months (range 6–111), the tube implant was successful in controlling the IOP in 9/11 eyes in the COSD group. Kaplan–Meier survival analysis showed a mean survival of AGDD surgery in the COSD group of 67 ± 16.1 months (Fig. 1). In the aniridia group, over a mean follow-up of 37.4 ± 17.9 months (range 31.4–68.5), the tube was successful in controlling the IOP in 7/8 eyes. Kaplan– Meier survival analysis shows a mean survival of 43.3 months; however, standard deviation could not be estimated due to the small sample (Fig. 2).
Int Ophthalmol Fig. 1 Kaplan–Meier survival analysis of success in intraocular pressure (IOP) control in cicatricial ocular surface disease (COSD). IOP control was successful with 90, 90, and 72 % of eyes at 12, 24, and 36 months, respectively. Mean survival of IOP control with Ahmed glaucoma device in COSD was 67 ± 16.13 months (95 % CI 35.9–99.2)
Fig. 2 Kaplan–Meier survival analysis of success of IOP control in the aniridia group using an Ahmed glaucoma device (AGD). IOP control was successful with 87 % at 1 year. Mean survival rate of the AGD in the aniridia group was 43.3 months
Life table analysis shows no significant survival rate differences between both groups (p value 0.477, log-rank test) Cox regression analysis did not identify any variables associated with AGDD failure in either group. AGDD had no significant effect over visual acuity in either group (p = 0.06 for COSD group, p = 0.8 for aniridia group, Friedman’s test) (Fig. 3).
the aniridia group had a persistent vitreous hemorrhage for 4 months following AGDD surgery, then an irreparable total retinal detachment resulting in perception of light vision only. One eye in the COSD group suffered a persistent hypotony as a result of tube exposure (Fig. 4). After a few attempts to cover the exposed tube, we had to replace the drainage implant with another one in the superior nasal quadrant, which then resulted in successful IOP control.
Complications Postoperative complications are summarized in Table 4. AGDD surgery resulted in complications for 3/11 eyes in the COSD group, and 1/8 in the aniridia group. One eye in the aniridia group suffered phthisis bulbi secondary to traumatic globe rupture, and therefore not related to the AGDD surgery. Another eye in
Discussion Aniridia is an ocular surface disease associated with glaucoma; however, it is not an inflammatory disease and not associated with the cicatricial subconjunctival scarring that occurs in COSD. High IOP in aniridia is
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Int Ophthalmol Fig. 3 Graph showing the mean visual acuity changes with standard deviation over a 1-year period after Ahmed glaucoma device surgery in eyes with cicatricial ocular surface disease (a) and aniridia (b)
Table 4 Complications associated with the Ahmed glaucoma drainage device in the cicatricial ocular surface disease group and the aniridia group Complicationsa
Cicatricial ocular surface disease no. (%)
Aniridia no. (%)
Hyphema
2 (18.1)
1 (12.5)
Bleb leakage
0.0
0.0
Choroidal effusion
1 (9.09)
0.0
Flat anterior chamber
1 (9.09)
0.0
Corneal touch Hypotony
0.0 1 (9.09)
0.0 0.0
Mild complications
Severe complications
a
Tube exposure
1 (9.09)
0.0
Vitreous hemorrhage
0.0
1 (12.5)
Phthisis bulbi
0.0
1 (12.5)
Tube obstruction
0.0
0.0
Endophthalmitis
0.0
0.0
Retinal detachment
0.0
1 (12.5)
The eye could have more than one complication
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Fig. 4 Ahmed device tube and plate exposure in a patient with cicatricial ocular pemphigoid
attributed to progressive anterior rotation of the rudimentary iris leading to angle closure [10]. Other mechanisms reported to cause high IOP in aniridia include an absence of Schlemm’s canal and secondary angle closure after miotic therapy [11]. Both aniridia and COSD are associated with a refractory type of
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glaucoma difficult to manage with conventional medical treatments [2, 10], cyclocryotherapy [12], or trabeculectomy with mitomycin C [2]. GDDs have become an important method for controlling IOP in these difficult cases [7, 8]. GDD success rate in controlling IOP associated with aniridia was reported to range from 66–100 % over a follow-up range of 1–9 years [13–15]. IOP control in our aniridia with AGDD group falls within that range (87.5 % over a follow-up of 37.4 ± 17.9 months). Tauber et al. [1] found that medical treatment of IOP associated with OCP was inadequate in 47 % of patients, and only one patient out of four (25 %) had adequate IOP control with trabeculectomy surgery over a follow-up of 24.2 months. In comparison