Two-year outcomes of patients presenting to Sydney Eye Hospital with neovascular glaucoma

Neovascular glaucoma (NVG) is an aggressive secondary glaucoma caused by anterior segment neovascularization leading to synechial angle closure and ocular hypertension. Iris neovascularization was first reported by Bader in 1868 [1]; however, it was not until 1963 that NVG was described by Weiss et al. [2] Further research discovered that NVG is caused by retinal ischemia [3]. NVG is most commonly a secondary complication of proliferative diabetic retinopathy (PDR), central retinal vein occlusion (CRVO) or ocular ischemic syndrome (OIS). [3]

Neovascular glaucoma has poor visual outcomes despite medical and surgical management and at times can require evisceration or enucleation to alleviate pain from a blind eye. Up to 50% of patients with NVG can be left with no light perception if poorly managed [4]. NVG accounts for approximately 3.9–4.3% of all glaucoma [5, 6] and 14% of secondary glaucoma [5] with an incidence of approximately 6.6 people per 100,000 reported in one study [7]. Limited population data exist in the literature. NVG seems to have a higher prevalence in males compared to females although the reason for this is unknown [6, 7].

We performed a retrospective audit of patients presenting to SEH with NVG between January 1, 2013, and December 31, 2018. Inclusion and exclusion criteria are given in Table 1. NVG cases were selected using ‘PC067: SNOMED Diagnosis by Enc,’ a search engine found within Cerner electronic medical records (eMR), as well as ‘the international statistical classification of disease and related health problems, tenth revision, Australian Modification’ (ICD 10-AM). Both databases were searched because SEH uses paper-based notes for outpatients and an eMR for inpatients.

A total of 93 patients were identified using inclusion and exclusion criteria. Of the 93 patients, five were excluded due to loss of follow-up and a further three were excluded because the diagnosis of NVG was not adequately documented. A further 27 patients were excluded from data analysis due to less than six months of documented follow-up, leaving 67 eyes from 58 patients remaining in the study. Data was collected from hospital medical records and private practices if applicable.

The initial presentation was defined as the patient’s first presentation to SEH; however, if there was no documentation of initial review at SEH prior to surgery, then the referring ophthalmologist’s review was used. The records were then searched to determine whether the patient required surgical intervention, which was then used as the start of the 24-month follow-up period. If surgery was not required within the first year after initial presentation, then the surgery they required was recorded as nil and the starting point was the initial presentation. Further details such as preoperative VEGFI and PRP, etiology and number of IOP-lowering medications were recorded. Patients who received either PRP or had a VEGFI injection intraoperatively within the first week of initial presentation were grouped with the patients who had these interventions preoperatively for data analysis purposes.

Data were collected at one month, 6 months, 12 months, 18 months and 24 months postoperatively. If patients were not reviewed within 3 months of the defined time, no data were recorded for that review. If patients did not have documentation regarding neovascularization, complications or pain during the review, then it was recorded as unknown.

Patient demographics are given in Table 2. Median follow-up time was 24 months (IR 6), and the mean was 20.42 months (SD 6.01, range 6 months to 6 years). The most common causes of NVG within the cohort were PDR (35 eyes; 52.2%) followed by CRVO (18 eyes; 26.9%) and OIS (7 patients 10.4%). BRVO (3 eyes), chronic retinal detachment (2 eyes), CRAO (1 eye) and Sticklers syndrome (1 eye) were found to be less common.

Neovascular glaucoma is a severe sight-threatening condition that has a very poor long-term visual prognosis. We have described 2-year outcomes of NVG patients presenting to a quaternary referral center. The results of two commonly used surgical interventions for the treatment of NVG, namely TSCPC and BVT, were compared.

The patient cohort identified in this study is similar to other retrospective audits such as those conducted at Songklanagarind Hospital (SH) in Thailand [10], Wenzhou Medical University Hospital (WMUH) in China [11] and the associacion para Evitar la Ceguera in Mexico [12]. The etiology of NVG among this cohort is consistent with the three most common causes of NVG: proliferative diabetic retinopathy, ischemic CRVO and ocular ischemic syndrome [6, 10]. This highlights that NVG may be preventable if underlying risk factors such as diabetes and hypertension are appropriately managed.

Tight control of blood glucose levels has been demonstrated to reduce the likelihood of patients with proliferative diabetic retinopathy developing NVG [13]. High HbA1c levels have been found to be a significant predictor of NVG in patients who have had a PPV for management of PDR [13]. During this audit, it was noted that documentation regarding strict advice to follow-up with an endocrinologist to improve their diabetic control was lacking within the notes. Referral to an endocrinologist and strict counseling about the importance of adherence to diabetic regimens as well as lifestyle changes need to be addressed and documented upon each review.

