Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the relative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular age-related macular degeneration (AMD). METHODS: Systematic literature review identifying RCTs comparing anti-VEGF agents to another treatment published before June 2016. Efficacy assessed by mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline at up to 2 years followup. Safety assessed by proportions of patients with death, arteriothrombotic and venous thrombotic events, and at least one serious systemic adverse event at up to 2 years of followup. RESULTS: Fifteen RCTs selected for meta-analysis (8320 patients). Two trials compared pegaptanib, and three trials compared ranibizumab versus control. Eight trials compared bevacizumab with ranibizumab. Two trials compared aflibercept with ranibizumab. There were no significant differences between bevacizumab and ranibizumab for BCVA at 1 or 2 years (weighted mean difference = - 0.57, 95% CI - 1.55 to 0.41, P = 0.25 and weighted mean difference = - 0.76, 95% CI - 2.25 to 0.73, P = 0.32, respectively). Ranibizumab was more effective in reducing CMT at 1 year (weighted mean difference = 4.49, 95% CI 1.13 to 7.84, P = 0.009). Risk ratios comparing rates of serious systemic adverse events at 1 and 2 years were slightly out of favour for bevacizumab. Aflibercept compared with ranibizumab demonstrated similar mean change in BCVA, reduction in CMT, and safety at 1 year. CONCLUSIONS: Bevacizumab and ranibizumab had equivalent efficacy for BCVA, while ranibizumab had greater reduction in CMT and less rate of serious systemic adverse events. Aflibercept and ranibizumab had comparable efficacy for BCVA and CMT. This provides information to balance comparable effects on vision and risk of adverse events between anti-VEGF agents.

Subretinal fluid may protect against macular atrophy in neovascular age-related macular degeneration: 5 years of follow-up from Fight Retinal Blindness registry.

PURPOSE: The purpose of the study was to assess the association of macular atrophy (MA) according to the activity of macular neovascularization (MNV) (inactive, only subretinal fluid [SRFL], or active, i.e. including intraretinal fluid [IRFL]) using optical coherence tomography (OCT) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Multicentric observational study. Treatment-naïve nAMD eyes without subfoveal MA or subretinal fibrosis (SF) at baseline were included since 1st January 2010 and 30th September 2016 to allow up to 5 years of treatment follow-up. Eyes were grouped based on their predominant activity status as: (1) mostly inactive, (2) mostly active non-SRFL only [IRFL] or (3) mostly active-SRFL only [onlySRFL]. Kaplan-Meier survival curves estimated the time to development of MA or SF. Cox proportional hazards models evaluated predictors of developing subfoveal MA or SF. The main outcome measure was the risk of developing MA according to predominant MNV activity. RESULTS: A total of 973 eyes were eligible for analysis. OnlySRFL eyes had lower risk of developing subfoveal MA (HR [95% CI]: 0.56 [0.36, 0.88]; p = 0.024) and extrafoveal MA (HR [95% CI]: 0.41 [0.27, 0.61]; p < 0.001) than IRFL eyes. IRFL eyes had lower visual acuity (VA) (54.5 letters) and the highest proportion of eyes with vision ≤35 letters (25%) at 5 years while onlySRFL eyes had comparable 5-year VA (63.7 letters) to inactive eyes (63.7 letters). CONCLUSION: Subretinal fluid appears to protect against MA. Distinguishing the compartment of retinal fluid and understanding its relationship with MA and SF can guide the management of nAMD.

POPPER MACULOPATHY: LONG-TERM FOLLOW-UP AND CASE SERIES.

PURPOSE: To report a case series of popper maculopathy. METHODS: Clinical history, examination findings, retinal imaging, and progress of the disease are described. RESULTS: Four male patients with a mean age of 37 years (range 25-48) and different duration of popper use (ranging from first time user to chronic user) presented with central scotomata, phosphenes, or photophobia. Optical coherence tomography in all cases demonstrated subfoveal disruption of the ellipsoid zone. Three cases also showed hyperreflectivity of the ellipsoid zone, and one case had a foveal detachment. Chronic user of poppers was associated with more severe macular changes. One patient had a 3-year follow-up and demonstrated complete resolution of signs on retinal imaging after ceasing popper use. CONCLUSION: Popper maculopathy may show complete resolution of signs on long-term follow-up, even after chronic popper ingestion.

Susac's syndrome: an update.

Susac's syndrome (SS) is a relatively rare cause of multiple recurrent branch retinal arterial occlusions (BRAO). SS is frequently misdiagnosed and probably underdiagnosed. Ophthalmic manifestations may be the sole presenting sign of SS. Comprehensive literature review The typical triad of encephalopathy, sensorineural hearing loss and multiple recurrent BRAO is seldom seen at presentation in SS. The characteristic ophthalmological feature in SS is the presence of recurrent multiple BRAO in the absence of intraocular inflammation. Yellow to yellow-white, non-refractile or refractile retinal arterial wall plaques (Gass plaques) found at midarteriolar segments not associated to bifurcations are commonly found in SS. Because of its ability to capture more peripheral retinal area, ultrawide field fluorescein angiography (FA) has definite advantages over conventional FA and its use should be encouraged in patients suspected of having SS. Optical coherence tomography (OCT), particularly spectral domain OCT complements FA. Patients with BRAO and hearing loss that do not develop encephalopathy during the initial 2 years will most likely not develop encephalopathy. However, these patients will be prone to recurrent BRAO and hearing loss. Imunosuppression is the cornerstone of treatment but the best regimen still needs to be defined. A minority of patients with SS present with the typical triad. A high index of suspicion is needed to make the diagnosis promptly. Early diagnosis and treatment are important to delay disease progression and prevent blindness, deafness and dementia.

