Choroidal Neovascularization Industry

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.

Nonstandard abbreviations used: AMD, age-related macular degeneration; BM, Bruch's membrane; CCL2, CC chemokine ligand 2; CCR2, CC chemokine receptor 2; CNV, choroidal neovascularization; CX3CL1, CX3C chemokine ligand 1; CX3CR1, CX3C chemokine receptor 1; MC, microglial cell; OS, outer segment; RPE, retinal pigment epithelium; SrMC, subretinal MC.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30 -50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD.

Macrophage recruitment to the choroid has been proposed to contribute to the pathogenesis of choroidal neovascularization (CNV) in AMD. The study was conducted to determine whether treatment with clodronate liposomes (CL 2 MDP-lip), which cause depletion of blood monocytes and lymph node macrophages, diminishes the severity of neovascularization in a mouse model of laser-induced CNV. METHODS. Laser-induced CNV was performed in female 16month-old C57BL/6 mice. Macrophages were depleted by use of CL 2 MDP-lip intraperitoneally and subcutaneously 72 and 24 hours before and every 2 to 3 days after laser injury. Control mice received injections of either PBS alone or PBS liposomes. Blood monocyte and choroidal macrophage depletion were documented by flow cytometry and choroidal flatmount preparation analysis, respectively. Two weeks after laser injury, mice were injected intravenously with fluoresceinated dextran. The right eyes were removed and prepared for flatmount analysis of CNV surface area (in relative disc areas or DA), vascularity (relative fluorescence), and cellularity (propidium iodide stain). The mice were then perfused with 10% formaldehyde, and the left eyes were removed for histopathology. The means of the various parameters for four CNV lesions per eye were calculated. Fluorescein angiography was also performed. RESULTS. Flow cytometry of circulating monocytes and immunohistochemical analysis of choroidal macrophage density confirmed the effective depletion of blood monocytes and choroidal macrophages respectively in CL 2 MDP-lip-treated mice. Compared with the control, flatmount analysis of macrophage depleted mice demonstrated a significant reduction in size of the CNV area (2.8 Ϯ 0.5 DA vs. 1.4 Ϯ 0.1 DA; P Ͻ 0.043). The treated group also revealed less vascularity (1.6 Ϯ 0.1 units vs. 1.1 Ϯ 0.0 units; P Ͻ 0.0092) and cellularity of CNV lesions (3.3 Ϯ 0.6 DA vs. 1.7 Ϯ 0.1 DA, P Ͻ 0.04). Histopathology revealed that, in the macrophage-depleted group, CNV was smaller in diameter (1270 Ϯ 73 pixels vs. 770 Ϯ 82 pixels, P Ͻ 0.0006) and thickness (120 Ϯ 7 pixels vs. 96 Ϯ 7 pixels, P Ͻ 0.019).

In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 (vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site and reduced its levels in cultured endothelial cells and in mouse models of retinal and choroidal neovascularization (CNV). Compared to injection of an inverted control sequence, quantitative reverse transcriptase-PCR demonstrated statistically significant reductions of 57 and 40% in vegfr1 mRNA after intravitreous or periocular injection of Sirna-027, respectively. Staining showed uptake of 5-bromodeoxyuridine-labeled Sirna-027 in retinal cells that lasted between 3 and 5 days after intravitreous injection and was still present 5 days after periocular injection. In a CNV model, intravitreous or periocular injections of Sirna-027 resulted in significant reductions in the area of NV ranging from 45 to 66%. In mice with ischemic retinopathy, intravitreous injection of 1.0 mg of Sirna-027 reduced retinal NV by 32% compared to fellow eyes treated with 1.0 mg of inverted control siRNA. These data suggest that VEGFR1 plays an important role in the development of retinal and CNV and that targeting vegfr1 mRNA with siRNA has therapeutic potential. Gene Therapy (2006) 13, 225-234.

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The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (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.

