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Sample records for myopic choroidal neovascular

  1. Current and emerging treatment options for myopic choroidal neovascularization

    PubMed Central

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra

    2015-01-01

    Choroidal neovascularization (CNV) is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. PMID:25987831

  2. Current and emerging treatment options for myopic choroidal neovascularization.

    PubMed

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra

    2015-01-01

    Choroidal neovascularization (CNV) is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. PMID:25987831

  3. Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application

    PubMed Central

    Zhang, Yan; Han, Qian; Ru, Yusha; Bo, Qiyu; Wei, Rui Hua

    2015-01-01

    Choroidal neovascularization (CNV) secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of “from bench to bedside”, initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia. PMID:26170626

  4. Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application.

    PubMed

    Zhang, Yan; Han, Qian; Ru, Yusha; Bo, Qiyu; Wei, Rui Hua

    2015-01-01

    Choroidal neovascularization (CNV) secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of "from bench to bedside", initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia. PMID:26170626

  5. Comparison of 1-year therapeutic effect of ranibizumab and bevacizumab for myopic choroidal neovascularization: a retrospective, multicenter, comparative study

    PubMed Central

    2014-01-01

    Background To compare the long-term efficacy of ranibizumab versus bevacizumab for myopic choroidal neovascularization (CNV). Methods This was a retrospective, multicenter, comparative, non-randomized study of 64 consecutive patients with myopic CNV treated with ranibizumab (22 patients) or bevacizumab (42 patients). Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. All the patients were followed for at least 12 months. Results BCVA (logarithm of the minimal angle of resolution) improved from 0.63 ± 0.30 to 0.43 ± 0.27, 0.41 ± 0.37, 0.40 ± 0.39, 0.39 ± 0.43, and 0.39 ± 0.42 at 1, 2, 3, 6, and 12 months after treatment in the ranibizumab group, and from 0.67 ± 0.28 to 0.52 ± 0.31, 0.49 ± 0.31, 0.47 ± 0.31, 0.42 ± 0.32, and 0.46 ± 0.43 in the bevacizumab group (all P < 0.05 compared with baseline BCVA in each group). CFT decreased by 20.21%, 19.58%, and 22.43% from the baseline 304 ± 76 μm at 3, 6, and 12 months after treatment in the former group, and by 15.20%, 15.67%, and 15.56% from the baseline 297 ± 62 μm in the latter group (all P < 0.05 compared with baseline CFT in each group). BCVA improvement and CFT reduction did not statistically differ when compared at the same periods from treatment between 2 groups. Neither ocular nor systemic safety problems appeared during follow up. Conclusions This study showed a similar functional and anatomical improvement after treatment of ranibizumab and bevacizumab for myopic CNV over a 12-month follow-up period. PMID:24884970

  6. Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study.

    PubMed

    Amoaku, Winfried M; Gale, Richard P; Lotery, Andrew J; Menon, Geeta; Sivaprasad, Sobha; Petrillo, Jennifer; Quinn, Jennifer

    2015-01-01

    The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24-78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0-72) and well-being measured with the W-BQ12 (score 0-36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest

  7. Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study

    PubMed Central

    Amoaku, Winfried M.; Gale, Richard P.; Lotery, Andrew J.; Menon, Geeta; Sivaprasad, Sobha; Petrillo, Jennifer; Quinn, Jennifer

    2015-01-01

    The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24–78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0–72) and well-being measured with the W-BQ12 (score 0–36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest

  8. Inflammatory Choroidal Neovascularization

    PubMed Central

    Neri, Piergiorgi; Lettieri, Marta; Fortuna, Cinzia; Manoni, Mara; Giovannini, Alfonso

    2009-01-01

    Purpose and Methods: Choroidal neovascularization (CNV) can be a severe sight-threatening sequela, which can be secondary to both infectious and noninfectious uveitis. This review summarizes the different diseases associated with CNV, highlighting new treatment modalities and the possible strategies, which could be applied for the therapy of this occurrence. Results: Since CNV can often originate from posterior pole lesions and can be hard to identify, an accurate examination is mandatory in order to identify the correct diagnosis. In the majority of cases, fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) enable the determination of the clinical characteristics of the CNV. An infectious disease should be looked for to include a suitable therapy when available. The treatment strategy for CNV secondary to noninfectious uveal inflammations should be directed at controlling the inflammatory process. Systemic corticosteroids with or without immunosuppressive agents are indicated even when the CNV occurs with apparently inactive uveitis: Chronic subclinical inflammation can be the basis for the pathogenesis of CNV. Additional therapies aimed directly at the neovascular process, such as the intravitreal anti-Vascular Endothelial Growth Factor (VEGF) agents, are recommended particularly when the therapy shows an insufficient response. Conclusion: CNV secondary to uveitis is a severe sequela leading to significant visual impairment. ICGA is mandatory in order to obtain relevant information about the choroidal status. Several therapeutic options have been considered, but no guidelines are provided at the moment. Moreover, the current data are still only based on case reports or small series. For such reasons, further trials are mandatory to validate the preliminary available results. PMID:20404991

  9. Treatment of choroidal neovascularization in high myopia.

    PubMed

    Montero, Javier A; Ruiz-Moreno, Jose M

    2010-05-01

    High myopia affects approximately 2% of general population, and is a major cause of legal blindness in many developed countries. Choroidal neovascularization (CNV) is the most common vision-threatening complication of high myopia. Different therapeutic approaches have been attempted such as thermal laser photocoagulation, surgery and photodynamic therapy with verteporfin (PDT). The visual outcome of these therapies has been reported to be better than the natural history of the condition. However, the limited visual acuity improvement after PDT monotherapy and the appearance of subretinal fibrosis and chorioretinal atrophy prompted the association of other therapies. In the past few years a tremendous advance in the knowledge of the mechanisms underling CNV secondary to high myopia and age related macular degeneration has been achieved, leading to new therapeutic targets and novel drugs and combined therapies. These new therapeutic weapons have been designed to achieve a selective shut down of choroidal new vessels. Recent reviews have been published on the natural history and therapies for myopic CNV. Ohno-Matsui reported on the natural history of the condition as well as the outcome of laser photocoagulation, surgical extraction of CNV, foveal translocation and photodynamic therapy on myopic CNV in the short-term. Soubrane et al reviewed the new advances on surgery, laser photocoagulation and PDT, considering some of the potential effects of triamcinolone, pegaptanib and ranibizumab in CNV secondary to age related macular degeneration (AMD). Novack et al reported on the pharmacological therapy of CNV in AMD. The aim of this review is to summarize the recent advances in myopic CNV pathophysiology and the new therapeutic targets and drugs that are changing the clinical management of myopic CNV. PMID:20196722

  10. Endogenous endostatin inhibits choroidal neovascularization.

    PubMed

    Marneros, Alexander G; She, Haicheng; Zambarakji, Hadi; Hashizume, Hiroya; Connolly, Edward J; Kim, Ivana; Gragoudas, Evangelos S; Miller, Joan W; Olsen, Bjorn R

    2007-12-01

    Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions. PMID:17526870

  11. Myopic choroidal neovascularisation: current concepts and update on clinical management

    PubMed Central

    Wong, Tien Y; Ohno-Matsui, Kyoko; Leveziel, Nicolas; Holz, Frank G; Lai, Timothy Y; Yu, Hyeong Gon; Lanzetta, Paolo; Chen, Youxin; Tufail, Adnan

    2015-01-01

    Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm. PMID:24990871

  12. Myopic choroidal neovascularisation: current concepts and update on clinical management.

    PubMed

    Wong, Tien Y; Ohno-Matsui, Kyoko; Leveziel, Nicolas; Holz, Frank G; Lai, Timothy Y; Yu, Hyeong Gon; Lanzetta, Paolo; Chen, Youxin; Tufail, Adnan

    2015-03-01

    Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm. PMID:24990871

  13. Aflibercept as primary treatment for myopic choroidal neovascularisation: a retrospective study

    PubMed Central

    Bruè, C; Pazzaglia, A; Mariotti, C; Reibaldi, M; Giovannini, A

    2016-01-01

    Aim The aim of this study is to evaluate long-term efficacy of intravitreal injections of aflibercept as primary treatment for subfoveal/juxtafoveal myopic choroidal neovascularisation (CNV). Methods Thirty-eight treatment-naive eyes of thirty-eight patients with subfoveal/juxtafoveal myopic CNV received initial intravitreal aflibercept injections and were followed for at least 18 months. Aflibercept was applied again for persistent or recurrent CNV, as required. Statistical analysis was carried out using SPSS. Results Mean patient age was 45.8 years, and mean eye refractive error was −7.79 D. For the total patient group (n=38 eyes), mean logMAR best-corrected visual acuity (BCVA) significantly improved from 0.69 at baseline to 0.15 at 18 months (P<0.01). Over half of the treated eyes obtained resolution with one aflibercept injection. Patients were also grouped according to age, as <50 years (n=20 eyes) and ≥50 years (n=18 eyes). Mean BCVA improvement was significantly greater in eyes of the younger myopic CNV group, compared with those of ≥50 years (0.21 vs 0.35; P<0.05). The mean number of aflibercept injections was 1.8 for the <50 years myopic CNV group, and 3.6 for the ≥50 years myopic CNV group (P<0.001). Correlation between spherical equivalent refraction and final visual acuity reached statistical significance only for the <50 years myopic CNV group (P<0.001; Levene's correlation). Conclusions Intravitreal aflibercept provides long-term visual acuity improvement in myopic CNV. The <50 years old myopic CNV group had significantly fewer injections, with greater visual acuity improvement. Intravitreal aflibercept in myopic CNV does not require the three-injection loading phase used for aflibercept treatment of neovascular age-related macular degeneration. PMID:26514244

  14. Pachychoroid neovasculopathy in extramacular choroidal neovascularization

    PubMed Central

    Gupta, Mrinali Patel; Rusu, Irene; Seidman, Carly; Orlin, Anton; D’Amico, Donald J; Kiss, Szilard

    2016-01-01

    Purpose To review a series of extramacular choroidal neovascular membranes (CNVMs) in the context of their choroidal features, as determined by optical coherence tomography (OCT). Methods Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA), and indocyanine angio-graphy (ICG). Results Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7%) exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM. Conclusion Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. PMID:27471372

  15. Doxycycline-mediated Inhibition of Choroidal Neovascularization

    PubMed Central

    Samtani, S.; Amaral, J.; Campos, M.; Fariss, R. N.; Becerra, S. P.

    2010-01-01

    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 epithelium-derived factor (PEDF). Methods Doxycycline was orally administered to rats at 500, 50, 5, and 0.5 mg/kg/day, using non-treated animals as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At seven days post-induction, animals were euthanized, and eyes collected. RPE/choroid flat-mounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and Volocity® software. MMP-2, MMP-9 and PEDF protein levels were determined by ELISA. MMP catalytic activity was determined in solution using fluorogenic gelatin and peptide substrates, by gelatin zymography in SDS-PAGE and by in situ DQ-gelatin zymography in RPE/choroid sections. Results CNV complex lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/day caused a 70% inhibition of CNV complex volume compared to control animals. Doxycycline elevated PEDF levels in plasma, and did not affect the plasma pro- and active MMP-2 and MMP-9 levels. However, the in vitro enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline. MMP-2, MMP-9 and gelatinolytic activities in situ increased early in CNV lesion development. Doxycycline treatments and exogenous additions inhibited gelatinolytic activities in CNV lesions. Conclusions Doxycycline effectively hampered the progression of experimental CNV. The results suggest that orally administrated doxycycline can reach the choroid to attenuate proteolytic enzymes that remodel Bruch's membrane and promote the anti-angiogenic PEDF to inhibit neovascularization. PMID:19516001

  16. Aqueous Concentrations of Vascular Endothelial Growth Factor in Eyes with High Myopia with and without Choroidal Neovascularization

    PubMed Central

    Wakabayashi, Taku; Ikuno, Yasushi; Oshima, Yusuke; Nishida, Kohji

    2013-01-01

    Purpose. To investigate aqueous concentrations of vascular endothelial growth factor (VEGF) in eyes with myopic choroidal neovascularization (CNV). Methods. Aqueous samples were collected, and VEGF concentrations were measured by enzyme-linked immunosorbent assay in 16 eyes (16 patients) with active myopic CNV, 23 eyes (16 patients) with high myopia without myopic CNV, and 8 control eyes (7 patients). Differences in the concentrations of VEGF in each group were compared. Results. The estimated mean VEGF concentrations were significantly lower in eyes with myopic CNV (82.0 pg/mL) (P = 0.016 ) and with high myopia without myopic CNV (58.9 pg/mL) (P < 0.001) compared with controls (116.6 pg/mL). The estimated mean VEGF concentration was significantly (P < 0.05) higher in eyes with myopic CNV than in those without myopic CNV in highly myopic eyes. In eyes with high myopia with and without CNV, the VEGF concentration was significantly (stepwise regression analysis, R = 0.325, P = 0.044) associated with the presence of myopic CNV but not with age, axial length, or intraocular pressure. Conclusion. Increased levels of VEGF may play a role in the pathogenesis of CNV in highly myopic eyes. PMID:23533702

  17. [Photodynamic therapy with Visudyne in macular degeneration associated with subfoveal classical choroidal neovascularization].

    PubMed

    Soucek, P; Boguzsaková, J; Cihelková, I

    2002-04-01

    Photodynamic therapy with the preparation Visudyne (PDT) is the only treatment which retards statistically significantly the decline of vision in patients with age related and myopic macular degeneration with a subfoveal, predominantly classic choroidal neovascularization. The authors present their own experience with the treatment of the first 12 patients. During 6-month treatment a loss of more than 3 lines of ETDRS optotypes was recorded in two patients (17%). The presented results of FTV are consistent with data published abroad. As the one-year therapeutic results in two patients are encouraging, it will be necessary in future to prolong the follow up time and increase the number of patients. PMID:12046251

  18. Is Asthma Related to Choroidal Neovascularization?

    PubMed Central

    Hou, Jing; Gong, Peihua; Zheng, Yi; Zhao, Mingwei; Zhou, Peng; Li, Xiaoxin

    2012-01-01

    Background Age-related degeneration(AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. Principal Findings The epidemiological study showed that asthma was related to choroidal neovascularization(CNV) subtype(OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α’-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. Significance This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice. PMID:22567103

  19. Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo

    PubMed Central

    Li, Tao; Aredo, Bogale; Zhang, Kaiyan; Zhong, Xin; Pulido, Jose S.; Wang, Shusheng; He, Yu-Guang; Huang, Xianming; Brekken, Rolf A.; Ufret-Vincenty, Rafael L.

    2015-01-01

    Purpose Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. Methods Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. Results We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. Conclusions We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV. PMID:26529048

  20. Regulation of Tumor Angiogenesis and Choroidal Neovascularization by Endogenous Angioinhibitors

    PubMed Central

    Gunda, Venugopal; Sudhakar, Yakkanti A

    2014-01-01

    Angiogenesis is the process of neovascularization from parent blood vessels, which is a prerequisite for many physiological and pathological conditions and is regulated by a balance between endogenous angioinhibitors and angioactivators or angiogenic factors. Imbalance between angioinhibitors and angioactivators is associated with neovascularization capacity during progression of tumor development and Choroidal Neovascularization (CNV). Normalization of pathological angiogenesis is considered as an alternative strategy to prevent the tumor growth in cancer progression or retinal damage in CNV. Various angioinhibitors are being identified and evaluated for their pathological angiogenesis regulation, of which endogenous angioinhibitors are one class derived either from extra cellular matrix or from non-extra cellular matrix of human origin. Endogenous angioinhibitors are gaining much significance as they interact with proliferating endothelial cells by binding to distinct integrins and non-integrin receptors, regulating different intracellular signaling mechanisms leading to inhibition of choroidal neovascularization and tumor growth. This review will focus on endogenous angioinhibitors and their receptor(s) mediated angioinhibitory signaling, which are of major concern in angiogenesis and their clinical and pharmaceutical implications. PMID:25258675

  1. Improved assessment of laser-induced choroidal neovascularization

    PubMed Central

    Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.; Kim, Stephen J.

    2011-01-01

    The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology. PMID:20553963

  2. Automated choroidal neovascularization detection algorithm for optical coherence tomography angiography

    PubMed Central

    Liu, Li; Gao, Simon S.; Bailey, Steven T.; Huang, David; Li, Dengwang; Jia, Yali

    2015-01-01

    Optical coherence tomography angiography has recently been used to visualize choroidal neovascularization (CNV) in participants with age-related macular degeneration. Identification and quantification of CNV area is important clinically for disease assessment. An automated algorithm for CNV area detection is presented in this article. It relies on denoising and a saliency detection model to overcome issues such as projection artifacts and the heterogeneity of CNV. Qualitative and quantitative evaluations were performed on scans of 7 participants. Results from the algorithm agreed well with manual delineation of CNV area. PMID:26417524

  3. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  4. Choroidal Neovascularization Secondary to Myopia, Infection and Inflammation.

    PubMed

    Weber, Marissa L; Heier, Jeffrey S

    2016-01-01

    Choroidal neovascularization (CNV) is a significant cause of vision loss in all age groups. The most common cause of CNV is age-related macular degeneration (AMD). However, CNV can also occur as a secondary manifestation of various inherited and acquired conditions, including pathologic myopia, presumed ocular histoplasmosis syndrome, angioid streaks, and various hereditary, traumatic or inflammatory disorders. Fluorescein angiography and optical coherence tomography are useful tools in the diagnosis and evaluation of CNV. Treatment options are similar to those for CNV secondary to AMD, specifically anti-angiogenic therapy, but including laser photocoagulation, photodynamic therapy and surgery. Anti-angiogenic therapy has been associated with better visual outcomes than other treatment modalities and is now advocated as the first-line therapy for CNV secondary to myopia, infection and inflammation. PMID:26501802

  5. An Angiogenic Role for Adrenomedullin in Choroidal Neovascularization

    PubMed Central

    Sakimoto, Susumu; Kidoya, Hiroyasu; Kamei, Motohiro; Naito, Hisamichi; Yamakawa, Daishi; Sakaguchi, Hirokazu; Wakabayashi, Taku; Nishida, Kohji; Takakura, Nobuyuki

    2013-01-01

    Purpose Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45− endothelial cells (ECs) than CD31−CD45− non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22–52). Intravitreous injection of ADM (22–52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. PMID:23520487

  6. Macrophage polarization in experimental and clinical choroidal neovascularization

    PubMed Central

    Yang, Yu; Liu, Fang; Tang, Miao; Yuan, Miner; Hu, Andina; Zhan, Zongyi; Li, Zijing; Li, Jiaqing; Ding, Xiaoyan; Lu, Lin

    2016-01-01

    Macrophages play an important role in the development of age-related macular degeneration (AMD). In this study, the spatial and temporal changes and the polarization of macrophages in murine laser-induced choroidal neovascularization (CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main infiltrating inflammatory cells in CNV lesions, were evidenced by a significant increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related markers were dramatically upregulated in the early stage, while the M2-related markers were slightly upregulated in the middle stage and sustained until the late stage. The results of immunostaining showed a similar early-but-transient M1 pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition, a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the controls. Our results suggested that the dynamic patterns of M1 and M2 were different in both the experimental and clinical CNV. The M2 macrophages were predominant and may play a more important role in the development of CNV. PMID:27489096

  7. IKK2 Inhibition Attenuates Laser-Induced Choroidal Neovascularization

    PubMed Central

    Lu, Huayi; Lu, Qingxian; Gaddipati, Subhash; Kasetti, Ramesh Babu; Wang, Wei; Pasparakis, Manolis; Kaplan, Henry J.; Li, Qiutang

    2014-01-01

    Choroidal neovascularization (CNV) is aberrant angiogenesis associated with exudative age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Inflammation has been suggested as a risk factor for AMD. The IKK2/NF-κB pathway plays a key role in the inflammatory response through regulation of the transcription of cytokines, chemokines, growth factors and angiogenic factors. We investigated the functional role of IKK2 in development of the laser-induced CNV using either Ikk2 conditional knockout mice or an IKK2 inhibitor. The retinal neuronal tissue and RPE deletion of IKK2 was generated by breeding Ikk2−/flox mice with Nestin-Cre mice. Deletion of Ikk2 in the retina caused no obvious defect in retinal development or function, but resulted in a significant reduction in laser-induced CNV. In addition, intravitreal or retrobulbar injection of an IKK2 specific chemical inhibitor, TPCA-1, also showed similar inhibition of CNV. Furthermore, in vitro inhibition of IKK2 in ARPE-19 cells significantly reduced heat shock-induced expression of NFKBIA, IL1B, CCL2, VEGFA, PDGFA, HIF1A, and MMP-2, suggesting that IKK2 may regulate multiple molecular pathways involved in laser-induced CNV. The in vivo laser-induced expression of VEGFA, and HIF1A in RPE and choroidal tissue was also blocked by TPCA-1 treatment. Thus, IKK2/NF-κB signaling appears responsible for production of pro-inflammatory and pro-angiogenic factors in laser-induced CNV, suggesting that this intracellular pathway may serve as an important therapeutic target for aberrant angiogenesis in exudative AMD. PMID:24489934

  8. NSAIDs inhibit neovascularization of choroid through HO-1-dependent pathway.

    PubMed

    Yoshinaga, Narimasa; Arimura, Noboru; Otsuka, Hiroki; Kawahara, Ko-Ichi; Hashiguchi, Teruto; Maruyama, Ikuro; Sakamoto, Taiji

    2011-09-01

    Intraocular neovascularization is the leading cause of severe visual loss and anti-vascular endothelial growth factor (VEGF) therapy is currently performed for choroidal neovascularization (CNV). Despite its potent anti-angiogenic effect, there are concerns about its long-term safety. Non-steroidal anti-inflammatory drugs (NSAIDs) are common therapeutic agents used for treating inflammatory diseases, and their anti-stress effects are attracting attention now. We studied the effects of topical NSAIDs on CNV, focusing on anti-stress proteins. Cultured retinal pigment epithelium (RPE) cells were treated with NSAIDs: bromfenac, indomethacin, or vehicle control. Transcription factor NF-E2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase (HO)-1 were assessed using western blot and immunohistochemistry. As a result, NSAIDs induced translocation of Nrf2 into the nucleus and the robust expression of HO-1 in a dose- and time-dependent manner. Flow cytometric analysis revealed that bromfenac inhibited H(2)O(2)-induced apoptosis in cultured RPE cells. Next, we studied the effects of topical bromfenac on laser-induced CNV model in rat. The expressions of Nrf2 and HO-1, infiltrations of ED-1-positive macrophages at CNV lesions and size were analyzed. VEGF in the ocular fluid of these rats was also measured using enzyme-linked immunosorbent assay. Rats administered an inhibitor of HO-1 stannic mesoporphyrin (SnMP) were also studied. The results showed that topical bromfenac led to translocation of Nrf2 and induction of HO-1 in CNV lesions and that the number of infiltrating macrophages at the CNV lesion decreased. The sizes of CNV lesions were significantly smaller in bromfenac-treated rats than control CNV, and the effects were diminished by SnMP. VEGF increased in the ocular fluid after laser treatment and was inhibited by bromfenac and SnMP canceling these effects. NSAIDs inhibit CNV through the novel anti-stress protein HO-1-dependent pathway

  9. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.

    PubMed

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-07-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  10. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

    PubMed Central

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-01-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  11. Enhanced Ccl2-Ccr2 signaling drives more severe choroidal neovascularization with aging.

    PubMed

    Robbie, Scott J; Georgiadis, Anastasios; Barker, Susie E; Duran, Yanai; Smith, Alexander J; Ali, Robin R; Luhmann, Ulrich F O; Bainbridge, James W

    2016-04-01

    The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pathways and myeloid cell populations involved in this increased neovascular response, we characterized the immune status of murine choroid and retina during aging and in the context of experimental CNV. In the choroid, but not in the retina, advancing age is associated with proinflammatory upregulation of CCL2-CCR2 signaling. Genetic excision of CCL2 diminishes age-related inflammatory changes in the choroid, with reduced recruitment of proinflammatory myeloid cells and attenuation of CNV. These findings indicate that CCL2-driven recruitment of myeloid cells contributes to increased severity of CNV with age. Similar mechanisms may be involved in other age-related inflammatory diseases. PMID:26973110

  12. Successful treatment of melanocytoma associated choroidal neovascular membrane with intravitreal bevacizumab.

    PubMed

    Al-Halafi, Ali M

    2013-04-01

    Melanocytoma of the optic disc is a benign melanocytic tumour that rarely causes visual impairment. We report a rare case of choroidal neovascularization (CNV) in association with optic disc melanocytoma and its response to intravitreal injection of the anti-vascular endothelial growth factor (VEGF), bevacizumab. The choroidal neovascular membrane regressed following a single intravitreal bevacizumab injection with formation of a scar. CNV associated with optic disc melanocytoma is rare. Intravitreal anti-VEGF treatment may be an effective treatment for CNV associated with optic disc melanocytoma. PMID:24227972

  13. Choroidal thickness profiles in myopic eyes of young adults in the Correction of Myopia Evaluation Trial cohort

    PubMed Central

    Harb, Elise; Hyman, Leslie; Gwiazda, Jane; Marsh-Tootle, Wendy; Zhang, Qinghua; Hou, Wei; Norton, Thomas T; Weise, Katherine; Dirkes, Keri; Zangwill, Linda M

    2015-01-01

    Purpose To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. Design Cross-sectional, multi-center, study Methods In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid (RTVue) in both eyes at their last visit (14 years after baseline). Using digital calipers, two independent readers measured choroidal thickness in the right eye (left eye if poor quality; n=37) at seven locations: fovea and 750, 1500, 2250μm nasal (N) and temporal (T) to the fovea. Results Choroidal thickness measurements were available from 294/346 (85%) of imaged participants (mean age: 24.3±1.4 years; 44.9% male) with mean myopia of -5.3±2.0D and mean AL of 25.5±1.0mm. Overall, choroidal thickness varied by location (p<0.0001) and was thickest at the fovea (273.8±70.9 μm) and thinnest nasally (N2250,191.5±69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (p≤0.001) and presence of peri-papillary crescent at all locations except T1500 and T2250 (p≤0.0001). Choroidal thickness varied by ethnicity at N2250 (p<0.0001), with Asians having the thinnest and African Americans the thickest choroids. Conclusion Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically. PMID:25896460

  14. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    PubMed Central

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  15. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion.

    PubMed

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-04-28

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  16. Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy

    PubMed Central

    Hohberger, Bettina; Rudolph, Michael; Bergua, Antonio

    2015-01-01

    Purpose Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. Case Report A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. Results Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. Conclusion Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC. PMID:26955337

  17. The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal Neovascularization and Subretinal Fibrosis

    PubMed Central

    Zhang, Ruoshuang; Liu, Zheli; Zhang, Han; Zhang, Yi; Lin, Dong

    2016-01-01

    Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium–choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-β2 in the retinal pigment epithelium–choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-β2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis. PMID:26760305

  18. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

    PubMed Central

    Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  19. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization.

    PubMed

    Chen, Qin; Yu, Xiaobing; Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with "tree-in-bud" form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  20. Targeting Platelet-Derived Growth Factor Receptor β(+) Scaffold Formation Inhibits Choroidal Neovascularization.

    PubMed

    Strittmatter, Karin; Pomeroy, Hayley; Marneros, Alexander G

    2016-07-01

    Neovascular age-related macular degeneration is among the most common causes of irreversible blindness and manifests with choroidal neovascularization (CNV). Anti-vascular endothelial growth factor-A therapies are only partially effective and their chronic administration may impair functions of the choriocapillaris and retina. Thus, novel therapeutic targets are needed urgently. We have observed in a laser-induced model of CNV that a platelet-derived growth factor receptor β positive (PDGFRβ(+)) scaffold is formed before infiltration of neovessels into this scaffold to form CNV lesions, and that this scaffold limits the extent of neovascularization. Based on these observations we hypothesized that ablation of proliferating PDGFRβ(+) cells to prevent the formation of this scaffold might inhibit CNV growth and present a novel therapeutic approach for neovascular age-related macular degeneration. To test this hypothesis we targeted proliferating PDGFRβ(+) cells through independent distinct approaches after laser injury: i) by using an inducible genetic model to inhibit specifically proliferating PDGFRβ(+) cells, ii) by treating mice with a neutralizing anti-PDGFRβ antibody, iii) by administering an anti-PDGF-AB/BB aptamer, and iv) by using small chemical inhibitor approaches. The results show that therapeutic targeting of proliferating PDGFRβ(+) cells potently inhibits the formation of the pericyte-like scaffold, with concomitant attenuation of CNV. Moreover, we show that early inhibition of PDGFRβ(+) cell proliferation before neovessel formation is sufficient to inhibit scaffold formation and neovascularization. PMID:27338108

  1. CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization

    PubMed Central

    Horie, Shintaro; Robbie, Scott J.; Liu, Jian; Wu, Wei-Kang; Ali, Robin R.; Bainbridge, James W.; Nicholson, Lindsay B.; Mochizuki, Manabu; Dick, Andrew D.; Copland, David A.

    2013-01-01

    Macrophages are rapidly conditioned by cognate and soluble signals to acquire phenotypes that deliver specific functions during inflammation, wound healing and angiogenesis. Whether inhibitory CD200R signaling regulates pro-angiogenic macrophage phenotypes with the potential to suppress ocular neovascularization is unknown. CD200R-deficient bone marrow derived macrophages (BMMΦ) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1β when stimulated with PGE2 or RPE-conditioned (PGE2-enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE2-conditioned CD200R−/− BMMΦ, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMΦ angiogenic and pro-inflammatory phenotypes. Translational potential of this pathway was investigated in the laser-induced model of choroidal neovascularization. Local delivery of a CD200R agonist mAb to target myeloid infiltrate alters macrophage phenotype and inhibits pro-angiogenic gene expression, which suppresses pathological angiogenesis and CNV development. PMID:24170042

  2. A systematic review and meta-analysis comparing intravitreal ranibizumab with bevacizumab for the treatment of myopic choroidal neovascularisation

    PubMed Central

    Loutfi, M.; Siddiqui, M.R.S.; Dhedhi, A.; Kamal, A.

    2014-01-01

    Intravitreal injections of ranibizumab (IVR) and bevacizumab (IVB) have both been used as treatments for myopic choroidal neovascularisation. We aimed to produce a meta-analysis of published literature comparing IVR with IVB for the treatment of myopic choroidal neovascularisation, by searching electronic databases from January 1950 to March 2013. Our search produced three suitable studies that reported on 117 patients in total. The results of the meta-analysis demonstrated that the mean number of lines improvement after IVR appeared better compared with IVB [fixed effects model: SMD = 0.46, 95% CI (0.09, 0.83), z = 2.44, p = 0.01]. The number of patients who had a greater than 3 line improvement was similar between groups [fixed effects model: RR = 0.95, 95% CI (0.67, 1.32), z = 0.33, p = 0.74]. At follow up there was no difference in number of those who had an absence of leakage [fixed effects model: RR = 1.04, 95% CI (0.93, 1.16), z = 0.64, p = 0.52]. There was no statistical significance between the two groups in relation to the number of injections [random effects model: SMD = −0.25, 95% CI (−1.12, 0.61), z = 0.57, p = 0.57]. Early evidence therefore suggests that intravitreal injections of ranibizumab are comparable to intravitreal injections of bevacizumab in the treatment of myopic choroidal neovascularisation. Both treatments result in a statistically significant increase in visual acuity with high numbers of patients maintaining stable vision. Further studies are still needed to strengthen results. PMID:25892935

  3. SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

    PubMed Central

    Bessho, Hiroaki; Honda, Shigeru; Negi, Akira

    2009-01-01

    Purpose A nonsynonymous coding variant in the manganese superoxide dismutase (SOD2) gene (V16A, rs4880) has been implicated in neovascular age-related macular degeneration (AMD). However, the findings have been inconsistent. Two studies in Japanese populations reported an opposite direction of association of the same allele at the V16A variant, whereas one study in a Northern Irish population found no effect of the variant on the risk of developing neovascular AMD. To address these apparently contradictory reports, we validated the association in a Japanese population. Methods In a Japanese population, we genotyped the V16A variant in 116 neovascular AMD patients, 140 polypoidal choroidal vasculopathy (PCV) patients, and 189 control participants. This association was also tested in a population of PCV participants to avoid variable findings across studies due to underlying sample heterogeneity and because disease phenotype was not well described in previous studies. We analyzed a tagging single nucleotide polymorphism (SNP) in addition to the V16A variant to capture all common SOD2 variations verified by the HapMap project. Genotyping was conducted using TaqMan technology. Associations were tested using single-SNP and haplotype analyses as well as a meta-analysis of the published literature. Population stratification was also evaluated in our study population. Results We found no detectable association of the V16A variant or any other common SOD2 variation with either neovascular AMD or PCV, as demonstrated by both single-SNP and haplotype analyses. Population structure analyses precluded stratification artifacts in our study cohort. A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association. Conclusions We found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV. Our study highlights the importance and

  4. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy.

    PubMed

    Mohla, Aditi; Khan, Kamron; Kasilian, Melissa; Michaelides, Michel

    2016-01-01

    We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography. PMID:27587748

  5. Quantification of choroidal neovascularization vessel length using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Gao, Simon S.; Liu, Li; Bailey, Steven T.; Flaxel, Christina J.; Huang, David; Li, Dengwang; Jia, Yali

    2016-07-01

    Quantification of choroidal neovascularization (CNV) as visualized by optical coherence tomography angiography (OCTA) may have importance clinically when diagnosing or tracking disease. Here, we present an automated algorithm to quantify the vessel skeleton of CNV as vessel length. Initial segmentation of the CNV on en face angiograms was achieved using saliency-based detection and thresholding. A level set method was then used to refine vessel edges. Finally, a skeleton algorithm was applied to identify vessel centerlines. The algorithm was tested on nine OCTA scans from participants with CNV and comparisons of the algorithm's output to manual delineation showed good agreement.

  6. Inhibition of choroidal neovascularization by anti-EphB4 monoclonal antibody

    PubMed Central

    SU, DONGFENG; LI, XIAOQIU; GAO, DIANWEN

    2013-01-01

    The aim of this study was to determine the effect of the EphB4 monoclonal antibody on experimental choroidal neovascularization (CNV) progression. Experimental CNV was established by argon laser photocoagulation. In the experimental group, the EphB4 monoclonal antibody was injected into the vitreous space in the eye specimens on days 0, 3, 6 and 9 after CNV model establishment. In the control group, an equal amount of balanced salt solution was injected at the same time points. On day 10 after CNV model establishment, fluorescein isothiocyanate-dextran endocardial perfusion and choroidal stretched preparation were conducted, respectively, for the two groups. The CNV area in each light spot and the mean values were determined. Histopathological examination was conducted and the ratio of the maximum thickness of the CNV in each light spot to the surrounding normal choroidal thickness, as well as the mean ratio, were calculated. Choroidal stretched preparation confirmed that the CNV of the experimental group was smaller, whereas the CNV of the control group was wider and larger. Quantitative analysis revealed that CNV in the experimental group was significantly inhibited (t=11.84, P<0.01) and that CNV progression in the experimental group was significantly suppressed (t=7.45, P<0.01). Histopathological examination revealed that CNV in the experimental group was thinner and smaller. Vitreous injection of the EphB4 monoclonal antibody inhibits experimental CNV progression. However, its specific mechanism remains unclear. Endogenous EphrinB2/EphB4 regulates ocular neovascularization and may become a new target in treating CNV diseases. PMID:23596494

  7. Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization.

    PubMed

    Lee, Jihwang; Ryoo, Na-Kyung; Han, Hyounkoo; Hong, Hye Kyoung; Park, Ji Yeon; Park, Sang Jun; Kim, Yong-Kyu; Sim, Changbeom; Kim, Kwangmeyung; Woo, Se Joon; Park, Kyu Hyung; Kim, Hyuncheol

    2016-06-01

    Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders. PMID:27173745

  8. Genetic loci that control the size of laser-induced choroidal neovascularization

    PubMed Central

    Nakai, Kei; Rogers, Michael S.; Baba, Takashi; Funakoshi, Taisaku; Birsner, Amy E.; Luyindula, Dema S.; D'Amato, Robert J.

    2009-01-01

    Angiogenesis is controlled by a balance between stimulators and inhibitors. We propose that the balance, as well as the general sensitivity of the endothelium to these factors, varies from individual to individual. Indeed, we have found that individual mouse strains have dramatically different responses to growth factor-induced neovascularization. Quantitative trait loci (QTLs), which influence the extent of corneal angiogenesis induced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), were previously identified by our laboratory. To investigate the genetic contribution to choroidal neovascularization (CNV), a leading cause of blindness, we have undertaken a similar mapping approach to identify QTLs that influence laser-induced CNV in the BXD series of recombinant inbred mouse strains. Composite interval mapping identified new angiogenic QTLs on chromosomes 2 and 19, in addition to confirming our previous corneal neovascularization QTLs of AngVq1 and AngFq2. The new QTLs are named AngCNVq1 and AngCNVq2. The newly mapped regions contain several candidate genes involved in the angiogenic process, including thrombospondin 1, delta-like 4, BclII modifying factor, phospholipase C, beta 2, adrenergic receptor, beta 1, actin-binding LIM protein 1 and colony stimulating factor 2 receptor, alpha. Differences in these regions may control individual susceptibility to CNV.—Nakai, K., Rogers, M. S., Baba, T., Funakoshi, T., Birsner, A. E., Luyindula, D. S., D’Amato, R. J. Genetic loci that control the size of laser-induced choroidal neovascularization. PMID:19237505

  9. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Jia, Yali; Bailey, Steven T.; Wilson, David J.; Tan, Ou; Klein, Michael L.; Flaxel, Christina J.; Potsaid, Benjamin; Liu, Jonathan J.; Lu, Chen D.; Kraus, Martin F.; Fujimoto, James G.; Huang, David

    2014-01-01

    Purpose To detect and quantify choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants Five normal subjects and five neovascular AMD patients were included. Methods Five eyes with neovascular AMD and five normal age-matched controls were scanned by a high-speed (100,000 A-scans/sec) 1050 nm wavelength swept-source OCT. The macular angiography scan covered a 3×3 mm area and comprised 200×200×8 A-scans acquired in 3.5 sec. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by three dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2D angiograms from the 3 layers. CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measurements CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNVs showed sizes and locations that were confirmed by fluorescein angiography. OCT angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in one case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch’s layer and classify type I and type II CNV. A feeder vessel could be identified in one case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions OCT angiography provides depth

  10. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  11. Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Clarkson, Donna R.; Valo, Lynn M.; Brown, Jeremiah, Jr.; Stuck, Bruce E.

    2003-06-01

    Purpose: To determine funduscopic criteria that will help predict when bridging choroidal neovascular (CNV) complexes will develop after laser retinal trauma and to define early preventive treatment targets. Methods: Ten rhesus monkeys were used and retinal lesions were produced by Nd:YAG exposures (20ns, 1-2mJ, 1064nm, min. spot size) simulating human accidental laser trauma to the central fundus. Funduscopy and fluorescein/ICG angiography were conducted at day 1, 4, and 14, and at 2 and 4 months, and animals terminated for histologic evaluation. Predisposition for bridging fibrovascular complexes was evaluated for single lesions, two small lesions showing coalescing hemorrhages, and multiple lesions involved with large field subretinal and vitreous hemorrhages. Results: Elevated CNVs were present in all single lesions with confined subretinal hemorrhages. All lesion sets that showed initial and small coalescing subretinal hemorrhages formed bridging CNV scars. No bridging CNVs occurred in lesion sets involving a vitreous hemorrhage adjacent to a confined, but small subretinal hemorrhage. In large field subretinal hemorrhages involving multiple laser lesions, complex CNV formation occurred. Extensive secondary photoreceptor losses occurred in confined hemorrhage and CNV zones. Conclusion: Trauma presenting with evidence of coalescing and confined subretinal hemorrhages between two adjacent lesions has a high chance of forming choroidal neovascular bridge complexes between the involved lesions. CNV formation may be related to the long residence time, break down products, and clearance processes of extravasated blood. Removal of trapped blood and curtailing angiogenesis and cellular proliferation may be helpful treatment strategies.

  12. Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: A report of two patients

    PubMed Central

    Ozkaya, Abdullah; Alkin, Zeynep; Faiz, Miray; Yazici, Ahmet Taylan; Demirok, Ahmet

    2013-01-01

    The aim of this study is to report clinical course of choroidal neovascularization secondary to angioid streaks (AS) in two patients who underwent intravitreal bevacizumab therapy. Fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT) revealed the diagnosis of subfoveal classic choroidal neovascularization (CNV) in the right eye in patient 1 and in the left eye in patient 2. After three consecutive bevacizumab injections, visual acuity improved from 20/40 to 20/25 in patient 1 and from 20/80 to 20/50 in patient 2. After 3 months of therapy, additional bevacizumab injection was administered when the lesion showed recurrence. After a follow-up time of 24-months, patient 1 received 14 intravitreal bevacizumab injections; patient 2 received only 4 injections. Visual acuities remained stable at 20/32 and 20/50 in patient 1 and patient 2, respectively. Though, the patients of CNV secondary to AS showed similar clinical appearance at the beginning, this report provides the data for different responses to intravitreal bevacizumab therapy. While fewer injections were required to control the disease in one patient, the other patient needed much more injections for stabilization of the CNV. Further studies are required to understand the cause of varied treatment responses in those patients. PMID:25473350

  13. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  14. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  15. A Rat Model for Choroidal Neovascularization Using Subretinal Lipid Hydroperoxide Injection

    PubMed Central

    Baba, Takayuki; Bhutto, Imran A.; Merges, Carol; Grebe, Rhonda; Emmert, David; McLeod, D. Scott; Armstrong, Donald; Lutty, Gerard A.

