Ophthalmologists and climate change.

It is indisputable that human activities have caused climate change and that, if left unchecked, these activities will lead to worsening of weather extremes including fire, drought, and flood with all their attendant human suffering. Reducing future climate change requires limiting cumulative emissions of CO2 and other greenhouse gases including methane. We have written this evidence-based perspective to highlight interventions with the largest effect to help the average ophthalmologist make the changes with the highest impact in their day-to-day lives.

The association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema.

Aim: To investigate the association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema (DME). Methods: Twenty-five patients with center-involved DME were recruited prospectively. Serum samples were collected from the patients before and 4 weeks after two ranibizumab injections. The levels of 32 cytokines at these two time points were assessed using a multiplex array assay. Results: Following two ranibizumab injections, there was a statistically significant decrease in the median [interquartile range] levels of Interleukin 1-1beta (IL-1ß) from 5.56 [3.6, 8.75] to 2.33 [1.51, 2.89], Interleukin 13 (IL-13) from 4.30 [1.84, 18.55] to 0.38 [0.38, 0.78], granulocyte-colony stimulating factor (G-CSF) from 64.65 [42.9, 108] to 37.8 [27.3, 46.37], Interferon gamma (IFN-γ) from 241 [103.33, 753.4] to 94.4626 [42.04, 118.58], Interferon gamma-induced protein 10 (IP-10) from 234.68 [144.16, 285.98] to 158.73 [94.71, 198.64], Macrophage Inflammatory Protein-1 alpha (MIP-1α) from 3.65 [2.62, 11.02] to 1.41 [0.94, 1.88], and Tumor necrosis factor- alpha (TNF-α) from 131.09 [100.68,28 240.27] to 45.19 [24.04, 68.55]. There was a statistically significant increase in the levels of Interleukin 9 (IL-9) from 0.76 [0.76, 7.03] to 19.67 [5.36 27.76], Macrophage Inflammatory Protein-1 beta (MIP-1ß) from 0.28 [0.28, 30 0.28] to 6.79 [I3.74, 14.16], Vascular endothelial growth factor (VEGF) from 2.55 [2.55, 2.55] to 25.24 [14.51, 41.73], and soluble vascular endothelial growth factor -1 (sVEGFR-1) from 333.92 [204.99, 440.43] to 500.12 [38.7, 786.91]. A Bonferroni-corrected p value of 0.00156 was considered statistically significant. Conclusions: In patients with DME, intravitreal ranibizumab therapy appears to influence the serum levels of a range of cytokines. After two injections, intravitreal ranibizumab therapy appears to be associated with a significant decrease in inflammatory mediators and a rise in VEGF and sVEGFR1.

Diabetic retinopathy progression 6 months post-cataract surgery with intravitreous bevacizumab vs triamcinolone: A secondary analysis of the DiMECAT trial.

IMPORTANCE: Diabetic retinopathy (DR) may progress following cataract surgery due to surgery-induced inflammation. The effect of intravitreal bevacizumab (BVB) and triamcinolone acetonide (TCA), which have differing anti-inflammatory properties, on DR progression following cataract surgery has not been reported. BACKGROUND: To report the progression of DR in diabetic patients undergoing cataract extraction treated with intravitreal BVB or TCA during the surgery. DESIGN: Post hoc analysis of 6-month data from a prospective, randomized, double-masked clinical trial. PARTICIPANTS: Diabetic patients with clinically significant cataract and fovea involving diabetic macular oedema (DME), or a recent history of DME. METHODS: Participants were randomly allocated 1:1 to receive intravitreal BVB 1.25 mg or TCA 4 mg during and post-cataract surgery as needed. The rate of DR progression between groups was compared. MAIN OUTCOME MEASURES: DR progression. RESULTS: There were 61 eyes included. Patients receiving BVB were older than those receiving TCA (70.2 vs 64.3 years; P < .05). Three participants (10.7%) in the BVB and three (9.09%) in the TCA group had a one-step progression, while none in BVB and only one (3%) in the TCA group demonstrated two-step DR progression. In the majority of these patients, DR progression was from mild to moderate non-proliferative diabetic retinopathy. CONCLUSION AND RELEVANCE: In this study, BVB and TCA groups had a similar, and lower rate of DR progression compared to previous studies where no adjunctive treatment was administered, suggesting that patients with DME may benefit from either intraoperative intravitreous BVB or TCA injection to reduce the risk of DR progression following cataract surgery.

