A new model of axon degeneration in the mouse optic nerve using repeat intraocular pressure challenge.

We characterize a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. C57BL/6J mice were subjected to two acute periods of intraocular pressure (IOP) elevation (50 mmHg for 30 min) by cannulation of the anterior chamber. We used full-field electroretinography and visual evoked potentials (VEPs) to measure subsequent changes in retina and optic nerve function, and histochemical techniques to assess RGC survival and optic nerve structure. In 12 month old mice, a single IOP challenge caused loss and subsequent recovery of RGC function over the following 28 days with minimal cell death and no observed axonal damage. A second identical IOP challenge resulted in persistent RGC dysfunction and significant (36%) loss of RGC somas. This was accompanied by a 16.7% delay in the latency and a 27.6% decrease in the amplitude of the VEP. Severe axonal damage was seen histologically with enlargement of axons, myelin disruption, reduced axon density, and the presence of glial scarring. In contrast, younger 3 month old mice when exposed to a single or repeat IOP challenge showed quicker RGC functional recovery after a single challenge and full functional recovery after a repeat challenge with no detectable optic nerve dysfunction. These data demonstrate a highly reproducible and minimally invasive method for inducing RGC degeneration and axonal damage in mice. Resilience of the optic nerve to damage is highly dependent on animal age. The time-defined nature of functional versus structural loss seen in this model stands to facilitate investigation of neuroglial responses in the retina after IOP injury and the associated evaluation of neuroprotective treatment strategies. Further, the model may be used to investigate the impact of aging and the cellular switch between neurorecovery and neurodegeneration.

Effects of age on retinal macrophage responses to acute elevation of intraocular pressure.

There is accumulating evidence that aging shifts the central nervous system milieu towards a proinflammatory state, with increased reactivity of microglia in the aging eye and brain having been implicated in the development of age-related neurodegenerative conditions. Indeed, alterations to microglial morphology and function have been recognized as a part of normal aging. Here, we sought to assess the effects of age on the retinal microglial and macrophage response to acute intraocular pressure (IOP) elevation. Further, we performed experiments whereby bone marrow from young or middle-aged mice was used to reconstitute the bone marrow of whole-body irradiated 12 month old mice. Bone marrow chimeric mice then underwent cannulation and IOP elevation 8 weeks after whole-body irradiation and bone marrow transplantation in order to determine whether the age of bone marrow alters the macrophage response to retinal injury. Our data show retinal macrophage reactivity and microglial morphological changes were enhanced in older mice when compared to younger mice in response to injury. When IOP elevation was performed after whole-body irradiation and bone marrow rescue, we noted subretinal macrophage accumulation and glial reactivity was reduced compared to non-irradiated mice that had also undergone IOP elevation. This effect was evident in both groups of chimeric mice that had received either young or middle-aged bone marrow, suggesting irradiation itself may alter the macrophage and glial response to injury rather than the age of bone marrow.

Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.

IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS: Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.

Bleb-associated endophthalmitis: Proportion, presentation, management and outcomes in Victoria, Australia.

IMPORTANCE: Bleb-associated endophthalmitis is a potentially vision-threatening complication of trabeculectomy. With improvements in surgical technique and changing patterns of intraoperative antimetabolite use, a re-evaluation of the incidence of bleb-associated endophthalmitis is warranted. BACKGROUND: To investigate changes in the incidence, presentation, management and outcomes of bleb-associated endophthalmitis between 1997 and 2015 in Victoria, Australia. DESIGN: A retrospective cohort analysis. PARTICIPANTS: Consecutive cases of bleb-associated endophthalmitis managed at the Royal Victorian Eye and Ear Hospital (RVEEH) between 1997 and 2015. METHODS: Medical record review of consecutive cases of bleb-associated endophthalmitis and statistical analysis were performed. MAIN OUTCOME MEASURES: Visual acuity, including loss of light perception, intraocular pressure, and need for further surgery. RESULTS: Sixty-seven eyes with bleb-associated endophthalmitis (BAE) were identified. Of these, 41 had trabeculectomy performed in Victoria during the study period, over which time 11 129 trabeculectomies were performed. The proportion of BAE was stable over time (0.4%). The mean age at presentation was 73.7 ± 12.1 years old and the majority of patients were Caucasian (79.1%). The mean duration between glaucoma filtration surgery and the development of bleb-associated endophthalmitis was 3 years (Interquartile Range = 0.4-6.0 years). The cultures were positive in 71.6% of cases. Approximately 1 in 8 patients required enucleation. The final visual acuity was poor with a Snellen Visual Acuity (VA) of 6/60 or worse in two-thirds of patients. CONCLUSIONS AND RELEVANCE: Bleb-associated endophthalmitis is an uncommon complication following glaucoma filtration surgery. The proportion has remained stable over time. Visual outcomes remain poor.

