Jpn J Ophthalmol DOI 10.1007/s10384-015-0372-6
CLINICAL INVESTIGATION
Surgical outcomes of inflammatory glaucoma: a comparison of trabeculectomy and glaucoma-drainage-device implantation Shawn M. Iverson • Namita Bhardwaj • Wei Shi • Mitra Sehi • David S. Greenfield Donald L. Budenz • Krishna Kishor
•
Received: 1 August 2014 / Accepted: 19 December 2014 Ó Japanese Ophthalmological Society 2015
Abstract Purpose Our aim was to compare surgical outcomes of trabeculectomy and nonvalved glaucoma-drainage-device (GDD) implantation in eyes with chronic inflammatory glaucoma and uncontrolled intraocular pressure (IOP). Methods A retrospective chart review was conducted on patients with glaucomatous optic neuropathy, chronic anterior or posterior segment inflammation, and C6 months postoperative follow-up. All eyes underwent trabeculectomy with either antifibrotic therapy or implantation of a Baerveldt GDD (Abbott Laboratories Inc., Abbott Park, IL, USA). Failure was defined as IOP [21 mmHg, \20 % reduction below baseline or IOP \5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision. Statistical methods consisted of Student’s t tests, v2 test, and Kaplan– Meier time to failure analysis. Results Nineteen trabeculectomies of 42 patients were followed for a mean of 31 ± 23 and 23 GDD eyes for a mean of 39 ± 19 months (P = 0.22). At last follow-up, mean IOP (11.83 ± 4.59 and 13.15 ± 6.11 mmHg, P = 0.45) and number of glaucoma medications (1.28 ± 1.56 and 1.26 ± 1.25, P = 0.97) were similar between the trabeculectomy and GDD groups. The frequency and types of postoperative complications in both
S. M. Iverson N. Bhardwaj W. Shi M. Sehi D. S. Greenfield K. Kishor (&) Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 7101 Fairway Drive, Palm Beach Gardens, FL 33418, USA e-mail: [email protected] D. L. Budenz Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
groups were similar. The cumulative probability of failure after 5 years of follow-up was significantly greater in trabeculectomy eyes (62 %) compared with GDD eyes (25 %) (P = 0.006). Conclusions Nonvalved tube-shunt surgery was more likely to maintain IOP control and avoid reoperation than trabeculectomy with antifibrotic therapy in eyes with chronic inflammatory glaucoma. Keywords Glaucoma Glaucoma drainage device Trabeculectomy Uveitis Intraocular pressure
Introduction Uveitis is a multietiological ocular inflammatory disease that leads to glaucomatous optic neuropathy in approximately 20 % of eyes [1–3]. Considerably higher rates of glaucoma (30–50 %) have been described in eyes with specific uveitic syndromes, including juvenile-rheumatoidarthritis-associated iridocyclitis, Fuchs’ heterochromic iridocyclitis, Lyme-associated uveitis, and cancer-associated uveitis [2, 4, 5]. Managing inflammatory glaucomas is particularly complex due to the number of clinical entities involved and the high likelihood of elevated intraocular pressure (IOP) secondary to long-term corticosteroid exposure [6, 7]. When uveitis is resistant to medical therapy, clinicians are presented with the challenge of determining which surgical procedure would best control IOP in the long term. The success rates of conventional filtering surgery in this population is reported to be highly variable (50–100 %) [8–12]. Glaucoma-drainage-device (GDD) implantation is thought to be an effective means of controlling IOP in the long term; however, success rates have been similarly varied (50–97 %) [13–18].
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A major challenge to successful filtration surgery in uveitis is the accelerated healing that occurs in the presence of postoperative inflammation. As a rule, suppression of inflammation in the perioperative period significantly improves outcomes [19]; however, there is no way to completely eliminate postoperative inflammation. The use of antifibrotics during filtering procedures may be employed to retard postoperative wound healing. However, up to 50 % of patients still develop bleb fibrosis and filtration failure within 5 years [8, 11, 12, 20]. Since the risk of failure in traditional filtration surgery in this cohort is high [8, 11, 12, 20], some specialists proceed directly to GDD implantation rather than attempting trabeculectomy [21]. Limited data exist comparing types of IOP-lowering surgery and its success rates in uveitic glaucoma. Gedde and colleagues [22] prospectively evaluated GDD versus trabeculectomy outcomes for the management of uncontrolled IOP. However, their study did not enroll several types of secondary glaucomas, including uveitic glaucoma. Because uveitic glaucoma can be particularly difficult to manage, we believe there should be a strong evidence base to support the type of IOP-lowering surgery that provides the best long-term IOP control in eyes that require reduction beyond what maximum medical therapy can attain. We performed this study to determine whether initial GDD implantation in uveitic glaucoma eyes provides superior outcomes and reduced complications compared with initial filtering surgery with adjuvant antifibrotic therapy.
Methods A retrospective chart review was conducted on consecutive patients with uveitic glaucoma who underwent surgical IOP reduction at Bascom Palmer Eye Institute (Miami, FL, USA) between 1 January 2002 and 31 December 2007. Glaucoma surgery was performed by two glaucoma specialists (DSG, DLB) based upon their clinical judgment. Eyes either underwent trabeculectomy with adjuvant antifibrotic therapy or received a GDD implant. The type of procedure was chosen based on what the surgeon thought would provide the best long-term outcome. Trabeculectomy was often chosen over GDD in eyes with minimal conjunctival scarring; however, there was no clear indication for a particular procedure in this cohort. The research was conducted in accordance with the Declaration of Helsinki for research involving humans, and Institutional Review Board approval was obtained from the office of Human Research at the University of Miami. The study complied with the requirements of the United States Health Insurance Portability and Accountability Act. Inclusion criteria consisted of a history of secondary inflammatory glaucoma, age C18 years, and uncontrolled IOP on
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maximal medical therapy necessitating surgical intervention. Glaucoma patients had glaucomatous optic nerve damage and a corresponding repeatable abnormal visual field (VF), defined as an abnormal glaucoma hemifield test or pattern standard deviation (PSD) outside 95 % normal limits. Glaucomatous optic neuropathy was defined as neuroretinal rim narrowing, notching, excavation, or retinal nerve fiber layer (RNFL) defect. All eyes were stable from an inflammatory standpoint and had no or trace cells prior to surgery. All eyes were followed for a postoperative period of C6 months or more. If both eyes of a patient were eligible, the left eye was excluded. Exclusion criteria consisted of any eyes with nonglaucomatous optic neuropathy, vitreoretinal disease, or prior glaucoma surgery. Trabeculectomy was performed in a standardized fashion using a limbus-based conjunctival flap and a modified Cairns technique. Mitomycin C or 5-fluorouracil was used to retard postoperative wound healing. Prednisolone acetate 1 % was used postoperatively, typically hourly while awake, with gradual titration to maintenance levels needed to control the uveitis. The surgeon was given the option to use subconjunctival or subtenon injection of triamcinolone acetonide perioperatively to assist with the control of uveitis. Systemic immunosuppression (e.g., prednisone, methotrexate, cyclosporine, adalimumab) was continued postoperatively in patients that required these medications for preoperative uveitis control. Laser suture lysis was performed at the discretion of the surgeon to maintain IOP control. GDD surgery was performed in a standardized fashion using either a 350-mm2 or 250-mm2 Baerveldt glaucoma implant (Abbott Medical Optics Inc., Abbott Park, IL, USA). The surgical technique has been described previously [14]. Briefly, a fornix-based conjunctival flap was dissected, and the implant was sutured to underlying sclera 10 mm posterior to the limbus. The implant was completely occluded to temporarily restrict flow through the device until encapsulation of the plate occurred. The surgeon was given the option of fenestrating the tube for early IOP reduction. The GDD was inserted into the anterior chamber through a 23-gauge needle track or into the pars plana through a 20-gauge microvitreoretinal track. Eyes that had the GDD placed in the pars plana also underwent vitrectomy to prevent vitreous from clogging the tube. A donor patch graft (sclera for superior GDD implants or half-thickness cornea for inferior GDD implants) was used to cover the limbal portion of the tube, and the conjunctiva was closed. We reviewed the medical records of patients satisfying enrollment criteria, and data was abstracted concerning patient demographics, type of glaucoma, method of surgical intervention, and postoperative complications. Data collected at each visit consisted of IOP measured by