with IOP control in our COSD with AGDD group, we had a higher success rate of 81.8 % over a longer follow-up of 41 ± 40.8 months. In our series the control of IOP was similar in both groups, and there was no statistically significant difference in AGDD survival (p = 0.477, log-rank test). One COSD patient with OCP had a severe complication with persistent hypotony which was related to tube exposure as a result of the limited and contracted conjunctiva available to cover the AGDD plate. Tran et al. [16] reported 37 % of cases of hypotony following AGDD for primary open-angle glaucoma. They suggested that the mechanism of the hypotony was a leakage around the tube or impaired valve function. One patient in our aniridia group, with the drainage tube placed in the anterior chamber, had a retinal detachment following 4 months of vitreous hemorrhage. Arroyave et al. [13] reported a series of aniridia patients who underwent GDD surgery, in which one patient developed retinal detachment associated with severe proliferative vitreoretinopathy and giant retinal tear 7 months after GDD placement. One patient in the aniridia group developed phthisis bulbi as a result of traumatic rupture; however, this was not related to the AGDD surgery. Ophthalmologists who follow-up patients with COSD must maintain a high index of suspicion for the coexistence or development of glaucoma. Often, visual field testing is not performed because of severe photophobia and corneal opacities. As visualization of the optic disc is typically difficult and often impossible, the success of glaucoma control can be demonstrated
objectively by adequate control of IOP measurements alone. According to our knowledge, this is the first case series using a GDD for control of IOP in COSD; the success rate mirrored the results of IOP control in the aniridia group, in which such devices have already proven to be effective [13–15]. Although we realize the limitation of our retrospective study because the small sample size prevented us from identifying variables that may affect implant survival, our results do show that the AGDD is an effective treatment for glaucoma in COSD, and we do recommend it as a firstline surgical treatment in preference to other surgical procedures that have a low success rate. Severe complications like vitreous hemorrhage and retinal detachment could complicate AGDD surgery and urgent referral to the surgical retinal service is mandatory for further management. A prospective study with a control group and larger sample is needed to confirm the success rate and the risk factors associated with IOP control with AGDD in COSD patients. Acknowledgments Helga Perry, Electronic Systems and Resources Librarian at University Hospitals Coventry and Warwickshire NHS Trust assisted with proof-reading and preparation of this paper. The authors have no proprietary or commercial interest in any materials discussed in this article. Conflict of interest Funding
None.
There was no funding for this study.
References 1. Tauber J, Melamed S, Foster S (1989) Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology 96:33–37 2. Tsai JH, Derby E, Holland EJ, Khatana AK (2006) Incidence and prevalence of glaucoma in severe ocular surface disease. Cornea 25:530–532 3. Kuckelkorn R, Kottek A, Reim M (1994) Intraocular complications after severe chemical burns-incidence and surgical treatment. Klin Monastbl Augenheilkd 205:86–92 4. Pfister DR, Pfister RR (2005) Alkali injuries of the eye. In: Krachmer JH, Mannis MJ, Holland EJ (eds) Cornea: volume 1. Fundamentals, diagnosis and management, 2nd edn. Philadelphia, Elsevier Mosby, pp 1285–1293 5. Patten Jt, Cavanagh HD, Allansmith MR (1976) Induced ocular pseudopemphigoid. Am J Ophthalmol 82:272–276 6. Rahi AS, Chapman CM, Garner A, Wright P (1976) Pathology of practolol-induced ocular toxicity. Br J Ophthalmol 60:312–323
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Int Ophthalmol 7. Al-Torbak AA (2004) Outcome of combined Ahmed glaucoma valve implant and penetrating keratoplasty in refractory congenital glaucoma with corneal opacity. Cornea 23:554–559 8. Al-Torbak AA (2003) Graft survival and glaucoma outcome after simultaneous penetrating keratoplasty and Ahmed glaucoma valve implant. Cornea 22:194–197 9. Tibbetts MD, Shah CP, Young LH, Duker JS, Maguire JI, Morley MG (2010) Treatment of acute retinal necrosis. Ophthalmology 117:818–824 10. Grant WM, Walton DS (1974) Progressive changes in the angle in congenital aniridia, with development of glaucoma. Am J Ophthalmol 78:842–847 11. Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L (1984) Aniridia. A review. Surv Ophthalmol 28:621–642 12. Wagle NS, Freedman SF, Buckley EG, Davis JS, Biglan AW (1998) Long-term outcome of cyclocryotherapy for refractory pediatric glaucoma. Ophthalmology 105:1921–1927
