Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy.

PURPOSE: We assess for frequency and predictive factors related to sustained intraocular pressure (IOP) elevation in eyes with neovascular age-related macular degeneration receiving intravitreal injections of ranibizumab and/or bevacizumab. METHODS: A total of 328 patients with neovascular age-related macular degeneration (449 eyes) who presented to a single physician over a 6-month period were retrospectively assessed for baseline demographic/clinical information, total number of bevacizumab and/or ranibizumab injections, and sustained IOP elevation on 2 or more consecutive visits (absolute IOP >25 mmHg, increase above baseline >10 mmHg, or IOP of >21 mmHg and increase of >5 mmHg). Cox regression survival analysis and multivariate logistic regression were performed to assess the influence of intravitreal injections on experiencing sustained IOP elevation. RESULTS: Overall, 32 eyes (7.1%) experienced sustained IOP elevation. Survival analysis showed a significant effect of the number of anti-vascular endothelial growth factor injections on sustained IOP elevation (hazard ratio, 1.085; 95% confidence interval: 1.06-1.11, P < 0.001). Also, there was an increased odds ratio (16.1, P = 0.008) of sustained IOP elevation in eyes receiving ≥29 injections compared with ≤12 injections. After controlling for the confounder (prior intravitreal steroid injection), total number of injections still showed a statistically significant association (P = 0.002). CONCLUSION: A greater number of intravitreal anti-vascular endothelial growth factor injections is associated with an increased risk for sustained IOP elevation in eyes with neovascular age-related macular degeneration receiving intravitreal ranbizumab and/or bevacizumab.

Comparative study of 1+PRN ranibizumab versus bevacizumab in the clinical setting.

PURPOSE: We compared the efficacy of intravitreal ranibizumab and bevacizumab for treating neovascular age-related macular degeneration using an on-demand regimen. METHODS: A total of 186 wet age-related macular degeneration eyes of 186 treatment-naïve patients were compared retrospectively (67 eyes treated with ranibizumab with 91 treated with bevacizumab). At baseline, mean age, best corrected visual acuity, and angiographic lesion types were similar in both groups. Best corrected visual acuity and ocular coherence tomography were evaluated. RESULTS: Sixty eyes treated with ranibizumab and 85 eyes treated with bevacizumab completed a 12-month evaluation. At 12 months, mean best corrected visual acuity increased by +6.65 letters with ranibizumab treatment and by +5.59 with bevacizumab treatment (P = 0.64). Visual acuity improved by ≥15 letters in 15 eyes treated with ranibizumab and in 21 eyes treated with bevacizumab (P = 0.75). An overall reduction in ocular coherence tomography central thickness occurred for all time points. The mean number of injections per eye was 5.97 with ranibizumab and 5.92 with bevacizumab (P = 0.90). CONCLUSION: Intravitreal therapies with ranibizumab or bevacizumab have similar visual and anatomical results. These results confirm those of comparison of Age-Related Macular Degeneration Treatment Trials in as-needed cohorts in clinical practice. Randomized long-term clinical trials are necessary to examine the systemic safety of these treatments.

Segregation of ophthalmoscopic characteristics according to choroidal thickness in patients with early age-related macular degeneration.

PURPOSE: To investigate the association of fundus features with choroidal thickness in eyes with early age-related macular degeneration. METHODS: Consecutive patients with age-related macular degeneration were evaluated. Major exclusionary criteria included late age-related macular degeneration (central geographic atrophy or choroidal neovascularization), macular laser therapy, myopia greater than -6 diopters, past vitreoretinal surgery, or central serous chorioretinopathy. Charts and multimodal imaging were reviewed for refraction, cataract, hypertension, diabetes, open-angle glaucoma, ß-zone peripapillary atrophy, fundus tessellation, pigmentary changes, drusen, subretinal drusenoid deposits (also known as reticular pseudodrusen). Data measured from enhanced-depth imaging spectral-domain optical coherence tomography included subfoveal choroidal thickness, central foveal thickness, outer nuclear layer thickness, inner segment to retinal pigment epithelium aggregate thickness, presence of subretinal drusenoid deposit, and outer retinal hyperreflective layers (including the band corresponding to overlap between retinal pigment epithelium apical processes and outer segments). Correlations were calculated among the measured variables, fundus features, open-angle glaucoma, and visual acuity. RESULTS: In 90 eyes of 70 early age-related macular degeneration patients with mean visual acuity 20/31 (logarithm of the minimum angle of resolution 0.193), subfoveal choroidal thickness showed a significant inverse correlation with age (P = 0.004) and increasing myopic spherical equivalent refractive error (P = 0.023). Subfoveal choroidal thickness was thinner in eyes with fundus tessellation (P < 0.001), subretinal drusenoid deposit (P = 0.023), an absence of conventional drusen (P < 0.001), the presence of ß-zone peripapillary atrophy (P < 0.001), and in eyes with a diagnosis of open-angle glaucoma (P = 0.003) or an absent band on optical coherence tomography corresponding to overlap between outer segment and retinal pigment epithelium apical processes (P = 0.022). CONCLUSION: Major ocular manifestations in early age-related macular degeneration and open-angle glaucoma are associated with the choroid-the main blood supply in the eye. Theories concerning the pathogenesis of these two diseases should incorporate interactions involving the choroid.

Vascular endothelial growth factor plasma levels before and after treatment of neovascular age-related macular degeneration with bevacizumab or ranibizumab.