Optic Nerve Head Drusen: An Update.

Optic nerve head drusen are benign acellular calcium concretions that usually form early in life, just anterior to the lamina cribrosa. Improving imaging using optical coherence tomography suggests they are common and may be present in many clinically normal discs. These drusen may change in appearance in early life, but are generally stable in adulthood, and may be associated with visual field defects, anterior ischaemic optic neuropathy, or rarer complications. Based on long-term clinical data and optical coherence tomography, we propose a refined hypothesis as to the cause of optic disc drusen. Here we summarise recent findings and suggest future studies to better understand the forces involved.

A short term high-fat high-sucrose diet in mice impairs optic nerve recovery after injury and this is not reversed by exercise.

The aim of the current work was to test whether increased intake of dietary fat and sucrose in mice modifies the response of retinal ganglion cells (RGCs) of the optic nerve to injury, and whether any effects of diet are influenced by physical activity levels. C57BL/6J mice were given a high-fat high-sucrose (HFS) diet for 7 weeks, with or without exposure to regular exercise by swimming (60 min/day, 5 days/week). Injury to RGCs was subsequently induced by acute elevation of intraocular pressure (IOP) and retinas were assessed for function and structure. We report that mice on a HFS diet had similar body mass and blood glucose levels compared to mice on a control diet but suffered a 30% greater loss of RGC function following injury, as measured in vivo with the electroretinogram. RGC dysfunction in retinas from mice on the HFS diet was accompanied by activation of retinal macroglia but was not associated with neuronal cell loss. Exercising mice by swimming did not prevent HFS-induced RGC dysfunction in response to injury. This study shows for the first time that a short term increase in dietary fat and sucrose enhances the vulnerability of RGCs to dysfunction and cell stress after an acute injury, and that this is independent of obesity or hyperglycemia. Furthermore, our results suggest that detrimental effects of diet predominate over protective effects of exercise.

Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity.

IMPORTANCE: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. BACKGROUND: This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. DESIGN: Retrospective chart review at a tertiary institution. SAMPLES: Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. METHODS: Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. MAIN OUTCOME MEASURES: Surgical outcomes as defined in Guidelines from World Glaucoma Association. RESULTS: Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. CONCLUSIONS AND RELEVANCE: Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.

Effects of ranibizumab on TGF-ß1 and TGF-ß2 production by human Tenon's fibroblasts: An in vitro study.

PURPOSE: Inhibiting exaggerated wound healing responses, which are primarily mediated by human Tenon's fibroblast (HTF) migration and proliferation, has become the major determining factor for a successful trabeculectomy. Antivascular endothelial growth factor (anti-VEGF) has showed promising results as a potential antifibrotic candidate for use concurrently in trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. However, the effects on HTFs remain unclear. This study was conducted to understand the effects of ranibizumab on transforming growth factor (TGF)-ß1 and transforming growth factor (TGF)-ß2 expression by HTFs. METHODS: The effect of ranibizumab on HTF proliferation and cell viability was determined using 3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/ml were administered for 24, 48, and 72 h in serum and serum-free conditions. Supernatants and cell lysates from samples were assessed for TGF-ß1 and TGF-ß2 mRNA and protein levels using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: At 48 h, 0.5 mg/ml of ranibizumab significantly induced cell death under serum-free culture conditions (p<0.05). Ranibizumab caused a significant reduction in TGF-ß1 mRNA, but not for TGF-ß2. However, the total protein production of TGF-ß1 and TGF-ß2 was unaffected by this anti-VEGF treatment. CONCLUSIONS: Exposure of HTFs to an intravitreal dose of ranibizumab significantly suppresses cell viability in vitro; however, the application seemed unable to affect the ultimate production of TGF-ß. Therefore, we highlighted ranibizumab as a potential antiscarring agent that acts via a different mechanism when used synergistically with another antifibrotic agent. Understanding the mechanism of actions of ranibizumab offers an additional view of a possible new rational therapeutic strategy.

