Combined anti-VEGF approach in neovascular glaucoma: clinical outcomes of intracameral and intravitreal bevacizumab administration

Abstract

Background

To evaluate short-term clinical outcomes of combined intracameral and intravitreal bevacizumab administration in patients with neovascular glaucoma (NVG), with emphasis on intraocular pressure (IOP), best-corrected visual acuity (BCVA), and regression of anterior segment neovascularization.

Methods

This retrospective study included 90 eyes of 81 patients with NVG who received simultaneous intracameral and intravitreal bevacizumab injections between January 2020 and January 2025. BCVA, IOP, and rubeosis iridis were assessed at baseline and at 1 week, 1 month, and 3 months post-treatment. Additional interventions, including panretinal photocoagulation (PRP), repeat anti-VEGF injections, and glaucoma surgeries, were documented.

Results

The mean patient age was 65.47 ± 10.06 years, and 69.2% were male. Diabetic retinopathy (66.7%) and central retinal vein occlusion (26.7%) were the most common underlying etiologies. Median BCVA demonstrated modest improvement, with statistically significant gains at 1 and 3 months compared with baseline (p < 0.01). Mean IOP decreased significantly from 32.9 ± 12.1 mmHg at baseline to 21.4 ± 10.1 mmHg at 3 months (p < 0.001). Regression of rubeosis iridis was observed in 71.5% of eyes by month 3. PRP was performed in 66.7% of cases, while trabeculectomy or cyclocryotherapy was required in 23.3% of eyes. Hyphema occurred in 3.3% of patients, with no other serious complications.

Conclusions

Combined intracameral and intravitreal bevacizumab appears to be a safe and effective short-term strategy for NVG management, providing significant IOP reduction and regression of anterior segment neovascularization. Although visual improvement was limited, this dual-route anti-VEGF approach may serve as an effective bridge therapy facilitating subsequent definitive retinal or glaucoma interventions, particularly in advanced cases with corneal edema.

Introduction

Neovascular glaucoma (NVG) is an aggressive type of glaucoma that can cause severe vision loss in the eye. It develops secondary ischemic diseases of the retina [1]. Its most prominent feature is the formation of new abnormal vessels on the iris and in the anterior chamber angle, resulting in increased intraocular pressure (IOP) [2]. NVG usually leads to permanent blindness if left untreated and requires urgent intervention [3]. Although it was first documented as congestive glaucoma in 1871, the term NVG was introduced into the literature by Weiss et al. in 1963 [2].

The most common cause of NVG is vascular disease leading to retinal ischemia. The most common of these are diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). Other causes include branch retinal vein occlusion (BRVO), ocular ischemic syndrome (OIS), retinal artery occlusion (RAO), trauma, eye tumors, radiation, uveitis, and chronic rhegmatogenous retinal detachments (CRRD) [1]. In children, conditions such as retinal tumors and premature retinopathy can cause NVG [4].

The pathophysiology of NVG, regardless of its cause, is characterized predominantly by retinal ischemia and an imbalance between angiogenic and anti-angiogenic factors [5]. Retinal ischemia leads to increased levels of pro-angiogenic factors, primarily vascular endothelial growth factor (VEGF). Retinal ischemia increases intraocular VEGF levels, leading to neovascularization in both the posterior and anterior segments; however, anterior segment neovascularization may develop even in the absence of clinically detectable retinal ischemia. VEGF generally causes neovascularization primarily in the retina; if ischemia is not controlled, it may also occur in the anterior chamber angle and on the iris [6]. Neovascularization and, over time, the accompanying fibrovascular membrane grow over the trabecular meshwork, thus obstructing the outflow of aqueous humor. As a result, IOP rises [7].

Staging of NVG can be important for determining the course of the disease, the treatment approach, and the prognosis. NVG is divided into 4 stages. (1) Prerubeosis (Pre-stage): There is no new vessel formation in the iris or angle yet, but there is an underlying ischemic disease. (2) Rubeosis Iridis (Early Stage): New vessels are seen on the iris, especially at the pupillary edge. This is the stage when most patients present for urgent eye care. (3) Open-Angle NVG: New vessels grow on the trabecular meshwork, disrupting intraocular fluid drainage and increasing IOP. In the open-angle stage, IOP can be controlled with medical treatment. (4) Angle-Closure NVG: The anterior chamber angle is completely closed by contraction of the fibrovascular membranes, IOP increases significantly, and surgical intervention is usually required [5].

