Choroidal Neovascularization Industry

Angiogenesis is a key aspect of the wet form of age-related neovascular (AMD), the leading cause of blindness in the elderly population. Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C, VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be generated due to alternative mRNA splicing. Various VEGF inhibitors have been clinically developed. Among these, ranibizumab is a high affinity recombinant Fab that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology of VEGF and then focuses on the path that led to clinical development of ranibizumab. The safety and efficacy of ranibizumab in the treatment of neovascular AMD have been evaluated in two large phase III, multicenter, randomized, double-masked, controlled pivotal trials in different neovascular AMD patient populations. Combined, the trial results indicate that ranibizumab results not only in a slowing down of vision loss but also in a significant proportion of patients experiencing a clinically meaningful vision gain. The visual acuity benefit over control was observed regardless of CNV lesion type. Furthermore, the benefit was associated with a low rate of serious adverse events. Ranibizumab represents a novel therapy that, for the first time, appears to have the potential to enable many AMD patients to obtain a meaningful and sustained gain of vision. On June 30 2006, ranibizumab was approved by the US Food and Drug Administration for the treatment of wet AMD.

The vast majority of diseases that cause catastrophic loss of vision do so as a result of ocular neovascularization. During normal retinal vascular development, vascular endothelial cells proliferate and migrate through the extracellular matrix in response to a variety of cytokines, leading to the formation of new blood vessels in a highly ordered fashion. During abnormal neovascularization of the iris, retina, or choroid, angiogenesis is unregulated and usually results in the formation of dysfunctional blood vessels. When these newly formed vessels leak fluid, hemorrhage, or are associated with fibrous proliferation, retinal edema, retinal/vitreous hemorrhage, or traction retinal detachments may occur resulting in potentially catastrophic loss of vision. In this review, we will briefly discuss the scope of the clinical problem and the general underlying principles of angiogenesis. We will focus on recent laboratory advances that have led to the development of therapeutics useful in the treatment of neovascular eye diseases. We will describe compounds currently in pre-clinical development stages as well as the results of clinical trials involving the use of these drugs as treatments for ocular neovascularization.

Central serous chorioretinopathy (CSCR) is an ocular disease characterized by serous detachment of the neurosensory retina at the posterior pole, with or without an associated retinal pigment epithelium (RPE) detachment. It is associated with different systemic diseases although the pathogenesis is unknown. Different therapies have been applied to treat CSCR with poor results. We reviewed the literature and found that in all the diseases associated with CSCR plasminogen activator inhibitor 1 (PAI-1) was increased. Acetyl salicylic acid (Aspirin) is effective in lowering PAI-1 levels and platelets aggregation; as such we decided to treat patients affected by CSCR with low dose Aspirin.

Purpose: To report long-term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis. Methods: Files of patients receiving 1.25 mg ⁄ 0.05 ml bevacizumab as primary local treatment for CNV were retrospectively reviewed. Main outcomes were change in best-corrected visual acuity (BCVA) and central foveolar thickness (CFT), treatment-related adverse events, and number and frequency of injections. Results: Fifteen eyes from fifteen patients were included. Multifocal choroiditis and panuveitis were the diagnosis in seven, ampiginous choroiditis in two, and for six remaining, serpiginous choroiditis, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, punctuate inner choroidopathy, tuberculosis and idiopathic inflammation. In 13 eyes, neovascularization was subfoveal, and peripapillary in two. Intraocular inflammation was strictly controlled in all cases by the time of injections. BCVA improved from logMar 0.53 to logMar 0.29 in 12 eyes (80%), while CFT decreased from 239.06 to 195.2 lm in 13 (87%). Twelve eyes received more than one injection; mean number in this group was 4.25 (2-8), and frequency 1 every 12.97 weeks. There were no adverse events related to bevacizumab or the procedure. Median follow-up was 17.6 months (8-25). Conclusions: First-intention IVT bevacizumab for inflammatory CNV showed transient improvement in BCVA and CFT, in eyes under controlled inflammation. Reinjection was needed in most cases. Further work should conclude about safety related to repeated injections.

Background Verteporfin photodynamic therapy (PDT) is approved for the treatment of predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), as well as for subfoveal CNV due to pathologic myopia and ocular histoplasmosis syndrome. Verteporfin PDT addresses the underlying pathology of ocular vascular disorders through its angio-occlusive mechanism of action, which reduces both visual acuity loss and the underlying leakage associated with lesions. Verteporfin PDT has also been associated with encouraging treatment outcomes in case studies involving patients with choroidal vascular disorders such as polypoidal choroidal vasculopathy, central serous chorioretinopathy, choroidal haemangioma, angioid streaks, and inflammatory CNV, i.e.