An acute intraocular pressure challenge to assess retinal ganglion cell injury and recovery in the mouse.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma.

Clinical audit examining the impact of benzalkonium chloride-free anti-glaucoma medications on patients with symptoms of ocular surface disease.

BACKGROUND: Ocular surface disease (OSD) is relatively common in glaucoma patients. OSD symptoms could be linked to prolonged exposure to preservatives in anti-glaucoma medications, especially benzalkonium chloride (BAK). The OBSERVE clinical audit was designed to track the impact of intraocular pressure lowering medications in patients with evidence of OSD to test the hypothesis that BAK-free anti-glaucoma preparations offer clinical advantages over BAK-containing products. DESIGN: Prospective clinical audit from March 2012 to April 2013, open to ophthalmologists practising in Australia. PARTICIPANTS: There were 375 patients enrolled, with a completion rate of 64%. The cohort was predominantly female (68%) with an average age of 71 years. METHODS: Patients were screened for inclusion during a routine consultation. If eligible, they were enrolled. At the ophthalmologist's discretion, some patients were switched to BAK-free anti-glaucoma products. Data were collected via an online survey completed by the ophthalmologist during three appointments over a 16- to 30-week period for all patients. MAIN OUTCOME MEASURES: Intraocular pressure, tear-film breakup time, McMonnies Dry Eye Questionnaire score and reported lubricant use. RESULTS: Patients who switched to BAK-free preparations reported a significant fall in the use of lubricants (P = <0.001). Patients in both groups experienced a significant improvement in McMonnies Dry Eye Questionnaire score (P = <0.0001). The percentage of patients with low tear-film breakup time decreased significantly in both groups (P = 0.0001). There was no significant change in intraocular pressure from pre-study levels for either group (P = 0.105). CONCLUSIONS: BAK-free anti-glaucoma preparations were associated with a change in lubricant use, suggesting reduction in some OSD symptoms, but more research is needed.

Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension.

BACKGROUND: Steroid-induced ocular hypertension is currently treated in the same way as primary open-angle glaucoma. However, the treatment is often suboptimal and is associated with adverse effects. We evaluated the oculohypotensive effects of topical trans-resveratrol in rats with steroid-induced ocular hypertension and involvement of adenosine receptors (AR) in intraocular pressure (IOP) lowering effect of trans-resveratrol. METHODS: The oculohypotensive effect of unilateral single-drop application of various concentrations of trans-resveratrol was first studied in oculonormotensive rats. Concentration with maximum effect was similarly studied in rats with steroid-induced ocular hypertension. Involvement of AR was studied by observing the alterations of IOP in response to trans-resveratrol after pretreating animals with AR subtype-specific antagonists. Additionally, we used computational methods, including 3D modelling, 3D structure generation and protein-ligand interaction, to determine the AR-trans-resveratrol interaction. RESULTS: All concentrations of trans-resveratrol produced significant IOP reduction in normotensive rat eyes. Maximum mean IOP reduction of 15.1% was achieved with trans-resveratrol 0.2%. In oculohypertensive rats, trans-resveratrol 0.2% produced peak IOP reduction of 25.2%. Pretreatment with A1 antagonist abolished the oculohypotensive effect of trans-resveratrol. Pretreatment with A3 and A2A AR antagonists produced significant IOP reduction in both treated and control eyes, which was further augmented by trans-resveratrol application in treated eyes. Computational studies showed that trans-resveratrol has highest affinity for A2B and A1, followed by A2A and A3 AR. CONCLUSION: Topically applied trans-resveratrol reduces IOP in rats with steroid-induced ocular hypertension. Trans-resveratrol-induced oculohypotension involves its agonistic activity at the A1 AR.

