Choroidal Neovascularization Diseases Research Articles

Differential diagnosis of myopic choroidal neovascularization (mCNV): insights from multimodal imaging and treatment implications.

The aim of this article is to conduct a comprehensive systematic review about the current understandings and differential diagnosis of myopic choroidal neovascularization (mCNV) and other several similar diseases, describing their multimodal imaging analysis, prognostic implications, and current types of management. This systematic review was performed based on a search on the PubMed database of relevant papers regarding mCNV and other entities discussed in the paper, according to our current knowledge. Through the integration of a multimodal imaging approach, especially optical coherence tomography (OCT), along with accurate demographic and clinical assessment, it becomes possible to effectively differentiate mCNV from similar yet heterogeneous entities. These conditions include macular hemorrhage due to new lacquer crack (LC) formation, inflammatory diseases such as punctate inner choroidopathy (PIC)/multifocal choroidits (MFC) and epiphenomenon multiple evanescent white dot syndrome (Epi-MEWDS), neovascular age-related macular degeneration (nAMD), idiopathic CNV (ICNV), dome-shaped macula (DSM) with subretinal fluid, retinal pigment epithelium (RPE) humps, angioid streaks (AS), choroidal rupture (CR), and choroidal osteoma (CO). Each one of these entities will be described and discussed in this article. Myopic choroidal neovascularization is a common retinal condition, especially among young individuals. Accurate diagnosis and differentiation from similar conditions are crucial for effective treatment. Multimodal imaging, particularly OCT, plays a crucial role in precise assessment. Future research should focus on defining biomarkers and distinguishing features to facilitate prompt treatment.

Chorioretinal Inflammatory Diseases in Pregnancy

Pregnancy is a long-term, temporary, physiological state that occurs in women's lives. Pregnancy is the period in which many anatomical and physiological changes occur to meet the needs of the developing fetus. During this period, various changes are seen in the eye. Some changes, especially in the immunological system, may cause some inflammatory chorioretinopathy in the posterior segment. This can cause different levels of vision loss. The main diseases seen during pregnancy are changes in choroid related to preeclampsia, hypertensive chorioretinopathy, central serous retinopathy, choroidal neovascularization, and vascular occlusive disease. This review, it is aimed to discuss the chorioretinal inflammatory diseases seen in pregnancy.

Key Multimodal Fundus Imaging Findings to Recognize Multifocal Choroiditis in Patients With Pathological Myopia.

Myopia represents a major socioeconomic burden with an increasing prevalence worldwide. Pathologic myopia refers to myopic patients with structural changes in the posterior pole including different patterns of chorioretinal atrophy, choroidal neovascularization (CNV) and vitreomacular tractional diseases. Multifocal choroiditis (MFC) is one of the most frequent noninfectious posterior uveitis, and epidemiologically typically affects young myopic females. Acute and chronic chorioretinal atrophic changes are the hallmark feature of MFC, with CNV developing in almost one third of cases. Thus, differentiation of inflammatory lesions due to MFC or neurodenegerative lesions due to pathologic myopic is key in order to establish a particular prognosis, follow-up schedule, and therapeutic approach. The aim of the present manuscript is to summarize and illustrate the main multimodal imaging features of these diseases.

Comparison of Intraocular Cytokine Levels of Choroidal Neovascularization Secondary to Different Retinopathies.

Purpose: To investigate and compare the aqueous concentrations of vascular endothelial growth factor (VEGF) and other inflammatory cytokines in various choroidal neovascularization (CNV) diseases and types.Methods: This observational study included 127 naive eyes with CNV and 43 control eyes with cataracts. Aqueous humor (AH) samples were obtained prior to intravitreal anti-VEGF injection or cataract surgery. Multiple inflammatory cytokines, including VEGF, interleukin (IL) 6, IL-8, IL-10, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels, were measured using a multiplex bead assay. The angiogenesis index was defined as the ratio of IP-10 to MCP-1. In addition, the relationship among AH cytokine levels, central macular thickness (CMT), and CNV size on optical coherence tomography angiography (OCTA) was evaluated.Results: Except in the myopic CNV group (P = 0.452), the AH concentration of VEGF was significantly higher in all other CNV groups than in the control group (P < 0.05 for all comparisons). IL-8, IL-10, IP-10, and MCP-1 levels (P < 0.05 for all groups) were significantly higher in all CNV diseases except those with neovascular central serous chorioretinopathy. The angiogenesis index was significantly higher in all CNV diseases (P < 0.05 for all comparisons). The VEGF level may be associated with the size of the CNV on OCTA (p = 0.043).Conclusions: The level of intraocular inflammatory cytokines varied among different CNV diseases and CNV types. Therefore, the angiogenesis index may be a more sensitive indicator of angiogenesis.

CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

Complement factor B gene polymorphisms and risk of age-related macular degeneration: A meta-analysis.

To investigate the potential correlation between complement factor B polymorphisms and age-related macular degeneration. We retrieved relevant articles systematically by searching PubMed and Web of Science databases. The pooled odds ratios and 95% confidence intervals were calculated for five complement factor B polymorphism rs641153, rs4151667, rs1048709, rs2072633, and rs12614 using data from included articles in both random effects and fixed effect models. Subgroup meta-analysis based on age-related macular degeneration type, choroidal neovascular disease (rs641153 and rs4151667), geographic atrophy (rs641153 and rs4151667), and races was also performed. In the overall comparison, we observed that the distribution of rs641153 and the risk of age-related macular degeneration were significantly correlated (p < 0.00001). Similar results were obtained in subgroup analysis based on race (Caucasians, p < 0.00001; Asians, p = 0.003) and age-related macular degeneration type (choroidal neovascular disease, p < 0.00001; geographic atrophy, p = 0.04). As for complement factor B rs4151667, the genotypic effects were also demonstrated statistically significant in overall analysis (p < 0.00001) and only in Caucasians diagnosed with choroidal neovascular disease (p = 0.004), but not in Asians. Moreover, no statistically significant correlations between the complement factor B polymorphisms rs1048709 (p = 0.63), rs2072633 (p = 0.72), rs12614 (p = 0.98) and susceptibility to age-related macular degeneration were detected in either overall or subgroup analysis. Collectively, we demonstrated that the complement factor B genes rs641153 and rs4151667, but not rs1048709, rs2072633, rs12614, were associated with the susceptibility of age-related macular degeneration and might play predictive roles in future age-related macular degeneration diagnosis. More studies are needed to verify these findings.

P‐9.4: High‐brightness Micro‐LED Matrix for Subfoveal Choroidal Neovascularization Applications

Subfoveal choroidal neovascularization (CNV) disease in human fundus is a universal illness which lead to low vision even blind. So there is an urgent need for an effective, noninvasive, accurate and portable probe to diagnosis and treatment. Here, we proposed a new probe design which consists of Micro‐LED arrays with light emission wavelength of 810nm considering its advantage of long lifetime, small size, low power consumption, high brightness and quick response frequency. Besides, we compared circuits in series and hybrid. The results show that hybrid one has a better performance which can greatly cut down the LED heat generation, reduce power consumption, and improve the accuracy of monitoring. A light spot with a diameter of 10mm from the probe will detect macular area disconnectedly to reach noninvasive monitoring. The light output power density(LOPD) of the Micro‐LED array was adjusted between 0.5mW/cm2 to 5mW/cm2 , and only 0.1mW/cm2 to 1mW/cm2 of LOPD arrive to the macular area that ensure no damage to the eyes. This new design is compact and can be attached onto wearable devices such as AR/VR glasses, which is very attractive for mobile medical devices and it will bring great convenience to the biomedical engineering.

VOLUME-RENDERED ANGIOGRAPHIC AND STRUCTURAL OPTICAL COHERENCE TOMOGRAPHY.

To demonstrate combined and integrated volume rendering of the retinal vasculature and selected structural abnormalities information derived from optical coherence tomography. The eyes were scanned using optical coherence tomography using split-spectrum amplitude-decorrelation techniques to derive flow information. Various sublayers could be color coded as needed. The corresponding structural optical coherence tomography information was segmented for salient anatomic structures of interest, such as areas of edema fluid or intraretinal lipid deposits. The angiographic and structural data were integrated on a plane-by-plane basis and used to create volume-rendered images. The combined volume-rendered angiographic and structural optical coherence tomography data could be rotated about three different axes for evaluation. Representative images from the eyes with diabetic macular edema, Type 1 macular telangiectasis, choroidal neovascularization, and retinal veno-occlusive disease are shown. The interrelationships between areas of cystoid fluid accumulation or intraretinal lipid accumulation could be visualized. Although structural and angiographic findings are typically shown in isolation, they can be integrated into a merged data set that is amenable to volume rendering. Using this new technique will allow investigation into the interrelationships between vascular and structural abnormalities of the retina and choroid.

Experience of intravitreal injections in a tertiary Hospital in Oman.

