Abstract
To analyze the treatment modalities and trends for neovascular glaucoma (NVG) over the past 10 years, we conducted a retrospective analysis at Zhongshan Ophthalmic Center on 1331 NVG inpatients who received 1459 treatments for 1383 eyes between January 1, 2012, and December 31, 2021. Over time, we observed a progressive annual increase in both the number of patients and the volume of surgeries for NVG, with an annual percentage change (APC) of 10.23 % (95 % confidence interval [CI]: 5.5–15.2 %, P = 0.001) and 11.59 % (95 % CI: 6.6–16.9 %, P = 0.001), respectively. Drainage valve implantation (46.88 %), cyclodestructive procedures (22.55 %) and trabeculectomy (6.24 %) were the three most commonly selected treatment options. The frequency of drainage valve implantation (APC = 6.59 %, 95 % CI = 0.9–12.6 %, P = 0.028), cyclodestructive procedures (APC = 17.26 %, 95 % CI = 9.3–25.8 %, P = 0.001) and trabeculectomy (APC = 21.93 %, 95 % CI = 1.6–46.3 %, P = 0.036) increased. The proportion of drainage valve implantation gradually decreased (APC = –4.48 %, 95 % CI = –8.6 to –0.2 %, P = 0.042), while that of cyclodestructive procedures increased (APC = 5.08 %, 95 % CI = 0.6–9.8 %, P = 0.042), with no significant alteration observed in the proportion of trabeculectomy (APC = 9.26 %, 95 % CI = –8.8–30.9 %, P = 0.290). Over the course of the study, both the cases of NVG and the volume of related surgeries escalated year by year. Among the three most frequently employed procedures—drainage valve implantation, cyclodestructive procedures and trabeculectomy—annual frequency trends revealed an increase in drainage valve implantation alongside a decreasing proportion, while cyclodestructive procedures exhibited a rising trend in both frequency and proportion; simultaneously, trabeculectomy showed an increasing frequency without a significant change in its proportion.
1
Introduction
Neovascular glaucoma (NVG) is a form of refractory glaucoma primarily induced by ocular or systemic conditions that lead to retinal ischemia and hypoxia. These conditions stimulate the secretion of various angiogenic factors, which promote neovascularization and subsequently obstruct the anterior chamber angle, ultimately culminating in elevated intraocular pressure (IOP). Treatment for NVG mainly includes treating the cause, inhibiting new blood vessels and lowering IOP. Traditionally, the main treatment for the late stage is lowering IOP with drainage valve implantation . With the development of anti–vascular endothelial growth factor (anti-VEGF) agents and cyclodestructive procedures, there are increasingly more treatment options available for NVG patients. Moreover, due to urbanization, economic growth and an aging population, the disease spectrum of NVG may have changed. Both phenomena can induce sudden changes in the choice of primary treatment modality. To date, there has been a lack of comprehensive longitudinal studies analyzing the evolving trends in NVG treatment methodologies over consecutive years. Consequently, we undertook a retrospective analysis to address this gap in the literature.
2
Methods
This study retrospectively included inpatients diagnosed with NVG and receiving NVG-related treatment at Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2012, and December 31, 2021. The diagnosis of NVG was based on neovascularization in the iris and/or anterior chamber angle, identified through slit-lamp biomicroscopy and gonioscopy. Two trained professionals collected detailed data, including age, sex, affected eye, best-corrected visual acuity (BCVA), IOP, clinical stage, etiology and treatment modality. We divided the cases into three clinical stages : I. Preglaucoma: Neovascularization can be observed in the iris or the anterior chamber angle, but the patient’s angles remain open and IOP is normal; II. Open-angle glaucoma: Fibrovascular tissue proliferates over the trabecular meshwork, obstructing aqueous outflow, which leads to increased IOP, though the angle remains open in most regions; III. Closed-angle glaucoma: Tightening of the fibrovascular membrane results in iridocorneal adhesions, which subsequently lead to angle closure and elevated IOP. In patients diagnosed with NVG in both eyes, the onset of NVG and subsequent treatments may not occur simultaneously in both eyes, as each eye may develop NVG and receive treatment at different times during the study period. The term “composition ratios” for different treatment modalities refers to the ratio between the frequency of a specific treatment modality and the total treatments performed in that year. The research protocol and data collection process conformed to the Helsinki Declaration’s guidelines and were approved by the Institutional Research and Ethics Board of the Zhongshan Ophthalmic Center, Sun Yat-sen University (No. 2022KYPJ194).
Statistical methods: The data were analyzed using SPSS version 26.0 (IBM Corporation, Chicago, IL, USA) and the Joinpoint Regression Program version 4.5 (Statistical Research and Applications Branch, National Cancer Institute, Bethesda, MD, USA). GraphPad Prism version 9.1.1 (225) ( www.graphpad.com ) was used to generate the figures. Means and standard deviations are used to present quantitative data, while frequencies and percentages are shown for categorical data. The annual percentage changes (APCs) and their 95 % confidence intervals (CI), obtained through multiphase regression analysis, revealed variations in the trend percentages throughout the study period. All P values were evaluated using a two-tailed test, with statistical significance defined as a P value below 0.05.
