Alexandros Rouvas

Inhibition of Corneal Neovascularization by Subconjunctival Bevacizumab in an Animal Model

PURPOSE To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. DESIGN Experimental animal study. METHODS Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 microl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. RESULTS On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7%+/-3.1%)<group 3 (13.3%+/-2.3%)<group 2 (41.0%+/-3.6%; P<.05, Mann-Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab (P>.1, one-way ANOVA). No side effects were noted. CONCLUSIONS Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.

Safety of repeat intravitreal injections of bevacizumab versus ranibizumab: our experience after 2,000 injections.

Purpose: To compare the safety of repeat intravitreal injections of bevacizumab versus ranibizumab performed on a large series of patients during the past 2 years period of time. Methods: Four hundred fifty patients receiving 2,000 injections (1,275 bevacizumab and 725 ranibizumab) were studied retrospectively. Injections performed in a usual examination room under the standard sterile conditions. Follow-up varied from 3 to 24 months. Results: Serious ocular adverse events were uncommon. Only one patient developed retinal detachment (0.05%). Most common procedure-related ocular adverse event was injection-site redness (64.75%). Postoperative subconjuctival hemorrhage occurred after 200 (10%) injections. Patients receiving aspirin treatment were more prone to have subconjuctival hemorrhage (P = 0.0002). Most common drug-related ocular adverse event was uveitis (1.90%), which was treated successfully and lasted no >12 days. There was no statistically significant difference between the patients treated with bevacizumab or ranibizumab regarding the noted adverse events (P > 0.5%). Conclusion: Multiple intravitreal injections of bevacizumab or ranibizumab were both well tolerated and safe. Performing injections on a usual examination room proved safe. Injection-site redness, subconjuctival hemorrhage, and uveitis were the most common ocular adverse events. Aspirin treatment was a risk factor for the development of subconjuctival hemorrhage.

Intravitreal ranibizumab, intravitreal ranibizumab with PDT, and intravitreal triamcinolone with PDT for the treatment of retinal angiomatous proliferation: a prospective study.

Purpose: To compare 1) intravitreal ranibizumab, 2) intravitreal ranibizumab plus photodynamic therapy (PDT), and 3) intravitreal triamcinolone plus PDT in retinal angiomatous proliferation. Methods: In this prospective study, 37 eyes of 37 patients with retinal angiomatous proliferation were randomly assigned in 1 of the 3 groups. The patients in Group 1 (n = 13) received 3 monthly injections of 0.5 mg of ranibizumab. The patients in Group 2 (n = 13) received one session of PDT and 3 monthly intravitreal injections of 0.5 mg ranibizumab and the patients in Group 3 (n = 11) received one session of PDT and 1 injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in each group, was considered in case of persistence or recurrence of subretinal fluid or intraretinal fluid. Results: All the patients completed at least 6 months of follow-up. A total of 61.53% patients in Group 1, 76.92% in Group 2, and all in Group 3 had the same or better visual acuity at the end of the follow-up (P = 0.0232). The mean central retinal thickness reduction in Group 1 was 32.23 &mgr;m (P = 0.548), in Group 2 20.31 &mgr;m (P = 0.042), and in Group 3 73.92 &mgr;m (P < 0.0001). Also, the patients in Group 3 received on average the lowest number of injections (P < 0.0001). Conclusion: All groups resulted in stabilization of the disease, while a significant trend towards better visual acuity and anatomic restoration of the affected area was observed in the intravitreal triamcinolone & PDT group.

Structural and Functional Impairment of the Retina and Optic Nerve in Alzheimer’s Disease

PURPOSE The purpose of this study was to evaluate the macular and retinal nerve fiber layer (RNFL) thickness, and the electrical activity of the macula in patients with Alzheimers disease (AD). MATERIAL AND METHODS 30 patients with AD and 30 age and sex matched healthy controls were studied. The thickness and the electrical activity of the macula were evaluated by means of optical coherence tomography (OCT) and multifocal-electroretinogram (mf-ERG). RESULTS Visual acuity, as well as visual fields and colour vision testing of all patients were normal. However, the mean foveal thickness was 148.50 μm (vs. 171.50 μm in the control group, p=0.001) and the RNFL thickness was 104.5 μm in the superior area (vs 123 μm in the control group, p < 0.0001) and 116.5 μm in the inferior area (vs. 138 μm in the control group, p < 0.0001) around the optic nerve. The mean P1 response density amplitude of the foveal area was 146.50 nV/deg2 (vs. 293 nV/deg2 in the control group, p < 0.0001) and the perifoveal area was 56.60 nV/deg2 (vs. 81.50 nv/deg2 in the control group, p < 0.001). CONCLUSION Our study showed that in patients with AD, even without visual failure there was a decrease in macular and RNFL thickness, as well as a decrease of the electrical activity of the macula.