The main goal of NVG treatment is to control IOP and suppress abnormal vascularization. To control IOP, antiglaucomatous eye drops, oral acetazolamide, or intravenous mannitol are the primary medical treatments. In refractory IOP elevation, Ahmed glaucoma valve, trabeculectomy, cyclophotocoagulation, or cyclocryotherapy (CCT) can be performed surgically [8]. However, the most important strategy is to treat retinal ischemia and prevent abnormal neovascularization. In recent years, the recommended treatment for this has been anti-VEGF drugs, panretinal photocoagulation (PRP), or a combination of these [9].

Bevacizumab is a VEGF inhibitor used to treat NVG. It is known that intravitreal and/or intracameral bevacizumab injections rapidly and significantly regress neovascularization in the iris and anterior chamber angle by suppressing VEGF, which is one of the important pro-angiogenic mediators in the pathogenesis of NVG [10–12]. Significant decreases in IOP have been reported after bevacizumab application [13]. While a rapid response is obtained in the short term for rubeosis, neovascularization may recur after a few months, and additional injections may be required [11]. Therefore, it is important to treat retinal ischemia with PRP. However, PRP is sometimes not feasible in advanced-stage NVGs with corneal edema. This increases the importance of anti-VEGF application in advanced-stage NVGs [14].

This study investigates the clinical efficacy of a combined anti-VEGF treatment approach involving intravitreal and intracameral bevacizumab administration in patients with neovascular glaucoma. Primary outcomes evaluated include control of intraocular pressure, regression of anterior segment neovascularization, and facilitation of subsequent retinal interventions such as panretinal photocoagulation.

The treatment method was chosen based on previous meta-analyses that reported the combined approach is effective and safe for reducing IOP [15]. Therefore, the combined treatment was selected to address both the posterior and anterior components of the disease: intravitreal injection targets VEGF production due to retinal ischemia, while intracameral administration provides a faster effect on anterior segment neovascularization that directly compromises aqueous flow. The aim was to determine whether this dual-path approach provides superior therapeutic benefits, particularly in advanced cases where corneal edema limits the effectiveness of standard treatment methods.

Materials and methods

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local Human Clinical Research and Ethics Committee with the approval code TÜTF-GOBAEK 2025/291.

In this study, data of patients diagnosed with NVG at different stages for various reasons and treated with intracameral and intravitreal bevacizumab between January 2020 and January 2025 were retrospectively reviewed. Demographic characteristics of all patients were recorded. Best corrected visual acuity (BCVA) was measured with the Snellen chart at each visit in all patients. Neovascularization of the iris was examined in detail during biomicroscopy, and intraocular pressure was measured with applanation tonometry. In addition, angle and fundus examinations were performed if possible.

Patients were questioned for systemic diseases that could cause NVG, and, if the fundus could be visualized, fundus fluorescein angiography (FFA) was performed to support the diagnosis and demonstrate ischemia and neovascularization. Patients were classified as DR, CRVO, BRVO, OIS, retinal artery occlusion (RAO), trauma, and CRRD according to their diagnoses.

As stated in the study by Călugăru et al. [5], NVG consists of 4 stages: Stage (1) Prerubeosis (Pre-stage), Stage (2) Rubeosis Iridis (Early Stage), Stage (3) Open-Angle NVG (Fig. 1), and Stage (4) Angle-Closure NVG. When patients presented, the stage was determined and recorded.

Fig. 1.

Representative anterior segment photographs of a patient with Stage 3 neovascular glaucoma. (A) Before treatment, showing marked rubeosis iridis and active neovascularization involving the anterior chamber angle. (B) Ten days after combined intracameral and intravitreal bevacizumab administration, there was a significant regression of iris neovascularization

Since stage 1 patients did not present with any symptoms during routine examination, they could not be detected and were not included in the study. Stage 2 and above patients were included in the study. All patients with rubeosis iridis were started on dexamethasone 0.1% eye drops 4 × 1, and stage 2–3 patients were also started on cyclopentolate 1% eye drops 3 × 1. Topical antiglaucomatous drops (Dorzolomide-Timolol 2% + 0.5% 2 × 1, Brimonidine 0.15% 2 × 1) were routinely added to patients with stages 3 and 4. In addition, oral Acetazolamide 250 mg 4 × 1 was applied to those without kidney disease until the procedure was performed. Patients with severe corneal edema and pain were administered intravenously 20% mannitol at the time of presentation and before the procedure.