TVT in uveitic glaucoma
Goldman applanation tonometry, number of IOP-lowering medications, number of immunomodulatory medications, visual acuity, and presence of postoperative complications. Data was collected at two baseline visits prior to surgery and postoperatively at 1 day; 1 week; 1, 3, and 6 months; and then at 6-month intervals. Statistical analysis was performed using JMP software version 8.0 (SAS Inc., Cary, NC, USA) and SPSS 18 (SPSS, Chicago, IL, USA). Clinical characteristics of the study population were compared using one-way analysis of variance (ANOVA) and independent samples t test. Univariate comparisons between treatment groups were conducted using a two-sided Student’s t test for continuous variables and the v2 test or Fisher’s exact test for categorical variables. Snellen visual acuity measurements were converted to logMAR equivalents for the purpose of data analysis. The primary outcome measure in this study was IOP reduction. A secondary outcome measure was surgical failure, defined as IOP[21 mmHg or not reduced by 20 % below baseline on two consecutive follow-up visits after 3 months, IOP B5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision [22]. The time to failure analysis was performed using Kaplan–Meier curves. Complications were divided into early (\3 months following IOP lowering surgery) or late (C3 months following IOP lowering surgery) onset. A P value of B0.05 was considered statistically significant.
Results Seventy-six eyes were identified as having inflammatory glaucoma requiring IOP-lowering surgery between January 2002 and December 2007 using billing record International Classification of Diseases, Ninth Revision (ICD9) 365.62 (glaucoma with ocular inflammation) and one of the following Current Procedural Terminology (CPT) codes: 66170 (trabeculectomy), 66172 (trabeculectomy with scarring), or 66180 (aqueous humor shunt implant). Thirtyfour eyes were excluded from the analysis due to insufficient follow-up, prior intraocular surgery, or comorbid ocular disease. Forty-two eyes of 42 patients met enrollment criteria. Four eyes receiving a trabeculectomy required a combined Cataract Extraction with Intra-Ocular Lens (CEIOL)/trabeculectomy procedure. However, no eyes receiving a GDD required a combined procedure. Baseline characteristics of the study population are summarized in Table 1. Nineteen eyes of 19 patients in the trabeculectomy group (mean age 66 ± 15 years) were followed for a mean of 31 ± 21 months; 23 eyes of 23 patients in the GDD group (mean age 59 ± 24 years) were followed for a mean of 39 ± 19 months (P = 0.22).
Eighteen trabeculectomy eyes received mitomycin C and one received 5-flourouracil. Twenty-three eyes received a 350-mm2 (n = 17) or 250-mm2 (n = 6) Baerveldt GDD. The etiology of uveitis was unknown in 50 % of eyes. The most common subtype of uveitis in both the tube and GDD cohorts consisted of anterior uveitis with mechanisms that included ankylosing spondylitis (n = 1), Fuchs heterochromic iridocyclitis (n = 2), herpes simplex virus (n = 2), juvenile rheumatoid arthritis (n = 2), nonHodgkin’s lymphoma (n = 1), Posner–Schlossman syndrome (n = 2), rheumatoid arthritis (n = 1), sarcoidosis (n = 1), uveitis-glaucoma-hyphema syndrome (n = 1), Vogt-Koyanagi-Harada (VKH) syndrome (n = 1), and unknown (n = 18). The mechanisms of intermediate uveitis included juvenile rheumatoid arthritis (n = 1) and multiple sclerosis (n = 1). One eye with posterior uveitis had a diagnosis of birdshot chorioretinopathy (n = 1). The mechanisms of panuveitis consisted of Bechet’s disease (n = 1), Crohn’s disease (n = 1), ocular histoplamosis (n = 1), tubulointerstitial nephritis and uveitis syndrome (n = 1), and unknown etiology (n = 3). As demonstrated in Table 2, the mean postoperative IOP was significantly lower in the trabeculectomy group through postoperative month 6; however, both groups had similar IOP (P [ 0.05) at all subsequent visits. The trabeculectomy group also received significantly fewer postoperative IOP-lowering medications at week 1 and months 1, 3, and 12; however, there were no significant differences beyond month 12. Figure 1 illustrates the cumulative probability of IOP failure, which was significantly greater in trabeculectomy eyes beyond 6 months’ follow-up compared with GDD eyes (P = 0.006). Overall failure rates during postoperative years 1, 2, 3, 4, and 5 were significantly higher in the trabeculectomy group (33 %, 55 %, 62 %, 62 %, 62 %) compared with the GDD group (9 %, 14 %, 14 %, 14 %, 25 %), (all P \ 0.05). Reasons for failure in the trabeculectomy group (n = 11) were eyes that underwent reoperation for uncontrolled IOP (n = 7) or hypotony (n = 1), two that had IOP[21 mmHg without reoperation, and one that developed persistent hypotony. The reasons for failure in the GDD group (n = 4) were IOP[21 mmHg in two eyes and the development of persistent hypotony in two. No eyes in either group failed due to loss of lightperception vision, and there was no significant difference in failure rates between eyes with anterior and nonanterior uveitis (P = 0.232). The cumulative probability of reoperation for IOP control (Fig. 2) was greater (P = 0.002) in the trabeculectomy group (8 eyes) compared with the GDD group (0 eyes). The overall frequency and types of postoperative complications were similar (P [ 0.05) between groups; however, the trabeculectomy group was significantly more likely to
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S. M. Iverson et al. Table 1 Baseline clinical characteristics of the study population (n = 42 eyes) Trabeculectomy (n = 19 eyes)
GDD (n = 23 eyes)
P value
Age (years)
66 ± 16
64 ± 20
0.65*
Male gender, n (%)
7 (37 %)
8 (35 %)
0.89**
Diabetes mellitus, n (%)
5 (26 %)
4 (17 %)
0.48**
Duration of follow-up (months)
31 ± 23
39 ± 19
0.22*
Intraocular pressure (mmHg)
26 ± 9
31 ± 12
0.16*
BCVA (logMAR)
0.63 ± 0.80
0.60 ± 0.67
0.91*
Number of IOP lowering medications
3.9 ± 1.0
3.5 ± 1.0
0.20*
Preoperative topical anti-inflammatory
13 (68 %)
17 (74 %)
0.70**
Preoperative anti-inflammatory orally
3 (15.8 %)
6 (26.1 %)
0.41**
Pseudophakia
10 (53 %)
19 (83 %)
Etiology, n (%) Idiopathic
11 (58 %)
10 (44 %)
Herpes simplex virus
2 (11 %)
0
Sarcoidosis
1 (5 %)
0
Fuchs heterochromic iridocyclitis
1 (5 %)
1 (4 %)
Birdshot
1 (5 %)
0
Ankylosing spondylitis
0
1 (4 %)
TINU syndrome
0
1 (4 %)
Vogt–Koyangi syndrome
0
1 (4 %)
Juvenile rheumatoid arthritis
1 (5 %)
2 (9 %)
Crohn’s disease
1 (5 %)
0
Uveitis-glaucoma-hyphema syndrome
0
1 (4 %)
Rheumatoid arthritis
0
1 (4 %)
Mucopolysaccharidosis
0
1 (4 %)
Behcet’s disease
1 (5 %)
0
Syphilis
0
1 (4 %)
Non-Hodgkin’s lymphoma Ocular histoplasmosis
0 0
1 (4 %) 1 (4 %)
Posner–Schlossman syndrome
0
1 (4 %)
Location of uveitis, n (%)
0.99***
Anterior
15 (78.9 %)
17 (73.9 %)
Intermediate
0
2 (8.7 %)
Posterior
1 (5.3 %)
0
Pan
3 (15.8 %)
4 (17.4 %)
1 (5 %)
3 (13 %)
Preoperative immunomodulatory therapy, n (%)
0.04** 0.22***
0.39**
GDD glaucoma drainage device, BCVA best-corrected visual acuity, logMAR logarithm of minimum angle of resolution, TINU tubulointerstitial nephritis and uveitis * Analysis of variance ** Chi-square test *** Fisher’s exact test
develop a postoperative complication (P [ 0.03) (Table 3): 16 (84 %) eyes in the trabeculectomy group and 12 (52 %) in the GDD group experienced at least one early or late postoperative complication. No eyes received intravitreal triamcinolone in the postoperative period; however, two in the trabeculectomy group required at least one subtenons triamcinolone injection for recurrent intermediate uveitis.