    2010-01-01

    The purpose of this study was to develop and characterize a rat model of choroidal neovascularization (CNV) as occurs in age-related macular degeneration. The lipid hydroperoxide 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (HpODE) is found in submacular Bruch’s membrane in aged humans and has been reported to generate neovascularization in a rabbit model. Three weeks after a single subretinal injection of 30 μg of HpODE, eyes of Sprague-Dawley rats were harvested. Follow-up fluorescein angiography was done on other animals until 5 weeks postinjection. Histological studies, immunohistochemical staining, and flatmount choroids for CNV measurements were performed. In addition, we used murine neuronal, bovine endothelial, and human ARPE19 cells for testing the in vitro effects of HpODE. CNV developed in 85.7% of HpODE-injected eyes. The neovascular areas were significantly greater in HpODE-injected eyes compared with those in control eyes (P = 0.023). The CNV had maximum dye leakage at 3 weeks, which subsided by the 5th week. Histologically, CNV extended from the choriocapillaris into the subretinal space. ED1-positive macrophages were recruited to the site. In vitro assays demonstrated that only 30 ng/ml HpODE induced cell proliferation and migration of endothelial cells. HpODE-induced CNV was highly reproducible, and its natural course seems to be ideal for evaluating therapeutic modalities. Because HpODE has been isolated from aged humans, the HpODE-induced rat model seems to be a relevant experimental model for CNV in age-related macular degeneration. PMID:20395434

  16. Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment

    PubMed Central

    Yin, Houfa; Fang, Xiaoyun; Ma, Jian; Chen, Min; Yang, Yabo; Guo, Shenchao; Chen, Zhiqing; Su, Zhaoan; Feng, Lei; Ye, Panpan; Wu, Fang; Yin, Jinfu

    2016-01-01

    Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV, and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF, and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF, and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL-2, IL-10, basic FGF, and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV. PMID:27558944

  17. 3D choroid neovascularization growth prediction based on reaction-diffusion model

    NASA Astrophysics Data System (ADS)

    Zhu, Shuxia; Chen, Xinjian; Shi, Fei; Xiang, Dehui; Zhu, Weifang; Chen, Haoyu

    2016-03-01

    Choroid neovascularization (CNV) is a kind of pathology from the choroid and CNV-related disease is one important cause of vision loss. It is desirable to predict the CNV growth rate so that appropriate treatment can be planned. In this paper, we seek to find a method to predict the growth of CNV based on 3D longitudinal Optical Coherence Tomography (OCT) images. A reaction-diffusion model is proposed for prediction. The method consists of four phases: pre-processing, meshing, CNV growth modeling and prediction. We not only apply the reaction-diffusion model to the disease region, but also take the surrounding tissues into consideration including outer retinal layer, inner retinal layer and choroid layer. The diffusion in these tissues is considered as isotropic. The finite-element-method (FEM) is used to solve the partial differential equations (PDE) in the diffusion model. The curve of CNV growth with treatment are fitted and then we can predict the CNV status in a future time point. The preliminary results demonstrated that our proposed method is accurate and the validity and feasibility of our model is obvious.

  18. Genetic loci that control the size of laser-induced choroidal neovascularization.

    PubMed

    Nakai, Kei; Rogers, Michael S; Baba, Takashi; Funakoshi, Taisaku; Birsner, Amy E; Luyindula, Dema S; D'Amato, Robert J

    2009-07-01

    Angiogenesis is controlled by a balance between stimulators and inhibitors. We propose that the balance, as well as the general sensitivity of the endothelium to these factors, varies from individual to individual. Indeed, we have found that individual mouse strains have dramatically different responses to growth factor-induced neovascularization. Quantitative trait loci (QTLs), which influence the extent of corneal angiogenesis induced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), were previously identified by our laboratory. To investigate the genetic contribution to choroidal neovascularization (CNV), a leading cause of blindness, we have undertaken a similar mapping approach to identify QTLs that influence laser-induced CNV in the BXD series of recombinant inbred mouse strains. Composite interval mapping identified new angiogenic QTLs on chromosomes 2 and 19, in addition to confirming our previous corneal neovascularization QTLs of AngVq1 and AngFq2. The new QTLs are named AngCNVq1 and AngCNVq2. The newly mapped regions contain several candidate genes involved in the angiogenic process, including thrombospondin 1, delta-like 4, BclII modifying factor, phospholipase C, beta 2, adrenergic receptor, beta 1, actin-binding LIM protein 1 and colony stimulating factor 2 receptor, alpha. Differences in these regions may control individual susceptibility to CNV. PMID:19237505

  19. Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of CXCR4 and CXCR7 Expression in Choroid Endothelial Cell

    PubMed Central

    Feng, Yi-fan; Guo, Hua; Yuan, Fei; Shen, Min-qian

    2015-01-01

    Stromal cell-derived factor-1 (SDF-1) has been confirmed to participate in the formation of choroidal neovascularization (CNV) via its two receptors: CXC chemokine receptors 4 (CXCR4) and CXCR7. Previous studies have indicated that the activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS) might elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological angiogenesis formation remains to be elucidated. The present study shows that LPS enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in choroid-retinal endothelial (RF/6A) cells. In addition, the transcriptional regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation of the extracellular signal-related kinase (ERK) 1/2 and activation of nuclear factor kappa B (NF-κB) signaling pathways, which were blocked by ERK- or NF-κB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4 and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat. SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in LPS-treated rat after a single intravitreal injection. Altogether, these results demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7 expression in endothelial cells, possibly providing a new perspective for the treatment of CNV-associated diseases. PMID:26288180

  20. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M. Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  1. Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal Neovascularization In Vivo

    PubMed Central

    McCloskey, Manabu; Wang, Haibo; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Hartnett, M. Elizabeth

    2013-01-01

    Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV) model of macular degeneration, Rap1b−/− mice exhibited larger CNV volumes compared to wild-type or Rap1a−/−. In vivo, intravitreal injection of a cAMP analog (8CPT-2′-O-Me-cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2′O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2′-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo with 8

  2. Neuroprotectin D1 Attenuates Laser-induced Choroidal Neovascularization in Mouse

    PubMed Central

    Sheets, Kristopher G.; Zhou, Yongdong; Ertel, Monica K.; Knott, Eric J.; Regan, Cornelius E.; Elison, Jasmine R.; Gordon, William C.; Gjorstrup, Per

    2010-01-01

    Purpose To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. Methods C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. Results At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. Conclusions NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-κB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be

  3. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  4. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice

    PubMed Central

    Mizutani, Takeshi; Fowler, Benjamin J.; Kim, Younghee; Yasuma, Reo; Krueger, Laura A.; Gelfand, Bradley D.; Ambati, Jayakrishna

    2015-01-01

    Purpose To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV). Methods We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3−/−, and P2rx7−/− mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2′, 3′-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA. Results Intravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3−/− mice (P < 0.05) but not in P2rx7−/− mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7−/− mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC. Conclusions Multiple clinically relevant NRTIs suppressed laser-induced CNV and downregulated VEGF-A, via P2X7. PMID:26529046

  5. Alcohol and nicotine consumption exacerbates choroidal neovascularization by modulating the regulation of complement system

    PubMed Central

    Kaliappan, Sankaranarayanan; Jha, Purushottam; Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2010-01-01

    The objective of the present study was to investigate the effect of alcohol and nicotine consumption on the pathogenesis of choroidal neovascularization (CNV) in rats after laser-photocoagulation. Confocal microscopic analysis demonstrated an increase in CNV complex size in rats fed with alcohol (2.3-fold), nicotine (1.9-fold), and the combination of alcohol and nicotine (2.7-fold) compared with the control groups. Immunohistochemical analysis revealed that alcohol and nicotine consumption increased MAC deposition and VEGF expression in laser spots. Expression of CD59 by RT-PCR and Western blot was drastically reduced in the animals that were fed with alcohol, nicotine and alcohol and nicotine compared to those fed with water alone and this was associated with exacerbation of CNV. PMID:18789935

  6. Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization

    PubMed Central

    Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.

    2012-01-01

    Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer’s disease and age-related macular degeneration. Sterculic acid demonstrated to be 5–10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. PMID:22342272

  7. AAV2 Delivery of Flt23k Intraceptors Inhibits Murine Choroidal Neovascularization

    PubMed Central

    Zhang, Xiaohui; Das, Subrata K; Passi, Samuel F; Uehara, Hironori; Bohner, Austin; Chen, Marcus; Tiem, Michelle; Archer, Bonnie; Ambati, Balamurali K

    2015-01-01

    Long-term inhibition of extracellular vascular endothelial growth factor (VEGF) in the treatment of age-related macular degeneration (AMD) may induce retinal neuronal toxicity and risk other side effects. We developed a novel strategy which inhibits retinal pigment epithelium (RPE)-derived VEGF, sparing other highly sensitive retinal tissues. Flt23k, an intraceptor inhibitor of VEGF, was able to inhibit VEGF in vitro. Adeno-associated virus type 2 (AAV2)–mediated expression of Flt23k was maintained for up to 6 months postsubretinal injection in mice. Flt23k was able to effectively inhibit laser-induced murine choroidal neovascularization (CNV). VEGF levels in the RPE/choroid complex decreased significantly in AAV2.Flt23k treated eyes. Neither retinal structure detected by Heidelberg Spectralis nor function measured by electroretinography (ERG) was adversely affected by treatment with AAV2.Flt23k. Hence AAV2.Flt23k can effectively maintain long-term expression and inhibit laser-induced CNV in mice through downregulation of VEGF while maintaining a sound retinal safety profile. These findings suggest a promising novel approach for the treatment of CNV. PMID:25306972

  8. Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage

    PubMed Central

    Hwang, Da-Eun; Ryou, Jeong-Hyun; Oh, Jong Rok; Han, Jung Woo; Park, Tae Kwann; Kim, Hak-Sung

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers. PMID:27015541

  9. Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography.

    PubMed

    Zhang, Anqi; Zhang, Qinqin; Wang, Ruikang K

    2015-10-01

    Current optical coherence tomography (OCT) based micro-angiography is prone to a projection (or tailing) effect due to the high scattering property of blood within overlying patent vessels, creating artifacts that interfere with the interpretation of retinal angiographic results. In this work, the projection effect in OCT micro-angiography is examined and its causality is explained by strong light scattering and photon propagation within blood. A simple practical approach is then introduced to minimize these artifacts presented in the outer retinal avascular space, especially useful for examining clinical cases with choroidal neovascularization (CNV). Demonstrated through in-vivo human posterior eye imaging of healthy and CNV subjects, the proposed method is shown effective to eliminate the projection artifacts in outer retinal space of OCT micro-angiography, resulting in better visualization of the pathological neovascularization when compared with the current common approaches. In addition, it is also shown that the proposed method is applicable to minimize the projection artifacts appearing in deep retinal layers. PMID:26504660

  10. Downregulation of p22phox in Retinal Pigment Epithelial Cells Inhibits Choroidal Neovascularization in Mice

    PubMed Central

    Li, Qiuhong; Dinculescu, Astra; Shan, Zhiying; Miller, Rehae; Pang, Jijing; Lewin, Alfred S; Raizada, Mohan K; Hauswirth, William W

    2016-01-01

    Choroidal neovascularization (CNV) occurs in a variety of chorioretinal diseases including age-related macular degeneration (AMD), and is the major cause of severe visual loss in patients with AMD. Oxidative stress has been thought to play an important role in the development of CNV. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the major intracellular sources of reactive oxygen species (ROS) in the vascular system. In this study, we examined the expression of p22phox, an integral subunit in the NADPH oxidase complex, in the mouse eye. We determined that p22phox is expressed in the retinal pigment epithelial (RPE) cells and inner retinal neurons. A small-interfering RNA (siRNA) designed against p22phox efficiently reduced the expression of the protein in the eye when delivered by means of recombinant adeno-associated virus (AAV) vector. Vector treatment inhibited CNV in the mouse when delivered into the subretinal space where RPE cells were transduced. These results suggest that NADPH oxidase–mediated ROS production in RPE cells may play an important role in the pathogenesis of neovascular AMD, and that this pathway may represent a new target for therapeutic intervention in AMD. PMID:18665154

  11. RECURRENT CHOROIDAL NEOVASCULARIZATION AFTER MACULAR TRANSLOCATION SURGERY WITH 360-DEGREE PERIPHERAL RETINECTOMY

    PubMed Central

    BAER, CLAXTON A.; RICKMAN, CATHERINE BOWES; SRIVASTAVA, SUNIL; MALEK, GOLDIS; STINNETT, SANDRA; TOTH, CYNTHIA A.

    2012-01-01

    Purpose To evaluate the pattern of age-related macular degeneration in the new foveal location after macular translocation surgery with 360 degree peripheral retinectomy for neovascular age-related macular degeneration. Methods Clinical data, fundus photos, and fluorescein angiograms of patients in the Duke Macular Translocation Study were reviewed with 2-year follow-up data. Results With 56 patients completing follow-up, no patient developed de novo choroidal neovascularization (CNV), geographic atrophy, or drusen in the new subfoveal retinal pigment epithelium bed. By 2 years, 14 patients (25%) developed recurrent CNV and 13 of these 14 recurrences clearly arose from the old CNV bed. Of the 13 recurrences clearly arising from the old bed, 12 of them had recurrent CNV that involved the margin of the bed closest to the repositioned fovea. Smokers were 5.3 times (95% confidence interval: 1.2–24) more likely to develop recurrent CNV over 2 years. Despite treatment, median visual acuity for the 14 eyes with recurrent CNV was 20/200 compared with 20/80 in eyes without recurrence. Conclusions Findings in this study support the hypotheses that the development of CNV occurs via a signaling mechanism from the fovea. PMID:18626416

  12. Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography

    PubMed Central

    Zhang, Anqi; Zhang, Qinqin; Wang, Ruikang K.

    2015-01-01

    Current optical coherence tomography (OCT) based micro-angiography is prone to a projection (or tailing) effect due to the high scattering property of blood within overlying patent vessels, creating artifacts that interfere with the interpretation of retinal angiographic results. In this work, the projection effect in OCT micro-angiography is examined and its causality is explained by strong light scattering and photon propagation within blood. A simple practical approach is then introduced to minimize these artifacts presented in the outer retinal avascular space, especially useful for examining clinical cases with choroidal neovascularization (CNV). Demonstrated through in-vivo human posterior eye imaging of healthy and CNV subjects, the proposed method is shown effective to eliminate the projection artifacts in outer retinal space of OCT micro-angiography, resulting in better visualization of the pathological neovascularization when compared with the current common approaches. In addition, it is also shown that the proposed method is applicable to minimize the projection artifacts appearing in deep retinal layers. PMID:26504660

  13. Inhibition of RACK1 ameliorates choroidal neovascularization formation in vitro and in vivo.

    PubMed

    Liu, Xiaojuan; Zhu, Manhui; Yang, Xiaowei; Wang, Ying; Qin, Bai; Cui, Chen; Chen, Hui; Sang, Aimin

    2016-06-01

    Choroidal neovascularization (CNV) occurs as a result of age-related macular degeneration (AMD) and causes severe vision loss among elderly patients. The receptor for activated C-kinase 1 (RACK1) serves as a scaffold protein which is recently found to promote angiogenesis. However, the impact of RACK1 on the vascular endothelial growth factor (VEGF) expression in endothelial cells and subsequent choroidal angiogenesis formation remains to be elucidated. In this study, we found that RACK1 and VEGF expression increased, and reached the peak at 7d in mouse CNV model by laser application. Furthermore, on RPE/choroid cryosections, RACK1 co-localized with CD31, suggesting that RACK1 was expressed in endothelial cells. In vitro, RF/6A cell hypoxia model showed that RACK1 expression was up-regulated in parallel with hypoxia-induced factor 1 (HIF-1α) and VEGF expression, reaching the peak at 6h. Silencing of RACK1 suppressed the invasion and tube formation activity of RF/6A cells in ARPE-19 and RF/6A co-culture system, possibly through VEGF signal pathway. Overexpression of RACK1 showed the opposite effect. Intravitreal injection of anti-RACK1 monoclonal antibody predominantly decreased RACK1 and VEGF expression in mouse laser-induced CNV model. Meanwhile, anti-RACK1 monoclonal antibody intravitreal injection also decreased incidence of CNV and leakage area. These data indicated that RACK1 promoted CNV formation via VEGF pathway. Additionally, anti-RACK1 monoclonal antibody significantly decreased CNV in mouse model and may have therapeutic potential in human CNV. PMID:27112838

  14. Optical coherence tomography characteristics of responses to intravitreal bevacizumab in idiopathic choroidal neovascularization

    PubMed Central

    Shah, Syed Nasir Ali; Kang, Qian-Yan; Fan, Xiao-Juan; Sun, Yue-Ming

    2016-01-01

    AIM To investigate factors associated with responses to intravitreal bevacizumab (IVB) in naive idiopathic choroidal neovascularization (iCNV) by high domain optical coherence tomography (OCT). METHODS We retrospectively reviewed clinical data of 40 eyes of iCNV patients who received a single or multiple IVB on an as-needed basis (1.25 mg/0.05 mL). One month after the first injection, subretinal fluid (SRF) volume was evaluated and the eyes were divided into 3 groups based on responses to IVB. Good, moderate, and poor responses were defined as 61%-99%, 30%-60%, and <30% resolution of SRF on OCT after IVB in iCNV, respectively. OCT findings were analyzed to find factors associated with difference in response levels. Comparisons were made using Wilcoxon's matched-pairs signed-rank test, the Mann-Whitney U test for means with continuous data and Fisher's exact test for categorical data. RESULTS The mean number of IVB was 1.28±1.50 and mean follow up time was 3.60±1.20mo. At postoperative 1mo, there were 8 (20%) eyes in good response, 20 (50%) in moderate response and 12 (30%) eyes in poor response group and at last visit there were 28 good responders (70%), 8 (20%) moderate responders and 4 (10%) poor responders. Statistically significant difference was detected between good responders and non good responders in choroidal neovessels thickness (P=0.029), SRF height (P=0.049) and SRF volume (P=0.031) at post treatment 1mo. CONCLUSION OCT is a valuable diagnostic tool. Decrease in choroidal neovessels thickness, SRF height and volume predicts favorable response of iCNV to IVB therapy. PMID:26949649

  15. Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats

    PubMed Central

    Yu, Ya-Jie; Mo, Bin; Liu, Lu; Yue, Yan-Kun; Yue, Chang-Li; Liu, Wu

    2016-01-01

    AIM To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1. PMID:27588264

  16. Block copolymers encapsulated poly (aryl benzyl ether) dendrimer silicon (IV) phthalocyanine for in vivo and in vitro photodynamic efficacy of choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Wang, Xiongwei; Chen, Kuizhi; Huang, Zheng; Peng, Yiru

    2015-03-01

    A novel series of poly (aryl benzyl ether) dendrimer silicon phthalocyanines loaded block copolymers ethoxypoly(ethylene glycol)-poly (lactic-co-glycolic acid) (MPEG-PLGA)were formed. The time-dependent intracellular uptake of nanoparticles in HUVECs cells increased as they were incorporated into nanoparticles. With its highly effective selective accumulation on choroidal neovascularization(CNV). This treatment resulted in a efficacious choroidal neovascularization (CNV) occlusion with minimal unfavorable phototoxicity.

  17. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases.

    PubMed

    Mello, Patrícia Correa de; Berensztejn, Patricia; Brasil, Oswaldo Ferreira Moura

    2016-01-01

    We report enhanced depth imaging optical coherence tomography (EDI-OCT) features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction. PMID:27463635

  18. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report

    PubMed Central

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China. PMID:26640540

  19. Metabolic Syndrome Triggered by High-Fructose Diet Favors Choroidal Neovascularization and Impairs Retinal Light Sensitivity in the Rat

    PubMed Central

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M.; Creuzot-Garcher, Catherine P.; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model. PMID:25380250

  20. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    PubMed Central

    2012-01-01

    Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID:22676316

  1. Effect of cytokeratin 17 on retinal pigment epithelium degeneration and choroidal neovascularization

    PubMed Central

    Shen, Yi; Zhuang, Pei; Xiao, Tao; Chiou, George CY

    2016-01-01

    AIM To study the effects of cytokeratin 17 (CK17) on sodium iodate (NaIO3) induced rat retinal pigment epithelium (RPE) degeneration, laser induced rat choroidal neovascularization (CNV), and oxidative stress of human retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cell (HUVEC). METHODS Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups, 10 rats in control group treated with solvent alone; 10 rats in NaIO3 group treated with solvent and 35 mg/kg NaIO3 injection through hypoglossal vein and 10 rats in CK17+NaIO3 group treated with 1% CK17 eye drop 3 times a day for 1wk before and 4wk after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Another 20 rats were randomly divided into 2 groups. Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1% CK17 eye drop before same as above; 10 rats in control were received Nd:YAG and treated with solvent. The development of choroidal neovascularization (CNV) was determined by fundus fluorescein angiography (FFA) performed on 4wk after laser. Methylthiazoly tetrazolium (MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro. RESULTS Four weeks after NaIO3 injection, the c-wave amplitude of ERG was 0.393±0.02 V in the control group, 0.184±0.018 V in NaIO3 group and 0.3±0.01 V in CK17+NaIO3 group. There was a significant reversal of the c-wave by CK17 as compared to NaIO3 group (P<0.01). Four weeks after laser, the size of the CNV lesion was 2.57±0.27 mm2 in control group and 1.64±0.08 mm2 in CK17 group. The lesion size significantly diminished in CK17 group (P<0.01). The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 µg/mL and enhanced the injury in HUVECs at different concentrations. CONCLUSION CK17 can significantly protect RPE from NaIO3 induced degeneration in vivo and in vitro and

  2. Surgery for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration: Ophthalmic Findings

    PubMed Central

    2005-01-01

    Purpose To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). Design Randomized clinical trial. Participants Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). Methods Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. Main Outcome Measure A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. Results Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. Conclusions Submacular surgery, as performed in this

  3. Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

    SciTech Connect

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

    2011-06-01

    Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

  4. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice

    PubMed Central

    Sun, Ye; Fu, Zhongjie; Liu, Chi-Hsiu; Evans, Lucy; Tian, Katherine; Saba, Nicholas; Fredrick, Thomas; Morss, Peyton; Chen, Jing; Smith, Lois E. H.

    2015-01-01

    The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model. PMID:26161975

  5. Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic

    PubMed Central

    2005-01-01

    Objective To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. Methods Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye (“study eye”). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. Results Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89–1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n=92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08–2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month

  6. Melissa officinalis Extract Inhibits Laser-Induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Lee, Eun Kyoung; Kim, Young Joo; Kim, Jin Young; Song, Hyun Beom; Yu, Hyeong Gon

    2014-01-01

    Purpose This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated. Methods Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs). Results The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P<0.001), 44.09±12.01 µm in the low-dose group (P = 0.016), and 51.00±12.37 µm in the control group. The proportion of CNV lesions with clinically significant fluorescein leakage was 9.2% in rats treated with high-dose M. officinalis, which was significantly lower than in control rats (53.4%, P<0.001). The levels of VEGF, MMP-2, and MMP-9 were significantly lower in the high-dose group than in the control group. Meanwhile, M. officinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. Conclusions Systemic administration of M. officinalis extract suppressed laser-induced CNV

  7. Photodynamic therapy for unilateral idiopathic peripapillary choroidal neovascularization in a child.

    PubMed

    Yıldırım, Cem; Çetin, Ebru Nevin; Yayla, Kemal; Avunduk, Avni Murat; Yaylalı, Volkan

    2011-08-01

    A 10-year-old girl presented with visual loss in her right eye. Best-corrected visual acuity was 20/50 in the right eye and 20/20 in the left eye. Dilated funduscopic examination revealed a yellowish elevated lesion near the optic disc with macular edema and hemorrhage on the inferotemporal vascular arcade in the right eye. Fluorescein angiography showed a hyperfluorescent lesion consistent with choroidal neovascularization (CNV) and optical coherence tomography (OCT) showed a peripapillary lesion with subretinal fluid elevating the neurosensory retina in the macular area. With a diagnosis of unilateral idiopathic peripapillary CNV, the patient underwent photodynamic therapy (PDT) with verteporfin. At the four month follow-up, visual acuity increased to 20/25 and OCT showed peripapillary scar formation and total resolution of the subretinal fluid. At the one year follow-up, visual acuity and fundus were stable without recurrence of the lesion. PDT for peripapillary CNV in children has not previously been reported. Although it seems to be a favorable treatment option for peripapillary lesions, there is a lack of knowledge about long-term follow-up in pediatric cases. PMID:21637978

  8. Therapeutic Effect of Oral Bisphosphonates on Choroidal Neovascularization in the Human Eye

    PubMed Central

    Honda, Shigeru; Nagai, Takayuki; Kondo, Naoshi; Fukuda, Masahide; Kusuhara, Sentaro; Tsukahara, Yasutomo; Negi, Akira

    2010-01-01

    Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM. PMID:20706646

  9. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization

    PubMed Central

    Wang, Haibo; Jiang, Yanchao; Shi, Dallas; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Wittchen, Erika S.; Li, Dean Y.; Hartnett, M. Elizabeth

    2014-01-01

    Activation of Rap1 GTPase can improve the integrity of the barrier of the retina pigment epithelium (RPE) and reduce choroidal neovascularization (CNV). Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1 inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a murine model of laser-induced CNV, we determined that reduced Rap1 activity in RPE/choroid occurred with CNV formation and that activation of Rap1 by 2′-O-Me-cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS. In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE barrier integrity via cadherin phosphorylation and facilitated choroidal EC migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b−/− mice reduced laser-induced CNV, in correlation with decreased ROS generation in RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier.—Wang, H., Jiang, Y., Shi, D., Quilliam, L. A., Chrzanowska-Wodnicka, M., Wittchen, E. S., Li, D. Y., Hartnett, M. E. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization. PMID:24043260

  10. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration.

    PubMed

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA(®)), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD. PMID:26719668

  11. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

    PubMed Central

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD. PMID:26719668

  12. Clinicopathological correlation of an excised choroidal neovascular membrane in pseudotumour cerebri

    PubMed Central

    Castellarin, A.; Sugino, I.; Nasir, M.; Zarbin, M.

    1997-01-01

    AIMS/BACKGROUND—To correlate the histopathology of an excised choroidal neovascular membrane (CNV) with the clinical and angiographic findings in a 32-year-old woman with pseudotumour cerebri and a peripapillary CNV with subfoveal extension.
METHODS—The patient's visual acuity was assessed by individuals experienced in low vision refraction and who were not members of the surgical team. The CNV was excised via a conventional three port vitrectomy with subretinal dissection. The excised tissue was studied with light and electron microscopy. Preoperative and serial postoperative fluorescein angiograms (FAs) and fundus photographs were obtained to study the dissection bed.
RESULTS—One week after surgery, the FA showed mottled subfoveal choriocapillaris perfusion. Three weeks after surgery, this area showed retinal pigment epithelium (RPE) atrophy clinically, and the FA showed choriocapillaris non-perfusion. Six months after surgery, the area of RPE atrophy and the corresponding area of choriocapillaris non-perfusion had expanded. Histologically, the excised CNV disclosed hyperplastic RPE, fibrovascular tissue, and no choriocapillaris. Fragments of RPE basement were present along the external edge of the specimen. The patient's visual acuity did not improve significantly after surgery.
CONCLUSIONS—Choriocapillaris non-perfusion can develop even in young patients following CNV excision. In this particular case, it is believed that choriocapillaris atrophy was caused by incomplete ingrowth of RPE into the dissection bed following RPE removal with CNV excision. As far as is known, this is the first report describing the results of surgery for CNV secondary to papilloedema associated with pseudotumour cerebri.

 PMID:9505826

  13. Methallothionein-3 contributes to vascular endothelial growth factor induction in a mouse model of choroidal neovascularization.

    PubMed

    Choi, Jeong A; Hwang, Jong-uk; Yoon, Young Hee; Koh, Jae-Young

    2013-10-01

    In the present study, we investigated possible roles of the zinc (Zn)-binding protein metallothionein-3 (MT3) and cellular Zn in a mouse model of laser-induced choroidal neovascularization (CNV) using wild-type (WT) and MT3-knockout (KO) mice. Quantitative RT-PCR was used for the detection of MT3 mRNA. CNV was induced in mice between 8 and 12 weeks of age by disrupting the Bruch's membrane using an argon laser. Fundus photography and fluorescein angiography (FA) were performed 2 weeks following laser photocoagulation. The possible connection between MT3 and vascular endothelial growth factor (VEGF) expression was explored by quantifying VEGF levels in WT and MT3-KO mouse retinas by enzyme-linked immunosorbent assay. The role of Zn in VEGF expression was tested in WT and MT3-KO cells treated with pyrithione, with or without additional Zn, using immunoblotting and fluorescence photomicrography. Following laser-treatment, MT3-KO mice exhibited substantially smaller areas of CNV compared to WT mice. In addition, retinal angiograms revealed less severe fluorescein leakage in MT3-KO mice than in WT mice. On day 14 following the induction of CNV, VEGF expression was markedly increased in WT mice, but remained unchanged in MT3-KO mice. Consistent with the possible involvement of Zn released from MT3, raising intracellular Zn levels increased VEGF levels and activated its receptor, Flk-1, in both WT and MT3-KO retinal cells. Present results demonstrated that neural retinal cells express high levels of MT3, which might play a role in the process of CNV development. Moreover, Zn released from MT3 may contribute to VEGF induction. PMID:23962989

  14. Surgical removal of subfoveal choroidal neovascularization in pathologic myopia: a 12-year follow-up study.

    PubMed

    Hera, R; Chiquet, C; Romanet, J P

    2013-12-01

    The purpose of this study was to review the 12-year visual outcomes of patients who underwent surgical removal for subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia. This retrospective study included 14 patients, with a mean age of 45.8 years, high myopia (>6 D) and classic subfoveal CNV. They were treated with pars plana vitrectomy and surgical removal of CNV. All patients were followed up every 3 months for 2 years, with visual acuity (VA), fundus examination, and fluorescein angiography and then every year for 5 years. Ten patients underwent a final visit with VA and fundus examination after a minimum 12-year follow-up. The main outcome measurement was VA and the secondary outcome measurement was the lesion size. After 12 years of follow-up, the mean VA did not significantly change over time, with a mean gain of 0.22 logMAR at 1 year, and 0.18, 0.12 and 0.05 at 2, 5 and 12 years, respectively. The anatomical evolution was characterized by a significant enlargement of the lesion size at 5 years. This study showed that final VA after surgical treatment with 12 years of follow-up was poor, due to the significant CNV scar enlargement over time. These results should prompt a prospective randomized study of other medical treatments, particularly anti-vascular endothelial growth factor therapy. PMID:23539478

  15. Diagnosis and Follow-Up of Nonexudative Choroidal Neovascularization With Multiple Optical Coherence Tomography Angiography Devices: A Case Report.

    PubMed

    Lane, Mark; Ferrara, Daniela; Louzada, Ricardo Noguera; Fujimoto, James G; Seddon, Johanna M

    2016-08-01

    Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:778-781.]. PMID:27548457

  16. A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration.

    PubMed

    Cashman, Siobhan M; Ramo, Kasmir; Kumar-Singh, Rajendra

    2011-01-01

    Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD. PMID:21552568

  17. In vivo bioluminescence imaging of hyperglycemia exacerbating stem cells on choroidal neovascularization in mice

    PubMed Central

    Gao, Xiang; Wang, Yu; Hou, Hui-Yuan; Lyu, Yang; Wang, Hai-Yan; Yao, Li-Bo; Zhang, Jian; Cao, Feng; Wang, Yu-Sheng

    2016-01-01

    AIM To investigate the influence of hyperglycemia on the severity of choroidal neovascularization (CNV), especially the involvement of bone marrow-derived cells (BMCs) and underlying mechanisms. METHODS BMCs from firefly luciferase (Fluc)/green fluorescent protein (GFP) double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin (STZ) daily for 5 consecutive days to induce diabetes mellitus (DM), followed by CNV laser photocoagulation. The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging (BLI) and in vitro Fluc assays. The CNV severity was evaluated by H&E staining and choroidal flatmount. The expression of vascular endothelial growth factor (VEGF) and stromal cell derived factor-1 (SDF-1) was detected by Western Blot. RESULTS BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc+GFP+ BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21 (121861.67±9948.81 vs 144998.33±13787.13 photons/second/cm2/sr for control and DM mice, P5d<0.05; 178791.67±30350.8 vs 240166.67±22605.3, P7d<0.05; 124176.67±16253.52 vs 196376.67±18556.79, P14d<0.05; 97951.60±10343.09 vs 119510.00±14383.76, P21d<0.05), which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc (RLU1)], 215.00±52.05 vs 707.33±88.65, P<0.05; RLU1/ relative light units of renilla luciferase (RLU2), 0.90±0.17 vs 1.83±0.17, P<0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and 21 (147.83±17.36 vs 220.33±20.17 µm, P5d<0.05; 212.17±24.63 vs 326.83±19.49, P7d<0.05; 163.17±18.24 vs 265.17±20.55, P14d<0.05; 132.00±10.88 vs 205.33±12.98, P21d<0.05). The average area of CNV in the DM

  18. Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

    PubMed Central

    Shirinifard, Abbas; Glazier, James Alexander; Swat, Maciej; Gens, J. Scott; Family, Fereydoon; Jiang, Yi; Grossniklaus, Hans E.

    2012-01-01

    Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression. PMID:22570603

  19. Effect of charred Radix et Rhizoma Rhei in a laser-induced choroidal neovascularization murine model.

    PubMed

    Han, Dongmei; Yao, Yuan; Sun, Yong; Gong, Yuanyuan; Wu, Xingwei

    2015-04-01

    A pharmaceutical composition (patent no. WO2012079419) exhibited favorable outcomes in a clinical trial of wet age‑related macular degeneration. The aims of the present study were to explore the effects of one composition component, charred Radix et Rhizoma Rhei (CRRR), in a laser‑induced choroidal neovascularization (CNV) murine model. A total of 30 eight‑week‑old C57BL/6 mice were subjected to diode laser treatment, and CNV was induced by rupturing the Bruch's membrane. The mice were then randomly divided into two groups: the CRRR‑treated group that was administered CRRR water extract (concentration, 0.6 g/100 ml; dose, 1 ml/0.1 kg twice a day for 21 days); and the control group that was treated with saline (dose, 1 ml/0.1 kg twice a day for 21 days). The retinal tissue was subjected to quantitative polymerase chain reaction (qPCR) and western blot analysis to determine the expression levels of interleukin‑10 (IL‑10) and vascular epithelial growth factor (VEGF) at day seven following laser treatment. At weeks 2 and 3 after laser treatment, fundus fluorescein angiography was performed and graded to assess the severity of lesion leakage. Retinal flat mounts were prepared for three‑dimensional confocal microscopy at day 22 after laser treatment. At days 14 and 21 after laser treatment, no statistically significant differences were observed between the clinically relevant lesions of the CRRR‑treated and control mice. CNV volumes were not found to be significantly different between the CRRR‑treated and control mice. The expression levels of IL‑10 were significantly increased in the CRRR‑treated mice (P<0.05). However, no statistically significant differences were observed between the VEGF expression levels of the CRRR‑treated and control mice. In conclusion, CRRR did not appear to significantly inhibit CNV in this murine model. The function of CRRR in the pharmaceutical composition may be due to the effects of IL‑10 and a synergistic effect

  20. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 108 viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  1. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  2. IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment.

    PubMed

    Gaddipati, Subhash; Lu, Qingxian; Kasetti, Ramesh Babu; Miller, M Clarke; Lu, Qingjun; Trent, John O; Kaplan, Henry J; Li, Qiutang

    2015-01-01

    The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 ¼m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retrobulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR) tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of TPCA-1 delivered

  3. Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

    SciTech Connect

    Hirasawa, Naoki . E-mail: naoki_h@nirs.go.jp; Tsuji, Hiroshi; Ishikawa, Hitoshi; Koyama-Ito, Hiroko; Kamada, Tadashi; Mizoe, Jun-Etsu; Ito, Yoshiyuki; Naganawa, Shinji; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    2007-02-01

    Purpose: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. Methods and Materials: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). Results: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 {+-} 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50{sub IC} (volume irradiated {>=}50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50{sub IC} {>=}0.127 mL and those with V50{sub IC} <0.127 mL were 71.4 {+-} 8.5% and 11.5 {+-} 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 {+-} 10.4% and 28.4 {+-} 8.0%, respectively. Conclusion: Dose-volume histogram analysis with computed tomography indicated that V50{sub IC} and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.

  4. Antiangiogenic Effects of Topically Administered Multiple Kinase Inhibitor, Motesanib (AMG 706), on Experimental Choroidal Neovascularization in Mice

    PubMed Central

    Rho, Chang Rae; Kang, Seungbum; Park, Ki Cheol; Yang, Keum-Jin; Choi, Hyunsu

    2015-01-01

    Abstract Purpose: To investigate the effect of topical motesanib, an inhibitor of receptor tyrosine kinase, on experimental choroidal neovascularization (CNV). Methods: CNV was induced in 46 nine-week-old male C57BL/6 mice using fundus laser photocoagulation. The right eye of each mouse was treated with motesanib eye drop (4 times daily) and the left eye with vehicle eye drop (4 times daily) for 14 days. To evaluate changes in the CNV lesions, fluorescein angiography, immunofluorescence staining with CD34, and histological examinations were performed 14 days after CNV induction. The expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) in choroidal tissues was determined using western blot analysis to demonstrate the inhibitory effect of topically administered motesanib on intracellular signaling pathways involved in CNV development. Results: Fluorescein angiography showed that fluorescence leakage in eyes treated with topical motesanib was significantly less than in mice treated with vehicle (P=0.01). On immunofluorescence staining, the CD34-labeled area was smaller in topical motesanib-treated eyes (P<0.001). The expression level of phosphorylated ERK1/2 relative to that of total ERK1/2 decreased in eyes treated with topical motesanib compared with eyes treated with vehicle. Conclusion: Topical motesanib significantly reduced laser-induced CNV in the experimental mouse model. PMID:25255037

  5. Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization

    PubMed Central

    Lytvynchuk, Lyubomyr; Sergienko, Andrii; Lavrenchuk, Galina; Petrovski, Goran

    2015-01-01

    Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro. PMID:26491557

  6. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration.

    PubMed

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-01

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas "plasma" that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV. PMID:25573059

  7. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration

    PubMed Central

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-01

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas “plasma” that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV. PMID:25573059

  8. Suppression of Laser-Induced Choroidal Neovascularization by the Oral Medicine Targeting Histamine Receptor H4 in Mice

    PubMed Central

    Ijima, Ryo; Kaneko, Hiroki; Ye, Fuxiang; Takayama, Kei; Nagasaka, Yosuke; Kataoka, Keiko; Funahashi, Yasuhito; Iwase, Takeshi; Kachi, Shu; Kato, Seiichi; Terasaki, Hiroko

    2015-01-01

    Purpose This study aimed to examine relationship of histamine receptor H4 (HRH4) and the pathogenesis of laser-induced choroidal neovascularization (laser-CNV) and to determine whether oral administration of HRH4 antagonists suppressed laser-CNV in mice. Methods Laser photocoagulation was performed in mice to induce the laser-CNV. Histamine was administered intravitreously, and CNV volume was measured. Laser photocoagulation and intravitreous injection of HRH4 antagonist JNJ7777120 were performed after intraperitoneal injection of clodronate liposome, which depletes circulating monocyte-derived macrophages; CNV volume was compared with that in mice injected with control (dimethyl sulfoxide [DMSO]/PBS). Three days after laser-CNV, the F4/80+CD11b+ macrophage population in retinal pigment epithelium (RPE)/choroid complex was quantified with flow cytometry in wild-type and Hrh4−/− mice. The long-acting HRH4 antagonist JNJ28307474 was then administrated periorally, and the laser-CNV volume was compared with controls. Results Intravitreous injection of histamine did not affect laser-CNV volume. The laser-CNV from the eye injected with JNJ7777120 was equivalent to that injected with the DMSO/PBS in mice that had intraperitoneally received clodronate liposome. Flow cytometry after laser-CNV induction revealed a smaller F4/80+CD11b+ macrophage population in the RPE/choroid complex of Hrh4−/− mice than in wild-type mice. Oral administration of JNJ28307474 significantly reduced laser-CNV volume in wild-type mice. Conclusions Our results suggested that HRH4-positive macrophages played an important role in the pathogenesis of laser-CNV and that they require a different ligand from that of histamine. The oral administration of an HRH4 antagonist successfully reduced laser-CNV. Translational Relevance Our results indicate that drugs targeting HRH4 are potentially a novel oral treatment for age-related macular degeneration. PMID:25774332

  9. [New drug VEGF Trap-Eye--Eylea--and its use in the treatment of age-related macular degeneration, central retinal vein occlusion, diabetic macular edema, and choroidal neovascularization secondary to pathologic myopia].

