Intravitreal ranibizumab for the management of serous maculopathy secondary to optic disc coloboma-associated choroidal neovascularisation.

We report the case of a 19-year-old patient with symptomatic unilateral serous maculopathy associated with an optic nerve coloboma. Fluorescein angiography detected a focal late leak at the temporal edge of the coloboma which was later found to correspond with an area of choroidal neovascularisation on optical coherence tomography angiography. A course of intravitreal ranibizumab achieved good clinical and structural response. This report contributes to the evidence that maculopathies associated with cavitary optic nerve anomalies may in some instances result from choroidal neovascularisation. It also highlights the importance of angiography to identify potential choroidal neovascular membranes, particularly in the absence of haemorrhages and neovascular membranes on fundus examination and conventional optical coherence tomography.

Post-injection endophthalmitis rates with reduced povidone-iodine prophylaxis in patients with self-reported iodine sensitivity.

BACKGROUND: Our objectives were (1) to report the post-injection endophthalmitis rate over 18 months, and (2) to determine any difference in the incidence of endophthalmitis in patients treated with reduced or no 5% povidone-iodine (PI) due to self-reported PI sensitivity. METHODS: We performed a retrospective cohort study of all patients who received intravitreal injections (IVIs) from January 1st, 2018 to June 26th, 2019. Information on patients' age, gender visual acuities, the number of injections, drug administered, self-reported iodine sensitivity and injection protocols were obtained from electronic and paper records. For endophthalmitis cases, vitreous culture results and treatment were also noted. Patients were divided into three cohorts based on the injection protocol used for statistical analysis. RESULTS: During the study period 22,046 IVIs were administered to 3332 eyes of 2709 patients. Intolerance to PI was reported by 2.4% of patients. The incidence of endophthalmitis was 0.02% (4/21,185) with the standard 5% PI protocol, 0.78% (6/769) with a reduced PI protocol involving fewer drops of 5% PI and chlorohexidine 0.05% for periorbital skin cleansing, and 1.09% (1/92) without any PI use. Receiving the standard PI protocol was associated with significantly lower rates of endophthalmitis compared to both the reduced PI and no PI protocols (p < 0.0001). CONCLUSIONS: Patients who opt for less or no PI use are likely at significantly increased risk of developing post-IVI endophthalmitis. It is imperative to educate, counsel and consent these patients accordingly while exploring alternative antiseptic solutions.

Short-term safety of dexamethasone implant for treatment of macular edema due to retinal vein occlusion, in eyes with glaucoma or treated ocular hypertension.

PURPOSE: To report the short-term safety of dexamethasone implants to treat macular edema due to retinal vein occlusion (RVO), in eyes with treated glaucoma or ocular hypertension at baseline using an as-needed re-treatment regimen. METHODS: Retrospective clinical database study from two centers using the same electronic medical record system. Extracted data included: intraocular pressure (IOP), visual acuity (VA), central 1 mm retinal thickness (CRT) by optical coherence tomography, phakic status, number of injections, glaucoma treatment, and peri-operative complications. RESULTS: Thirty-three eyes of 33 patients on IOP-lowering treatment for glaucoma or ocular hypertension (OHT) at baseline and mean IOP of 16 mmHg at baseline received one to four (mean, 1.8; median, 1) dexamethasone implants over 18 months for RVO-related macular edema. Fourteen eyes (42 %) had IOP of ≥21 mmHg, and three eyes (9 %) had IOP of ≥35 mmHg at one or more visits during the study period. Nine of 14 eyes (64 %) with raised IOP required additional topical treatment only for a mean (SE) period of 8.5 months (3.2), while the remaining five eyes (36 %) required long-term additional IOP-lowering treatment for a mean (SE) of 16 months (1.44). Surgery for IOP lowering was not required in any eye. Mean VA (SE) improved from 44 (3) ETDRS letters at baseline to 47 letters (5) at 2 months (p = 0.049), 48 (8) letters at 6 months and 46 (4) letters at 12 months. Mean CRT (SE) improved from 530 (25) µm at baseline to 323 (27) µm at 2 months (p < 0.001), 498 (76) µm at 6 months, and 359 (25) µm at 12 months (p < 0.001). CONCLUSION: The short-term IOP rise after intravitreal dexamethasone implant in eyes with glaucoma or ocular hypertension at baseline was acceptable and consistent with previous reports in patients without preexisting glaucoma. Treated OHT or glaucoma may not be a strict contraindication against the use of dexamethasone implant, but close monitoring of IOP is required.

