Purpose To assess the outcomes of the non-valved Aurolab aqueous drainage implant (AADI) in neovascular glaucoma (NVG).
Methods Data of consecutive patients with NVG who underwent AADI and had a minimum follow-up of 2 years were included. The primary outcome measure was the cumulative rate of surgical failure defined as intraocular pressure (IOP) >21 mm Hg or reduced <20% below baseline, IOP ≤5 mm Hg, reoperation for glaucoma or a complication, or loss of light perception vision.
Results We included 85 eyes of 85 patients with NVG, with a mean age of 61.2±9.3 years. The most common aetiologies were proliferative diabetic retinopathy (n=43) and central retinal vein occlusion (n=24). The mean IOP decreased from 36.8±12.5 mm Hg at baseline to 15.8±7.5 mm Hg at 2-year follow-up (p<0.001) and the number of IOP-lowering medications reduced from 3.4±0.8 to 1.5±1.1 (p<0.001). The cumulative rate of failure increased from 3.1% (95% CI 1.1% to 11.8%) at 1 year to 33.8% (95% CI 20.4% to 52.5%) at 2 years. Multivariable analysis showed that eyes with open angles had a lower risk of failure (HR 0.17, 95% CI 0.10 to 1.03, p=0.09). The logarithm of minimum angle of resolution visual acuity declined from 0.98±0.7 to 1.8±1.0 at 2 years (p<0.001).
Conclusion Approximately one-third of NVG eyes that received the AADI failed after 2 years of follow-up similar to other series. Early AADI implantation at the open angle stage of NVG may yield better results.
- intraocular pressure
- treatment surgery
Data availability statement
Data are available on reasonable request. Not applicable.
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Utilisation of glaucoma drainage devices (GDDs) to manage eyes with refractory glaucoma has increased over time,1 and a growing number of glaucoma specialists are selecting GDDs as an alternative to trabeculectomy.2 Neovascular glaucoma (NVG) is a subset of refractory glaucoma that is especially difficult to manage and involves iris and angle neovascularisation secondary to an ischaemic disease process affecting the eye. With the advent of antivascular endothelial growth factor (VEGF) agents to manage retinal diseases, the incidence of NVG may be on the decline,3 yet it is still prevalent in many resource-poor settings across the world.
Medical management of NVG involves treatment of the underlying retinal ischaemia with panretinal photocoagulation (PRP) with or without anti-VEGF injections, and use of intraocular pressure (IOP)-lowering medications to control the IOP. The open angle stage of NVG responds relatively well to medical management in most instances, however, the closed angled stage of NVG usually requires surgical management.4 Trabeculectomy with mitomycin C has a high risk of failure with survival rates dropping from 62%–82% at 1 year to below 50% at 2 years.5–7 The preoperative use of anti-VEGF reduces the risk of hyphema after trabeculectomy,7 and likely helps with bleb survival. Given the high failure rate of trabeculectomy, GDDs have become preferred for the management of NVG.2 8 9
The Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, California, USA) is often used in eyes with NVG because of the immediate lowering of IOP and reduced risk of hypotony.4 8 10 11 Many previous studies have shown the prolonged beneficial effects of the AGV in NVG.8 10–14 However, the use of non-valved implants have not been well studied for NVG. As seen from previous studies as well as from the Ahmed vs Baerveldt (AVB) Study,15 the Baerveldt Glaucoma Implant (BGI; Abbott Medical Optics, Abbott Park, Illinois, USA) has greater IOP lowering effect over prolonged periods of time, although with a slightly higher incidence of hypotony, hence it may be a viable option for IOP lowering in eyes with NVG as well.
The Aurolab aqueous drainage implant (AADI; Aurolab, Madurai, India) is now an established cost-effective variant of the BGI and has been proven to significantly reduce IOP in various settings in both adult and paediatric glaucoma.16 17 Our previous study in adult eyes with refractory glaucomas included NVG,17 however, the numbers were small and subgroup analysis for eyes with NVG was not possible. Here, we report the efficacy and safety outcomes from an expanded cohort of 85 eyes with NVG that received the AADI surgery and had a minimum follow-up of 2 years.
Case records of consecutive adult patients who underwent the AADI surgery for NVG between January 2012 and December 2018 were identified from a computerised database using International Classification of Diseases-10 coding, and case records of patients with a minimum of 2 years follow-up were included.