3
Results
A total of 1331 NVG inpatients were included in this study, and Table 1 provides a summary of their essential information. Among the patients, 891 were male (66.94 %) and 440 were female (33.06 %), with a mean age of 53.02 ± 16.49 years. There were 1279 patients (96.09 %) with a single eye involved and 52 patients (3.91 %) with both eyes involved, resulting in a total of 1383 eyes. The average BCVA was 2.09 ± 0.97 LogMAR, and the average IOP was 34.69 ± 14.22 mm Hg. The percentages of eyes in the preglaucoma and angle-opening stages of NVG were 3.18 % and 4.19 %, respectively, while the angle-closure stage accounted for 92.63 %. Among these cases, 1311 eyes (94.79 %) underwent a single surgery, while 72 eyes (5.21 %) required multiple surgeries, resulting in a total of 1459 procedures, of which 164 were preceded by anti-VEGF injections, including 96 before drainage valve implantation, 24 before cyclodestructive procedures and 10 before trabeculectomy, with the remaining 34 procedures preceding all other types of treatments.
| Characteristics | Results |
|---|---|
| Gender, n (%) | |
| Male | 891 (66.94 %) |
| Female | 440 (33.06 %) |
| Age, years | |
| Mean ± SD | 53.02 ± 16.49 |
| Laterality, n (%) | |
| Unilateral | 1279 (96.09 %) |
| Right eye | 613 (46.05 %) |
| Left eye | 666 (50.04 %) |
| Bilateral | 52 (3.91 %) |
| logMAR BCVA | |
| Mean ± SD | 2.09 ± 0.97 |
| IOP, mmHg | |
| Mean ± SD | 34.69 ± 14.22 |
| Stage, eyes (%) | |
| Preglaucoma | 44 (3.18 %) |
| Open-angle | 58 (4.19 %) |
| Angle-closure | 1281 (92.63 %) |
| No. operations, eyes (%) | |
| Once | 1311 (94.79 %) |
| More than Once | 72 (5.21 %) |
The distributions of treatment modalities among NVG patients at different stages and with different etiologies are shown in Table 2 and Fig. 1 . Overall, drainage valve implantation (684 cases, 46.88 %), cyclodestructive procedures (329 cases, 22.55 %) and trabeculectomy (91 cases, 6.24 %) were the primary treatment approaches, with a detailed description of the 87 cases (5.55 %) categorized as “other surgeries” provided in Supplementary Table 1 . Among the 329 cyclodestructive procedures, 276 cases (83.9 %) were cyclophotocoagulation and 53 cases (16.1 %) were ultrasound cycloplasty (UCP). In patients with preglaucoma, intravitreal anti-VEGF drug injections were the main treatment modality ( P < 0.01), accounting for approximately 34.04 % (16 out of 47) of preglaucoma patients. For patients in the angle-open stage ( P < 0.01) and angle-closure stage ( P < 0.01), drainage valve implantation was the predominant treatment modality, accounting for 48.28 % (28 out of 58) and 48.45 % (656 out of 1354) of the patients, respectively. Fig. 1 shows that patients with NVG secondary to diabetic retinopathy (DR, P < 0.01), retinal vein occlusion (RVO, P < 0.01), retinal detachment (RD, P < 0.01), ocular trauma ( P < 0.01), retinal vasculitis ( P < 0.01), other etiologies ( P < 0.05) or unknown causes ( P < 0.01) primarily underwent drainage valve implantation (DR: 50.3 %; RVO: 56.4 %; RD: 26.3 %; ocular trauma: 25.6 %; retinal vasculitis: 37.5 %; other etiologies: 38.5 %; unknown causes: 42.3 %) or cyclodestructive procedures (DR: 17.2 %; RVO: 17.7 %; RD: 30.3 %; ocular trauma: 44.2 %; retinal vasculitis: 12.5 %; other etiologies: 11.5 %; unknown causes: 35.1 %). Among those patients with NVG secondary to ocular tumors ( P < 0.01), enucleation or evisceration was the most common treatment strategy, accounting for approximately 75 % (15 out of 20) of that subgroup.
| Treatment strategy, No. operations (%) | Preglaucoma | Open-angle stage | Angle-closure stage |
|---|---|---|---|
| DVI, 684 (46.88 %) | – | 28 (1.92 %) | 656 (44.96 %) |
| Trabeculectomy, 91 (6.24 %) | – | 1 (0.07 %) | 90 (6.17 %) |
| Cyclodestructive Procedures, 329 (22.55 %) | – | 3 (0.21 %) | 326 (22.34 %) |
| Intravitreal Anti-VEGF Injections, 73 (5.00 %) | 16 (1.10 %) | 4 (0.27 %) | 53 (3.63 %) |
| Enucleation or Evisceration, 41 (2.81 %) | 3 (0.21 %) | – | 38 (2.60 %) |
| Cataract Surgery, 35 (2.40 %) | 9 (0.62 %) | 3 (0.21 %) | 23 (1.58 %) |
| Vitrectomy, 70 (4.80 %) | 10 (0.69 %) | 15 (1.03 %) | 45 (3.08 %) |
| Vitrectomy combined with Anti-VEGF Injections, 24 (1.64 %) | 5 (0.34 %) | 1 (0.07 %) | 18 (1.23 %) |
| DVI combined with Anti-VEGF Injections, 25 (1.71 %) | – | – | 25 (1.71 %) |
| Other Surgeries, 87 (5.55 %) | 4 (0.27 %) | 3 (0.21 %) | 80 (5.48 %) |
| Total, 1459 (100 %) | 47 (3.22 %) | 58 (3.98 %) | 1354 (92.80 %) |
| P value | 0.000 * * | 0.000 * * | 0.000 * * |
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