Diabetic retinopathy: intravitreal vascular endothelial growth factor inhibitors for diabetic macular oedema.

INTRODUCTION: Diabetic retinopathy is the most common microvascular complication of diabetes. It is also the most common cause of blindness in working-age adults in industrialised nations. Older people and those with worse diabetes control, hypertension, and hyperlipidaemia are most at risk. Diabetic macular oedema, which can occur at any stage of diabetic retinopathy, is related to increased vascular permeability and breakdown of the blood retinal barrier, in part related to increased vascular endothelial growth factor (VEGF) levels. About 1% to 3% of people with diabetes suffer vision loss because of diabetic macular oedema. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of intravitreal VEGF inhibitors versus each other for diabetic macular oedema? What are the effects of intravitreal VEGF inhibitors plus laser therapy versus intravitreal VEGF inhibitors alone for diabetic macular oedema? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 240 studies. After deduplication and removal of conference abstracts, 149 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 90 studies and the further review of 59 full publications. Of the 59 full articles evaluated, eight systematic reviews and four RCTs were added at this update. We performed a GRADE evaluation for four PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for six comparisons based on information about the effectiveness and safety of intravitreal VEGF inhibitors aflibercept, bevacizumab, and ranibizumab, and each of these intravitreal VEGF inhibitors plus laser therapy.

Incidence and baseline clinical characteristics of treated neovascular age-related macular degeneration in a well-defined region of the UK.

AIMS: To analyse the incidence and baseline clinical characteristics of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in a defined UK region. METHODS: A standardised dataset was collected prospectively using an electronic medical record (EMR) system from 1 January 2008 to 21 June 2012 for all patients living in Gloucestershire who received intravitreal anti-VEGF injections for nAMD. RESULTS: Over the study period, 1207 eyes from 1033 patients began intravitreal anti-VEGF injections for nAMD. The annual incidence in the years after National Institute for Health and Care Excellence (NICE) technology appraisal 155 implementation was stable at 120 (95% CI 110 to 138) eyes or 100 (89 to 115) people per 100 000 population. The most common indication was occult choroidal neovascularisation (51%). Median baseline visual acuity (VA) was significantly higher for second treated than first treated eyes (66 and 56 letters, respectively; p<0.0001). Median baseline VA of fellow eyes increased from 47 (2008) to 67 letters (2012; p<0.005). The proportion of patients with baseline VA in the better eye ≥70 letters increased from 27.6% (2008) to 51.4% (2012; p<0.0001), while the proportion eligible at baseline for full or partial certificate of visual impairment decreased from 13.8% (2008) to 7.1% (2012; p<0.05). CONCLUSIONS: The incidence of patients undergoing anti-VEGF therapy for nAMD increased substantially following NICE approval of ranibizumab (August 2008), and has been stable since 2009. This equates to an annual UK incidence of 26 850 (21 320 to 32 440) eyes, similar to NICE estimates. Patients eligible for blindness certification before treatment decreased by half from 2008-2012. Prospective data collection using an EMR system is invaluable for efficient monitoring of real-world clinical care.

Diabetic retinopathy (treatment).

INTRODUCTION: Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with diabetic retinopathy? What are the effects of treatments for vitreous haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: peripheral retinal laser photocoagulation, focal and grid laser photocoagulation for maculopathy, corticosteroids for macular oedema, vascular endothelial growth factor inhibitors, and vitrectomy for vitreous haemorrhage.

Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study.