Abnormal angiogenesis plays a key role in diseases of aging such as heart disease, certain cancers, and eye diseases including age-related macular degeneration. Macrophages have been shown previously to be both anti-and proangiogenic, and their role in regulating angiogenesis at sites of tissue injury is critical and complex. In this study, we analyzed cytokine gene expression patterns of mouse macrophages by realtime quantitative PCR and tested the functional effects of senescence on gene expression and macrophage polarization. Following laser injury to the retina, IL-10 was upregulated and Fas ligand (FasL), IL-12, and TNF-α were downregulated in ocular macrophages of old mice (>18 months of age). Downregulation of FasL on macrophages led to a loss of the antiangiogenic phenotype, as evidenced by the inability of these macrophages to inhibit vascular endothelial cells. Our results demonstrate that senescence, FasL, and IL-10 are key determinants of macrophage function that alter the growth of abnormal postdevelopmental blood vessels in disease processes including blinding eye disease.

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).

To assess the safety, pharmacokinetics, and biological activity of IV administration of vascular endothelial growth factor trap (VEGF Trap), a recombinant protein containing the binding domains of VEGF receptors 1 and 2, in patients with neovascular age-related macular degeneration (AMD).

Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration" RPE tears after intravitreal bevacizumab injections Abstract Purpose: To determine the incidence of and the risk factors for the development of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab (Avastin) injection for the treatment of exudative age-related macular degeneration (AMD).

PURPOSE. Age-related macular degeneration (ARMD) is the primary cause of blindness in people aged of 50 years or more. The wet form leads to severe loss of central vision. Recent evidence supports that adult hematopoietic stem cells (HSCs) contribute to preretinal neovascularization. In the current study, it was determined whether HSCs, by producing both blood and blood vessels, provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice. METHODS. Gfp chimeric mice were developed by bone marrow ablation of C57BL/6J mice and reconstitution with donor tissue from gfp ϩ/ϩ transgenic mice. Gfp chimeric mice underwent laser rupture of Bruch's membrane and were killed and eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by confocal microscopy of retinal flatmounts. Because endothelial progenitor cells (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the EPC contribution to CNV. RESULTS. Laser injury alone was sufficient to induce stem cell recruitment and subsequent CNV. Gfp ϩ cells formed part of the functional vasculature in the choroid as early as 1 week after injury and were present for the duration of the study. The relative EPC contribution to CNV remained fairly constant throughout the study and constituted almost 50% of the total vasculature. CONCLUSIONS. Adult stem cells are recruited to the choroid in a model of CNV, where they contribute to forming aberrant new vessels. This observation suggests that targeting stem cell recruitment to the eye may offer a novel therapeutic strategy for ARMD. (Invest Ophthalmol Vis Sci. 2003;44:4908 -4913)

To study the long-term effects of photodynamic therapy (PDT), using liposomal benzoporphyrin derivative (BPD) or Verteporfin, on experimental choroidal neovascularization (CNV) and on normal retina and choroid (with no CNV) in the cynomolgus monkey eye. Photodynamic therapy was performed in 8 cynomolgus monkey eyes with experimental CNV induced by laser injury. The effect of PDT on normal retina and choroid (with no CNV) was studied in 9 monkey eyes. Liposomal BPD was administered intravenously (0.375 mg/kg) either as a bolus, as a slow infusion over 32 minutes, or as a fast infusion over 10 minutes. Photodynamic therapy was performed using light at a wavelength of 689 or 692 nm, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2. Follow-up studies, including fundus photography and FA, were performed at 24 hours after PDT and then weekly. Indocyanine green and BPD angiography were performed in selected cases. Tissues were examined with light and electron microscopy at the end...

Purpose: To report the efficacy of a single intravitreal injection of bevacizumab (IVB) alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as primary treatment for diabetic macular edema (DME). Methods: This randomized three-arm clinical trial included 103 eyes of 97 patients with clinically significant DME and no previous treatment. The eyes were randomly assigned to one of the three study arms: the IVB group received 1.25 mg IVB (37 eyes), the IVB/IVT group received 1.25 mg IVB together with 2 mg IVT (33 eyes), and the MPC group underwent focal or modified grid laser photocoagulation (33 eyes). Primary outcome measure was change in best-corrected visual acuity (BCVA). Results: Changes in BCVA (logMAR) at 12 weeks were -0.22±0.23, -0.13±0.31 and +0.08±0.31 in the IVB, IVB/IVT and MPC groups, respectively. The marginal regression model based on generalized estimating equation analysis demonstrated that changes in visual acuity was statistically significant in the IVB group at both 6 (P<0.001) and 12 (P=0.024) weeks but only at 6 weeks in the IVB/IVT group. Significant decrease in central macular thickness (CMT) was observed in the IVB and IVB/IVT groups at 6 weeks. Conclusion: Up to 12 weeks, IVB treatment in eyes with DME yielded better visual outcome than laser photocoagulation, although it was not associated with a significant decrease in CMT. IVT seemed to have no further beneficial effect in combination with IVB.

