Structural and Functional Measures of Efficacy in Response to Bevacizumab Monotherapy in Diabetic Macular Oedema: Exploratory Analyses of the BOLT Study (Report 4)

Background To describe structural and functional changes associated with diabetic macular oedema (DMO) treated with intravitreal bevacizumab over 24 months. Methods A post-hoc analysis of the data of 34 patients that completed 24 months follow-up in the intravitreal bevacizumab arm of a prospective, randomized controlled trial (BOLT study) was performed. The outcome measures previously used in clinical trials of intravitreal ranibizumab in DMO were employed to describe the visual acuity and macular thickness changes at 12 and 24 months. Results The standard outcomes of mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) in participants treated with bevacizumab were comparable to those reported in association with ranibizumab. However, exploratory analyses showed that thick maculae at baseline defined as CMT of ≥400 µm, remained significantly thicker than those <400 µm with intensive bevacizumab therapy, despite a comparable gain in visual acuity at both 12 and 24 months. The proportion of subjects that attained a dry macula doubled in both CMT groups between the 12 and 24-month time-points. Conclusions These findings provide valuable information both for clinical practice and trials. Further studies are required to investigate the impact of intravitreal bevacizumab on retinal thickness profiles in DMO

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

CONTEXT: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear. AIMS: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting. SETTINGS AND DESIGN: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact. MATERIALS AND METHODS: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients’ demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined. RESULTS: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected. CONCLUSION: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment

The role of the angiopoietin/tie-2 system in retinal neovascularisation

Purpose: To investigate the interaction between the Tie-2 receptor and Angiopoietins -1 (Ang-1) and -2 (Ang-2) in bovine retinal microvascular endothelial cells (BRMEC) and microvascular pericytes. Methods: The expression of the Tie-2 receptor in cultured BRMEC and pericytes was analysed by immunoprecipitation with corresponding antibodies and Western blotting. Cultivated BRMEC were exposed to varying concentrations of Ang-1 and -2 (5 ng/ml - 400 ng/ml) for up to 48 h. The relative cell number was determined by monitoring the uptake of crystal violet by fixed cultures. Migration of BRMEC was measured using an in vitro wound healing model. Results: Western blotting analyses of whole cell lysates revealed that the Tie-2 receptor was expressed by both BRMEC and pericytes (a band at 140 kDa was detected). However, expression levels of Tie-2 were greatest for BRMEC. Ang-1 and Ang-2 exhibited no proliferative effect on endothelial cells. Ang-2 was only weakly mitogenic for pericytes (20% increase in cell number), meantime Ang-1 had no effect. Ang-1 led to a significant, dose-dependent increase in directed migration of BRMEC, up to 50% higher than unstimulated cells. Ang-2 over a wide dose range did not exert any chemotactic properties. Conclusion: The findings indicate that the Angiopoietin system may play a role in retinal neovascularisation via the Tie-2 receptor, which may be partially due to an increase in endothelial cells motility, a key step of angiogenesis. Furthermore, expression of the Tie-2 receptor on pericytes may allow their participation in the maintenance of capillary integrity, which is significantly disturbed, in diabetic retinopathy

Photodynamic therapy of subfoveal neovascular membrane in type 2A idiopathic juxtafoveolar retinal telangiectasis.

PURPOSE: To evaluate the effect of photodynamic therapy on subfoveal neovascular membrane related to type 2A idiopathic juxtafoveolar retinal telangiectasia. DESIGN: Interventional case series. METHODS: Retrospective review of four eyes of four patients who underwent photodynamic therapy for subfoveal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasia. Ocular photodynamic therapy with verteporfin was performed in all cases using standard protocols. Results are given in terms of final visual acuity and neovascular membrane activity based on clinical examination, fluorescein and indocyanin green angiography, and, in two cases, optical coherence tomography. RESULTS: Baseline visual acuity of 20/30 and 20/40 (x2) was maintained in three patients after one, two, and three sessions of photodynamic therapy respectively, and a follow-up of 23, 21, and 9 months. Leakage specific to the subfoveal neovascular membrane ceased on the fluorescein angiography. In the other patient, the final vision decreased from 20/50 to 20/200 after four sessions of photodynamic therapy and a follow-up of 14 months. Although there was still mild persistent leakage on the fluorescein angiography, neovascular membrane size was unchanged, and no subretinal fluid was demonstrated on optical coherence tomography. CONCLUSIONS: Data from this case series suggest that photodynamic therapy may be effective in managing subfoveal neovascular membrane associated with idiopathic juxtafoveolar retinal telangiectasia, which usually carries a poor visual prognosis. Prospective study is required to confirm the beneficial effect of this treatment

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). MAIN OUTCOME MEASURES: 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