All patients received intracameral bevacizumab 0.05 ml (1.25 mg) and intravitreal bevacizumab 0.05 ml (1.25 mg) procedures; any complications were noted. After the procedure, topical antibiotic drops 4 × 1 were added to their current topical treatments, and they were discharged. They were called for 1st-week, 1st-month, and 3rd-month controls, and BCVA, intraocular pressure measurement with applanation tonometry, and the presence of iris neovascularization with biomicroscopy were noted. PRP was applied to patients without pathologies that obstructed vision, such as corneal edema, lens opacity, or intravitreal hemorrhage. Intracameral and intravitreal bevacizumab injections were repeated in patients whose iris neovascularization recurred or did not resolve. Monthly intravitreal bevacizumab injections were continued for patients with macular edema, and these were noted. In patients whose pain persisted despite treatment and whose intraocular pressure did not reach the desired level, trabeculectomy with mitomycin C (MMC) was performed if there was a visual prognosis; if there was no visual prognosis, CCT procedures were performed, and these patients were recorded. It was checked whether the patients had pain at the first application and after the treatment. The success criteria were based on the relief of pain, regression of rubeosis, and decrease in intraocular pressure.

Combined bevacizumab application steps: Intracameral bevacizumab and intravitreal bevacizumab

The procedure was explained to all patients, and consent was obtained. All procedures were performed in operating room conditions. In accordance with antisepsis rules, the patients’ faces were covered with a bagged drape used for eye surgery, and the eyelids were opened with a retractor. 5% povidone-iodine ophthalmic solution was applied to the eye surface for 2 min, then washed with balanced salt solution. Then, 0.05 ml (1.25 mg) bevacizumab was administered intravitreally with a 30G syringe by marking a distance of 4 mm from the limbus in phakic eyes and 3.5 mm in pseudophakic eyes in the inferior temporal quadrant with a marker, and this stage was completed by massaging with the help of a cotton to prevent vitreous hemorrhage. In these patients with high intraocular pressure and poor visualization of anterior segment structures due to corneal edema, an access route to the anterior chamber was created from the limbus using a 2 mm MVR instead of a 30 gauge needle, and 0.05 ml (1.25 mg) of bevacizumab was injected into the anterior chamber via a cannula, and the wound sites were sealed with stromal hydration. The procedure was completed by applying moxifloxacin 0.5% eye drops to the eye surface. The patients’ eyes were kept closed for 2 h, then opened, and dexamethasone 0.1% 4 × 1, moxifloxacin 0.5% 4 × 1, and, if a topical antiglaucomatous agent was used, the patients were discharged to come for a check-up in the first week.

Statistical analysis

The normality of quantitative data was examined using the Shapiro-Wilk test. Results are presented as mean±standard deviation for normally distributed values ​​and as median (mean±standard deviation) for non-normally distributed values. In repeated measures, ANOVA was used to compare normally distributed variables, and the Friedman test was used to compare non-normally distributed variables. The Bonferroni method was used to compare normally distributed variables between groups, and the Wilcoxon test was used to compare non-normally distributed variables. A p < 0.05 cutoff value was used for statistical significance. Statistical analyses were performed using SPSS 26.0.

Results

Ninety eyes of 81 patients were included in this study. Twenty-five of the patients were female (30.8%), and 56 were male (69.2%). 48 of the eyes were right (53.3%), and 42 of them (42.7%) were left. The mean age of the patients was 65.47 ± 10.06 (min: 38, max: 92). When the diseases causing NVG were examined in the patients, DR was detected in 60 (66.7%), CRVO in 23 (26.7%), BRVO in 2 (2.2%), RAO in 2 (2.2%), trauma in 1 (1.1%), and CRRD in 1 (1.1%) (Table 1). When the NVG staging at the time of first presentation was examined, 21 patients (23.3%) were detected as stage 2 (preglaucoma), 54 patients (60%) as stage 3 (open-angle glaucoma), and 15 patients as stage 4 (angle-closure glaucoma) (16.7%) (Table 1). Pain was present in 44 (48.9%) of the patients at the time of first presentation, and accompanying corneal epithelial edema was observed in 51 (56.7%). 34 patients (37.8%) had a history of intravitreal anti-VEGF injection before NVG, and 56 patients (62.2%) were treatment naive.