Photodynamic Therapy, Ranibizumab, And Ranibizumab With Photodynamic Therapy For The Treatment Of Polypoidal Choroidal Vasculopathy

Purpose: The purpose of this study was to compare photodynamic therapy (PDT), ranibizumab, and ranibizumab with PDT in polypoidal choroidal vasculopathy. Methods: In this retrospective comparative study, 30 eyes of 30 patients with polypoidal choroidal vasculopathy were assigned to 1 of the 3 groups. The patients in Group 1 (n = 11) received 1 session of PDT. The patients in Group 2 (n = 10) received 3 monthly intravitreal injections of 0.5 mg ranibizumab, and the patients in Group 3 (n = 9) received 1 session of PDT and 3 injections of 0.5 mg ranibizumab. Retreatment, with the same therapeutic scheme in each group, was considered in case of leaking polyps on the indocyanine green angiography in Groups 1 and 3 and persistence or recurrence of subretinal fluid, intraretinal fluid, and/or hemorrhages in Group 2. Results: All the patients completed 12 months of follow-up. The visual acuity in the patients of Group 1 improved by 0.25 logarithm of the minimum angle of resolution units (P < 0.001), whereas the differences in the visual acuity in the other 2 groups were not statistically significant (0.04 logarithm of the minimum angle of resolution, P = 0.8118 in Group 2 and 0.18 logarithm of the minimum angle of resolution, P > 0.05 in Group 3). Of the patients in Group 1, 45.45% gained more than 3 lines (P = 0.0056), whereas no patient in Groups 2 and 3 experienced such a difference. No patient in Group 1 and 11.1% (n = 1) in Group 3 had angiographically evident polyps at 12 months, whereas 90% (n = 9) of the patients in Group 2 had persistent leakage. No extensive submacular hemorrhage or other complications were noted during the follow-up period. Conclusion: Photodynamic therapy resulted in a significantly better outcome at the end of the follow-up, whereas the patients who received ranibizumab or PDT and ranibizumab experienced a stabilization of the disease.

Intravitreal bevacizumab combined with photodynamic therapy for the treatment of occult choroidal neovascularization associated with serous pigment epithelium detachment in age-related macular degeneration.

Purpose: To evaluate the efficacy of intravitreal injection of bevacizumab combined with photodynamic therapy (PDT) for the treatment of occult choroidal neovascularization (CNV) associated with serous pigment epithelium detachment (s-PED) due to age-related macular degeneration (AMD). Methods: In this retrospective study, six patients (six eyes) with subfoveal occult CNV associated with s-PED due to AMD were treated with intravitreal bevacizumab combined with PDT. All patients were treated at baseline with PDT followed by intravitreal bevacizumab 1.25 mg 1 hour later. Afterwards, according to the findings of optical coherence tomography and fluorescein angiography, repeat bevacizumab injections were given, if necessary, monthly for three doses followed by further doses every 3 months. PDT was repeated every 3 months according to the same criteria. Follow-up time was 9 months. Results: All patients completed their treatment during the first 3 months from baseline. Best-corrected visual acuity (BCVA) improved or remained stable related to the baseline values in all patients at the end of the follow-up time. Mean BCVA improved from 20/67 to 20/42. S-PED and subretinal fluid decreased or disappeared. The mean central 1-mm retinal thickness was reduced from baseline value for the 9-month follow-up period by 128 &mgr;m. Conclusion: Intravitreal bevacizumab combined with PDT seems to be a promising treatment with good functional and anatomical results for occult CNV associated with s-PED due to AMD.

Photodynamic therapy with verteporfin of choroidal neovascularization in angioid streaks: Conventional versus early retreatment

Purpose To evaluate the effectiveness of conventional photodynamic therapy with verteporfin (PDT) in a series of patients with macular choroidal neovascularization (CNV) due to angioid streaks and to compare it to the effectiveness of early PDT retreatment. Methods This is a retrospective study of 24 eyes (22 consecutive patients) with subfoveal or juxtafoveal CNV secondary to angioid streaks treated with PDT from September 2000 through February 2003 and that completed at least the first year of follow-up. Until August 2001, retreatments were performed according to the conventional protocol for PDT every 3 months (Group 1, consisting of 11 eyes of 9 patients). After August 2001 (13 more eyes of 13 new patients), retreatments were performed earlier (every 8 weeks) when indicated (Group 2). The follow-up time ranged from 30 to 42 months and from 12 to 30 months in Groups 1 and 2. Results At the end of the follow-up, final best-corrected visual acuity decreased in 21 (87.5%), stabilized in 2 (8.3%), and improved in 1 (4.2%) of the total 24 eyes. In all, 19 of the 24 eyes (79.2%) had a final best-corrected visual acuity equal to or less than 20/400. There were not any statistically significant differences in final visual acuity between the two groups. Conclusions In this large series of patients with macular CNV secondary to angioid streaks, the functional and the anatomic results of PDT were not satisfactory, even when retreatments were performed earlier than the conventional time of 3 months.