Early worsening of diabetic retinopathy due to intensive glycaemic control.

The prevalence of diabetes and diabetic retinopathy is increasing around the world. Glycaemic control is important in reducing the long-term risk of complications of diabetes, however intensive glycaemic control, particularly in patients with longstanding and poorly controlled diabetes, is associated with the risk of early worsening of diabetic retinopathy and vision loss. We present two clinical cases to illustrate the presentation of early worsening and to highlight a role for intravitreal anti-vascular endothelial growth factor therapies in ameliorating this phenomenon, as well as a review of the current understanding of this phenomenon. We emphasise the importance of identifying individuals at risk of early worsening of diabetic retinopathy and recommend regular ophthalmological review during the period of intensive glycaemic control to ensure optimal visual outcomes.

Paracentral acute middle maculopathy as a finding in patients with severe vision loss following phacoemulsification cataract surgery.

IMPORTANCE: Paracentral acute middle maculopathy (PAMM) diagnosed by spectral domain optical coherence tomography (SD-OCT) in patients with poor visual outcome post cataract surgery. BACKGROUND: Case series of severe vision loss due to PAMM after cataract surgery. DESIGN: Retrospective case series. PARTICIPANTS: Cases from five surgical centres in Victoria, Australia. METHODS: Retrospective analysis of cases with unexplained 'patch-off' vision loss post cataract surgery. All patients in our cohort had PAMM and presumed diagnosis of central or transient retinal artery occlusion. MAIN OUTCOME MEASURES: A review of the patient histories focusing on pre-operative ocular and systemic vascular risk factors, anaesthetic and operative factors. RESULTS: Ten cases were included. All patients had 6/72 Snellen visual acuity or worse noted on day one post surgery. Three patients had features of central retinal artery occlusion consisting of retinal pallor with a 'cherry red' macula but absent relative afferent pupillary defect. Seven had no features of retinal pallor or attenuation of retinal arterioles. On SD-OCT, all eyes had evident PAMM. Six patients had a history of cardiovascular disease or blood dyscrasia. CONCLUSIONS AND RELEVANCE: PAMM should be considered in patients with 'patch off' visual loss and absence of other fundal signs. We hypothesise that spasm or transient occlusion of central retinal artery leads to arterial hypoperfusion with subsequent ischaemia or infarction of the retina. Underlying arterial disease may have led to pre-existing hypoperfusion that may have been further compromised by raised intraocular pressure during the procedure itself or via raised orbital pressure from the anaesthesia.

Diabetic retinopathy in pregnancy: a review.

The prevalence of diabetes in pregnancy is increasing. Pre-existing diabetes is present in 1 in 167 pregnancies in Australia, divided equally between type 1 and type 2 diabetes. Diabetic retinopathy is a leading cause of blindness in women during their childbearing years, and pregnancy increases the short-term risk of diabetic retinopathy progression. We examine the risk factors for progression of diabetic retinopathy during pregnancy including duration of diabetes, baseline level of retinopathy, level of glycaemic control and hypertension. We also examine current screening and management guidelines and their levels of evidence, current treatment options for diabetic retinopathy and avenues for further research.

Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery - preliminary 6 month results.

BACKGROUND: To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME). DESIGN: Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne. PARTICIPANTS: Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months. METHODS: Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months. MAIN OUTCOME MEASURES: Change in central macular thickness (CMT) and best corrected visual acuity at 6 months. RESULTS: Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of ≥6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (-43.8-µm reduction TA vs. +37.3-µm increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up; BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group. CONCLUSIONS: When administered at the time of cataract surgery in patients with DME, at 6 months both TA and BVB improve visual acuity; however, only TA results in a sustained reduction in CMT. Further follow-up will determine whether this translates into better long-term visual outcomes in the TA group.

