Imaging of aqueous outflow in health and glaucoma. Justifying the re-direction of aqueous.

A wave of less invasive surgical options that target or bypass the conventional aqueous outflow system has been incorporated into routine clinical practice to mitigate surgical risks associated with traditional glaucoma drainage surgery. A blanket surgical approach for open-angle glaucoma is unlikely to achieve the desired IOP reduction in an efficient or economical way. Developing a precise approach to selecting the most appropriate surgical tool for each patient is dependent upon understanding the complexities of the aqueous outflow system and how devices influence aqueous drainage. However, homoeostatic control of aqueous outflow in health and glaucoma remains poorly understood. Emerging imaging techniques have provided an opportunity to study aqueous outflow responses non-invasively in clinic settings. Haemoglobin Video Imaging (HVI) studies have demonstrated different patterns of aqueous outflow within the episcleral venous system in normal and glaucomatous eyes, as well as perioperatively after trabecular bypass surgery. Explanations for aqueous outflow patterns remain speculative until direct correlation with findings from Schlemm's canal and the trabecular meshwork are possible. The redirection of aqueous via targeted stent placement may only be justifiable once the role of the aqueous outflow system in IOP homoeostasis has been defined.

Intraocular Pressure Spikes Following iStent Inject and the Relationship to Aqueous Outflow in Open Angle Glaucoma.

PRCIS: Adding trabecular bypass surgery (TBS) to phacoemulsification creates unpredictable short-term intraocular pressure (IOP) control that may be undesirable for patients with advanced glaucoma. Aqueous outflow (AO) responses after TBS are complex and probably multifactorial. PURPOSE: To assess IOP spikes in patients with open angle glaucoma up to 1 month after iStent inject and their relationship to AO patterns measured by hemoglobin video imaging (HVI). PARTICIPANTS AND METHODS: We studied IOP for 4 weeks after TBS with iStent inject in 105 consecutive eyes with open angle glaucoma (6 TBS only and 99 combined with phacoemulsification). The change in IOP after surgery at each time point was compared with baseline measurements and the prior postoperative visit. IOP-lowering medications were stopped on the day of surgery in all patients. A smaller pilot study of 20 eyes (TBS only = 6 and combined = 14) underwent concurrent HVI to observe and quantify perioperative AO. Aqueous column cross-sectional area (AqCA) of one nasal and one temporal aqueous vein was calculated at each time point, and qualitative observations were documented. An additional 5 eyes were studied after phacoemulsification only. RESULTS: Mean IOP for the entire cohort (preoperative 17.3 ± 5.6 mm Hg) was lowest the day after TBS (13.1 ± 5.0 mm Hg) and peaked at 1 week (17.2 ± 8.0 mm Hg), before stabilizing by 4 weeks (15.2 ± 5.2 mm Hg; P < 0.00001). The same IOP pattern was seen when separating the group into a larger cohort without HVI (respectively 15.9 ± 3.2 mm Hg, 12.8 ± 4.9 mm Hg, 16.4 ± 7.4 mm Hg, and 14.1 ± 4.1 mm Hg; N = 85, P < 0.00001) and the smaller HVI pilot study (respectively 21.4 ± 9.9 mm Hg, 14.2 ± 4.9 mm Hg, 20.2 ± 9.7 mm Hg, and 18.9 ± 7.6 mm Hg; N = 20, P < 0.001). More than 30% IOP elevation above baseline occurred in 13.3% of the entire cohort at 1 week after surgery. This increased to 46.7% when IOP was compared with 1 day after surgery. Inconsistent AqCA values and patterns of aqueous flow were demonstrated after TBS. AqCA after phacoemulsification alone was maintained or increased within 1 week in all 5 eyes. CONCLUSION: After iStent inject surgery in patients with open angle glaucoma, intraocular spikes were most commonly seen at 1 week. AO patterns were variable and additional studies are needed to understand the pathophysiology underlying IOP responses after this procedure.