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13. Arroyave CP, Scott IU, Gedde SJ, Parrish RK, Feuer WJ (2003) Use of glaucoma drainage devices in the management of glaucoma associated with aniridia. Am J Ophthalmol 135:155–159 14. Billson F, Thomas R, Aylward W (1989) The use of two stage Molteno implants in developmental glaucoma. J Pediatr Ophthalmol Strabismus 26:3–8 15. Adachi M, Dickens CJ, Hetherington J et al (1997) Surgical experience of trabeculotomy for the surgical treatment of aniridic glaucoma. Ophthalmology 104:2121–2125 16. Tran D, Souza C, Ang M et al (2009) Comparison of longterm surgical success of Ahmed valve implant versus trabeculectomy in open-angle glaucoma. Br J Ophthalmol 93:1504–1509
ORIGINAL PAPER
Intraocular pressure control with Ahmed glaucoma drainage device in patients with cicatricial ocular surface disease-associated or aniridia-related glaucoma Radwan Almousa • Damian B. Lake
Received: 16 June 2013 / Accepted: 7 October 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract To analyze the control of intraocular pressure (IOP) with an Ahmed glaucoma drainage device (AGDD) in two groups of glaucoma patients— one with cicatricial ocular surface disease (COSD) and one with aniridia. This is a retrospective comparative case series of nine patients (11 eyes) with COSD and six patients (8 eyes) with aniridia who underwent AGDD surgery to control IOP. The main outcome measure in both groups was stability of IOP between 6 and 21 mmHg. Mean IOP decreased significantly in both groups after AGDD surgery (29.6 ± 8.7 vs 14.7 ± 2.5, p = 0.008 in the COSD group; 26.3 ± 8.2 vs 15.3 ± 5.8, p = 0.008 in the aniridia group). Over a mean post-surgery follow-up of 37.1 months in the COSD group, we managed to control IOP in nine eyes; IOP control was successful in 87 % of eyes at 12 months and 58 % of eyes at 26 months. Over a mean post-surgery follow-up of 37.4 months in the aniridia group, we managed to control the IOP in seven eyes; IOP control was successful in 87 % of eyes at 12 months. AGDD surgery had no significant deleterious effect on visual acuity in either group. A severe complication occurred R. Almousa D. B. Lake Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, UK R. Almousa (&) Ophthalmology Department, University Hospitals Coventry and Warwickshire, Coventry CV2 2DX, UK e-mail: [email protected]
in one eye (1/8) in the aniridia group (lost vision due to retinal detachment) and in one eye (1/11) in the COSD group (tube exposure). AGDD surgery is effective in controlling IOP and has a low complication rate in COSD and aniridia patients; however, some of the complications are severe and prompt management is needed to prevent deleterious results. Keywords Ahmed glaucoma device Intraocular pressure Cicatricial pemphigoid Aniridia
Introduction Glaucoma is a frequent complication in the clinical course of patients with severe cicatricial ocular surface disease (COSD) [1–3]. The etiology of the refractory increased intraocular pressure (IOP) in this group of ocular surface diseases is related to impaired outflow facility due to raised episcleral and scleral venous pressure and trabeculitis [1–4]. The prevalence of glaucoma in ocular cicatricial pemphigoid (OCP) patients has been reported to be in the range of 26–42.8 % [1, 2]; 46 % in patients with Stevens–Johnson syndrome (SJS) [2], and 37.7–55 % in patients with severe chemical injury [2, 3]. Medical treatment for IOP associated with COSD is usually poor [1]; furthermore, topical medication could induce
123
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or increase ocular surface cicatrization, further complicating IOP management [5, 6]. Conventional trabeculectomy surgery has low efficacy in IOP control in COSD, presumably related to hyperproliferation of fibroblasts in a thin, scarred and inflamed conjunctiva [1]. Unlike COSD, aniridia-related ocular surface disease is not characterized with cicatrization changes [1]. Glaucoma drainage devices (GDDs) such as the Ahmed glaucoma drainage device (AGDD) (New World Medical, Inc., Rancho Cucamonga, CA, USA) have become an important method for IOP control in difficult cases [7, 8]. We report our results of AGDD implantation in patients with COSD-associated glaucoma and in patients with aniridia-related glaucoma. The results of the two groups were compared and the risk factors affecting AGDD survival in both groups were analyzed.