Table 1.

Demographic characteristics, etiology, and clinical staging of NVG patients

Parameter	n (%) / Mean ± Standard Deviation (Range)
Number of eyes	90
Number of patients	81
Sex
— Female	25 (30.8%)
— Male	56 (69.2%)
Laterality
— Right eye	48 (53.3%)
— Left eye	42 (46.7%)
Age (years)	65.47 ± 10.06 (38–92)
Etiology of NVG
— DR	60 (66.7%)
— CRVO	23 (26.7%)
— BRVO	2 (2.2%)
— RAO	2 (2.2%)
— Ocular Trauma	1 (1.1%)
— CRRD	1 (1.1%)
NVG Stage at Presentation
— Stage 2 (Rubeosis Iridis (Early Stage))	21 (23.3%)
— Stage 3 (Open-angle glaucoma)	54 (60.0%)
— Stage 4 (Angle-closure glaucoma)	15 (16.7%)

BRVO: Branch retinal vein occlusion; CRVO: Central retinal vein occlusion; DR: Diabetic retinopathy; NVG: Neovascular glaucoma; RAO: Retinal artery occlusion; CRRD: Chronic rhegmatogenous retinal detachment;

* Stage 1 (Pre Rubeosis) patients were excluded from the study because they did not have any presenting complaints and did not have any anterior segment findings that could be detected during routine examination

When the best corrected visual acuity (BCVA) of the patients was examined, it was determined that the median value of best corrected visual acuity (BCVA) was 0.001 (Mean: 0.046 ± 0.129) at the initial examination, 0.003 (Mean: 0.051 ± 0.135) at the first week after the procedure, 0.003 (Mean: 0.076 ± 0.187) at the first month and 0.001 (Mean: 0.087 ± 0.189) at the third month. When the BCVA groups were compared, no statistically significant difference was found (p = 0.387). When the groups were compared within themselves in pairs, no significant difference was found between the initial BCVA and the first-week BCVA after the procedure (p = 0.4). However, a statistically significant difference was found between the initial BVCA at the initial examination and the first- and third-month BCVA after the procedure (p = 0.005, p = 0.006). There was also a statistically significant difference between the first week BCVA after the procedure and the first and third month BCVA after the procedure (p = 0.004, p = 0.023), while no significant difference was found between the first and third months after the procedure (p = 0.77).

Intraocular pressures measured with applanation tonometry were 32.91 ± 12.15 at the initial examination, 26 ± 11.3 at the first week, 19.9 ± 6.4 at the first month, and 21.44 ± 10.06 at the third month. When the IOP groups were compared, a statistically significant difference was found (p < 0.001). When the groups were compared in pairs, a statistically significant difference was found between the initial examination IOP and the IOPs of the 1st week, 1st month, and 3rd month after the procedure (p < 0.001). Similarly, a statistically significant difference was found between the IOP of the 1st week after the procedure and the IOPs of the 1st and 3rd months after the procedure (p < 0.001, p = 0.001). However, no significant difference was found between the IOPs of the 1st and 3rd months after the procedure (p = 0.177) (Table 2).

Table 2.

