Ioannis Vergados

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.

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 ranibizumab for the treatment of inflammatory choroidal neovascularization.

Purpose: To evaluate the effect of individualized repeated intravitreal injections of ranibizumab (Lucentis) on visual acuity and central foveal thickness in patients with choroidal neovascular membrane (CNV) associated with various ocular inflammatory clinical entities. Methods: Our study was a retrospective, noncomparative, interventional, and observational case series. Sixteen eyes of 15 consecutive patients diagnosed with inflammatory CNV treated with repeated intravitreal injections of ranibizumab were evaluated. The underlying diagnoses were toxoplasmosis (n = 4), serpiginous choroidopathy (n = 2), punctate inner choroidopathy (n = 5), multifocal choroiditis (MFC, n = 3), and scleroderma (n = 2). All patients underwent monthly optical coherence tomography (OCT) scans and fluorescein angiography/indocyanine green angiography every 1 month after every injection and then every 3 months. Optical coherence tomography scans and fluorescein angiography were performed by the same experienced physician. Repeated intravitreal injections were performed when persistent/recurrent fluid on OCT and/or signs of active CNV on angiography were present. Changes in Early Treatment Diabetic Retinopathy Study visual acuity and central foveal thickness were statistically analyzed. Results: The mean follow-up time was 70.4 ± 24 weeks (17.6 months; range, 44-116 weeks [11-29 months]). The mean number of injections performed was 2.3, and the mean best-corrected visual acuity improved from 55 Early Treatment Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution, 0.9 ± 0.4 [mean ± SD]) at baseline to 70.3 Early Treatment Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution, 0.6 ± 0.4) at the end of the follow-up, a statistically significant change compared with baseline (P < 0.0001). The mean letter gain was 15.3 letters, and best-corrected visual acuity improved in 14 of 16 patients (88%) and remained stable in 2 patients (12.5%) without any patient demonstrating deterioration. The mean central foveal thickness (although not excessively increased at baseline) improved from 285 ± 20 μm at baseline to 233 ± 21 μm (statistically significant compared with baseline, P < 0.0001) at the end of the follow-up. At the end of the follow-up, all patients demonstrated CNV regression, and retinal pigment epithelial atrophy surrounding the regressed CNV was developed in 11 of the 16 eyes (68.8%). During the same period, no CNV recurrence was observed and no injection-related complications such as cataract, retinal detachment, endophthalmitis, or exacerbation of uveitis were noted. Conclusion: Overall, our findings suggest that intravitreal injections of ranibizumab have shown promising results in visual acuity improvement and a decrease in macular thickness in patients with inflammatory CNV. Of course, further studies are needed to confirm the exact benefit and standardize the optimal treatment regimen.

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.

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.

The epidemiology of cataract: a study in Greece

Purpose:  We conducted a case–control study to identify risk factors for cataract in the Mediterranean Greek population. Three hundred and fourteen cases and 314 frequency‐matched controls of both genders, aged 45–85, attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study.

Intravitreal ranibizumab (Lucentis) for branch retinal vein occlusion-induced macular edema: nine-month results of a prospective study.

Purpose:The purpose of this study was to evaluate the effect of individualized repeated intravitreal injections of ranibizumab (Lucentis, Genentech, South San Francisco, CA) on visual acuity and central foveal thickness (CFT) for branch retinal vein occlusion-induced macular edema. Methods:This study was a prospective interventional case series. Twenty-eight eyes of 28 consecutive patients diagnosed with branch retinal vein occlusion-related macular edema treated with repeated intravitreal injections of ranibizumab (when CFT was >225 μm) were evaluated. Optical coherence tomography and fluorescein angiography were performed monthly. Results:The mean best-corrected distance visual acuity improved from 62.67 Early Treatment of Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution = 0.74 ± 0.28 [mean ± standard deviation]) at baseline to 76.8 Early Treatment of Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution = 0.49 ± 0.3; statistically significant, P < 0.001) at the end of the follow-up (9 months). The mean letter gain (including the patients with stable and worse visual acuities) was 14.3 letters (2.9 lines). During the same period, 22 of the 28 eyes (78.6%) showed improved visual acuity, 4 (14.2%) had stable visual acuity, and 2 (7.14%) had worse visual acuity compared with baseline. The mean CFT improved from 349 ± 112 μm at baseline to 229 ± 44 μm (significant, P < 0.001) at the end of follow-up. A mean of six injections was performed during the follow-up period. Our subgroup analysis indicated that patients with worse visual acuity at presentation (≤50 letters in our series) showed greater visual benefit from treatment. “Rebound” macular edema was observed in 5 patients (17.85%) at the 3-month follow-up visit and in none at the 6- and 9-month follow-ups. In 18 of the 28 patients (53.6%), the CFT was <225 μm at the last follow-up visit, and therefore, further treatment was not instituted. No ocular or systemic side effects were noted. Conclusion:Individualized repeated intravitreal injections of ranibizumab showed promising short-term results in visual acuity improvement and decrease in CFT in patients with macular edema associated with branch retinal vein occlusion. Further studies are needed to prove the long-term effect of ranibizumab treatment on patients with branch retinal vein occlusion.

Intravitreal ranibizumab in a patient with choroidal neovascularization secondary to multiple evanescent white dot syndrome

Purpose To report the effect of a single intravitreal injection of ranibizumab in a patient with choroidal neovascularization (CNV) secondary to multiple evanescent white dot syndrome (MEWDS). Methods A 65-year-old woman with visual acuity (VA) 20/40, mild vitreous inflammation, optic disc edema, and white deep retinal round lesions in the right eye underwent fluorescein angiography, indocyanine green angiography, and optical coherence tomography. The diagnosis of MEWDS with peripapillary CNV was made and a single injection of ranibizumab (0.5 mg) was administered. Results At the 6-month follow-up visit, the VA in the right eye was 20/20, the CNV completely regressed, and the MEWDS findings disappeared. Conclusions Intravitreal ranibizumab appears to be a safe and effective treatment option in cases of CNV secondary to MEWDS, resulting in fast resolution of the macular edema and regression of the CNV. On the other hand, it is unclear whether the administration of ranibizumab contributed to a prompt regression of MEWDS.