Purpose: To investigate the relationship between optical coherence tomography (OCT)-derived measurements of retinal morphology and visual acuity in patients with diabetic macular edema. Design: Retrospective cross-sectional study. Participants: A total of 67 consecutive patients (67 eyes) with diabetic macular edema (DME) who underwent Stratus OCT imaging (Carl Zeiss Meditec, Inc., Dublin, CA).

Purpose: To investigate the relationship between optical coherence tomography (OCT)-derived measurements of retinal morphology and visual acuity in patients with neovascular age-related macular degeneration (AMD). Design: Retrospective cross-sectional study. Participants: A total of 216 consecutive patients (216 eyes) newly diagnosed with neovascular AMD who underwent StratusOCT imaging at the time of diagnosis.

In this report, spectral-domain optical coherence tomography (OCT) was used to characterize the acute morphologic alterations that occur when photodynamic therapy with verteporfin results in an acute severe visual decrease. The clinical and imaging records of a patient with neovascular age-related macular degeneration who suffered this complication were reviewed. Using spectral-domain OCT, two relatively distinct subretinal fluid compartments were visualized: a sparsely hyperreflective pocket of subretinal fluid overlying the fibrovascular pigment epithelial detachment, consistent with fibrinous exudation, and a more homogenously hyporeflective compartment at the periphery of the choroidal neovascular lesion, consistent with serous exudation. The higher axial resolution, and greater sensitivity, of spectral-domain OCT allows improved visualization of the subretinal space. As experience with spectral-domain OCT grows, new parameters will emerge-such as those related to subretinal fluid-that will facilitate improvements in both the qualitative and quantitative evaluation of macular disease. [Ophthalmic Surg Lasers Imaging 200;4:SXX-SXX.]

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD).

Background To correlate the volume of various spaces on optical coherence tomography (OCT) with fluorescein angiographic (FA) parameters in neovascular age-related macular degeneration (AMD). Methods Sixty-five consecutive cases of active subfoveal choroidal neovascularization (CNV) associated with AMD were retrospectively collected. Area and greatest linear dimension of CNV lesion components were calculated on FA. Corresponding StratusOCT image sets were analyzed using custom software (termed OCTOR), which allows manual measurement of the volume of the neurosensory retina, subretinal fluid, subretinal tissue, and pigment epithelial detachment (PED). Results Area of occult CNV on FA correlated with PED (R=0.62) and subretinal fluid (R=0.28) volume and negatively with subretinal tissue volume (R= −0.26) on OCT. Area of classic CNV on FA correlated with subretinal tissue (R=0.60) and retinal (R=0.38) volume on OCT. Automated StratusOCT output values showed poorer correlations than manually calculated OCTOR values.

To evaluate the safety and efficacy of photodynamic therapy (PDT) with verteporfin in the treatment of patients with choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSC). Open-label, two-center, noncomparative, prospective interventional case series. Consecutive patients with subfoveal or juxtafoveal CNV secondary to CSC were recruited and treated with a standard regimen of PDT with verteporfin. At regular 3-month follow-up examinations, re-treatment was considered if fluorescein angiography showed evidence of leakage. Outcome measures included the proportion of patients who had improvement (gained 2 more lines), stable, or loss (dropped in 2 or more lines) in vision at the final follow-up and the changes in best-corrected visual acuity (BCVA) from baseline. Ten eyes of 10 patients were recruited into the study. The mean age of the patients was 57.3 years with a mean follow-up duration of 12.6 months. At the last follow-up, six (60%) eyes gained 2 or more lines of BCVA with four (40%) patients having final BCVA of within 1 line. No patient lost 2 or more lines of BCVA. The mean logarithm of the minimal angle of resolution BCVA improvement after PDT was 2.4 lines (Wilcoxon signed-rank test, P =.013). No patient suffered serious ocular or systemic complications from PDT. Photodynamic therapy with verteporfin therapy is a safe and well-tolerated treatment in patients with CNV associated with CSC. A randomized, controlled trial with a longer follow-up period is warranted to further study the efficacy of PDT in the management of CNV secondary to CSC.

Age-related macular degeneration (AMD) is the major cause of blindness in the elderly. Those with the neovascular end-stage of disease have irreversible loss of central vision. AMD is a complex disorder in which genetic and environmental factors play a role. Polymorphisms in the complement factor H (CFH) gene, LOC387715, and the HTRA1 promoter are strongly associated with AMD. Smoking also contributes to the etiology. We aimed to provide a model of disease risk based on these factors.

