PURPOSE
To elucidate risk factors for revision or removal of glaucoma drainage devices (GDD) in glaucoma patients in the United States.
DESIGN
Retrospective cohort study.
METHODS
IRIS Registry (Intelligent Research in Sight) patients who underwent GDD insertion between January 1, 2013 and December 31, 2018 were included. Various demographic and clinical factors were collected. Kaplan-Meier survival plots, Cox proportional-hazard models utilizing Firth’s Penalized Likelihood, and multivariate linear regression models were used. The main outcome measures were hazard ratios (HR) and beta coefficient (β) estimates.
RESULTS
A total of 44,330 distinct patients underwent at least 1 GDD implantation, and 3354 of these underwent subsequent GDD revision or removal surgery. With failure defined as GDD revision/removal, factors significantly associated with decreased failure included unknown race (HR = 0.83; P = .004) and unknown ethnicity (HR = 0.68; P < .001). Factors associated with increased risk of GDD revision/removal surgery included presence of chronic angle-closure glaucoma (HR = 1.32; P < .001) and dry eye disease (HR = 1.30; P = .007). Additionally, factors associated with a decreased average time (in days) to GDD revision/removal included male sex (β = -25.96; P = .044), unknown race (β = -55.28; P = .013), and right-eye laterality (β = -38.67; P = .026). Factors associated with an increased average time to GDD revision/removal included having a history of a past eye procedure (β = 104.83; P < .001) and being an active smoker (β = 38.15; P = .024).
CONCLUSIONS
The size and scope of the IRIS Registry allows for detection of subtle associations between risk factors and GDD revision or removal surgery. The aforementioned demographic and clinical factors may all have an impact on GDD longevity and can inform the treatment options available for glaucoma patients.
INTRODUCTION
G laucoma drainage devices (GDDs) reduce intraocular pressure (IOP) by creating an alternate drainage route for aqueous humor to bypass diseased trabecular meshwork. Over the past few decades and since results from the Tube Versus Trabeculectomy (TVT) study suggested that GDD implantation had comparable IOP-lowering ability and long-term effectiveness to trabeculectomy, with potentially fewer perioperative complications, GDDs have increasingly been used in the management of refractory glaucoma. , Similarly, a review of Medicare claims data between 1995 and 2004 demonstrated a 53% decrease in the number of trabeculectomies performed in eyes without scarring and a 184% increase in the number of aqueous shunting devices placed in eyes with and without scarring over the study period. Interestingly, in the primary TVT study, rates of surgical failure of trabeculectomies and GDD implantation surgery in eyes without prior surgery were comparable at 3 years postoperatively, although trabeculectomies may result in a slightly lower IOP and medication burden compared with GDD implantation surgery.
Despite the promising benefits of GDD surgery compared with trabeculectomy, GDDs are not without complications that may necessitate repeat surgery. For example, GDD erosion through the conjunctiva causes tube exposure, which poses a major risk of endophthalmitis and subsequent vision loss. Prior studies have reported rates of GDD revision or removal surgery between 2% to 12%, , , , and rates of tube exposure between 1% to 8.9%. , , , ,
As the use of GDDs continues to rise, it is important to elucidate risk factors for complications requiring GDD revision or removal surgery. Given that GDD tube exposures almost always require surgical correction and that risk factors for GDD tube exposure have previously been explored in the literature, this study evaluated the findings in the context of the current literature for GDD tube exposures. In addition, some studies have noted that tube exposure is one of the most common causes for repeat GDD surgery. , Since GDD revision or removal surgery may also be performed for a reason other than tube exposure—such as tube malpositioning or occlusion, conjunctival erosion, IOP elevation due to bleb fibrosis, corneal decompensation, chronic inflammation, iris-tube touch, and cornea-tube touch— the incidence of GDD revision or removal surgery should be inclusive of and greater than the expected incidence of GDD exposure. Prior studies have suggested that factors such as sex, age, Hispanic race, history of smoking, prior ocular surgeries, and topical steroid use are associated with GDD exposure specifically; , , , , the current study hypothesized that similar factors may increase the risk of GDD revision or removal surgery among those who have a revision or removal. However, there is no current consensus in the literature regarding risk factors for GDD exposure ( Tables 1 and 2 ).