    PubMed

    Rejdak, Robert; Szkaradek, Małgorzata; Taslaq, Wesam; Kałuzny, Jakub J; Grieb, Pawel; Jünemann, Anselm G M

    2012-01-01

    Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of choroidal and retinal neovascularization. Anti-VEGF therapy changed the standard-of-care for ocular disease with neovascularisation. This article presents one promising new drug--VEGF Trap-Eye--and results of clinical trials evaluating its efficacy in the treatment of wet age-related macular degeneration, central retinal vain occlusion, diabetic macular edema and choroidal neovascularization secondary to pathologic myopia. PMID:23461161

  10. Roles of NFκB-miR-29s-MMP-2 circuitry in experimental choroidal neovascularization

    PubMed Central

    2014-01-01

    Background Previous reports have indicated that matrix metallopeptidase-2 (MMP-2) regulates angiogenic processes, which are involved in choroidal neovascularization (CNV). However, the regulation of MMP-2 in CNV has not been well-characterized. To gain more information about the regulation of MMP-2 in CNV, we analyzed the circuitry associated with MMP-2 regulation in a CNV model and in cell cultures, focusing on NFκB and the microRNA-29 family (miR-29s). Methods The CNV model was established by subjecting C57BL/6 mice to fundus photocoagulation with a krypton red laser. In choroidal-retinal pigment epithelial (RPE) tissues of the model, immunohistochemistry was used to evaluate the angiogenesis and MMP-2 expression; reverse-transcription quantitative PCR (RT-qPCR) was used to determine the levels of miR-29s; and western blot was used to analyze the protein levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitor, IκBα, and its phosphorylated form, phospho-IκBα. At the cellular level, RT-qPCR was used to examine the levels of miR-29s following NFκB activation by tumor necrosis factor alpha (TNFα); and western blot and luciferase assay were used to determine the regulation of MMP-2 by miR-29s in a human RPE cell line (ARPE-19) and in an umbilical vein endothelial cell line (EA hy926). Results MMP-2 staining was increased in the choroidal neovascular membrane of laser-treated retina. Also, the NFκB pathway was induced in choroid-RPE tissue, as evidenced by a lower protein level of IκBα and a higher level of phospho-IκBα in the tissue homogenates than in those from non-treated eyes. During the period when the NFκB pathway was induced, reduced miR-29s were detected in the choroidal-RPE tissue of the laser-treated eyes. In cultured ARPE-19 cells, TNFα decreased miR-29a, b, and c, and the effects were rescued by NFκB decoy. In ARPE-19 and EA hy926, miR-29s mimics reduced the contents of secreted MMP-2 in the culture media

  11. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

    PubMed Central

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J.; Bainbridge, James W.; Gale, David C.; Pierre, Esaie; Krauss, Achim H.P.; Adamson, Peter; Shima, David T.; Ng, Yin-Shan

    2016-01-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. PMID:26188133

  12. Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice.

    PubMed

    Iwanishi, Hiroki; Fujita, Norihito; Tomoyose, Katsuo; Okada, Yuka; Yamanaka, Osamu; Flanders, Kathleen C; Saika, Shizuya

    2016-06-01

    We evaluated the effects of the loss of Smad3 on the development of experimental argon laser-induced choroidal neovascularization (CNV) in mice. An in vitro angiogenesis model was also used to examine the role of transforming growth factor-β1 (TGFβ1)/Smad3 signaling in vessel-like tube formation by human umbilical vein endothelial cells (HUVECs). CNV was induced in eyes of 8-12-week-old B6.129-background Smad3-deficient (KO) mice (n=47) and wild-type (WT) mice (n=47) by argon laser irradiation. Results showed that the size of the CNV induced was significantly smaller in KO mice as compared with WT mice at day 14 as revealed by high-resolution angiography with fluorescein isothiocyanate-dextran. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction of RNA extracted from laser-irradiated choroidal tissues were conducted on specimens at specific timepoints. Invasion of macrophages (F4/80+), but not neutrophils (myeloperoxidase+), and appearance of myofibroblasts (α-smooth muscle actin+) were suppressed in laser-irradiated KO tissues. mRNA expression of inflammation-related factors, that is, vascular endothelial growth factor (VEGF), macrophage-chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and TGFβ1 in choroidal tissues was suppressed by the loss of Smad3. We then examined the effects of adding a Smad3 inhibitor, SIS3, or an ALK5 inhibitor, SB431542, on tube formation promoted by TGFβ1 or VEGF in HUVECs cocultured with fibroblast feeder. Further addition of SIS3 or SB431542 augmented vessel-like tube formation by HUVECs in the presence of TGFβ1 or VEGF. In conclusion, lack of Smad3 attenuated the growth of laser-induced CNV with suppression of inflammation by macrophages in mice. Because blocking TGFβ1/Smad3 signal stimulated the activity of angiogenesis of HUVECs in vitro, the reduction of CNV in vivo in KO mice is attributed to a decrease in growth factor levels in the tissue by the loss of Smad3. PMID:26950486

  13. Therapeutic effect of intravitreal injections of ranibizumab for the treatment of macular choroidal neovascularization caused by pathological myopia

    PubMed Central

    JI, LEIBING; LV, WENJUAN; XIAO, YUN; XU, ZHENGHUA; ZHANG, XIAOLING; ZHANG, WEI

    2015-01-01

    The aim of the present study was to evaluate the clinical efficacy and safety of intravitreal ranibizumab injections for the treatment of macular choroidal neovascularization (CNV) caused by pathological myopia. Between one and four intravitreal injections of ranibizumab were administered to 61 eyes from 61 patients who were diagnosed with macular CNV caused by pathological myopia. Following injection, the best-corrected visual acuity (BCVA), central macular thickness (CMT) and fundus fluorescein angiography (FFA) findings were evaluated monthly for a period of 6 months. Among the 61 eyes, 10 eyes received one injection, 44 received two injections, six received three injections and one received four injections (average, 1.97 injections). The BCVA was 0.02±0.01 prior to treatment and 0.30±0.03 subsequent to treatment, and this difference was statistically significant (P<0.01). The CMT was reduced by an average of 45.1 µm. Regarding the FFA results, 56 eyes had no CNV fluorescence leakage and five eyes had CNV fluorescence leakage following treatment; however, the intensity of CNV fluorescence leakage in the five eyes following treatment was lower than that prior to treatment. As a treatment for pathological myopia-induced macular CNV, intravitreal injections of ranibizumab may improve eyesight as well as the macular retinal tissue structure; thus, this is a safe and effective treatment method. PMID:26622450

  14. Myeloid-Specific Blockade of Notch Signaling Attenuates Choroidal Neovascularization through Compromised Macrophage Infiltration and Polarization in Mice

    PubMed Central

    Dou, Guo-Rui; Li, Na; Chang, Tian-Fang; Zhang, Ping; Gao, Xiang; Yan, Xian-Chun; Liang, Liang; Han, Hua; Wang, Yu-Sheng

    2016-01-01

    Macrophages have been recognized as an important inflammatory component in choroidal neovascularization (CNV). However, it is unclear how these cells are activated and polarized, how they affect angiogenesis and what the underlining mechanisms are during CNV. Notch signaling has been implicated in macrophage activation. Previously we have shown that inducible disruption of RBP-J, the critical transcription factor of Notch signaling, in adult mice results in enhanced CNV, but it is unclear what is the role of macrophage-specific Notch signaling in the development of CNV. In the current study, by using the myeloid specific RBP-J knockout mouse model combined with the laser-induced CNV model, we show that disruption of Notch signaling in macrophages displayed attenuated CNV growth, reduced macrophage infiltration and activation, and alleviated angiogenic response after laser induction. The inhibition of CNV occurred with reduced expression of VEGF and TNF-α in infiltrating inflammatory macrophages in myeloid specific RBP-J knockout mice. These changes might result in direct inhibition of EC lumen formation, as shown in an in vitro study. Therefore, clinical intervention of Notch signaling in CNV needs to pinpoint myeloid lineage to avoid the counteractive effects of global inhibition. PMID:27339903

  15. Intravenous Bevacizumab Causes Regression of Choroidal Neovascularization Secondary to Diseases Other Than Age-related Macular Degeneration

    PubMed Central

    NGUYEN, QUAN DONG; SHAH, SYED MAHMOOD; HAFIZ, GULNAR; DO, DIANA V.; HALLER, JULIA A.; PILI, ROBERTO; ZIMMER-GALLER, INGRID E.; JANJUA, KASHIF; SYMONS, R. C. ANDREW; CAMPOCHIARO, PETER A.

    2016-01-01

    PURPOSE To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN Nonrandomized clinical trial. METHODS Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 μm. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 μm representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV. PMID:18054887

  16. Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration

    PubMed Central

    Biswas, Partha; Sengupta, Subhrangshu; Choudhary, Ruby; Home, Subhankar; Paul, Ajoy; Sinha, Sourav

    2011-01-01

    Context: Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD). Aims: To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD. Settings and Design: Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India. Materials and Methods: One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant. Results: The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed. Conclusions: Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD. PMID:21586838

  17. Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials

    PubMed Central

    Maguire, Maureen G.; Daniel, Ebenezer; Shah, Ankoor R.; Grunwald, Juan E.; Hagstrom, Stephanie A.; Avery, Robert L.; Huang, Jiayan; Martin, Revell W.; Roth, Daniel B.; Castellarin, Alessandro A.; Bakri, Sophie J.; Fine, Stuart L.; Martin, Daniel F.

    2013-01-01

    Objective To assess the influence of drug, dosing regimen, and traditional, non-traditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Design Cohort study of patients enrolled in a multicenter randomized clinical trial. Participants Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Methods Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography (OCT) of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to three different regimens for dosing over a two-year period. The genotypes for four single nucleotide polymorphisms (SNPS) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. CATT ophthalmologists examined patients every four weeks through two years and recorded treatment for CNV in the fellow eye. Main Outcome Measures Development of CNV in the fellow eye. Results Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At two years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference 4.0%, 95% confidence interval (−1.7%, 9.6%); p=0.17). The risk ratio for pro re nata (PRN) dosing relative to monthly dosing was 1.1 (95% confidence interval (0.8, 1.6)). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3

  18. Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage

    PubMed Central

    Tan, Xue; Fujiu, Katsuhito; Manabe, Ichiro; Nishida, Junko; Yamagishi, Reiko; Terashima, Yuya; Matsushima, Kouji; Kaburaki, Toshikatsu; Nagai, Ryozo; Yanagi, Yasuo

    2016-01-01

    Purpose To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. Methods We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. Results In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4–/–or Rag2–/–mice and controls, whereas lesion size was significantly reduced in CCR2−/− mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular

  19. A reproducible and quantifiable model of choroidal neovascularization induced by VEGF A165 after subretinal adenoviral gene transfer in the rabbit

    PubMed Central

    Kreppel, Florian; Beck, Susanne; Heiduschka, Peter; Brito, Veronica; Schnichels, Sven; Kochanek, Stefan; Schraermeyer, Ulrich

    2008-01-01

    Purpose To determine the effects of the vascular endothelial growth factor (VEGF)-A165 delivered using a high capacity adenoviral vector (HC Ad.VEGF-A) on vascular growth and pathological changes in the rabbit eye. To combine different detection methods of VEGF-A165 overexpression-induced neovascularization in the rabbit. Methods HC Ad.VEGF-A165 was constructed and injected at 5x106 infectious units (iu) into the subretinal space of rabbit eyes. Two and four weeks postinjection, the development of neovascularization and the expression of HC Ad-transduced VEGF-A165 protein were followed up in vivo by scanning laser ophthalmoscopy, fluorescein and indocyanine green angiographies and ex vivo by electron microscopy and immunohistochemistry Results We observed a choroidal neovascularization (CNV) with leakage in 83% of the rabbit eyes. Our findings present clear indications that there is a significant effect on the endothelial cells of the choriocapillaris after subretinal transduction of the retinal pigment epithelium (RPE) with VEGF-A165 vector. The choroidal endothelial cells were activated, adherent junctions opened, and the fenestration was minimized, while the extracellular matrix localized between the RPE and the endothelium of the choriocapillaris was enlarged toward the lumen of the vessels, inducing a deep invagination of the endothelial cells into the vessel lumen. They also proliferated and formed pathological vessels in the subretinal space. Moreover,there was an increased expression of basic fibroblast growth factor and VEGF-A accompanied by macrophage stimulation, retinal edema, and photoreceptor loss. Conclusions This is the first model of VEGF-induced CNV in the rabbit in which the pathological events following overexpression of VEGF by RPE cells have been described in detail. Many of the features of our experimental CNV resemble those observed clinically in patients having wet age-related macular degeneration. PMID:18682809

  20. Targeting the IRE1α/XBP1 and ATF6 Arms of the Unfolded Protein Response Enhances VEGF Blockade to Prevent Retinal and Choroidal Neovascularization

    PubMed Central

    Liu, Li; Qi, Xiaoping; Chen, Zhijuan; Shaw, Lynn; Cai, Jun; Smith, Layton H.; Grant, Maria B.; Boulton, Michael E.

    2014-01-01

    Although anti-vascular endothelial growth factor (VEGF) treatments reduce pathological neovascularization in the eye and in tumors, the regression is often not sustainable or is incomplete. We investigated whether vascular endothelial cells circumvent anti-VEGF therapies by activating the unfolded protein response (UPR) to override the classic extracellular VEGF pathway. Exposure of endothelial cells to VEGF, high glucose, or H2O2 up-regulated the X-box binding protein-1/inositol-requiring protein-1 (IRE1) α and activating transcription factor 6 (ATF6) arms of the UPR compared with untreated cells. This was associated with increased expression in α-basic crystallin (CRYAB), which has previously bound VEGF. siRNA knockdown or pharmacological blockade of IRE1α, ATF6, or CRYAB increased intracellular VEGF degradation and decreased full-length intracellular VEGF. Inhibition of IRE1α, ATF6, or CRYAB resulted in an approximately 40% reduction of in vitro angiogenesis, which was further reduced in combination with a neutralizing antibody against extracellular VEGF. Blockade of IRE1α or ATF6 in the oxygen-induced retinopathy or choroidal neovascularization mouse models caused an approximately 35% reduction in angiogenesis. However, combination therapy of VEGF neutralizing antibody with UPR inhibitors or siRNAs reduced retinal/choroidal neovascularization by a further 25% to 40%, and this inhibition was significantly greater than either treatment alone. In conclusion, activation of the UPR sustains angiogenesis by preventing degradation of intracellular VEGF. The IRE1α/ATF6 arms of the UPR offer a potential therapeutic target in the treatment of pathological angiogenesis. PMID:23395094

  1. Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME

    PubMed Central

    Nickla, Debora L.; Damyanova, Petya; Lytle, Grace

    2010-01-01

    In birds, the choroid plays a role in the visual regulation of eye growth, thickening in response to myopic defocus, and thinning in response to hyperopic defocus, in both cases moving the retina towards the image plane. This response is rapid, occurring within hours of the defocus stimulus. These changes are consistently associated with slower changes in the sclera, that result in the appropriate changes in axial elongation, decreasing growth in response to myopic defocus and increasing it in response to hyperopic defocus. The molecular mechanisms underlying the scleral response involve changes in the synthesis of extracellular matrix molecules, however, those underlying the changes in choroidal thickness are not known. However, evidence suggests that it may involve the gaseous signal molecule nitric oxide, as nitric oxide is a potent smooth muscle relaxant, and injections of the non-specific nitric oxide synthase inhibitor L-NAME transiently inhibits the thickening response. Interestingly, it also dis-inhibits ocular growth, in accordance with a mechanistic link between the two responses. If nitric oxide is part of the signal cascade underlying the visual regulation of eye growth, it would be important to ascertain the source of the molecule. As a first step towards doing so, we used various more specific NOS inhibitors and studied their effects on the choroidal and growth responses. Birds (7–12 days old) were fitted with +10 D lenses on one eye. On that day, single intravitreal injections (30 μl) of the following inhibitors were used: nNOS inhibitor N ω-propyl-L-arginine (n=12), iNOS inhibitor L-NIL (n=16), eNOS/iNOS inhibitor L-NIO (n=15), non-specific inhibitor L-NMMA (n=30) or physiological saline (n=18). Ocular dimensions were measured using high-frequency A-scan ultrasonography at the start of the experiment, and at 7, 24 and 48 hours after. We found that the nNOS inhibitor N ω-propyl-L-arginine had the same inhibitory effects on the choroidal response

  2. Morphologic Changes in Patient with Drusen and Drusenoid Pigment Epithelial Detachment after Intravitreal Ranibizumab for Choroidal Neovascular Membrane : A Case Report

    PubMed Central

    Kim, Sukjin; Oh, Jeongjae; Kim, Kiseok

    2016-01-01

    The authors present a case of morphologic changes of drusen and drusenoid pigment epithelial detachment (DPED) after treating choroidal neovascularization (CNV) using ranibizumab in age-related macular degeneration (AMD). A 71-year-old woman has noticed mild visual acuity deterioration in the right eye for several months. She was presented with some drusen and DPED associated with CNV. This patient was given intravitreal injection of 0.5 mg of ranibizumab five times at monthly intervals for treating CNV. DPED in the temporal and drusen in the superior to macula were diminished, which continued up to 2 months. Intravitreal ranibizumab injection may have influenced with diminishment of drusen and DPED. After 2 months, CNV was recurred. PMID:27014379

  3. Morphologic Changes in Patient with Drusen and Drusenoid Pigment Epithelial Detachment after Intravitreal Ranibizumab for Choroidal Neovascular Membrane : A Case Report.

    PubMed

    Kim, Sukjin; Oh, Jeongjae; Kim, Kiseok

    2016-01-01

    The authors present a case of morphologic changes of drusen and drusenoid pigment epithelial detachment (DPED) after treating choroidal neovascularization (CNV) using ranibizumab in age-related macular degeneration (AMD). A 71-year-old woman has noticed mild visual acuity deterioration in the right eye for several months. She was presented with some drusen and DPED associated with CNV. This patient was given intravitreal injection of 0.5 mg of ranibizumab five times at monthly intervals for treating CNV. DPED in the temporal and drusen in the superior to macula were diminished, which continued up to 2 months. Intravitreal ranibizumab injection may have influenced with diminishment of drusen and DPED. After 2 months, CNV was recurred. PMID:27014379

  4. COL8A1 rs13095226 polymorphism shows no association with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in Chinese subjects

    PubMed Central

    Yu, Yang; Huang, Lvzhen; Wang, Bin; Zhang, Chunfang; Bai, Yujing; Li, Xiaoxin

    2015-01-01

    Purpose: Age-related macular degeneration (AMD) is the main cause of visual impairment and legal blindness in older individuals. COL8A1 rs13095226 variants have recently been implicated associated with neovascular age-related macular degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV) in American studies. The aim of this study was to investigate the association between the COL8A1 rs13095226 Polymorphism and neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese people. Methods: 900 Chinese subjects-300 cases with nAMD, 300 cases with PCV and 300 controls, were enrolled in a cross-sectional observational study. The diagnoses of nAMD and PCV were confirmed by Fundus photography, Fluorescence Fundus Angiography (FFA) and Indocyanine Green Angiography (ICGA). Genomic DNA was extracted from venous blood leukocytes and genotypes of rs13095226 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Differences in allele distribution between cases and controls were tested by chi-square tests, with age and gender adjusted by logistic regression analysis. Result: The COL8A1 rs13095226 polymorphism was not statistically significantly different from the nAMD or PCV to the normal controls (P>0.05) in Chinese Population. The association remained insignificant after adjustmentfor age and gender differences (P>0.05). Conclusions: This case-control study indicated that the COL8A1 rs13095226 polymorphism is not associated with nAMD or PCV, which suggesting this gene maybe not a susceptibility gene locus for nAMD or PCV in Chinese subjects. PMID:26617902

  5. Review of Choroidal Osteomas

    PubMed Central

    Alameddine, Ramzi M.; Mansour, Ahmad M.; Kahtani, Eman

    2014-01-01

    Choroidal osteomas are rare benign ossifying tumors that appear as irregular slightly elevated, yellow-white, juxtapapillary, choroidal mass with well-defined geographic borders, depigmentation of the overlying pigment epithelium; and with multiple small vascular networks on the tumor surface. Visual loss results from three mechanisms: Atrophy of the retinal pigment epithelium overlying a decalcified osteoma; serous retinal detachment over the osteoma from decompensated retinal pigment epithelium, and most commonly from choroidal neovascularization. Recent evidence points to the beneficial effects of intravitreal vascular endothelial growth factor antagonists in improving visual acuity in serous retinal detachment with or without choroidal neovascularization. PMID:25100910

  6. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    PubMed Central

    Kanavi, Mozhgan Rezaie; Darjatmoko, Soesiawati; Wang, Shoujian; Azari, Amir A.; Farnoodian, Mitra; Kenealey, Jason D.; van Ginkel, Paul R.; Albert, Daniel M.; Sheibani, Nader; Polans, Arthur S.

    2015-01-01

    The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. PMID:25361423

  7. Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

    PubMed

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2015-11-01

    Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. PMID:26368850

  8. Intravitreal anti-vascular endothelial growth factor combined with half-fluence photodynamic therapy for choroidal neovascularization in chronic central serous chorioretinopathy.

    PubMed

    Smretschnig, E; Hagen, S; Glittenberg, C; Ristl, R; Krebs, I; Binder, S; Ansari-Shahrezaei, S

    2016-06-01

    PurposeTo evaluate the results of indocyanine green angiography (ICGA)-guided verteporfin photodynamic therapy (PDT) with half-fluence rate combined with intravitreal application of anti-VEGF in treating choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSCR).Patients and methodsIn this retrospective cohort study 17 consecutive patients with secondary CNV due to chronic CSCR had their diagnosis verified with fluorescein angiography (FA) and ICGA at baseline. All eyes received either intravitreal ranibizumab (IVR) or bevacizumab (IVB). On the consecutive day following the initial IVR/IVB treatment, ICGA-guided verteporfin (6 mg/m(2)) PDT with half-fluence rate (25 J/cm(2)) was performed on every patient. IVR or IVB was rescheduled on a pro re nata regimen. Main outcome measures were changes in visual acuity (VA) according to the ETDRS letter score and changes in the central foveal thickness (CFT).ResultsBest-corrected VA at baseline was 65.6 letters (±6.7; n=17) according to the ETDRS letter score. At 12 months, mean ETDRS letter score improved to 71.2 letters (P=0.34). CFT was 309 μm and decreased to 216 μm at month 12 control (P=0.0004). Nine eyes (52.9%) received additional treatment with IVR/IVB due to recurrence of subretinal fluid, with an overall mean number of IVR/IVB treatment of 1.8±3.6 per patient with no systemic side effects during 12 months' follow-up.ConclusionsIVR or IVB combined with ICGA-guided half-fluence PDT with verteporfin is effective in treating CNV in chronic CSCR, with choroidal hyperpermeability in ICGA, resulting in stable vision and significant reduction of CFT. PMID:26965012

  9. Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization.

    PubMed

    Kachi, Shu; Binley, Katie; Yokoi, Katsutoshi; Umeda, Naoyasu; Akiyama, Hideo; Muramatu, Daisuke; Iqball, Sharifah; Kan, On; Naylor, Stuart; Campochiaro, Peter A

    2009-01-01

    Equine infectious anemia virus (EIAV) is a nonprimate lentivirus that does not cause human disease. Subretinal injection into mice of a recombinant EIAV lentiviral vector in which lacZ is driven by a CMV promoter (EIAV CMV LacZ) resulted in rapid and strong expression of LacZ in retinal pigmented epithelial (RPE) cells and some other cells including ganglion cells, resulting in the presence of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside within the optic nerve. Substitution of the RPE-specific promoter from the vitelliform macular dystrophy (VMD2) gene for the CMV promoter resulted in prolonged (at least 1 year) expression of LacZ that was restricted to RPE cells, albeit reduced 6- to 10-fold compared with the CMV promoter. Similarly, the amount of FLAG-tagged endostatin detected in eyes injected with the EIAV VMD2 Endo(FLAG) vector was similar to that seen in eyes injected with a vector that expressed both endostatin and angiostatin [EIAV VMD2 Endo(FLAG)/Angio]; expression was approximately 6-fold lower than with identical vectors in which the CMV promoter drove expression. Compared with murine eyes treated with a control EIAV vector, subretinal injection of EIAV vectors expressing murine endostatin alone or in combination with angiostatin driven by either the CMV or VMD2 promoter caused significant suppression of choroidal neovascularization (NV) at laser-induced rupture sites in Bruch's membrane. These data support proceeding toward clinical studies with EIAV-based gene therapy for choroidal NV, using the VMD2 promoter to selectively drive expression of a combination of endostatin and angiostatin in RPE cells. PMID:20377369

  10. Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells

    PubMed Central

    Coughlin, Beth; Schnabolk, Gloriane; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Johnson, Krista; Moore, Kristi; Wang, Yi; Rohrer, Bärbel

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment. PMID:27029558

  11. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

    PubMed Central

    Li, Y.; Liu, X.; Zhou, T.; Kelley, M.R.; Edwards, P.; Gao, H.; Qiao, X.

    2014-01-01

    The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

  12. Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population.

    PubMed

    Zhang, Xiongze; Li, Meng; Wen, Feng; Zuo, Chengguo; Chen, Hui; Wu, Kunfang; Zeng, Renpan

    2013-03-01

    Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are both major serosanguinous maculopathies among the Asian elderly. They are similar in phenotype. Genetic variants in high-density lipoprotein (HDL) pathway were discovered to be associated with AMD in two genome-wide association studies. In this study with a Chinese Han cohort, we investigated the impacts of these genetic variants on nAMD and PCV separately. The missense coding variants and previously identified variants at LIPC, ABCA1, CETP, LPL and FADS1 loci were genotyped in 157 nAMD patients, 250 PCV patients and 204 controls without any macular abnormality. The known variants in CFH, ARMS2 and near HTRA1 were also genotyped. Fasting serum cholesterol levels were determined. The variants in CFH, ARMS2 and near HTRA1 were strongly associated with both PCV (P < 10(-6), 10(-7) and 10(-7) respectively) and nAMD (P < 10(-6), 10(-16) and 10(-17) respectively). None of the studied HDL-related variants were significantly associated with nAMD. A missense variant in CETP, rs5882, was significantly associated with PCV (P = 2.73 × 10(-4)). The rs5882 GG genotype had a 3.53-fold (95% CI: 1.93-6.45) increased risk for PCV, and conferred a significantly lower serum HDL-cholesterol level for PCV patients than the AA genotype (P = 0.048). These results suggest the need to separate PCV from nAMD in association studies especially with Asian cohorts, and that the HDL pathway may involve in the pathogenesis of PCV and nAMD differently. PMID:23274582

  13. Effect of High-Density Lipoprotein Metabolic Pathway Gene Variations and Risk Factors on Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in China

    PubMed Central

    Sun, Yaoyao; Bai, Yujing; Wang, Bin; Yu, Wenzhen; Zhao, Mingwei; Li, Xiaoxin

    2015-01-01

    Purpose To investigate the effect of genetic variants in the high-density lipoprotein (HDL) metabolic pathway and risk factors on neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in China. Methods A total of 742 Chinese subjects, including 221 controls, 230 cases with nAMD, and 291 cases with PCV, were included in the present study. Five single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway (HDLMP) including cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC) and lipoprotein lipase (LPL) were genotyped in all study subjects with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Risk factors including gender, hypertension, hyperlipidemia, diabetes mellitus, and coronary artery disease were identified. Chi-square tests or Fisher’s exact tests were applied to discover associations between SNPs and risk factors for PCV and nAMD. Gene-gene interactions and gene-environment interactions were evaluated by the multifactor-dimensionality reduction (MDR) method. Results CETP rs3764261 were significantly associated with an increased risk for PCV (odds ratio (OR) = 1.444, P = 0.0247). LIPC rs1532085 conferred an increased risk for PCV (OR = 1.393, P = 0.0094). We found no association between PCV and LPL rs12678919, LIPC rs10468017 or CETP rs173539. No association was found between five SNPs with nAMD. Regarding risk factors, females were found to have significantly decreased risks for both PCV and nAMD (P = 0.006 and 0.001, respectively). Coronary artery disease (CAD) was a risk factor in PCV patients but played a protective role in nAMD patients. Hyperlipidemia was associated with PCV but not with nAMD. Neither hypertension nor diabetes mellitus was associated with PCV or nAMD. The MDR analysis revealed that a three-locus model with rs12678919, rs1532085, and gender was the best model for nAMD, while a five-locus model consisting of rs

  14. Choroid Plexus

    MedlinePlus

    ... spread widely via the cerebrospinal fluid. Choroid plexus papilloma is a rare, benign (noncancerous) tumor. Choroid plexus ... the malignant (cancerous) form of the choroid plexus papilloma. Choroid plexus carcinoma occurs primarily in children. Location ...

  15. Polypoidal choroidal vasculopathy.

    PubMed

    Ciardella, Antonio P; Donsoff, Irene M; Huang, Sheau J; Costa, Danielle L; Yannuzzi, Lawrence A

    2004-01-01

    Polypoidal choroidal vasculopathy was first described as a peculiar hemorrhagic disorder of the macula, characterized by recurrent sub-retinal and sub-retinal pigment epithelium bleeding in middle aged black women. The use of indocyanine green angiography and subsequently of optical coherent tomography has widened our ability to study and understand the pathophysiology of this disorder. The primary abnormality involves the choroidal circulation, and the characteristic lesion is an inner choroidal vascular network of vessels ending in an aneurysmal bulge or outward projection, visible clinically as a reddish orange, spheroid, polyp-like structure. We have also recognized that individuals of African-American and Asian descents are more at risk for developing polypoidal choroidal vasculopathy as the disorder seems to preferentially affect pigmented individuals. However, it has been shown that while that still holds true, patients of other racial backgrounds may be afflicted. Particularly, polypoidal choroidal vasculopathy has been found to be present in about 8-13% of white patients with clinical appearance of exudative age-related macular degeneration. Polypoidal choroidal vasculopathy has also been reported in Irish, French, German, and Italian patients. The natural course of the disease often follows a remitting-relapsing course, and clinically, it is associated with chronic, multiple, recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina with long-term preservation of good vision. Photodynamic treatment appears to be a promising alternative to conventional laser therapy, for the treatment of polypoidal choroidal vasculopathy. In conclusion, polypoidal choroidal vasculopathy seems to be a distinct clinical entity that should be differentiated from other types of choroidal neovascularization associated with age-related macular degeneration and other known choroidal degenerative, inflammatory, and ischemic disorders. PMID

  16. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

    SciTech Connect

    Toyama, Shingo; Tsuji, Hiroshi; Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi; Tokumaru, Sunao; Mizota, Atsushi; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    2013-06-01

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

  17. Combined therapy (intravitreal bevacizumab plus verteporfin photodynamic therapy) versus intravitreal bevacizumab monotherapy for choroidal neovascularization due to age-related macular degeneration: a 1-year follow-up study

    PubMed Central

    Saviano, Sandro; Leon, Pia Easter; Mangogna, Alessandro; Tognetto, Daniele

    2016-01-01

    Purpose To assess the efficacy and safety of combined intravitreal bevacizumab and low-fluency-rate photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) and to compare it with intravitreal bevacizumab monotherapy. Methods A total of 62 eyes of 62 patients with angiographic evidence of CNV were divided into 2 groups: the eyes of one group were treated with a combined therapy of 1 intravitreal bevacizumab injection (1.25 mg) and PDT within 7 days; the eyes of the other group received intravitreal bevacizumab monotherapy. Clinical evidence of complications, best-corrected visual acuity (BVCA) and fluorescein leakage were evaluated. Best-corrected visual acuity and optical coherence tomography (OCT) were tested monthly and followed for 12 months. Results In the combined group the mean BCVA increased from 0.61 logMAR before the treatment to 0.54 logMAR at 12 months’ follow-up. In the monotherapy group the mean BCVA increased from 0.65 logMAR to 0.60 logMAR at 12 months’ follow-up. There was no significant difference in visual acuity outcomes between groups (P > 0.05). In the combined group the mean number of treatments was 1.19 per patient; in the monotherapy group, 5.31 per patient (P < 0.01). Conclusions Combined therapy appears to be an effective option for CNV associated with AMD treatment allowing a significant reduction of intravitreal injections. PMID:27582675

  18. Peripapillary choroidal thickness in childhood.

    PubMed

    Read, Scott A; Alonso-Caneiro, David; Vincent, Stephen J; Collins, Michael J

    2015-06-01

    Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p < 0.001) and sector position (p < 0.001) in this population of children. The innermost annulus (closest to the edge of the optic disc) exhibited the thinnest choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p < 0.001). RNFL thickness also varied significantly with annulus location and sector (p < 0.001), and showed differences in thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle

  19. In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

    PubMed

    Crespo-Garcia, Sergio; Reichhart, Nadine; Hernandez-Matas, Carlos; Zabulis, Xenophon; Kociok, Norbert; Brockmann, Claudia; Joussen, Antonia M; Strauss, Olaf

    2015-10-01

    Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach

  20. Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary to choroidal osteoma.

    PubMed

    Papastefanou, V P; Pefkianaki, M; Al Harby, L; Arora, A K; Cohen, V M L; Andrews, R M; Sagoo, M S

    2016-06-01

    PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography-where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15 months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 μm (6 to -230 μm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma. PMID:27034203

  1. Gene–gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population

    PubMed Central

    Huang, L; Meng, Q; Zhang, C; Sun, Y; Bai, Y; Li, S; Deng, X; Wang, B; Yu, W; Zhao, M; Li, X

    2015-01-01

    Purpose To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population. Methods A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene–gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction (MDR) method. Results The risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1 rs3793917 showed significant difference between nAMD or PCV patients and controls (all P<0.01). The homozygosity of risk alleles for rs800292, rs2274700, rs3750847, and rs3793917 were significantly different between nAMD patients and controls (all P<0.01), and predisposed to PCV patients (all P<0.01). After cross-validation consistency (CVC) and permutation tests, the two-locus model rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847 has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk, respectively. Furthermore, CFH rs1065489 did not show significant association with nAMD (P>0.01), but was strongly associated with PCV in Chinese patients (P<0.001). Conclusions In this study, we found that the interaction of ARMS2 and ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and ARMS2 is pronounced in PCV development in Chinese population. PMID:25771815

  2. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report.

    PubMed

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim; Hemati, Karim

    2015-05-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

  3. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report

    PubMed Central

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim

    2015-01-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

  4. Pediatric genetic macular and choroidal diseases

    PubMed Central

    Bergman, Mica Y.; Nallasamy, Sudha

    2014-01-01

    Genetic diseases of the macula and choroid have various inheritance patterns and varying degrees of impact on vision. Herein, we review the literature including most recent advances in the understanding of the genetics of these diseases. Although many of these disorders have limited treatment options, knowledge of inheritance patterns can aid in early detection and with close monitoring can help the ophthalmologist preserve as much vision as possible (for example with early treatment of choroidal neovascularization).

  5. Choroidal OCT

    NASA Astrophysics Data System (ADS)

    Esmaeelpour, Marieh; Drexler, Wolfgang

    Novel imaging devices, imaging strategies and automated image analysis with optical coherence tomography have improved our understanding of the choroid in health and pathology. Non-invasive in-vivo high resolution choroidal imaging has had its highest impact in the investigation of macular diseases such as diabetes macular edema and age-related macular degeneration. Choroidal thickness may provide a clinically feasible measure of disease stage and treatment success. It will even support disease diagnosis and phenotyping as is demonstrated in this chapter. Utilizing color coded thickness mapping of the choroid and its Sattler's and Haller's layer may further strengthen the sensitivity of the investigation findings.

  6. Myopic anisometropia: ocular characteristics and aetiological considerations.

    PubMed

    Vincent, Stephen J; Collins, Michael J; Read, Scott A; Carney, Leo G

    2014-07-01

    Anisometropia represents a unique example of ocular development, where the two eyes of an individual, with an identical genetic background and seemingly subject to identical environmental influences, can grow asymmetrically to produce significantly different refractive errors. This review provides an overview of the research examining myopic anisometropia, the ocular characteristics underlying the condition and the potential aetiological factors involved. Various mechanical factors are discussed, including corneal structure, intraocular pressure and forces generated during near work that may contribute to development of anisomyopia. Potential visually guided mechanisms of unequal ocular growth are also explored, including the influence of astigmatism, accommodation, higher-order aberrations and the choroidal response to altered visual experience. The association between binocular vision, ocular dominance and asymmetric refraction is also considered, along with a review of the genetic contribution to the aetiology of myopic anisometropia. Despite a significant amount of research into the biomechanical, structural and optical characteristics of anisometropic eyes, there is still no unifying theory, which adequately explains how two eyes within the same visual system grow to different endpoints. PMID:24939167

  7. [Intraocular neovascularization].

    PubMed

    Inomata, H; Ishibashi, T; Murata, T; Iwasaki, M; Tahara, A; Hata, K; Yoshida, A; Yoshida, S; Onishi, Y; Murakami, M; Yamamoto, M; Kubota, T; Kawano, Y; Sugai, S; Sakamoto, T; Okada, T; Ishimoto, S; Fujisawa, K; Honda, T; Sakamoto, M; Shigefuji, M; Tsuji, I; Nishioka, K; Ueno, A; Nagatomi, Y

    1997-12-01

    To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future. PMID:9436356

  8. Intrachoroidal Neovascularization in Transgenic Mice Overexpressing Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium

    PubMed Central

    Schwesinger, Catherine; Yee, Charles; Rohan, Richard M.; Joussen, Antonia M.; Fernandez, Antonio; Meyer, Tobias N.; Poulaki, Vassiliki; Ma, Joseph J. K.; Redmond, T. Michael; Liu, Suyan; Adamis, Anthony P.; D’Amato, Robert J.

    2001-01-01

    Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch’s membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF164 cDNA with a rabbit β-globin-3′ UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch’s membrane. These results support the hypothesis that additional insults to the integrity of Bruch’s membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. PMID:11238064

  9. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren

    PubMed Central

    Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8–16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia. PMID:27537606

  10. Choroidal melanoma

    PubMed Central

    Singh, Parul; Singh, Abhishek

    2012-01-01

    Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma. PMID:22557869

  11. Myopic foveoschisis: a clinical review.

    PubMed

    Gohil, R; Sivaprasad, S; Han, L T; Mathew, R; Kiousis, G; Yang, Y

    2015-05-01

    To review the literature on epidemiology, clinical features, diagnostic imaging, natural history, management, therapeutic approaches, and prognosis of myopic foveoschisis. A systematic Pubmed search was conducted using search terms: myopia, myopic, staphyloma, foveoschisis, and myopic foveoschisis. The evidence base for each section was organised and reviewed. Where possible an authors' interpretation or conclusion is provided for each section. The term myopic foveoschisis was first coined in 1999. It is associated with posterior staphyloma in high myopia, and is often asymptomatic initially but progresses slowly, leading to loss of central vision from foveal detachment or macular hole formation. Optical coherence tomography is used to diagnose the splitting of the neural retina into a thicker inner layer and a thinner outer layer, but compound variants of the splits have been identified. Vitrectomy with an internal limiting membrane peel and gas tamponade is the preferred approach for eyes with vision decline. There has been a surge of new information on myopic foveoschisis. Advances in optical coherence tomography will continually improve our understanding of the pathogenesis of retinal splitting, and the mechanisms that lead to macular damage and visual loss. Currently, there is a good level of consensus that surgical intervention should be considered when there is progressive visual decline from myopic foveoschisis. PMID:25744445

  12. Photodynamic therapy for treatment subretinal neovascularization

    NASA Astrophysics Data System (ADS)

    Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

  13. Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

    PubMed Central

    Yanai, Ryoji; Mulki, Lama; Hasegawa, Eiichi; Takeuchi, Kimio; Sweigard, Harry; Suzuki, Jun; Gaissert, Philipp; Vavvas, Demetrios G.; Sonoda, Koh-Hei; Rothe, Michael; Schunck, Wolf-Hagen; Miller, Joan W.; Connor, Kip M.

    2014-01-01

    Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)–epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD. PMID:24979774

  14. Choroidal imaging: A review

    PubMed Central

    Chhablani, Jay; Wong, Ian Y.; Kozak, Igor

    2014-01-01

    Being the most vascular tissue of the eye, importance of the choroid has been very well established in various retinal and chorio-retinal diseases. Understanding of the choroidal structures has improved significantly since the evolution of enhanced depth imaging. Quantitative assessment of choroidal measurements has been found to be reproducible using different devices. This review article describes factors affecting choroidal thickness and choroidal changes in several diseases and reports its clinical importance. Evaluation of choroid would provide insight into the pathogenesis, treatment planning and follow up in chorioretinal diseases. PMID:24843305

  15. [Polypoidal choroidal vasculopathy].