Materials and methods We performed a retrospective chart review of all patients who had AGDD surgery between May 24, 2000 and September 9, 2009. The study was conducted in a corneal tertiary referral center in the south-east of England. Inclusion criteria were AGDD surgery for IOP control in aniridia or COSD, IOP [21 mmHg, and age [21 years. Exclusion criteria were AGDD surgery for IOP control not related to aniridia or COSD, extensive missing data (e.g., no documentation of IOP), and no follow-up. The study was approved by the institutional review board and followed the tenets of the 1995 Helsinki Declaration (Edinburgh revision 2000). Informed consent was obtained from all patients. One surgeon performed all surgeries. The AGDD surgery involved forming a fornix-based conjunctival flap. In cases of severe subconjunctival cicatricial changes, the conjunctival flap was made posterior to the surgical limbus, where the conjunctiva and tenon could be separated from the underlying sclera and dissected posteriorly past the equator. The plate of the AGDD implant (model FP-7) was passed under the conjunctival flap and secured C9 mm posterior to the surgical limbus with 9-0 nylon sutures. In the majority of cases this was in the superior temporal quadrant; however, in cases with underlying pathology in the superior temporal quadrant, the plate was inserted in the superior nasal or the inferior temporal quadrant. The
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tube was irrigated with balanced salt solution and was cut to the appropriate length before insertion into the anterior chamber through a 23-gauge needle track. The tube was covered with a superficial rectangular scleral flap and secured with a 9-0 nylon suture. In cases of severe cicatricial changes, the scleral flap was extended from the surgical limbus to the limit of the severe scleral/episcleral adhesion to cover the tube. All eyes received subconjunctival steroid and antibiotic injections at the end of the procedure. Routine postoperative medications included topical antibiotics and steroids. The main outcome variable was IOP control. Successful control was defined as IOP[5 and\22 mmHg with or without ocular hypotensive medication at last followup and without loss of light perception and no other subsequent glaucoma surgical procedure. Secondary outcomes were risk factors associated with AGDD failure in both groups. IOP was assessed by Reichert Tono-penÒ XL (Reichert Inc., Depew, NY, USA) at 1 month before AGDD insertion and at 1, 3, 6, 12, 18, and 24 months and at last follow-up. Data were collected on visual acuity preoperatively and at 1, 3, 6 and 12 months post-insertion. If an eye was noted to have reduced vision post-insertion then the potential cause was also documented. We stratified the severity of the COSD as mild (subconjunctival fibrosis), moderate (fornix shortening), or severe (symblepharon, limbal stem cell deficiency, and corneal conjunctivalization). Statistical analysis For statistical analysis, p values \0.05 were considered to be statistically significant. Kaplan–Meier survival method was used to estimate the success of IOP control. We compared the AGDD survival rate between the COSD and the aniridia group with life table analysis. We used the univariate Cox proportional hazards model to determine the effect on AGDD survival of the following variables—age, use of subconjunctival antimetabolites during the procedure, position of the AGDD plate (superior temporal, superior nasal), associated surgeries, lens status (phakic, pseudophakic, aphakic), number of previous penetrating keratoplasty, number of preoperative glaucoma medications, the mean IOP of the 2 months before AGDD surgery, number of preoperative intraocular surgeries, number of postoperative intraocular surgeries, complications, and severity of COSD.
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The distribution of data was examined using the Shapiro–Wilk test of normality. Comparison between pre- and postoperative (at the last follow-up) medical treatment and IOP was performed using t test and Wilcoxon signed-rank test where appropriate. Comparison of IOP at last follow-up between the two groups was performed with two-sample t test. Visual acuity data were converted to the logarithm of minimum angle of resolution (logMAR). The following conversion to logMAR was used for vision worse than 20/400—counting fingers = 1.6, hand movements = 2.0, light perception = 2.5, and no light perception = 3.0 [9]. Friedman’s test was applied to the comparisons of visual acuity between the different follow-ups.
Results The case notes of 24 patients who had undergone AGDD surgery for COSD or aniridia were reviewed.