PURPOSE. Cigarette smoking is the strongest environmental risk factor for all forms of age-related macular degeneration (AMD). In the present study, the influence of nicotine on the severity of choroidal neovascularization (CNV) in a mouse model of neovascular AMD and its effects on vascular smooth muscle cells derived from mouse choroid were investigated.

To determine the effects of an adenovirus vector encoding vascular endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the rat. An E1-deleted adenoviral vector encoding VEGF was injected into the subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF expression. Histopathologic changes in the retina were determined by light and electron microscopy, immunohistochemistry, fluorescein angiography, and examination of wholemounts of choroid and retina. Increased expression of VEGF only in the retinal pigment epithelium (RPE) was detected after Ad.VEGF injection. Histopathology of these eyes revealed minimal subretinal exudation at 1 week followed by the appearance of vascular structures in the subretinal space by week 2, which persisted up to 4 weeks. Shortening of photoreceptor outer segments and reduction of the outer nuclear layer were present overlying areas of neovascularization. Fluorescein angiography of animals injected with fluorescei...

To investigate the role of the leukocyte adhesion molecules CD18 and intercellular adhesion molecule (ICAM)-1 in the development of choroidal neovascularization (CNV). METHODS. Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CD18 or ICAM-1 gene. Expression of CD18 and ICAM-1 after laser injury was assessed by immunostaining. CNV responses were compared on the basis of en masse volumetric measurements obtained by confocal microscopy 2 weeks after laser injury and by determination of fluorescein angiographic leakage at 1, 2, and 4 weeks after laser injury. RESULTS. The site of laser injury showed upregulation of ICAM-1 and invasion by CD18-positive leukocytes within 1 day of laser injury. Significantly fewer lesions exhibited fluorescein leakage defined to be pathologically significant in CD18-deficient mice at weeks 1, 2, and 4 weeks and in ICAM-1-deficient mice at 1 and 4 weeks, compared with the control. There were a significantly greater number of lesions without fluorescein leakage in CD18-deficient mice than in the other two groups at all time points. The volume of CNV in CD18-and ICAM-1-deficient mice was significantly less than in wild type. CONCLUSIONS. These data suggest a nonredundant role for leukocyte adhesion to vascular endothelium in the development of laser-induced choroidal neovascularization. (Invest Ophthalmol Vis Sci.

To investigate the effects of ranibizumab on retinal morphology in patients with neovascular age-related macular degeneration (AMD) using optical coherence tomography (OCT) quantitative subanalysis. METHODS. Data from 95 patients receiving intravitreal ranibizumab for neovascular AMD were collected. StratusOCT images were analyzed using custom software that allows precise positioning of prespecified boundaries on every B-scan. Changes in thickness/volume of the retina, subretinal fluid (SRF), subretinal tissue (SRT), and pigment epithelial detachments (PEDs) at week 1 and at months 1, 3, 6, and 9 after treatment were calculated. RESULTS. Total retinal volume reached its nadir at month 1, with an average reduction of 0.43 mm 3 (P Ͻ 0.001). By month 9, this initial change had been reduced to a mean reduction of 0.32 mm 3 (P ϭ 0.0011). Total SRF volume reached its lowest level by month 1, with an average reduction of 0.24 mm 3 (P Ͻ 0.001). This reduction lessened subsequently, to 0.18 mm 3 , by month 9. There was an average 0.3-mm 3 decrease in total PED volume by month 1 (P Ͻ 0.001), and this later declined further, to 0.45 mm 3 , by month 9 (P ϭ 0.0014). Total SRT volume was reduced by an average of 0.07 mm 3 at month 1 (P ϭ 0.0159) and subsequently remained constant. CONCLUSIONS. Although neurosensory retinal edema and SRF showed an early reduction to nadir after the initiation of ranibizumab therapy, the effect on the retina was attenuated over time, suggesting possible tachyphylaxis. PED volume showed a slower but progressive reduction. Manual quantitative OCT subanalysis may allow a more precise understanding of anatomic outcomes and their correlation with visual acuity. (Invest Ophthalmol Vis Sci. 2008;49:3115-3120)