    PubMed

    Yuzawa, Mitsuko

    2012-03-01

    Polypoidal choroidal vasculopathy (PCV) is characterized by a branching vascular network with polypoidal lesions under the retinal pigment epithelium (RPE). In Japan, it is classified as a specific form of exudative age-related macular degeneration. However, several issues which we investigated regarding the pathogenesis and treatment of PCV remain unresolved. We investigated the pathogenesis, clinical findings and treatment of PCV. 1. Indocyanine green angiographic findings. There were two different patterns on indocyanine green angiograms. In the first pattern, both feeder and draining vessels were visible and network vessels showed characteristic findings of choroidal neovascularization (CNV). Points of focal dilatation on marginal vessels were comprised of polypoidal lesions. In the second pattern, neither feeder nor draining vessels were visible and there were few network vessels. The points of deformation of network vessels appeared to be polypoidal lesions. The former represents a deformation of CNV, i.e. polypoidal CNV; the latter is thought to result from abnormalities of the choroidal vessels, i.e. PCV in the strict sense. 2. Pathological findings of PCV in the strict sense. The histopathological characteristics of PCV in the strict sense, which had been eliminated by vitrectomy, were dilatation and hyalinization of vessels, massive exudative changes in blood plasma, basement membrane-like deposits and scant granulomatous tissue. These vessels were located beneath Bruch's membrane. The findings indicate that PCV in the strict sense arises from hyalinized arteriolosclerosis of choroidal vessels. 3. Optical coherence tomographic findings. A break was found in the high reflective line which revealed Bruch's membrane. Low reflective tissue was observed at the break corresponding to a feeder vessel. The high reflective line which corresponded to the retinal pigment epithelium was uneven, and highly elevated portions of the RPE corresponded to thick network

  16. Polypoidal Choroidal Vasculopathy in Asians

    PubMed Central

    Wong, Chee Wai; Wong, Tien Y.; Cheung, Chui Ming Gemmy

    2015-01-01

    Age related macular degeneration (AMD) in Asians has been suggested to differ from their Western counterparts in terms of epidemiology, pathogenesis, clinical presentation and treatment. In particular, polypoidal choroidal vasculopathy (PCV) appears to be the predominant subtype of exudative AMD in Asian populations, in contrast to choroidal neovascularization secondary to AMD (CNV-AMD) in Western populations. Epidemiological data on PCV has been largely limited to hospital-based studies and there are currently no data on the incidence of PCV. Similarities and differences in risk factor profile between PCV and CNV-AMD point to some shared pathogenic mechanisms but also differential underlying mechanisms leading to the development of each phenotype. Serum biomarkers such as CRP, homocysteine and matrix metalloproteinases suggest underlying inflammation, atherosclerosis and deranged extracellular matrix metabolism as possible pathogenic mechanisms. In addition, recent advances in genome sequencing have revealed differences in genetic determinants of each subtype. While the standard of care for CNV-AMD is anti-vascular endothelial growth factor (VEGF) therapy, photodynamic therapy (PDT) has been the mainstay of treatment for PCV, although long-term visual prognosis remains unsatisfactory. The optimal treatment for PCV requires further clarification, particularly with different types of anti-VEGF agents and possible benefits of reduced fluence PDT. PMID:26239448

  17. Localized choroidal thickness variation and pigment epithelial detachment in dome-shaped macula with subretinal fluid.

    PubMed

    Deobhakta, Avnish; Ross, Adam H; Helal, John; Maia, André; Freund, K Bailey

    2015-03-01

    The objective of this report is to demonstrate that individuals with dome-shaped macula can develop persistent subretinal fluid due to abrupt changes in the thickness of the choroid, making it unlikely to be reported. Additionally, these patients often have pigment epithelial detachments, suggestive of possible choroidal neo-vascularization. These two qualities can often lead to persistent subretinal fluid that is refractory to treatment. PMID:25835309

  18. Apelin Is Required for Non-Neovascular Remodeling in the Retina

    PubMed Central

    McKenzie, Jenny A.G.; Fruttiger, Marcus; Abraham, Sabu; Lange, Clemens A.K.; Stone, Jay; Gandhi, Pranita; Wang, Xiaomeng; Bainbridge, James; Moss, Stephen E.; Greenwood, John

    2012-01-01

    Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up-regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non-neovascular remodeling. PMID:22067912

  19. [Consensus on neovascular glaucoma].

    PubMed

    Hamard, P; Baudouin, C

    2000-03-01

    Neovascular glaucoma is a dreadful pathology with a rapid spontaneous evolution responsible for painful and blind eye. The main cause is an anterior neovascular proliferation following a broad retinal ischemia. Early diagnosis and treatment are required in order to maintain a good visual status and a satisfactory IOP control with medical, surgical or cylodestructive procedures. In any case, the treatment of the retinal ischemia has to be performed. One must keep in mind that the most efficient way to avoid the incidence of neovascular glaucoma is a strict control of clinical situations potentially responsible for retinal ischemia, namely VRO in elderly patients and diabetic retinopathy in younger patients. PMID:10740059

  20. In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid

    NASA Astrophysics Data System (ADS)

    Unterhuber, Angelika; Povazay, B.; Hermann, B.; Sattmann, H.; Chavez-Pirson, A.; Drexler, W.

    2005-05-01

    For the first time in vivo retinal imaging has been performed with a new compact, low noise Yb-based ASE source operating in the 1 μm range (NP Photonics, λc = 1040 nm, Δλ = 50 nm, Pout = 30 mW) at the dispersion minimum of water with ~7 μm axial resolution. OCT tomograms acquired at 800 nm are compared to those achieved at 1040 nm showing about 200 μm deeper penetration into the choroid below the retinal pigment epithelium. Retinal OCT at longer wavelengths significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroids interface and superficial choroidal layers as well as reduces the scattering through turbid media and therefore might provide a better diagnosis tool for early stages of retinal pathologies such as age related macular degeneration which is accompanied by choroidal neovascularization, i.e., extensive growth of new blood vessels in the choroid and retina.

  1. Lack of netrin-4 modulates pathologic neovascularization in the eye

    PubMed Central

    Kociok, Norbert; Crespo-Garcia, Sergio; Liang, Yong; Klein, Sabrina V.; Nürnberg, Christina; Reichhart, Nadine; Skosyrski, Sergej; Moritz, Eva; Maier, Anna-Karina; Brunken, William J.; Strauß, Olaf; Koch, Manuel; Joussen, Antonia M.

    2016-01-01

    Netrins are a family of matrix-binding proteins that function as guidance signals. Netrin-4 displays pathologic roles in tumorigenesis and neovascularization. To answer the question whether netrin-4 acts either pro- or anti-angiogenic, angiogenesis in the retina was assessed in Ntn-4−/− mice with oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), mimicking hypoxia-mediated neovascularization and inflammatory mediated angiogenesis. The basement membrane protein netrin-4 was found to be localised to mature retinal blood vessels. Netrin-4, but not netrin-1 mRNA expression, increased in response to relative hypoxia and recovered to normal levels at the end of blood vessel formation. No changes in the retina were found in normoxic Ntn-4−/− mice. In OIR, Ntn-4−/− mice initially displayed larger avascular areas which recovered faster to revascularization. Ganzfeld electroretinography showed faster recovery of retinal function in Ntn-4−/− mice. Expression of netrin receptors, Unc5H2 (Unc-5 homolog B, C. elegans) and DCC (deleted in colorectal carcinoma), was found in Müller cells and astrocytes. Laser-induced neovascularization in Nnt-4−/− mice did not differ to that in the controls. Our results indicate a role for netrin-4 as an angiogenesis modulating factor in O2-dependent vascular homeostasis while being less important during normal retinal developmental angiogenesis or during inflammatory neovascularization. PMID:26732856

  2. THE MULTIFUNCTIONAL CHOROID

    PubMed Central

    Nickla, Debora L.; Wallman, Josh

    2010-01-01

    The choroid of the eye is primarily a vascular structure supplying the outer retina. It has several unusual features: It contains large membrane-lined lacunae, which, at least in birds, function as part of the lymphatic drainage of the eye and which can change their volume dramatically, thereby changing the thickness of the choroid as much as four-fold over a few days (much less in primates). It contains non-vascular smooth muscle cells, especially behind the fovea, the contraction of which may thin the choroid, thereby opposing the thickening caused by expansion of the lacunae. It has intrinsic choroidal neurons, also mostly behind the central retina, which may control these muscles and may modulate choroidal blood-flow as well. These neurons receive sympathetic, parasympathetic and nitrergic innervation. The choroid has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn. In addition to focusing the eye, more slowly than accommodation and more quickly than emmetropization, we argue that the choroidal thickness changes also are correlated with changes in the growth of the sclera, and hence of the eye. Because transient increases in choroidal thickness are followed by a prolonged decrease in synthesis of extracellular matrix molecules and a

  3. Profile of conbercept in the treatment of neovascular age-related macular degeneration

    PubMed Central

    Lu, Xinmin; Sun, Xiaodong

    2015-01-01

    In developed countries, age-related macular degeneration (AMD) is the leading cause of irreversible blindness in individuals over the age of 65 years. Vascular endothelial growth factor (VEGF) plays a vital role in the formation of neovascular AMD. VEGF regulates angiogenesis, enhances vascular permeability, and drives the formation of choroidal neovascularization. As a result of the introduction of anti-VEGF drugs, the incidence of blindness from neovascular AMD has greatly reduced. Anti-VEGF drugs are used as a first-line treatment for neovascular AMD. The most recent anti-VEGF drug is conbercept, also named KH902, which was approved for the treatment of neovascular AMD by the China Food and Drug Administration in December 2013. In this review, recent clinical information regarding the use of conbercept to treat neovascular AMD is summarized. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity to VEGF and a long half-life in vitreous. Preclinical studies have demonstrated its anti-angiogenesis activity in both ocular neovascular disease models and tumor models. Clinical trials of conbercept have shown its superior efficacy and safety. Patients respond well even with 3-month treatment intervals following loading doses once a month for 3 months. The potential therapeutic effect of conbercept on the treatment of polypoidal choroidal vasculopathy, a special type of neovascular AMD, is also promising. In summary, conbercept is a new treatment option for ophthalmologists and their patients and may help address the limitations of current anti-VEGF drugs. PMID:25960634

  4. Profile of conbercept in the treatment of neovascular age-related macular degeneration.

    PubMed

    Lu, Xinmin; Sun, Xiaodong

    2015-01-01

    In developed countries, age-related macular degeneration (AMD) is the leading cause of irreversible blindness in individuals over the age of 65 years. Vascular endothelial growth factor (VEGF) plays a vital role in the formation of neovascular AMD. VEGF regulates angiogenesis, enhances vascular permeability, and drives the formation of choroidal neovascularization. As a result of the introduction of anti-VEGF drugs, the incidence of blindness from neovascular AMD has greatly reduced. Anti-VEGF drugs are used as a first-line treatment for neovascular AMD. The most recent anti-VEGF drug is conbercept, also named KH902, which was approved for the treatment of neovascular AMD by the China Food and Drug Administration in December 2013. In this review, recent clinical information regarding the use of conbercept to treat neovascular AMD is summarized. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity to VEGF and a long half-life in vitreous. Preclinical studies have demonstrated its anti-angiogenesis activity in both ocular neovascular disease models and tumor models. Clinical trials of conbercept have shown its superior efficacy and safety. Patients respond well even with 3-month treatment intervals following loading doses once a month for 3 months. The potential therapeutic effect of conbercept on the treatment of polypoidal choroidal vasculopathy, a special type of neovascular AMD, is also promising. In summary, conbercept is a new treatment option for ophthalmologists and their patients and may help address the limitations of current anti-VEGF drugs. PMID:25960634

  5. Neovascularization in Tissue Engineering

    PubMed Central

    Chung, Jennifer C.-Y.; Shum-Tim, Dominique

    2012-01-01

    A prerequisite for successful tissue engineering is adequate vascularization that would allow tissue engineering constructs to survive and grow. Angiogenic growth factors, alone and in combination, have been used to achieve this, and gene therapy has been used as a tool to enable sustained release of these angiogenic proteins. Cell-based therapy using endothelial cells and their precursors presents an alternative approach to tackling this challenge. These studies have occurred on a background of advancements in scaffold design and assays for assessing neovascularization. Finally, several studies have already attempted to translate research in neovascularization to clinical use in the blossoming field of therapeutic angiogenesis. PMID:24710553

  6. Treatment of neovascular age-related macular degeneration: Current therapies

    PubMed Central

    Augustin, Albert J; Scholl, Stefan; Kirchhof, Janna

    2009-01-01

    Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition. PMID:19668562

  7. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    PubMed Central

    Keane, Pearse A; de Salvo, Gabriella; Sim, Dawn A; Goverdhan, Srini; Agrawal, Rupesh; Tufail, Adnan

    2015-01-01

    Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. PMID:25733802

  8. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration.

    PubMed

    Keane, Pearse A; de Salvo, Gabriella; Sim, Dawn A; Goverdhan, Srini; Agrawal, Rupesh; Tufail, Adnan

    2015-01-01

    Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and "real-world" outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. PMID:25733802

  9. Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

    PubMed Central

    Liu, Chi-Hsiu; Sun, Ye; Li, Jie; Gong, Yan; Tian, Katherine T.; Evans, Lucy P.; Morss, Peyton C.; Fredrick, Thomas W.; Saba, Nicholas J.; Chen, Jing

    2015-01-01

    Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization. PMID:26374840

  10. Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization.

    PubMed

    Liu, Chi-Hsiu; Sun, Ye; Li, Jie; Gong, Yan; Tian, Katherine T; Evans, Lucy P; Morss, Peyton C; Fredrick, Thomas W; Saba, Nicholas J; Chen, Jing

    2015-09-29

    Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization. PMID:26374840

  11. Blind and myopic ants in heterogeneous networks.

    PubMed

    Hwang, S; Lee, D-S; Kahng, B

    2014-11-01

    The diffusion processes on complex networks may be described by different Laplacian matrices due to heterogeneous connectivity. Here we investigate the random walks of blind ants and myopic ants on heterogeneous networks: While a myopic ant hops to a neighbor node every step, a blind ant may stay or hop with probabilities that depend on node connectivity. By analyzing the trajectories of blind ants, we show that the asymptotic behaviors of both random walks are related by rescaling time and probability with node connectivity. Using this result, we show how the small eigenvalues of the Laplacian matrices generating the two random walks are related. As an application, we show how the return-to-origin probability of a myopic ant can be used to compute the scaling behaviors of the Edwards-Wilkinson model, a representative model of load balancing on networks. PMID:25493841

  12. Blind and myopic ants in heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Hwang, S.; Lee, D.-S.; Kahng, B.

    2014-11-01

    The diffusion processes on complex networks may be described by different Laplacian matrices due to heterogeneous connectivity. Here we investigate the random walks of blind ants and myopic ants on heterogeneous networks: While a myopic ant hops to a neighbor node every step, a blind ant may stay or hop with probabilities that depend on node connectivity. By analyzing the trajectories of blind ants, we show that the asymptotic behaviors of both random walks are related by rescaling time and probability with node connectivity. Using this result, we show how the small eigenvalues of the Laplacian matrices generating the two random walks are related. As an application, we show how the return-to-origin probability of a myopic ant can be used to compute the scaling behaviors of the Edwards-Wilkinson model, a representative model of load balancing on networks.

  13. Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia

    PubMed Central

    Chen, Wei; Guan, Yubo; He, Guanghui; Li, Zhiwei; Song, Hui; Xie, Shiyong; Han, Quanhong

    2015-01-01

    Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV). Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography. Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P < 0.001) and control (P < 0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P < 0.001) group. A statistically significant difference (P = 0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P = 0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups. Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV. PMID:26491554

  14. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  15. A Case of Ampiginous Choroiditis

    PubMed Central

    Lambrecht, Pieter; Claeys, Marnix; De Schryver, Ilse

    2015-01-01

    Purpose Presentation of a case report of a unilateral ampiginous choroiditis. Methods This is an observational case report. Results A 70-year-old woman was referred to us with unilateral scattered chorioretinal lesions. The multifocal pattern of the lesions and the angiographic features led to the diagnosis of ampiginous choroiditis. Conclusion Ampiginous choroiditis is a primary inflammatory choriocapillaropathy with characteristics of both acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. PMID:26955348

  16. Successful Treatment of Subretinal Neovascularization with Intravitreal Ranibizumab in a Child with Optic Nerve Head Drusen.

    PubMed

    Gregory-Evans, Kevin; Rai, Poornima; Patterson, Julian

    2009-08-21

    An 11-year-old boy presented with visual acuity reduced to 20/100 in his left eye. Investigations revealed optic disc drusen associated with a minimally classic choroidal neovascular membrane. The patient underwent a 3-month course of intravitreal ranibizumab. Six months of follow-up revealed remarkable visual acuity improvement to 20/20 and complete resolution of exudative maculopathy. PMID:20842978

  17. Broad Spectrum Antiangiogenic Treatment for Ocular Neovascular Diseases

    PubMed Central

    Benny, Ofra; Nakai, Kei; Yoshimura, Takeru; Bazinet, Lauren; Akula, James D.; Nakao, Shintaro; Hafezi-Moghadam, Ali; Panigrahy, Dipak; Pakneshan, Pouya; D'Amato, Robert J.

    2010-01-01

    Pathological neovascularization is a hallmark of late stage neovascular (wet) age-related macular degeneration (AMD) and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV), while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF) exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD. Methods and Findings Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH), Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2). Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1). The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG) assessing retinal and by histology. Conclusions Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially

  18. STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

    PubMed Central

    Chen, Mei; Lechner, Judith; Zhao, Jiawu; Toth, Levente; Hogg, Ruth; Silvestri, Giuliana; Kissenpfennig, Adrien; Chakravarthy, Usha; Xu, Heping

    2016-01-01

    Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD. PMID:27009107

  19. Circumscribed Choroidal Hemangioma

    PubMed Central

    Karimi, Saeed; Nourinia, Ramin; Mashayekhi, Arman

    2015-01-01

    Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities. PMID:26730320

  20. Bilateral Presumed Tuberculous Choroiditis

    PubMed Central

    Mohammadi, Naseh; Ghassemi, Fariba; Shojaei, Esfandiar; Moradnejad, Pardis

    2016-01-01

    Purpose: To describe a case of bilateral presumed tuberculous choroiditis which resolved promptly with a short course of antituberculous therapy. Case Report: A 44-year-old lady presented with bilateral visual loss of 8 months’duration. Considering the presence of pan-uveitis, severe macular edema, multifocal leakage on fluorescein angiography, positive tuberculin skin test, and after excluding other diseases, she underwent anti-tuberculous therapy (ATT) for disseminated choroiditis due to presumed ocular tuberculosis. She improved promptly and completely. There were no signs of relapse 18 months after completion of the treatment course. In a young patient with disseminated choroiditis and relatively short duration of symptoms, a course of ATT for 6 months may effectively treat the disease preventing relapse for a considerable period of time. Conclusion: In Presumed Tuberculous chroiditis early diagnosis is crucial for prompt and complete improvement. PMID:27413507

  1. Identification of RALDH2 as a Visually Regulated Retinoic Acid Synthesizing Enzyme in the Chick Choroid

    PubMed Central

    Hollaway, Lindsey R.; Lam, Wengtse; Li, Nan; Napoli, Joseph L.

    2012-01-01

    Purpose. All-trans-retinoic acid (atRA) has been implicated in the local regulation of scleral proteoglycan synthesis in vivo. The purpose of the present study was to identify the enzymes involved in the synthesis of atRA during visually guided ocular growth, the cells involved in modulation of atRA biosynthesis in the choroid, and the effect of choroid-derived atRA on scleral proteoglycan synthesis. Methods. Myopia was induced in White leghorn chicks by form deprivation for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of atRA synthesizing enzymes was evaluated by semiquantitative qRT-PCR, in situ hybridization, and immunohistochemistry. atRA synthesis was measured in organ cultures of isolated choroids using LC-tandem MS quantification. Scleral proteoglycan synthesis was measured in vitro by the incorporation of 35SO4 in CPC-precipitable glycosaminoglycans. Results. RALDH2 was the predominant RALDH transcript in the choroid (>100-fold that of RALDH3). RALDH2 mRNA was elevated after 12 and 24 hours of recovery (60% and 188%, respectively; P < 0.01). The atRA concentration was significantly higher in cultures of choroids from 24-hour to 15-day recovering eyes than in paired controls (∼195%; P < 0.01). Choroid conditioned medium from recovering choroids inhibited proteoglycan synthesis to 43% of controls (P < 0.02, paired t-test; n = 16) and produced a relative inhibition corresponding to a RA concentration of 7.20 × 10−8 M. Conclusions. The results of this study suggest that RALDH2 is the major retinal dehydrogenase in the chick choroid and is responsible for increased atRA synthesis in response to myopic defocus. PMID:22323456

  2. Polymeric materials for neovascularization

    NASA Astrophysics Data System (ADS)

    DeVolder, Ross John

    Revascularization therapies have emerged as a promising strategy to treat various acute and chronic wounds, cardiovascular diseases, and tissue defects. It is common to either administer proangiogenic growth factors, such as vascular endothelial growth factor (VEGF), or transplant cells that endogenously express multiple proangiogenic factors. Additionally, these strategies utilize a wide variety of polymeric systems, including hydrogels and biodegradable plastics, to deliver proangiogenic factors in a sophisticated manner to maintain a sustained proangiogenic environment. Despite some impressive results in rebuilding vascular networks, it is still a challenging task to engineer mature and functional neovessels in target tissues, because of the increasing complexities involved with neovascularization applications. To resolve these challenges, this work aims to design a wide variety of proangiogenic biomaterial systems with tunable properties used for neovascularization therapies. This thesis describes the design of several biomaterial systems used for the delivery of proangiogenic factors in neovascularization therapies, including: an electrospun/electrosprayed biodegradable plastic patch used for directional blood vessel growth (Chapter 2), an alginate-g-pyrrole hydrogel system that biochemically stimulates cellular endogenous proangiogenic factor expression (Chapter 3), an enzyme-catalyzed alginate-g-pyrrole hydrogel system for VEGF delivery (Chapter 4), an enzyme-activated alginate-g-pyrrole hydrogel system with systematically controllable electrical and mechanical properties (Chapter 5), and an alginate-g-pyrrole hydrogel that enables the decoupled control of electrical conductivity and mechanical rigidity and is use to electrically stimulate cellular endogenous proangiogenic factor expression (Chapter 6). Overall, the biomaterial systems developed in this thesis will be broadly useful for improving the quality of a wide array of molecular and cellular based

  3. Blood Flow Velocity in the Choroid in Punctate Inner Choroidopathy and Vogt-Koyanagi Disease:. and Multifractal Analysis of Choroidal Blood Flow in Age-Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Yoshida, K.; Saito, W.; Fujii, H.; Yakubo, K.

    2007-07-01

    Recently, the important role of the choroidal circulation has been recognized in various fundus diseases, such as punctate inner choroidopathy (PIC), Vogt-Koyanagi-Harada (VKH) disease, and age-related macular degeneration (AMD). An apparatus based on the laser speckle phenomenon, which we call laser speckle flowgraphy (LSFG) has been used to measure the blood flow velocity in the retina and choroid with the diode laser. PIC presents in myopic women who complain of decreased visual acuity. VKH disease is a bilateral, granulomatous chorioretinitis. The composite map of the LSFG represent that blood flow velocity in the choroid was decreased in PIC and VKH. After the treatment, blood flow velocity in this area was increased in both disease and visual acuity recovered. LSFG appears to be a safe and sensitive means to evaluate these disease progression and response to therapy. A multifractal analysis has been performed for blood flow data in the composite map of the LSFG. In consequence, multifractality becomes clearly worse for the AMD patient compared to normal choroidal blood flows. The multifractal analysis of LSFG data represents an additional useful method to detect the early stage of AMD.

  4. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  5. Implants for draining neovascular glaucoma.

    PubMed Central

    Molteno, A C; Van Rooyen, M M; Bartholomew, R S

    1977-01-01

    The implant design, surgical technique, and pharmacological methods of controlling bleb fibrosis, used to treat neovascular glaucoma, are described, together with the results of 14 operations performed on 12 eyes. Images PMID:843508

  6. Regulation of signaling events involved in the pathophysiology of neovascular AMD

    PubMed Central

    Wang, Haibo

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual’s genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than half of patients treated for neovascular AMD, and treatments remain inadequate for atrophic AMD. Many studies focus on genetic predisposition or the association of outcomes in trials of human neovascular AMD but are unable to evaluate the effects between different cell types involved in AMD and the signaling events that take place to cause pathologic biologic events. This manuscript complements other reviews in that it describes what is known generally in human AMD studies and clinical trials testing methods to inhibit vascular endothelial growth factor (VEGF inhibitors) and presents pathologic signaling events that develop in two important cell types, the RPE cells and the CECs, when stimulated by stresses or placed into conditions similar to what is currently understood to occur in neovascular AMD. This manuscript complements other reviews by discussing signaling events that are activated by cell–cell or cell–matrix interactions. These considerations are particularly important when considering growth factors, such as VEGF, which are important in physiologic and pathologic processes, or GTPases that are present but active only if GTP bound. In either case, it is essential to understand the role of signaling activation to distinguish what is pathologic from what is physiologic. Particularly important is the essential role of activated Rac1 in CEC transmigration of the RPE monolayer, an important step in blindness associated with neovascular AMD. Other concepts discussed

  7. Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

    PubMed Central

    Lee, Hyungjun; Sulaiman, Rania S.; An, Hongchan; Magaña, Carlos; Shadmand, Mehdi; Vayl, Alexandra; Rajashekhar, Gangaraju; Kim, Eun-Yeong; Suh, Young-Ger; Lee, Kiho

    2016-01-01

    Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an anti-angiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogs, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis, and had efficacy in the oxygen-induced retinopathy model in vivo. PMID:26035340

  8. Optical Coherence Tomography Angiography of Type 2 Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Souied, Eric H; El Ameen, Ala; Semoun, Oudy; Miere, Alexandra; Querques, Giuseppe; Cohen, Salomon Yves

    2016-01-01

    Well-defined choroidal neovascularization, known as type 2 neovascularization (NV) or classic NV, is the least representative phenotype of exudative age-related macular degeneration. Clinical aspects of type 2 NV have been widely described in the literature, and to date fluorescein angiography remains the gold standard for imaging age-related macular degeneration at initial presentation. Optical coherence tomography angiography (OCT-A) can be used to image vessels based on flow characteristics without any dye injection. Type 2 NV can be visualized using OCT-A with very typical patterns. A neovascular membrane appears as either a medusa-shaped complex or a glomerulus-shaped lesion in the outer retina and the choriocapillaris layer. Furthermore, in the choriocapillaris layer, the external borders of the lesion appear as a dark ring in most cases, and one or more central feeder vessels that extend deeply into the more profound choroidal layers are visible. Identification of type 2 NV is easily feasible for any clinician using OCT-A, especially in areas where there are normally no vessels, like in subretinal space, if the interpretation rules are respected. PMID:27023798

  9. Corneal Biomechanics Determination in Healthy Myopic Subjects

    PubMed Central

    Qiu, Kunliang; Lu, Xuehui; Zhang, Riping; Wang, Geng

    2016-01-01

    Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82 ± 1.34 mmHg and 9.64 ± 1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r = −0.27, 0.23, 0.45, and 0.21, resp.; all with p ≤ 0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r = 0.52 and 0.70, resp.; all with p < 0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration. PMID:27525109

  10. Photochemical Thrombosis Of Retinal And Choroidal Vessels Using Rose Bengal

    NASA Astrophysics Data System (ADS)

    Lewis, Mary Lou; Winward, Kirk; Watson, Brant D.; Hernandez, Eleut

    1989-09-01

    Rose bengal is an effective photosensitizing agent which interacts with argon green light to induce photochemical thrombosis of irradiated vessels. We used focal, low energy irradiation to occlude retinal and choroidal vessels in both albino and pigmented rabbits. Immediately after intravenous injection of rose bengal at concentrations of 10 and 20 mg/kg, irradiation was performed via a slit lamp-delivered argon green laser (514.5 nm) with the aid of fundus contact lens. In 11 eyes, arteries were treated with 50-100 interrupted bursts of 75u spot size at 0.2 sec and 40-100 mW (9 choroidal vessels, serous elevation of the retina, and disc neovascularization. In eight eyes choroidal vessels were irradiated with 10-20 mW, 15-60 sec, 500u spot size (31 choroidal vessels. There was minimal damage to surrounding tissue. Control eyes in all three groups irradiated utilizing the same parameters, but without rose bengal, demonstrated no evidence of thermal injury.

  11. Sustained delivery of a HIF-1 antagonist for ocular neovascularization.

    PubMed

    Iwase, Takeshi; Fu, Jie; Yoshida, Tsunehiko; Muramatsu, Daisuke; Miki, Akiko; Hashida, Noriyasu; Lu, Lili; Oveson, Brian; Lima e Silva, Raquel; Seidel, Christopher; Yang, Ming; Connelly, Sheila; Shen, Jikui; Han, Bing; Wu, Mingsheng; Semenza, Gregg L; Hanes, Justin; Campochiaro, Peter A

    2013-12-28

    Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity by blocking its binding to DNA. Intraocular injections of DXR or DNR suppressed choroidal and retinal neovascularization (NV), but also perturbed retinal function as demonstrated by electroretinograms (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular injection of DXR-PSA-PEG3 nanoparticles (1 or 10 μg DXR content) reduced HIF-1-responsive gene products, strongly suppressed choroidal and retinal NV, and did not cause retinal toxicity. In transgenic mice that express VEGF in photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 μg DXR content) suppressed NV for at least 35 days. Intraocular injection of DXR-PSA-PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained DXR-conjugate release with detectable levels in aqueous humor and vitreous for at least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate formulated into controlled-release particles that maximizes efficacy and duration of activity, minimizes toxicity, and provides a promising new chemical entity for treatment of ocular NV. PMID:24126220

  12. Sustained Delivery of a HIF-1 Antagonist for Ocular Neovascularization

    PubMed Central

    Iwase, Takeshi; Fu, Jie; Yoshida, Tsunehiko; Muramatsu, Daisuke; Miki, Akiko; Hashida, Noriyasu; Lu, Lili; Oveson, Brian; Silva, Raquel Lima e; Seidel, Christopher; Yang, Ming; Connelly, Sheila; Shen, Jikui; Han, Bing; Wu, Mingsheng; Semenza, Gregg L.; Hanes, Justin; Campochiaro, Peter A.

    2013-01-01

    Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity by blocking its binding to DNA. Intraocular injections of DXR or DNR suppressed choroidal and retinal neovascularization (NV), but also perturbed retinal function as demonstrated by electroretinograms (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular injection of DXR-PSA-PEG3 nanoparticles (1 or 10 μg DXR content) reduced HIF-1-responsive gene products, strongly suppressed choroidal and retinal NV, and did not cause retinal toxicity. In transgenic mice that express VEGF in photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 μg DXR content) suppressed NV for at least 35 days. Intraocular injection of DXR-PSA-PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained DXR-conjugate release with detectable levels in aqueous humor and vitreous for at least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate formulated into controlled-release particles that maximizes efficacy and duration of activity, minimizes toxicity, and provides a promising new chemical entity for treatment of ocular NV. PMID:24126220

  13. Choroid plexus cysts and aneuploidy.

    PubMed Central

    Peleg, D; Yankowitz, J

    1998-01-01

    The association of choroid plexus cysts with fetal aneuploidy, particularly trisomy 18, was first noted in 1986. Through the years there have been numerous reports on this subject, but no consensus has been reached with regard to chromosomal risk. In this review, we attempt to summarise published reports on second trimester choroid plexus cysts, with an emphasis on the strengths and weaknesses of each report. Based on these reports, additional malformations are a significant risk factor for aneuploidy and an indication for determination of fetal karyotype. The management of isolated choroid plexus cysts remains controversial. PMID:9678699

  14. Growing Hemorrhagic Choroidal Fissure Cyst

    PubMed Central

    Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit

    2016-01-01

    Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426

  15. Retention of good visual acuity in eyes with neovascular age-related macular degeneration and chronic refractory subfoveal subretinal fluid

    PubMed Central

    Bhavsar, Kavita V.; Freund, K. Bailey

    2014-01-01

    Purpose To describe the clinical characteristics of a subset of eyes with neovascular age-related macular degeneration (NVAMD) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy which retain good visual acuity despite chronic, persistent subfoveal subretinal fluid (SRF). Design Retrospective, observational case series. Methods Study eyes were identified from a consecutive series of 186 patients treated with anti-VEGF therapy seen for regular follow-up over a 3-month period. The clinical histories of 10 eyes of 9 patients with NVAMD, chronic subfoveal SRF despite continuous anti-VEGF therapy, and good long-term visual acuity of 20/40 or greater were reviewed. Demographic factors, baseline and final visual acuity, neovascular lesion type, duration of persistent fluid, baseline and final subfoveal choroidal thickness, presence of geographic atrophy, and number of anti-VEGF injections were analyzed. Results The mean age of patients was 78 years (range 55–91). The mean duration of persistent fluid was 5.2 years (range 1.3–11.0). Long-term visual acuities remained stable at 20/40 or better in all eyes. All eyes had type 1 (sub-retinal pigment epithelial) neovascularization. Average baseline subfoveal choroidal thickness was 285.3 μm and the average follow-up subfoveal choroidal thickness was 239.7 μm. No eyes had the presence of geographic atrophy. The mean number of injections was 36.5 (range 17–66). Conclusion Some eyes with type 1 neovascularization associated with chronic persistent subfoveal subretinal fluid despite continuous intravitreal anti-VEGF therapy may maintain good long-term visual outcomes. We hypothesize that type 1 neovascularization and greater subfoveal choroidal thickness may exert a protective effect on photoreceptor integrity. Further studies are necessary to assess long-term visual prognosis and predictive factors in patients with type 1 neovascularization leading to persistent subretinal fluid that is

  16. Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy

    PubMed Central

    Liu, Ke; Lai, Timothy Y. Y.; Ma, Li; Lai, Frank H. P.; Young, Alvin L.; Brelen, Marten E.; Tam, Pancy O. S.; Pang, Chi Pui; Chen, Li Jia

    2015-01-01

    Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene with neovascular AMD and PCV. Two haplotype-tagging SNPs, rs1005510 and rs11603020, of SERPING1 were genotyped in 708 unrelated Chinese individuals: 200 neovascular AMD, 233 PCV and 275 controls. A meta-analysis was also performed for all reported associations of SERPING1 SNPs with AMD and PCV. None of the tagging SNPs had a significant association with neovascular AMD or PCV (P > 0.05) in our study cohort. The meta-analyses showed that the most-studied SNP rs2511989 was not significantly associated with all forms of AMD, neovascular AMD, or PCV in East Asians (P = 0.98, 0.93 and 0.30, respectively) but was associated with AMD in Caucasians (P = 0.04 for all AMD and 0.004 for neovascular AMD). Therefore, the results of our study and meta-analysis suggest that SERPING1 is not a major genetic component of AMD or PCV in East Asians but is a genetic risk factor for AMD in Caucasians, providing evidence for an ethnic diversity in the genetic etiology of AMD. PMID:25800435

  17. Emerging Treatments for Choroidal Metastases

    PubMed Central

    Chen, Connie J.; McCoy, Allison N.; Brahmer, Julie; Handa, James T.

    2015-01-01

    It has been over a century since Perls described the first case of choroidal metastasis. For the next six decades only 230 cases were described in the literature. Today, however, ocular metastasis is recognized as the most common intraocular malignancy. Thanks to recent advances in treatment options for metastatic disease, patients are living longer, and choroidal metastases will become an increasingly important issue for oncologists and ophthalmologists alike. We summarize the current knowledge of choroidal metastases and examine their emerging systemic and local therapies. Targeted therapies for metastatic lung, breast, and colon cancer—the most common causes of choroidal metastases—are reviewed in detail with the goal of identifying the most effective treatment strategies. PMID:22117885

  18. Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

    PubMed Central

    Zampros, Ilias; Praidou, Anna; Brazitikos, Periklis; Ekonomidis, Panagiotis; Androudi, Sofia

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes. PMID:22174998

  19. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  20. Radiotherapy for choroidal melanoma. An 18-year experience with radon

    SciTech Connect

    Davidorf, F.H.; Pajka, J.T.; Makley, T.A. Jr.; Kartha, M.K.

    1987-03-01

    Twenty-three patients were treated with radon therapy for choroidal melanoma at the Ohio State University Hospitals, Columbus, between 1968 and 1976. We present an 18-year experience, including follow-up of at least eight years, in all those receiving therapy. Three patients (13%) died of metastatic disease. Four patients (17.4%) died of other causes. Sixteen patients (69.6%) were alive, with no signs of metastatic disease. Eight patients subsequently required enucleation due to inadequate tumor response. Of the 15 patients who demonstrated successful tumor destruction and retained their eyes, 13 (86.7%) developed substantial irradiation-induced retinopathy, including hard exudates, telangiectasias, neovascularization, microaneurysms, intraretinal and vitreous hemorrhages, secondary glaucoma, and irradiation-induced cataract. Our long-term results indicate a high incidence of both vascular complications and decreased visual acuity.

  1. Xanthogranuloma of the choroid plexus

    SciTech Connect

    Pear, B.L.

    1984-08-01

    Uncommon tumefactions known as xanthogranulomas can occur throughout the body. Some appear to develop as benign or malignant neoplasms. An even less familiar xanthogranuloma occurs within the choroid plexus. Most are tiny plaques only a few millimeters in diameter. However, they can present as masses of significant size within the glomus. When large and unilateral, they are included in the differential diagnosis of choroid plexus tumors. A computed tomographic (CT) study of such a tumor is presented.

  2. [Current treatments for corneal neovascularization].

    PubMed

    Benayoun, Y; Petellat, F; Leclerc, O; Dost, L; Dallaudière, B; Reddy, C; Robert, P-Y; Salomon, J-L

    2015-12-01

    The extension of blood vessels into the normally avascular stroma defines corneal neovascularization. Though this phenomenon, pathophysiological and clinical features are well characterized, therapeutic modalities have been hindered by a lack of safe, efficacious and non-controversial treatments. In this literature review, we focus on available therapeutic options in light of recent evidence provided by animal and clinical studies. First, this review will focus on pharmacological treatments that target angiogenesis. The low cost and market availability of bevacizumab make it the first anti-angiogenic therapy choice, and it has demonstrable efficacy in reducing corneal neovascularization when administered topically or subconjunctivally. However, novel anti-angiogenic molecules targeting the intracellular pathways of angiogenesis (siRNA, antisense oligonucleotides) provide a promising alternative. Laser therapy (direct photocoagulation or photo-dynamic therapy) and fine needle diathermy also find a place in the treatment of stabilized corneal neovascularization alone or in association with anti-angiogenic therapy. Additionally, ocular surface reconstruction using amniotic membrane graft or limbal stem cell transplantation is essential when corneal neovascularization is secondary to primary or acquired limbal deficiency. PMID:26522890

  3. Myopic random walkers and exclusion processes: Single and multispecies

    NASA Astrophysics Data System (ADS)

    Landman, Kerry A.; Fernando, Anthony E.

    2011-10-01

    A motility mechanism based on a simple exclusion process, where the probability of movement of an agent depends on the number of unoccupied nearest-neighbor sites is considered. Such interacting agents are termed myopic. This problem is an extension of the famous blind or myopic ant in a labyrinth problem. For the interacting agent models considered here, each agent plays the role of an ant in a labyrinth, where the paths of allowed sites though the labyrinth consist of sites not occupied by other agents. We derive a nonlinear diffusion equation for the average occupancy of the discrete agent-based model for myopic agents. In contrast, interacting blind agents have a constant probability of movement to each of their nearest-neighbor sites, giving rise to a linear diffusion equation. Insight into the various terms in the nonlinear diffusion coefficient is obtained from a study of multiple subpopulations of interacting myopic agents, where an advection-diffusion equation for each subpopulation is derived, and from tracking an individual agent within the crowd, where a motility coefficient is extracted. Averaged discrete simulation data compares very well with the solution to the continuum models. We also compare the behavior of myopic and blind agents. The myopic motility mechanism is biologically motivated to emulate information an individual cell gathers from environment cues. The multispecies model developed and investigated here assists with the interpretation of experimental data involving the tracking subpopulations of cells within a total cell population.

  4. Morphological patterns of indirect choroidal rupture on spectral domain optical coherence tomography

    PubMed Central

    Nair, Unnikrishnan; Soman, Manoj; Ganekal, Sunil; Batmanabane, Vaishnavi; Nair, KGR

    2013-01-01

    Purpose To evaluate the morphological types of indirect choroidal rupture (ICR) using spectral domain optical coherence tomography (SD-OCT). Methods This was a prospective interventional study of 18 eyes of 18 patients who presented with a history of blunt ocular trauma resulting in choroidal rupture. All patients underwent detailed ophthalmic evaluation and SD-OCT examination. Results Mean age of the patients was 32±9.6 years. Morphologically, two types of choroidal rupture were seen on SD-OCT. The first type seen (Type 1 ICR) was a forward protrusion of the retinal pigment epithelium-choriocapillaris (RPE-CC) layer with an acutely angled pyramid or dome shape. This was associated with either a small loss of continuity of the retinal pigment epithelium layer or elevated RPE-CC projection accompanied by a significant quantity of subretinal hemorrhage. The second type observed (Type 2 ICR) was a larger area of disruption of the RPE-CC layer, photoreceptor inner segment/outer segment junction, and external limiting membrane, with a posteriorly directed concave contour depression at that area and downward sliding of tissues into the defect. At presentation, ten eyes were observed to have Type 1 ICR and eight to have Type 2 ICR. Of the 18 eyes, one with Type 1 ICR and two with Type 2 ICR developed choroidal neovascularization (16.6%). Conclusion Two distinct tomographic patterns of choroidal ruptures were identified on SD-OCT, which may allow ruptures to be classified into two morphological types. There are morphometric and clinical differences between the two types, which may help to prognosticate visual outcome and anticipate complications following choroidal ruptures. PMID:23901259

  5. Treatment of choroidal neovascularisation secondary to membranoproliferative glomerulonephritis type II with intravitreal ranibizumab

    PubMed Central

    McCullagh, Donal; Silvestri, Giuliana; Maxwell, Alexander P

    2014-01-01

    Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by electron-dense deposits of complement components in the glomerular basement membrane and retinal pigment epithelium. Approximately, 10% of affected individuals develop serious ocular complications similar to age-related macular degeneration such as choroidal neovascularisation (CNV), which has been managed with photocoagulation or photodynamic therapy; however, these treatments can impact visual acuity. We report the case of a 42-year-old woman with MPGN II presenting with decreased visual acuity and paracentral scotoma in her left eye due to an extrafoveal choroidal neovascular membrane (growth of new vessels under the retina). The patient was successfully treated with intravitreal ranibizumab (Lucentis) with restoration of visual function. This case highlights the successful management of CNV secondary to MPGN II with the antivascular endothelial growth factor agent ranibizumab and emphasises the importance of early referral of patients with MPGN II who are reporting of visual ‘distortion’. PMID:24895384

  6. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1.