Five patients had extensive missing data, and two patients underwent follow-up at a different hospital. Eleven eyes (9 patients) were included in the COSD group, and eight eyes (6 patients) in the aniridia group. Patient characteristics and baseline data are summarized in Table 1. Mean follow-up was 41.1 ± 40.8 months (range 6–111) for the COSD group, and 37.4 ± 17.9 months (range 31.4–68.5) for the aniridia group. All patients were Caucasian with a median age of 69 years (range 37–80) in the COSD group and 49 years (range 12–60) in the aniridia group (p value 0.029, t test). The COSD group comprised five OCP eyes, five chemical injuries, and one patient with SJS. Six of the COSD eyes presented with severe ocular surface disease and five had moderate changes. The AGDD plate was placed in the superior temporal quadrant for most of the patients in both groups, unless there was a previous trabeculectomy bleb (n = 1), or to avoid a quadrant with previous living-related conjunctival limbal allograft (n = 1), or to avoid a previous Morcher lens insertion incision (n = 1), or to avoid an
Table 1 Patient characteristics and baseline data No. of eyes
Cicatricial ocular surface group no. (%)
Aniridia group no. (%)
p value
0.446
11 (100)
8 (100)
Male
5 (45.4)
1 (12.5)
Female
6 (54.5)
7 (87.5)
28.09 ± 8.7
26.3 ± 8.2
5FU/MMC
5 (45.4)
1 (12.5)
None
6 (54.5)
7 (87.5)
Superior temporal
8 (72.7)
5 (62.5)
Superior nasal
1 (9.09)
3 (37.5)
Inferior temporal
2 (18.1)
0
Yes
1 (9.09)
1 (12.5)
No
10 (90.9)
7 (87.5)
2 (18.1)
0
Baseline IOP mean ± SD Antimetabolites
AGDD position
Associated surgery
Lens status Phakic
MMC mitomycin, 5FU 5 fluorouracil, AGDD Ahmed glaucoma drainage device a
Mean ± standard deviation (range)
Pseudophakic
8 (72.7)
5 (62.5)
Aphakic
1 (9.09)
3 (37.5)
No. of intraocular surgeries before AGDD procedure
1.8 ± 1.8 (0–5)a
2.1 ± 1.2 (0–4)a
No. of intraocular surgeries post AGDD procedure
2.09 ± 3.1(0–9)a
0.8 ± 0.9(0–3)a
Topical steroid treatment before AGDD
10 (90.9)
2 (25 %)
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area of severe conjunctival cicatrization (n = 3), for which the plate was placed in the superior nasal quadrant (n = 4) and in the inferior temporal quadrant (n = 2). Tables 2 and 3 summarize the surgery that was performed before and during the study period, respectively. One patient with a severe shortening of the fornices secondary to OCP, suffered from exposed superior temporal AGDD tube at 1 month postoperatively, which was treated by scleral patch graft, conjunctival suturing, n-butyl cyanoacrylate glue, amniotic membrane transplant with autologous blood subconjunctival injection, buccal membrane graft, and tying of the Ahmed tube. The Ahmed valve was finally replaced with another one placed in the superior nasal quadrant to stop the leak.