PURPOSE. Age-related macular degeneration (AMD), with its complex traits and multiple risk factors, is the leading cause of blindness in the elderly. A strong association between a coding variant, Y402H, in the complement factor H gene (CFH) and AMD has been recently identified in white patients. This study was conducted to investigate the association between the Y402H polymorphism in CFH and neovascular AMD in Chinese patients.

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.

The pro-inflammatory cytokine IL-1␤ has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1␤ in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1␤ expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1 ؊/؊ model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1 ؉/؉ and Cx3cr1 ؊/؊ mice (enzymelinked immunoabsorbent assay) after light injury. IL-1␤ was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1␤ significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1␤ on choroidal endothelial cell proliferation. Inhibition of IL-1␤ in light-and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1 ؊/؊ mice. Our results suggest that IL-1␤ inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.

Purpose To evaluate the efficacy and safety of intravitreal bevacizumab therapy for neovascular age-related macular degeneration (ARMD). Methods Patients with diagnosis of neovascular ARMD without any other ocular pathology were injected with 2.5 mg of intravitreal bevacizumab. A complete ophthalmic examination was undertaken in all patients, including best corrected visual acuity (BCVA), slit lamp biomicroscopy and ocular fundus examination. Ophthalmic follow-up evaluations included visual acuity measurements, optical coherence tomography (OCT) imaging, and fluorescein angiography at first, second and fourth week post injection. Results 39 eyes of 39 patients were injected. The median age was 76 years-old (range 65–90), median visual acuity was 1.18 logMAR (range 0.18–3.00) and median retinal thickness was 388 microns (range 157–1237). By the fourth week of treatment, the median visual acuity was 0.88 (range 0.18–2.78) and median retinal thickness was 247 microns (range 108–1262). Statistically significant differences were found in visual acuity and retinal thickness before and after intravitreal injection (p=0.002, p Conclusions Our results suggest that intravitreal bevacizumab is well tolerated and is associated with improvement in BCVA and decreased mean retinal thickness by OCT. Further controlled and long term evaluation of intravitreal bevacizumab for the treatment of neovascular ARMD is warranted.

To report two cases of exudative idiopathic polypoidal choroidal vasculopathy treated by photodynamic therapy with verteporfin. Interventional case reports. Two patients, a man aged 58 years and a woman aged 57 years, with recent visual impairment in the right eye (OD) (both eyes best-corrected visual acuity: 10/50 and Pelli-Robson contrast sensitivity 1.35 and 1.20) and angiographically proved subfoveal idiopathic polypoidal choroidal vasculopathy were treated with photodynamic therapy using verteporfin (Visudyne; Novartis SA, Rueil Malmaison, France). Functional and angiographic outcomes were assessed 6 weeks and 3, 6, and 12 months after treatment. In Patient 1, 3 months after treatment, best-corrected visual acuity and contrast sensitivity improved (10/16 and 1.50) and then remained stable throughout the 12 months after treatment. In Patient 2, 6 weeks after treatment, vision and contrast sensitivity were 10/20 and 1.35; and at 3 months, were improved and stabilized at 10/12.5 and 1.50. Angiographically, photodynamic therapy with verteporfin was associated with nonperfusion and occlusion of the exudative polypoidal dilations. No acute recurrence was noted during the follow-up period. In subfoveal exudative idiopathic polypoidal choroidal vasculopathy, photodynamic therapy with verteporfin may be associated with beneficial functional results.