Aflibercept for diabetic macular oedema: a Meta-analysis of randomized controlled trials.

AIM: To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema (DMO). METHODS: A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials (RCTs) comparing intravitreal anti-vascular endothelial growth factor (anti-VEGF) versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS: Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients (331 in the aflibercept, and 330 in the photocoagulation group). Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION: Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.

Topical non-steroidal anti-inflammatory drugs in allergic conjunctivitis: meta-analysis of randomized trial data.

PURPOSE: To assess the effect of topical Non-Steroidal Anti Inflammatory drugs in the treatment of allergic conjunctivitis. METHOD: Systematic Review. DATA SOURCES AND STUDY SELECTION: Reports of comparative randomized trials of topical NSAIDs and placebo identified by searches of Medline, Embase, the Cochrane Register of Controlled Trials. DATA EXTRACTION AND SYNTHESIS: Two reviewers assessed trials for eligibility and quality and extracted data independently. Data were synthesized (random effects model) and results expressed results for dichotomous outcomes as relative risk and continuous outcomes as weighted mean difference. Sensitivity analysis was used to examine potential heterogeneity by differences in study quality. RESULTS: Eight studies incorporating 712 patients were included. The difference between the decrease in allergic sign and symptom score for NSAID treatment compared to placebo was between 4 and 19 percentage points. Topical NSAIDs produced significantly greater relief for conjunctival itching (cardinal symptom) than did placebo (combined standardized mean difference -0.54 (p < 0.001; 95% confidence interval -0.84 to -0.24). The results for the other allergic symptoms: ocular burning/pain, eyelid swelling, photophobia and foreign sensation were not significant. Topical NSAIDs produced significantly greater reduction of conjunctival injection than did placebo (combined standardized mean difference -0.51 (p = 0.03; 95% confidence interval -0.97 to -0.05). Topical NSAIDs did not reduce the allergic signs of conjunctival chemosis, conjunctival mucus, eyelid swelling and corneal disturbance. Topical NSAIDs had a significantly higher rate of burning/stinging on application of medication compared to placebo (P < 0.0001; odds ratio 3.97 (95% CI 2.67 to 5.89). CONCLUSION: This meta-analysis confirms that topical NSAID are significantly more effective at relieving the cardinal symptom: conjunctival itching and improving the cardinal sign: conjunctival injection than placebo treatment. A systematic review comparing topical NSAIDs to topical antihistamines/mast cell stabilizers in treatment of allergic conjunctivitis is warranted as this will compare the topical NSAIDs to current therapeutic guidelines.

Management of periocular basal and squamous cell carcinoma: a series of 485 cases.

PURPOSE: To analyze the outcome of management of patients with basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) in a tertiary referral eye center in Sydney, Australia. DESIGN: Retrospective case series. METHODS: Review of medical records of 485 consecutive cases (469 patients) with confirmed eyelid cancer. Intervention procedures: Surgical excision with 3- to 5-mm clinically clear margins and histologic confirmation of the surgical margins. Frozen section histology or Mohs' micrographic surgery (MMS) was used for incompletely excised cases, and those located in the medial canthus or close to the lacrimal drainage system. Standard reconstruction techniques were employed. MAIN OUTCOME MEASURES: Survival period free of tumor, incomplete excision, recurrences, type of closure, and complications. RESULTS: Excision was initially incomplete in 25.4% of all tumors. Morpheaform type of BCC (chi(2)P < .001), and medial canthus location BCCs (chi(2)P < .05) were associated with a higher incomplete resection rate. A 35.9% incomplete excision rate was associated with a significantly higher recurrence rate compared with complete excision (8.4% and 4.6%, respectively, chi(2)P < .05). Twenty-seven patients (5.6%) had a recurrent tumor. After incomplete excision, there was no recurrence with MMS, but 4.7% recurrence rate when frozen section technique was used (P < .05). Local postoperative complications occurred in 41 patients (8.5%). CONCLUSIONS: In the setting of a tertiary referral center, incomplete primary resection of an eyelid skin cancer is the main risk factor for recurrence. Incomplete resection is significantly associated with medial canthus location and morpheaform type of BCC and with moderately differentiated SCC. MMS is the safer technique after incomplete tumor excision.

Localised herpes zoster infection and SIADH.