Aim:To find out statistical data regarding intravitreal injections in an outpatient department setup at a tertiary center in Oman.Design:Retrospective chart review.Methods:Data collection of patients who underwent intravitreal injections from November 2009 to May 2013 at Sultan Qaboos University Hospital.Results:Throughout a period of 42 months, a total of 711 intravitreal injections were performed. That included 214 patients (275 eyes). Around one-third of the eyes received two injections or more. The injected agents were bevacizumab (59.8%), ranibizumab (32.3%), triamcinolone (7.5%), and very few patients with endophthalmitis received intravitreal antibiotics and antifungal agents. The three most common indications for the injection therapy were diabetic macular edema (50.9%), choroidal neovascularization (24.3%), and retinal vein occlusive diseases (11.5%). Serious adverse events were rare, and they occurred as ocular (0.9% per patient) and systemic (3.3% per patient). There were 42 eyes received intravitreal triamcinolone, and 24% of them developed intraocular hypertension that required only medical treatment.Conclusion:Different intravitreal agents are currently used to treat many ocular diseases. Currently, therapy with intravitreal agents is very popular, and it carries a promising outcome with more efficiency and safety.

Antiangiogenic effect of ALS‐L1023 on experimental choroidal neovascularization in mice

AbstractPurpose This study was conducted to evaluate the effect of ALS‐L1023 on experimental choroidal neovascularization (CNV) in mice.Methods C57BL/6 mice were administered either vehicle or ALS‐L1023 daily by oral gavage for three weeks (day 0‐21). CNV was induced in each mouse by rupturing Bruch’s membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by choroidal flat mounts using fluorescein‐labeled dextran, immunofluorescence staining with isolectin IB4, and fluorescence angiography. The effects of ALS‐L1023 on endothelial cell tube formation and on the expression of phosphorylated extracellular signal‐regulated kinase (p‐ERK1/2) were evaluated using human umbilical vein endothelial cells (HUVECs).Results ALS‐L1023 reduced the extent of CNV. The groups treated with 100 and 200 mg/kg/day showed 43.3 and 68.1 % reduction of CNV lesions, respectively, compared to the vehicle group (P &lt; 0.001). The size of isolectin IB4 labeled area was also significantly decreased in the ALS‐L1023‐treated group (P &lt; 0.001). On fluorescein angiography, ALS‐L1023‐treated mice had significantly less fluorescence leakage than vehicle‐treated mice. ALS‐L1023 decreased VEGF‐stimulated tube formation of HUVECs in a dose‐dependent manner. The expression of p‐ERK was suppressed by ALS‐L1023.Conclusion ALS‐L1023 can inhibit laser‐induced CNV in mice and may have therapeutic potential for treatment of choroidal neovascularization diseases.

Geographic Atrophy

Geographic atrophy (GA) is the major cause of blind registration in Western communities, although, with few exceptions, it is less common than choroidal neovascular disease. The variation of phenotype implies that age-related macular degeneration (AMD) does not follow the same course from one case to another and that phenotyping may be important before initiating a therapeutic trial. To document photoreceptor and retinal pigment epithelium (RPE) cell loss and other changes at the RPE-choroid interface in donated human eyes in which visual loss was deemed to be due to GA. Histological study of a consecutive series of eyes donated by individuals previously diagnosed clinically as having GA. Donors were chosen on the basis of available clinical records (from MidAmerica Transplant Services, St Louis, Missouri; the Iowa Lions Eye Bank, Iowa City; and the Utah Lions Eye Bank, Salt Lake City) and selected were those considered to have GA due to AMD. Tissues in the regions of atrophy were examined with light, electron, and autofluorescence microscopy. In most of the 37 donors examined, there was marked loss of photoreceptor cells for variable distances distal from the edge of the GA. Rod loss was greater than cone loss. An inverse relationship existed between the quantity of autofluorescent inclusions in the RPE and the thickness of sub-RPE basal laminar deposit. Integrity of the choroid varied from one eye to another and was not related strictly to photoreceptor survival. In some eyes, photoreceptor loss existed in the absence of obvious morphological changes in the Bruch membrane or RPE. The findings support the view that photoreceptor loss occurs early in AMD in a proportion of cases and imply that photoreceptor-cell loss may contribute to the functional loss recorded in early stages of AMD at least in part. The variation of changes from one eye to another implies that patients selected for a specific prophylactic therapy for early AMD should be chosen on the basis of the characteristics of their disease.