    PubMed

    Peterson, Lynda J; Wittchen, Erika S; Geisen, Pete; Burridge, Keith; Hartnett, M Elizabeth

    2007-04-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that "contact" with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  7. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

    PubMed Central

    Peterson, Lynda J.; Wittchen, Erika S.; Geisen, Pete; Burridge, Keith; Hartnett, M. Elizabeth

    2008-01-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that “contact” with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  8. Corneal neovascularization and biological therapy

    PubMed Central

    Voiculescu, OB; Voinea, LM; Alexandrescu, C

    2015-01-01

    Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their ability to reduce blood and lymphatic vessel ingrowth into the cornea, and to reduce inflammation. Numerous studies have shown that biologics with specificity for VEGF A such as bevacizumab and ranibizumab (a recombinant antibody and an antibody fragment, respectively) or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization. PMID:26664467

  9. Retinoic acid metabolic change in retina and choroid of the guinea pig with lens-induced myopia

    PubMed Central

    Mao, Jun-Feng; Liu, Shuang-Zhen; Dou, Xiu-Qiong

    2012-01-01

    AIM To investigate the role of retinoic acid (RA) and retinaldehyde dehydrogenase-2 (RALDH2) of retina and choroid in the guinea pig lens-induced myopic eyes. METHODS Totally 45 guinea pigs, at age of three weeks, were randomly assigned into three groups: the normal control, the lens-induced group and the recovering group. Out of focus was induced by the -6.00D concave lens on the left eye, and lasted for 15 days. All animals underwent biometric measurement (corneal radius of curvature, refraction and axial length). Subsequently, RA content in the retina and RPE/choriod complex was detected by reversed-phase high-performance liquid chromatography. RALDH2 protein in the retina and RPE/choriod complex was evaluated by the immunohistochemical staining and Western blotting. RESULTS After wearing -6.00D lens for 15 days, axial length of the lens-induced eye extends and myopia was formed, with RA contents increasing in both the neural retina and RPE/choroid complex. Comparing with the lens-induced group, myopic degree significantly relieved, and its RA contents in both the neural retina and RPE/choroid complex decreased in the recovering group. In the normal control, RALDH2 protein was expressed positively in the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL) and lateral border of outer nuclear layer (ONL). Retinal RALDH2 protein increased in the lens-induced group, and was also positive in the outer plexiform layer (OPL). In the recovering group, retinal RALDH2 protein attenuated the expression in the OPL turns to negative. RALDH2 protein was not expressed in the choroid of any group. CONCLUSION RA of retina and chorid participates in the regulation of the lens-induced myopia in guinea pigs, which may be related with retinal RALDH2 protein. PMID:23275899

  10. Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization

    PubMed Central

    Lee, Christopher Seungkyu; Choi, Eun Young; Lee, Sung Chul; Koh, Hyoung Jun; Lee, Joon Haeng

    2015-01-01

    Purpose To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice. Materials and Methods ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1α, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1α were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4. Results In ARPE-19 cells, resveratrol significantly inhibited HIF-1α and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1α degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner. Conclusion Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization. PMID:26446654

  11. [Current trends in neovascular glaucoma treatment].

    PubMed

    Vancea, P P; Abu-Taleb, A

    2005-01-01

    Neovascular glaucoma is divided in three clinical stages: rubeosis iridis, secondary open-angle glaucoma, and synechia of the angle-closure glaucoma. 36% of neovascular glaucomas occurs after central retinal vein occlusion, 32% after diabetic proliferative retinopathy, and 13% occurs after carotid artery obstructive. The key of success in the treatment of neovascular glaucoma is the early and rightly diagnosis, the treatment is aimed mainly at relieving pain, as the prognosis for maintaining visual function is extremely poor. The most important surgical procedures are trabeculectomy, artificial drainage shunts and cyclo-distraction by trans-scleral diode laser. This essay presents a synthesis of modern principle data concerning neovascular glaucoma. PMID:16607783

  12. Hemodynamics of focal choroidal excavations.

    PubMed

    Soma, Ryoko; Moriyama, Muka; Ohno-Matsui, Kyoko

    2015-04-01

    The purpose of this study was to investigate the hemodynamics of focal choroidal excavations (FCEs). Four eyes of four patients with a FCE were studied. Indocyanine green angiography (ICGA), laser speckle flowgraphy (LSFG), optical coherence tomography (OCT), and multi-focal electroretinography (mfERG) were performed to investigate the choroidal hemodynamics and the morphological and functional changes. The mean depth of the FCE determined by OCT was 222.5 ± 49.5 μm with a range of 164-272 μm. In one case, subretinal fluid was observed in the excavation, and in three cases, subretinal fluid was not observed. ICGA showed hypofluorescence, and laser flowgraphy (LSFG) showed decreased choroidal blood flow at the excavation in all cases. Three cases were symptomatic, and the amplitudes of the mfERGs were reduced. FCEs cause a decrease of choroidal blood flow. In three of four cases, the mfERGs were depressed over the FCEs leading to symptoms. PMID:25626897

  13. Associations of 6p21.3 Region with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy

    PubMed Central

    Ye, Zimeng; Shuai, Ping; Zhai, Yaru; Li, Fang; Jiang, Lingxi; Lu, Fang; Wen, Feng; Huang, Lulin; Zhang, Dingding; Liu, Xiaoqi; Lin, Ying; Luo, Huaichao; Zhang, Houbin; Zhu, Xianjun; Wu, Zhengzheng; Yang, Zhenglin; Gong, Bo; Shi, Yi

    2016-01-01

    Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD-associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 × 10−4 and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 × 10−4, OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders. PMID:26861912

  14. Associations of 6p21.3 Region with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

    PubMed

    Ye, Zimeng; Shuai, Ping; Zhai, Yaru; Li, Fang; Jiang, Lingxi; Lu, Fang; Wen, Feng; Huang, Lulin; Zhang, Dingding; Liu, Xiaoqi; Lin, Ying; Luo, Huaichao; Zhang, Houbin; Zhu, Xianjun; Wu, Zhengzheng; Yang, Zhenglin; Gong, Bo; Shi, Yi

    2016-01-01

    Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD-associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 × 10(-4) and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 × 10(-4), OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders. PMID:26861912

  15. Tamponade or Filling Effect: Changes of Forces in Myopic Eyes

    PubMed Central

    Morescalchi, Francesco; Romano, Mario R.

    2014-01-01

    Myopia is the most common ocular abnormality. Its high and growing prevalence has contributed to a recent surge in surgical interest in the disorder, since retinal detachment in eyes with high myopia differs from that in emmetropic eyes or eyes with low myopia. The myopic eye, because of its specific anatomy, poses special challenges that need to be overcome to ensure the appropriate use of vitreous substitutes. However, intraocular tamponades have shown great potential for revolutionizing retinal detachment surgery and vitreomacular surgery in general in myopic eyes. We provide an updated review of the clinical use of vitreous substitutes in the myopic eye, paying particular attention to analyzing the ideal function of endotamponade agents and comparing the effects of these agents on the physical and biological properties of the eye. PMID:25101290

  16. Morphometry of the myopic optic nerve head using FDOCT

    NASA Astrophysics Data System (ADS)

    Lee, Sieun; Young, Mei; Lebed, Evgeniy; Mackenzie, Paul J.; Beg, Mirza F.; Sarunic, Marinko V.

    2011-03-01

    In this paper we present imaging and morphometric analysis of a myopic Optic Nerve Head (ONH) using an 830nm wavelength Fourier domain optical coherence tomography system. The thinner prelaminar neural tissue and shallower optic cup in the myopic subject allows visualization of the tissue structures such as anterior laminar surface and lamina cribrosa that are often challenging to image due to their depth. From these structures we measured volumetric anatomical parameters and topographical tissue thickness correlated with glaucomatous structural damage in the ONH.

  17. Relationship between paravascular abnormalities and foveoschisis in highly myopic patients

    PubMed Central

    Kamal-Salah, R; Morillo-Sanchez, M J; Rius-Diaz, F; Garcia-Campos, J M

    2015-01-01

    Purpose To describe the prevalence of paravascular abnormalities in highly myopic patients and its relationship with myopic foveoschisis (MF). Methods Cross-sectional study of 250 highly myopic eyes. All of the patients underwent a complete ophthalmologic examination that included optical coherence tomography . Results Optical coherence tomography images showed 170 eyes (68%) with paravascular microfolds (PM), 121 eyes (48.4%) presented paravascular retinal cysts (PC), and 35 eyes (14%) with paravascular lamellar holes . All the eyes with PCs had PMs. Out of the 250 eyes, 48 (19.2%) had paravascular retinoschisis (PR). All the eyes (100%) with PR had paravascular cysts and PMs. Sixteen eyes (6.4%) had foveoschis. The spherical equivalent (P<0.00), PR (P=0.01), and the presence of tractional structures (P<0.00) were associated with increased risk for foveoschsis in the multivariate study. Conclusions PMs were the lesions most often observed in the paravascular area in highly myopic eyes. MF would be a result of the action of different forces (intra- and extra-ocular forces), specially tractional structures, on precursor lesions (paravascular cyst and paravascular restinoschisis). Further studies are needed to confirm these results. PMID:25359287

  18. Oxidative Stress Levels in Aqueous Humor from High Myopic Patients

    PubMed Central

    Kim, Eun Bi; Kim, Ha Kyoung; Hyon, Joon Young; Wee, Won Ryang

    2016-01-01

    Purpose To compare oxidative stress status in the aqueous humor of highly myopic eyes and control eyes. Methods Aqueous humor samples were collected from 15 highly myopic eyes (high myopia group) and 23 cataractous eyes (control group) during cataract surgery. Central corneal thickness, corneal endothelial cell density, hexagonality of corneal endothelial cells, and cell area of corneal endothelial cells were measured using specular microscopy. Axial length was measured using ultrasound biometry. 8-Hydroxydeoxyguanosine (8-OHdG) and malondialdehyde levels were measured using enzyme-linked immunosorbent assay. Results 8-OHdG level was lower in the aqueous humor of myopic patients than in that of control group (p = 0.014) and was positively correlated with central corneal thickness and negatively correlated with axial length (r = 0.511, p = 0.02; r = -0.382, p < 0.001). There was no correlation between 8-OHdG level and corneal endothelial cell density, hexagonality, or cell area. Malondialdehyde level did not show any correlation with any parameters evaluated. Conclusions 8-OHdG might be a sensitive biomarker for evaluating oxidative stress status in the eye. Oxidative stress level was lower in the aqueous humor of highly myopic eyes compared to that in control eyes, which indicates lower metabolic activity in these eyes. PMID:27247516

  19. In vivo ZW800-microbead imaging of retinal and choroidal vascular leakage in mice.

    PubMed

    Gupta, Isha; Cahoon, Judd; Zhang, Xiaohui; Jones, Alex D; Ahmed, Faisal; Uehara, Hironori; Messenger, Wyatt; Ambati, Balamurali K

    2015-05-01

    The eye is an attractive organ for non-invasive discovery and monitoring of disease progression. Traditionally, fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been used for dynamic evaluation of the retina and its vasculature. However, both fluorescein and indocyanine green (ICG) possess considerable disadvantages. FA is limited to assessing superficial retinal blood flow and often results in an unclear view due to fluorescein leakage. This obscures important pathologies such as neovascularization, ischemia and inflammation. ICG, a near-infrared fluorophore (NIRF), has nonspecific binding, high uptake and retention in tissues, as well as detrimental effects on the hepatobiliary tract. Here, we present a potential contrast agent for imaging ocular vascular permeability with ZW800, a heptamethine indocyanine NIRF, conjugated to polystyrene latex beads (ZW800m). ZW800 is an excellent alternative for near-infrared imaging, as it has excellent contrast, superior clearance, and is amendable to conjugation. ZW800m conjugation is an easy, attractive method of in vivo imaging and real-time tracking of ocular vascular pathologies. ZW800m is readily imaged via commercially available laser ophthalmoscope (SLO, HRA OCT, Spectralis) to assess vascular permeability in the mouse retina and choroid. In Type 1 diabetic Ins2Akita mice, ZW800m was observed in mouse retina but not in wild-type mice. After laser-induced choroidal neovascularization (CNV), ZW800m was observed in mouse choroid but not in control. In both CNV and diabetic mice, ZW800 imaging showed increased hyperfluorescence on ICG modality (ICGA) not seen on FA. Presence of ZW800m in respective tissues was confirmed ex vivo with flatmounts visualized with EVOS 800 nm light cube. ZW800 imaging may be easily employed in the research laboratory. PMID:25536533

  20. Clinical applications of choroidal imaging technologies.

    PubMed

    Chhablani, Jay; Barteselli, Giulio

    2015-05-01

    Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography. PMID:26139797

  1. Posterior scleral reinforcement combined with vitrectomy for myopic foveoschisis

    PubMed Central

    Li, Xiu-Juan; Yang, Xiao-Peng; Li, Qiu-Ming; Wang, Yu-Ying; Wang, Jing; Lyu, Xiao-Bei; Jia, Heng

    2016-01-01

    AIM To investigate the effects of posterior scleral reinforcement (PSR) combined with vitrectomy for myopic foveoschisis. METHODS Thirty-nine highly myopic eyes of 39 patients with myopic foveoschisis underwent PSR combined with vitrectomy. Best corrected visual acuity (BCVA), refraction error, and the foveal thickness by optical coherence tomography (OCT) were recorded before and after the surgery, and complications were noted. RESULTS The follow-up period was 12mo, and the main focus was on the results of the 12-month follow-up visit. The mean preoperative BCVA was 0.96±0.43 logMAR. At the final follow-up visit, the mean BCVA was 0.46±0.28 logMAR, which significantly improved compared with the preoperative one (P=0.003). The BCVA improved in 33 eyes (84.62%), and unchanged in 6 eyes (15.38%). At the end of follow-up, the mean refractive error was -15.13±2.55 D, and the improvement was significantly compared with the preoperative one (-17.53±4.51 D) (P=0.002). Twelve months after surgery, OCT showed complete resolution of the myopic foveoschisis and a reat-tachment of the fovea in 37 eyes (94.87%) and partial resolution in the remained two eyes (5.13%). The foveal thickness was obviously reduced at 12-month follow-up visit (196.45±36.35 µm) compared with the preoperative one (389.32±75.56 µm) (P=0.002). There were no serious complications during the 12mo follow-up period. CONCLUSION PSR combined with vitrectomy is a safe and effective procedure for myopic foveoschisis with both visual and anatomic improvement. PMID:26949646

  2. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration

    SciTech Connect

    Hori, Katsuyoshi . E-mail: k-hori@idac.tohoku.ac.jp; Saito, Sachiko; Tamai, Makoto

    2004-12-01

    Purpose: Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation. Methods and materials: Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured. Results: Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values. Conclusion: These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.

  3. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography

    PubMed Central

    Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  4. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography.

    PubMed

    Lee, Hoyoung; Bae, Kunho; Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  5. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  6. Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

    PubMed

    Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

    2013-07-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. PMID:23603148

  7. Choroidal Haller's and Sattler's Layer Thickness Measurement Using 3-Dimensional 1060-nm Optical Coherence Tomography

    PubMed Central

    Esmaeelpour, Marieh; Kajic, Vedran; Zabihian, Behrooz; Othara, Richu; Ansari-Shahrezaei, Siamak; Kellner, Lukas; Krebs, Ilse; Nemetz, Susanne; Kraus, Martin F.; Hornegger, Joachim; Fujimoto, James G.; Drexler, Wolfgang; Binder, Susanne

    2014-01-01

    Objectives To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy eyes Methods Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidalsublayers. Results The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001). Conclusions Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability correspondingto reported manual segmentation. Sublayers in healthy eyes thinnedsignificantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss. PMID:24911446

  8. Cooperation enhanced by moderate tolerance ranges in myopically selective interactions

    NASA Astrophysics Data System (ADS)

    Chen, Xiaojie; Wang, Long

    2009-10-01

    We present a mode of myopically selective interaction to study the evolutionary prisoner’s dilemma game in scale-free networks. Each individual has a reputation-based tolerance range and only tends to interact with the neighbors whose reputation is within its tolerance range. Moreover, its reputation is assessed in response to the interactions in the neighborhood. Interestingly, we show that moderate values of tolerance range can result in the best promotion of cooperation due to the emergence of group selection mechanism. Furthermore, we study the effects of weighting factor in the assessment rule of reputation on the evolution of cooperation. We also show how cooperation evolves in some extended situations, where an interaction stimulus payment is considered for individuals, and where the strategy and reputation of individuals can spread simultaneously. Our results may enhance the understanding of evolutionary dynamics in graph-structured populations where individuals conditionally play with their neighbors according to some myopic selection criteria.

  9. Response AC/A ratios are elevated in myopic children.

    PubMed

    Gwiazda, J; Grice, K; Thorn, F

    1999-03-01

    In children little is known about the relationship between the AC/A ratio and the development of myopia, although they have been linked in adults. The purpose of this study was to investigate the interaction between accommodation and convergence and its relationship to refractive errors in children. Accommodation was measured for the right eye using the Canon R-1 autorefractor, and concomitant changes in vergence were assessed using a Maddox rod and a Risley prism before the left eye. Thirty-three myopic and 68 emmetropic children were tested wearing best subjective correction while looking at a distant (4.0 m) letter array and a near (0.33 m) one through additional plus and minus lenses. Lens-induced and distance-induced response AC/A ratios were calculated from the data. Both types of AC/A ratios are elevated in myopic children, who show reduced accommodation and enhanced accommodative convergence. Myopic children with esophoria underaccommodate at near. This suggests that a child who is esophoric must relax accommodation to reduce accommodative convergence and maintain single binocular vision. The reduction in accommodation could produce blur during near work, which could induce myopia as in animal models. PMID:10615453

  10. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  11. Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy

    PubMed Central

    Cheng, Yu; Liu, Xiao-Hong; Shen, Xi; Zhong, Yi-Sheng

    2013-01-01

    AIM To report on the outcome of Ahmed glaucoma valve (AGV) implantation for the management of neovascular glaucoma (NVG) after 23-gauge vitrectomy for proliferative diabetic retinopathy (PDR). METHODS Twelve medically uncontrolled NVG with earlier 23-gauge vitrectomy for PDR underwent AGV implantation. The control of intraocular pressure (IOP), preoperative and postoperative best-corrected visual acuity, the development of intraoperative and postoperative complications were evaluated during the follow-up. RESULTS The mean follow-up was 15.4±4.3 months (9-23 months). Mean preoperative IOP was 49.4±5.1mmHg and mean postoperative IOP at the last visit was 17.5±1.6mmHg. The control of IOP was achieved at the final follow-up visits in all patients, however, 8 of 12 patients still needed anti-glaucoma medication (mean number of medications, 0.8±0.7). The visual acuity improved in nine eyes, and the visual acuity unchanged in three eyes at the final follow-up visits. The complications that occurred were minor hyphema in three eyes, choroid detachment in two eyes, and the minor hyphema and choroid detachments were reabsorbed without any surgical intervention. CONCLUSION AGV implantation is a safe and effective procedure that enables successful IOP control and vision preservation in the NVG patients with the history of earlier 23-gauge vitrectomy for PDR. PMID:23826525

  12. Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.

    PubMed

    Lückoff, Anika; Caramoy, Albert; Scholz, Rebecca; Prinz, Marco; Kalinke, Ulrich; Langmann, Thomas

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon-β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-α/β receptor (Ifnar) using Ifnar1(-/-) mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser-treated Cx3cr1(Cre) (ER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN-β therapy of laser-treated wild-type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN-β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. PMID:27137488

  13. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  14. Enucleation versus plaque irradiation for choroidal melanoma

    SciTech Connect

    Straatsma, B.R.; Fine, S.L.; Earle, J.D.; Hawkins, B.S.; Diener-West, M.; McLaughlin, J.A.

    1988-07-01

    The Collaborative Ocular Melanoma Study (COMS) is an international, multicenter-controlled study. The organization includes an Executive Committee, Steering Committee, 6 Central Units, 32 Clinical Centers, and a Data and Safety Monitoring Committee. Scientifically, the COMS consists of (1) a randomized trial of patients with medium choroidal melanoma treated with enucleation versus iodine-125 plaque irradiation, (2) a randomized trial of patients with large choroidal melanoma treated with enucleation versus preenucleation external beam irradiation and enucleation, and (3) a prospective observational study of patients with small choroidal melanoma to determine whether a randomized trial of treatment is appropriate. In design and conduct of the COMS, special consideration is given to biostatistics and sample size considerations, iodine-125 plaque irradiation of choroidal melanoma, and coordinated ocular melanoma research. Recruitment is in progress. However, the pool of eligible patients is limited and the COMS needs the continued support and cooperation of ophthalmologists throughout the United States and Canada.

  15. Choroidal physiology and primary angle closure disease.

    PubMed

    Zhang, Xiulan; Wang, Wei; Aung, Tin; Jonas, Jost B; Wang, Ningli

    2015-01-01

    Primary angle closure disease (PACD), prevalent in Asian countries, is generally associated with a shallower anterior chamber, a shorter axial length, thicker lens, hyperopia, and female sex. Other physiologic factors, however, may be important, especially with regard to triggering acute primary angle closure. Thickening of the choroid has been demonstrated in untreated and treated, acute and chronic PACD eyes. Recently, there has been growing interest in studying the role of the choroid in the pathophysiology of PACD. The emergence of new imaging technology such as the enhanced depth imaging mode of spectral-domain optical coherence tomography and swept-source optical coherence tomography has contributed to understanding PACD pathologies. We summarize the functions of the choroid and choroidal changes in the pathogenesis of PACD, and discuss potential future developments. PMID:26164737

  16. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

    PubMed Central

    Bhutto, Imran A.; McLeod, D. Scott; Hasegawa, Takuya; Kim, Sahng Y.; Merges, Carol; Tong, Patrick; Lutty, Gerard A.

    2016-01-01

    , VEGF and PEDF immunostaining was the most intense in RPE-Bruch’s membrane-choriocapillaris complex. In AMD, PEDF was significantly lower in RPE cells, RPE basal lamina, Bruch’s membrane and choroidal stroma. These data suggest that a critical balance exists between PEDF and VEGF, and PEDF may counteract the angiogenic potential of VEGF. The decrease in PEDF may disrupt the balance and be permissive for the formation of choroidal neovascularization (CNV) in AMD. PMID:16019000

  17. Host immune cellular reactions in corneal neovascularization

    PubMed Central

    Abdelfattah, Nizar S.; Amgad, Mohamed; Zayed, Amira A

    2016-01-01

    Corneal neovascularization (CNV) is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV. PMID:27162740

  18. Choroid plexus papilloma with a hyperdiploid karyotype

    SciTech Connect

    Roland, B.; Pinto, A.

    1994-09-01

    An 11-month-old male underwent surgery for a choroid plexus neoplasm, which on histologic examination was diagnosed as a benign papilloma. Chromosome analysis showed a karyotype of 55,XY,+7+7,+8,+9,+12,+12,+15,+20,+21 in all 20 metaphases analyzed. This is only the third benign choroid plexus papilloma that has been karyotyped, with the others being normal and hypodiploid (33 chromosomes). Three malignant choroid plexus carcinomas have also been analyzed, two with normal karyotypes and one hypodiploid (34 - 35 chromosomes). The two hypoidiploid neoplasms lack chromosomes 2, 3, 4, 5, 10, 13, 14, 17 and 18. Since the chromosomes that are lost in the hypodiploid neoplasms are different from the chromosomes gained in our tumor, it appears that the dosage of specific chromosomes is important in the origin of choroid plexus neoplasms. Benign choroid plexus papillomas can be difficult to differentiate from choroid plexus carcinomas. With the data available so far, it does not appear that cytogenetics can assist in making the diagnosis.

  19. Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2012-05-01

    Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

  20. Corneal Neovascularization: An Anti-VEGF Therapy Review

    PubMed Central

    Chang, Jin-Hong; Garg, Nitin K.; Lunde, Elisa; Han, Kyu-Yeon; Jain, Sandeep; Azar, Dimitri T.

    2013-01-01

    Corneal neovascularization is a serious condition that can lead to a profound decline in vision. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Corneal neovascularization occurs when the balance between angiogenic and antiangiogenic factors is tipped toward angiogenic molecules. Vascular endothelial growth factor (VEGF), one of the most important mediators of angiogenesis, is upregulated during neovascularization. In fact, anti-VEGF agents have efficacy in the treatment of neovascular age-related macular degeneration, diabetic retinopathy, macular edema, neovascular glaucoma, and other neovascular diseases. These same agents have great potential for the treatment of corneal neovascularization. We review some of the most promising anti-VEGF therapies, including bevacizumab, VEGF trap, siRNA, and tyrosine kinase inhibitors. PMID:22898649

  1. Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice

    PubMed Central

    Zhi, Zhongwei; Yin, Xin; Dziennis, Suzan; Wietecha, Tomasz; Hudkins, Kelly L.; Alpers, Charles E.; Wang, Ruikang K

    2012-01-01

    We present a novel application of optical microangiography (OMAG) imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able to provide true capillary level imaging of the retinal and choroidal vasculature. The microvascular patterns within different retinal layers are presented. An en face Doppler OCT approach [Srinivasan et al., Opt Express 18, 2477 (2010)] was adopted for retinal blood flow measurement. The flow is calculated by integrating the axial blood flow velocity over the vessel area measured in an en face plane without knowing the blood vessel angle. Total retinal blood flow can be measured from both retinal arteries and veins. The results indicate that OMAG has the potential for qualitative and quantitative evaluation of the microcirculation in posterior eye compartments in mouse models of retinopathy and neovascularization. PMID:23162733

  2. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.

    PubMed

    Huang, Lulin; Zhang, Houbin; Cheng, Ching-Yu; Wen, Feng; Tam, Pancy O S; Zhao, Peiquan; Chen, Haoyu; Li, Zheng; Chen, Lijia; Tai, Zhengfu; Yamashiro, Kenji; Deng, Shaoping; Zhu, Xianjun; Chen, Weiqi; Cai, Li; Lu, Fang; Li, Yuanfeng; Cheung, Chui-Ming G; Shi, Yi; Miyake, Masahiro; Lin, Yin; Gong, Bo; Liu, Xiaoqi; Sim, Kar-Seng; Yang, Jiyun; Mori, Keisuke; Zhang, Xiongzhe; Cackett, Peter D; Tsujikawa, Motokazu; Nishida, Kohji; Hao, Fang; Ma, Shi; Lin, He; Cheng, Jing; Fei, Ping; Lai, Timothy Y Y; Tang, Sibo; Laude, Augustinus; Inoue, Satoshi; Yeo, Ian Y; Sakurada, Yoichi; Zhou, Yu; Iijima, Hiroyuki; Honda, Shigeru; Lei, Chuntao; Zhang, Lin; Zheng, Hong; Jiang, Dan; Zhu, Xiong; Wong, Tien-Ying; Khor, Chiea-Chuen; Pang, Chi-Pui; Yoshimura, Nagahisa; Yang, Zhenglin

    2016-06-01

    Polypoidal choroidal vasculopathy (PCV), a subtype of 'wet' age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent cohorts identified a rare c.986A>G (p.Lys329Arg) variant in the FGD6 gene as significantly associated with PCV (P = 2.19 × 10(-16), odds ratio (OR) = 2.12) but not with CNV (P = 0.26, OR = 1.13). The intracellular localization of FGD6-Arg329 is distinct from that of FGD6-Lys329. In vitro, FGD6 could regulate proangiogenic activity, and oxidized phospholipids increased expression of FGD6. FGD6-Arg329 promoted more abnormal vessel development in the mouse retina than FGD6-Lys329. Collectively, our data suggest that oxidized phospholipids and FGD6-Arg329 might act synergistically to increase susceptibility to PCV. PMID:27089177

  3. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    SciTech Connect

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed; Corriveau, Christine; Edelstein, Chaim; Deschenes, Jean; Ruo, Russel; Patrocinio, Horacio; Cury, Fabio L.B.; DeBlois, Francois; Shenouda, George

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

  4. Choroidal thickness changes with photodynamic therapy for a diffuse choroidal hemangioma in Sturge–Weber syndrome.

    PubMed

    Cacciamani, Andrea; Scarinci, Fabio; Parravano, Mariacristina; Giorno, Paola; Varano, Monica

    2014-10-01

    The aim of this study was to evaluate the choroidal thickness (CT) changes associated with visual function following photodynamic therapy (PDT) for a diffuse choroidal hemangioma in Sturge–Weber syndrome. We report a case of Sturge–Weber syndrome and symptomatic serous retinal detachment (SRD) with diffuse choroidal hemangioma treated with PDT. Visual acuity (VA), macular sensitivity measured by means of MP1 microperimeter (Nidek Technologies, Padova, Italy), retinal and CT, measured by means of enhanced depth optical coherence tomography (EDI–OCT, Spectralis, Heidelberg Engineering, Heidelberg, Germany) were analyzed at baseline, 3 and 12 months follow-up.After the PDT VA and macular sensitivity improved.The OCT examination showed the resolution of SRD. The choroid was measured after PDT using EDI–OCT. At baseline, the subfoveal CT showed a progressive thickness reduction from 251 to 83 lm during follow-up. To our knowledge, this is the first report of CT changes after PDT for a diffuse choroidal hemangioma in Sturge–Weber syndrome in a longterm follow-up. The CT measurement represents a potential parameter to better follow choroidal hemangiomas and their response to treatment. However,the long-term choroidal changes should be carefully taken into account. PMID:24658736

  5. Functional and genetic analysis of choroid plexus development in zebrafish

    PubMed Central

    Henson, Hannah E.; Parupalli, Chaithanyarani; Ju, Bensheng; Taylor, Michael R.

    2014-01-01

    The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFP)sj2, that expresses enhanced green fluorescent protein (EGFP) in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFP)sj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease. PMID:25426018

  6. Choroidal and cutaneous metastasis from gastric adenocarcinoma.

    PubMed

    Kawai, Shoichiro; Nishida, Tsutomu; Hayashi, Yoshito; Ezaki, Hisao; Yamada, Takuya; Shinzaki, Shinichiro; Miyazaki, Masanori; Nakai, Kei; Yakushijin, Takayuki; Watabe, Kenji; Iijima, Hideki; Tsujii, Masahiko; Nishida, Kohji; Takehara, Tetsuo

    2013-03-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. PMID:23538460

  7. Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients

    PubMed Central

    Gu, Yong-Hao; Ke, Gen-Jie; Wang, Lin; Gu, Qi-Hong; Zhou, En-Liang; Pan, Hong-Biao; Wang, Shi-Ying

    2016-01-01

    AIM To comprehensively analyze the risk factors of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope (UBM). Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60±3.62 vs 12.96±3.55, P<0.001), best-corrected visual acuity was worse [3.00 (2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and larger extent of retinal detachment (P<0.001) were significant and independent risk factors for developing CD. CONCLUSION For CD in RRD, related factors include BCVA, IOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low IOP are significant and independent risk factors. PMID:27500106

  8. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2015-07-01

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD. PMID:25524721

  9. Vitreous histocytology of primary choroidal malignant melanoma.

    PubMed

    Traboulsi, E I; Jalkh, A E; Frangieh, G T; Tomb, J

    1987-02-01

    The cytomorphologic findings of a vitrectomy specimen from the right eye of an 80-year-old woman with an unsuspected primary choroidal malignant melanoma are described. The patient had undergone a closed vitrectomy because of chronic vitreous hemorrhage. Histocytology of the vitreous fluid specimens revealed melanoma cells of variable shape and size (from 30-150 microns) with eccentric nuclei. Many of these cells were binucleated or multinucleated with small, uniform, evenly dispersed intracytoplasmic melanin granules. The histocytologic findings together with the postoperative tumor characteristics by ultrasonography and fluorescein angiography suggested the diagnosis of choroidal malignant melanoma. PMID:3566022

  10. Enlargement of choroid plexus in complex regional pain syndrome

    PubMed Central

    Zhou, Guangyu; Hotta, Jaakko; Lehtinen, Maria K.; Forss, Nina; Hari, Riitta

    2015-01-01

    The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms. PMID:26388497

  11. Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group.

    PubMed

    1990-06-01

    The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K. PMID:1693496

  12. The Choroidal Eye Oximeter - An instrument for measuring oxygen saturation of choroidal blood in vivo

    NASA Technical Reports Server (NTRS)

    Laing, R. A.; Danisch, L. A.; Young, L. R.

    1975-01-01

    The Choroidal Eye Oximeter is an electro-optical instrument that noninvasively measures the oxygen saturation of choroidal blood in the back of the human eye by a spectrophotometric method. Since choroidal blood is characteristic of blood which is supplied to the brain, the Choroidal Eye Oximeter can be used to monitor the amount of oxygen which is supplied to the brain under varying external conditions. The instrument consists of two basic systems: the optical system and the electronic system. The optical system produces a suitable bi-chromatic beam of light, reflects this beam from the fundus of the subject's eye, and onto a low-noise photodetector. The electronic system amplifies the weak composite signal from the photodetector, computes the average oxygen saturation from the area of the fundus that was sampled, and displays the value of the computed oxygen saturation on a panel meter.

  13. Use of angle kappa in myopic photorefractive keratectomy

    PubMed Central

    Khakshoor, Hamid; McCaughey, Michael V; Vejdani, Amir Hossein; Daneshvar, Ramin; Moshirfar, Majid

    2015-01-01

    Purpose To explore utilization of the coaxially sighted corneal light reflex (CSCLR) for centration during myopic photorefractive keratectomy (PRK) for patients with relatively high angle kappa (κ) values. Methods Patients were stratified into two groups preoperatively, on the basis of angle κ values. Group A was composed of 166 eyes with an angle κ value <5°. Group B consisted of 182 eyes with an angle κ value >5°. Intraoperative centering of ablation was performed within group A by utilizing the pupillary center, and within group B by using the CSCLR. Visual acuities were evaluated and compared at 6 months and 12 months postoperatively between groups. Results Mean uncorrected visual acuities (UCVA) for all patients at 6 months and 12 months were −0.073 logMAR and −0.080 logMAR, respectively. A total of 98.9% of patients had a UCVA of 0.00 logMAR (≈20/20 Snellen) 12 months postoperatively. There was not a significant between-group difference in regard to residual refractive error at 6 months or 12 months (P=0.53 and P=0.97), or in UCVA at 6 months and 12 months (P=0.76 and P=0.17). There were no subjective complaints of monocular diplopia, glare, or haloes within either group at any time during follow-up. Conclusion Availing use of the CSCLR for centration of ablation within myopic patients with high angle κ values may aid in providing better refractive outcomes after performance of PRK. PMID:25678767

  14. CHOROIDAL IMAGING USING SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    Regatieri, Caio V.; Branchini, Lauren; Fujimoto, James G.; Duker, Jay S.

    2012-01-01

    Background A structurally and functionally normal choroidal vasculature is essential for retinal function. Therefore, a precise clinical understanding of choroidal morphology should be important for understanding many retinal and choroidal diseases. Methods PUBMED (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed) was used for most of the literature search for this article. The criterion for inclusion of an article in the references for this review was that it included materials about both the clinical and the basic properties of choroidal imaging using spectral-domain optical coherence tomography. Results Recent reports show successful examination and accurate measurement of choroidal thickness in normal and pathologic states using spectral-domain optical coherence tomography systems. This review focuses on the principles of the new technology that make choroidal imaging using optical coherence tomography possible and on the changes that subsequently have been documented to occur in the choroid in various diseases. Additionally, it outlines future directions in choroidal imaging. Conclusion Optical coherence tomography is now proven to be an effective noninvasive tool to evaluate the choroid and to detect choroidal changes in pathologic states. Additionally, choroidal evaluation using optical coherence tomography can be used as a parameter for diagnosis and follow-up. PMID:22487582

  15. Chronologic versus Biologic Aging of the Human Choroid

    PubMed Central

    May, Christian Albrecht

    2013-01-01

    Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch's membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease. PMID:24453840

  16. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  17. Microwave plaque thermoradiotherapy for choroidal melanoma.

    PubMed Central

    Finger, P. T.

    1992-01-01

    Microwave thermoradiotherapy was used as a primary treatment for 44 patients with choroidal melanoma. An episcleral dish-shaped microwave antenna was placed beneath the tumour at the time of plaque brachytherapy. While temperatures were measured at the sclera, the tumour's apex was targeted to receive a minimum of 42 degrees C for 45 minutes. In addition, the patients received full or reduced doses of plaque radiotherapy. No patients have been lost to follow-up. Two eyes have been enucleated: one for rubeotic glaucoma, and one for uveitic glaucoma. Though six patients have died, only one death was due to metastatic choroidal melanoma (39 months after treatment). Clinical observations suggest that the addition of microwave heating to plaque radiation therapy of choroidal melanoma has been well tolerated. There has been a 97.7% local control rate (with a mean follow-up of 22.2 months). We have reduced the minimum tumour radiation dose (apex dose) to levels used for thermoradiotherapy of cutaneous melanomas (50 Gy/5000 rad). Within the range of this follow-up period no adverse effects which might preclude the use of this microwave heat delivery system for treatment of choroidal melanoma have been noted. Images PMID:1622949

  18. Variants in the APOE Gene Are Associated with Improved Outcome after Anti-VEGF Treatment for Neovascular AMD

    PubMed Central

    Xie, Jing; Lim, Jonathan; Chauhan, Devinder S.; Robman, Luba; Richardson, Andrea J.; Hageman, Gregory; Baird, Paul N.; Guymer, Robyn

    2011-01-01

    Purpose. Anti-vascular endothelial growth factor (anti-VEGF) drugs have dramatically improved the treatment of neovascular AMD. In pivotal studies, almost 90% of patients maintain vision, with approximately 30% showing significant improvement. Despite these successes, 10% to 15% of patients continue to lose vision, even with treatment. It has been reported that variants in some AMD-associated genes influence treatment outcome. This study showed an association of treatment outcome with variants in the apolipoprotein E (APOE) gene. Methods. One hundred ninety-two patients receiving anti-VEGF treatment for subfoveal choroidal neovascularization secondary to AMD were enrolled. Information on demographics, lesion characteristics, delay until treatment, visual acuity (VA), and number of treatments was collected, and variants of APOE were assessed in all patients at baseline. Best corrected logarithm of the minimum angle of resolution (logMAR) VA was recorded in all patients. Results. The presence of the APOE ε4 allele was associated with improved treatment outcome at 3 (P = 0.02) and 12 (P = 0.06) months, compared with the presence of the ε2 allele, after adjustment for baseline acuity, treatment delay after first symptoms, age, and sex. Patients with an APOE ε4 allele had an odds ratio (OR) of 4.04 (95% confidence interval [CI], 1.11–14.70) for a 2-line gain in vision from baseline at 3 months (P = 0.03) and an OR of 2.54 (95% CI, 0.61–10.52; P = 0.20) at 12 months after treatment, based on multivariate analysis. Conclusions. In patients with neovascular AMD, the presence of the APOE ε4 allele conferred significantly better visual outcomes after anti-VEGF treatment than did the ε2 allele. These findings suggest a possible role for a personalized approach to treatment with anti-VEGF. PMID:21245410

  19. Angiographic results of retinal-retinal anastomosis and retinal-choroidal anastomosis after treatments in eyes with retinal angiomatous proliferation

    PubMed Central

    Saito, Masaaki; Iida, Tomohiro; Kano, Mariko; Itagaki, Kanako

    2012-01-01

    Background The purpose of this study was to evaluate the angiographic results of retinal-retinal anastomosis (RRA) and retinal-choroidal anastomosis (RCA) for eyes with retinal angiomatous proliferation (RAP) after treatment with intravitreal bevacizumab injections as monotherapy or intravitreal bevacizumab combined with photodynamic therapy. Methods In this interventional, consecutive case series, we retrospectively reviewed five naïve eyes from four patients (mean age 80 years) treated with three consecutive monthly intravitreal bevacizumab (1.25 mg/0.05 mL) injections as initial treatment, and followed up for at least 3 months. In cases with over 3 months of follow-up and having recurrence of RAP or leakage by fluorescein angiography, retreatment was performed with a single intravitreal bevacizumab injection and photodynamic therapy. Results Indocyanine green angiography showed RRA in three eyes with subretinal neovascularization and RCA in two eyes with choroidal neovascularization at baseline. At 3 months after baseline (month 3), neither the RRA nor RCA was occluded in any eye on indocyanine green angiography. Retreatment with intravitreal bevacizumab plus photodynamic therapy was performed in three eyes at months 3 (persistent leakage on fluorescein angiography), 6, and 7 (recurrence of RAP lesion), which achieved obvious occlusion of the RRA and RCA. Mean best-corrected visual acuity improved from 0.13 to 0.21 at month 3 (P = 0.066). No complications or systemic adverse events were noted. Conclusion Although intravitreal bevacizumab for RAP was effective in improving visual acuity during short-term follow-up, intravitreal bevacizumab could not achieve complete occlusion of RRA and RCA, which could lead to recurrence of a RAP lesion and exudation. Retreatment with intravitreal bevacizumab plus photodynamic therapy ultimately achieved complete occlusion of the RRA and RCA. PMID:22969283

  20. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  1. A case of giant nodular posterior scleritis mimicking choroidal malignancy

    PubMed Central

    Liu, Andrea T; Luk, Fiona O; Chan, Carmen K

    2015-01-01

    To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biospy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure. PMID:26862098

  2. Choroid Melanoma Metastasis to Spine: A Rare Case Report.

    PubMed

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  3. Nanoparticles for the treatment of ocular neovascularizations.