| Publication Author, Year | Present study | Al-Beishri et al., 2019 | Zhou et al., 2018 | Chaku et al., 2016 | Trubnik et al., 2015 |
|---|---|---|---|---|---|
| Journal | – | J Glaucoma. | J Ophthal Vis Res. | Clin Ophthal. | J Glaucoma. |
| Study type | R | R | R | R | R |
| Follow-up (months) | – | – | Mean 39.8 (erosion group), 30.1 (non-erosion group) | Mean 27.6 | Mean 24.1 (erosion group), 20.3 (non-erosion group) |
| Total number of eyes | 44,330 (with GDDs) | 836 (53-53 matched case-control) | 306 | 64 (32-32 matched case-control) | 339 |
| Number of GDD tube exposures or removals | 3354 (7.57%) over 6 years | 53 (6.3%) over 7 years | 23 (7.52%) over 10 years | – | 28 (8.3%) over 5 years |
| Risk factors associated with GDD exposure or repeat GDD surgery | Factors associated with risk of revision/ removal GDD surgery – Dry eye disease – CACG – Unknown race/ ethnicity (protective) Factors associated with time to revision/removal surgery – Smoking status – Prior eye procedure – Unknown race – Male sex (shorter time) – Right-eye laterality (shorter time) | – Older age – Female sex – Baerveldt GDD compared with Ahmed GDD – History of ocular surgeries | – Aphakia – Uveitic glaucoma – Longer use of postoperative steroids | – Younger age – Ocular inflammation – Pediatric and uveitic glaucoma | – Concomitant surgical procedures at time of GDD implantation |
| Factors not associated with GDD exposure or repeat GDD surgery | – Asian race – Black race – Other race – Age | – Diabetes mellitus – Cardiac disease – Scleral patch graft (protective) – GDD location – Suture material used to secure the tube or plate – Prior history of intraoperative MMC/5-FU – Preoperative use of alpha-agonists – Preoperative use of CAI – Preoperative use of cholinergic drugs – Preoperative use of beta-blockers | – Age – Sex – Race – Hypertension – Diabetes mellitus – Prior glaucoma laser procedure – Prior glaucoma surgery – Type of patch graft – Implant location (superior versus inferior) – Concomitant surgical procedures – Preoperative BCVA, IOP, or number of meds – Preoperative or postoperative prostaglandin use | – Diabetes mellitus (Protective) – GDD type – GDD location – Sex – Ethnicity/race – Eye laterality – Lens status – Number of prior surgical procedures – Hypertension – Immune system abnormalities | – Prior surgeries – Post-GDD surgeries – Smoking – Seasonal allergies – Dry eye syndrome – Hypertension – Diabetes – Rheumatological conditions – Oral steroids/immunomodulators – MMC/Avastin/Triescence – Type of glaucoma – Contact lens use – Number of preoperative topical medications – GDD type – GDD location – GDD position in eye (ie, AC, PC, PP) – Patch graft material |
| Publication, Author, Year | Geffen et al., 2014 | Muir et al., 2014 | Koval et al., 2013 | Stewart et al., 2010 | Byun et al., 2009 |
|---|---|---|---|---|---|
| Journal | J Glaucoma. | BMJ Open. | J Ophthal. | Eur J Ophthal. | Jpn J Ophthal. |
| Study type | R | R | R | R (meta-analysis) | R |
| Follow-up (months) | Mean 43.5 (range 12-103) | Mean 41 (range 12-84) | Mean 56.6 (range 0.3-161) (control group) | Mean 26.1 | – |
| Total number of eyes | 158 | 1073 | 121 (41-80 matched case-control) | 3255 | 266 (11-44 matched case-control) |
| Number of GDD tube exposures | 14 (8.9%) over 8 years | 67 (6.24%) over 6 years | – | 64 (2.0%) (0.09% per month) | 11 (4.1%) over 4 years |
| Risk factors associated with GDD exposure | – Higher number of preoperative hypotensive medications | – Female sex – White race compared to Black race – Older age for men | – Hispanic ethnicity – Neovascular glaucoma – Previous trabeculectomy – Combined surgery | – Length of follow-up | – Number of prior ocular surgeries |
