THE LATEST PUBLISHED RESEARCH

Effect of Intravitreal Bevacizumab on Subfoveal CNV Secondary to AMD
Sixty-three eyes of 63 consecutive patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a minimum of 12 months (mean 55.5 ± 6.2 weeks) of follow up participated in this interventional, retrospective, multicenter case series in seven centers from six countries. The mean age of patients was 73.7 ± 7.5 years and they were treated with at least one intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, optical coherence tomography and fluorescein angiography at baseline and at follow-up visits. Investigators used repeated measures analysis of variance to compare mean values and reported the 12-month anatomic and ETDRS BCVA response.

The mean number of intravitreal bevacizumab injections per eye was 3.5 (range, 1-8). Mean baseline BCVA was 20/320 and logarithm of the minimum angle of resolution = 1.2; mean final BCVA was 20/200 and logarithm of the minimum angle of resolution – 1.0 (p < 0.001). The investigators reported that central macular thickness at baseline by optical coherence tomography had a mean of 389.2 ± 149.6 µm, which was significantly reduced to a mean of 281.0 ± 96.1 µm, 268.2 ± 82.6 µm, 262.6 ± 92.3 µm and 241.3 ± 76.7 µm at 1, 3, 6 and 12 months after initial treatment, respectively (p < 0.0001). Ocular adverse events included transient increased intraocular pressure in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes and transient hypotony in 1 (1.1%) eye. They observed no systemic adverse events.

Primary intravitreal bevacizumab (1.25 mg or 2.5 mg) seems to provide stability or improvement in BCVA, optical coherence tomography and fluorescein angiography in subfoveal CNV secondary to AMD degeneration at 12 months.

Source: Arevalo JF, Fromow-Guerra J, Sanchez JG, et al. Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration: results of the Pan-American Collaborative Retina Study Group at 12 months follow-up. Retina 2008; 28(10):1387-1394.

Incidence of Acute Intraocular Inflammation After Intravitreous Bevacizumab for Neovascular AMD
This retrospective case series describes acute intraocular inflammation after intravitreous injection of bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). The authors retrospectively reviewed cases of acute intraocular inflammation from two Australian states (Victoria and South Australia) after intravitreous injection of bevacizumab for the treatment of neovascular AMD. The detection and description of inflammation in a large cohort of patients was the main outcome measure.

From a total of 1278 injections given, there were 14 cases (11 women and 3 men) and the mean age of patients was 83.7 years (range, 74-98). The majority had a prior injection of bevacizumab, with a mean number of injections of 2.7 (range, 1-6). Within 24 hours of intravitreous injection, most patients presented with rapid reduction in vision, but minimal discomfort and there were associated signs of ocular inflammation in the anterior and posterior segments of the eye. Although visual acuity at presentation was substantially reduced compared with the preinjection acuity, it rapidly improved with treatment over a 7- to 25-day period toward preinjection visual acuity.

Following their review of the cases, the authors concluded that intravitreous injection of bevacizumab for the treatment of neovascular AMD may be associated with acute intraocular inflammation; therefore, differentiation from infectious endophthalmitis is important for appropriate management of this condition.

Source: Wickremasinghe SS, Franzco KM, Gihotra J, et al. Acute intraocular inflammation after intravitreous injections of bevacizumab for treatment of neovascular age-related macular degeneration. Ophthalmol 2008; 115(11):1911-1915.e1

Progression of Pure Geographic Atrophy
This population-based cohort study examined the change in size and location of pure geographic atrophy (GA). Researchers identified 95 patients with GA either at baseline, at one of the three five-year follow-up examinations or both and calculated the lesion area and greatest linear dimension (GLD) using computer-assisted software. Thirty-two persons (53 multiple eye-visit pairs) were seen at multiple visits five years apart with GA in the same eye to evaluate changes in total area and GLD.

At the first occasion when pure GA was indentified, 45% had a single GA lesion, 18% had multifocal GA lesions and 37% had a merged GA lesion and of 53 eyes with multiple visits, the overall increase in atrophy was 6.4 mm² over a five-year period. According to the researchers, the atrophy progressed to involve the foveal center in 47% of 19 eyes, and there was a mean decrease of 17 letters read correctly. They found that eyes with multifocal GA were most likely to have the area of atrophy increase (mean, 12 mm²), to have atrophy progress to the foveal center (83%) and to have a decrease in vision (mean, 22 letters), whereas eyes with a single GA lesion were least likely to have the area of atrophy increase (mean, 2 mm²), to have the lesion progress to the foveal center (22%) and to have a decrease in vision (mean, 10 letters). These are the first population-based data describing the five-year change in eyes with pure GA.

Information on progression of GA will be useful for clinical trials of new interventions for GA.

Source: Klein R, Meuer SM, Knudtson MD, Klein BEK. The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye Study. Am J Ophthalmol 2008; 146(5):692-699.e1

Role of VLDL Receptor and Retinal Vascular Endothelial Cells in Angiogenesis
In examining the effects of very low-density lipoprotein receptor (VLDLR) on angiogenic functions of retinal vascular endothelial cells (RVECs) in vivo and in vitro, investigators at Indiana University School of Medicine in Indianapolis, Indiana, found that loss of VLDLR activates RVECs and significantly enhances angiogenesis in vivo and in vitro. (The VLDLR knockout (vldlr -/-) mouse has been identified as a model for retinal angiomatous proliferation with subretinal neovascularization [SNV] evolving from retinal vessels.)