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

BACKGROUND: Neovascular glaucoma (NVG) is a sight-threatening condition that is often refractory to treatment. Current management principles are yet to be standardized due to lack of evidence. We studied the interventions used to treat NVG at Sydney Eye Hospital (SEH) and the two-year surgical outcomes. METHODS: We performed a retrospective audit of 67 eyes of 58 patients with NVG from January 1, 2013, to December 31, 2018. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of medications, repeat surgery, recurrent neovascularization, loss of light perception and pain were studied. RESULTS: The average age of the cohort was 59.67 years (SD 14.22). The most common etiologies were proliferative diabetic retinopathy (35 eyes; 52.2%), central retinal vein occlusion (18 eyes; 26.9%) and ocular ischemic syndrome (7 eyes; 10.4%). 70.1% of eyes (47) received vascular endothelial growth factor injections (VEGFI), 41.8% (28 eyes) received pan-retinal photocoagulation (PRP) and 37.3% (25 eyes) received both prior to or within the first week of presentation to SEH. The most common initial surgical interventions were trans-scleral cyclophotocoagulation (TSCPC) (36 eyes; 53.7%) and Baerveldt tube insertion (18 eyes; 26.9%). 62.7% of eyes (42 eyes) failed (IOP > 21 or < 6 mmHg for two consecutive reviews, further IOP-lowering surgery or loss of light perception) during follow-up. Initial TSCPC failed in 75.0% (27/36 eyes) compared with 44.4% (8/18 eyes) after Baerveldt tube insertion. CONCLUSION: Our study reinforces the refractory nature of NVG, often despite intensive treatment and surgery. Improvements in patient outcomes may be achieved with earlier consideration of VEGFI and PRP. This study identifies the limitations of surgical interventions for NVG and highlights the need for a standardized management approach.

Multicenter Effectiveness and Disease Stability Through 3 Years After iStentTrabecular Micro-Bypass with Phacoemulsification in Glaucoma and Ocular Hypertension.

Purpose: To evaluate 3-year safety and efficacy of two second-generation trabecular micro-bypass stents. (iStent inject ®) with phacoemulsification. Materials and Methods: This multicenter retrospective study of iStent inject implantation with phacoemulsification included data from eight surgeons across Australia. Eyes with cataract and mild to advanced glaucoma [predominantly primary open-angle (POAG), primary angle closure (PAC), or normal-tension (NTG) glaucoma] or ocular hypertension (OHT) were included. Study assessments included intraocular pressure (IOP); number of ocular hypotensive medications; proportions of eyes with 0, 1, 2, or ≥3 IOP-lowering medications; IOP ≤15 mmHg or ≤18 mmHg; visual fields (VF); retinal nerve fiber layer thickness (RNFL); central corneal thickness (CCT); intraoperative complications; adverse events; and secondary surgeries. Results: A total of 273 eyes underwent surgery and had 36-month follow-up. At 36 months versus preoperative, mean IOP decreased by 15.5% (16.4±4.6 mmHg to 13.9±3.5 mmHg; p<0.001), and 70.3% of eyes achieved IOP of ≤15 mmHg (versus 49.1% preoperatively; p<0.001). The mean medication burden decreased by 68.5% (from 1.51±1.17 to 0.48±0.89 medications; p<0.001); 71.4% of eyes were medication-free (versus 21.6% preoperatively; p<0.001), while 6.2% of eyes were on ≥3 medications (versus 22.3% preoperatively; p<0.001); 96.3% of eyes maintained or reduced medications vs preoperative. Significant IOP and medication reductions occurred across glaucoma subtypes (POAG, PAC, NTG, OHT): 13-22% for IOP (p<0.05 for all) and 42-94% for medication (p<0.05 for all). Favorable safety included few adverse events; stable VF, RNFL, and CCT; and filtering surgery in only 8 eyes (2.9%) over 3 years. Conclusion: In this multicenter cohort from 8 surgeons across Australia, significant IOP and medication reductions were sustained through 3 years after iStent inject implantation with phacoemulsification. Results were favorable across different glaucoma subtypes (including POAG, PAC, NTG, OHT), severities, and surgeons, thereby underscoring the real-world relevance and efficacy of iStent inject implantation for glaucoma treatment.