Cataract and quality of life in patients with glaucoma.

BACKGROUND: To assess the impact of cataract on quality of life (QoL) for patients with glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred forty-two patients with mild (n = 67), moderate (n = 80) or severe (n = 45) glaucoma and 50 controls (glaucoma suspects). Patients with cataract of any severity were included. METHODS: The following data were collected: sociodemographic information, phakic/pseudophakic status, cataract grade according to the Lens Opacities Classification System (LOCS) III, visual acuity and visual field test parameters. Glaucoma severity was stratified according to binocular visual field loss. Visually significant cataract was defined as: LOCS III criteria nuclear cataract ≥3/6.9, cortical cataract ≥3/5.9 or posterior subcapsular cataract ≥2/5.9. MAIN OUTCOME MEASURES: Patients' QoL was measured using Rasch-transformed scores from the Glaucoma Activity Limitation-9 (GAL-9) questionnaire. Multiple linear regression models were used to determine the association between cataract and GAL-9 (logit) score. RESULTS: Fifty-six (23.1%) patients had at least one visually significant cataract. At least one visually significant cataract (standardized coefficient [ß] 1.19, 95% confidence interval 1.04-1.34, P = 0.011) and poor visual field index (better eye) (ß 1.47, 95% confidence interval 1.36-1.88, P < 0.001) were independently associated with worse GAL-9 score. CONCLUSIONS: Cataract influences glaucoma-related QoL among glaucoma patients of all severity levels and is an important cause of potentially reversible visual impairment among glaucoma patients. The Rasch-analysed GAL-9 questionnaire is a useful metric to quantify visual disability related to cataract in glaucoma patients.

Validation of rebound tonometry for intraocular pressure measurement in the rabbit.

Rabbits play a growing role in research into glaucoma surgical models and ocular drug delivery models. However, the lack of an accurate method for measuring intraocular pressure (IOP) in this animal has been a significant deficit. In this study we validated the use of the TonoVet rebound tonometer and provide conversion tables for its use in rabbits. Experiments were performed on 18 adult New Zealand White rabbits. The TonoVet measurements were obtained and compared to manometric readings by anterior chamber (AC) cannulation. The TonoVet position and 'd' (dog or cat) and 'p' (other species) modes were compared. The sensitivity of the TonoVet tonometer in assessing IOP changes was also tested. There was a strong linear correlation for both the 'd' mode (mean slope = 0.84 ± 0.03, r(2) = 0.99 ± 0.03) and the 'p' mode (mean slope = 0.64 ± 0.02, r2 = 0.97 ± 0.01) of the TonoVet with manometric IOP. However, the TonoVet had a tendency to underestimate IOP compared to manometry and conversion formulae were possible to calculate for both modes. The orientation of the TonoVet handle had no effect on IOP reading, as long as the groove was horizontal. No significant differences were observed when comparing right and left eyes (P > 0.05). IOP recovered four days after cannulation. Younger rabbits had lower IOP compared with older rabbits (P < 0.01). Timolol produced a 2.5 mmHg reduction in IOP 2 h later as detected by the TonoVet. Using the conversion table presented, the TonoVet is a reliable and precise tool for the measurement of IOP in rabbits.

Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast.

Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p < 0.05). Ranibizumab caused significant reduction of collagen type 1 alpha 1 (COL1A1) mRNA, but not for fibronectin (FN). Meanwhile, COL1A1 and FN protein levels were found upregulated in treated monolayers compared to control monolayers. Ranibizumab at 0.5 mg/mL significantly reduced cell viability in cultured HTF. From this study, we found that single application of ranibizumab is inadequate to induce the anti-fibrotic effects on HTF, suggesting the importance of adjunctive therapy. Further studies are underway to understand mechanism of actions of ranibizumab on HTF.