Changes in BCVA and IOP over time and pairwise statistical comparisons

Time Point	BCVA Median (Mean ± SD)	Statistical Comparison (BCVA)	IOP Mean ± SD (mmHg)	Statistical Comparison (IOP)
Baseline	0.001 (0.046 ± 0.129)	Initial vs. 1st week: p = 0.4	32.91 ± 12.15	Initial vs. 1st week: p < 0.001
1st Week	0.003 (0.051 ± 0.135)	Initial vs. 1st month: p = 0.005	26 ± 11.3	Initial vs. 1st month: p < 0.001
1st Month	0.003 (0.076 ± 0.187)	Initial vs. 3rd month: p = 0.006	19.9 ± 6.4	Initial vs. 3rd month: p < 0.001
3rd Month	0.001 (0.087 ± 0.189)	1st week vs. 1st month: p = 0.004	21.44 ± 10.06	1st week vs. 1st month: p < 0.001
		1st week vs. 3rd month: p = 0.023		1st week vs. 3rd month: p = 0.001
		1st month vs. 3rd month: p = 0.77		1st month vs. 3rd month: p = 0.177
		Overall comparison: p = 0.387 (not significant)		Overall comparison: p < 0.001 (significant)

BCVA: Best-corrected visual acuity; IOP: Intraocular pressure; SD: Standard deviation

When examining whether rubeosis iridis persisted, it was observed that it persisted in 40 patients (44.4%) in the first week, 33 patients (36.7%) in the first month, and 20 patients (28.5%) in the 3rd month. Intracameral and intravitreal bevacizumab was applied to all patients. Trabeculectomy with MMC was performed in 10 patients (11.1%) whose rubeosis persisted or whose intraocular pressure did not decrease, but who expected to see, and CCT was performed in 11 patients (12.2%) who did not expect to see and whose pain persisted. Panretinal photocoagulation was performed in 60 patients (66.7%). Intracameral and intravitreal bevacizumab was applied to 13 patients (14.4%) for a second time for persistent rubeosis iridis one month later. Intravitreal bevacizumab treatments continued in 52 patients (57.8%). Hyphema developed as a complication after intracameral and intravitreal bevacizumab administration in 3 patients (3.3%); no other complications were observed. Pain persisted in 4 patients (4.4%) at the end of the 3rd month, but they did not accept CCT treatment (Table 3).

Table 3.

Summary of clinical outcomes (n = 90)

Criteria / Intervention	Number of Patients (n)	Percentage (%)
Persistence of Rubeosis Iridis
• At 1st week	40	44.4%
• At 1st month	33	36.7%
• At 3rd month	20	28.5%
Treatments Applied
• Intracameral + intravitreal bevacizumab (initial; all patients)	90	100%
• Trabeculectomy with mitomycin C (for patients with persistent rubeosis/high IOP & vision potential)	10	11.1%
• CCT (for blind and painful eyes)	11	12.2%
• PRP	60	66.7%
• Second dose of combined bevacizumab (for persistent rubeosis at 1 month)	13	14.4%
• Ongoing intravitreal bevacizumab treatments	52	57.8%
Complications
• Hyphema (after intracameral + intravitreal bevacizumab)	3	3.3%
• Persistent pain (refused CCT)	4	4.4%

CCT: Cyclocryotherapy; IOP: Intraocular pressure; PRP: Panretinal photocoagulation

When looking at BCVAs according to NVG stages, a negative correlation was found between NVG stage and BCVA at admission, BCVA at 1 week, 1 month, and 3 months after the procedure, but only the negative correlation between BCVA and stage at 3 months was found to be statistically significant (p = 0.159, p = 0.053, p = 0.201, p = 0.016). When looking at IOPs according to NVG stages, a positive correlation was found between NVG stage and IOP at admission, 1 week, 1 month, and 3 months after the procedure; all but the 3-month IOP were statistically significant (p < 0.001, p < 0.001, p = 0.001, p = 0.051).

Discussion

Neovascular glaucoma (NVG) is a complex and aggressive type of secondary glaucoma that poses significant diagnostic and therapeutic challenges due to its rapidly progressive nature and poor visual prognosis. In this study, the clinical outcomes of an approach combining intracameral and intravitreal bevacizumab administration were evaluated for best-corrected visual acuity (BCVA), intraocular pressure (IOP), and regression of rubeosis iridis during a 3-month follow-up period.

In general, NVG is more common in adults, particularly men and individuals over 50 [16]. Similarly, in another study by Ajvazi et al., 63.9% of patients were male, with an average age of 60.9 years [17]. In this study, the male gender accounts for 69.2%, which is consistent with the literature and slightly higher than reported, and the average age is 65.47, which is consistent with other studies. NVG usually develops due to severe retinal ischemia. According to the literature, the most common etiological causes are DR, ischemic CRVO, and OIS; less frequently, ocular tumors, trauma, uveitis, eye radiation, and CRRD can also lead to NVG [5, 7, 18, 19]. In this study, the two most common etiological factors were DR (66.7%) and CRVO (26.7%), consistent with previous studies.