| Factors not associated with GDD exposure | – Age – Sex – Type of glaucoma – Prior glaucoma procedures – Prior ocular trauma – Prevalence of ocular inflammatory and surface diseases requiring treatment – Postoperative use of topical steroids – Incision type (ie, fornix versus limbal base) – Inferotemporal valve position (protective) | – Age in females – Diabetes mellitus – GDD location (superior versus inferior) – Patch graft material – Pre-existing GDD prior to surgery – GDD type | – Age – Sex – Diabetes mellitus – Hypertension – Preoperative IOP – Number of glaucoma medications – Prior GDD implantation – Prior laser procedure – Prior EL/PRP, PK/PKP, or vitrectomy – GDD type – GDD location – Patch graft type | – GDD type – Study length | – Age – Sex – GDD location – Diabetes mellitus – Hypertension – Type of glaucoma |
Given that prior studies may have been limited by the availability of patient data at a single institution, the American Academy of Ophthalmology (AAO) Intelligent Research in Sight
(IRIS) Registry provides a unique opportunity to identify subtle biomarkers and risk factors related to ocular diseases in patients across multiple practices throughout the United States. As of September 2019, the Registry contained 252.95 million patient encounters comprising 60.78 million unique patients. Using the big-data characteristics of the IRIS Registry, this study aimed to examine characteristics of patients undergoing GDD insertion, determine the incidence of GDD revision and removal surgery among these patients, and to elucidate potential risk factors associated with the need for repeat surgery and the time at which surgery is needed.
METHODS
The methods of data collection of the IRIS Registry have previously been described. The AAO provided access to a limited version of the IRIS Registry for academic research to 4 different academic institutions in the spring of 2019. The version of the IRIS Registry used in this study was frozen on October 23, 2020 and accessed on November 12, 2020. This study was conducted in accordance with the Declaration of Helsinki. Given the use of de-identified data, the study was exempt from approval by the Mass General Brigham Institutional Review Board.
All patients with a documented GDD insertion between January 1, 2013 and December 31, 2018, from the IRIS Registry were included in this study. Glaucoma drainage device insertions were identified by Current Procedure Terminology (CPT) (Fourth edition) codes 66179 and 66180. Patients with repeat GDD surgery were identified using CPT codes for GDD revision surgery (66184 or 66185) or GDD removal surgery (67120). If a patient had more than 1 GDD insertion, only the first (earliest recorded) instance was used. Revision and removal cases were further identified by including only instances where GDD revision or removal surgery occurred after the date of GDD insertion, and where the laterality aligned with that of the GDD insertion. If there were multiple instances of GDD revision or removal, the instance recorded in closest proximity to the date of GDD insertion was included.
The following demographic and clinical factors were extracted: age; sex; race; ethnicity; smoking history; glaucoma diagnosis based on International Classification of Disease (ICD) (9th and 10th editions) codes; history of trabeculectomy based on CPT codes; and several systemic disease diagnoses based on ICD codes, including rheumatoid arthritis, diabetes mellitus (type 1 and type 2), systemic lupus erythematosus, hypertension, chronic obstructive pulmonary disease, and asthma. Presence or absence of precipitating diagnoses to revision/removal—such as tube shunt exposure, conjunctival erosion, tube occlusion/malposition, IOP elevation due to bleb fibrosis, corneal decompensation, chronic inflammation, iris-tube touch, cornea-tube touch, or other mechanical complications of ocular prosthetic devices, implants, and grafts—were also extracted using ICD codes. Race was categorized as ‘Other’ for individuals who chose not to self-identify as Caucasian, Asian, or Black or African American, and as ‘Unknown’ if individuals chose not to self-identify at all. Similarly, ethnicity was also categorized as ‘Unknown’ if individuals chose not to self-identify in this regard. Individuals who self-identified as ‘Non-Hispanic or Latino’ are those that identified as neither Hispanic nor Latino and will henceforth be referred to as ‘Non-Hispanic/Latino’. A full list of ICD and CPT codes used in this study is presented in Table 3 .