Hemoglobin Video Imaging Detects Differences in Aqueous Outflow Between Eyes With and Without Glaucoma During the Water Drinking Test.

PRCIS: Hemoglobin video imaging (HVI) demonstrates increased aqueous outflow (AO) in response to the water drinking test (WDT) in patients with and without glaucoma. In glaucomatous eyes, increased AO was not sustained, and characteristic flow patterns were seen. PURPOSE: To observe how variations in intraocular pressure (IOP) correlate with the flow of aqueous in episcleral veins. DESIGN: Prospective observational cohort study. PARTICIPANTS: The WDT increased AO into the episcleral venous system in 30 eyes recruited from Sydney Eye Hospital. A comparison was made between glaucomatous (n=20) and nonglaucomatous eyes (n=10). METHODS: Each patient had baseline IOP and HVI before drinking 10 mL/kg body weight of water. IOP and HVI were then repeated every 15 minutes for 1 hour. Aqueous column cross-sectional area (AqCA) of the most prominent nasal and temporal aqueous veins was used to semi-quantify conventional AO. MAIN OUTCOME MEASURES: Change in IOP and AqCA from baseline during the WDT. Aqueous flow characteristics were also observed. RESULTS: Peak IOP elevation above baseline was significantly higher in the glaucoma group, with an average IOP rise of 39.7% on 1.6 1.1 medications, compared with 22.9% in the control group ( P =0.04). AqCA significantly increased for glaucomatous and nonglaucomatous eyes in response to water ingestion ( P <0.05). AqCA fell by 50% in glaucomatous eyes ( P =0.003) and 33% in nonglaucomatous eyes ( P =0.08) at study completion compared with the peak measurement. IOP remained >30% elevated in 8 glaucomatous eyes (40%) after 60 minutes and no control eyes. Variations in qualitative aqueous flow patterns were observed in glaucomatous eyes but not in controls. CONCLUSIONS: AO volume, estimated by AqCA, increases in response to IOP elevation induced by an ingested water bolus in patients with and without glaucoma. The increase in aqueous drainage was not sustained in glaucomatous eyes and may have led to incomplete recovery of IOP. Using HVI in combination with the WDT may assist with clinical decision-making and facilitate the monitoring of responses to treatment.

Infective Necrotizing Scleritis After XEN Gel Stent With Mitomycin-C.

PURPOSE: The purpose of this study was to report a case of infective necrotizing scleritis following XEN Gel Stent with mitomycin-C. METHODS: Case report. This is a case report of a 68-year-old woman. RESULTS: XEN Gel Stent glaucoma surgery enhanced with mitomycin-C 0.04% and combined with cataract surgery was performed at a regional center to manage the patient's primary open-angle glaucoma. Past medical history was significant for rheumatoid arthritis requiring treatment with methotrexate and adalimumab. Periocular pain and swelling developed 14 months after the initial operation, followed by a rapid deterioration of visual acuity to 20/60, intraocular pressure of 4 mm Hg, and worsening pain 5 months later. On initial presentation to Sydney Eye Hospital, 180 degrees of scleral necrosis was evident with a moderate anterior segment inflammatory reaction and a large temporal choroidal effusion due to hypotony. Empirical hourly topical ofloxacin and cephalothin 5% drops, with oral moxifloxacin, were initiated. Conjunctival swab grew Staphylococcus aureus and Staphylococcus lugdunensis. Significant clinical improvement occurred, but the XEN Gel Stent became exposed after 9 days of treatment with worsening hypotony. Urgent surgical revision was performed to remove the XEN Gel Stent and apply a tutoplast plug with overlying amniotic membrane graft. Intraocular pressure gradually improved over 6 weeks to 15 mm Hg with reversal of hypotonous changes, and visual acuity stabilized at 20/40. CONCLUSIONS: To our knowledge, this is the first reported case of necrotizing scleritis following XEN Gel Stent insertion. It is a reminder that infection should always be the primary differential diagnosis in patients with surgical-induced necrotizing scleritis.