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Discussion Uveitis is a complex multifactorial ocular inflammatory disease process that often requires a multidisciplinary approach. Glaucoma is documented to occur in 20 % of all patients with chronic uveitis [1, 23], and considerably higher rates are reported in those with rheumatoid-arthritis-
TVT in uveitic glaucoma Table 2 Intraocular pressure (IOP) and number of glaucoma medications throughout follow-up
GDD glaucoma drainage device a
Values represent mean ± standard deviation
IOPa Trabeculectomy
Glaucoma medicationsa GDD
P
Trabeculectomy
GDD
P
Baseline
27.5 ± 8.8
30.8 ± 10.0
0.27
3.9 ± 0.9
3.7 ± 1.0
0.54
Day 1
15.4 ± 11.8
23.7 ± 13.6
0.045
0±0
0.3 ± 1.1
0.28
Week 1
9.8 ± 6.2
21.8 ± 11.8
\0.001
1.2 ± 1.4
2.5 ± 1.7
0.01
Month 1
12.3 ± 12.1
15.5 ± 12.7
0.42
0.8 ± 1.3
2.9 ± 1.7
\0.001
Month 3
9.9 ± 6.6
14.1 ± 5.6
0.05
0.8 ± 1.4
1.8 ± 1.4
0.04
Month 6
10.2 ± 5.1
14.0 ± 6.4
0.055
1.1 ± 1.5
1.6 ± 1.5
0.32
Month 12
15.3 ± 10.5
9.6 ± 4.5
0.10
1.0 ± 1.5
2.2 ± 1.5
0.04
Month 24
14.6 ± 4.1
13.8 ± 5.7
0.76
1.3 ± 1.7
1.2 ± 1.4
0.93
Month 36
11.0 ± 5.9
13.5 ± 4.2
0.33
1.2 ± 1.6
1.4 ± 1.4
0.78
Month 48
13.6 ± 7.7
11.1 ± 5.2
0.43
1.0 ± 1.3
1.6 ± 1.3
0.36
Month 60
12.0 ± 3.0
14.8 ± 5.6
0.45
1.3 ± 1.2
1.3 ± 1.4
1.00
Fig. 1 Kaplan–Meier plot of the cumulative probability of surgical failure defined as inadequate intraocular pressure (IOP) reduction \20 % from the baseline or [21 mmHg or an IOP measurement of B5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision (P = 0.006, log-rank test). Uveitic glaucoma patients who underwent trabeculectomy had a higher probability of failure after 12 months
associated iridocyclitis, Fuchs’ heterochromic iridocyclitis, Lyme-associated uveitis, and cancer-associated uveitis [2, 4, 5]. Inflammatory glaucoma often affects a younger patient population than primary open-angle glaucoma, so surgical interventions with good long-term IOP control should be sought when medical management fails to adequately control IOP. Due to the accelerated healing and an increased incidence of prolonged postoperative inflammation in this population, a noncomparative retrospective study suggests that GDD implantation may be the preferred
Fig. 2 Cumulative probability of reoperation for intraocular pressure (IOP) control was greater in the trabeculectomy group compared with the GDD group (P = 0.002, log-rank test). There were no reoperations for complications in the GDD group; however, eight eyes underwent reoperation for glaucoma in the trabeculectomy group
initial choice for surgical management of uveitic glaucoma resistance to medical therapy [13]. Our study was conducted to compare surgical outcomes of trabeculectomy and nonvalved GDD implantation in eyes with chronic inflammatory glaucoma and uncontrolled IOP. The surgical success rates in eyes with inflammatory glaucoma are highly variable. Studies report overall success rates of 50–100 % [9–12, 19, 24, 25] for trabeculectomy and 50–97 % [13–18] for GDD implantation, with higher failure rates typically reported in studies with longer follow-up. Other potential confounding variables include
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S. M. Iverson et al. Table 3 Postoperative complications among the study group (n = 42)
Trabeculectomya n = 19 (%)
GDDa n = 23 (%)
P value
Early postoperative complications (\3 months) Choroidal effusion
4 (21)
3 (13)
0.10
Hyphema
1 (5)
0
0.27
Vitreous hemorrhage
2 (11)
0
0.11
Shallow or flat anterior chamber
2 (11)
2 (9)
0.84
Cystoid macular edema
3 (16)
1 (4)
0.21
Hypotony
5 (26)
3 (13)
0.28
Diplopia
0
2 (9)
0.19
Corneal edema
2 (11)
0
0.11
Revision of tube
0
1 (4)
0.38
Hypotony maculopathy
2 (11)
0
0.11
Bleb revision
1(5)
0
0.27
Bleb encapsulation
1 (5)
0
0.27
Epiretinal membrane
1 (5)
0
0.27
Scleritis Vitritis
1 (5) 1 (5)
0 0
0.27 0.27
Serious retinal detachment
0
1 (4)
0.38
11 (58)
5 (22)
0.02
No. of eyes with early complications
Late postoperative complications (C3 months)
GDD glaucoma drainage device, PSC posterior subcapsular cataract
Persistent corneal edema
2 (11)
2 (9)
0.84
Encapsulated bleb
1 (5)
0
0.27
Choroidal effusion
1 (5)
1 (4)
0.89
Cystoid macular edema
2 (11)
5 (22)
0.33
Tube erosion
0
2 (9)
0.19
Tube obstruction/malposition
0
1 (4)
0.38
Microbial keratitis
0
1 (4)
0.36
Hypotony
0
1 (4)
0.36
Bleb revision
1 (5)
0
0.27
Epiretinal membrane
2 (11)
1 (4)
0.44
White PSC
0
1 (4)
0.36
5 (26) 16 (84)
8 (35) 12 (52)
0.56 0.03
No. of eyes with late complications Total no. of eyes with complications
ocular comorbidity, antifibrosis use, and GDD size, material, shape, and plate location [11, 17, 18, 26–28]. Molteno et al. [17] reported the results of Molteno implants in 40 eyes of 35 patients with uveitic glaucoma, with an 87 % success rate at 5 years. Papadaki et al. [18] evaluated outcomes after Ahmed glaucoma-valve implantation and found success rates of 77 % at 1 year and 50 % at 4 years. Ceballos and colleagues [13] reported a success rate of 91.7 % at 24 months after Baerveldt GDD implantation. In our study, the cumulative probability of surgical failure was greater in the trabeculectomy group compared with the GDD group (P = 0.006) during postoperative year 1–5. The most common reason for failure in the trabeculectomy group was glaucoma reoperation (n = 8) due to persistent IOP elevation (n = 7); however, one eye required reoperation for hypotony. Failure due to IOP [21 mmHg or IOP not reduced by 20 % occurred in two
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trabeculectomy (10.5 %) and two GDD (8.7 %) eyes. The 5-year failure rate in trabeculectomy eyes (62 %) was greater than the 47 % reported in the Treatment Outcomes in the Tube Versus Trabeculectomy (TVT) trial; uveitis was an exclusion criteria in that study [22]. Eyes in our study were at increased risk for excessive postoperative healing leading to episcleral fibrosis and bleb failure owing to chronic ocular inflammation. The 5-year failure rate of GDDs observed in our study (25 %) was comparable with the 29 % reported in the TVT trial [22]. This suggests that GDD surgical outcomes may be less influenced by postoperative inflammation compared with traditional glaucoma filtration surgery. We speculate that this may be related to the posterior-plate location, which results in less postoperative fibrosis compared with the perilimbal region. There was a significantly greater frequency of early complications in the trabeculectomy group compared with
