Angela Carneiro

Short-term Efficacy And Safety Of Intravitreal Ranibizumab For Myopic Choroidal Neovascularization

Purpose: To evaluate the safety and efficacy of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia (PM). Metohds: Retrospective, multicenter, consecutive, nonrandomized, interventional case series. Participants: Twenty-six eyes of 26 patients with CNV secondary to pathologic myopia; 11 eyes with previous photodynamic therapy; and 15 eyes with no previous treatment. Follow-up: 3 or more months. Best-corrected visual acuity (BCVA), ocular coherence tomography, and the presence of metamorphopsia were assessed monthly. Results: At 1 month, 31% of the eyes had an improvement in visual acuity of 3 or more lines. Twenty-six eyes completed 3 months of follow-up, and nine eyes completed 6 months of follow-up. Visual acuity improved significantly from 20/100 at baseline to 20/80 at 1 month (P = 0.003) to 20/63 at 3 months (P < 0.001), and 20/50 at 6 months (P = 0.01). A significant reduction in ocular coherence tomography central thickness was observed at 1, 3, and 6 months. No cases of severe visual acuity loss occurred, and no systemic or ocular side effects were registered during the follow-up. Conclusion: Short-term results of intravitreal ranibizumab for myopic CNV are encouraging. Further prospective long-term studies are necessary to evaluate safety and efficacy of intravitreal ranibizumab in the treatment of myopic CNV.

Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome

Objective To report the visual outcome after 4-year follow-up in a series of highly myopic eyes with choroidal neovascularisation (CNV) treated with antivascular endothelial growth factor (anti-VEGF) drugs. Methods A retrospective, non-randomised, multicentre, consecutive, interventional case series study was performed. 92 highly myopic eyes with subfoveal CNV were treated with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3 injections) was dictated by surgeons’ preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyse BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives. Results The mean age of the patients was 57 years (SD 14, range 30–93). The mean number of letters read was 46.1 (SD 16.8, range 5–70) at baseline, 55.5 (SD 18.6, range 10–85) at 12 months, 50.1 (SD 20.1, range 5–82) at 24 months, 54.2 (SD 21.9, range 2–85) at 36 months and 53.1 (SD 22.5, range 1–83) at 48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months; Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4, range 1–29). SE and treating drug had no influence on the final visual outcome and number of injections required. Conclusions Intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at 4-year follow-up.

Bevacizumab and ranibizumab on microvascular endothelial cells: A comparative study

Given its broad effects in endothelium, vascular endothelial growth factor (VEGF) represents the primary rate‐limiting step of angiogenesis. Therefore, VEGF targeting therapies were soon developed. Bevacizumab and ranibizumab are two of these therapeutic agents already in clinical use. Bevacizumab was first used for cancer treatment, whereas ranibizumab was designed to target choroidal neovascularization, the main cause of blindness in age‐related macular degeneration. The present study aims to compare the multiple effects of bevacizumab and ranibizumab in human microvascular endothelial cells (HMECs). HMEC cultures were established and treated during 24 h with the anti‐VEGF agents within the intravitreal‐established concentration range or excipients. Analyses of VEGF content in cell media and VEGF receptor‐2 (VEGFR‐2) expression in cell lysates were performed. No cell cytotoxicity (MTS assay) was found in anti‐VEGF‐treated cultures at any concentration. Apoptosis (TUNEL assay) was significantly increased and cell proliferation (BrdU assay), migration (transwell assay) and assembly into vascular structures were significantly reduced by incubation with both agents at the two doses used. These findings were accompanied by a strong decrease in VEGF release, and in phosphorylated VEGFR‐2 and Akt expression for both agents at the clinical concentration. Interestingly, phosphorylated Erk was only significantly reduced upon bevacizumab treatment. In addition, proliferation was more affected by ranibizumab, whereas migration, capillary formation, and phosphorylated VEGFR2 expression were significantly reduced by bevacizumab as compared to ranibizumab. Therefore, although both agents presented anti‐angiogenic actions, distinct effects were exerted by the two molecules in HMEC. These findings suggest that a careful confirmation of these effects in clinical settings is mandatory. J. Cell. Biochem. 108: 1410–1417, 2009.

Choroidal and macular thickness changes induced by cataract surgery

Background The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid. Methods In 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated. Results There was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 μm (P<0.001), and in vertical scans, the mean increase was +8.80±7.07 μm (P=0.001). However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 μm; P=0.47) whilst in horizontal scans a nonsignificant decrease was recorded (−9.11±39.59 μm; P=0.41). In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 μm; P=0.36). Conclusion Uncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of phacoemulsification is mainly observed at the retinal level, and seems to be independent of choroidal thickness changes.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

Purpose: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. Methods: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. Results: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Students t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1–9). Conclusion: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.