Review of the role of refined dietary sugars (fructose and glucose) in the genesis of retinal disease.

This review examines the current evidence of the relationship between sugar consumption and the development of retinal and other eye diseases including diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataract. Sucrose is comprised of fructose and glucose. Sugar consumption has increased five-fold over the last century, with high quantities of sucrose and high-fructose corn syrup found in processed food and soft drinks. This increased consumption is increasingly recognized as a central factor in the rapidly rising rates of obesity and type 2 diabetes. The body metabolizes fructose and glucose differently, with fructose appearing to have the greater propensity to contribute to the metabolic syndrome. This review examines the effect of high rates of dietary consumption of refined carbohydrates on the eye, including the effect of chronic hyperglycaemia on microvascular disease in diabetic retinopathy, and the pathophysiological changes in the retinal circulation in hypertensive retinopathy.

Intravitreal injections: a review of the evidence for best practice.

Intravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics.

Retinal venular calibre dilatation after intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

BACKGROUND: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. DESIGN: Prospective interventional case series. PARTICIPANTS: Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. METHODS: Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. MAIN OUTCOME MEASURE: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. RESULTS: Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). CONCLUSION: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.

Prevalence of optical coherence tomography-diagnosed postoperative cystoid macular oedema in patients following uncomplicated phaco-emulsification cataract surgery.

BACKGROUND: Postoperative cystoid macular oedema is a complication of uneventful cataract surgery. Whereas improved surgical techniques have decreased the incidence of cystoid macular oedema, it remains a cause of unfavourable visual outcome following surgery. Fundus fluorescein angiography has been the 'gold standard' for diagnosing subclinical cystoid macular oedema; however, non-invasive cross-sectional imaging of the retina with optical coherence tomography may be equally effective at detecting the condition and offers the ability to quantify and repeat results over time. DESIGN: Prospective pre-post case series of patients undergoing routine phaco-emulsification surgery. PARTICIPANTS: Eighty consecutive patients (100 eyes) with cataracts and an age range of 40 to 90 years (mean 76.18). METHODS: Macular thickness of participants was determined using time-domain optical coherence tomography preoperatively and after surgery at 1 day, 1 week, 4 weeks and 6 months. Optical coherence tomography was used to diagnose postoperative cystoid macular oedema. MAIN OUTCOME MEASURES: Presence of cysts at the macula, identified by optical coherence tomography, in addition to foveal and macular thickness (µm). RESULTS: Cystoid macular oedema was present in 5% of eyes. Macular thickness increased after surgery and central foveal thickness increased by almost 7% but returned to preoperative levels after 6 months. Findings also indicate that patients who developed postoperative cystoid macular oedema had significantly thicker central foveal thickness of approximately 5% compared with those that did not. CONCLUSIONS: Optical coherence tomography is a useful, non-invasive diagnostic tool in determining subclinical cystoid macular oedema in uncomplicated cataract surgery patients and detects the presence of retinal thickening and intra-retinal cysts very soon after surgery, thereby facilitating earlier diagnosis and treatment of postoperative cystoid macular oedema.

Therapeutic targeting of the complement system in age-related macular degeneration: a review.

The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management; targeting of specific molecular constituents in the complement pathway thus producing dampening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease.

Methodology and early findings of the Diabetes Management Project: a cohort study investigating the barriers to optimal diabetes care in diabetic patients with and without diabetic retinopathy.