TVT in uveitic glaucoma
the GDD group (P = 0.02): 11 (58 %) eyes in the trabeculectomy group and five (22 %) in the GDD group developed at least one early complication; however, there was no significant difference in the frequency of late postoperative complications between groups. These findings are consistent with complication frequencies and types reported in the TVT trial [29] and other studies [13, 20], suggesting a safety profile similar to trabeculectomy and GDD surgery for noninflammatory glaucoma. Eyes with chronic inflammation are predisposed to postoperative complications. In our study, ocular hypotony was the most common early (\3 months) adverse event. We found no difference in the incidence of postoperative hypotony (P = 0.50) or failure rates (P = 0.10) between eyes with 250- versus 350-mm2 GDD implant sizes. Cystoid macular edema (CME) was the most common late postoperative complication. Four eyes had a documented history of CME prior to surgery. Among the 11 eyes (5 trabeculectomy, 6 GDD) that developed postoperative CME, nine (82 %) were using topical corticosteroids and/or topical nonsteroidal therapy prior to surgery. No eyes required intravitreal triamcinolone during the postoperative period. This study has potential limitations. Due to the retrospective design, eyes were not randomized to treatment groups. We also had a relatively small sample size, and it was not possible to examine the influence of surgical intervention on postoperative uveitis control. The majority of patients in our study had anterior uveitis. Although we found no difference in overall failure rates between eyes with anterior and nonanterior uveitis (P = 0.47), these results may not be generalizable to eyes with intermediate, posterior, or pan uveitis. As patients were not randomized to treatment, it is possible that our results may have been influenced by inadvertent selection bias. In summary, nonvalved tube-shunt surgery was more likely to maintain IOP control and avoid reoperation for glaucoma compared with trabeculectomy with antifibrotic therapy in eyes with chronic inflammatory glaucoma. Both surgical procedures produced similar IOP reduction and use of supplemental medical therapy at mean follow-up of 3 years. Prospective randomized controlled trials are necessary to more fully explore the risks and benefits of each procedure in eyes with specific mechanisms of ocular inflammatory disease. Acknowledgments This study received a University of Miami Core Grant (P30-EY014801), Bethesda, MD; an unrestricted grant from Research to Prevent Blindness, New York, NY; a grant from the Department of Defense (W81XWH-09-1-0675); The Maltz Family Endowment for Glaucoma Research, Cleveland, OH. Conflicts of interest S. M. Iverson, None; N. Bhardwaj, None; W. Shi, None; M. Sehi, None; D. S. Greenfield, None; D. L. Budenz, None; K. Kishor, None.
References 1. Panek WC, Holland GN, Lee DA, Christensen RE. Glaucoma in patients with uveitis. Br J Ophthalmol. 1990;74:223–7. 2. Merayo-Lloves J, Power WJ, Rodriquez A, Pedroza-Seres M, Foster CS. Secondary glaucoma in patients with uveitis. Ophthalmologica. 1999;213:300–4. 3. Takahashi T, Ohtani S, Miyata K, Miyata N, Shirato S, Mochizuki M. A clinical evaluation of uveitis-associated secondary glaucoma. Jpn J Ophthalmol. 2002;46:556–62. 4. Foster CS, Havrlikova K, Baltatzis S, Christen WG, Merayo-Lloves J. Secondary glaucoma in patients with juvenile rheumatoid arthritisassociated iridocyclitis. Acta Ophthalmol Scand. 2000;78:576–9. 5. La Hey E, de Vries J, Langerhorst CT, Baarsma GS, Kijlstra A. Treatment and prognosis of secondary glaucoma in Fuchs heterochromic cyclitis. Am J Ophthalmol. 2002;46:556–62. 6. Jones R III, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17:163–7. 7. Razeghinejad MR, Katz LJ. Steroid-induced iatrogenic glaucoma. Ophthalmic Res. 2012;47:66–80. 8. Jampel HD, Jabs DA, Quigley HA. Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma. Am J Ophthalmol. 1990;109:168–73. 9. Prata JA Jr, Neves RA, Minckler DS, Mermoud A, Heuer DK. Trabeculectomy with mitomycin C in glaucoma associated with uveitis. Ophthalmic Surg. 1994;25:616–20. 10. Write MM, McGehee RF, Pederson JE. Intraoperative mitomycin-C for glaucoma associated with ocular inflammation. Ophthalmic Surg Lasers. 1997;28:370–6. 11. Patitsas CJ, Rockwood EJ, Meisler DM, Lowder CY. Glaucoma filtering surgery with postoperative 5-fluorouracil in patients with intraocular inflammatory disease. Ophthalmology. 1992;99:594–9. 12. Towler HM, Bates AK, Broadway DC, Lightman S. Primary trabeculectomy with 5-fluorouracil for glaucoma secondary to uveitis. Ocul Immunol Inflamm. 1995;3:163–70. 13. Ceballos EM, Parrish RK II, Schiffman JC. Outcome of Baerveldt glaucoma drainage implants for the treatment of uveitic glaucoma. Ophthalmology. 2002;109:2256–60. 14. Da Mata A, Burk SE, Netland PA. Management of uveitic glaucoma with Ahmed glaucoma valve implantation. Ophthalmology. 1999;106:2168–72. 15. Ozdal PC, Vianna RN, Deschenes J. Ahmed valve implantation in glaucoma secondary to chronic uveitis. Eye. 2006;20:178–83. 16. Rachmiel R, Trope GE, Buys YM, Flanagan JG, Chipman ML. Ahmed glaucoma valve implantation in uveitic glaucoma versus open-angle glaucoma patients. Can J Ophthalmol. 2008;43:462–7. 17. Molteno AC, Sayawat N, Herbison P. Glaucoma surgery outcome study: long-term results of uveitis with secondary glaucoma drained by Molteno implants. Ophthalmology. 2001;108:605–13. 18. Papadaki TG, Zacharopoulos IP, Pasquale LR, Christen WB, Netland PA, Foster CS. Long-term results of Ahmed glaucoma valve implantation for uveitic glaucoma. Am J Ophthalmol. 2007;144:62–9. 19. Sung VCT, Barton K. Management of uveitic glaucoma. Curr Opin Ophthalmol. 2004;15:136–40. 20. Ceballos EM, Beck AD, Lynn MJ. Trabeculectomy with antiproliferative agents in uveitic glaucoma. J Glaucoma. 2002;11:189–96. 21. Siddique SS, Suelves AM, Baheti U, Foster CS. Glaucoma and uveitis. Surv Ophthalmol. 2013;58:1–10. 22. Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brand JD, Budens DL. Tube versus trabeculectomy study group. Treatment outcomes in the tube versus trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153:789–803.