Ranibizumab Treatment for Choroidal Neovascularization from Causes Other than Age-Related Macular Degeneration and Pathological Myopia

Aim: Evaluation of safety and efficacy of intravitreal ranibizumab in the treatment of choroidal neovascularization (CNV) secondary to causes other than age-related macular degeneration (AMD) or pathological myopia (PM). Methods: Retrospective and multicentric analysis of 21 eyes with CNV. Nine eyes had angioid streaks, 5 inflammatory chorioretinal diseases, 3 central serous chorioretinopathy and 4 idiopathic CNV. Follow-ups lasted ≧3 months. Best-corrected visual acuity (BCVA), ocular coherence tomography (OCT) and fundus examination were assessed monthly. Results: Sixteen eyes (76%) completed 180 days of follow-up. Overall BCVA increased by +9.8 letters with treatment (p = 0.015). Visual acuity improvements ≧15 letters occurred in 43%. A significant reduction in OCT central thickness was observed. No cases of severe visual acuity loss, systemic or ocular side effects were registered. Conclusion: Short-term results of intravitreal ranibizumab for CNV unrelated to AMD or PM are encouraging. This treatment may constitute the only option for some of these patients.

Characterization of neovascular age-related macular degeneration patients with outer retinal tubulations.

Purpose: To characterize the neovascular lesions of patients with age-related macular degeneration (AMD) and outer retinal tubulations (ORTs). Methods: A retrospective study of 377 eyes with exudative AMD, submitted to intravitreal anti-angiogenic treatment. Patients were divided into 2 groups according to the presence or absence of ORTs on spectral-domain optical coherence tomography (SD-OCT; group 1 - with ORTs; group 2 - without ORTs). Age, best corrected visual acuity (BCVA), fluorescein angiography characteristics, presence of subretinal fibrosis and subfoveal photoreceptor integrity on SD-OCT were analyzed. Results: Although both groups had a BCVA gain during the follow-up period, initial and final BCVA were lower in group 1 (p = 0.020 and p = 0.042, respectively). There was no statistically significant difference in the BCVA variation between the 2 groups (p = 0.907). Regarding the initial angiographic lesion type, there was a statistically significant difference between the 2 groups (p = 0.008): group 1 had more lesions with a classic component and group 2 had more occult lesions with no classic component. There was a statistically significant difference concerning the loss of subfoveal photoreceptor integrity (p = 0.0007). Conclusions: Even though AMD patients with ORTs were associated with poor visual outcomes, we reported BCVA improvement. AMD patients with a classical component in their lesions are prone to develop ORTs.

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.

Multiple effects of bevacizumab in angiogenesis: implications for its use in age‐related macular degeneration

Purpose:  This study aimed to elucidate the precise effects of bevacizumab in all steps in the neovascularization process in endothelial cells.

Intravitreal bevacizumab for neovascular age-related macular degeneration with or without prior treatment with photodynamic therapy: one-year results.

Purpose: The purpose of this study was to elucidate the effect of prior photodynamic therapy (PDT) on the efficacy of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration. Methods: One hundred and nine eyes of 102 patients with neovascular age-related macular degeneration were evaluated—80 eyes without prior treatment (group 1) and 29 with prior PDT (group 2). Best-corrected visual acuity, ocular coherence tomography, and funduscopy were assessed monthly. Results were evaluated at 1, 3, 6, and 12 months. Results: One hundred and one eyes completed a 12-month evaluation. At 12 months, best-corrected visual acuity increased 5.6 letters with treatment (P = 0.001): +5.7 letters in group 1 and +5.4 in group 2 (P = 0.92). Overall, visual acuity improved ≥15 letters in 22.5% of eyes: 24.0% of naive eyes versus 18.5% with prior PDT (P = 0.56). Best-corrected visual acuity loss ≥15 letters occurred in 6 eyes, 5 with naive lesions. An overall reduction in ocular coherence tomography central retinal thickness was observed at all time points. Mean number of injections per eye per year was 5.6, 6.13 in group 1 versus 4.22 in group 2 (P = 0.01). Two retinal pigment epithelial tears, one subretinal macular hemorrhage, and two strokes occurred in naive lesions. Conclusion: The authors showed similar efficacy for intravitreal bevacizumab independently of prior PDT treatment. Eyes with prior PDT needed a statistically significantly lower number of injections to control their lesions.