    PubMed

    Hennig, Robert; Goepferich, Achim

    2015-09-01

    Neovascular diseases of the posterior eye like age-related macular degeneration, proliferative diabetic retinopathy or retinopathy of prematurity carry a tremendous burden for patient and health care system alike. Although intravitreal injections of anti-VEGF based therapeutics have significantly improved the visual outcome for many patients, current therapeutic options still show significant drawbacks such as the injection-related risk of contracting an infection. Due to their ability to encapsulate drugs with otherwise poor bioavailability, accumulate in areas of increased vascular permeability and control the release of active ingredients over time, nanoparticle systems have been widely researched to enhance current therapeutic strategies and expand the therapeutic arsenal. In this review, emphasis is placed both on the possibilities and drawbacks that a systemic nanoparticle-based therapy could have in the context of neovascular posterior eye diseases. Recent investigations into intravenous and intravitreal administration of nanomaterials and their potential to deliver potent drugs and genes to pathologic lesions will also be presented. Furthermore, we will focus on the exceptional anti-oxidative and anti-angiogenic properties of selected nanoscale systems that carve out new paths for the treatment of these severe posterior eye diseases. PMID:25758124

  4. Carotid intraplaque neovascularization quantification software (CINQS).

    PubMed

    Akkus, Zeynettin; van Burken, Gerard; van den Oord, Stijn C H; Schinkel, Arend F L; de Jong, Nico; van der Steen, Antonius F W; Bosch, Johan G

    2015-01-01

    Intraplaque neovascularization (IPN) is an important biomarker of atherosclerotic plaque vulnerability. As IPN can be detected by contrast enhanced ultrasound (CEUS), imaging-biomarkers derived from CEUS may allow early prediction of plaque vulnerability. To select the best quantitative imaging-biomarkers for prediction of plaque vulnerability, a systematic analysis of IPN with existing and new analysis algorithms is necessary. Currently available commercial contrast quantification tools are not applicable for quantitative analysis of carotid IPN due to substantial motion of the carotid artery, artifacts, and intermittent perfusion of plaques. We therefore developed a specialized software package called Carotid intraplaque neovascularization quantification software (CINQS). It was designed for effective and systematic comparison of sets of quantitative imaging biomarkers. CINQS includes several analysis algorithms for carotid IPN quantification and overcomes the limitations of current contrast quantification tools and existing carotid IPN quantification approaches. CINQS has a modular design which allows integrating new analysis tools. Wizard-like analysis tools and its graphical-user-interface facilitate its usage. In this paper, we describe the concept, analysis tools, and performance of CINQS and present analysis results of 45 plaques of 23 patients. The results in 45 plaques showed excellent agreement with visual IPN scores for two quantitative imaging-biomarkers (The area under the receiver operating characteristic curve was 0.92 and 0.93). PMID:25561454

  5. An examination of the relation between intraocular pressure, fundal stretching and myopic pathology.

    PubMed

    McMonnies, Charles W

    2016-03-01

    Pathological myopia is one of the leading causes of visual impairment worldwide. Myopic development and progression is biomechanical and dominated by axial elongation. This clinical perspective examines some of the stretch-related fundal changes, which are associated with axial elongation and myopic pathology. The biomechanics of stretching of the fundus appears to depend on genetically and/or visual experience-based scleral changes, which reduce its thickness and elastic modulus so that it becomes more susceptible to the distending forces of intraocular pressure. These changes include reduced collagen synthesis, altered collagen fibres, tissue loss, altered proteoglycans and increased matrix metalloproteinase activity. Such changes are associated with reduced scleral rigidity and related increased potential to stretch in response to intraocular pressure. As axial elongation progresses, the sclera appears likely to continue to reduce in thickness and in its capacity to resist intraocular pressure, especially when pressure becomes elevated. Tessellation, lacquer cracks, myopic crescents, staphylomata, chorioretinal atrophy and retinal detachment are examined within a model for stretching of the fundus. Age, refractive error and axial length, for example, are associated with increased pathological progression. Myopic pathological progression can become dominated by vascular changes and include a greater risk of loss of acuity and blindness. Measures to control myopic pathology, which successfully slow or prevent stretching of the fundus, appear to be key factors in reducing or even avoiding permanent visual loss associated with this condition. For example, limiting axial elongation and related myopic fundus pathology by inhibiting changes which reduce the elastic modulus of scleral tissue is a desirable outcome from interventions to control myopia. Similarly, reducing exposure to the distending stress of elevated intraocular pressure appears to be a desirable form of

  6. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  7. Is There Any Role for the Choroid in Glaucoma?

    PubMed

    Goharian, Iman; Sehi, Mitra

    2016-05-01

    The choroid is part of the uveal tract and is a heavily vascularized bed that also contains connective tissue and melanin pigment. Given the role of the choroidal vasculature in the blood supply of the anterior laminar and prelaminar regions of the optic nerve head, the peripapillary choroid might be a relevant target for investigation in patients with glaucoma. The purpose of this paper is to critically review the current understanding of potential role of the choroid in the pathogenesis of glaucomatous damage. PMID:25265007

  8. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    SciTech Connect

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  9. Retinal and Choroidal Folds in Papilledema

    PubMed Central

    Sibony, Patrick A.; Kupersmith, Mark J.; Feldon, Steven E.; Wang, Jui-Kai; Garvin, Mona

    2015-01-01

    Purpose To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). Methods Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. Results We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. Conclusions Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.) PMID:26335066

  10. Choroid plexus cyst in a dog.

    PubMed

    Galano, Heather R; Platt, Simon R; Neuwirth, Lisa; Quist, Charlotte F; de Lahunta, Alexander

    2002-01-01

    A 6-year-old male Doberman Pinscher had a 2-month history of dysequilibrium. Lesion localization was determined to be the cerebellomedullary pontine angle. In computed tomographic images, a well-defined, circular, hypoattenuating mass was visible at the cerebellomedullary pontine angle. The lesion, which was isoattenuating to cerebrospinal fluid, was 4 x 8 mm in diameter. Peripheral ring enhancement was evident after contrast medium administration. A choroid plexus cyst was diagnosed histopathologically. PMID:12174999

  11. Retinal oxygenation via the choroidal circulation.

    PubMed Central

    Landers, M B

    1978-01-01

    The possibility of supplying normal amounts of oxygen to the inner layers of the retina by diffusion from the choroid in the presence of retinal arterial obstruction was studied in cats and rhesus monkeys. While the animals were under general anesthesia, an oxygen electrode was placed in the vitreous cavity immediately adjacent to the retina, and a retinal artery blocker probe was used to occlude various segments of the retina blood supply. The inspired oxygen concentration was alternated between 20% and 100%. The choroidal circulation was intermittently occluded by elevating the intraocular pressure. In all animals it was possible to return the oxygen tension of the innermost retina to normal concentrations or above while the retinal arterial circulation alone was occluded, by having the animal breathe 100% oxygen at one atmosphere pressure. This could not be done when the intraocular pressure was elevated to 85 mm Hg, occluding the choroidal as well as the retinal circulation. The electroretinogram and the visually evoked response were recorded in cats while the retinal circulation was occluded and the inspired oxygen concentration changed from 20% to 100% at one atmosphere pressure. The electroretinogram and the visually evoked response were extinguished by occluding the retinal circulation while the animal was breathing 20% oxygen, and these responses were returned to normal by changing to a 100% inspired oxygen concentration. Images FIGURE 6 PMID:112752

  12. Increased macular choroidal blood flow velocity and decreased choroidal thickness with regression of punctate inner choroidopathy

    PubMed Central

    2014-01-01

    Background Changes in choroidal circulation hemodynamics during the course of punctate inner choroidopathy (PIC) remain unknown. The aim of this study was to quantitatively evaluate changes in choroidal blood flow velocity by using laser speckle flowgraphy (LSFG) in patients with PIC. Case presentation This PIC patient was initially treated with systemic corticosteroids for 4 months. LSFG measurements were taken 10 consecutive times before treatment and at 1, 3, 12, 20 and 23 months after the initiation of therapy. The mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Circles 1, 2 and 3 were set at the fovea, a lesion site, and an area of normal-appearing retina, respectively. The PIC lesions scarred after treatment along with improvements in visual function and outer retinal morphology. When the changing rate of macular flow over the 12-month follow-up period was compared with the MBR before treatment (100%), an increase of 16–37%, 24–49% and 15–18% was detected in Circles 1, 2 and 3, respectively. At the time of PIC recurrence after 20 months, the MBR decreased temporarily but subsequently increased after retreatment with systemic corticosteroids. This trend was accompanied by a decrease in choroidal thickness at the lesion site after retreatment. Conclusions Macular choroidal blood flow velocity increased and choroidal thickness decreased concurrently with regression of PIC. The present findings suggest that inflammation-related impairments in choroidal circulation may relate to the pathogenesis of PIC, extending over a wider area in the posterior pole than the PIC lesions per se. PMID:24885365

  13. Myopic shift and its mechanism in nephropathia epidemica or Puumala virus infection.

    PubMed Central

    Kontkanen, M; Puustjärvi, T; Lähdevirta, J

    1994-01-01

    Nephropathia epidemica (NE) is a zoonose caused by Puumala virus. NE belongs to the group of haemorrhagic fevers with renal syndrome. Transient myopia has been described in the acute phase of the disease. This prospective study presents the changes of refraction and the results of ophthalmic A scan measurements of patients who were managed at Savonlinna Central Hospital for NE during an epidemic in the winter of 1992-3. This involved 37 patients and 74 eyes. The incidence of transient myopia was 8.1% and that of myopic shift 40.5%. A scan ultrasound measurements were performed in patients in the acute phase and after total recovery of their general illness. Statistical analysis revealed that there were significant differences in anterior chamber depth and lens thickness between the acute and control phases of the disease and between the patients who had myopic shift compared with those who did not have a significant myopic change in refraction. Based on these results it seems that the reason for transient myopic shift of NE is mainly a combination of two factors: forward movement of the anterior diaphragm and thickening of the crystalline lens. The term myopic shift should be used rather than transient myopia because it better describes the overall refractive change in NE. PMID:7819173

  14. Nd: YAG Laser Posterior Capsulotomy Rates in Myopic Eyes after Implantation of Capsular Tension Ring

    PubMed Central

    Keles, Sadullah; Kartal, Baki; Apil, Aytekin; Ondas, Osman; Kozan, Betul Dertsiz; Topdagi, Elif; Ekinci, Metin; Ceylan, Erdinc; Baykal, Orhan

    2014-01-01

    Background The aim f this study was to evaluate the effect of capsular tension ring implantation during cataract surgery on the incidence of neodymium: YAG (Nd: YAG) laser posterior capsulotomy in myopic (axial length [AL] ≥25.00 mm) eyes. Material/Methods In this retrospective study, the records of the cases of 117 myopic patients who underwent cataract surgery between January 2004 and January 2011 were reviewed. A total of 153 eyes with an axial length of 25 mm or higher were included in the study with consideration of exclusion criteria mentioned below. Eyes were grouped by presence or lack of capsular tension ring (CTR+ and CTR−, respectively). Results The study included 153 eyes from 107 myopic patients. Hydrophilic acrylic IOL and capsular tension ring (CTR) were implanted in 78 eyes (CTR+ group), and 75 eyes received only the hydrophilic acrylic IOL (CTR− group). Six eyes (7.6%) in CTR+ and 16 eyes (21.3%) in CTR− required Nd: YAG laser capsulotomy within 7 years. The difference between the 2 groups was statistically significant (p=0.021). Conclusions Because CTRs significantly decrease subsequent need for Nd: YAG laser posterior capsulotomy in myopic patients, are very inexpensive, and provide other benefits, our data suggest that the use of CTRs in myopic eyes undergoing cataract surgery with an hydrophilic acrylic IOL implantation is advantageous and should be standard practice. PMID:25132225

  15. Psammoma bodies - friends or foes of the aging choroid plexus.

    PubMed

    Jovanović, Ivan; Ugrenović, Sladjana; Vasović, Ljiljana; Petrović, Dragan; Cekić, Sonja

    2010-06-01

    Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma

  16. Angiogenesis and parasitic helminth-associated neovascularization.

    PubMed

    Dennis, Roger D; Schubert, Uwe; Bauer, Christian

    2011-04-01

    Successful metazoan parasitism, among many other factors, requires a supply of nutrients and the removal of waste products. There is a prerequisite for a parasite-defined vasculature. The angiogenic mechanism(s) involved presumably depend on the characteristics of the tissue- and vascular system-dwelling, parasitic helminths. Simplistically, 2 possibilities or a combination of both have been considered in this review. The multifactorial induction of parasitic helminth-associated neovascularization could arise through, either a host-, a parasite- or a host-/parasite-dependent, angiogenic switch. Most studies appear to support the first and third hypotheses, but evidence exists for the intrahepatic cestode Echinococcus multilocularis, the free-living nematode Caenorhabditis elegans and the intravascular trematode Schistosoma mansoni for the second inference. In contrast, the nematode anti-coagulant protein NAPc2 from adult Ancylostoma caninum is also an anti-angiogenic factor. PMID:21232174

  17. Retinal Image Quality during Accommodation in Adult Myopic Eyes

    PubMed Central

    Sreenivasan, Vidhyapriya; Aslakson, Emily; Kornaus, Andrew; Thibos, Larry N.

    2014-01-01

    Purpose Reduced retinal image contrast produced by accommodative lag is implicated with myopia development. Here, we measure accommodative error and retinal image quality from wavefront aberrations in myopes and emmetropes when they perform visually demanding and naturalistic tasks. Methods Wavefront aberrations were measured in 10 emmetropic and 11 myopic adults at three distances (100, 40, and 20 cm) while performing four tasks (monocular acuity, binocular acuity, reading, and movie watching). For the acuity tasks, measurements of wavefront error were obtained near the end point of the acuity experiment. Refractive state was defined as the target vergence that optimizes image quality using a visual contrast metric (VSMTF) computed from wavefront errors. Results Accommodation was most accurate (and image quality best) during binocular acuity whereas accommodation was least accurate (and image quality worst) while watching a movie. When viewing distance was reduced, accommodative lag increased and image quality (as quantified by VSMTF) declined for all tasks in both refractive groups. For any given viewing distance, computed image quality was consistently worse in myopes than in emmetropes, more so for the acuity than for reading/movie watching. Although myopes showed greater lags and worse image quality for the acuity experiments compared to emmetropes, acuity was not measurably worse in myopes compared to emmetropes. Conclusions Retinal image quality present when performing a visually demanding task (e.g., during clinical examination) is likely to be greater than for less demanding tasks (e.g., reading/movie watching). Although reductions in image quality lead to reductions in acuity, the image quality metric VSMTF is not necessarily an absolute indicator of visual performance because myopes achieved slightly better acuity than emmetropes despite showing greater lags and worse image quality. Reduced visual contrast in myopes compared to emmetropes is consistent

  18. Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2)

    PubMed Central

    Yanagisawa, Suiho; Miki, Akiko; Matsumiya, Wataru; Kusuhara, Sentaro; Tsukahara, Yasutomo; Honda, Shigeru; Negi, Akira

    2011-01-01

    Purpose To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. Results The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71–3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91–2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%–48.4%) and 29.7% (95% CI, 25.4%–34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. Conclusions Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease

  19. Effects of vasoactive stimuli on blood flow to choroid plexus

    SciTech Connect

    Faraci, F.M.; Mayhan, W.G.; Williams, J.K.; Heistad, D.D. )

    1988-02-01

    The goal of this study was to examine effects of vasoactive stimuli on blood flow to choroid plexus. The authors used microspheres to measure blood flow to choroid plexus and cerebrum in anesthetized dogs and rabbits. A critical assumption of the microsphere method is that microspheres do not pass through arteriovenous shunts. Blood flow values obtained with simultaneous injection of 15- and 50-{mu}m microspheres were similar, which suggest that shunting of 15-{mu}m microspheres was minimal. Blood flow to choroid plexus under control conditions was 287 {plus minus} 26 (means {plus minus} SE) ml {center dot} min{sup {minus}1} {center dot} 100 g{sup {minus}1} in dogs and 385 {plus minus} 73 ml {center dot} min{sup {minus}1} 100 g{sup {minus}1} in rabbits. Consecutive measurements under control conditions indicated that values for blood flow are reproducible. Adenosine did not alter blood flow to cerebrum but increased blood flow to choroid plexus two- to threefold in dogs and rabbits. Norepinephrine and phenylephrine did not affect blood flow to choroid plexus and cerebrum but decreased blood flow to choroid plexus by {approx} 50%. The authors suggest that (1) the microsphere method provides reproducible valid measurements of blood flow to the choroid plexus in dogs and rabbits and (2) vasoactive stimuli may have profoundly different effects on blood flow to choroid plexus and cerebrum.

  20. The choroid plexuses and their impact on developmental neurogenesis

    PubMed Central

    Johansson, Pia A.

    2014-01-01

    During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development. PMID:25386116

  1. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    SciTech Connect

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    1986-02-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.

  2. Metastatic Small-Cell Neuroendocrine Carcinoma Simulating Circumscribed Choroidal Hemangioma

    PubMed Central

    Leahy, Kate E.; Karaconji, Tanya; Thanni, Valli; Achan, Anita; Fung, Adrian T.

    2015-01-01

    Aim To report a case of metastatic small-cell neuroendocrine carcinoma presenting as an isolated choroidal mass and initially misdiagnosed as a circumscribed choroidal hemangioma. Methods The clinical history, fundus findings, imaging, cytology and immunohistochemical features are described. Results An otherwise healthy 66-year-old man was referred for a left nasal scotoma and a diagnosis of circumscribed choroidal hemangioma. Cytology showed cohesive clusters of small-to-intermediate malignant cells. The atypical cells stained positively for chromogranin, thyroid transcription factor-1 and synaptophysin consistent with small-cell neuroendocrine carcinoma. Conclusion Small-cell neuroendocrine carcinoma metastatic to the choroid is extremely rare; however, it is particularly aggressive and should be included in the differential diagnosis of isolated choroidal lesions, even in otherwise healthy patients. PMID:27171748

  3. NADPH oxidase 2 plays a role in experimental corneal neovascularization.

    PubMed

    Chan, Elsa C; van Wijngaarden, Peter; Chan, Elsie; Ngo, Darleen; Wang, Jiang-Hui; Peshavariya, Hitesh M; Dusting, Gregory J; Liu, Guei-Sheung

    2016-05-01

    Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans. PMID:26814205

  4. Recurrent Annular Peripheral Choroidal Detachment after Trabeculectomy

    PubMed Central

    Liu, Shaohui; Sun, Lisa L.; Kavanaugh, A. Scott; Langford, Marlyn P.; Liang, Chanping

    2013-01-01

    We report a challenging case of recurrent flat anterior chamber without hypotony after trabeculectomy in a 54-year-old Black male with a remote history of steroid-treated polymyositis, cataract surgery, and uncontrolled open angle glaucoma. The patient presented with a flat chamber on postoperative day 11, but had a normal fundus exam and intraocular pressure (IOP). Flat chamber persisted despite treatment with cycloplegics, steroids, and a Healon injection into the anterior chamber. A transverse B-scan of the peripheral fundus revealed a shallow annular peripheral choroidal detachment. The suprachoroidal fluid was drained. The patient presented 3 days later with a recurrent flat chamber and an annular peripheral choroidal effusion. The fluid was removed and reinforcement of the scleral flap was performed with the resolution of the flat anterior chamber. A large corneal epithelial defect developed after the second drainage. The oral prednisone was tapered quickly and the topical steroid was decreased. One week later, his vision decreased to count fingers with severe corneal stromal edema and Descemet's membrane folds that improved to 20/50 within 24 h of resumption of the oral steroid and frequent topical steroid. The patient's visual acuity improved to 20/20 following a slow withdrawal of the oral and topical steroid. Eight months after surgery, the IOP was 15 mm Hg without glaucoma medication. The detection of a shallow anterior choroidal detachment by transverse B-scan is critical to making the correct diagnosis. Severe cornea edema can occur if the steroid is withdrawn too quickly. Thus, steroids should be tapered cautiously in steroid-dependent patients. PMID:24348402

  5. Angioid streaks - a rare cause of neovascular glaucoma. Case report.

    PubMed

    Ungureanu, E; Geamanu, A; Careba, I; Grecescu, M; Gradinaru, S

    2014-01-01

    Rationale. Neovascular glaucoma is the type of glaucoma most refractory to treatment. The most frequent causes are those associated with retinal hypoxia, such as proliferative diabetic retinopathy, central retinal vein occlusion, branch retinal vein occlusion, central retinal arterial occlusion, ischemic ocular syndrome etc. Rare causes of neovascular glaucoma are multiple and are due to VEGF synthesis associated with chorioretinal inflammations or degenerations. We present a case with neovascular glaucoma associated with an extremely rare cause, angioid streaks Objective. The objective of our prsentation was to asses efficacy of the 5-FU associated trabeculectomy following bevacizumab intravitreal administration Methods and results. Case report of a 48 years old female patient which presented at the emergency room with painful red left eye. At presentation best corrected left eye visual acuity was 1/10, intraocular pressure was 36 mm Hg. Examination established the diagnosis of Neovascular glaucoma associated with angioid streaks. After intravenous Manitol, oral Acetazolamide and topical treatment with fixed combination timolol-brinzolamide, topical steroid and mydriatic intraocular pressure decreased. Intravitreal bevacizumab injection was performed, followed after 3 weeks by trabeculectomy. Discussion. Angioid streaks are an extremely rare cause of neovascular glaucoma. The treatment is similar to the treatment for other causes of neovascular glaucoma. PMID:27057253

  6. Angioid streaks - a rare cause of neovascular glaucoma. Case report.

    PubMed Central

    Ungureanu, E; Geamanu, A; Careba, I; Grecescu, M; Gradinaru, S

    2014-01-01

    Rationale. Neovascular glaucoma is the type of glaucoma most refractory to treatment. The most frequent causes are those associated with retinal hypoxia, such as proliferative diabetic retinopathy, central retinal vein occlusion, branch retinal vein occlusion, central retinal arterial occlusion, ischemic ocular syndrome etc. Rare causes of neovascular glaucoma are multiple and are due to VEGF synthesis associated with chorioretinal inflammations or degenerations. We present a case with neovascular glaucoma associated with an extremely rare cause, angioid streaks Objective. The objective of our prsentation was to asses efficacy of the 5-FU associated trabeculectomy following bevacizumab intravitreal administration Methods and results. Case report of a 48 years old female patient which presented at the emergency room with painful red left eye. At presentation best corrected left eye visual acuity was 1/10, intraocular pressure was 36 mm Hg. Examination established the diagnosis of Neovascular glaucoma associated with angioid streaks. After intravenous Manitol, oral Acetazolamide and topical treatment with fixed combination timolol-brinzolamide, topical steroid and mydriatic intraocular pressure decreased. Intravitreal bevacizumab injection was performed, followed after 3 weeks by trabeculectomy. Discussion. Angioid streaks are an extremely rare cause of neovascular glaucoma. The treatment is similar to the treatment for other causes of neovascular glaucoma PMID:27057253

  7. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  8. Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes

    SciTech Connect

    Seddon, J.M.; Gragoudas, E.S.; Albert, D.M.

    1983-09-01

    Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression.

  9. Choroidal abnormalities and masquerade syndromes confounding the diagnosis of laser-induced eye injuries

    NASA Astrophysics Data System (ADS)

    Hacker, Henry D.; Zwick, Harry; Brown, Jeremiah, Jr.; Dicks, Ronald; Cheramie, Rachel; Stuck, Bruce E.

    2005-04-01

    The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.

  10. Idiopathic Choroidal Neovascularisation as the Inaugural Sign of Multiple Evanescent White Dot Syndrome

    PubMed Central

    Papadia, Marina; Herbort, Carl P

    2010-01-01

    We report a case of multiple evanescent white dot syndrome (MEWDS) that presented with putative idiopathic choroidal neovascularisation (ICNV) before showing angiographic signs typical of MEWDS. A 16-year-old male presented with unilateral metamorphopsias and visual loss in his left eye. ICNV with subretinal hemorrhage was diagnosed and treated with intravitreal Avastin®. Fifteen days later, regression of choriodal neovascularization (CNV) was documented together with the appearance of fluorescein angiography (FA) and indocyanine green angiography (ICGA) signs typical for MEWDS, that included faint mottled FA hyperfluorescence in the mid-peripheral fundus, irregularly shaped mid-peripheral ICGA dark areas in the intermediate angiographic phase that were clearly delineated in the late phase as well as peripapillary hypofluorescence. Fundus examination appeared completely normal during the follow-up except for the CNV hemorrhage noted at the initial visit. This case demonstrates the need to consider ICNV as a diagnosis of exclusion until inflammatory causes have been eliminated. In this case, the underlying occult inflammatory condition would have been missed without the ICGA data that clearly showed signs of MEWDS that was supported by FA findings. PMID:20844686

  11. Brief light exposure at night disrupts the circadian rhythms in eye growth and choroidal thickness in chicks.

    PubMed

    Nickla, Debora L; Totonelly, Kristen

    2016-05-01

    myopic refractive error. It also abolished the increase in choroidal thickness that normally occurs between 6 pm and 12 am. We conclude that light at night alters the rhythms in axial length and choroidal thickness in an animal model of eye growth, and that these circadian disruptions might lead to the development of ametropias. These results have implications for the use of light during the night in children. PMID:26970497

  12. Analysis of Choroidal Morphology and Vasculature in Healthy Eyes Using Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Branchini, Lauren A; Adhi, Mehreen; Regatieri, Caio V; Nandakumar, Namrata; Liu, Jonathan J; Laver, Nora; Fujimoto, James G; Duker, Jay S

    2013-01-01

    Objective To analyze the morphology and vasculature of the choroid in healthy eyes using spectral-domain optical coherence tomography (SD-OCT). Design Cross-sectional retrospective review. Participants Forty-two healthy subjects (42 eyes), with no ocular disease who underwent high-definition scanning with Cirrus HD-OCT at the New England Eye Center, Boston, Massachusetts between November 2009 and September 2010. Methods The SD-OCT images were evaluated for morphological features of the choroid, including the shape of the choroid-scleral border, location of the thickest point of choroid and regions of focal choroidal thinning. Total choroidal thickness and large choroidal vessel layer thickness were measured by two independent observers experienced in analyzing OCT images using the Cirrus linear measurement tool at the fovea, 750μm nasal and temporal to the fovea. Custom software was used to calculate the ratio of choroidal stroma to the choroidal vessel lumen. Main Outcome Measures Qualitative assessment of the choroidal morphology, quantitative analysis of choroidal vasculature and use of a novel automated software to determine the ratio of choroidal stromal area to the area of choroidal vessel lumen. Results The 42 subjects had a mean age of 51.6 years. All subjects (100%) had a “bowl” or convex shape to the choroid-sclera junction and the thickest point of the choroid was under the fovea in 88.0% of the subjects. The mean choroidal thickness was 256.8±75.8μm, thickness of the large choroidal vessel layer was 204.3±65.9μm and that of medium choroidal vessel layer/choriocapillaris layer was 52.9±20.6μm beneath the fovea. The ratio of large choroidal vessel layer thickness to the total choroidal thickness beneath the fovea was 0.7±0.06. The software generated ratio of choroidal stromal area to the choroidal vessel lumen area to be 0.27±0.08, suggesting that choroidal vessel lumen forms a greater proportion of the choroid than choroidal stroma in

  13. Age-based analysis of choroidal thickness and choroidal vessel diameter in primary open-angle glaucoma.

    PubMed

    Toprak, Ibrahim; Yaylalı, Volkan; Yildirim, Cem

    2016-04-01

    We aimed to assess choroidal thickness and vessel diameter in patients with primary open-angle glaucoma (POAG) using enhanced depth imaging (EDI) optical coherence tomography (OCT) with age-based analysis. Fifty-four patients with a confirmed diagnosis of POAG and 44 age-sex matched healthy subjects were included into the study. A masked physician performed measurements of largest choroidal vessel diameter and choroidal thicknesses (subfoveal, nasal, and temporal) using EDI OCT. Subgroup analyses were performed to compare choroidal measurements based on age (with a cut point of 70 years). The study cohort comprised 54 patients with POAG (mean age of 63.2 ± 8.8 years) and 44 healthy control subjects (mean age of 62.9 ± 8.5 years) (P = 0.870). We found no significant differences in terms of choroidal measurements (P > 0.05) between the glaucoma and control groups. However, in the glaucoma group, patients with an age ≥70 years had significantly thinner subfoveal and nasal choroid compared to those of the patients with <70 years of age (P = 0.017, 0.002 respectively). In the control group, choroidal thickness and vessel measurements showed no significant difference when the subjects were subgrouped according to the age cut point (P > 0.05). Choroidal thickness and vessel caliber seem not to differ between patients with POAG and healthy controls. However, an age ≥70 years might be associated with thinning in subfoveal and nasal choroid in patients with POAG. Further studies are needed to elucidate whether choroidal thinning is a cause or result in POAG. PMID:26077882

  14. Fibrosis of the Choroid Plexus Filtration Membrane

    PubMed Central

    Parratt, John D. E.; Kirwan, Paul D.

    2016-01-01

    We report a previously undescribed inflammatory lesion consisting of deposition of activated complement (C3d and C9neo) in association with major histocompatibility complex type II (MHC2)-positive activated microglia in choroid plexus villi exhibiting classical fibrous thickening of the pericapillary filtration membrane. The proportion of villi affected ranged from 5% to 90% in 56 adult subjects with diseases of the CNS and 11 subjects with no preexisting disease of the CNS. In 3 of the 4 children studied, 2% or less of examined villi showed stromal thickening, complement deposition, and the presence of MHC2-positive microglia; in adults, the proportion of villi affected increased with age. Other features of the lesion included loss of capillaries and failure by macrophages to clear extracellular particulate electron-dense material by clathrin-mediated phagocytosis. This choroid plexus lesion may relate pathogenetically to age-related macular degeneration and to Alzheimer disease, 2 other conditions with no known risk factors other than increasing age. All 3 conditions are characterized by the presence of damaged capillaries, inflammatory extracellular aggregates of mixed molecular composition and defective clearance of the deposits by macrophages. PMID:27444353

  15. Central Serous Chorioretinopathy Mistaken for Tuberculous Choroiditis

    PubMed Central

    Papadia, Marina; Herbort, Carl P.

    2011-01-01

    Purpose To report a patient erroneously diagnosed with tuberculous choroiditis who was accordingly treated with long term steroids which in turn, worsened the actual disease process that turned out to be central serous chorioretinopathy (CSC). Case Report A 59-year-old Caucasian man developed a chorioretinal disease in his right eye in 1997. Having a positive tuberculin skin test, tuberculous chorioretinitis was suspected and antituberculous therapy was administered for 4 months. In 2005, visual symptoms in the same eye recurred and despite negative interferon gamma release assay, tuberculous choroiditis was considered as the diagnosis and the patient further received massive corticosteroid therapy along with antituberculous agents. Despite a deteriorating clinical picture, therapy was continued. Upon initial examination at our center, no sign of inflammation was observed and a diagnosis of CSC was made, consequently steroid therapy was terminated. Conclusion In some chorioretinopathies, it is difficult to differentiate inflammatory from non-inflammatory causes. One should observe the course of the disease and question the initial diagnosis when no improvement or deterioration occurs despite therapy. PMID:22454755

  16. Influence of cycloplegia with topical cyclopentolate on higher-order aberrations in myopic children

    PubMed Central

    Hiraoka, T; Miyata, K; Nakamura, Y; Ogata, M; Okamoto, F; Oshika, T

    2014-01-01

    Purpose To investigate the influence of cycloplegia with topical cyclopentolate on wavefront aberrations in myopic children. Design This is a prospective, comparative study. Methods Twenty-eight myopic children with a mean age of 7.25±2.55 were enrolled in this study. We evaluated refraction and wavefront aberrations before and after cycloplegia with 1% cyclopentolate hydrochloride. Ocular and corneal aberrations were simultaneously measured and compared with each other. Individual Zernike components were also analyzed up to the sixth order. All these parameters were compared before and after cycloplegia. Results Ocular higher-order aberrations (HOAs) significantly increased after cycloplegia (P=0.012 for spherical-like and P=0.015 for total HOAs). Corneal HOAs did not change after cycloplegia. When corneal and ocular HOAs were compared, the ocular HOAs were significantly smaller than the corneal HOAs in spherical-like aberrations (P<0.001) and total HOAs (P=0.006). As for individual Zernike components, ocular aberration generally showed smaller or equivalent values in comparison with corneal aberration. In addition, each Zernike component showed a large standard deviation. Conclusions Internal optics compensates for corneal HOAs in myopic children, and paralysis of tonic accommodation with cyclopentolate considerably affects ocular HOAs. However, inter-individual variation in each Zernike component is quite large in myopic children. PMID:24577253

  17. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    ERIC Educational Resources Information Center

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  18. Corneal Biomechanical Properties in Myopic Eyes Measured by a Dynamic Scheimpflug Analyzer

    PubMed Central

    Wang, Jingyi; Li, Ying; Jin, Yumei; Yang, Xue; Zhao, Chan; Long, Qin

    2015-01-01

    Purpose. To evaluate the corneal biomechanical parameters in myopic and emmetropic eyes using Corneal Visualization Scheimpflug Technology (CorVis ST). Methods. 103 myopic and emmetropic eyes of 103 patients were examined. Corneal biomechanical parameters, axial length, and mean keratometry were measured using CorVis ST, IOL Master, and topography, respectively. Corneal biomechanical properties were compared within four groups. Bivariate correlation analysis was used to assess the relationship between corneal biomechanical parameters and ocular characteristics. Results. Four of ten corneal biomechanical parameters, namely, deformation amplitude (DA), first- and second-applanation time (A1-time, A2-time), and radius at highest concavity (HC radius), were significantly different within the four groups (P < 0.05). In correlation analysis, DA was positively correlated with axial length (r = 0.20, P = 0.04); A2-time was positively correlated with spherical equivalent (SE) (r = 0.24, P = 0.02); HC radius was positively correlated with SE (r = 0.24, P = 0.02) and was negatively correlated with mean keratometry (r = −0.20, P = 0.046) and axial length (r = −0.21, P = 0.03). Conclusions. The corneal refraction-related biomechanical alterations were associated with ocular characteristics. Highly myopic eyes exhibited longer DA and smaller HC radius than do moderately myopic eyes; the eyes with longer axial length tend to have less corneal stiffness and are easier to deform under stress. PMID:26576291

  19. Fetal choroid plexus vascularization assessed by color flow ultrasonography.

    PubMed

    Kurjak, A; Schulman, H; Predanic, A; Predanic, M; Kupesic, S; Zalud, I

    1994-11-01

    We investigated the development of intracranial vascularization in the human fetus, with particular emphasis on the choroid plexus. The fetal brain was visualized in 102 patients with healthy pregnancies between 9 and 16 weeks' gestation. Imaging was done transvaginally except in the pregnancies of longer duration with unfavorable fetal positions. Color flow imaging was used to identify vessels in the cranium and within the choroid plexus. Pulsed Doppler signals were obtained from an internal carotid-middle cerebral artery and from a choroid plexus vessel. The pulsatility index was calculated from the Doppler spectral envelope. A major cerebral vessel could be seen at 9 weeks' gestation. Choroid plexus vessels were first seen at 10 weeks 3 days. Visualization rates ranged from 35 to 75% for plexus vessels, and 65 to 100% for cerebral vessels. Visualization of choroid plexus vessels was maximal at 13 weeks. The pulsatility index for the cerebral arteries at this gestational period averaged 2.6 +/- 0.6. The result for the choroid plexus was 1.66 +/- 0.5. (P < 0.001). Visualization of the vessels of the choroid plexus increases and decreases as the gland develops and shrinks. This developmental period also is the time of active neurogenesis. PMID:7837329

  20. Matrilin-1 Is an Inhibitor of Neovascularization*

    PubMed Central

    Foradori, Matthew J.; Chen, Qian; Fernandez, Cecilia A.; Harper, Jay; Li, Xin; Tsang, Paul C. W.; Langer, Robert; Moses, Marsha A.

    2014-01-01

    In the course of conducting a series of studies whose goal was to discover novel endogenous angiogenesis inhibitors, we have purified matrilin-1 (MATN-1) and have demonstrated, for the first time, that it inhibits neovascularization both in vitro and in vivo. Proteins were extracted from cartilage using a 2 m NaCl, 0.01 m HEPES buffer at 4 °C, followed by concentration of the extract. The concentrate was fractionated by size exclusion chromatography, and fractions were then screened for their ability to inhibit capillary endothelial cell (EC) proliferation in vitro. Fractions containing EC inhibitory activity were pooled and further purified by cation exchange chromatography. The resulting fractions from this step were then screened to isolate the antiangiogenic activity in vitro. This activity was identified by tandem mass spectrometry as being MATN-1. Human MATN-1 was cloned and expressed in Pichia pastoris and purified to homogeneity. Purified recombinant MATN-1, along with purified native protein, was shown to inhibit angiogenesis in vivo using the chick chorioallantoic membrane assay by the inhibition of capillary EC proliferation and migration. Finally, using a MATN-1-deficient mouse, we showed that angiogenesis during fracture healing was significantly higher in MATN-1−/− mice compared with the wild type mice as demonstrated by in vivo imaging and by elevated expression of angiogenesis markers including PECAM1, VEGFR, and VE-cadherin. PMID:24692560

  1. Choroidal and macular thickness changes induced by cataract surgery

    PubMed Central

    Falcão, Manuel S; Gonçalves, Nuno M; Freitas-Costa, Paulo; Beato, João B; Rocha-Sousa, Amândio; Carneiro, Ângela; Brandão, Elisete M; Falcão-Reis, Fernando M

    2014-01-01

    Background The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid. Methods In 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated. Results There was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 μm (P<0.001), and in vertical scans, the mean increase was +8.80±7.07 μm (P=0.001). However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 μm; P=0.47) whilst in horizontal scans a nonsignificant decrease was recorded (−9.11±39.59 μm; P=0.41). In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 μm; P=0.36). Conclusion Uncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of phacoemulsification is mainly observed at the retinal level, and seems to be independent of choroidal thickness changes. PMID:24368877

  2. Characterization of a Spontaneous Retinal Neovascular Mouse Model

    PubMed Central

    Hasegawa, Eiichi; Sweigard, Harry; Husain, Deeba; Olivares, Ana M.; Chang, Bo; Smith, Kaylee E.; Birsner, Amy E.; D’Amato, Robert J.; Michaud, Norman A.; Han, Yinan; Vavvas, Demetrios G.; Miller, Joan W.; Haider, Neena B.; Connor, Kip M.