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S. M. Iverson et al. 23. Moorthy RS, Mermoud A, Baerveldt G, Minckler DS, Lee PP, Rao NA. Glaucoma associated with uveitis. Surv Ophthalmol. 1997;41:361–94. 24. Towler HM, Mcclusky P, Shaer B, Lightman S. Long-term follow-up of trabeculectomy with intraoperative 5-fluorouracil for uveitis-related glaucoma. Ophthalmology. 2000;107:1822–8. 25. Noble J, Derzko-Dzulynsky L, Rabinovitch T, Birt C. Outcome of trabeculectomy with intraoperative mitomycin C for uveitic glaucoma. Can J Ophthalmol. 2007;42:89–94. 26. Mills RP, Reynolds A, Emond MJ, Barlow WE, Leen MM. Longterm survival of Molteno glaucoma drainage devices. Ophthalmology. 1996;130:299–305.
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27. Valimaki J, Airaksinen PJ, Tuulonen A. Molteno implantation for secondary glaucoma in juvenile rheumatoid arthritis. Arch Ophthalmol. 1997;115:1253–6. 28. Vuori ML. Molteno aqueous shunt as a primary surgical intervention for uveitic glaucoma: long-term results. Acta Ophthalmol. 2010;88:33–6. 29. Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC. Tube versus trabeculectomy study group. Postoperative outcomes in the tube versus trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012;153:804–14.
CLINICAL INVESTIGATION
Surgical outcomes of inflammatory glaucoma: a comparison of trabeculectomy and glaucoma-drainage-device implantation Shawn M. Iverson • Namita Bhardwaj • Wei Shi • Mitra Sehi • David S. Greenfield Donald L. Budenz • Krishna Kishor
•
Received: 1 August 2014 / Accepted: 19 December 2014 Ó Japanese Ophthalmological Society 2015
Abstract Purpose Our aim was to compare surgical outcomes of trabeculectomy and nonvalved glaucoma-drainage-device (GDD) implantation in eyes with chronic inflammatory glaucoma and uncontrolled intraocular pressure (IOP). Methods A retrospective chart review was conducted on patients with glaucomatous optic neuropathy, chronic anterior or posterior segment inflammation, and C6 months postoperative follow-up. All eyes underwent trabeculectomy with either antifibrotic therapy or implantation of a Baerveldt GDD (Abbott Laboratories Inc., Abbott Park, IL, USA). Failure was defined as IOP [21 mmHg, \20 % reduction below baseline or IOP \5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision. Statistical methods consisted of Student’s t tests, v2 test, and Kaplan– Meier time to failure analysis. Results Nineteen trabeculectomies of 42 patients were followed for a mean of 31 ± 23 and 23 GDD eyes for a mean of 39 ± 19 months (P = 0.22). At last follow-up, mean IOP (11.83 ± 4.59 and 13.15 ± 6.11 mmHg, P = 0.45) and number of glaucoma medications (1.28 ± 1.56 and 1.26 ± 1.25, P = 0.97) were similar between the trabeculectomy and GDD groups. The frequency and types of postoperative complications in both
S. M. Iverson N. Bhardwaj W. Shi M. Sehi D. S. Greenfield K. Kishor (&) Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 7101 Fairway Drive, Palm Beach Gardens, FL 33418, USA e-mail: [email protected] D. L. Budenz Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
groups were similar. The cumulative probability of failure after 5 years of follow-up was significantly greater in trabeculectomy eyes (62 %) compared with GDD eyes (25 %) (P = 0.006). Conclusions Nonvalved tube-shunt surgery was more likely to maintain IOP control and avoid reoperation than trabeculectomy with antifibrotic therapy in eyes with chronic inflammatory glaucoma. Keywords Glaucoma Glaucoma drainage device Trabeculectomy Uveitis Intraocular pressure
Introduction Uveitis is a multietiological ocular inflammatory disease that leads to glaucomatous optic neuropathy in approximately 20 % of eyes [1–3]. Considerably higher rates of glaucoma (30–50 %) have been described in eyes with specific uveitic syndromes, including juvenile-rheumatoidarthritis-associated iridocyclitis, Fuchs’ heterochromic iridocyclitis, Lyme-associated uveitis, and cancer-associated uveitis [2, 4, 5]. Managing inflammatory glaucomas is particularly complex due to the number of clinical entities involved and the high likelihood of elevated intraocular pressure (IOP) secondary to long-term corticosteroid exposure [6, 7]. When uveitis is resistant to medical therapy, clinicians are presented with the challenge of determining which surgical procedure would best control IOP in the long term. The success rates of conventional filtering surgery in this population is reported to be highly variable (50–100 %) [8–12]. Glaucoma-drainage-device (GDD) implantation is thought to be an effective means of controlling IOP in the long term; however, success rates have been similarly varied (50–97 %) [13–18].
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A major challenge to successful filtration surgery in uveitis is the accelerated healing that occurs in the presence of postoperative inflammation. As a rule, suppression of inflammation in the perioperative period significantly improves outcomes [19]; however, there is no way to completely eliminate postoperative inflammation. The use of antifibrotics during filtering procedures may be employed to retard postoperative wound healing. However, up to 50 % of patients still develop bleb fibrosis and filtration failure within 5 years [8, 11, 12, 20]. Since the risk of failure in traditional filtration surgery in this cohort is high [8, 11, 12, 20], some specialists proceed directly to GDD implantation rather than attempting trabeculectomy [21]. Limited data exist comparing types of IOP-lowering surgery and its success rates in uveitic glaucoma. Gedde and colleagues [22] prospectively evaluated GDD versus trabeculectomy outcomes for the management of uncontrolled IOP. However, their study did not enroll several types of secondary glaucomas, including uveitic glaucoma. Because uveitic glaucoma can be particularly difficult to manage, we believe there should be a strong evidence base to support the type of IOP-lowering surgery that provides the best long-term IOP control in eyes that require reduction beyond what maximum medical therapy can attain. We performed this study to determine whether initial GDD implantation in uveitic glaucoma eyes provides superior outcomes and reduced complications compared with initial filtering surgery with adjuvant antifibrotic therapy.
