Background/aims Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. Methods Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. Results 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. Conclusions In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. Trial registration number NCT01447043.

Proliferative diabetic retinopathy is the most common cause of severe sight impairment in people with diabetes. Proliferative diabetic retinopathy has been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We report the 1 year safety and efficacy of intravitreal aflibercept. In this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged ≥18 years) with type 1 or 2 diabetes and previously untreated or post-laser treated active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic centres. Patients were randomly assigned (1:1) to repeated intravitreal aflibercept (2 mg/0·05 mL at baseline, 4 weeks, and 8 weeks, and from week 12 patients were reviewed every 4 weeks and aflibercept injections were given as needed) or PRP standard care (single spot or mutlispot laser at baseline, fractionated fortnightly thereafter, and from week 12 patients were assessed every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by minimisation with a web-based computer generated system. Primary outcome assessors were masked optometrists. The treating ophthalmologists and participants were not masked. The primary outcome was defined as a change in best-corrected visual acuity at 52 weeks with a linear mixed-effect model that estimated adjusted treatment effects at both 12 weeks and 52 weeks, having excluded fluctuations in best corrected visual acuity owing to vitreous haemorrhage. This modified intention-to-treat analysis was reapplied to the per protocol participants. The non-inferiority margin was prespecified as -5 Early Treatment Diabetic Retinopathy Study letters. Safety was assessed in all participants. This trial is registered with ISRCTN registry, number 32207582. We recruited 232 participants (116 per group) between Aug 22, 2014 and Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group) contributed to the modified intention-to-treat model, and 210 participants (104 in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was non-inferior and superior to PRP in both the modified intention-to-treat population (mean best corrected visual acuity difference 3·9 letters [95% CI 2·3-5·6], p<0·0001) and the per-protocol population (4·0 letters [2·4-5·7], p<0·0001). There were no safety concerns. The 95% CI adjusted difference between groups was more than the prespecified acceptable margin of -5 letters at both 12 weeks and 52 weeks. Patients with proliferative diabetic retinopathy who were treated with intravitreal aflibercept had an improved outcome at 1 year compared with those treated with PRP standard care. The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.

The high prevalence of cardiovascular disease particularly in the elderly population is associated with retinal vascular disease. Retinal vein occlusions represent severe disturbances of the hypoxia-sensitive neurosensory retina. Acute and excessive leakage leads to the diagnostic hallmarks of retinal hemorrhage and edema with substantial retinal thickening. Advanced diagnostic tools such as OCT angiography allow to evaluate retinal ischemia and identify the risk for late complications and will soon reach clinical routine besides fluorescein angiography. Accordingly, the duration of non-perfusion is a crucial prognostic factor requiring timely therapeutic intervention. With immediate inhibition of vascular leakage, anti-VEGF substances excel as treatment of choice. Multiple clinical trials with optimal potential for functional benefit or a lesser regenerative spectrum have evaluated aflibercept, ranibizumab, and bevacizumab. As retinal vein occlusion is a chronic disease, long-term monitoring should be individualized to combine maintenance with practicability. While steroids may be considered in patients with systemic cardiovascular risk, surgery remains advisable only for very few patients. Destructive laser treatment is an option if reliable monitoring is not feasible. Ophthalmologists are also advised to perform a basic systemic workup to recognize systemic concomitants. The current edition of the EURETINA guidelines highlights the state-of-the-art recommendations based on the literature and expert opinions in retinal vein occlusion.