Physical inactivity as a risk factor for diabetic retinopathy? A review.

Physical inactivity and sedentary behaviour have been identified as modifiable risk factors for diabetes. However, little is known of the associations between physical activity, sedentary behaviour and diabetic retinopathy. The development of diabetic retinopathy is associated with longer duration of diabetes, elevated blood pressure and poor glycaemic control. However these factors only explain a proportion of the risk of retinopathy in individuals with diabetes. Several studies have suggested a protective role for physical activity in diabetic retinopathy. Other work has shown that the time spent watching television is independently associated with abnormal retinal vascular signs. Limitations of the existing studies, such as the absence of objective measures of physical activity, a lack of sedentary behaviour measures, the inclusion of only those with type 1 diabetes and a lack of longitudinal data, make it difficult to draw firm conclusions about the strength of these associations.

Interferon-alpha and interferon-gamma modulate Fas-mediated apoptosis in mitomycin-C-resistant human Tenon's fibroblasts.

BACKGROUND: The aim of the study was to investigate, using a native mitomycin-C-resistant human Tenon's fibroblast cell line, the possibility that interferon-alpha and gamma could be used with Fas agonists as an alternative anti-fibrotic strategy to mitomycin-C in trabeculectomy. METHODS: A clinically resistant and in vitro verified mitomycin-C-resistant human Tenon's fibroblast cell line was pretreated with interferon-alpha and interferon-gamma for 48 h before stimulation with an agonistic Fas antibody (CH11) for 2 days to induce cell death. Cell death assays were undertaken. Changes in apoptosis-related proteins were determined by flow cytometry and Western blot. RESULTS: Pretreatment with interferon-alpha or interferon-gamma for 48 h increased Fas, Fas-associated protein with death domain and caspase-8 expression. Protein expression was further increased by combined exposure to interferon-alpha and gamma. Pretreatment with cytokines had no effect on Fas-L and Bcl-2. Interferon-alpha alone did not change the rate of induced cell death. A combination of interferon-alpha and gamma synergistically increased the sensitivity of mitomycin-C-resistant human Tenon's fibroblast cell line to induced cell death. An antagonistic anti-Fas antibody (ZB4) completely blocked induced cell death. Broad caspase inhibitors specific for caspases-8 and -3 reduced induced deaths in interferon pretreated mitomycin-C-resistant human Tenon's fibroblast cell line in a dose-dependent manner. CONCLUSIONS: Interferon-alpha and interferon-gamma render mitomycin-C-resistant human Tenon's fibroblast cell line sensitive to Fas-mediated apoptosis. The mechanism involves increased death-inducing signalling complex formation by upregulation of Fas, Fas-associated protein with death domain and caspase-8 expression.

Effect of phacoemulsification on trabeculectomy function.

BACKGROUND: To evaluate the effect of phacoemulsification on trabeculectomy function. DESIGN: Retrospective case-control study. PARTICIPANTS: Forty-eight patients who underwent trabeculectomy surgery and had at least 2 years of follow up. METHODS: Patients were classified into two groups: patients who had phacoemulsification subsequent to trabeculectomy (Trab_phaco, n = 18) and patients who were pseudophakic for greater than 6 months preceding their trabeculectomy (Phaco_trab, n = 30). Groups were matched for length of follow up of 2 years from time of trabeculectomy. MAIN OUTCOME MEASURES: The primary outcome measures were target intraocular pressure of criteria A, ≤12 mmHg; B, ≤15 mmHg; C, ≤18 mmHg with or without additional topical treatment. A separate measure for bleb function failure was also used; with failure defined as the need for additional topical antiglaucoma therapy or surgical intervention to achieve control of intraocular pressure. RESULTS: There was no significant difference in achieving each intraocular pressure criterion between groups (12 months, P = 1.0; 24 months, P = 0.330). In the first 12 months, significantly more trabeculectomies in the Trab_phaco group failed, requiring additional intervention to control the IOP (39%) compared with the Phaco_trab (10%) group (P = 0.028). Although this trend continued at 24 months, there were no significant differences in failure rates (P = 0.522). CONCLUSIONS: Phacoemulsification performed after trabeculectomy significantly increased rates of bleb failure in the following 12 months but not at 24 months.