Polarization sensitive OCT has recently been shown to provide tissue specific contrast, enabling direct identification of retinal layers based on the intrinsic properties of their interaction with light. However, the capabilities of displaying and analyzing 3D datasets in scientific publications were rather limited. Within the framework of the Interactive Science Publishing project, we present new ways of displaying and analyzing 3D sets of various polarization parameters recorded in healthy and diseased human retinas. These datasets can be interactively explored by the reader. Furthermore, we provide data of the 3D distribution of backscattered Stokes vectors to allow the reader to develop and test their own data processing algorithms.

To use optical coherence tomography (OCT) to quantify intraretinal cystoid spaces (ICSs) and the outer nuclear layer (ONL) in patients with neovascular age-related macular degeneration (AMD) and to investigate the correlation of these parameters with visual acuity. METHODS. StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) images were collected from 53 patients receiving their initial treatment with intravitreous ranibizumab. Images were analyzed with custom software (OCTOR) that allows accurate manual segmentation of OCT B-scans and provides thickness/ volume measurements of ICS, ONL, neurosensory retina, pigment epithelial detachments (PEDs), subretinal fluid (SRF), and subretinal tissue (SRT). Univariate and multivariate analyses were used to correlate OCT parameters with best corrected Snellen visual acuity. Reproducibility was assessed with weighted statistics and intraclass correlation coefficients.

To determine the characteristics of patients with neovascular age-related macular degeneration who show initial anatomic improvements on optical coherence tomography in response to treatment with ranibizumab, but who subsequently regress toward their anatomic baseline.

Purpose: To evaluate best-corrected visual acuity (BCVA) and foveal thickness (FT) changes in occult subfoveal choroidal neovascularization (CNV) from agerelated macular degeneration (AMD) after intravitreal bevacizumab (IVB, 1.25 mg ⁄ 0.05 ml), pegaptanib (IVP, 0.3 mg ⁄ 0.09 ml) and triamcinolone acetonide (IVTA, 4 mg ⁄ 0.1 ml) injected on an as needed basis. Methods: Retrospective, interventional, comparative study. BCVA (Early Treatment Diabetic Retinopathy Study LogMAR) and FT by optical coherence tomography (OCT) were evaluated during 12 months from first treatment. Patients were retreated if signs of neovascular activity were still present on angiography or OCT. Results: Forty-eight eyes received IVB, 43 eyes received IVP, 52 eyes received IVTA. BCVA and FT at baseline were 1.22 ± 0.49 LogMAR and 410.2 ± 41.83 lm in the IVB group, 1.25 ± 0.43 LogMAR and 452.3 ± 44.83 lm in the IVP group and 1.31 ± 0.4 LogMAR and 456.6 ± 48.27 lm in the IVTA group. BCVA and FT improved in the three groups during follow-up. A significantly greater improvement of BCVA was present at month-3, month-6 and at month-12 in the IVB and IVP groups (p = 0.01). Improvement of FT was greater in the IVTA group at month-3 (p = 0.02), while it was greater in the anti-Vascular Endothelial Growth Factor (VEGF) groups at month-6 and month-12 (p = 0.01). A postoperative increase of intraocular pressure was detected in 9 ⁄ 52 (17.3%) eyes treated with IVTA, and in two cases it was resistant to topical therapy. Conclusion: Intravitreal injection of anti-VEGF drugs administered on an as needed basis for AMD-related occult CNVs provided functional and anatomic improvement during 12 months of follow-up.

To evaluate the quality of reporting in the neovascular age-related macular degeneration (nvAMD) literature by applying the Consolidated Standards for Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement writing standards. CONSORT and STROBE impact analysis; literature review. Phase III randomized controlled trials (RCTs) of verteporfin photodynamic therapy, pegaptanib, and ranibizumab, and interventional case studies of bevacizumab for nvAMD. A literature search identified eligible articles published before October 31, 2007. We assessed the report quality of Phase III RCTs using the CONSORT statement and case series publications using the STROBE statement, both with indicators relevant to nvAMD. Presence or absence of CONSORT or STROBE statement indicators. Seven publications of Phase III RCTs and 29 publications on bevacizumab interventional case studies for nvAMD met our inclusion criteria. Of 37 possible CONSORT writing guideline items, the mean report quality for RCTs was 30.6 (83%), with a range from 23 to 35 (65%-95%). Of 35 possible STROBE writing guideline items, the mean report quality grade for intravitreal bevacizumab case series was 23 (70%), with a range from 16 to 31 (46%-94%). Among the bevacizumab studies, more than 90% reported scientific background, drug dose and administration, baseline characteristics, unadjusted results, and adverse events. Fewer than 20% reported study size calculations, handling of missing data, or a discussion of bias. Since the adoption of the CONSORT standards by Ophthalmology and other journals in 1996, the reporting quality for RCTs has further improved among this cohort of nvAMD articles. On the other hand, no reporting standards for case series have existed until the recent publication of the STROBE statement. In this first application of the STROBE standards to ophthalmology, we found that the small interventional studies in our series had an average reporting score lower than the RCTs, but also that some individual scores were higher than the RCTs. This outcome demonstrates that good, useful articles can be written about small studies. Although not a direct measure of the quality of a study, good reporting allows a reader to assess the validity and applicability of the study's findings. Proprietary or commercial disclosure may be found after the references.