Methods A retrospective chart review was conducted on consecutive patients with uveitic glaucoma who underwent surgical IOP reduction at Bascom Palmer Eye Institute (Miami, FL, USA) between 1 January 2002 and 31 December 2007. Glaucoma surgery was performed by two glaucoma specialists (DSG, DLB) based upon their clinical judgment. Eyes either underwent trabeculectomy with adjuvant antifibrotic therapy or received a GDD implant. The type of procedure was chosen based on what the surgeon thought would provide the best long-term outcome. Trabeculectomy was often chosen over GDD in eyes with minimal conjunctival scarring; however, there was no clear indication for a particular procedure in this cohort. The research was conducted in accordance with the Declaration of Helsinki for research involving humans, and Institutional Review Board approval was obtained from the office of Human Research at the University of Miami. The study complied with the requirements of the United States Health Insurance Portability and Accountability Act. Inclusion criteria consisted of a history of secondary inflammatory glaucoma, age C18 years, and uncontrolled IOP on
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maximal medical therapy necessitating surgical intervention. Glaucoma patients had glaucomatous optic nerve damage and a corresponding repeatable abnormal visual field (VF), defined as an abnormal glaucoma hemifield test or pattern standard deviation (PSD) outside 95 % normal limits. Glaucomatous optic neuropathy was defined as neuroretinal rim narrowing, notching, excavation, or retinal nerve fiber layer (RNFL) defect. All eyes were stable from an inflammatory standpoint and had no or trace cells prior to surgery. All eyes were followed for a postoperative period of C6 months or more. If both eyes of a patient were eligible, the left eye was excluded. Exclusion criteria consisted of any eyes with nonglaucomatous optic neuropathy, vitreoretinal disease, or prior glaucoma surgery. Trabeculectomy was performed in a standardized fashion using a limbus-based conjunctival flap and a modified Cairns technique. Mitomycin C or 5-fluorouracil was used to retard postoperative wound healing. Prednisolone acetate 1 % was used postoperatively, typically hourly while awake, with gradual titration to maintenance levels needed to control the uveitis. The surgeon was given the option to use subconjunctival or subtenon injection of triamcinolone acetonide perioperatively to assist with the control of uveitis. Systemic immunosuppression (e.g., prednisone, methotrexate, cyclosporine, adalimumab) was continued postoperatively in patients that required these medications for preoperative uveitis control. Laser suture lysis was performed at the discretion of the surgeon to maintain IOP control. GDD surgery was performed in a standardized fashion using either a 350-mm2 or 250-mm2 Baerveldt glaucoma implant (Abbott Medical Optics Inc., Abbott Park, IL, USA). The surgical technique has been described previously [14]. Briefly, a fornix-based conjunctival flap was dissected, and the implant was sutured to underlying sclera 10 mm posterior to the limbus. The implant was completely occluded to temporarily restrict flow through the device until encapsulation of the plate occurred. The surgeon was given the option of fenestrating the tube for early IOP reduction. The GDD was inserted into the anterior chamber through a 23-gauge needle track or into the pars plana through a 20-gauge microvitreoretinal track. Eyes that had the GDD placed in the pars plana also underwent vitrectomy to prevent vitreous from clogging the tube. A donor patch graft (sclera for superior GDD implants or half-thickness cornea for inferior GDD implants) was used to cover the limbal portion of the tube, and the conjunctiva was closed. We reviewed the medical records of patients satisfying enrollment criteria, and data was abstracted concerning patient demographics, type of glaucoma, method of surgical intervention, and postoperative complications. Data collected at each visit consisted of IOP measured by
TVT in uveitic glaucoma
Goldman applanation tonometry, number of IOP-lowering medications, number of immunomodulatory medications, visual acuity, and presence of postoperative complications. Data was collected at two baseline visits prior to surgery and postoperatively at 1 day; 1 week; 1, 3, and 6 months; and then at 6-month intervals. Statistical analysis was performed using JMP software version 8.0 (SAS Inc., Cary, NC, USA) and SPSS 18 (SPSS, Chicago, IL, USA). Clinical characteristics of the study population were compared using one-way analysis of variance (ANOVA) and independent samples t test. Univariate comparisons between treatment groups were conducted using a two-sided Student’s t test for continuous variables and the v2 test or Fisher’s exact test for categorical variables. Snellen visual acuity measurements were converted to logMAR equivalents for the purpose of data analysis. The primary outcome measure in this study was IOP reduction. A secondary outcome measure was surgical failure, defined as IOP[21 mmHg or not reduced by 20 % below baseline on two consecutive follow-up visits after 3 months, IOP B5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision [22]. The time to failure analysis was performed using Kaplan–Meier curves. Complications were divided into early (\3 months following IOP lowering surgery) or late (C3 months following IOP lowering surgery) onset. A P value of B0.05 was considered statistically significant.
Results Seventy-six eyes were identified as having inflammatory glaucoma requiring IOP-lowering surgery between January 2002 and December 2007 using billing record International Classification of Diseases, Ninth Revision (ICD9) 365.62 (glaucoma with ocular inflammation) and one of the following Current Procedural Terminology (CPT) codes: 66170 (trabeculectomy), 66172 (trabeculectomy with scarring), or 66180 (aqueous humor shunt implant). Thirtyfour eyes were excluded from the analysis due to insufficient follow-up, prior intraocular surgery, or comorbid ocular disease. Forty-two eyes of 42 patients met enrollment criteria. Four eyes receiving a trabeculectomy required a combined Cataract Extraction with Intra-Ocular Lens (CEIOL)/trabeculectomy procedure. However, no eyes receiving a GDD required a combined procedure. Baseline characteristics of the study population are summarized in Table 1. Nineteen eyes of 19 patients in the trabeculectomy group (mean age 66 ± 15 years) were followed for a mean of 31 ± 21 months; 23 eyes of 23 patients in the GDD group (mean age 59 ± 24 years) were followed for a mean of 39 ± 19 months (P = 0.22).