Long-term results of half-fluence photodynamic therapy for chronic central serous chorioretinopathy.

Purpose To report long-term functional and anatomic results of safety-enhanced photodynamic therapy (PDT) with half-dose verteporfin for chronic central serous chorioretinopathy (CSC). Methods A retrospective analysis of 29 eyes of 27 patients with chronic CSC was performed. All eyes received half-dose PDT. Visual acuity, central foveal thickness, and angiographic features were evaluated. Results Mean follow-up time was 20 months (range 12-40). Mean best-corrected visual acuity improved from 0.45±0.23 logMAR to 0.08±0.08 logMAR. Twenty-five eyes (86%) had a complete resolution of the subretinal fluid after only one session and 4 eyes had recurrences, 3 of them at the same leaking area observed at baseline. At the end of the follow-up all eyes (100%) showed resolution of the subretinal fluid. There was no visual loss secondary to exaggerated response to the PDT, nor any other adverse events. Conclusions The long-term results of this study further support the safety and effectiveness of safety-enhanced PDT with half dose of verteporfin for the treatment of chronic CSC.

The Effect of Intravitreal Ranibizumab on the Fellow Untreated Eye with Subfoveal Scarring due to Exudative Age-Related Macular Degeneration

Aim: Our purpose was to evaluate the possible effect of intravitreal ranibizumab on the fellow untreated eye with choroidal neovascularization (CNV) and subfoveal scarring associated with age-related macular degeneration (AMD). Methods: A retrospective observational study was conducted. One hundred eighty-seven ranibizumab-treated patients diagnosed as having subfoveal CNV scarring in the untreated eye were compared with a control group of untreated unilateral subfoveal CNV scarring. Inclusion criteria concerning treated eyes in the ranibizumab group complied with the MARINA and ANCHOR studies. Demographic data, clinical course, visual acuity, fluorescein angiography and optical coherence tomography findings were evaluated. Results: Clinical improvement was confirmed in 24% of the patients in the ranibizumab group and in only 12.9% of the controls. Improvement was noted as early as 2–4 months (2.83 ± 0.75 months) after the initiation of treatment in the fellow eye compared with 33.25 ± 9.43 months in the control group (p = 0.01; Mann-Whitney U test). Kaplan-Meier curves demonstrate the positive impact of ranibizumab on the visual acuity of the fellow untreated eye (p = 0.016; Log-Rank test). Conclusions: Ranibizumab might induce some therapeutic effect in selected cases of end-stage CNV scarring, which needs to be further examined. The VEGF levels in the compartments of the fellow eye of patients with age-related macular degeneration treated with ranibizumab need to be further evaluated.

Long-term Results Of Intravitreal Ranibizumab, Intravitreal Ranibizumab With Photodynamic Therapy, And Intravitreal Triamcinolone With Photodynamic Therapy For The Treatment Of Retinal Angiomatous Proliferation

Purpose: To compare intravitreal ranibizumab, intravitreal ranibizumab plus photodynamic therapy (PDT), and intravitreal triamcinolone plus PDT in retinal angiomatous proliferation, presenting the results of a 3-year follow-up. Methods: Thirty-seven eyes of 37 patients with retinal angiomatous proliferation were randomized to 1 of the 3 groups. Group 1 (n = 13) received 3 monthly injections of 0.5 mg ranibizumab, Group 2 (n = 13) received 1 session of PDT and 3 monthly injections of ranibizumab, and Group 3 (n = 11) received 1 session of PDT and 1 injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in each group, was considered in case of persistence or recurrence of subretinal/intraretinal fluid. Results: Twelve patients in Groups 1 and 2 and 9 patients in Group 3 completed the 3-year follow-up. A total of 58% of patients in Group 1, 50% in Group 2, and 88.9% in Group 3 had the same or better visual acuity at the end of the follow-up (P = 0.081). Patients in Group 3 exhibited considerable improvement in visual acuity (P = 0.032) and statistically significant decrease in central retinal thickness (P < 0.0001) than the 2 other groups at the end of the follow-up. Also, the patients in Group 3 received on average the lowest number of injections (P < 0.0001). Of note, geographic atrophy mainly at the place of previous retinal angiomatous proliferation lesion was detected in 0% in Group 1, 25% in Group 2, and 55.6% in Group 3 (P = 0.203), while 33.3% of patients in Group 1 developed retinal scar. Conclusion: Treatment with ranibizumab or ranibizumab plus PDT resulted in stabilization of the disease, while treatment with IVT plus PDT achieved better results in terms of functional and anatomical features compared with the other groups.