PURPOSE: To report the use of intravitreal injection of triamcinolone acetonide during the acute phase of Vogt-Koyanagi-Harada disease. DESIGN: Prospective interventional case series. METHODS: Three eyes from two patients at the acute phase of Vogt-Koyanagi-Harada disease with serous retinal detachments were treated with a 4-mg intravitreal injection of triamcinolone acetonide. The following variables were evaluated: visual acuity, intraocular pressure, and height of the serous retinal detachment using optical coherence tomography. RESULTS: The optical coherence tomography images showed a marked decrease in the retinal detachment in the first week after the injection with subsequent return to normal retinal thickness in all eyes. CONCLUSIONS: Intravitreal triamcinolone acetonide provides short-term improvement in visual acuity and serous retinal detachments associated with Vogt-Koyanagi-Harada disease. These findings should be followed by

Purpose To evaluate the effect of photodynamic therapy (PDT) on the choriocapillaris and retinal pigment epithelium (RPE) in the irradiated area surrounding choroidal neovascularization (CNV) during 12 months of follow-up. Methods We reviewed the medical records, and indocyanine green angiography (IA), fluorescein angiography (FA), and fundus photographic findings of 72 eyes (72 patients) with CNV associated with age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). Patients were divided into three groups based on the number of PDT sessions. Twelve months after PDT, we evaluated the relationship between the number of sessions and both the presence of hypofluorescence in the late phase of IA and window defects observed on FA in the irradiated areas. Results Twenty-three patients had one PDT session (group I), 25 had two (group II), and 24 had three or four (group III). IA revealed hypofluorescence indicating a choriocapillaris filling defect within the irradiated area in 11 eyes (48%) in group I, 18 (72%) in group II, and 22 (91%) in group III. The correlation between the number of PDT sessions and hypofluorescence in the irradiated areas was significant. FA showed window defects surrounding CNV in 26%, 52%, and 71% of eyes from groups I, II, and III, respectively. Subretinal hemorrhages had been present in 23 eyes (32%) and exudation in 13 (18%) prior to PDT. Areas without hemorrhages or exudation prior to PDT had a normal appearance within the irradiated area in all 72 eyes. Conclusions Although the RPE in the irradiated area was preserved, 12 months after PDT, mild choriocapillaris occlusion was detected in the irradiated area in eyes that had undergone multiple PDT sessions.

Choroidal neovascularization (CNV) is a common manifestation of age-related macular degeneration (AMD). It is characterized by the growth of abnormal blood vessels in the choroidal layer causing blurring and deterioration of the vision. In late stages, these abnormal vessels can rupture the retinal layers causing complete loss of vision at the affected regions. Determining the CNV size and type in fluorescein angiograms is required for proper treatment and prognosis of the disease. Computer-aided methods for CNV segmentation is needed not only to reduce the burden of manual segmentation but also to reduce inter-and intraobserver variability. In this paper, we present a framework for segmenting CNV lesions based on parametric modeling of the intensity variation in fundus fluorescein angiograms. First, a novel model is proposed to describe the temporal intensity variation at each pixel in image sequences acquired by fluorescein angiography. The set of model parameters at each pixel are used to segment the image into regions of homogeneous parameters. Preliminary results on datasets from 21 patients with Wet-AMD show the potential of the method to segment CNV lesions in close agreement with the manual segmentation.

While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls.

Purpose-Doxycycline, a broad spectrum antibiotic, has certain anti-angiogenic properties and can inhibit matrix metalloproteinases (MMPs/gelatinases). We investigated the effects of doxycycline on choroidal neovascularization (CNV), and regulation of MMP-2/-9 and pigment epitheliumderived factor (PEDF).

Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 ml of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 ml of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 ml of Matrigel only; three rabbits used as controls received subretinal injections of 20 ml phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.