Another important consideration is the heterogeneity of underlying etiologies in neovascular glaucoma. Although NVG may arise from diverse conditions such as DR, RVO, OIS, trauma, or retinal detachment, retinal ischemia remains the central common pathway driving VEGF upregulation and subsequent neovascularization [5]. Nevertheless, the clinical course and dynamics of rubeosis may vary depending on the primary disease. For instance, neovascularization associated with retinal vein occlusion may develop more rapidly, whereas in ocular ischemic syndrome it may follow a more chronic, progressive course. In contrast, trauma- or detachment-related cases may demonstrate more variable behavior depending on the extent of ischemia and inflammatory response [1]. In this cohort, the uneven distribution of etiologies limited the ability to perform a statistically robust subgroup analysis. However, these differences should be taken into account when interpreting treatment response and may be relevant for individualized management strategies in clinical practice. Future studies with larger and more balanced cohorts are needed to better characterize etiology-specific treatment responses.

The results of this study showed that although there was no significant improvement in BCVA when all patient groups were compared, there were significant differences from baseline in pairwise comparisons over time, especially at the first and third months. These findings suggest that although anti-VEGF therapy does not provide significant visual gain in all patients – probably due to chronic damage from the underlying ischemia – it may stabilize or slightly improve vision in some patients, especially in the early stages. Furthermore, this improvement may be misleading due to possible regression of corneal edema or to the reduction of ischemia, the main cause, by the PRP. Previous studies have also shown that the effect of intracameral bevacizumab on BCVA is limited and variable: some reported significant improvement in BCVA [20, 21], while others did not detect a statistically significant change [22, 23].

The effect of treatment on IOP is more pronounced. A statistically significant decrease in IOP was observed at all follow-up points from the beginning, especially at the first and third months. These results are consistent with the literature, which reports that bevacizumab reduces angle neovascularization and increases aqueous humor outflow. The fact that IOP reduction was achieved even in some advanced-stage cases emphasizes the importance of anti-VEGF therapy as a complementary method, especially in patients who cannot undergo PRP due to corneal edema or anatomic obstacles. The partial regression in rubeosis iridis during the follow-up period - from 44.4% in the first week to 28.5% in the third month - supports the effectiveness of bevacizumab in reducing anterior segment neovascularization. However, a significant number of patients required additional injections, and surgical interventions (trabeculectomy or CCT) were required in resistant cases. These results are consistent with the literature, indicating that anti-VEGF therapy, while effective in the acute phase, does not completely eliminate the need for PRP or surgery in advanced-stage disease [11, 24]. Previous studies have shown that intracameral bevacizumab is an effective and safe adjunctive treatment for rapid IOP reduction and regression of neovascularization in NVG, but its effect is transient, and additional treatments are needed for long-term control [25, 26].

In analyses stratified by stage, a negative correlation was found between NVG stage and BCVA, and a positive correlation with IOP. This confirms the progressive nature of the disease. In particular, the correlation between stage and BCVA at the third month was statistically significant (p = 0.016), indicating a cumulative effect of disease severity on visual function over time. On the other hand, the correlation between stage and IOP at the third month lost statistical significance (p = 0.051), suggesting that bevacizumab treatment may reach a plateau in pressure control in the late stages. Therefore, treatment for NVG should not be a single-stage treatment; PRP or intravitreal anti-VEGF treatment should be continued, and additional surgeries should be planned if necessary. Previous studies have also shown that combined treatment approaches (PRP and anti-VEGF) yield better results in early and mid-stage NVG, while the response to treatment and visual prognosis are more limited in advanced stages [9, 27, 28]. Previous studies have indicated that NVG is most frequently referred to in Stage 2, namely rubeosis iridis, with 54.4% [29]. However, in this study, 60% of patients were referred to Stage 3, namely open-angle glaucoma, which shows that patients are referred after they become symptomatic. This may be due to the fact that DR, which is the most common cause of ischemic retinal diseases geographically, is more frequently seen uncontrolled. Routine eye checks for patients with systemic diseases that predispose to DR or CRVO may prevent NVG or enable NVG to be detected at earlier stages.