Incidence and predictors of glaucoma following surgery for congenital cataract in the first year of life in Victoria, Australia.

AIM: To determine the incidence and predictors of glaucoma following surgery for congenital and infantile cataract in an Australian population. DESIGN: Retrospective cohort study. PARTICIPANTS: Infants (<12 months) having had lens extraction between January 1992 and May 2006, from two tertiary referral centres. METHODS: Children with uveitis, anterior segment dysgenesis, aniridia, retinopathy of prematurity, and lens subluxation were excluded. Potential predictors of incident glaucoma were examined using Cox proportional hazards regression with adjustment for clustering between eyes. MAIN OUTCOME MEASURES: Incidence and predictors of secondary glaucoma. RESULTS: One hundred and forty-seven eyes of 101 patients (46 bilateral cataract; 55 unilateral cataract) were included, with median follow-up of 9.9 years (range 1.2-18.9 years). Cumulative incidence of glaucoma was 32.0% for eyes (n = 47) and 30.7% (n = 31) for subjects. Incidence was higher in children with bilateral cataract (38.9 vs. 17.1%, p = 0.004). There were 3.9 cases of glaucoma per 100 person years of follow-up, the incidence rate being highest for surgery performed in the first month of life. Children with glaucoma had longer median follow-up (11.8 vs. 9.3 years, p = 0.005). Risk of glaucoma decreased with increasing months of age at operation: hazard ratio 0.79, 95% confidence interval 0.69-0.91, p = 0.001. Median visual acuity was worse in children with unilateral cataract (p < 0.001). CONCLUSIONS: We identified an increased risk of glaucoma when cataract surgery was performed in younger infants, and in those with bilateral cataract. As glaucoma may develop over a decade following lens extraction, life-long surveillance is needed to prevent glaucoma-associated vision loss.

Sociodemographic factors and utilization of eye care services: is there an association with patients presenting to a tertiary referral hospital in acute angle-closure?

BACKGROUND: The aim of this study is to examine the relationship between sociodemographic factors and utilization of eye care services in patients presenting in acute angle-closure (AAC). DESIGN: A hospital-based retrospective, case-control study. PARTICIPANTS: Fifty-five patients consecutively presenting to the emergency department of the Royal Victorian Eye and Ear Hospital with AAC (cases), and 43 patients consecutively referred to the outpatient department for prophylactic laser peripheral iridotomy (controls) over a 3-year period. METHODS: Standardized telephone questionnaires. MAIN OUTCOME MEASURES: Comparisons were made for sociodemographic factors, utilization of eye care services and provision of information on glaucoma and premonitory symptoms of AAC. RESULTS: No significant differences across a range of socioeconomic and demographic factors were found. Fewer cases reported having attended an eye care professional ever (P = 0.02), or in the 12 months preceding their acute hospital attendance (P = 0.002), and had less awareness of angle closure glaucoma (P = 0.001). Logistic regression modelling demonstrated premonitory symptoms of AAC (odds ratio 3.96, [95% confidence interval 1.52-10.32], P < 0.001) and a period of greater than 12 months since the last eye examination (odds ratio 3.89, [95% confidence interval 1.64-9.21]) were significantly associated with the risk of AAC. CONCLUSIONS: No significant differences in socioeconomic or demographic parameters between cases and controls were identified. Control subjects had a history of more frequent and recent access to eye care services than cases. The finding that more than one-third of patients presenting with AAC had consulted an eye care provider in the preceding year suggests that a significant proportion of individuals at risk of AAC remain undetected.