    2014-01-01

    Background Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. Methods The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. Results We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. Conclusions The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease. PMID:25188381

  3. Evolving European guidance on the medical management of neovascular age related macular degeneration

    PubMed Central

    Chakravarthy, U; Soubrane, G; Bandello, F; Chong, V; Creuzot‐Garcher, C; Dimitrakos, S A; Korobelnik, J‐F; Larsen, M; Monés, J; Pauleikhoff, D; Pournaras, C J; Staurenghi, G; Virgili, G; Wolf, S

    2006-01-01

    Background Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)—thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT‐V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. Methods Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT‐V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. Results PDT‐V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size ⩽4 Macular Photocoagulation Study (MPS) disc areas (DA). The new classes of anti‐angiogenic agents—namely, pegaptanib sodium and ranibizumab (the latter when peer reviewed phase III data become available) are recommended for subfoveal lesions with any proportion of classic CNV or occult with no classic CNV. For juxtafoveal classic CNV, PDT‐V or anti‐angiogenic therapy should be considered if the new vessels are so close to the fovea that laser photocoagulation would almost certainly extend under the centre of the foveal avascular zone. For all other well demarcated juxtafoveal lesions and for extrafoveal classic lesions, laser photocoagulation remains the standard treatment. Therapy should be undertaken within 1 week of the fluorescein angiogram on which

  4. Failure of intravitreal bevacizumab in the treatment of choroidal metastasis

    PubMed Central

    Maudgil, A; Sears, K S; Rundle, P A; Rennie, I G; Salvi, S M

    2015-01-01

    Background Metastasis to choroid is the most common intraocular malignancy, arising most frequently from carcinoma of breast in women and lung in men. Recent case reports have described successful use of intravitreal bevacizumab to achieve local control of such tumours. Materials and methods Five cases of choroidal metastases from varying primaries: breast, lung, and colon were treated with intravitreal bevacizumab, and tumour response observed and documented with serial photographs and B-scans. Results Four of the five tumours were seen to progress despite intravitreal bevacizumab treatment. Conclusions Intravitreal bevacizumab as the primary treatment of choroidal metastases is not recommended and should not delay more effective alternative treatments. PMID:25771814

  5. Choroid plexus papilloma in a beluga whale (Delphinapterus leucas).

    PubMed

    Thomas, Christian; Mergl, June; Gehring, Erica; Paulus, Werner; Martineau, Daniel; Hasselblatt, Martin

    2016-07-01

    We report herein a choroid plexus papilloma in a beluga whale (Delphinapterus leucas). This case was positive for choroid plexus tumor marker Kir7.1 on immunohistochemistry. These results and the high conservation of Kir7.1 across species at the amino acid sequence level strongly suggest that antibodies directed against Kir7.1 not only can be employed for the diagnosis of choroid plexus tumors in cetaceans, but are also likely to be diagnostically useful in other animal species. PMID:27216722

  6. Bilateral anterior choroidal artery infarction presenting with progressive somnolence.

    PubMed

    van Son, Brechtje; Vandevenne, Jan; Viaene, Pieter

    2014-09-01

    A 55-year-old woman was admitted with a 3 days history of increasing lethargy with bradyphrenia and apathy. She progressively developed severe somnolence with marked abulia, right hemiparesis, right hemianopsia, and pseudobulbar palsy. Brain magnetic resonance imaging showed the rare image of bilateral acute anterior choroidal artery infarction. Pseudobulbar mutism and in rare cases abulia have been described in acute anterior choroidal artery infarction contralateral to an older lesion in mirror position. Although neurologic deterioration is not infrequent in anterior choroidal artery territory infarcts, the absence of focal neurologic signs on admission is rare and did not raise suspicion of acute stroke. PMID:25106836

  7. Can current models of accommodation and vergence predict accommodative behavior in myopic children?

    PubMed

    Sreenivasan, Vidhyapriya; Irving, Elizabeth L; Bobier, William R

    2014-08-01

    Investigations into the progression of myopia in children have long considered the role of accommodation as a cause and solution. Myopic children show high levels of accommodative adaptation, coupled with accommodative lag and high response AC/A (accommodative convergence per diopter of accommodation). This pattern differs from that predicted by current models of interaction between accommodation and vergence, where weakened reflex responses and a high AC/A would be associated with a low not high levels of accommodative adaptation. However, studies of young myopes were limited to only part of the accommodative vergence synkinesis and the reciprocal components of vergence adaptation and convergence accommodation were not studied in tandem. Accordingly, we test the hypothesis that the accommodative behavior of myopic children is not predicted by current models and whether that departure is explained by differences in the accommodative plant of the myopic child. Responses to incongruent stimuli (-2D, +2D adds, 10 prism diopter base-out prism) were investigated in 28 myopic and 25 non-myopic children aged 7-15 years. Subjects were divided into phoria groups - exo, ortho and eso based upon their near phoria. The school aged myopes showed high levels of accommodative adaptation but with reduced accommodation and high AC/A. This pattern is not explained by current adult models and could reflect a sluggish gain of the accommodative plant (ciliary muscle and lens), changes in near triad innervation or both. Further, vergence adaptation showed a predictable reciprocal relationship with the high accommodative adaptation, suggesting that departures from adult models were limited to accommodation not vergence behavior. PMID:24954685

  8. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    NASA Astrophysics Data System (ADS)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  9. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD. PMID:16787141

  10. Intravitreal bevacizumab and Ahmed glaucoma valve implantation in patients with neovascular glaucoma

    PubMed Central

    Zhang, Hai-Tao; Yang, Yu-Xin; Xu, Ying-Ying; Yang, Rui-Min; Wang, Bao-Jun; Hu, Jun-Xi

    2014-01-01

    AIM To explore the efficacy of preoperative intravitreal bevacizumab (IVB) injection combined with Ahmed glaucoma valve (AGV) implantation in the treatment of neovascular glaucoma (NVG). METHODS This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure (IOP) number of anti-glaucoma medications, visual acuity (VA), surgical success rates, and complications were recorded. RESULTS After AGV implantation, IOP was 18.2±4.0 mm Hg, 15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36mo, significantly decreased compared with pre-IOP (P<0.01). The number of anti-glaucoma medications was 0.9±0.5, 0.8±0.9 and 0.8±0.6 at 6, 12 and 36mo, significantly decreased compared to pre-treatment (P<0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%, 74.1% and 71.0% at 12, 24 and 36mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity <2/400 (P<0.05). Post-operative complications occurred in 8 eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes. CONCLUSION The procedure of preoperative IVB and AGV implantation should be one of treatments for NVG because of its safety and effectiveness. PMID:25349803

  11. [Cyclocryocoagulation in treatment of neovascular glaucoma].

    PubMed

    Kovacić, Zeljko; Ivanisević, Milan; Rogosić, Veljko; Plavec, Andrea; Karelović, Deni

    2004-01-01

    Neovascular glaucoma (NVG) is a pathological condition of the eye with fast deterioration, accompanied with eyeball pain and loosing sight. The aim of the study was to examine the efficacy of cryotherapy in the treatment of NVG which is resistant to medical and surgical therapy, concerning intraocular pressure (IOT) and eyeball pain immediately after the treatment and 6 months after. In the Department of Ophthalmology, Split University Scool of Medicine, during three years 70 patients with NVG, which were resistant to medical and surgical treatment, were included in the prospective study. There were 50 males and 21 women, average age 74 +/- 6.94 (45-87). The patients were treated with transconjuctival cyclocryocoagulation, machine ERBOKRYIO AE-ERBE was used. The average value of IOT was: at admission 44.8 mmHg, 7 days after the treatment 30.7 mmHg with the tendency of falling down 30 and 90 days later, to finally 19.9 mmHg 180 days after the treatment. The IOT was significantly lower after the treatment. At admission, the average value of eyeball pain intensity was high (4.2), 7 days after the treatment it was 2.1 with the tendency of falling down to finally 1.1 180 days after the treatment. The eyeball pain intensity was significantly lower after the treatment. Cyclocryocoagulation is a method of choice in the treatment of NVG resistant to medical and surgical treatment. Cyclocryocoagulation, as a treatment of noncontrolled progressive NVG, does not have any effect on the improvement of sight in these patient. PMID:15918320

  12. Statistical segmentation of carotid plaque neovascularization

    NASA Astrophysics Data System (ADS)

    Akkus, Zeynettin; Bosch, Johan G.; Sánchez-Ferrero, Gonzalo V.; Carvalho, Diego D. B.; Renaud, Guillaume; van den Oord, Stijn C. H.; ten Kate, Gerrit L.; Schinkel, Arend F. L.; de Jong, Nico; van der Steen, Antonius F. W.

    2013-03-01

    In several studies, intraplaque neovascularization (IPN) has been linked with plaque vulnerability. The recent development of contrast enhanced ultrasound enables IPN detection, but an accurate quantification of IPN is a big challenge due to noise, motion, subtle contrast response, blooming of contrast and artifacts. We present an algorithm that automatically estimates the location and amount of contrast within the plaque over time. Plaque pixels are initially labeled through an iterative expectation-maximization (EM) algorithm. The used algorithm avoids several drawbacks of standard EM. It is capable of selecting the best number of components in an unsupervised way, based on a minimum message length criterion. Next, neighborhood information using a 5×5 kernel and spatiotemporal behavior are combined with the known characteristics of contrast spots in order to group components, identify artifacts and finalize the classification. Image sequences are divided into 3-seconds subgroups. A pixel is relabeled as an artifact if it is labeled as contrast for more than 1.5 seconds in at least two subgroups. For 10 plaques, automated segmentation results were validated with manual segmentation of contrast in 10 frames per clip. Average Dice index and area ratio were 0.73+/-0.1 (mean+/-SD) and 98.5+/-29.6 (%) respectively. Next, 45 atherosclerotic plaques were analyzed. Time integrated IPN surface area was calculated. Average area of IPN was 3.73+/-3.51 mm2. Average area of 45 plaques was 11.6+/-8.6 mm2. This method based on EM contrast segmentation provides a new way of IPN quantification.

  13. Sector iris hemangioma in association with diffuse choroidal hemangioma.

    PubMed

    Shields, Carol L; Atalay, Hatice Tuba; Wuthisiri, Wadakarn; Levin, Alex V; Lally, Sara E; Shields, Jerry A

    2015-02-01

    Two patients referred for iris lesions were found to have sector hemangioma of the iris stroma in contiguity with diffuse choroidal hemangioma. Neither patient had other manifestations of Sturge-Weber syndrome. PMID:25727597

  14. Choroid Metastasis from Testicular Carcinoma: A Rare Entity.

    PubMed

    Singh, Dig Vijay; Gupta, Vishali; Singh, Shrawan Kumar

    2016-01-01

    The aim of this report is to contribute to the clinical understanding of choroid metastasis from testicular carcinoma. A young male patient presented with loss of vision in his left eye with ptosis and proptosis. Fundoscopy revealed bullous retinal detachment with dark hazy vitreous. The preliminary diagnosis of choroid carcinoma with vitreous involvement was made by an ophthalmologist. Later in the physical examination, there was a firm painless left testicular swelling. Testicular tumor markers were raised. Based on ultrasonography, MRI and PET-CT, a clinical diagnosis of left testicular carcinoma metastasizing to the left choroid and vitreous was made. A mixed germ cell tumor was reported on histopathological examination. After cisplatin-based chemotherapy, serum tumor markers normalized and vision improved. Exceptional choroidal and vitreous metastases with absence of other visceral and bony involvement constituted the presenting sign. Although rare, testicular carcinoma must be considered to metastasize to the eye, especially if loss of vision is the chief complaint. PMID:23969474

  15. A mixed choroid plexus papilloma and ependymoma.

    PubMed

    Lee, Yujin; Kim, Seong Ik; Kim, Seung-Ki; Kim, In One; Park, Sung-Hye

    2016-04-01

    We report a novel case of a mixed choroid plexus papilloma (CPP) and ependymoma with cartilaginous differentiation. This kind of mixed tumor has not been previously reported in the English literature. The patient was a 5-year-old girl, who presented with a 1-week history of fever and numbness of the right lower limb. Magnetic resonance imaging of the brain with gadolinium revealed a heterogeneously enhancing mass in the occipital horn of the left lateral ventricle. Histologically, the tumor showed an intermixed CPP area and a low-grade papillary ependymoma-like area, which was studded with cartilage islands and psammoma bodies. In many foci, direct transition of CPP and ependymoma was observed, but there were no high-grade features. We report this novel case, describe the unique microscopic and immunohistochemical features, and speculate on the pathogenesis. PMID:26670168

  16. Treatment of choroid hemangioma with argon laser

    NASA Astrophysics Data System (ADS)

    Yang, Chuanzhu; Song, Man

    1993-03-01

    The treatment effects of 7 cases of choroid hemangioma are reported. Of them, 4 cases were men and 3 cases were women. Ages varied from 34 to 52 years. The mean age was 43 years. All of their eyesight was between 0.01 and 0.4. Six of the seven cases were solitary hemangioma, the other one was Sturge-Weber syndrome. After treatment photography, the color of the hemangioma body gradually got weak and the local presented pigmentation. The results of the fluorescein fundus angiography indicated that the hemangioma body reduced, then got atrophy and fibrosis. In five cases eyesight increased, and it didn't in the other two cases.

  17. Ischemic retinopathy and neovascular proliferation secondary to severe head injury.

    PubMed

    Coban-Karatas, Muge; Altan-Yaycioglu, Rana

    2014-01-01

    We report a case with severe head trauma and perforating globe injury in one eye and ischemic retinopathy and neovascular proliferation in the other eye. A 37-year-old male was brought to the emergency department after a motor vehicle accident with severe maxillofacial trauma. Ophthalmic examination revealed hematoma of the left eyelids as well as traumatic rupture and disorganization of the left globe. On the right eye, anterior segment and fundoscopic examination were normal. Primary globe repair was performed. At postoperative one-month visit, the right eye revealed no pathology of the optic disc and macula but severe neovascularization in the temporal peripheral retina. The patient was diagnosed as ischemic retinopathy and neovascular proliferation due to head trauma. PMID:25143848

  18. Uncommon presentation of choroid plexus papilloma in an infant

    PubMed Central

    Pandey, Sharad; Sharma, Vivek; Singh, Kulwant; Ghosh, Amrita; Gupta, Praveen Kumar

    2016-01-01

    Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension. PMID:27195037

  19. Retino-choroidal ischemia in central retinal vein occlusion

    PubMed Central

    Hussain, Nazimul; Hussain, Anjli

    2014-01-01

    A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia. PMID:25473353

  20. Complement Factor H Expressed by Retinal Pigment Epithelium Cells Can Suppress Neovascularization of Human Umbilical Vein Endothelial Cells: An in vitro Study.

    PubMed

    Zhang, Yi; Huang, Qing; Tang, Min; Zhang, Junjun; Fan, Wei

    2015-01-01

    Complement factor H (CFH) is one of the most important soluble complement regulatory proteins and is closely associated with age-related macular degeneration (AMD), the leading cause of irreversible central vision loss in the elderly population in developed countries. Our study searches to investigate whether CFH expression is changed in oxidative damaged retinal pigment epithelium (RPE) cells and the role of CFH in the in vitro neovascularization. First, it was confirmed by immunofluorescence staining that CFH was expressed by ARPE-19 cells. CFH mRNA and protein in oxidative (H2O2) damaged ARPE-19 cells were both reduced, as determined by Real-time PCR and Western blotting analysis. Enzyme-linked immunosorbent assay (ELISA) also showed that ARPE-19 cells treated with H2O2 caused an increase in C3a content, which indicates complement activation. Then, wound assays were performed to show that CFH expression suppression promoted human umbilical vein endothelial cell (HUVECs) migration. Thereafter, ARPE-19 cells were transfected with CFH-specific siRNA and CFH knockdown was confirmed with the aid of Real-time PCR, immunofluorescence staining and Western blotting. The ELISA results showed that specific CFH knockdown in ARPE-19 cells activated the complement system. Finally, in vitro matrigel tube formation assay was performed to determine whether change of CFH expression in RPE would affect tube formation by HUVECs. More tubes were formed by HUVECs co-cultured with ARPE-19 cells transfected with CFH specific-siRNA when compared with controls. Our results suggested that RPE cells might be the local CFH source, and RPE cell injuries (such as oxidative stress) may cause CFH expression suppression, which in turn may lead to complement activation and promotion of tube formation by HUVECs. This finding is of importance in elucidating the role of complement in the pathogenesis of ocular neovascularization including choroidal neovascularization. PMID:26091360

  1. Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

    PubMed Central

    Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

    2014-01-01

    Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

  2. CHOROIDAL MORPHOLOGY IN A PATIENT WITH HELLP SYNDROME

    PubMed Central

    Kasai, Ayaka; Sugano, Yukinori; Maruko, Ichiro

    2016-01-01

    Purpose: We report here, the morphological characteristics of the retina and choroid in a patient with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, who was not aware of her pregnancy before visiting our hospital. Methods: Case report. Results: The patient complained of visual disturbances in both eyes for a few days. Extensive serous retinal detachment and hyperreflective foci were observed in both eyes on spectral domain optical coherence tomography (SDOCT). Enhanced depth imaging technique using SDOCT revealed choroidal thickening and unclear choroidal vessel contour. Her blood pressure was 230/168 mmHg. Laboratory data showed hemolysis and liver dysfunction. Obstetrical examination disclosed her pregnancy. She was diagnosed as having HELLP syndrome. Because her general condition improved after prompt Cesarean delivery, the fundus lesions were rapidly resolved with choroidal thinning. Conclusion: The eyes in a patient with HELLP syndrome showed characteristic choroidal morphology. The choroidal morphology shown with SDOCT might be one of the pathognomonic signs for a diagnosis of HELLP syndrome. PMID:26595148

  3. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Costagliola, Ciro; Semeraro, Francesco; Romano, Mario R; Rinaldi, Michele; Gallenga, Carla Enrica; Serino, Maria Luisa; Incorvaia, Carlo; D’Angelo, Sergio; De Nadai, Katia; Dell’Omo, Roberto; Russo, Andrea; Gemmati, Donato; Perri, Paolo

    2015-01-01

    Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti

  4. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.

    PubMed

    Parmeggiani, Francesco; Costagliola, Ciro; Semeraro, Francesco; Romano, Mario R; Rinaldi, Michele; Gallenga, Carla Enrica; Serino, Maria Luisa; Incorvaia, Carlo; D'Angelo, Sergio; De Nadai, Katia; Dell'Omo, Roberto; Russo, Andrea; Gemmati, Donato; Perri, Paolo

    2015-01-01

    Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti

  5. A protocol for a lung neovascularization model in rodents

    PubMed Central

    Jones, Rosemary C; Capen, Diane E; Petersen, Bodil; Jain, Rakesh K; Duda, Dan G

    2009-01-01

    By providing insight into the cellular events of vascular injury and repair, experimental model systems seek to promote timely therapeutic strategies for human disease. The goal of many current studies of neovascularization is to identify cells critical to the process and their role in vascular channel assembly. We propose here a protocol to analyze, in an in vivo rodent model, vessel and capillary remodeling (reorganization and growth) in the injured lung. Sequential analyses of stages in the assembly of vascular structures, and of relevant cell types, provide further opportunities to study the molecular and cellular determinants of lung neovascularization. PMID:18323809

  6. Clinical correlates of common corneal neovascular diseases: a literature review

    PubMed Central

    Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal

    2015-01-01

    A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930

  7. Outcomes of Proton Radiation Therapy for Peripapillary Choroidal Melanoma at the BC Cancer Agency

    SciTech Connect

    Tran, Eric; Ma, Roy; Paton, Katherine; Blackmore, Ewart; Pickles, Tom

    2012-08-01

    Purpose: To report toxicity, local control, enucleation, and survival rates for patients with peripapillary choroidal melanoma treated with proton therapy in Canada. Methods and Materials: We performed a retrospective analysis of patients with peripapillary choroidal melanoma ({<=}2 mm from optic disc) treated between 1995 and 2007 at the only Canadian proton therapy facility. A prospective database was updated for follow-up information from a chart review. Descriptive and actuarial data are presented. Results: In total, 59 patients were treated. The median age was 59 years. According to the 2010 American Joint Committee on Cancer TNM classification, there were 20 T1 tumors (34%), 28 T2 tumors (48%), and 11 T3 tumors (19%). The median tumor diameter was 11.4 mm, and the median thickness was 3.5 mm. Median follow-up was 63 months. Nineteen patients received 54 cobalt gray equivalents (CGE) and forty patients received 60 CGE, each in 4 fractions. The 5-year actuarial local control rate was 91% (T1, 100%; T2, 93%; and T3, 59%) (p = 0.038). There was a suggestive relationship between local control and dose. The local control rate was 97% with 60 CGE and 83% with 54 CGE (p = 0.106). The metastasis-free survival rate was 82% and related to T stage (T1, 94%; T2, 84%; and T3, 47%) (p < 0.001). Twelve patients died, including eleven with metastases. The 5-year actuarial rate of neovascular glaucoma was 31% (23% for T1-T2 and 68% for T3, p < 0.001), and that of enucleation was 0% for T1, 14% for T2, and 72% for T3 (p < 0.001). Radiation retinopathy (74%) and optic neuropathy (64%) were common within-field effects. Conclusions: Proton therapy provides excellent local control with acceptable toxicity while conserving the globe in 80% of cases. These results are consistent with other single-institution series using proton radiotherapy, and toxicity rates were acceptable. T3 tumors carry a higher rate of both local recurrence and metastasis.

  8. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    SciTech Connect

    Krema, Hatem

    2013-07-01

    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  9. Influence of progressive addition lenses on reading posture in myopic children

    PubMed Central

    Bao, Jinhua; Wang, Yuwen; Zhuo, Zuopao; Yang, Xianling; Tan, Renjing; Drobe, Björn; Chen, Hao

    2016-01-01

    Aims To determine the influence of single-vision lenses (SVLs) and progressive addition lenses (PALs) on the near vision posture of myopic children based on their near phoria. Methods Sixty-two myopic children were assigned to wear SVLs followed by PALs. Eighteen children were esophoric (greater than +1), 18 were orthophoric (−1 to 1) and 26 were exophoric (less than −1) at near. Reading distance, head tilt and ocular gaze angles were measured using an electromagnetic system after adaptation to each lens type. Results The lens type did not influence reading distance or head tilt angle (p>0.05 for both), but ocular gaze angle decreased significantly with the PALs (F=9.25, p=0.004). With the PALs, exophoric children exhibited significantly increased head tilt angle (p=0.003) and reduced ocular gaze angle (p=0.004) compared with esophoric children. Near non-exophoric children exhibited similar eye and head postures when wearing SVLs and PALs, whereas exophoric children exhibited reduced ocular gaze angle (t=−3.18, p=0.04) with PALs compared with SVLs. Using PALs for reading, the mean addition power employed by esophoric children was significantly greater than exophoric children (p=0.04). Conclusions The lens type and the near phoria state affected near vision posture. During reading, myopic esophoric children used a lower portion of their PALs compared with exophoric children, resulting in greater addition power. These results may partially explain why myopic children with near esophoria exhibited superior treatment effects in myopia control trials using PALs. PMID:26608026

  10. Myopic aberrations: Simulation based comparison of curvature and Hartmann Shack wavefront sensors

    NASA Astrophysics Data System (ADS)

    Basavaraju, Roopashree M.; Akondi, Vyas; Weddell, Stephen J.; Budihal, Raghavendra Prasad

    2014-02-01

    In comparison with a Hartmann Shack wavefront sensor, the curvature wavefront sensor is known for its higher sensitivity and greater dynamic range. The aim of this study is to numerically investigate the merits of using a curvature wavefront sensor, in comparison with a Hartmann Shack (HS) wavefront sensor, to analyze aberrations of the myopic eye. Aberrations were statistically generated using Zernike coefficient data of 41 myopic subjects obtained from the literature. The curvature sensor is relatively simple to implement, and the processing of extra- and intra-focal images was linearly resolved using the Radon transform to provide Zernike modes corresponding to statistically generated aberrations. Simulations of the HS wavefront sensor involve the evaluation of the focal spot pattern from simulated aberrations. Optical wavefronts were reconstructed using the slope geometry of Southwell. Monte Carlo simulation was used to find critical parameters for accurate wavefront sensing and to investigate the performance of HS and curvature sensors. The performance of the HS sensor is highly dependent on the number of subapertures and the curvature sensor is largely dependent on the number of Zernike modes used to represent the aberration and the effective propagation distance. It is shown that in order to achieve high wavefront sensing accuracy while measuring aberrations of the myopic eye, a simpler and cost effective curvature wavefront sensor is a reliable alternative to a high resolution HS wavefront sensor with a large number of subapertures.

  11. The effect of preoperative keratometry on visual outcomes after moderate myopic LASIK

    PubMed Central

    Christiansen, Steven M; Neuffer, Marcus C; Sikder, Shameema; Semnani, Rodmehr T; Moshirfar, Majid

    2012-01-01

    Purpose To evaluate visual outcomes in moderately myopic eyes with flat and steep corneas (preoperatively) that have been treated with laser-assisted in situ keratomileusis (LASIK). Patients and methods Records of ninety-six eyes with average preoperative keratometry (K) values between 39.9 and 42.0 diopters (D) (flat) were matched with 103 eyes with preoperative K values between 46.0 and 47.2 D (steep) that underwent LASIK between March 2007 and March 2010 for moderate myopia, and were retrospectively reviewed. The primary outcome measures used to determine the effect of preoperative keratometry on visual prognosis were refraction, visual acuity, change in keratometry (ΔK), and change in spherical equivalent (ΔSE), measured at 1, 3, 6, and 12 months postoperatively. Results Significant differences were found at 6 months postoperatively between the flat group and steep group in SE (P = 0.029), sphere (P = 0.018), ΔK (P = 0.002), percentage of eyes achieving SE of −0.25 to + 0.25 D (P = 0.0125), −0.26 to −0.50 D (P = 0.003), −0.51 to −1.00 D (P = 0.044), and the percentage of eyes achieving uncorrected distance visual acuity of 20/15 or better (P = 0.0006). Conclusion Moderately myopic eyes with flatter corneas preoperatively have better visual prognosis following LASIK compared with moderately myopic eyes with steeper corneas. PMID:22536037

  12. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings.

    PubMed

    Sun, Chuan-Bin; You, Yong-Sheng; Liu, Zhe; Zheng, Lin-Yan; Chen, Pei-Qing; Yao, Ke; Xue, An-Quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was -17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  13. Macular Thickness Assessed with Optical Coherence Tomography in Young Chinese Myopic Patients

    PubMed Central

    Zhao, Minghui; Wu, Qiang; Hu, Ping; Jia, Lili

    2015-01-01

    Purpose. To evaluate the variations in macular thickness in young Chinese myopic persons and the association with axial length (AL), spherical equivalence refraction (SE), age, intraocular pressure, and sex. Methods. In total, 133 young Chinese myopic subjects between 18 and 30 years of age were selected. The macular thickness was assessed using third-generation optical coherence tomography. AL, intraocular pressure, and SE were also measured. Results. The mean central foveal thickness was 191.1 ± 15.3 µm. The macula was consistently thinner in women than in men. Central foveal thickness had a significant positive correlation with AL and a negative correlation with SE. In the inner and outer regions, the macular thickness had a positive correlation with SE and negative correlation with AL. Conclusions. The retina was thinner in women than in men. Associated with myopic progression and AL extension, the central foveal thickness increased, while the retinal thickness of the inner and outer regions decreased. PMID:26609427

  14. Anterior and Posterior Corneal Astigmatism after Refractive Lenticule Extraction for Myopic Astigmatism

    PubMed Central

    Yamagishi, Mayumi; Igarashi, Akihito

    2015-01-01

    Purpose. To assess the amount and the axis orientation of anterior and posterior corneal astigmatism after refractive lenticule extraction (ReLEx) for myopic astigmatism. Methods. We retrospectively examined 53 eyes of 53 consecutive patients (mean age ± standard deviation, 33.2 ± 6.5 years) undergoing ReLEx to correct myopic astigmatism (manifest cylinder = 0.5 diopters (D)). Power vector analysis was performed with anterior and posterior corneal astigmatism measured with a rotating Scheimpflug system (Pentacam HR, Oculus) and refractive astigmatism preoperatively and 3 months postoperatively. Results. Anterior corneal astigmatism was significantly decreased, measuring 1.42 ± 0.73 diopters (D) preoperatively and 1.11 ± 0.53 D postoperatively (p < 0.001, Wilcoxon signed-rank test). Posterior corneal astigmatism showed no significant change, falling from 0.44 ± 0.12 D preoperatively to 0.42 ± 0.13 D postoperatively (p = 0.18). Refractive astigmatism decreased significantly, from 0.92 ± 0.51 D preoperatively to 0.27 ± 0.44 D postoperatively (p < 0.001). The anterior surface showed with-the-rule astigmatism in 51 eyes (96%) preoperatively and 48 eyes (91%) postoperatively. By contrast, the posterior surface showed against-the-rule astigmatism in all eyes preoperatively and postoperatively. Conclusions. The surgical effects were largely attributed to the astigmatic correction of the anterior corneal surface. Posterior corneal astigmatism remained unchanged even after ReLEx for myopic astigmatism. PMID:26097749

  15. Retinal measurements using time domain optical coherence tomography imaging before and after myopic Lasik

    PubMed Central

    Lei, Feng; Burns, Stephen A.; shao, Liqin; Yang, Yabo

    2014-01-01

    Purpose To compare retinal measurements obtained by time domain optical coherence tomography (OCT) devices before and after myopic laser in situ keratomileusis (Lasik) and to assess the interaction of Lasik and retinal structures as measured by time domain OCT. Methods 53 patients randomly selected participated in the study. Only the right eye of each subject was included in the study. Comprehensive ophthalmic examinations including refraction examination, slitlamp examination, dilated fundus examination, corneal topography, corneal thickness, intraocular pressure, and retinal Stratus OCT scans were acquired for each patient before myopic Lasik and 3 months after surgery. Results Total macular volume (TMV) changed significantly between preoperative and postoperative measurements (p=0.003). No statistical differences were found between preoperative and postoperative disc area, rim area, cup/disk vert. ratio, or average foveal thickness (p>0.05). The variation in TMV correlated significantly with the change in spherical refraction equivalent, maximal corneal curvature, minimal corneal curvature, and corneal ablation depth. Conclusion Most retinal OCT measurements undergo no obvious changes after myopic Lasik. The increased TMV measurements we measured after Lasik seem to be correlated with the alteration in corneal shape. The exact mechanism for this change is not clear, while we examined several possibilities including subclinical macular edema, magnification changes, errors in OCT analysis and IOP, none of these seem to be a likely cause. PMID:22512373

  16. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings

    PubMed Central

    Sun, Chuan-bin; You, Yong-sheng; Liu, Zhe; Zheng, Lin-yan; Chen, Pei-qing; Yao, Ke; Xue, An-quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was −17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  17. Radiation therapy for neovascular age-related macular degeneration

    PubMed Central

    Petrarca, Robert; Jackson, Timothy L

    2011-01-01

    Antivascular endothelial growth factor (anti-VEGF) therapies represent the standard of care for most patients presenting with neovascular (wet) age-related macular degeneration (neovascular AMD). Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET). Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002), with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections. PMID:21311657

  18. Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT.

    PubMed

    Torun, Nese; Reyhan, Mehmet; Yapar, Ali Fuat; Karatas, Muge

    2016-05-01

    We report a 68-year-old woman with papillary thyroid carcinoma metastasizing to choroid. The choroid metastasis was diagnosed with SPECT-CT and then was treated with high-dose radioactive iodine therapy. PMID:26825205

  19. Inhibition of Elastin Peptide-Mediated Angiogenic Signaling Mechanism(s) in Choroidal Endothelial Cells by the α6(IV)NC1 Collagen Fragment

    PubMed Central

    Gunda, Venugopal; Verma, Raj Kumar; Sudhakar, Yakkanti Akul

    2013-01-01

    Purpose. The inhibitory effects and mechanism(s) of type IV collagen α-6 chain–derived noncollagenous domain (α6[IV]NC1 or hexastatin) on elastin-derived peptide (EDP)–activated choroidal endothelial cell migration, kinase signaling, and membrane type 1 metalloproteinase (MT1-MMP) activation are explored. Methods. Mouse choroidal endothelial cells (MCECs) were incubated in media with soluble EDPs (kappa elastin, mouse elastin, and Val-Gly-Val-Ala-Pro-Gly [VGVAPG] hexapeptide) for different time intervals with or without α6(IV)NC1. The MCECs proliferation, migration, tube formation, MT1-MMP expression, and angiogenic signaling were analyzed in cells subjected to EDP and α6(IV)NC1 treatments. The MCECs also were subjected to EDPs, and specific inhibitors for evaluation of focal adhesion kinase (FAK) and protein kinase B (Akt) phosphorylation. Results. Kappa elastin, mouse elastin, and VGVAPG enhanced the migration, without affecting the proliferation of MCECs. The α6(IV)NC1 inhibited survival and EDP-activated migration of MCECs. The EDP-activated MCEC tube formation on matrigel also was inhibited by α6(IV)NC1. Further, EDP-activated MT1-MMP expression and FAK/phosphoinositide-3-kinase (PI-3K)/mammalian target of rapamycin (mToR)/Akt phosphorylation in MCECs, were reduced by α6(IV)NC1. The EDP-induced FAK and Akt phosphorylation was blocked by FAK- and Akt-specific inhibitors. Conclusions. The EDPs and α6(IV)NC1 are identified to exhibit opposing effects on MCEC angiogenic behavior and signaling. The α6(IV)NC1 inhibited cell survival, EDP-mediated migration, MT1-MMP expression and, FAK/PI-3K/mToR/Akt phosphorylation in MCECs. This work demonstrates α6(IV)NC1 as a prospective endogenous molecule for the treatment of diseases involving choroidal neovascularization in the eye. PMID:24194191

  20. Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.

    PubMed

    Wang, Haibo; Fotheringham, Lori; Wittchen, Erika S; Hartnett, M Elizabeth

    2015-12-01

    Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α-induced ROS generation. Apocynin reduced TNF-α-induced NF-κB and Rac1 activation, and inhibited TNF-α-induced CEC migration. TNF-α-induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α-induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2'-O-Me-cAMP prevented TNF-α-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α-induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process. PMID:26476350

  1. A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors

    SciTech Connect

    Daftari, I. K.; Petti, P. L.; Larson, D. A.; O'Brien, J. M.; Phillips, T. L.

    2009-03-15

    A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

  2. Gamma Knife Radiosurgery for Choroidal Hemangioma

    SciTech Connect

    Kim, Yun Taek; Kang, Se Woong; Lee, Jung-Il

    2011-12-01

    Purpose: Patients with choroidal hemangioma (CH), a benign ocular hamartoma, frequently presents with visual disturbance as a result of exudative retinal detachment (RD), which originates in subretinal fluid accumulation. We report our experience using the Leksell Gamma Knife in the management of symptomatic CH. Methods and Materials: Seven patients with symptomatic CH (circumscribed form in 3 patients and diffuse form in 4) were treated with the Leksell Gamma Knife at our institution during a 7-year period. All patients presented with exudative RD involving the macula that resulted in severe visual deterioration. The prescription dose to the target margin was 10 Gy in all cases. The mean tumor volume receiving the prescription dose was 536 mm{sup 3} (range, 151-1,057). The clinical data were analyzed in a retrospective fashion after a mean follow-up of 34.4 months (range, 9-76). Results: The resolution of exudative RD was achieved within 6 months, and the visual acuity of the affected eye had improved at the latest follow-up examination (p = .018) in all patients. No recurrence of exudative RD occurred. Thinning of the CHs was observed in most patients; however, symptomatic radiation toxicity had not developed in any of the patients. Conclusion: Symptomatic CHs can be safely and effectively managed with Gamma Knife radiosurgery using a marginal dose of 10 Gy.

  3. Peripapillary choroidal thickness in healthy Turkish subjects

    PubMed Central

    Erbagci, Hulya; Oren, Burak; Okumus, Seydi; Kenan, Serhat; Celemler, Pelin; Erbagci, Ibrahim

    2015-01-01

    Aim The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT), measured by enhanced depth imaging optical coherence tomography (EDI-OCT), in healthy Turkish volunteers. Materials and methods In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. Results The mean age of the 25 female and 32 male patients in the study was 30.9±10.6 years (range, 18–56 years). The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225±57, 183±47, 220±57, and 233±59 μm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all), whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. Conclusion The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. PMID:26257510

  4. Evidence of a novel gene HERPUD1 in polypoidal choroidal vasculopathy

    PubMed Central

    Jin, Enzhong; Bai, Yujing; Huang, Lvzhen; Zhao, Min; Zhang, Chunfang; Zhao, Mingwei; Li, Xiaoxin

    2015-01-01

    Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age-related macular degeneration (nAMD) which is the leading cause of irreversible blindness in the elderly. Our studies focused on the genetic background and function of a novel gene HERPUD1 in PCV. HERPUD1 has been reported to increase the level of amyloid β (Aβ), which is a component of drusen deposits underlying the retinal pigment epithelium (RPE) layer. To verify the genetic functional associations of HERPUD1 with PCV, exome sequencing of HERPUD1 was performed in unrelated Chinese individuals, including nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for HERPUD1 were performed in the subretinal membranes of PCV patients. The relationship between HERPUD1 and amyloid beta precursor was determined using real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns of angiogenesis cytokines and chemokines in both Aβ-treated RPE cells and in Brown Norway rats that received Aβ subretinal injections were determined. We showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma Aβ42 protein was significantly higher in PCV patients compared to nAMD and control subjects. Aβ could upregulate angiogenic factors, chemokines and matrix metalloproteinases both in RPE cells and in a rat model of subretinal Aβ injection. The imbalance of the cytokines may be one of the mechanisms for the formation and development of PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV patients. PMID:26823705

  5. Evidence of a novel gene HERPUD1 in polypoidal choroidal vasculopathy.

    PubMed

    Jin, Enzhong; Bai, Yujing; Huang, Lvzhen; Zhao, Min; Zhang, Chunfang; Zhao, Mingwei; Li, Xiaoxin

    2015-01-01

    Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age-related macular degeneration (nAMD) which is the leading cause of irreversible blindness in the elderly. Our studies focused on the genetic background and function of a novel gene HERPUD1 in PCV. HERPUD1 has been reported to increase the level of amyloid β (Aβ), which is a component of drusen deposits underlying the retinal pigment epithelium (RPE) layer. To verify the genetic functional associations of HERPUD1 with PCV, exome sequencing of HERPUD1 was performed in unrelated Chinese individuals, including nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for HERPUD1 were performed in the subretinal membranes of PCV patients. The relationship between HERPUD1 and amyloid beta precursor was determined using real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns of angiogenesis cytokines and chemokines in both Aβ-treated RPE cells and in Brown Norway rats that received Aβ subretinal injections were determined. We showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma Aβ42 protein was significantly higher in PCV patients compared to nAMD and control subjects. Aβ could upregulate angiogenic factors, chemokines and matrix metalloproteinases both in RPE cells and in a rat model of subretinal Aβ injection. The imbalance of the cytokines may be one of the mechanisms for the formation and development of PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV patients. PMID:26823705

  6. Choroidal thickness changes in patients with pseudoexfoliation syndrome.

    PubMed

    Zengin, Mehmet Ozgur; Cinar, Esat; Karahan, Eyyup; Tuncer, Ibrahim; Yilmaz, Sami; Kocaturk, Tolga; Kucukerdonmez, Cem

    2015-08-01

    To evaluate the choroidal thickness using spectral-domain optical coherence tomography (OCT) in patients with pseudoexfoliation syndrome (PXS) and to compare them with healthy controls. This observational comparative study consisted of 35 PXS patients and 35 age- and sex-matched control cases. The control cases had neither systemic nor ocular disease. All 70 patients underwent a complete ophthalmic examination as well as choroidal thickness measurement using a high speed and high resolution SD-OCT device (Topcon 3D OCT-2000, Japan). There was no significant difference with respect to mean refractive error and intraocular pressure measurement between patients with PXS and controls (p = 0.237 and 0.433, respectively). The mean choroidal thickness was found as 206.6 ± 37.6 µm in the PXS group and 215.9 ± 47.3 µm in controls, respectively. The mean choroidal thickness was not significant between the PXS patients and the control cases (p = 0.362). Although PXS patients had lower mean choroidal thickness than controls, our results did not reach any statistical significance. PMID:25059402

  7. Evaluation of Retinal and Choroidal Thickness in Fuchs' Uveitis Syndrome

    PubMed Central

    Ozsutcu, Mustafa

    2016-01-01

    Purpose. We aimed to investigate retinal and choroidal thickness in the eyes of patients with Fuchs' uveitis syndrome (FUS). Methods. Fifteen patients with unilateral FUS and 20 healthy control subjects were enrolled. Spectral domain optical coherence tomography (Spectralis HRA+OCT, 870 nm; Heidelberg Engineering, Heidelberg, Germany) was used to obtain retinal and choroidal thickness measurements. The retinal nerve fiber layer (RNFL) thickness, macular thickness, and choroidal thickness of the eyes with FUS were compared with the unaffected eye and the eyes of healthy control subjects. Results. The mean choroidal thickness at fovea and at each point within the horizontal nasal and temporal quadrants at 500 μm intervals to a distance of 1500 µm from the foveal center was significantly thinner in the affected eye of FUS patients compared with the unaffected eye of FUS patients or the eyes of healthy control subjects. However, there were no significant differences in RNFL or macular thickness between groups. Conclusions. Affected eyes in patients with FUS tend to have thinner choroids as compared to eyes of unaffected fellow eyes and healthy individuals, which might be a result of the chronic inflammation associated with the disease. PMID:27579176

  8. [Effects of brovincamine fumarate on choroidal blood volume in rabbits].

    PubMed

    Tawara, A; Tanaka, T; Tsujioka, K; Sudo, Y; Ohnishi, Y

    1998-10-01

    We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits. PMID:9834607

  9. Bone Remodeling in Choroidal Osteoma Monitored by Fundus Photography and Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Kamalden, Tengku Ain; Lingam, Gopal; Sundar, Gangadhara

    2014-01-01

    Choroidal osteoma is a benign ossifying tumor of the choroid, consisting of mature bone tissue. It has been described to enlarge and evolve at varying rates over time. Here, we report and quantify the progression of a unilateral choroidal osteoma in a 7-year-old boy by fundus photography, and document tumor remodeling by spectral domain optical coherence tomography images. PMID:27175357

  10. Optical Coherence Tomography of Retinal and Choroidal Tumors

    PubMed Central

    Say, Emil Anthony T.; Shah, Sanket U.; Ferenczy, Sandor; Shields, Carol L.

    2011-01-01

    Optical coherence tomography (OCT) has revolutionized the field of ophthalmology since its introduction 20 years ago. Originally intended primarily for retina specialists to image the macula, it has found its role in other subspecialties that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT provides axial resolution to approximately 7 microns with cross-sectional images of the retina, delivering valuable information on the effects of intraocular tumors on the retinal architecture. Some effects include retinal edema, subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning, and retinal pigment epithelial detachment. With more advanced technology, OCT now provides imaging deeper into the choroid using a technique called enhanced depth imaging. This allows characterization of the thickness and reflective quality of small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma. Future improvements in image resolution and depth will allow better understanding of the mechanisms of visual loss, tumor growth, and tumor management. PMID:21811667

  11. Optical Coherence Tomography of Retinal and Choroidal Tumors

    PubMed Central

    Say, Emil Anthony T.; Shah, Sanket U.; Ferenczy, Sandor; Shields, Carol L.