Nonstandard abbreviations used: ALK1, activin receptor-like kinase 1; AMD, age-related macular degeneration; BMOV, bis(maltolato)oxovanadium(IV); CNV, choroidal neovascularization; PAI-1, plasminogen activator inhibitor type I; PlGF-1, placental growth factor-1; PTP, protein tyrosine phosphatase; RPE, retinal pigmented epithelium; SH2, Src homology domain 2; SHP-1, SH2-containing tyrosine phosphatase-1; SPARC, secreted protein, acidic and rich in cysteine.

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. Oral administration of PKC412, a kinase inhibitor that blocks several isoforms of protein kinase C (PKC) and receptors for vascular endothelial growth factor (VEGF), plateletderived growth factor, and stem cell factor, inhibits ocular neovascularization in a murine model. The purpose of this study was to determine whether sustained local delivery of PKC412 in a human-sized eye inhibits choroidal neovascularization (CNV). METHODS. Laser photocoagulation was used to rupture Bruch's membrane in young domestic pigs, and then a periocular injection of control microspheres or microspheres containing 25% or 50% PKC412 was given. After 10 days the integrated area of CNV at Bruch's membrane rupture sites was measured by image analysis. The levels of PKC412 in choroid, retina, and vitreous were measured either 10 or 20 days after periocular injection of 50% PKC microspheres or at 20 days after injection of 25% PKC412 microspheres. RESULTS. The areas of CNV at Bruch's membrane rupture sites were significantly smaller in eyes that received a periocular injection of microspheres containing 25% (P ϭ 0.0042) or 50% (P ϭ 0.0012) PKC412 than those in eyes injected with control microspheres. Ten days after periocular injection of 50% PKC412 microspheres, PKC412 was detected in the choroid, but not in the retina or vitreous. Twenty days after periocular injection of 50% PKC412, high levels of PKC412 were measured in the choroid, vitreous, and retina. Levels were lower but still substantial in all three compartments 20 days after periocular injection of 25% microspheres.

PURPOSE: To evaluate the effects of subfoveal choroidal neovascularization secondary to age-related macular degeneration on functional parameters obtained by scanning laser ophthalmoscope microperimetry. • DESIGN: Retrospective observational case series and cross-sectional study. • METHODS: At the Doheny Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration was studied. The onset of visual symptoms, best-corrected visual acuity, fluorescein angiography, evaluation of fundus microperimetry and fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained for each patient. The main outcome measures were central retinal sensitivity and fixation pattern (fixation location and fixation stability) in eyes with subfoveal choroidal neovascularization and their relationship to the length of disease, type and characteristics of choroidal neovascularization, and visual acuity. • RESULTS: Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor central fixation, and 17 (9%)

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.

PURPOSE: To identify predictive factors for visual outcome and need for retreatment after treating myopic choroidal neovascularization (CNV) with ranibizumab. • DESIGN: A prospective interventional case series. • METHODS: Sixty-seven eyes of 67 patients with myopic CNV were treated with 3 intravitreal ranibizumab injections given monthly. Best-corrected visual acuity (BCVA) and optical coherence tomography-determined central macular thickness (CMT) were recorded monthly during follow-up. Fluorescein angiography changes and the number of injections needed were also assessed. • RESULTS: Mean follow-up was 15.9 months. Mean BCVA improved by 7.8 letters after the first injection, 12.5 letters after 3 injections, and 12 letters by end follow-up. In 53 eyes (79.1%), BCVA improved; 40.3% gained more than 15 letters. No differences were detected in visual outcome between treatment-naïve and previously treated patients. Myopic CNV area and greatest linear dimension had diminished at the study end. The mean reduction in CMT was 93.6 m. The mean number of injections given was 4.2. A total of 53.7% of eyes received only 3 injections. Through regression analysis, baseline BCVA (P ‫؍‬ .006) and myopic CNV location (P ‫؍‬ .026) were significantly correlated with BCVA at the end of follow-up. Myopic CNV location (P ‫؍‬ .023) and prior treatment (P ‫؍‬ .047) were significantly linked to the number of injections given. No major complications arose. • CONCLUSION: An initial treatment regimen of 3 monthly ranibizumab injections seems effective and safe to treat myopic CNV. Baseline BCVA and myopic CNV location emerged as predictive factors for visual outcome. A need for retreatment was associated with myopic CNV location and prior treatment. (Am J Ophthalmol 2011; 151:529 -534.