Although PRP was applied to 66.7% of patients, corneal edema and visual impairment limited its application in the remaining patients. This situation underscores the value of intracameral anti-VEGF therapy by providing initial regression of neovascularization and creating suitable conditions for PRP. Previous studies have also shown that anti-VEGF treatment is effective in reducing IOP and regression of iris vessels in the short term, but its long-term effectiveness is uncertain [30], and in clinical practice, early suppression of neovascularization with anti-VEGF and then completion of PRP as soon as possible is the most effective approach to prevent progression of NVG [31].

The safety profile of this study was also acceptable; only 3 patients (3.3%) developed hyphema, and no other serious complications were reported. This is consistent with the literature supporting the safety of bevacizumab in intravitreal and intracameral applications [20].

Based on the findings of this study, a practical, step-by-step management approach is proposed to guide clinicians in real-world NVG management (Table 4).

Table 4.

Practical approach to NVG management based on clinical presentation

Clinical scenario	Suggested approach
Stage 1) Prerubeosis (Pre-stage)	Early and complete PRP, aggressive control of systemic causes (DM, RVO, OIS).
Stage 2) Rubeosis Iridis (Early Stage): Clear media	PRP ± intravitreal or combined anti-VEGF
Stage 3) Open-Angle NVG: High IOP, active rubeosis ± pain	Combined anti-VEGF + medical therapy → PRP or glaucoma surgery
Stage 4) Angle-Closure NVG: High IOP, active rubeosis, pain, poor visual prognosis	Combined anti-VEGF + medical therapy → glaucoma surgery / cyclodestructive procedures

Anti-VEGF: Anti–vascular endothelial growth factor; DM: Diabetes mellitus; IOP: Intraocular pressure; NVG: Neovascular glaucoma; OIS: Ocular ischemic syndrome; PRP: Panretinal photocoagulation; RVO: Retinal vein occlusion

This study has several limitations, including its retrospective design, short follow-up period, and lack of a control group that did not receive anti-VEGF therapy. Randomized controlled trials with longer follow-up are needed. Another limitation of this study is the lack of standardized photographic documentation across all stages of the disease. Due to the retrospective design, comparable images were not consistently available across stages. Prospective studies incorporating standardized anterior segment imaging could further improve the assessment and staging of NVG.

Abbreviations

ANOVA

Analysis of variance

BCVA

Best-corrected visual acuity

BRVO

Branch retinal vein occlusion

CCT

Cyclocryotherapy

CRRD

Chronic rhegmatogenous retinal detachment

CRVO

Central retinal vein occlusion

DR

Diabetic retinopathy

FFA

Fundus fluorescein angiography

IOP

Intraocular pressure

MMC

Mitomycin C

MVR

Microvitreoretinal blade

NVG

Neovascular glaucoma

OIS

Ocular ischemic syndrome

PRP

Panretinal photocoagulation

RAO

Retinal artery occlusion

SPSS

Statistical Package for the Social Sciences

VEGF

Vascular endothelial growth factor

Author contributions

Significant contribution to conception and design: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR Data Acquisition: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR, Ahmet Kürşad SAKALLIOĞLU, Rüveyde GARİP, Hande GÜÇLÜ Data Analysis and Interpretation: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR Manuscript Drafting: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR Significant intellectual content revision of the manuscript: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR, Ahmet Kürşad SAKALLIOĞLU, Rüveyde GARİP, Hande GÜÇLÜ Have given final approval of the submitted manuscript (mandatory participation for all authors): Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR, Ahmet Kürşad SAKALLIOĞLU, Rüveyde GARİP, Hande GÜÇLÜ Statistical analysis: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR Obtaining funding: The author(s) reported that there is no funding associated with the work featured in this article. Supervision of administrative, technical, or material support: Abdulkadir Can ÇINAR, Ayça KÜPELİ ÇINAR, Ahmet Kürşad SAKALLIOĞLU, Rüveyde GARİP, Hande GÜÇLÜ.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local Human Clinical Research Ethics Committee (approval number: TÜTF-GOBAEK 2025/291). Informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.