PURPOSE: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of ranibizumab or bevacizumab in patients with exudative age-related macular degeneration (AMD). METHODS: Forty-three patients with exudative AMD and 19 age- and sex-matched control patients without chorioretinal diseases were studied. Nineteen patients were treated with intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood samples were collected just before the first injection, and 28 days after three initial consecutive injections performed in 4-weekly intervals (loading dose). Concentration of VEGF in the plasma was measured by ELISA. RESULTS: At baseline, the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma concentrations in patients with wet AMD were comparable to controls (p = 0.225). Twenty-eight days after the third injection, a significant reduction of 42% in the median VEGF plasma levels was found in bevacizumab-treated patients (109.97 pg/ml; p = 0.0002) but not in ranibizumab-treated patients (189.97 pg/ml; p = 0.198) where a reduction of 0.7% in the median value was found. CONCLUSIONS: Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days after intravitreal injection in patients with exudative AMD. Ranibizumab did not achieve a significant plasma VEGF reduction at the same time-point. These findings alert to the potential systemic safety differences between the two drugs after intravitreal administration.

Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration.

PURPOSE: To describe a series of previously normotensive eyes experiencing sustained elevated intraocular pressure (IOP) associated with long-term intravitreal antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Clinical data were reviewed for 25 eyes of 23 patients with neovascular AMD who had increased IOP while receiving interval doses of intravitreal ranibizumab and/or bevacizumab. All eyes had tolerated multiple anti-VEGF injections in the past without IOP elevations. RESULTS: After a mean of 20.0 anti-VEGF injections (range, 8-40 injections), the mean IOP was 29.8 mm Hg (range, 22-58 mm Hg), compared with a baseline of 16.9 mm Hg (range, 14-21 mm Hg). The mean highest IOP while receiving intravitreal anti-VEGF therapy was 35.8 mm Hg (range, 23-58 mm Hg). Overall, 23 of 25 cases required IOP management. In the remaining 2 cases, anti-VEGF dosing was switched from regular interval dosing to an optical coherence tomography-guided variable regimen, with subsequent improvement in IOP without antiglaucoma treatment. CONCLUSIONS: Serial injections of anti-VEGF agents may lead to persistent IOP elevations that require glaucoma therapy. The clinician should recognize this phenomenon, as it can occur even if the patient has tolerated multiple prior injections without IOP elevation. Further exploration of the relationship between anti-VEGF therapy and IOP is needed.

Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections.

PURPOSE: We assessed the frequency and predictive factors related to intraocular pressure (IOP) elevation in neovascular age-related macular degeneration (AMD) patients undergoing unilateral intravitreal ranibizumab and/or bevacizumab injections. DESIGN: Retrospective cohort study. PARTICIPANTS: Charts of 207 patients with neovascular AMD who presented to a single physician at a retinal referral practice over a 6-month period were retrospectively reviewed. METHODS: Data recorded included demographic information, clinical findings, total number of bevacizumab and ranibizumab injections received and IOP at each visit. Increases above baseline IOP of >5, >10, or >15 mmHg on ≥2 consecutive visits while under treatment were noted. MAIN OUTCOME MEASURES: The frequency of IOP elevation was compared between treated and untreated eyes. In addition, among treated eyes, frequency and odds ratio of experiencing IOP elevation >5 mmHg above baseline on ≥2 consecutive visits was stratified by number of injections. For the main regression analysis, the outcome variable was IOP elevation >5 mmHg on ≥2 consecutive visits and the main independent variable was total number of injections. RESULTS: On ≥2 consecutive visits, 11.6% of treated versus 5.3% of untreated/control eyes experienced IOP elevation of >5 mmHg. The mean number of injections was higher in those with (24.4; 95% confidence interval [CI], 20.9-28.0; range, 9-39) than without IOP elevation of >5 mmHg (20.4; 95% CI, 18.9-21.8; range, 3-48) on ≥2 consecutive visits. There was an increased odds ratio (5.75; 95% CI, 1.19-27.8; P = 0.03) of experiencing IOP elevation >5 mmHg on ≥2 consecutive visits in patients receiving ≥29 injections compared with ≤12 injections. Of the factors considered, only the total number of injections showed a statistically significant association with IOP elevation >5 mmHg above baseline on ≥2 consecutive visits in treated eyes (P = 0.05). CONCLUSIONS: A greater number of intravitreal anti-vasular endothelial growth factor injections is associated with an increased risk for IOP elevation >5 mmHg on ≥2 consecutive visits in eyes with neovascular AMD receiving intravitreal ranbizumab and/or bevacizumab.

Arterial thromboembolic events in patients with exudative age-related macular degeneration treated with intravitreal bevacizumab or ranibizumab.

BACKGROUND/AIMS: To compare retrospectively the incidence of arterial thromboembolic events (ATEs) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration. METHODS: Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were reviewed to calculate the incidence of ATEs. Only patients under monotherapy were analyzed. RESULTS: ATEs occurred in 15 patients: 12 (12/97) with bevacizumab (12.4%) and 3 (3/219) with ranibizumab (1.4%) - odds ratio 10.16; 95% confidence interval 2.80-36.93; p < 0.0001. ATEs in the bevacizumab and ranibizumab cohorts included stroke, myocardial infarction, angina pectoris, peripheral thromboembolic disease, transient ischemic attack, sudden death and lethal stroke. CONCLUSION: In this series, bevacizumab raised the risk of ATEs when compared to ranibizumab. In an elderly population with multiple cardiovascular risk factors, the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration. These findings raise an issue that must be confirmed in randomized clinical trials.