Clinical management of a patient with polypoidal choroidal vasculopathy

Clinical management of a patient with polypoidal choroidal vasculopathy Todd PeabodyIndiana University School of Optometry, Bloomington, IN, USAAbstract: Polypoidal choroidal vasculopathy (PCV) is an often-misdiagnosed condition affecting the choroidal vasculature and retina of the posterior pole. The clinical identity of PCV was understood fully only recently, but shows unique demographics, clinical findings, and outcomes. Clinically, PCV can be confused with typical choroidal neovascularization and other diseases of the choroid, but generally shows a more favorable outcome. It is important to make the distinction between PCV and other diseases to ensure that patients are treated properly and not exposed to unnecessary procedures. This case report reviews the clinical findings and management of a patient with PCV as well as other studies, demographics of PCV, and current management options for patients with PCV.Keywords: polypoidal choroidal vasculopathy, retinal pigment epithelium detachment, indocyanine green angiography

Cirrus High-Definition Optical Coherence Tomography (OCT) Imaging in normal retina and laser-induced choroidal neovascularization in rats

BACKGROUND: To evaluate the Cirrus High-Definition Optical Coherence Tomography (OCT) features of the retina of rats. MATERIAL AND METHODS: Sixteen eyes of 16 adult BN rats were used. Histologic sections and OCT images of normal retinas and retinas with laser-induced choroidal neovascularization were studied. RESULTS: OCT showed a double-layered structure in the normal retina with a highly reflective layer located in the inner retina and a low reflective layer located in the outer retina. The retinal pigment epithelium (RPE) and choriocapillaris were imaged as a layer with the highest reflection. On the first day after photocoagulation, OCT image showed a disruption of the highly reflective layer corresponded to the RPE and choriocapillaris. Choroidal neovascularisation was seen as a highly reflective area located beneath the subretinal space. The retinal atrophy which appeared 4 weeks after photocoagulation was seen as a thinning reflection of the sensory retina. The retinal layer and thickness maps provided additional information that greatly complemented the OCT images. The histopathological appearance was well correlated with the OCT images. CONCLUSIONS: Cirrus OCT image combined with retinal layer and thickness maps will be a useful tool for the evaluation of animal studies of choroidal neovascularization and other retinal diseases.

Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration

Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD) are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI) and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs) than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV) disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history) or non-static factors (BMI, education status) that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model development and test model validation to present estimates of classification performance anticipated in the larger clinical setting. The model contained nine SNPs tagging variants in the regulators of complement activation (RCA) locus spanning the complement factor H (CFH), complement factor H-related 4 (CFHR4), complement factor H-related 5 (CFHR5) and coagulation factor XIII B subunit (F13B) genes; the four remaining SNPs targeted polymorphisms in the complement component 2 (C2), complement factor B (CFB), complement component 3 (C3) and age-related maculopathy susceptibility protein 2 (ARMS2) genes. The pooled sample size (1,132 CNV cases, 822 controls) allowed for both model development and model validation to confirm the accuracy of risk prediction. At the validation stage, our test model yielded 82 per cent sensitivity and 63 per cent specificity, comparable with metrics reported with earlier testing models that included environmental risk factors. Our test had an area under the curve of 0.80, reflecting a modest improvement compared with tests reported with fewer SNPs.

Inhibition of proliferation, migration and tube formation of choroidal microvascular endothelial cells by targeting HIF-1α with short hairpin RNA-expressing plasmid DNA in human RPE cells in a coculture system

Retinal pigment epithelial (RPE) cells and choroidal microvascular endothelial cells (CECs) are the main cells involved in choroidal neovascularization (CNV), and hypoxia plays an important role in CNV formation via hypoxia inducible factor 1 (HIF-1). Our aim was to evaluate the role of HIF-1 in human RPE cells with regard to proliferation, migration and tube formation of CECs under hypoxia. RPE cells were cultured under chemical hypoxia induced by 200 muM CoCl(2), and RNA interference (RNAi) technique was used to knock down HIF-1alpha gene in RPE cells. mRNA and protein expression of HIF-1alpha and VEGF in RPE cells were investigated by real-time RT-PCR and Western blot. Three kinds of coculture models were used to observe the effects of RPE cells transfected by short hairpin RNA (shRNA)-expressing plasmid DNA (pDNA) (pshHIF-1alpha) on the proliferation, migration and tube formation of CECs respectively. Transfection of shRNA-expressing pDNA targeting HIF-1alpha to RPE cells resulted in the knock down of HIF-1alpha gene and reduction of the corresponding mRNA and protein of HIF-1alpha and VEGF under hypoxia. Consequently, the proliferation, migration and tube formation of CECs were significantly inhibited by the knocked-down RPE cells compared with the control in the coculture system. The proliferation rates of CECs decreased by 40.2%, 36.6% and 36.8% on days 3, 4 and 5 respectively. Migration reduced by 49.6% at 5 h, and tube formation decreased by 40.4% at 48 h. RNAi of HIF-1alpha in RPE cells can inhibit angiogenesis in vitro and provide a possible strategy for treatment of choroidal neovascularization diseases by targeting HIF-1alpha.