We recorded the patient demographics information, best-corrected visual acuity (BCVA) at the time of AADI and clinical characteristics at baseline including underlying aetiology for NVG (central retinal vein occlusion (CRVO), proliferative diabetic retinopathy (PDR) and others), previous PRP and the number of treatments, anti-VEGF injections in the past along with the number of injections, the number of glaucoma medications, previous ocular surgery, automated visual field parameters (mean deviation and pattern SD), and the date of AADI surgery from case files. Eyes with NVG with no documented peripheral anterior synechiae on gonioscopy were classified as open angle glaucoma. The IOP, number of IOP-lowering medications, BCVA, complications and reoperations were also recorded at day 1 and then at 1, 3, 6, 9, 12, 18 and 24 months postoperatively. All procedures were performed by two surgeons (GVP and SRK) both of whom were well versed with the technique of AGV implantation prior to the advent of the AADI. The surgical technique and the postoperative regimen have been described in detail elsewhere.17 18 The tube was ligated in a watertight fashion near the tube-explant junction using two interrupted 6–0 polyglactin sutures (braided coated polyglactin 910 violet; Ethicon, Johnson & Johnson, Mumbai, India). A piece of donor cornea or sclera was secured over the tube entry site in eyes in which the tube was inserted into the anterior chamber through a 23-gauge needle track initiated 2–2.5 mm posterior to the limbus. Donor patch free technique of tube implantation was followed in eyes in which the 23-gauge needle track was initiated 4 mm posterior to the limbus.
Patients underwent AADI implantation only after quiescence of the underlying retinal pathology responsible for the NVG was achieved.
Primary outcome measure
Surgical failure of the AADI was defined as IOP >21 mm Hg or reduced <20% below baseline on two consecutive follow-up visits after 3 months, IOP ≤5 mm Hg on two consecutive follow-up visits after 3 months, reoperation for glaucoma or a complication, or loss of light perception vision. Eyes that had not failed by the above criteria and were not receiving IOP-lowering medications were considered complete success, and those receiving IOP-lowering medications were qualified success.
Continuous variables were expressed as mean with SD and group differences were analysed using Student’s t-test or the Wilcoxon ranksum test for non-parametric variables when comparing across two groups. The analysis of variance (ANOVA) or the Kruskall-Wallis test was used to compare continuous variables across three or more groups. Categorical variables were expressed as proportions (n, %), and group differences were analysed using the χ2 or the Fischer’s exact test. Visual acuity was converted to logarithm of minimum angle of resolution for statistical analysis. The comparison of IOP between pre-AADI and post-AADI at different time intervals was carried out using one-way ANOVA with Bonferroni adjustments.
Survival analysis was performed and Kaplan-Meier curves were plotted to depict cumulative survival rates at various time points in eyes with NVG. Kaplan-Meier curves were also plotted to compare outcomes with respect to different types of NVG aetiologies (PDR, CRVO and others), as well as for comparing open angle vs closed angle NVG. Differences in survival rates between these groups were determined using log-rank test. The risk of failure was also assessed using the Cox proportional hazards models and displayed using HR with 95% CI. Data were entered into Microsoft Excel and analysed using STATA (V.12.1, I/C) statistical analysis software package and a p<0.05 was considered statistically significant.
A total of 882 AADI implantations were performed during the 7-year study period, of which 626 (71%) were in adults and 256 (29%) were in paediatric patients (age <18 years). We included 85 eyes of 85 patients with NVG that satisfied the inclusion criteria. A summary of the baseline demographics and clinical characteristics of patients are shown in table 1. The median age of patients was 63 years (IQR=55–68 years, range=32–84 years) and a majority (80%) were males. The AADI was the first IOP lowering surgery in most eyes with only 6% having undergone prior trabeculectomy. Patients had quiescent retinal disease status following PRP (mean of 2.8±1.3 treatments) and anti-VEGF injections (mean of 1.6±1.3 injections) before AADI surgery, although residual NVI and/or NVA was seen in more than half of the eyes in the study. Seventy (82%) patients in our study cohort received anti-VEGF injection prior to AADI surgery. The average follow-up post-AADI was 30 months.