Median BCVA within the cohort deteriorated over the 24-month follow-up period, although NVG was only one of the contributing factors to poor visual outcomes. Initial BCVA was 1.9 log units (IR 1.7) and worsened to 2.3 log units (IR 1.82) at 12 months. A similar pattern was seen at SH (mean BCVA at baseline of 1.77 ± 0.76 and final follow-up BCVA of 1.99 ± 0.86) [10]. BCVA worsened in 65.2% of patients at SEH after 24 months of follow-up when compared with baseline. More favorable results were reported at King Khaled Eye specialist hospital (KKEH) in Saudi Arabia (38% of eyes at 24 months) [7, 14] and SH (45% of eyes at 21 ± 18 months) [10]. Non-glaucomatous disease processes that initially lead to NVG may be a confounder when using BCVA as an outcome. PDR, CRVO and OIS can often lead to macular edema or ischemia, both of which can significantly reduce BCVA.

Failure rates in our study highlight the challenges associated with surgical management of NVG. The primary surgery performed on 62.7% of patients within the cohort had failed by the 24-month review. Lower failure rates were seen at SH (IOP > 21 or < 6, further operations, loss of light perception or any severe complications) and WMUH (IOP > 21 or < 6 or any decrease in visual acuity) with similar definitions of failure [10, 11]. SH had a surgical failure rate of 50.3% after an average of 21-month follow-up [10] and WMUH had a 37.4% failure rate at 2 years [10]. The lowest failure rate within SH was seen in the trabeculectomy with MMC and intraocular (intravitreal or intracameral) bevacizumab with a failure rate of 44% [10]. A similar failure rate was seen in the BVT group at SEH (44.4%).

Timely administration of intravitreal VEGFI and application of PRP may improve outcomes for patients with NVG [15‐23]. The goal should be for all patients to receive VEGFI on initial presentation and PRP as soon as possible (fundus view permitting). Bevacizumab is the VEGFI of choice for NVG at SEH, which is consistent with reported VEGFI use at other institutions. [15‐20] VEGFI use for NVG is ‘off label’ in Australia, and so, the most cost-effective VEGFI choice is bevacizumab. Within this study, 80.6% of patients received VEGFI therapy and 62.7% of patients received PRP (either top-up or initial PRP) prior to or within one month of presentation. This decreased to 70.1% and 41.8%, respectively, when only including those patients who received these interventions prior to, or within, one week of presentation. This highlights that large proportion of patients did not receive these interventions in a timely manner. It was not clearly documented as to why some patients did not receive VEGFI. One patient had a traumatic AC paracentesis in preparation for VEGFI, and hence, VEFI was not inserted. Some patients may have had VEGFI without it being documented. Patients presenting with a dense vitreous hemorrhage or large hyphema were unable to have initial PRP. This was the case for three patients who received intraoperative PRP with PPV ± anterior chamber washout within the first week and hence were included. 80.6% of patients received initial or additional PRP during the study period. An additional 6% of patients had evidence of previous PRP but did not receive additional PRP since diagnosis of NVG. Retinal cryotherapy was rarely used at SEH with only two (3%) patients receiving this. Cryotherapy may warrant further research as favorable outcomes have been demonstrated in a small study combining 360-degree retinal cryotherapy with PRP and IVB in patients with NVG [14, 24].

The timing and choice of IOP-lowering surgical intervention is critical when managing NVG. Choice of surgical intervention in this study was made by each individual glaucoma surgeon and was based on factors such as visual acuity, intraocular pressure and angle status. This has limited the conclusions that can be drawn from this study. The two most selected surgical interventions to lower IOP in patients with NVG at SEH were TSCPC (53.7%) and BVT (26.8%). Other retrospective reviews at KKEH and WMUH demonstrated similar preferences for TSCPC and GDD [7, 11, 14]. IOP was significantly reduced in our study after 24 months regardless of surgery used.

There were no standardized protocols for administration of TSCPC or insertion of BVT at SEH. BVTs were placed both in the AC and in the sulcus depending on surgeon preference. Number and power of shots of TSCPC varied greatly but were titrated to avoid ‘pops.’

This study highlights differences in outcomes between TSCPC and BVT. There was no statistically significant difference in number of systemic comorbidities, age or median BCVA on presentation between those who initially had TSCPC, BVT or another procedure. Median IOP up to 12 months was significantly lower in the BVT group when compared to TSCPC. BVT failure rate during the study was also lower (44.4%) when compared to TSCPC (75.0%). Excluding patients presenting with BCVA of 2.7 log units or 3.0 log units marginally reduced failure rates for BVT and TSCPC were seen.

Further surgical interventions were more common in the TSCPC group when compared to other groups. This is not surprising because TSCPC is difficult to titrate and may be used as a temporizing measure until a more definitive surgery can be performed.

From this audit, we would recommend timely use of VEGFI and PRP with VEGFI to be given at initial presentation if possible. We would also recommend early referral to a general practitioner and/or endocrinologist to manage risk factors for NVG. Finally, we recommend that further research be completed to establish what the most effective surgical intervention is for managing ocular hypertension in NVG.

Neovascular glaucoma is a potentially devastating condition with ocular and systemic implications. Timely intervention is critical, but there is a lack of management standardization particularly at initial presentation. We have outlined retrospective real-world data from SEH, which reflects experiences reported by other international eye centers. Surgical failure rates are high, and prospective studies are required to guide surgical decision making. Immediate consideration of VEGFI and PRP on initial presentation of NVG may improve patient outcomes and reduce the need for surgical interventions.