Eighteen trabeculectomy eyes received mitomycin C and one received 5-flourouracil. Twenty-three eyes received a 350-mm2 (n = 17) or 250-mm2 (n = 6) Baerveldt GDD. The etiology of uveitis was unknown in 50 % of eyes. The most common subtype of uveitis in both the tube and GDD cohorts consisted of anterior uveitis with mechanisms that included ankylosing spondylitis (n = 1), Fuchs heterochromic iridocyclitis (n = 2), herpes simplex virus (n = 2), juvenile rheumatoid arthritis (n = 2), nonHodgkin’s lymphoma (n = 1), Posner–Schlossman syndrome (n = 2), rheumatoid arthritis (n = 1), sarcoidosis (n = 1), uveitis-glaucoma-hyphema syndrome (n = 1), Vogt-Koyanagi-Harada (VKH) syndrome (n = 1), and unknown (n = 18). The mechanisms of intermediate uveitis included juvenile rheumatoid arthritis (n = 1) and multiple sclerosis (n = 1). One eye with posterior uveitis had a diagnosis of birdshot chorioretinopathy (n = 1). The mechanisms of panuveitis consisted of Bechet’s disease (n = 1), Crohn’s disease (n = 1), ocular histoplamosis (n = 1), tubulointerstitial nephritis and uveitis syndrome (n = 1), and unknown etiology (n = 3). As demonstrated in Table 2, the mean postoperative IOP was significantly lower in the trabeculectomy group through postoperative month 6; however, both groups had similar IOP (P [ 0.05) at all subsequent visits. The trabeculectomy group also received significantly fewer postoperative IOP-lowering medications at week 1 and months 1, 3, and 12; however, there were no significant differences beyond month 12. Figure 1 illustrates the cumulative probability of IOP failure, which was significantly greater in trabeculectomy eyes beyond 6 months’ follow-up compared with GDD eyes (P = 0.006). Overall failure rates during postoperative years 1, 2, 3, 4, and 5 were significantly higher in the trabeculectomy group (33 %, 55 %, 62 %, 62 %, 62 %) compared with the GDD group (9 %, 14 %, 14 %, 14 %, 25 %), (all P \ 0.05). Reasons for failure in the trabeculectomy group (n = 11) were eyes that underwent reoperation for uncontrolled IOP (n = 7) or hypotony (n = 1), two that had IOP[21 mmHg without reoperation, and one that developed persistent hypotony. The reasons for failure in the GDD group (n = 4) were IOP[21 mmHg in two eyes and the development of persistent hypotony in two. No eyes in either group failed due to loss of lightperception vision, and there was no significant difference in failure rates between eyes with anterior and nonanterior uveitis (P = 0.232). The cumulative probability of reoperation for IOP control (Fig. 2) was greater (P = 0.002) in the trabeculectomy group (8 eyes) compared with the GDD group (0 eyes). The overall frequency and types of postoperative complications were similar (P [ 0.05) between groups; however, the trabeculectomy group was significantly more likely to
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S. M. Iverson et al. Table 1 Baseline clinical characteristics of the study population (n = 42 eyes) Trabeculectomy (n = 19 eyes)
GDD (n = 23 eyes)
P value
Age (years)
66 ± 16
64 ± 20
0.65*
Male gender, n (%)
7 (37 %)
8 (35 %)
0.89**
Diabetes mellitus, n (%)
5 (26 %)
4 (17 %)
0.48**
Duration of follow-up (months)
31 ± 23
39 ± 19
0.22*
Intraocular pressure (mmHg)
26 ± 9
31 ± 12
0.16*
BCVA (logMAR)
0.63 ± 0.80
0.60 ± 0.67
0.91*
Number of IOP lowering medications
3.9 ± 1.0
3.5 ± 1.0
0.20*
Preoperative topical anti-inflammatory
13 (68 %)
17 (74 %)
0.70**
Preoperative anti-inflammatory orally
3 (15.8 %)
6 (26.1 %)
0.41**
Pseudophakia
10 (53 %)
19 (83 %)
Etiology, n (%) Idiopathic
11 (58 %)
10 (44 %)
Herpes simplex virus
2 (11 %)
0
Sarcoidosis
1 (5 %)
0
Fuchs heterochromic iridocyclitis
1 (5 %)
1 (4 %)
Birdshot
1 (5 %)
0
Ankylosing spondylitis
0
1 (4 %)
TINU syndrome
0
1 (4 %)
Vogt–Koyangi syndrome
0
1 (4 %)
Juvenile rheumatoid arthritis
1 (5 %)
2 (9 %)
Crohn’s disease
1 (5 %)
0
Uveitis-glaucoma-hyphema syndrome
0
1 (4 %)
Rheumatoid arthritis
0
1 (4 %)
Mucopolysaccharidosis
0
1 (4 %)
Behcet’s disease
1 (5 %)
0
Syphilis
0
1 (4 %)
Non-Hodgkin’s lymphoma Ocular histoplasmosis
0 0
1 (4 %) 1 (4 %)
Posner–Schlossman syndrome
0
1 (4 %)
Location of uveitis, n (%)
0.99***
Anterior
15 (78.9 %)
17 (73.9 %)
Intermediate
0
2 (8.7 %)
Posterior
1 (5.3 %)
0
Pan
3 (15.8 %)
4 (17.4 %)
1 (5 %)
3 (13 %)
Preoperative immunomodulatory therapy, n (%)
0.04** 0.22***
0.39**
GDD glaucoma drainage device, BCVA best-corrected visual acuity, logMAR logarithm of minimum angle of resolution, TINU tubulointerstitial nephritis and uveitis * Analysis of variance ** Chi-square test *** Fisher’s exact test
develop a postoperative complication (P [ 0.03) (Table 3): 16 (84 %) eyes in the trabeculectomy group and 12 (52 %) in the GDD group experienced at least one early or late postoperative complication. No eyes received intravitreal triamcinolone in the postoperative period; however, two in the trabeculectomy group required at least one subtenons triamcinolone injection for recurrent intermediate uveitis.
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Discussion Uveitis is a complex multifactorial ocular inflammatory disease process that often requires a multidisciplinary approach. Glaucoma is documented to occur in 20 % of all patients with chronic uveitis [1, 23], and considerably higher rates are reported in those with rheumatoid-arthritis-
TVT in uveitic glaucoma Table 2 Intraocular pressure (IOP) and number of glaucoma medications throughout follow-up
GDD glaucoma drainage device a
Values represent mean ± standard deviation
IOPa Trabeculectomy
Glaucoma medicationsa GDD
P
Trabeculectomy
GDD
P
Baseline
27.5 ± 8.8
30.8 ± 10.0
0.27
3.9 ± 0.9
3.7 ± 1.0
0.54
Day 1
15.4 ± 11.8
23.7 ± 13.6
0.045
0±0
0.3 ± 1.1
0.28
Week 1
9.8 ± 6.2
21.8 ± 11.8
\0.001
1.2 ± 1.4
2.5 ± 1.7
0.01
Month 1
12.3 ± 12.1
15.5 ± 12.7
0.42
0.8 ± 1.3
2.9 ± 1.7
\0.001
Month 3
9.9 ± 6.6
14.1 ± 5.6
0.05
0.8 ± 1.4
1.8 ± 1.4
0.04
Month 6
10.2 ± 5.1
14.0 ± 6.4
0.055
1.1 ± 1.5
1.6 ± 1.5
0.32
Month 12
15.3 ± 10.5
9.6 ± 4.5
0.10
1.0 ± 1.5
2.2 ± 1.5
0.04
Month 24
14.6 ± 4.1
13.8 ± 5.7
0.76
1.3 ± 1.7
1.2 ± 1.4
0.93
Month 36
11.0 ± 5.9
13.5 ± 4.2
0.33
1.2 ± 1.6
1.4 ± 1.4
0.78
Month 48
13.6 ± 7.7
11.1 ± 5.2
0.43
1.0 ± 1.3
1.6 ± 1.3
0.36
Month 60
12.0 ± 3.0
14.8 ± 5.6
0.45
1.3 ± 1.2
1.3 ± 1.4
1.00
Fig. 1 Kaplan–Meier plot of the cumulative probability of surgical failure defined as inadequate intraocular pressure (IOP) reduction \20 % from the baseline or [21 mmHg or an IOP measurement of B5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision (P = 0.006, log-rank test). Uveitic glaucoma patients who underwent trabeculectomy had a higher probability of failure after 12 months
associated iridocyclitis, Fuchs’ heterochromic iridocyclitis, Lyme-associated uveitis, and cancer-associated uveitis [2, 4, 5]. Inflammatory glaucoma often affects a younger patient population than primary open-angle glaucoma, so surgical interventions with good long-term IOP control should be sought when medical management fails to adequately control IOP. Due to the accelerated healing and an increased incidence of prolonged postoperative inflammation in this population, a noncomparative retrospective study suggests that GDD implantation may be the preferred
