EXIT STRATEGY IN A TREAT-AND-EXTEND REGIMEN FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the outcome of an exit strategy in a treat-and-extend regimen for neovascular age-related macular degeneration. METHODS: Five hundred and ninety-eight eyes of 488 patients with neovascular age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor injections according to a treat-and-extend regimen were included in this retrospective study. A treat-and-extend regimen with either interval extension by 2 weeks or shortening by 1 week was used. "Exit criteria" were defined as 3 consecutive injections 16 weeks apart with stable findings after which the patient was exited from treatment and followed up at 3 to 4 monthly intervals without therapy. Best-corrected visual acuity, central retinal thickness at treatment initiation and termination, incidence of recurrence after treatment termination, presence of characteristics in the optical coherence tomography, duration of therapy, number and intervals of injections were analyzed. RESULTS: Seventeen percent of all included eyes met the exit criteria. The mean number of anti-vascular endothelial growth factor injections was 23.7 ± 14.7 with a mean treatment duration of 4.5 ± 2.5 years. Twelve percent reached exit with the minimal number of injections. Thirteen percent had recurrent disease after a mean of 37 ± 16 weeks. In the subgroup with recurrent disease, rate of pigment epithelial detachment at treatment termination was significantly higher than without recurrence (77% vs. 30%, P = 0.0018) with a significant higher proportion of serous pigment epithelial detachment (31% vs. 7%, P = 0.0247). CONCLUSION: The high percentage of patients meeting the exit criteria and the relatively low incidence of recurrences underline the usefulness of a predefined exit strategy. However, in a subgroup of patients, continuation of therapy may be advisable.

The Impact of the Vitreomacular Interface in Neovascular Age-Related Macular Degeneration in a Treat-and-Extend Regimen with Exit Strategy.

PURPOSE: To evaluate the impact of the vitreomacular interface (VMI) in a treat-and-extend (TREX) regimen with exit strategy in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Five hundred ninety-three eyes of 498 patients with nAMD. METHODS: Eyes were treated according to a TREX regimen with an exit criterion, which was defined as no signs of disease activity during 3 consecutive 16-week injection visits. The impact of the VMI and the presence of an epiretinal membrane (ERM) assessed by spectral-domain OCT were evaluated based on the parameters mentioned below. MAIN OUTCOME MEASURES: Effect of vitreomacular adhesion (VMA) and ERM on mean treatment interval, number of injections, likelihood of fulfilling the exit criterion, choroidal neovascularization recurrences, CRT decrease, and BCVA improvement. RESULTS: During the TREX period, posterior vitreous detachment (PVD) eyes needed significantly fewer injections (mean, 10.6 ± 5.9) than VMA eyes (mean, 12.6 ± 6.7; P = 0.0008), and the mean injection interval was shorter in VMA eyes (8.3 ± 3.1 weeks) than in PVD eyes (9.5 ± 3.5 weeks; P = 0.0008). Eyes with PVD at baseline and without an ERM were 9.2 and 11.4 times more likely to fulfill the exit criterion than eyes with VMA and ERM, respectively (P = 0.006 and P = 0.004, respectively, corrected). Although CRT decrease (P = 0.16) and BCVA improvement (P = 0.32) did not differ with respect to the VMI configuration, ERM had a significant impact on CRT decrease (ERM present, +11 ± 198 µm vs. ERM absent, -92 ± 136 µm; P = 0.041). Vitreomacular adhesion at treatment cessation was associated significantly with disease recurrence (likelihood ratio, 7.8; P = 0.013, corrected), whereas the presence of an ERM was not associated with choroidal neovascularization recurrence (P = 0.18). CONCLUSIONS: The configuration of the VMI and the presence of an ERM have a significant impact on the treatment frequency, the chance to meet the exit criterion in this TREX regimen, and the recurrence risk after treatment cessation. This indicates that eyes with VMA should be monitored carefully for new disease activity after treatment cessation.

Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish.

A fascinating difference between teleost and mammals is the lifelong potential of the teleost retina for retinal neurogenesis and regeneration after severe damage. Investigating the regeneration pathways in zebrafish might bring new insights to develop innovative strategies for the treatment of retinal degenerative diseases in mammals. Herein, we focused on the induction of a focal lesion to the outer retina in adult zebrafish by means of a 532 nm diode laser. A localized injury allows investigating biological processes that take place during retinal degeneration and regeneration directly at the area of damage. Using non-invasive optical coherence tomography (OCT), we were able to define the location of the damaged area and monitor subsequent regeneration in vivo. Indeed, OCT imaging produces high-resolution, cross-sectional images of the zebrafish retina, providing information which was previously only available with histological analyses. In order to confirm the data from real-time OCT, histological sections were performed and regenerative response after the induction of the retinal injury was investigated by immunohistochemistry.

Effect of disease states on α1 -adrenoceptor binding and signal transduction parameters in isolated perfused heart: quantification by pharmacokinetic-pharmacodynamic modelling.

OBJECTIVES: To employ a pharmacokinetic-pharmacodynamic modelling approach for analysing the effect of experimental endotoxemia and mild hypoxia on α1 -adrenoceptor (α1 AR) binding and signal transduction. METHODS: In Langendorff-perfused rat hearts, phenylephrine was continuously infused, and [(3) H]-prazosin was injected as single dose (infused over 1 min). Simultaneous analysis of the time courses of prazosin outflow concentration and inotropic response (left ventricular developed pressure) using an agonist-antagonist interaction model and nonlinear regression allowed to estimate receptor affinity, as well as the parameters of the operational model of agonism. KEY FINDINGS: Both endotoxemia and hypoxia, significantly reduced the maximum response achievable in the system to 67% and 49% of the control group mean, respectively. In addition, endotoxemia decreased the efficiency of stimulus-response coupling and increased the steepness of the stimulus-response curve. In both disease models, no change in receptor affinity and density were found. CONCLUSIONS: The results revealed the causes of reduced α1 AR-mediated inotropic responsiveness in endotoxemia and hypoxia. In contrast with traditional dose-response studies, it was possible to quantify separately the underlying changes in α1 AR binding and signal transduction.