Localised herpes zoster infection ('shingles') in older patients is a common presentation to primary, and sometimes secondary, care physicians. However, symptoms of hyponatraemia, caused by the rare complication of 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH), may be mistaken for constitutional symptoms of the infection itself. Such patients may require closer monitoring or hospitalisation.

Optic nerve and retinal features in uveitis associated with juvenile systemic granulomatous disease (Blau syndrome).

PURPOSE: To determine whether patients with juvenile systemic granulomatous disease (JSGD) (Blau syndrome) and uveitis have a characteristic ocular phenotype. METHODS: Clinical and imaging data were collected retrospectively from patients attending the Regional Combined Paediatric Rheumatology and Ocular Inflammatory Service, Bristol Eye Hospital. General demographic information, laterality of the uveitis, age at onset, anatomical classification and course of the uveitis, clinical phenotype and specific NOD2 mutation were recorded for each patient. RESULTS: Seventeen eyes from nine patients (five males; four females) were included in the study. Mean age at the disease onset was 15 months, range 1-84 months. Eight patients had bilateral uveitis. Anterior uveitis was present in five eyes, intermediate uveitis in two eyes, and there were 10 eyes with panuveitis, manifesting as multifocal choroiditis. Appearance of optic disc included indistinct disc margins in six eyes, optic nerve head pallor in six eyes, optic disc vessel sheathing in four eyes, and there was peripapillary hypo/hyperpigmentation in 13 eyes accompanied with characteristic peripapillary nodular excrescences. Among NOD2 mutations, the p.R334W was the most commonly detected (n: four cases), and three patients carried novel variants, the p.E338D and p.D390V variants in one patient, and the p.H520Y and p.Q809K variants in two different patients. CONCLUSIONS: Chronic bilateral panuveitis and a nodular peripapillary appearance in childhood onset uveitis are characteristic features of JSGD, which support the need for an appropriate genetic NOD2 analysis.

Plasma exchange and rituximab in the management of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus.

PURPOSE: To report a case of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus (SLE) successfully treated with plasma exchange and rituximab METHODS: Case report. RESULTS: A 25-year-old female presenting acutely with lupus retinal vasculitis was treated urgently with plasma exchange after failure to respond to intravenous methylprednisolone. Following this, fluorescein angiography demonstrated reperfusion of occluded arterioles. Visual acuity improved from 6/60 to 6/6 bilaterally. Remission was maintained following rituximab (Rituxan) in combination with mycophenolatemofetil and oral prednisolone. CONCLUSIONS: Early treatment with plasma exchange achieved reperfusion of the occluded microvascular circulation with correspondingly good visual recovery and should be considered when patients present with corticosteroid refractory retinal vasculitis associated with SLE.

Bevacizumab (Avastin) for the treatment of neovascular glaucoma.

Herein three cases of angle closure secondary to neovascularization (elevated intraocular pressure in two of the cases) treated with the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) are reported. In all three cases there was rapid resolution of neovascularization and control of intraocular pressure. One patient with corneal anaesthesia from diabetes developed infectious keratitis, potentially as a consequence of inhibition of VEGF wound healing and neurotrophic functions. Avastin appears to have a promising role in the treatment of neovascular glaucoma but is not without potential local and systemic side-effects.

Unilateral amiodarone keratopathy.

Vortex keratopathy is characterized by bilateral symmetrical superficial corneal deposits in a vortex pattern. It is the most common ocular finding among patients being treated with amiodarone. An unusual case of unilateral amiodarone vortex keratopathy in an elderly woman with corneal dysplasia in the second eye is presented. The pathophysiology of amiodarone keratopathy is explored, and a cause for the unilateral keratopathy in this patient proposed.

Evidence-based guidelines for fixing broken hips: an update.

OBJECTIVE: To update evidence-based guidelines for the treatment of proximal femoral fractures published in the Journal in 1999. DATA SOURCES: Systematic literature search of MEDLINE, CINAHL and EMBASE from January 1996 to September 2001 and the Cochrane Database of Systematic Reviews (most recent issue searched - Issue 2, 2002). STUDY SELECTION: Randomised controlled trials and meta-analyses of all aspects of acute-care hospital treatment and rehabilitation of proximal femoral fractures among subjects aged 50 years and over with proximal femoral fractures not associated with metastatic disease or multiple trauma. DATA EXTRACTION: All studies were read independently by two reviewers. Reviewers recorded individual study results, and an assessment of study quality and treatment conclusions according to Cochrane Collaboration protocols. If necessary, a third review was performed to reach consensus. RESULTS: 93 new studies were identified and 82 met our inclusion criteria. Recommendations for thromboprophylaxis, anaesthesia, surgical fixation of fractures and nutritional status have been altered to incorporate new evidence. Recommendations have been added regarding postoperative blood transfusion, the management of subtrochanteric fractures, and the type of surgical swabs which should be used. CONCLUSIONS: Although there have been few significant changes to the previous recommendations, updating the guidelines has required substantial effort. The common clinical problem of hip fracture should be treated according to the most up-to-date evidence to achieve the best possible outcomes and optimal utilisation of limited resources. Guideline updates also require resourcing.