OBJECTIVES: To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration. DESIGN: Prospective, double masked, multicentre, randomised controlled trial. SETTING: Three ophthalmology centres in the United Kingdom. PARTICIPANTS: 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control. INTERVENTIONS: Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration). PRIMARY OUTCOME: proportion of patients gaining >or=15 letters of visual acuity at one year (54 weeks). SECONDARY OUTCOMES: proportion of patients with stable vision and mean change in visual acuity. RESULTS: Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P<0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) v 67% (44) in standard care group; P<0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P<0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care. CONCLUSIONS: Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks. Trial registration number Current controlled trials ISRCTN83325075.

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration using a variable frequency regimen in eyes with no previous treatment.

PURPOSE: To evaluate a variable frequency regimen with intravitreal bevacizumab for treatment of neovascular age-related macular degeneration (AMD) in eyes that have not received any previous treatment. METHODS: Retrospective review of patients with neovascular AMD who were treated with three consecutive monthly intravitreal injections of bevacizumab (1.25 mg) and retreated based on the PrONTO study criteria. Outcome measures included visual acuity (VA) and central retinal thickness. Subgroup analysis was conducted to identify pretreatment characteristics that could determine visual outcome with treatment. RESULTS: A total of 109 eyes of 109 patients were treated. The mean age was 82 years, and the mean follow-up period was 9.4 months (range 6-12 months). At baseline, the mean VA was 45.6 letters (6/37.5) and mean central retinal thickness 343 microm. This improved to 51 letters (6/30) (P < 0.001)) and 231 microm (P < 0.001) at 6 months. At 6 months, VA was improved by at least five letters in 50%, remained stable in 30% and worsened by at least five letters in 20% of patients. Patients with large intraretinal cysts on optical coherence tomography before treatment had an increased risk of worse vision (odds ratio 10.5, 95% confidence interval 1.69-64.99; P = 0.018). CONCLUSIONS: The majority of patients had improvement or stability of VA regardless of the angiographic type of choroidal neovascularization. Intravitreal bevacizumab with this tailored regimen is beneficial in the treatment of neovascular AMD in the short term. The presence of large intraretinal cysts on optical coherence tomography is a poor prognostic factor for visual improvement with this treatment.

Management of diabetic retinopathy: a systematic review.

CONTEXT: Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain. OBJECTIVE: To review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema. EVIDENCE ACQUISITION: Systematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies. EVIDENCE SYNTHESIS: Forty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR. CONCLUSIONS: Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.

Interventions for branch retinal vein occlusion: an evidence-based systematic review.

TOPIC: To assess the evidence on interventions to improve visual acuity (VA) and to treat macular edema and/or neovascularization secondary to branch retinal vein occlusion (BRVO). CLINICAL RELEVANCE: Branch retinal vein occlusion is the second most common retinal vascular disease. METHODS/LITERATURE REVIEWED: English and non-English articles were retrieved using a keyword search of Medline (1966 onwards), Embase, the Cochrane Collaboration, the National Institute of Health Clinical Trials Database, and the Association for Research in Vision and Ophthalmology Annual Meeting Abstract Database (2003-2005). This was supplemented by hand searching references of review articles. Two investigators independently identified all randomized clinical trials (RCTs) with more than 3 months' follow-up. RESULTS: From 4332 citations retrieved, 12 RCTs were identified. There were 5 RCTs on laser photocoagulation. Grid macular laser photocoagulation was effective in improving VA in 1 large multicenter RCT, the Branch Vein Occlusion Study (BVOS), but 2 smaller RCTs found no significant difference. The BVOS showed that scatter retinal laser photocoagulation was effective in preventing neovascularization and vitreous hemorrhage in patients with neovascularization, but a subsequent RCT found no significant effect. Randomized clinical trials evaluating intravitreal steroids (n = 2), hemodilution (n = 3), ticlopidine (n = 1), and troxerutin (n = 1) showed limited or no benefit. CONCLUSIONS: There is limited level I evidence for any interventions for BRVO. The BVOS showed that macular grid laser photocoagulation is an effective treatment for macular edema and improves vision in eyes with VA of 20/40 to 20/200, and that scatter laser photocoagulation can effectively treat neovascularization. The effectiveness of many new treatments is unsupported by current evidence.