The most common underlying aetiologies for NVG in our series was PDR (n=43, 50%) and CRVO (n=24, 28%). The other eyes with NVG had ocular ischaemic syndrome (n=7), postmultiple VR surgery (n=3), vasculitis (n=2), branch vein occlusion (n=2) and one eye each with aphakia, exudative vitreoretinopathy, hemiretinal vein occlusion and central retinal artery occlusion. A comparison of baseline factors among PDR and CRVO (table 1) showed that patients with CRVO were significantly older. Both groups had received anti-VEGF injections and PRP sittings in the past for their retinal disease. About a quarter of eyes with PDR had undergone vitrectomy compared with none in the CRVO group. There were no other differences between these groups.
A comparison of IOP, visual acuity and IOP-lowering medications at baseline and across follow-up overall and between the PDR and CRVO groups is shown in table 2. The IOP dropped by 5 mm Hg on an average at 1-month follow-up (p=0.02), was significantly lower from baseline at 3-month time point (figure 1) and this was maintained over the 2-year follow-up period (p<0.001 for all time points compared with baseline). A similar trend was seen in IOP-lowering medications, with a significant reduction at 3 months and this was maintained over the 2 years of follow-up. However, there was a continuous drop in vision from approximately 20/200 at baseline to counting fingers vision at the 2-year time point (p<0.001). Comparing across PDR and CRVO groups, the drop in vision was apparent earlier in the CRVO group (at 6 months) while this occurred at a slightly later time point in PDR eyes (at about 12 months). Both groups had similar levels of vision at the 2-year time point. Additionally, there were no differences in the IOP and number of IOP-lowering medications between these two groups.
The outcomes of patients at 2 years unadjusted for follow-up time are presented in table 3. All patients who completed 2-year follow-up visits and/or experienced treatment failure were included in this analysis. The most common reason for treatment failure was inadequate IOP control. The overall cumulative rate of failure increased from 3.1% (95% CI 1.1% to 11.8%) at 1 year to 33.8% (95% CI 20.4% to 52.5%) at 2 years (figure 2). There were no differences in the absolute and cumulative success rates (figure 3) in eyes with CRVO or PDR (table 3) or between eyes with open and closed angle NVG (figure 4). Multivariable Cox proportional hazards analysis showed that eyes with open angles had a tendency towards a lower risk of failure (HR 0.17, 95% CI 0.10 to 1.03, p=0.09). None of the other factors including underlying aetiology was associated with success of AADI in NVG eyes.
Surgical complications are listed in table 4. About one-third of the eyes experienced complications in this cohort, vitreous haemorrhage occurred most frequently in 14% eyes overall. Of these, early vitreous haemorrhage, within 1 month of surgery was seen in only two eyes, and both were associated with hypotony. Corneal decompensation was the next most frequent complication seen and occurred in 9 (11%) eyes overall. Two of the eyes which developed corneal decompensation had coexisting pseudoexfoliation, two eyes had persistent hypotony and the rest had uncontrolled IOP and progressive disease pathology. Choroidal detachment occurred in three eyes in our cohort, two of the eyes with choroidal detachment had associated flat anterior chamber and required tube religation to reverse hypotony. None of the patients in our study had a tube or plate exposure. With respect to underlying aetiology, vitreous haemorrhage was significantly more common in eyes with PDR whereas corneal decompensation was more common in eyes with CRVO. Reoperations for glaucoma and complications were required in 9% eyes (table 5). There were no differences in rates of reoperation between eyes with PDR ad CRVO.
The surgical management of NVG is challenging, and risk of failure of conventional filtering surgery has been shown to be higher in eyes with NVG. Though success rates of trabeculectomy have improved with use of antimetabolites, preoperative anti-VEGF injections and PRP, the 5-year survival rates are still around 50% for NVG.5–7 These results have prompted many surgeons to select GDD as the preferred procedure to manage NVG, as seen from our study. The prohibitive cost/unavailability of AGV and BGI is a barrier to their use in resource-poor communities and the AADI with its comparable IOP-lowering efficacy and safety profile has provided an economic alternative in the management of refractory glaucoma in low/middle-income countries.