| Diagnosis/Procedure | ICD 10 | ICD 9 | CPT |
|---|---|---|---|
| Ocular hypertension | H40.04 | 365.04 | |
| Unspecified open-angle | H40.10 | 365.10 | |
| Primary open-angle | H40.11 | 365.11 | |
| Low-tension | H40.12 | 365.12 | |
| Pigmentary | H40.13 | 365.13 | |
| Pseudoexfoliation | H40.14 | 365.52 | |
| Residual stage | H40.15 | 365.15 | |
| Unspecified primary open-angle | H40.20 | 365.20 | |
| Acute angle-closure attack | H40.21 | 365.22 | |
| Chronic angle-closure | H40.22 | 365.23 | |
| Intermittent angle-closure | H40.24 | 365.24 | |
| Secondary to trauma | H40.3 | 365.65 | |
| Secondary to inflammation | H40.4 | 365.62 | |
| Secondary to other eye disorders | H40.5 | 365.60 | |
| Secondary to drugs | H40.6 | 365.3 | |
| Increased episcleral venous pressure | H40.81 | 365.82 | |
| Hypersecretion | H40.82 | 365.81 | |
| Congenital | Q15.0 | 365.4 | |
| Rheumatoid arthritis | M06.9 | 714.0 | |
| Systemic lupus erythematosus | M32.9 | 710.0 | |
| Diabetes mellitus type I | E10 | 250.01 | |
| Diabetes mellitus type II | E11 | 250.00 | |
| Hypertension | I10, I11, I12, I13, I15, I16 | 401.0, 401.1, 401.9 | |
| Asthma | J45.0-J45.998 | 493.00-494.99 | |
| Chronic obstructive pulmonary disease | J40, J41.0, J41.1, J41.8, J42, J43.0, J43.1, J43.2, J43.8, J43.9, J44.0, J44.1, J44.9, J47 | 491.0, 491.1, 491.2, 491.21, 491.22, 491.8, 491.9, 492.0, 492.8, 494.0, 494.1, 496, 506.4 | |
| Dry eye | H04.121, H04.123, H04.129 | 375.15 | |
| Tube shunt exposure | Y77.2 | ||
| Conjunctival erosion | H11.10 | 372.50 | |
| Tube occlusion/malposition | T85.39 | ||
| IOP elevation due to bleb fibrosis | H59.4 | 379.60 | |
| Corneal decompensation | H18.899 | 371.89 | |
| Implant extrusion | T85.39 | 996.59 | |
| Chronic inflammation | H20.9 | 364.3 | |
| Iris-tube touch | Y77.2 | ||
| Cornea-tube touch | Y77.2 | ||
| Wound dehiscence | T81.31 | 998.32 | |
| Other mechanical complication of other ocular prosthetic devices, implants, and grafts | T85.39 | 996.59 | |
| GDD insertion | 66179, 66180 | ||
| GDD revision | 66184, 66185 | ||
| GDD removal | 67120 | ||
| Trabeculectomy | 66170 |
Descriptive statistics and frequencies were calculated for all relevant variables. Survival analysis was performed with failure defined as having GDD revision or removal surgery. Kaplan-Meier (KM) plots of survival were constructed and stratified by baseline and clinical characteristics. Survival curves between groups were compared using log-rank tests. Despite the small overall incidence of repeat GDD surgery relative to the patient cohort, the log-rank test results were able to offer insight into differences in the pattern of survival over time between each stratum of interest, even though the curves themselves failed to clearly visualize these differences due to the non-parametric nature of the test and given that it is robust to censoring, assuming that the censoring is non-informative.
To appropriately account for the small number of events in this sample, particularly relative to the number of censored observations, Cox regression models utilizing Firth’s Penalized Likelihood correction (CRFPL) were fit to the data to reduce bias in the estimates. , Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from the CRPFL models using baseline characteristics. Univariate and multivariate linear regression models were also fit to model the average days from GDD insertion to revision or removal against baseline characteristics. Fully saturated models using all baseline covariates were fit first for both model types. Final multivariate linear regression models were derived from the full model via automated stepwise selection utilizing Akaike’s Information Criterion. Akaike’s Information Criterion is used as a quality metric to evaluate how well a model fits the data, relative to other models, using a weighted log-likelihood formula. The automated stepwise selection package used on the multivariate linear regression model was not compatible with the CRFPL model; therefore, the final CRFPL model was derived using backward selection with a P -value selection threshold of P = .05. All models and selection procedures were run on the full cohort of patients with a GDD insertion without stratifying on repeat surgery type, and were also separately run on GDD revision patients only and GDD removal patients only to determine if there were different risk factors between these two types of repeat surgeries. All analyses were conducted in R statistical programming software (version 3.5.1).