The researchers performed immunofluorescent staining of markers for activated endothelial cells using CD105 and CD106 antibodies. They carried out proliferation, tube formation and migration assays in RVECs isolated from wild-type and vldlr -/- mice to assess the angiogenic functions in vitro and also examined the effect of VLDLR blockage on wild-type RVEC proliferation.

The expression of CD105 and CD106 was significantly upregulated in the retina of adult vldlr -/- mice, especially at lesion sites and the researchers found an intense CD105 signal in the inner retina of vldlr -/- mice starting at P14 before the onset of SNV. In vitro proliferation assays revealed a significantly enhanced (20-200%) growth rate in vldlr -/- RVECs compared with that in the wild type. Formation of capillary-like structures in vldlr -/- RVECs was 3-11 times more than that in wild-type RVECs. Migration of vldlr -/- RVECs was 1.3-3.7 times of the wild type. VLDLR blockage using a receptor-associated protein or neutralizing anti-VLDLR antibodies significantly enhanced the proliferation rate in wild-type RVECs by more than 200% and 30%, respectively. According to the researchers, loss of VLDLR activates RVECs and significantly enhances angiogenesis in vivo and in vitro.

Source: Jiang AH, Hu W, Meng, H, et al. Loss of VLDL receptor activates retinal vascular endothelial cells and promotes angiogenesis. Invest Ophthalmol Vis Sci 2008; Oct 20 [Epub ahead of print].

Efficacy of Treatments with Photodynamic Therapy for Retinal Angiomatous Proliferation
This retrospective, interventional, nonrandomized multicentric study compared the relative efficacy of photodynamic therapy (PDT), PDT associated with intravitreal triamcinolone (PDT-IT) and PDT associated with periocular triamcinolone (PDT-PT) to treat retinal angiomatous proliferation (RAP) stage III. The results indicate that combined therapy PDT-IT may offer better results than PDT monotherapy and PDT associated with periocular triamcinolone in patients with RAP stage III.

Researchers in Spain retrospectively examined the files, Optical Coherence Tomography (OCT) scans, indocyanine green and fluorescein angiograms of patients with RAP stage III who had been referred to a regional center for PDT. They considered final visual acuity and chorioretinal atrophy, as well as the need to retreat and the appearance of recurrences, as main outcome indicators.

Forty-two eyes were treated by PDT as monotherapy, 18 eyes by PDT-PT and 19 eyes by PDT-IT. The mean age in each group was 79.1 ± 5.2, 77.0 ± 5.9 and 80.2 ± 5.1 years, respectively. The mean initial best corrected visual acuity (BCVA) was 0.17 ± 0.19, 0.21 ± 0.20 and 0.20 ± 0.18 respectively, whereas mean BCVA was 0.14 ± 0.19, 0.17 ± 0.15 and 0.17 ± 0.23 respectively at six months (p = 0.27, 0.33 and 0.21 respectively) and 0.12 ± 0.18, 0.10 ± 0.10 and 0.17 ± 0.26 respectively at 12 months (p = 0.12, 0.0 and 0.60 respectively, comparing vision at 6 months and 12 months to baseline, Student t test for paired data). The researchers noted retinal pigment epithelium rips in three eyes in Group 1, in one eye in Group 2 and in two eyes in Group 3.

Source: Montero JA, Ruiz-Moreno JM, Sanabria RM, Fernandez-Munoz M. Efficacy of intravitreal and periocular traimcinolone associated with photodynamic therapy to treat retinal angiomatous proliferation. Br J Ophthalmol 2008; Oct 29 [Epub ahead of print].

Therapeutic Effect of Intravitreal Bevacizumab on Active Progressive Proliferative Diabetic Retinopathy
To evaluate the efficacy of intravitreal administration of bevacizumab (IVB) in eyes with active, progressive proliferative diabetic retinopathy (PDR), 38 eyes of 38 patients (mean age = 54.7 ± 10.1 years) received one to three IVB injections (1.25 mg) at intervals of either 6 or 12 weeks. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12 and 20 weeks after the first injection, while fluorescein angiography (FA) was performed before injection and 20 weeks after. The primary outcome measures were clearing of vitreous hemorrhage (VH) and regression of active fibrovascular tissue (FVT). The secondary outcomes were any change in best-corrected visual acuity (BCVA) and any incidence of adverse events.

VH resolved significantly after 1 week (p = 0.014), 12 weeks (p = 0.0001) and 20 weeks (p = 0.002). The vascular component of FVT regressed, though the FVT area did not change. Mean BCVA improved significantly compared to baseline at all follow-up examinations. Two cases showing moderate fibrous proliferation developed traction retinal detachment (TRD).

While IVB has significant therapeutic effect on eyes with active, progressive PDR, it causes a significant amount of VH resolution and neovessel regression and the procedure may increase the risk of TRD in eyes with fibrous proliferation.

Source: Moradian S, Ahmadieh H, Malihi M, et al. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2008; 246(12):1699-1705.