Aqueous outflow imaging techniques and what they tell us about intraocular pressure regulation.

Recent advances in the medical and surgical management of open-angle glaucoma have increased the number of treatment options available. Several new intraocular pressure (IOP)-lowering treatments target the conventional aqueous outflow (AO) system. However, success rates are variable and outcomes in individual patients are often difficult to predict. Variable treatment responses remain unexplained and highlight deficiencies in our current understanding of AO regulation and IOP homeostasis. Imaging is often relied upon to confirm diagnoses and monitor treatment responses in other ocular and systemic pathologies. As yet no suitable AO imaging tool has been developed to fulfil this role in glaucoma. A variety of imaging techniques have been used to study the AO tracts of humans and animals in ex vivo and in vivo eyes. In this review, results from novel imaging techniques that assess aqueous drainage through the episcleral venous system are considered and we argue these provide new insights into AO regulation. We suggest that the ability to objectively measure AO responses to interventions would be a significant clinical advance, and we have demonstrated that this can be achieved with direct visualisation of aqueous drainage. We predict that the evolution of AO imaging technology will continue to reveal critical components of AO and IOP regulation, and that personalised IOP-lowering treatment in glaucoma care may well become a reality in the near future.

The Latest Drugs in Development That Reduce Intraocular Pressure in Ocular Hypertension and Glaucoma.

Glaucoma causes irreversible vision loss, with elevated intraocular pressure (IOP) being the only known modifiable risk factor. There are a variety of medical and interventional options for lowering IOP; however, despite these treatments, glaucoma continues to be a leading cause of visual impairment. Further research continues to strive for treatment options with improved side effect profiles, additional IOP-lowering effects, and ease of use. This review provides a brief summary of current IOP-lowering therapies and then outlines pipeline ocular hypotensive agents, their mechanisms of action, benefits, and side effect profiles. Advancements are seen within currently used eye drop classes such as prostaglandin analogues, Rho kinase inhibitors and nitric oxide donors, whilst there are also new drug classes, such as tyrosine protein kinase activators. Most developing drugs are topical drop formulations, with a number already having entered Phase III trials. Alternative drug delivery methods are also in development and will be briefly discussed. Pharmacological and drug delivery developments continue to provide glaucoma patients and clinicians with new options and the promise of better outcomes, particularly in terms of improved tolerance and reduced frequency of dosing.

The Effects of Trabecular Bypass Surgery on Conventional Aqueous Outflow, Visualized by Hemoglobin Video Imaging.

PRECIS: Hemoglobin Video Imaging (HVI) provides a noninvasive method to quantify aqueous outflow (AO) perioperatively. Trabecular bypass surgery (TBS) is able to improve, and in some cases re-establish, conventional AO. PURPOSE: The purpose of this study was to use HVI to illustrate and quantify effects of TBS on AO through the episcleral venous system. DESIGN: This is a prospective observational cohort study. PARTICIPANTS: Patients were recruited from Sydney Eye Hospital, Australia. The study included 29 eyes from 25 patients, 15 with glaucoma and 14 normal controls. TBS (iStent Inject) was performed on 14 glaucomatous eyes (9 combined phacoemulsification/TBS and 5 standalone TBS). Cataract surgery alone was performed on the remaining eye from the glaucoma group and 2 eyes from the control group. METHODS: We used HVI, a novel clinic-based tool, to visualize and quantify AO perioperatively during routine follow-up to 6 months. Angiographic blood flow patterns were observed within prominent aqueous veins on the nasal and temporal ocular surface. Aqueous column cross-section area (AqCA) was compared before and after surgery. MAIN OUTCOME MEASURES: AqCA, number of aqueous veins, intraocular pressure (IOP) before and after surgery, and number of IOP-lowering medications. RESULTS: Patients with glaucoma had reduced AqCA compared with normal controls (P=0.00001). TBS increased AqCA in 13 eyes at 1 month (n=14; P<0.002), suggesting improved AO. This effect was maintained at 6 months in 7 eyes (n=9, P≤0.05). All patients with unrecordable AO before surgery (n=3; 2 standalone TBS, 1 combined cataract/TBS) established measurable flow after TBS. IOP and/or medication burden became reduced in every patient undergoing TBS. Cataract surgery alone (n=3) increased AqCA in nasal and temporal vessels at 4 weeks after surgery. CONCLUSIONS: HVI provides a safe method for detecting and monitoring AO perioperatively in an outpatient setting. Improvement of AO into the episcleral venous system is expected after TBS and can be visualized with HVI. TBS is able to improve, and in some cases re-establish, conventional AO. Cataract surgery may augment this. Some aqueous veins were first seen after TBS and these patients had unstable postoperative IOP control, which possibly suggests reorganization of aqueous homeostatic mechanisms. HVI may confirm adequacy of surgery during short-term follow-up, but further work is required to assess the potential of HVI to predict surgical outcomes and assist with personalized treatment decisions.

