An 8-year follow-up of anti-vascular endothelial growth factor treatment with a treat-and-extend modality for neovascular age-related macular degeneration.

PURPOSE: To investigate long-term visual results of treatment with anti-vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD) following a treat-and-extend regimen. METHODS: Retrospective review of 155 patients who initiated treatment with bevacizumab for nAMD in one eye. At the final 8-year visit, 40 patients (26%) remained for follow-up. Mean change in best-corrected visual acuity (BCVA) was calculated compared to baseline values. RESULTS: Mean BCVA improved significantly from baseline during the first year of treatment, with -0.11 logMAR units equivalent to 6.1 approximate Early Treatment Diabetic Retinopathy Study (approxETDRS) letters (p = <0.001). Mean BCVA was still significantly improved after 4 years of treatment for the entire group of patients and after 6 years of treatment for the subgroup of 40 patients who remained at the final 8-year visit. Thereafter, BCVA gradually declined and at 8 years, there was a mean change of 0.05 logMAR units equivalent to 2.1 approxETDRS letters below baseline (p = 0.530). Mean number of injections during the first year was 6.1 ± 2.8 and during year 8 was 5.4 ± 3.5. At 5 years, fundus autofluorescence showed some degree of macular atrophy in all eyes. At the final 8-year visit, 87.5% of the eyes had stable neovascular lesions with no fluid on optical coherence tomography (OCT). CONCLUSION: In an everyday clinical setting, treatment of nAMD patients with a treat-and-extend modality provided improvement and stability of vision for several years. After 8 years of follow-up, there was a decline in visual acuity (VA) that could be explained by macular atrophic development.

Recovery of plasma vascular endothelial growth factor concentrations during aflibercept loading phase and after the transition to bimonthly treatment for neovascular age-related macular degeneration.

AIMS: To provide data on plasma vascular endothelial growth factor (VEGF) concentration during three consecutive monthly intravitreal aflibercept injections and after transition to bimonthly treatment in patients with neovascular age-related macular degeneration (nAMD). METHODS: Sixteen consecutive treatment-naïve Caucasian patients with nAMD were included in the study. The treatment consisted of one intravitreal aflibercept (2 mg) injection every 28 days for three consecutive months followed by a fourth injection 8 weeks later. VEGF plasma concentrations were measured with Luminex on day 0 (baseline, prior to first injection); days 1, 6 and 27 (prior to second injection); day 55 (prior to third injection) and days 97 and 111 (after third injection). RESULTS: Baseline plasma VEGF concentration was 59.6±13.3 pg/mL. Aflibercept decreased plasma VEGF concentration to 32.5±3 pg/mL on day 1 (p<0.0001) and 34.7±6.3 pg/mL on day 6 (p<0.0001). On day 27, the VEGF plasma level increased to 50.6±6.5 pg/mL (p=0.009) and on day 55 to 52.8±8.8 pg/mL (p=0.027). There was no statistically significant difference between mean plasma VEGF concentrations on days 27 and 55 (p=0.139). Plasma VEGF concentration recovered completely 6 weeks after the third injection, reaching 57.9±9.6 pg/mL on day 97 (p=0.600) and 59.5±11.6 pg/mL on day 111 (p=0.987). CONCLUSIONS: Intravitreal aflibercept decreases plasma VEGF concentration mostly in the first week after treatment. Despite repeated monthly intravitreal injections, there was a monthly increase in plasma VEGF values to near baseline levels, with complete recovery 6 weeks after the third injection. TRIAL REGISTRATION NUMBER: Identifier no. NCT02125864.

Renal hemodynamics during development of hypertension in young spontaneously hypertensive rats.

BACKGROUND/AIMS: Cross-transplantation studies between animals with genetic hypertension and normotensive animals indicate a key role of the kidney in development of hypertension, and studies in young spontaneously hypertensive rats (SHR) have shown reduced glomerular filtration rate (GFR) and renal blood flow (RBF) for a short period at the age of 4-6 weeks during blood pressure increase. We tested the hypothesis that a decline in GFR during development of hypertension in SHR might be more pronounced in juxtamedullary cortex than other cortical zones. METHODS: By use of the aprotinin method, total and zonal cortical GFR was measured in anaesthetized Wistar-Kyoto (WKY) rats and SHR at the ages of 2, 4, 6, 8 and 10 weeks. RBF was measured by a transit time flowmeter. RESULTS: Body and kidney weights in SHR and WKY were not significantly different in any age group (p >0.05). Mean arterial blood pressure (MAP) was not different at the age of 2 weeks (79 +/- 6 mm Hg in SHR and 74 +/- 5 mm Hg in WKY, p > 0.05), but was significantly higher in 4-week-old SHR (104 +/- 1 mm Hg) compared to 4-week-old WKY (77 +/- 3 mm Hg) (p < 0.01). The difference in blood pressure increased with age from 4 to 10 weeks. RBF, total GFR, and outer, middle, and inner cortical GFR increased with age but were not different in SHR and WKY in any age group (p >0.05). Renal vascular resistance was increased from 4 weeks of age in SHR (21.5 +/- 1.8), significantly higher than WKY (14.4 +/- 0.9 mm Hg x ml(-1) x min.g) (p < 0.01) and stayed at higher values in older age groups (p < or = 0.01). CONCLUSION: RBF, total and zonal GFR are not significantly different in anaesthetized SHR compared to WKY at ages from 2 to 10 weeks and GFR in juxtamedullary cortex is not decreased in SHR during onset of hypertension. The results from the present study indicate that development of hypertension cannot be explained by a temporary decline in RBF or total or zonal GFR.

Attenuated buffering of renal perfusion pressure variation in juxtamedullary cortex in SHR.

Renal tissue damage is substantially more pronounced in the juxtamedullary than in the superficial cortex in hypertensive rats, and the pathogenesis of the morphological changes are only partly understood. Glomerular capillary pressure (P(GC)) is increased, and steady-state autoregulation is normal in the deep renal cortex. We tested the hypothesis that the transient period from one pressure level to another may induce greater variation in local perfusion before stable autoregulation is established. An acute increase in local perfusion was compared in the superficial and juxtamedullary cortex of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) after an abrupt increase in perfusion pressure. Total renal blood flow (RBF) was measured by a Transonic flow probe and local renal perfusion by laser Doppler flowmetry. Renal perfusion pressure was lowered to 50% of initial values and released abruptly. The maximal RBF increased from 6.3 +/- 0.4 to a maximal value of 7.6 +/- 0.3 ml/min (P < 0.001) in SHR and from 7.3 +/- 0.3 to 8.2 +/- 0.6 ml/min (P < 0.001) in WKY. These changes were not significantly different from each other. The change in superficial cortical perfusion was also not different between SHR and WKY. Pressure release increased juxtamedullary perfusion in SHR from 146 +/- 8 to a maximal value of 228 +/- 17 units (P < 0.001) and in WKY from 160 +/- 13 to 179 +/- 11 units (P < 0.001). The results were significantly different from each other (P < 0.001). The time for maximal flow response was shorter in the deep cortex of SHR, and the time for normalization was longer than in WKY. These data indicate that the buffering of perfusion pressure variation is significantly attenuated in the juxtamedullary cortex, and significantly more so in SHR than in WKY, assuming a covariation of RBF and P(GC), and this finding may explain the extensive morphological damage in the juxtamedullary cortex of SHR.