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis*1

Purpose Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. Design Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. Methods Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. Results The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. Conclusions High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis

Purpose Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. Design Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. Methods Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. Results The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. Conclusions High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.

Photodynamic therapy for choroidal neovascular disease: photosensitizers and clinical trials

Photodynamic therapy with visudyne for choroidal neovascular disease (CNV) has proved effective at preventing moderate to severe visual loss in eyes with subfoveal predominantly classic CNV or occult-only CNV caused by age-related macular degeneration (AMD) and in eyes with subfoveal CNV caused by pathologic myopia. PDT is not meant to improve visual acuity. It should, therefore, be used in eyes with potentially useful macular vision. Clinical trials are under way to evaluate the usefulness of early retreatment with PDT and visudyne at 6 weeks for reducing the risk for moderate visual loss in eyes with predominantly classic CNV, the efficacy of PDT with visudyne for the treatment of AMD in eyes with minimally classic CNV, and the efficacy of PDT for use with SnET2, lutetium texaphyrin, and Npe6.

Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1-3 of angiostatin reduce retinal neovascularization.

Neovascular diseases of the retina include age-related macular degeneration and diabetic retinopathy, and together they comprise the leading causes of adult-onset blindness in developed countries. Current surgical, pharmaceutical, and laser therapies for age-related macular degeneration (AMD) rarely result in improved vision, do not significantly prevent neovascularization (NV), and often result in at least some vision loss. To address this therapeutic gap, we determined the efficacy of recombinant adeno-associated viral (rAAV) serotype-2-mediated expression of pigment epithelium-derived factor (PEDF) or Kringle domains 1-3 of angiostatin (K1K3) in reducing aberrant vessel formation in a mouse model of ischemia-induced retinal NV. Both PEDF and K1K3 are potent inhibitors of NV when injected directly, hence expression of these therapeutic factors from rAAV may provide long-term protection from neovascular eye disease. rAAV vectors expressing the therapeutic gene were injected into one eye of postnatal day 0 (P0) newborn mouse pups. Retinal NV was induced in P7 mice by exposure to elevated oxygen for 5 days followed by room air for another five days. Retinal NV was quantified by the number of vascular-endothelial-cell nuclei above the inner-limiting membrane in P17 eyes. The number of such vascular endothelial cell nuclei in eyes treated with rAAV-PEDF or rAAV-K1K3 was significantly reduced (both P < 0.0000002) compared with control eyes. Ocular protein levels detected by ELISA correlate well with the reduction in NV and confirm that expression of antineovascular agents from rAAV vectors may be a therapeutically useful treatment of retinal or choroidal neovascular disease.

Optical coherence tomography (OCT) findings in normal retina and laser-induced choroidal neovascularization in rats.

To evaluate the optical coherence tomographic (OCT) features of the retina of rats, we compared the OCT images with the histological appearance of normal retinas and retinas with laser-induced choroidal neovascularization. Twelve eyes of 12 adult pigmented rats (Brown-Norway) were used. Color fundus photography, fluorescein angiography (FAG), and OCT images of normal retinas and retinas with laser photocoagulation-induced choroidal neovascularization were studied. OCT showed a double-layered structure in the normal sensory retina with a highly reflective layer located in the inner retina and a low reflective layer located in the outer retina. The retinal pigment epithelium (RPE) and choriocapillaris were imaged as a layer with the highest reflection. On the first day after photocoagulation, OCT showed a disruption of the highly reflective layer corresponding to the RPE, and an enhanced reflectivity in the choroid under the lesion. Choroidal neovascularizations (CNVs) which appeared 2 weeks after photocoagulation was seen as a multi-layered, highly reflective area protruding from the RPE into the subretinal space A CNV beneath a subretinal hematoma was difficult to detect because of the low transmission of the scanning light through the hematoma. The histopathological appearance was well correlated with the OCT images. The two reflective bands in the OCT images were identified as coming from the inner layers of the retina and from the photoreceptors. The highest reflective band arose from the RPE and choriocapillaris. In the future, OCT combined with FAG or indocyanine-green angiography will be a useful tool for the evaluation of animal studies of choroidal neovascularization and other retinal diseases.