Posterior hyaloid changes following intravitreal triamcinolone and macular laser for diffuse diabetic macular edema.

PURPOSE: To compare the effects of intravitreal triamcinolone and macular grid laser photocoagulation on the vitreomacular relationship in diffuse diabetic macular edema. METHODS: Review of optical coherence tomography images gathered in a prospective, interventional randomized clinical trial. SETTING: Institutional Practice. PROCEDURES: Seventy-seven optical coherence tomography images of 88 consecutive patients entered into a randomized clinical trial of the treatment of persistent diffuse diabetic macular edema were reviewed by two independent observers. All patients in the trial had diabetic macular edema following at least two macular grid laser treatments and were randomized to intravitreal injections of 4 mg triamcinolone or to further macular grid laser. Optical coherence tomography images were recorded at baseline, 4, 8, and 12 months and the patterns of vitreomacular relationship were classified into six categories. MAIN OUTCOME MEASURES: The patterns of vitreomacular relationship in the two groups were compared and correlated with the response to treatment. Outcome measures were defined as changes in best-corrected visual acuity Early Treatment Diabetic Retinopathy Study letters and central macular thickness on optical coherence tomography. RESULTS: Six eyes had peri-foveal vitreous detachment with or without traction in each group at baseline. At 12 months, the prevalence of peri-foveal vitreous detachment was significantly higher after intravitreal triamcinolone (n = 11) than macular grid laser (n = 8). These patients had poorer visual outcome (P = 0.01) and increased central macular thickness (P = 0.002). The development of complete posterior vitreous detachment was associated with significantly decreased central macular thickness (P = 0.001) but not better visual outcome (P = 0.72). CONCLUSION: These results suggest that posterior hyaloid changes may play a more influential role in the response to intravitreal triamcinolone than laser treatment for diffuse diabetic macular edema.

Angiopoietin modulation of vascular endothelial growth factor: Effects on retinal endothelial cell permeability.

PURPOSE: Vascular permeability is important at many sites, but particularly so in diabetic retinopathy where macular oedema is the major cause of blindness. Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are important factors involved in neovascularization and vascular leakage, but there is little data on their interaction to promote increased vascular permeability. METHODS: Porcine retinal endothelial cells (PREC) were seeded into permeable inserts and cultured in 24-well plates that permit measurement of permeability using fluorescent dextrans. Cell purity was assessed immunohistochemically. At confluency, PREC were treated with increasing concentrations of VEGF (20-100ng/ml) and Ang-2 (15-75ng/ml). The effect on tight junctions was assessed by visualization with an anti-ZO-1 antibody. RESULTS: Immunohistochemistry showed high purity of isolated PREC. Permeability of untreated PREC monolayers was low. The increase in permeability in Ang-2 treated cells (25-30% compared with non-treated cells) was less than that for cells treated with VEGF only (20-100% compared with untreated cells). Highest permeability was seen with a combination of Ang-2 and VEGF (100-400% compared with untreated cells). Permeability increased with time after growth factor application. Preliminary ZO-1 immunohistochemistry appeared to demonstrate the presence of tight junctions between untreated PREC, and loss of tight junctions after treatment with VEGF and Ang-2. CONCLUSIONS: VEGF alone is twice as potent in interrupting tight junctions in an endothelial cell monolayer as Ang-2. However, both growth factors acting together increase permeability three times as much as VEGF alone. Treatments designed to reduce vascular permeability in diabetic macular oedema should consider that crosstalk between growth factors including VEGF and the Ang-2/Tie-2 system can multiply their effects.

Differential apicobasal VEGF signaling at vascular blood-neural barriers.

The vascular endothelium operates in a highly polarized environment, but to date there has been little exploration of apicobasal polarization of its signaling. We show that VEGF-A, histamine, IGFBP3, and LPA trigger unequal endothelial responses when acting from the circulation or the parenchymal side at blood-neural barriers. For VEGF-A, highly polarized receptor distribution contributed to distinct signaling patterns: VEGFR2, which was found to be predominantly abluminal, mediated increased permeability via p38; in contrast, luminal VEGFR1 led to Akt activation and facilitated cytoprotection. Importantly, such differential apicobasal signaling and VEGFR distribution were found in the microvasculature of brain and retina but not lung, indicating that endothelial cells at blood-neural barriers possess specialized signaling compartments that assign different functions depending on whether an agonist is tissue or blood borne.

Botulinum toxin as a postoperative diplopia test - it can also reduce the angle of deviation prior to surgery.

PURPOSE: To investigate how frequently botulinum toxin, when used as a postoperative diplopia test, reduces the angle of deviation prior to subsequent strabismus surgery. METHODS: A retrospective study of 39 adult patients with constant concomitant horizontal strabismus who had undergone botulinum toxin injections to assess the risk of postoperative diplopia and then subsequently underwent strabismus surgery. RESULTS: Fourteen out of 39 patients (36%) sustained a reduction of 15 prism diopters or more for near and/or distance when comparing the pre-injection angle of deviation with the preoperative angle of deviation. CONCLUSION: Approximately one-third of patients receiving botulinum toxin as a postoperative diplopia test maintained a significant reduction in the angle of their deviation prior to undergoing surgery.