Several studies have evaluated the AGV in management of NVG.8 10–12 Surprisingly, there are very few studies evaluating outcomes of non-valved GDDs in NVG. In the AVB study,15 the BGI had 19% eyes (22 eyes) with NVG. Though a specific subgroup analysis for NVG was not available, these eyes were found to have a higher failure rate at 5 years, (56% vs 40% in non–neovascular disease), and this was the same for both devices. We report a lower cumulative rate of failure that is, 34%, however, this was at the 2-year time point. In our series of refractory adult glaucoma using the AADI, we report a cumulative failure rate of approximately 30% at the 2-year time point,17 marginally lower than observed in this study in eyes with NVG. In spite of the differences in the definitions of success between the AVB study and ours, it is apparent that NVG eyes have a much higher failure rate. In another study comparing the AGV vs the Molteno implant for NVG, Yalvac et al19 found that the cumulative success rates for 27 eyes in the Molteno group were only about 30% at 2 years, much lower than ours and that reported in the BGI arm of the AVB study. The AGV group (n=38 eyes) had better success rates (56% at 2 years) in this study, though the differences were not statistically significant, presumably due to small sample size in each of the groups. The prospective model of the Ahmed Baerveldt comparison (ABC) study included secondary glaucomas and out of 276 patients recruited 80 (29%) had NVG.20 With similar criteria for surgical failure in the ABC study and ours, the cumulative probability of failure was 44.7% in the AGV group and 39.4% in the BGI group at 5 years. The hazard rate of failure was highest in first 2 years of follow-up. The failure rate in both the groups was approximately 10% per year in the first 3 years, which decreased to 5% from 3 to 5 years in both the groups with stable IOP and number of medications between 3 and 5 years.21 Though there are several studies assessing outcomes after pars plana vitrectomy combined with BGI insertion,22–24 to the best of our knowledge, these are the only three studies evaluating the outcomes of non-valved tubes alone in eyes with NVG.
Majority of patients in our cohort continued to lose vision during the 2-year study period as average vision dropped from 20/200 at baseline to 20/600 at the 2-year time point. Similar visual acuity outcomes have also been seen in the AVB study were, out of the 14 eyes with very poor vision, 7 were due to NVG.15 Vitreous haemorrhage, corneal oedema, phthisis bulbi and hyphema were significantly more common in the NVG stratum than other strata at 3 years follow-up in the ABC study.25 Out of 25 patients whose vision deteriorated to no perception of light in the ABC study, 24 (96%) were in the NVG stratum signifying the poor visual prognosis in neovascular disease.21 Vision is mainly governed by the macular status and perfusion in eyes with NVG and occurrence of glaucoma suggests that these eyes are at the extreme end of the spectrum with the extent of retinal ischaemia not viable with good vision. None of the eyes in our series had poor vision due to complications of surgery or resurgery, suggesting that the poor vision was due to the macular ischaemia.
We did not find any differences in failure rates between eyes with PDR, CRVO and other aetiologies, suggesting that the underlying aetiology may not influence outcomes of AADI in NVG. However, a trend towards better results was found in eyes with open angles compared with those with closed angles, indicating that it may be prudent to plan AADI surgery earlier in the course of the disease.
Our study has several limitations. All procedures were performed in a single hospital in India with one type of implant, and the results may not be generalisable to other patient populations and implant types. Use of glaucoma medications and reoperations for glaucoma and complications were left to the discretion of the surgeon, and no standard protocols were used to guide postoperative management. The study included a relatively large number of eyes with NVG. However, the subgroups based on underlying aetiology and angle anatomy were small, and this limited the power to detect significant differences.
In summary, we found that the AADI was effective in reducing IOP in the early postoperative period in eyes with NVG. The majority of patients in our study cohort did not have prior trabeculectomy indicating a preference towards use of a GDD in eyes with NVG. The predominant causes of NVG in our series were PDR and CRVO, and comparisons between these groups did not show any difference in failure rates. Eyes with open angles tended to have better IOP control after AADI placement, but this did not reach the level of statistical significance. Despite IOP control, BCVA declined over time likely due to the underlying ischaemic retinal disease. To the best of our knowledge, this is the first study demonstrating the effectiveness of the AADI in eyes with NVG.
Data availability statement
Data are available on reasonable request. Not applicable.
Patient consent for publication
This was a retrospective study and was approved by the institutional ethics committee of the Aravind Eye Hospital, Madurai (RET201200351). The study adhered to the tenets of the Declaration of Helsinki.
The authors acknowledge the inputs from Ms R Kumaragurupari, Chief Librarian, Aravind Eye Care System for literature search.
Contributors All authors made substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work. GVP: concept and design of the work, critical revision of the content, final approval of the version to be published, accountable for all aspects of work in ensuring questions related to the accuracy or integrity of any part of work are appropriately investigated and resolved. SG, HKW, SRK and SJG: concept and design of the work, critical revision of the content, final approval of the version to be published. KPC, VR and IM: data acquisition, analysis, preparation of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.