In both groups, medical treatment of the glaucoma had reduced significantly at last follow-up compared to preoperatively (COSD 0.6 ± 1.02 vs 3.6 ± 1.12, p = 0.004, Wilcoxon signed-rank test; Aniridia 1.25 ± 1.3 vs 3.8 ± 1.6, p = 0.004, t test). IOP had also reduced
Table 2 Surgical procedures before the study period Cicatricial ocular surface disease no. of eyes (%)
Aniridia no. of eyes (%)
Phacoemulsification
3 (27.2)
1 (12.5)
ECCE
2 (18.1)
3 (37.5)
SFIOL
0
1 (12.5)
Morcher lens
0
2 (25)
Morcher ring Corneal surgery
0
1 (12.5)
Cataract surgery
Penetrating keratoplasty
4 (36.3)
3 (37.5)
DSEK
1 (9.09)
0
KLAL
1 (9.09)
0
LrCLAL
1 (9.09)
0
Amniotic membrane transplant Trabeculectomy
0
0
0
2 (25)
ECCE extracapsular cataract extraction, SFIOL scleral fixed intraocular lens, DSEK Descemet’s stripping and endothelial keratoplasty, KLAL keratolimbal allograft, LrCLAL livingrelated conjunctival limbal allograft
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Surgery
Cicatricial ocular surface disease no. of eyes (%)
Aniridia no. of eyes (%)
Cataract and related surgeries Phacoemulsification
1 (9.09)
0
ECCE
0
0
IOL exchange
1 (9.09)
0
Penetrating keratoplasty
3 (27.2)
0
KLAL
0
0
Keratoprosthesis
2 (18.1)
0
EXVSCAL
1 (9.09)
3 (37.5)
LrCLAL
1 (9.09)
0
Corneal graft resuturing
0
1 (12.5)
Corneal surgery
Glaucoma surgery
Glaucoma outcome
Procedure
Table 3 Surgeries performed during the study period
Scleral patch for exposed tube
1 (9.09)
1 (12.5)
Conjunctiva suturing of exposed plate
1 (9.09)
0
Buccal membrane graft for exposed plate
1 (9.09)
0
AGD replacement
1 (9.09)
1 (12.5)
PPV
1 (9.09)
0
Anterior vitrectomy
0
1 (12.5)
Vitreoretinal surgery
ECCE extracapsular cataract extraction, IOL intraocular lens implant, KLAL keratolimbal allograft, EXVSCAL ex vivo stem cell allograft, LrCLAL living-related conjunctival limbal allograft, PPV pars plana vitrectomy
significantly in both groups at the last follow-up (COSD 28.09 ± 8.6 vs 15.09 ± 3.1, p = 0.008, t test; Aniridia 26.3 ± 8.2 vs 15.3 ± 5.8, p = 0.008, t test), and there was no difference in the final IOP measurement between both groups (p value 0.78, t test). Over a mean follow-up of 41 ± 40.8 months (range 6–111), the tube implant was successful in controlling the IOP in 9/11 eyes in the COSD group. Kaplan–Meier survival analysis showed a mean survival of AGDD surgery in the COSD group of 67 ± 16.1 months (Fig. 1). In the aniridia group, over a mean follow-up of 37.4 ± 17.9 months (range 31.4–68.5), the tube was successful in controlling the IOP in 7/8 eyes. Kaplan– Meier survival analysis shows a mean survival of 43.3 months; however, standard deviation could not be estimated due to the small sample (Fig. 2).
Int Ophthalmol Fig. 1 Kaplan–Meier survival analysis of success in intraocular pressure (IOP) control in cicatricial ocular surface disease (COSD). IOP control was successful with 90, 90, and 72 % of eyes at 12, 24, and 36 months, respectively. Mean survival of IOP control with Ahmed glaucoma device in COSD was 67 ± 16.13 months (95 % CI 35.9–99.2)
Fig. 2 Kaplan–Meier survival analysis of success of IOP control in the aniridia group using an Ahmed glaucoma device (AGD). IOP control was successful with 87 % at 1 year. Mean survival rate of the AGD in the aniridia group was 43.3 months
Life table analysis shows no significant survival rate differences between both groups (p value 0.477, log-rank test) Cox regression analysis did not identify any variables associated with AGDD failure in either group. AGDD had no significant effect over visual acuity in either group (p = 0.06 for COSD group, p = 0.8 for aniridia group, Friedman’s test) (Fig. 3).
the aniridia group had a persistent vitreous hemorrhage for 4 months following AGDD surgery, then an irreparable total retinal detachment resulting in perception of light vision only. One eye in the COSD group suffered a persistent hypotony as a result of tube exposure (Fig. 4). After a few attempts to cover the exposed tube, we had to replace the drainage implant with another one in the superior nasal quadrant, which then resulted in successful IOP control.