RESULTS
Between January 1, 2013 and December 31, 2018, 44,330 distinct patients in the IRIS registry underwent at least 1 GDD implantation. Of these, 3354 patients underwent at least 1 subsequent GDD revision or removal surgery in the same eye, hereafter known as “repeat GDD surgery.” The incidence of repeat GDD surgery was 3354 of 44,330 patients (7.57%) over the course of 6 years. Of these patients, 2933 of 3354 (87.45%) had a GDD revision, while 421 (12.55%) had a GDD removal. The demographic and clinical characteristics of these patients are listed in Table 4 . Some of the most common characteristics (> 75% of total cohort) among patients included in the total cohort were: Non-Hispanic/Latino ethnicity (77.97%), aged ≥ 55 years (82.21%), and no history of prior eye procedures (94.90%).
| Variable | N (%) | Variable | N (%) |
|---|---|---|---|
| Number of patients | 44,330 | Age at GDD insertion | |
| Sex | 0-18 | 488 (1.10) | |
| Female | 20,706 (46.71) | 19-25 | 408 (0.92) |
| Male | 23,624 (53.29) | 26-54 | 6990 (15.77) |
| Race | 55+ | 36,444 (82.21) | |
| Asian | 1332 (3.00) | Smoking status | |
| Black or African American | 11,678 (26.35) | Active | 7637 (17.23) |
| Caucasian | 24,604 (55.50) | Former | 4147 (9.35) |
| Other | 1321 (2.98) | Never | 32,546 (73.42) |
| Unknown | 5395 (12.17) | Laterality | |
| Ethnicity | Right | 11,894 (26.83) | |
| Hispanic or Latino | 5438 (12.27) | Left | 11,496 (25.93) |
| Not Hispanic or Latino | 34,565 (77.97) | Unknown | 20,940 (47.24) |
| Unknown | 4327 (9.76) | Prior eye procedures | |
| Severity | Yes | 2259 (5.10) | |
| Mild | 5646 (12.7) | No | 42,071 (94.90) |
| Moderate | 5470 (12.3) | Had revision/removal surgery | |
| Severe | 53 (0.2) | Yes | 3354 (7.57) |
| Unknown | 33,161 (74.80) | No | 40,976 (92.43) |
| Revision/removal surgery type 1 | |||
| Revision | 2933 (87.45) | ||
| Removal | 421 (12.55) | ||
| Comorbid systemic diseases 2 | |||
| Asthma | 50 (0.11) | Dry eye disease | 1214 (2.74) |
| COPD | 25 (0.06) | Systemic hypertension | 789 (1.78) |
| Diabetes mellitus, type I | 276 (0.62) | Rheumatoid arthritis | 26 (0.06) |
| Diabetes mellitus, type II | 2833 (6.39) | Systemic lupus erythematosus | 8 (0.02) |
| Glaucoma types 2 | |||
| Primary open-angle | 13,117 (29.59) | Increased episcleral venous pressure | 28 (0.06) |
| Angle-closure | 2260 (5.10) | Low-tension | 242 (0.55) |
| Congenital | 112 (0.25) | Ocular hypertension | 1575 (5.3) |
| Medication-induced | 379 (0.85) | Pigmentary | 372 (0.84) |
| Secondary to eye trauma | 774 (1.75) | Pseudoexfoliation | 939 (2.12) |
| Quantitative Characteristics | |||
| Variable | Mean (SD) | Range (Min-Max) | Median |
| Days to GDD revision/removal 1 | 293.82 (373.45) | (1.00-2133.00) | 133.00 |
| Days of total follow-up 3 | 1744.75 (709.35) | (1.00-3173.00) | 1689.00 |
| Age at GDD insertion (in years) | 65.42 (14.16) | (0.00-86.00) | 68.00 |
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