Fig. 2 Cumulative probability of reoperation for intraocular pressure (IOP) control was greater in the trabeculectomy group compared with the GDD group (P = 0.002, log-rank test). There were no reoperations for complications in the GDD group; however, eight eyes underwent reoperation for glaucoma in the trabeculectomy group
initial choice for surgical management of uveitic glaucoma resistance to medical therapy [13]. Our study was conducted to compare surgical outcomes of trabeculectomy and nonvalved GDD implantation in eyes with chronic inflammatory glaucoma and uncontrolled IOP. The surgical success rates in eyes with inflammatory glaucoma are highly variable. Studies report overall success rates of 50–100 % [9–12, 19, 24, 25] for trabeculectomy and 50–97 % [13–18] for GDD implantation, with higher failure rates typically reported in studies with longer follow-up. Other potential confounding variables include
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S. M. Iverson et al. Table 3 Postoperative complications among the study group (n = 42)
Trabeculectomya n = 19 (%)
GDDa n = 23 (%)
P value
Early postoperative complications (\3 months) Choroidal effusion
4 (21)
3 (13)
0.10
Hyphema
1 (5)
0
0.27
Vitreous hemorrhage
2 (11)
0
0.11
Shallow or flat anterior chamber
2 (11)
2 (9)
0.84
Cystoid macular edema
3 (16)
1 (4)
0.21
Hypotony
5 (26)
3 (13)
0.28
Diplopia
0
2 (9)
0.19
Corneal edema
2 (11)
0
0.11
Revision of tube
0
1 (4)
0.38
Hypotony maculopathy
2 (11)
0
0.11
Bleb revision
1(5)
0
0.27
Bleb encapsulation
1 (5)
0
0.27
Epiretinal membrane
1 (5)
0
0.27
Scleritis Vitritis
1 (5) 1 (5)
0 0
0.27 0.27
Serious retinal detachment
0
1 (4)
0.38
11 (58)
5 (22)
0.02
No. of eyes with early complications
Late postoperative complications (C3 months)
GDD glaucoma drainage device, PSC posterior subcapsular cataract
Persistent corneal edema
2 (11)
2 (9)
0.84
Encapsulated bleb
1 (5)
0
0.27
Choroidal effusion
1 (5)
1 (4)
0.89
Cystoid macular edema
2 (11)
5 (22)
0.33
Tube erosion
0
2 (9)
0.19
Tube obstruction/malposition
0
1 (4)
0.38
Microbial keratitis
0
1 (4)
0.36
Hypotony
0
1 (4)
0.36
Bleb revision
1 (5)
0
0.27
Epiretinal membrane
2 (11)
1 (4)
0.44
White PSC
0
1 (4)
0.36
5 (26) 16 (84)
8 (35) 12 (52)
0.56 0.03
No. of eyes with late complications Total no. of eyes with complications
ocular comorbidity, antifibrosis use, and GDD size, material, shape, and plate location [11, 17, 18, 26–28]. Molteno et al. [17] reported the results of Molteno implants in 40 eyes of 35 patients with uveitic glaucoma, with an 87 % success rate at 5 years. Papadaki et al. [18] evaluated outcomes after Ahmed glaucoma-valve implantation and found success rates of 77 % at 1 year and 50 % at 4 years. Ceballos and colleagues [13] reported a success rate of 91.7 % at 24 months after Baerveldt GDD implantation. In our study, the cumulative probability of surgical failure was greater in the trabeculectomy group compared with the GDD group (P = 0.006) during postoperative year 1–5. The most common reason for failure in the trabeculectomy group was glaucoma reoperation (n = 8) due to persistent IOP elevation (n = 7); however, one eye required reoperation for hypotony. Failure due to IOP [21 mmHg or IOP not reduced by 20 % occurred in two
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trabeculectomy (10.5 %) and two GDD (8.7 %) eyes. The 5-year failure rate in trabeculectomy eyes (62 %) was greater than the 47 % reported in the Treatment Outcomes in the Tube Versus Trabeculectomy (TVT) trial; uveitis was an exclusion criteria in that study [22]. Eyes in our study were at increased risk for excessive postoperative healing leading to episcleral fibrosis and bleb failure owing to chronic ocular inflammation. The 5-year failure rate of GDDs observed in our study (25 %) was comparable with the 29 % reported in the TVT trial [22]. This suggests that GDD surgical outcomes may be less influenced by postoperative inflammation compared with traditional glaucoma filtration surgery. We speculate that this may be related to the posterior-plate location, which results in less postoperative fibrosis compared with the perilimbal region. There was a significantly greater frequency of early complications in the trabeculectomy group compared with
TVT in uveitic glaucoma
the GDD group (P = 0.02): 11 (58 %) eyes in the trabeculectomy group and five (22 %) in the GDD group developed at least one early complication; however, there was no significant difference in the frequency of late postoperative complications between groups. These findings are consistent with complication frequencies and types reported in the TVT trial [29] and other studies [13, 20], suggesting a safety profile similar to trabeculectomy and GDD surgery for noninflammatory glaucoma. Eyes with chronic inflammation are predisposed to postoperative complications. In our study, ocular hypotony was the most common early (\3 months) adverse event. We found no difference in the incidence of postoperative hypotony (P = 0.50) or failure rates (P = 0.10) between eyes with 250- versus 350-mm2 GDD implant sizes. Cystoid macular edema (CME) was the most common late postoperative complication. Four eyes had a documented history of CME prior to surgery. Among the 11 eyes (5 trabeculectomy, 6 GDD) that developed postoperative CME, nine (82 %) were using topical corticosteroids and/or topical nonsteroidal therapy prior to surgery. No eyes required intravitreal triamcinolone during the postoperative period. This study has potential limitations. Due to the retrospective design, eyes were not randomized to treatment groups. We also had a relatively small sample size, and it was not possible to examine the influence of surgical intervention on postoperative uveitis control. The majority of patients in our study had anterior uveitis. Although we found no difference in overall failure rates between eyes with anterior and nonanterior uveitis (P = 0.47), these results may not be generalizable to eyes with intermediate, posterior, or pan uveitis. As patients were not randomized to treatment, it is possible that our results may have been influenced by inadvertent selection bias. In summary, nonvalved tube-shunt surgery was more likely to maintain IOP control and avoid reoperation for glaucoma compared with trabeculectomy with antifibrotic therapy in eyes with chronic inflammatory glaucoma. Both surgical procedures produced similar IOP reduction and use of supplemental medical therapy at mean follow-up of 3 years. Prospective randomized controlled trials are necessary to more fully explore the risks and benefits of each procedure in eyes with specific mechanisms of ocular inflammatory disease. Acknowledgments This study received a University of Miami Core Grant (P30-EY014801), Bethesda, MD; an unrestricted grant from Research to Prevent Blindness, New York, NY; a grant from the Department of Defense (W81XWH-09-1-0675); The Maltz Family Endowment for Glaucoma Research, Cleveland, OH. Conflicts of interest S. M. Iverson, None; N. Bhardwaj, None; W. Shi, None; M. Sehi, None; D. S. Greenfield, None; D. L. Budenz, None; K. Kishor, None.
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