Complications Postoperative complications are summarized in Table 4. AGDD surgery resulted in complications for 3/11 eyes in the COSD group, and 1/8 in the aniridia group. One eye in the aniridia group suffered phthisis bulbi secondary to traumatic globe rupture, and therefore not related to the AGDD surgery. Another eye in
Discussion Aniridia is an ocular surface disease associated with glaucoma; however, it is not an inflammatory disease and not associated with the cicatricial subconjunctival scarring that occurs in COSD. High IOP in aniridia is
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Int Ophthalmol Fig. 3 Graph showing the mean visual acuity changes with standard deviation over a 1-year period after Ahmed glaucoma device surgery in eyes with cicatricial ocular surface disease (a) and aniridia (b)
Table 4 Complications associated with the Ahmed glaucoma drainage device in the cicatricial ocular surface disease group and the aniridia group Complicationsa
Cicatricial ocular surface disease no. (%)
Aniridia no. (%)
Hyphema
2 (18.1)
1 (12.5)
Bleb leakage
0.0
0.0
Choroidal effusion
1 (9.09)
0.0
Flat anterior chamber
1 (9.09)
0.0
Corneal touch Hypotony
0.0 1 (9.09)
0.0 0.0
Mild complications
Severe complications
a
Tube exposure
1 (9.09)
0.0
Vitreous hemorrhage
0.0
1 (12.5)
Phthisis bulbi
0.0
1 (12.5)
Tube obstruction
0.0
0.0
Endophthalmitis
0.0
0.0
Retinal detachment
0.0
1 (12.5)
The eye could have more than one complication
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Fig. 4 Ahmed device tube and plate exposure in a patient with cicatricial ocular pemphigoid
attributed to progressive anterior rotation of the rudimentary iris leading to angle closure [10]. Other mechanisms reported to cause high IOP in aniridia include an absence of Schlemm’s canal and secondary angle closure after miotic therapy [11]. Both aniridia and COSD are associated with a refractory type of
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glaucoma difficult to manage with conventional medical treatments [2, 10], cyclocryotherapy [12], or trabeculectomy with mitomycin C [2]. GDDs have become an important method for controlling IOP in these difficult cases [7, 8]. GDD success rate in controlling IOP associated with aniridia was reported to range from 66–100 % over a follow-up range of 1–9 years [13–15]. IOP control in our aniridia with AGDD group falls within that range (87.5 % over a follow-up of 37.4 ± 17.9 months). Tauber et al. [1] found that medical treatment of IOP associated with OCP was inadequate in 47 % of patients, and only one patient out of four (25 %) had adequate IOP control with trabeculectomy surgery over a follow-up of 24.2 months. In comparison with IOP control in our COSD with AGDD group, we had a higher success rate of 81.8 % over a longer follow-up of 41 ± 40.8 months. In our series the control of IOP was similar in both groups, and there was no statistically significant difference in AGDD survival (p = 0.477, log-rank test). One COSD patient with OCP had a severe complication with persistent hypotony which was related to tube exposure as a result of the limited and contracted conjunctiva available to cover the AGDD plate. Tran et al. [16] reported 37 % of cases of hypotony following AGDD for primary open-angle glaucoma. They suggested that the mechanism of the hypotony was a leakage around the tube or impaired valve function. One patient in our aniridia group, with the drainage tube placed in the anterior chamber, had a retinal detachment following 4 months of vitreous hemorrhage. Arroyave et al. [13] reported a series of aniridia patients who underwent GDD surgery, in which one patient developed retinal detachment associated with severe proliferative vitreoretinopathy and giant retinal tear 7 months after GDD placement. One patient in the aniridia group developed phthisis bulbi as a result of traumatic rupture; however, this was not related to the AGDD surgery. Ophthalmologists who follow-up patients with COSD must maintain a high index of suspicion for the coexistence or development of glaucoma. Often, visual field testing is not performed because of severe photophobia and corneal opacities. As visualization of the optic disc is typically difficult and often impossible, the success of glaucoma control can be demonstrated
objectively by adequate control of IOP measurements alone. According to our knowledge, this is the first case series using a GDD for control of IOP in COSD; the success rate mirrored the results of IOP control in the aniridia group, in which such devices have already proven to be effective [13–15]. Although we realize the limitation of our retrospective study because the small sample size prevented us from identifying variables that may affect implant survival, our results do show that the AGDD is an effective treatment for glaucoma in COSD, and we do recommend it as a firstline surgical treatment in preference to other surgical procedures that have a low success rate. Severe complications like vitreous hemorrhage and retinal detachment could complicate AGDD surgery and urgent referral to the surgical retinal service is mandatory for further management. A prospective study with a control group and larger sample is needed to confirm the success rate and the risk factors associated with IOP control with AGDD in COSD patients. Acknowledgments Helga Perry, Electronic Systems and Resources Librarian at University Hospitals Coventry and Warwickshire NHS Trust assisted with proof-reading and preparation of this paper. The authors have no proprietary or commercial interest in any materials discussed in this article. Conflict of interest Funding
None.
There was no funding for this study.
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