Successful corneal autograft after clearance of anterior chamber cytomegalovirus with oral valganciclovir in a patient with multiple failed corneal allografts.

PURPOSE: To report a case of recurrent corneal graft failure because of cytomegalovirus (CMV) infection and to demonstrate successful clearance of the virus with oral valganciclovir, confirmed by polymerase chain reaction (PCR) assay. This allowed for a successful corneal autograft to be performed. METHODS: Interventional case report. RESULTS: A 90-year-old white man with 4 previous corneal graft failures in his right eye is presented. His visual acuity was no light perception in the left eye subsequent to ocular trauma. His initial penetrating keratoplasty for pseudophakic bullous keratopathy was from a human leukocyte antigen-matched multiorgan donor who was CMV-seropositive. An anterior chamber paracentesis was performed to exclude an infective etiology. CMV was detected on PCR of aqueous humor. After a 12-week course of oral valganciclovir, a repeat aqueous PCR test confirmed the clearance of CMV. A corneal autograft from his left eye was subsequently performed with good outcome. CONCLUSIONS: We present a case of successful corneal autograft after clearance of CMV from the anterior chamber (PCR confirmed) in a patient treated with oral valganciclovir.

Primary trabeculectomy with mitomycin C: safety and efficacy at 2 years.

PURPOSE: To examine the rates of intermediate-term intraocular pressure (IOP) control after trabeculectomy with adjunctive mitomycin C (MMC) and assess for associated complications. METHODS: Medical records of patients undergoing primary trabeculectomy with MMC at Concord Repatriation Hospital, Sydney between January 1997 and December 2005 were reviewed. All eyes with a minimum of 2-year follow up were included. Follow-up data were collected in a standardized form on postoperative IOP, bleb-related and other complications. Success was measured as IOP ≤ 18 mmHg and ≥ 6 mmHg (criteria 1) with (qualified success) or without (absolute success) the use of glaucoma medications. A secondary outcome measure was an IOP reduction of greater than 20% from baseline (criteria 2). Eyes with preoperative IOP of 18 mmHg or less were included, but also analysed separately to those eyes with preoperative IOP above 18 mmHg. RESULTS: Sixty eyes from 42 patients were included in the study, with 3-year follow up on 48 eyes. Mean preoperative IOP was 25.3 mmHg (range 8-45) and mean postoperative IOP was 14.0 mmHg at 1- and 2-year follow up, and 14.7 mmHg at 3 years (ranges: 3-31, 4-30 and 8-45 mmHg respectively). Cumulative success for criteria 1 was 85.0% at 2 years and 83.3% at 3 years, and for criteria 2 it was 80.0% and 79.2%, respectively. The number of eyes on glaucoma medications was reduced from 51 preoperatively to 30 at 3 years. Complications were infrequent. There was one eye with a shallow anterior chamber beyond the immediate postoperative period. One eye required cataract surgery at 1-year follow up. Subgroup analysis was performed using the first operated eye only, and results did not differ significantly from overall results. CONCLUSION: MMC-augmented trabeculectomy can significantly reduce IOP in the short and intermediate term, with a favourable safety profile.