BACKGROUND: The Diabetes Management Project is investigating the clinical, behavioural and psychosocial barriers to optimal diabetes care in individuals with and without diabetic retinopathy. DESIGN: Prospective cohort. PARTICIPANTS: Two hundred and twenty-three and 374 patients without and with diabetic retinopathy, respectively. METHODS: All individuals underwent a comprehensive dilated eye test, anthropometric measurements, blood and urine samples, and psychosocial questionnaires. MAIN OUTCOME MEASURES: Good glycaemic control was defined as glycosylated haemoglobin < 7%, good blood pressure control as systolic and diastolic values ≤130 and 80 mmHg, respectively, and good diabetes control as glycosylated haemoglobin < 7% and blood pressure values ≤130 and 80 mmHg. RESULTS: Four hundred and one males (65.4%) and 212 females (34.6%) aged 26-90 years (mean age ± standard deviation = 64.6 ± 11.6) were examined. The median glycosylated haemoglobin for all participants was 7.5% (interquartile range = 1.7%). Average systolic and diastolic blood pressure values were 139.7 mmHg (standard deviation = 18.8) and 92.7 mmHg (standard deviation = 30.9), respectively. Initial data analyses indicate that over two-thirds of participants with diabetes have poor glycaemic control, which was worse in those with diabetic retinopathy compared with those without (76.3% vs. 49.3%; P < 0.001). Blood pressure control was similar for those with and without diabetic retinopathy, with almost a third (28.5%) of the total sample having poor blood pressure control. Overall, those with diabetic retinopathy had poorer diabetes control than those without (24.3% vs. 13.7%; P = 0.002). CONCLUSIONS: Our findings substantiate the implementation of the Diabetes Management Project, developed to assess factors associated with suboptimal diabetes care.

Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results.

AIM: To report the 6-month results of a clinical trial that compared intravitreous bevacizumab (BVB) 1.25 mg versus triamcinolone acetonide (TA) 4 mg when administered as an adjunct during cataract surgery to patients with diabetic macular oedema (DMO). METHODS: Prospective, double-masked, single-centre (Royal Victorian Eye and Ear Hospital, Melbourne) clinical trial. Patients with visually significant cataract and centre-involving DMO (either current or prior) were randomised (1: 1) to receive either intravitreous BVB 1.25 mg or TA 4 mg at the time of cataract surgery and if required at review. Main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to the 6-month time point of this 12-month study. RESULTS: 61 eyes of 58 patients were enrolled. At baseline, both groups were similar in terms of BCVA and CMT (p>0.2). At 6 months, there was no significant difference in vision between the groups, with mean letter gain of +21.4 (95% CI +14.5 to +28.4) in the TA group and +17.3 (95% CI +12.1 to +22.6) in the BVB group (p=0.35). The TA group had a significant sustained anatomical improvement at 6 months, with a reduction in CMT (-51.4 µm; 95% CI -98.2 to -4.7) compared with thickening in the BVB group (+15.6 µm; 95% CI -26.4 to +57.7, p=0.04). CONCLUSIONS: When given as an adjunct to cataract surgery, both TA and BVB improved visual outcomes at 6 months postoperatively. However, only TA resulted in sustained improvement in CMT, with the majority not requiring any further treatment postoperatively.

Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration.

PURPOSE: Bevacizumab is an inhibitor of vascular endothelial growth factor widely used as an "off-label" treatment of neovascular age-related macular degeneration (AMD), despite the lack of clinical trial data on efficacy or safety of this drug. We describe acute intraocular inflammation after intravitreous injection of bevacizumab for the treatment of neovascular AMD. DESIGN: A retrospective case series. PARTICIPANTS: Patients with neovascular AMD treated with intravitreous injection of bevacizumab from clinical practices in 2 states (Victoria and South Australia) in Australia. METHODS: We retrospectively reviewed cases of acute intraocular inflammation after intravitreous injection of bevacizumab for the treatment of neovascular AMD. MAIN OUTCOME MEASURES: The detection and description of inflammation in a large cohort of patients. RESULTS: There were 14 cases (11 women and 3 men), from a total of 1278 injections given. The mean age of patients was 83.7 years (range, 74-98). The majority had a prior injection of bevacizumab, with a mean number of injections of 2.7 (range, 1-6). Most patients presented within 24 hours of intravitreous injection, with rapid reduction in vision, but minimal discomfort. There were associated signs of ocular inflammation in the anterior and posterior segments of the eye. Visual acuity at presentation was substantially reduced compared with the preinjection acuity, although the vision rapidly improved with treatment over a period of 7-25 days toward preinjection visual acuity. CONCLUSIONS: Intravitreous injection of bevacizumab for the treatment of neovascular AMD may be associated with acute intraocular inflammation. Differentiation from infectious endophthalmitis is important for appropriate management of this condition.