    2012-01-01

    Optical coherence tomography (OCT) has revolutionized the field of ophthalmology since its introduction 20 years ago. Originally intended primarily for retina specialists to image the macula, it has found its role in other subspecialties that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT provides axial resolution to approximately 7 microns with cross-sectional images of the retina, delivering valuable information on the effects of intraocular tumors on the retinal architecture. Some effects include retinal edema, subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning, and retinal pigment epithelial detachment. With more advanced technology, OCT now provides imaging deeper into the choroid using a technique called enhanced depth imaging. This allows characterization of the thickness and reflective quality of small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma. Future improvements in image resolution and depth will allow better understanding of the mechanisms of visual loss, tumor growth, and tumor management. PMID:23008756

  12. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Zhang, Yan; Wildsoet, Christine F.

    2016-01-01

    Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia. PMID:26310157

  13. Regulation of neural stem cells by choroid plexus cells population.

    PubMed

    Roballo, Kelly C S; Gonçalves, Natalia J N; Pieri, Naira C G; Souza, Aline F; Andrade, André F C; Ambrósio, Carlos E

    2016-07-28

    The choroid plexus is a tissue on the central nervous system responsible for producing cerebrospinal fluid, maintaining homeostasis and neural stem cells support; though, all of its functions still unclear. This study aimed to demonstrate the niches of choroid plexus cells for a better understanding of the cell types and functions, using the porcine as the animal model. The collected material was analyzed by histology, immunohistochemistry, and cell culture. The cell culture was characterizated by immunocytochemistry and flow cytometry. Our results showed OCT-4, TUBIII, Nestin, CD45, CD73, CD90 positive expression and GFAP, CD105 negative expression, also methylene blue histological staining confirmed the presence of telocytes cells. We realized that the choroid plexus is a unique and incomparable tissue with different niches of cells as pluripotent, hematopoietic, neuronal progenitors and telocyte cells, which provide its complexity, differentiated functionality and responsibility on brain balance and neural stem cells regulation. PMID:27181512

  14. Massive choroidal hemorrhage associated with low molecular weight heparin therapy.

    PubMed

    Neudorfer, M; Leibovitch, I; Goldstein, M; Loewenstein, A

    2002-04-01

    An 84-year-old woman with unstable angina pectoris was treated with subcutaneous enoxaparine (Clexane) for several days before presenting with severe pain and decreased vision in her left eye. The intraocular pressure was 70 mmHg, and fundus examination showed a pigmented choroidal lesion and associated choroidal and retinal detachment. Ultrasonography was consistent with choroidal hemorrhage, and she was diagnosed as having acute glaucoma secondary to massive subchoroidal hemorrhage. Medical control of the intraocular pressure resulted in a significant clinical improvement. Intraocular hemorrhage and angle-closure glaucoma are rare and previously unreported complications in patients treated with low molecular weight heparin. It is important to be aware of this ocular complication as these drugs are so often used. PMID:11943940

  15. Laser-induced macular holes demonstrate impaired choroidal perfusion

    NASA Astrophysics Data System (ADS)

    Brown, Jeremiah, Jr.; Allen, Ronald D.; Zwick, Harry; Schuschereba, Steven T.; Lund, David J.; Stuck, Bruce E.

    2003-06-01

    Choroidal perfusion was evaluated following the creation of a laser induced macular hole in a nonhuman primate model. Two Rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green (ICG) angiography . Each lesion produced vitreous hemorrhage and progressed to a full thickness macular hole. ICG angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. Nd:YAG, laser-induced macular holes result in long term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris.

  16. Chorioretinal temperature monitoring during transpupillary thermotherapy for choroidal neovascularisation

    PubMed Central

    Miura, S; Nishiwaki, H; Ieki, Y; Hirata, Y; Honda, Y; Sugino, Y; Okazaki, Y

    2005-01-01

    Aims: To investigate the difference in temperature rise between normal choroid and choroidal revascularisation (CNV) during transpupillary thermotherapy (TTT) and the relation between laser spot size and power in the rat fundus. Methods: A modified slit lamp, which was installed with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Temperature rise during TTT was monitored by observing fluorescence released from thermosensitive liposomes encapsulating carboxyfluorescein. Two types of liposomes were prepared; their phase transition temperatures were 40°C and 46°C, respectively. Laser power settings required to observe fluorescence released from 46°C liposome in normal choroid or CNV were compared. Next, the power settings with 0.5 mm and 0.25 mm spot sizes were compared following administration of 40°C liposome or 46°C liposome. Results: The minimum power values when release from 46°C liposome was observed showed a significant difference in distribution of power values between normal choroid and CNV. CNV required significantly higher power than normal choroid. With 40°C liposome, the power was 9.7 (1.9) mW (mean (SD)) at a spot size of 0.25 mm, and 12.1 (1.6) mW at 0.5 mm, respectively. When using 46°C liposome, the power setting was 10.2 (1.2) mW at a spot size of 0.25 mm, and 14.6 (2.2) mW at 0.5 mm, respectively. Conclusions: CNV demonstrated varying heat conduction, compared with normal choroid. Laser power required to raise the temperature should not necessarily be doubled, even when the spot size is doubled. Close attention should be given to the selection of power settings when performing TTT for CNV. PMID:15774927

  17. Development of the choroid plexus and blood-CSF barrier

    PubMed Central

    Liddelow, Shane A.

    2015-01-01

    Well-known as one of the main sources of cerebrospinal fluid (CSF), the choroid plexuses have been, and still remain, a relatively understudied tissue in neuroscience. The choroid plexus and CSF (along with the blood-brain barrier proper) are recognized to provide a robust protective effort for the brain: a physical barrier to impede entrance of toxic metabolites to the brain; a “biochemical” barrier that facilitates removal of moieties that circumvent this physical barrier; and buoyant physical protection by CSF itself. In addition, the choroid plexus-CSF system has been shown to be integral for normal brain development, central nervous system (CNS) homeostasis, and repair after disease and trauma. It has been suggested to provide a stem-cell like repository for neuronal and astrocyte glial cell progenitors. By far, the most widely recognized choroid plexus role is as the site of the blood-CSF barrier, controller of the internal CNS microenvironment. Mechanisms involved combine structural diffusion restraint from tight junctions between plexus epithelial cells (physical barrier) and specific exchange mechanisms across the interface (enzymatic barrier). The current hypothesis states that early in development this interface is functional and more specific than in the adult, with differences historically termed as “immaturity” actually correctly reflecting developmental specialization. The advanced knowledge of the choroid plexus-CSF system proves itself imperative to understand a range of neurological diseases, from those caused by plexus or CSF drainage dysfunction (e.g., hydrocephalus) to more complicated late-stage diseases (e.g., Alzheimer's) and failure of CNS regeneration. This review will focus on choroid plexus development, outlining how early specializations may be exploited clinically. PMID:25784848

  18. Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis.

    PubMed

    Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

    2015-01-01

    This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell &Green's retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, -1, and -2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of -3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, -1, -2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

  19. Risk Characteristics of the Combined Geographic Atrophy and Choroidal Neovascularisation Phenotype in Age-Related Macular Degeneration

    PubMed Central

    Saade, Celine; Ganti, Bhaskar; Marmor, Michael; Freund, K. Bailey; Smith, R. Theodore

    2014-01-01

    Aim To investigate the risk characteristics of the combined geographic atrophy (GA) and choroidal neovascularization (CNV) phenotype of age-related macular degeneration (AMD) compared to GA or CNV. Methods Patients with advanced AMD were identified and divided into three groups using multimodal imaging: patients with GA in at least one eye, patients with CNV in at least one eye, and patients with simultaneous GA and CNV in at least one eye. Epidemiologic and clinical factors were gathered from patient questionnaires. Genotypes for age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) were determined. Results 42 patients with GA or CNV and 16 patients with combined GA/CNV were identified. Patients with the combined phenotype were older (86.4 vs. 81.8 years, p=0.049) and had a higher prevalence of advanced AMD in the fellow eye (81.3% vs. 31.0%, p<0.001). CFH and ARMS2 risk alleles were not associated with the combined phenotype. Conclusion The combined GA/CNV phenotype has similar epidemiologic, clinical, and genetic features as GA and CNV but occurs at an older age and is more associated with advanced AMD in the fellow eye, suggesting that all these phenotypes are part of the same spectrum of disease and that the combined phenotype represents an even more advanced form of AMD than either GA or CNV. PMID:25091949

  20. A rare case of congenital choroid plexus carcinoma.

    PubMed

    Wilhelm, Miriam; Hirsch, Wolfgang; Merkenschlager, Andreas; Stepan, Holger; Geyer, Christian; Kiess, Wieland

    2012-10-01

    We report a 1-year-old child with the prenatal (week 29 + 5) diagnosis of a brain tumor. The parents were informed about all aspects of prognosis and options concerning termination of pregnancy. The parents opted for an aggressive therapeutic approach after extensive and informative case conferences and counseling. The histopathological diagnosis after partial tumor resection was choroid plexus carcinoma, two weeks thereafter tumor size was progressive. The parents opted for palliative treatment at this stage. The patient died at the age of one year. Ethical aspects have to be actively considered and addressed when caring for children with choroid plexus carcinoma. PMID:22881717

  1. EN FACE IMAGING OF THE CHOROID IN POLYPOIDAL CHOROIDAL VASCULOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    Alasil, Tarek; Ferrara, Daniela; Adhi, Mehreen; Brewer, Erika; Kraus, Martin F; Baumal, Caroline R; Hornegger, Joachim; Fujimoto, James G; Witkin, Andre J; Reichel, Elias; Duker, Jay S; Waheed, Nadia K

    2014-01-01

    Objective To define morphological features of polypoidal choroidal vasculopathy (PCV) using en face images from swept source optical coherence tomography (SS-OCT). Design Prospective cross-sectional study. Methods Ten eyes from 6 patients with PCV and 10 eyes from 5 age-matched normal subjects. All subjects were prospectively scanned with a prototype SS-OCT system. A motion correction algorithm was applied to correct and merge scans into a single volumetric dataset. En face images were generated at intervals of 4.13 μm (1 pixel) relative to the Bruch’s membrane. Results Age ± standard deviation for the normal group was 62.4 (±12.1) years and for the PCV group was 68.3 (±5.2) years. En face SS-OCT imaging of PCV eyes demonstrated the relationship between larger pigment epithelial detachments (PEDs) and small adjoining PEDs which correlated with the polypoidal lesions seen on indocyanine green angiography in all PCV eyes. En face SS-OCT demonstrated choroidal vascular abnormalities in 7 out of 7 eyes with PCV, and in 2 out of 3 enrolled fellow eyes in patients with unilateral PCV. Out of 7 PCV eyes, focal choroidal vascular dilatation was noted in 3 eyes and diffuse choroidal vascular dilatation was noted in 1 eye. In addition, a branching vascular network was noted above Bruch’s membrane in 1 eye, below Bruch’s membrane within the choriocapillaris in 1 eye, and in the larger choroidal vascular layer in 1 eye. Conclusions En face SS-OCT provides an in vivo tool to visualize the pathological features and the choroidal vasculature in PCV. PMID:25528955

  2. Neovascular glaucoma in a child: an unusual presentation of medulloepithelioma

    PubMed Central

    Kassa, Enoch; Li, Helen; Sun, Yang

    2014-01-01

    A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.

  3. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis.

    PubMed

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  4. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis

    PubMed Central

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  5. TRAIL-deficient mice exhibit delayed regression of retinal neovascularization.

    PubMed

    Hubert, Kristin E; Davies, Michael H; Stempel, Andrew J; Griffith, Thomas S; Powers, Michael R

    2009-12-01

    While it is well established that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various cell types, the role of TRAIL in regulation of retinal neovascularization (NV) has not been described. Here we determined the role of TRAIL in retinal NV during oxygen-induced retinopathy using TRAIL deficient ((-/-)) mice. TRAIL and its receptor, DR5, were expressed in wild-type retinas at all time points evaluated (postnatal days 12, 17, 21, 24) during oxygen-induced retinopathy and in age-matched room air control animals. Localization of TRAIL(+) cells within the neovascular tufts of hyperoxia- exposed wild-type mice suggested TRAIL plays a role in oxygen-induced retinopathy. Retinal vascular development appeared normal in the TRAIL(-/-) mice, except for a small but significant difference in the capillary-free zone surrounding major arteries. A minimal difference in avascularity was observed at postnatal day 12 in the retinas of TRAIL(-/-) mice after hyperoxia-exposure compared with wild-type mice, suggesting that TRAIL does not play a major role in the vaso-obliterative phase of oxygen-induced retinopathy. However, at the peak of NV, TRAIL(-/-) mice had a significant increase in retinal neovascularization. In addition, when NV naturally regresses in wild-type mice, TRAIL(-/-) mice continued to display significantly high levels of NV. This was attributed to a significant decrease in neovascular tuft cells undergoing apoptosis in TRAIL(-/-) mice. Together, these data strongly suggest that TRAIL plays a role in the control of retinal NV. PMID:19893042

  6. Risk Factors of Myopic Shift among Primary School Children in Beijing, China: A Prospective Study

    PubMed Central

    Wu, Li-Juan; Wang, You-Xin; You, Qi-Sheng; Duan, Jia-Li; Luo, Yan-Xia; Liu, Li-Juan; Li, Xia; Gao, Qi; Zhu, Hui-Ping; He, Yan; Xu, Liang; Song, Man-Shu; Jonas, Jost B; Guo, Xiu-Hua; Wang, Wei

    2015-01-01

    Objective: To evaluate factors associated with myopic shift among primary school children. Methods: In a one-year prospective school-based study, 5052 children from ten schools were enrolled using a multi-stage random cluster approach. The baseline examination included non-cycloplegic auto-refractometry and questionnaire interview. Measurements were repeated at the follow-up. Results: Among 5052 students at baseline investigated, 4292 students (85.0%) returned for the follow-up examination. The mean refractive error (-1.13±1.57 diopters) had changed -0.52±0.73 diopters from the baseline to the follow-up examination. 2170 (51.0%) had a rate of significant myopic shift (significant myopic shift is defined as the change of spherical equivalent of the refraction ≤ -0.50D between the follow-up and baseline measures). We confirmed that common associated factors (older age, parental myopia, lower refractive status at baseline, shorter reading distance and lower frequency of outdoor activities during class recesses) were associated with greater shift towards myopia. After controlling for age, sex, region of habitation, parental myopia and refractive status at baseline, greater shift towards myopia was independently associated with distance from near-work (OR=1.48 , 95% CI=1.26-1.74, P<0.001) and longer time outdoors for leisure (OR=0.87, 95% CI=0.78-0.97, P<0.013). Conclusion: Greater shift towards myopia was independently associated with modifiable factors (distance from near-work and longer time outdoors for leisure) might suggest that encouraging children to go outside for outdoor activities during class recess and after school may be a promising and feasible intervention against myopia development. PMID:26283882

  7. Comparison and interchangeability of macular thickness measured with Cirrus OCT and Stratus OCT in myopic eyes

    PubMed Central

    Wang, Geng; Qiu, Kun-Liang; Lu, Xue-Hui; Zhang, Ming-Zhi

    2015-01-01

    AIM To investigate the difference of macular thickness measurements between stratus optical coherence tomography (OCT) and Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA) in the same myopic patient and to develop a conversion equation to interchange macular thickness obtained with these two OCT devices. METHODS Eighty-nine healthy Chinese adults with spherical equivalent (SE) ranging from -1.13 D to -9.63 D were recruited. The macular thickness was measured by Cirrus OCT and Stratus OCT. The correlation between macular thickness and axial length and the agreement between two OCT measurements were evaluated. A formula was generated to interchange macular thickness obtained with two OCT devices. RESULTS Average macular thickness measured with Stratus OCT (r=-0.280, P=0.008) and Cirrus OCT (r=-0.224, P=0.034) were found to be negatively correlated with axial length. No statistically significant correlation was found between axial length and central subfield macular thickness (CMT) measured with Stratus OCT (r=0.191, P=0.073) and Cirrus OCT (r=0.169, P=0.113). The mean CMT measured with Cirrus OCT was 53.63±7.94 µm thicker than with Stratus OCT. The formula CMTCirrus OCT=78.328+0.874×CMTStratus OCT was generated to interchange macular thickness obtained with two OCT devices. CONCLUSION Macular thickness measured with Cirrus OCT were thicker than with Stratus OCT in myopic eyes. A formula can be used to interchange macular thickness measured with two OCT devices in myopic eyes. Studies with different OCT devices and larger samples are warranted to enable the comparison of macular values measured with different OCT devices. PMID:26682172

  8. A new role for cofilin in retinal neovascularization.

    PubMed

    Kumar, Raj; Janjanam, Jagadeesh; Singh, Nikhlesh K; Rao, Gadiparthi N

    2016-03-15

    Pak1 plays an important role in several cellular processes, including cell migration, but its role in pathological angiogenesis is not known. Here, we have determined its role in pathological retinal angiogenesis using an oxygen-induced retinopathy (OIR) model. VEGFA induced phosphorylation of Pak1 and its effector cofilin in a manner that was dependent on time as well as p38MAPKβ (also known as MAPK11) in human retinal microvascular endothelial cells (HRMVECs). Depletion of the levels of any of these molecules inhibited VEGFA-induced HRMVEC F-actin stress fiber formation, migration, proliferation, sprouting and tube formation. In accordance with these observations, hypoxia induced Pak1 and cofilin phosphorylation with p38MAPKβ being downstream to Pak1 and upstream to cofilin in mouse retina. Furthermore, Pak1 deficiency abolished hypoxia-induced p38MAPKβ and cofilin phosphorylation and abrogated retinal endothelial cell proliferation, tip cell formation and neovascularization. In addition, small interfering RNA (siRNA)-mediated downregulation of p38MAPKβ or cofilin levels in the wild-type mouse retina also diminished endothelial cell proliferation, tip cell formation and neovascularization. Taken together, these observations suggest that, although the p38MAPKβ-Pak1-cofilin axis is required for HRMVEC migration, proliferation, sprouting and tubulogenesis, Pak1-p38MAPKβ-cofilin signaling is also essential for hypoxia-induced mouse retinal endothelial cell proliferation, tip cell formation and neovascularization. PMID:26857814

  9. Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

    PubMed Central

    Rakoczy, Elizabeth P.; Rahman, Ireni S. Ali; Binz, Nicolette; Li, Cai-Rui; Vagaja, Nermina N.; de Pinho, Marisa; Lai, Chooi-May

    2010-01-01

    One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors—hyperglycemia and vascular endothelial growth factor—interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema. PMID:20829433

  10. Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy

    PubMed Central

    Cham, Abdourahman; Bansal, Mayank; Banda, Himanshu K; Kwon, Young; Tlucek, Paul S; Bassuk, Alexander G; Tsang, Stephen H; Sobol, Warren M; Folk, James C; Yeh, Steven; Mahajan, Vinit B

    2016-01-01

    Objective The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. Patients and methods A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. Results Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. Conclusion ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid-response glaucoma, angle closure glaucoma, and hypotony. PMID:27390515

  11. Ablation algorithms and corneal asphericity in myopic correction with excimer lasers

    NASA Astrophysics Data System (ADS)

    Iroshnikov, Nikita G.; Larichev, Andrey V.; Yablokov, Michail G.

    2007-06-01

    The purpose of this work is studying a corneal asphericity change after a myopic refractive correction by mean of excimer lasers. As the ablation profile shape plays a key role in the post-op corneal asphericity, ablation profiles of recent lasers should be studied. The other task of this research was to analyze operation (LASIK) outcomes of one of the lasers with generic spherical ablation profile and to compare an asphericity change with theoretical predictions. The several correction methods, like custom generated aspherical profiles, may be utilized for mitigation of unwanted effects of asphericity change. Here we also present preliminary results of such correction for one of the excimer lasers.

  12. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation.

    PubMed

    Bakunowicz-Łazarczyk, Alina; Urban, Beata

    2016-03-01

    This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy. PMID:26651127

  13. The neural milieu of the developing choroid plexus: neural stem cells, neurons and innervation.

    PubMed

    Prasongchean, Weerapong; Vernay, Bertrand; Asgarian, Zeinab; Jannatul, Nahin; Ferretti, Patrizia

    2015-01-01

    The choroid plexus produces cerebrospinal fluid and plays an important role in brain homeostasis both pre and postnatally. In vitro studies have suggested that cells from adult choroid plexus have stem/progenitor cell-like properties. Our initial aim was to investigate whether such a cell population is present in vivo during development of the choroid plexus, focusing mainly on the chick choroid plexus. Cells expressing neural markers were indeed present in the choroid plexus of chick and also those of rodent and human embryos, both within their epithelium and mesenchyme. ß3-tubulin-positive cells with neuronal morphology could be detected as early as at E8 in chick choroid plexus and their morphological complexity increased with development. Whole mount immunochemistry demonstrated the presence of neurons throughout choroid plexus development and they appeared to be mainly catecholaminergic, as indicated by tyrosine-hydroxylase reactivity. The presence of cells co-labeling for BrdU and the neuroblast marker, doublecortin, in organotypic choroid plexus cultures supported the hypothesis that neurogenesis can occur from neural precursors within the developing choroid plexus. Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested. Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally. Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life. PMID:25873856

  14. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  15. A Case of Choroidal Melanoma Metastatic to the Breast

    PubMed Central

    Taran-Munteanu, L.; Hartkopf, A.; Eigentler, T. K.; Vogel, U.; Brucker, S.; Taran, F. A.

    2016-01-01

    A 61-year-old woman developed blurred vision in her left eye in December 2006. A clinical diagnosis of choroidal melanoma was made. The patient underwent excision of the left lens, followed by vitrectomy and stereotactic radiotherapy. She remained systemically healthy until 50 months later when, during a CT scan done for staging purposes, a newly visible lump was noted in the lower quadrant of her left breast. Core needle biopsy of the lesion in the left breast was performed, and histologic examination revealed metastasis from the choroidal melanoma. The patient underwent breast-conserving surgery of the left breast. Definitive histological examination showed clear tumor margins in the resected specimen and one sentinel lymph node without evidence of metastatic cells. Twenty-nine months after surgery, a similar nodule was detected in the upper quadrant of the left breast. Core biopsy again showed metastatic melanoma, and similar breast-conserving surgery was performed. Systemic examination, including magnetic resonance imaging of the head and computed tomography of the pelvis, abdomen, and chest, was done regularly and revealed no significant findings. Solitary breast metastases from choroidal melanoma are extremely rare. Nevertheless, clinicians should be aware of this rare form of metastasis when treating patients with suspicious breast lesions and a history of choroidal melanoma. If solitary metastasis is confirmed, then breast-conserving surgery may be recommended. PMID:27239068

  16. Silent polypoidal choroidal vasculopathy in a patient with angioid streaks.

    PubMed

    Cebeci, Zafer; Bayraktar, Serife; Oray, Merih; Kir, Nur

    2016-01-01

    We present a case of silent polypoidal choroidal vasculopathy (PCV) in a patient with angioid streaks. PCV was detected during a routine ophthalmic examination and confirmed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. After 2 years of follow-up, the PCV remained silent without any complications. We report this rare coexistence and review literature on this topic. PMID:27463636

  17. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration

    PubMed Central

    Solomon, Sharon D.; Lindsley, Kristina; Vedula, Satyanarayana S.; Krzystolik, Magdalena G.; Hawkins, Barbara S.

    2014-01-01

    Background Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. Objectives To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. Selection criteria We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Data collection

  18. Retinal and vitreal neovascularization in retinopathy of prematurity. A scanning electron microscopic study in the kitten.

    PubMed

    Yoneya, S; Tso, M O

    1991-12-01

    The angioarchitecture of vitreal and retinal neovascularizations produced experimentally in the eyes of kittens aged 2 to 9 weeks was studied with scanning electron microscopy. Various forms of new retinal and vitreal vessels were observed depending on topographic locations. Intraretinal neovascularization was observed at the retinal periphery as it grew toward the avascular zone in forms of short vascular buds, aneurysmal outgrowths, and neovascular loops. Posterior or to this frond of neovascularization, intertwining intraretinal telangiectasia was observed. At the posterior pole, capillaries with microaneurysms extended posteriorly toward the deeper layers of the retina from the vascular trunks at the nerve fiber layer. Vitreal neovascularization broke through the internal limiting membrane and exhibited aneurysmal outgrowths, clusters of glomerular swellings, and sinusoidal vascular channels. At the optic disc, vitreous neovascularization took the form of aneurysmal outgrowths and long vascular buds. Vitreal neovascularization showed different characteristics from the intraretinal neovascularization. We hypothesize that the topographic variation of the angioarchitecture of retinal and vitreal neovascularizations depends on the maturity of the vessels and might be related to the hemodynamics at each site. PMID:1726774

  19. Kir7.1 immunoreactivity in canine choroid plexus tumors.

    PubMed

    Choi, Eun Ju; Sloma, Erica A; Miller, Andrew D

    2016-07-01

    Choroid plexus neoplasms are uncommon brain tumors in dogs. Choroid plexus carcinomas often spread diffusely throughout the ventricular system and subarachnoid space and, in aggressive forms, can mimic histologic patterns of other carcinomas, including being embedded in a desmoplastic reaction. Although choroid plexus tumors (CPTs) heterogeneously express pan-cytokeratin, little is known about other markers to identify choroid plexus and their associated tumors. Kir7.1, an inward-rectifier potassium channel, is reported to have high diagnostic utility in human neuropathology to distinguish CPTs from other primary brain tumors and cerebral metastases. To determine Kir7.1 expression in the dog brain, we analyzed the immunoreactivity of Kir7.1 in normal brain, gliomas, ependymomas, CPTs, meningiomas, and carcinomas. In normal brain tissue, the immunostaining was restricted to the choroid plexus where there was robust membrane immunoreactivity along the apical border of the cells with less intense cytoplasmic staining. Similar strong immunoreactivity was detected in 12 of 12 CPTs, whereas 5 of 5 gliomas, 4 of 5 ependymomas, 5 of 5 meningiomas, and 5 of 6 carcinomas had no immunoreactivity. One ependymoma and 1 nasal carcinoma with squamous metaplasia were up to 75% immunopositive, with moderate cytoplasmic and membranous immunoreactivity, but lacking the robust apical immunoreactivity pattern. Analysis for immunoreactivity in a tissue microarray failed to yield any other locations in which immunoreactivity was detected. These results, including the distinctive pattern of immunostaining in CPTs, suggest that Kir7.1 is an excellent marker for CPTs in the dog. PMID:27216721

  20. Choroidal Blood Flow Change in Eyes with High Myopia

    PubMed Central

    Yang, Young Seong

    2015-01-01

    Purpose To evaluate choroidal blood flow changes in eyes with high myopia according to the pulsatile components of ocular blood flow analysis. Methods A total of 104 subjects (52 males and 52 females) were included in this study. One eye of each participant was randomly selected and assigned to one of four refractive groups, designated as, hyperopes (n = 20; refractive error, ≥+1.00 diopter [D]), emmetropes (n = 28; refractive error, ±0.75 D), lower myopes (n = 33; refractive error, -1.00 to -4.75 D), and high myopes (n = 23; refractive error, ≤-5.00 D). Components of pulse amplitude (OBFa), pulse volume (OBFv), pulse rate (OBFr), and pulsatile ocular blood flow (POBF) were analyzed using a blood flow analyzer. Intraocular pressure and axial length were measured. Results Pulsatile components of OBFa, OBFv, and POBF showed positive correlations with refractive error and showed negative correlations with axial length (r = 0.729, r = 0.772, r = 0.781, respectively, all p < 0.001; r = -0.727, r = -0.762, r = -0.771, respectively, all p < 0.001). The correlations of refractive error and axial length with OBFr were irrelevant (r = -0.157, p = 0.113; r = 0.123, p = 0.213). High myopes showed significantly lower OBFa, OBFv, and POBF than the other groups (all p < 0.001). Conclusions Axial length changes in high myopes potentially influence choroidal blood flow, assuming the changes are caused by narrowing of the choroidal vessel diameter and increasing rigidity of the choroidal vessel wall. These finding explains the influence of axial length on OBFa, OBFv, and POBF, but not on OBFr. Thus, changes in axial length and the possible influence of these changes on the physical properties of choroidal vessels is the mechanism believed to be responsible for putting high myopes at risk for ocular vascular diseases. PMID:26457036

  1. Choroidal thickness in pregnant women: a cross-sectional study

    PubMed Central

    Liu, Ru; Kuang, Guo-Ping; Luo, Di-Xian; Lu, Xiao-He

    2016-01-01

    AIM To investigate choroidal thickness in pregnant women and compare the measurements with those of normal nonpregnant women. METHODS Using enhanced depth imaging optical coherence tomography (EDI-OCT), choroidal thickness was measured at the fovea and at 1 mm and 3 mm superior, inferior, temporal, and nasal to the fovea in both healthy pregnant women and nonpregnant women. Pearson correlation analysis was performed to evaluate the relationships between subfoveal choroidal thickness (SFCT) and the demographic and ocular parameters. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects model when Meta-analyses were conducted. RESULTS Comparison of choroidal thickness between the groups showed that it was significantly greater in healthy pregnant women's eyes than in normal nonpregnant women's eyes at all locations except at 3 mm superior and 3 mm temporal from the fovea (P<0.05). The mean SFCT was 344.13±50.94 µm in healthy pregnant women's eyes and 315.03±60.57 µm in normal nonpregnant women's eyes, with a statistically significant difference (P=0.008). Pearson correlation analysis showed that age and axial length were significantly related to SFCT in healthy pregnant women, normal nonpregnant women, and all subjects. The results of our cross-sectional study were consistent with the results of the further Meta-analysis, with a pooled weighted mean difference (WMD) of 33.66 µm (95% CI: 26.16 to 41.15) for SFCT. CONCLUSION Our results, along with the comprehensive Meta-analysis, suggest that choroidal thickness in healthy pregnant women is greater than that in normal nonpregnant women. PMID:27588276

  2. Effect of wavefront optimized LASIK on higher order aberrations in myopic patients

    PubMed Central

    Khan, Muhammad Saim; Humayun, Sadia; Fawad, Aisha; Ishaq, Mazhar; Arzoo, Sabahat; Mashhadi, Fawad

    2015-01-01

    Objective: To determine mean change induced in root mean square value of higher order aberrations in myopic patients undergoing wavefront optimized laser assisted in situ keratomileusis. Methods: This quasi experimental study was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from Jan 2014 to Dec 2014. Sixty eyes of 35 myopic patients were included in the study. All patients underwent wavefront optimized (WFO) laser assisted in situ keratomileusis (LASIK) using femtosecond laser (FM 200Wavelight technologies) and excimer laser (Ew 500Wavelight technologies). Higher order aberrations (HOAs) were measured with aberrometer (Wavelight allegro analyzer version 1073) during preoperative assessment and one month after surgery. Results: All 35 patients ranged from 20 to 32 years with a mean age of 24 ± 3.41 years. Refractive error ranged from -1.00 to -9.50 DS with a mean spherical equivalent (SE) of -3.73 ± 1.95 before surgery and - 0.36 ± 1.50DS one month after LASIK. Uncorrected visual acuity (UCVA) was improved to 0.00 or better in all 60 eyes. An increase of 1.56 fold was observed in RMS of total HOAs. Among the HOAs, a statistically significant positive correlation was observed between spherical aberrations (4th order aberration) and preoperative spherical equivalent. Conclusion: In spite of excellent improvement in refractive error, significant amount of higher order aberrations were induced after WFO LASIK. PMID:26649018

  3. Comparison of Subjective Refraction under Binocular and Monocular Conditions in Myopic Subjects.

    PubMed

    Kobashi, Hidenaga; Kamiya, Kazutaka; Handa, Tomoya; Ando, Wakako; Kawamorita, Takushi; Igarashi, Akihito; Shimizu, Kimiya

    2015-01-01

    To compare subjective refraction under binocular and monocular conditions, and to investigate the clinical factors affecting the difference in spherical refraction between the two conditions. We examined thirty eyes of 30 healthy subjects. Binocular and monocular refraction without cycloplegia was measured through circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D visual function trainer-ORTe. Stepwise multiple regression analysis was used to assess the relations among several pairs of variables and the difference in spherical refraction in binocular and monocular conditions. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition (p < 0.001), whereas no significant differences were seen in subjective cylindrical refraction (p = 0.99). The explanatory variable relevant to the difference in spherical refraction between binocular and monocular conditions was the binocular spherical refraction (p = 0.032, partial regression coefficient B = 0.029) (adjusted R(2) = 0.230). No significant correlation was seen with other clinical factors. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition. Eyes with higher degrees of myopia are more predisposed to show the large difference in spherical refraction between these two conditions. PMID:26218972

  4. Comparison of Subjective Refraction under Binocular and Monocular Conditions in Myopic Subjects

    PubMed Central

    Kobashi, Hidenaga; Kamiya, Kazutaka; Handa, Tomoya; Ando, Wakako; Kawamorita, Takushi; Igarashi, Akihito; Shimizu, Kimiya

    2015-01-01

    To compare subjective refraction under binocular and monocular conditions, and to investigate the clinical factors affecting the difference in spherical refraction between the two conditions. We examined thirty eyes of 30 healthy subjects. Binocular and monocular refraction without cycloplegia was measured through circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D visual function trainer-ORTe. Stepwise multiple regression analysis was used to assess the relations among several pairs of variables and the difference in spherical refraction in binocular and monocular conditions. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition (p < 0.001), whereas no significant differences were seen in subjective cylindrical refraction (p = 0.99). The explanatory variable relevant to the difference in spherical refraction between binocular and monocular conditions was the binocular spherical refraction (p = 0.032, partial regression coefficient B = 0.029) (adjusted R2 = 0.230). No significant correlation was seen with other clinical factors. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition. Eyes with higher degrees of myopia are more predisposed to show the large difference in spherical refraction between these two conditions. PMID:26218972

  5. Brightness perception under transient glare conditions with myopic observers wearing contact lenses and spectacles

    NASA Astrophysics Data System (ADS)

    Issolio, Luis; Lopez-Gil, Norberto; Colombo, Elisa M.; Miro, Ignacio

    2001-08-01

    Transient glare reduces the perceived brightness for stimulus luminances within the scotopic-mesopic range. This work studies this effect in myopic observers with lens and spectacles corrections and in one emmetrope. The task of the subject consists of compare brightness of two uniform luminance fields sequentially displayed, one of which had a reference luminance of 1 cd/m2. The reference stimulus was presented under glare condition the angle between the glare source and the lie of sight was 10 degrees. The reference field and he glare source were onset at the same time. Subjects had to report which field was brighter with respect to one another. A YES-NO method with constant stimulus was adopted to determine the perceptual matching luminance. Then duration of each stimulus was 300 msec and the interval between both of them was 1.2 msec. We found the effect of the transient glare is stronger as myopic subjects wear glasses corrections than they wear contact lens and the effect is even less for emmetropic subject with the naked eyes. Results could be explained considering an additional ectoptic light veil due to scattering on the glasses and lens.

  6. Effect of accommodation training by stereoscopic movie presentation on myopic youth

    NASA Astrophysics Data System (ADS)

    Sugiura, A.; Takada, H.; Yamamoto, T.; Miyao, M.

    2010-02-01

    The abnormal contraction of ciliary muscles due to the performance of a near visual task for several hours causes various vision problems such as asthenopia and visual loss. However, these problems can be resolved by activating the muscles by alternately repeating negative and positive accommodation. In this study, we have verified the effect of accommodation training that uses the strategy of presenting a stereoscopic movie to myopic youth and measuring the uncorrected distant visual acuity, spherical diopter (SPH), and subjective index of asthenopia obtained using a visual analog scale (VAS). Stereoscopic movies are prepared by using the POWER 3D method (Olympus Visual Communications Co., Ltd.), which reduces the inconsistency between the experienced and the actual senses. Thirty two myopic students aged 20 +/- 1 years (16 males and 16 females) were chosen as the subjects. One group performed the accommodation training for 6 min, and the other group underwent a near visual task during the same period as the control group. We concluded the following from each item of verification: (a) The accommodation training using a stereoscopic movie had temporarily improved visual acuity. (b) This training led to a decrease in asthenopia. (c) The training improved the near-point accommodation function.

  7. The development and evolution of full thickness macular hole in highly myopic eyes

    PubMed Central

    Lin, C-W; Ho, T-C; Yang, C-M

    2015-01-01

    Purpose To evaluate the morphological changes before and after the formation of a full-thickness macular hole (MH) in highly myopic eyes. Patients and methods Retrospective observational case series. From 2006 to 2013, clinical records of patients with MH and high myopia who had optical coherence tomography (OCT) before the development of MH were reviewed. All patients had been followed for more than 1 year since MH formation to observe the morphological changes. Results Twenty-six eyes of 24 patients were enrolled. The initial OCT images could be classified into four types: (1) normal foveal depression with abnormal vitreo-retinal relationship (eight cases), (2) macular schisis without detachment (six cases), (3) macular schisis with concomitant/subsequent detachment (nine cases), and (4) macular atrophy with underlying/adjacent scar (three cases). After MH formation, one case in type 1 and one case in type 4 group developed retinal detachment (RD). In type 2 group, four cases developed RD at the same time of MH formation. The preexisting detachment in type 3 group extended in eight cases and improved in one case. Among all the cases, 14 eyes received vitrectomy and 7 eyes received gas injection. MH sealed in nine eyes after vitrectomy and four eyes by gas injection. Conclusion The study revealed four pathways of MH formation in highly myopic eyes. MH from macular schisis tended to be associated with detachment. However, the evolution and the results of surgical intervention were not always predictable. PMID:25572579

  8. Effectiveness of Scraping and Mitomycin C to Treat Haze After Myopic Photorefractive Keratectomy

    PubMed Central

    Spadea, Leopoldo; Verrecchia, Valerio

    2011-01-01

    To report the possibility of post myopic photorefractive keratectomy (PRK) haze treatment in a patient with expressed reluctance for any additional laser therapy. Seven months after bilateral PRK with subsequent development of corneal haze and refractive regression in both eyes, a 37-old-year male patient presented a best-spectacle corrected visual acuity (BSCVA) of 20/30 in the right eye and of 20/22 in the left eye. Both eyes were sequentially treated by scraping the stromal surface and application of mitomycin C (MMC) for 2 minutes. Both eyes had significant improvement in corneal transparency. Eighteen months after this treatment BSCVA had improved to 20/20 in each eye. No toxic effects were observed during either re-epithelialization or follow-up periods. In conclusion scraping and application of MMC could be considered a good tool in the treatment of selected cases of haze after myopic PRK, especially with patients that are reluctant to undergo a secondary laser procedure. PMID:22262990

  9. Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration*

    PubMed Central

    Hirasawa, Manabu; Takubo, Keiyo; Osada, Hideto; Miyake, Seiji; Toda, Eriko; Endo, Motoyoshi; Umezawa, Kazuo; Tsubota, Kazuo; Oike, Yuichi; Ozawa, Yoko

    2016-01-01

    Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser-induced CNV model, we found that Angptl2 KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1β (Il-1β), Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor-β1 (Tgf-β1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in the Angptl2 KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived from Angptl2 KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins α4 and β2, followed by the downstream activation of NF-κB and ERK. The activation of NF-κB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration. PMID:26839315

  10. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    NASA Astrophysics Data System (ADS)

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-02-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

  11. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    PubMed Central

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-01-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases. PMID:26868048

  12. Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization.

    PubMed

    Zhu, Yanji; Tan, Wei; Demetriades, Anna M; Cai, Yujuan; Gao, Yushuo; Sui, Ailing; Lu, Qing; Shen, Xi; Jiang, Chunhui; Xie, Bing; Sun, Xinghuai

    2016-04-01

    Neovascularization (NV), as a cardinal complication of several ocular diseases, has been intensively studied, and research has shown its close association with inflammation and immune cells. In the present study, the role of interleukin-17A (IL-17A) in angiogenesis in the process of ocular NV both in vivo and in vitro was investigated. Also, a paracrine role of IL-17A was demonstrated in the crosstalk between endothelial cells and macrophages in angiogenesis. In the retinas of mice with retinopathy of prematurity, the IL-17A expression increased significantly at postnatal day 15 (P15) and P18 during retinal NV. Mice given IL-17A neutralizing antibody (NAb) developed significantly reduced choroidal NV and retinal NV. Studies on vascular endothelial growth factor (VEGF) over-expressing mice suggested that IL-17A modulated NV through the VEGF pathway. Furthermore, IL-17A deficiency shifted macrophage polarization toward an M2 phenotype during retinal NV with significantly reduced M1 cytokine expression compared with wild-type controls. In vitro assays revealed that IL-17A treated macrophage supernatant gave rise to elevated human umbilical vascular endothelial cell proliferation, tube formation and VEGF receptor 1 and receptor 2 expression. Therefore, IL-17A could potentially serve as a novel target for treating ocular NV diseases. The limitation of this study involved the potential mechanisms, such as which transcription accounted for macrophage polarization and how the subsequent cytokines were modulated when macrophages were polarized. Further studies need to be undertaken to definitively determine the extent to which IL-17A neutralizing anti-angiogenic activity depends on macrophage modulation compared with anti-VEGF treatment. PMID:26694999

  13. Prospective Evaluation of Subretinal Vessel Location in Polypoidal Choroidal Vasculopathy (PCV) and Response of Hemorrhagic and Exudative PCV to High-Dose Antiangiogenic Therapy (An American Ophthalmological Society Thesis)

    PubMed Central

    Kokame, Gregg T.

    2014-01-01

    Purpose: The purpose of this study was to determine the following: (1) Is polypoidal choroidal vasculopathy (PCV) a subretinal neovascular process, rather than a choroidal vascular anomaly? and (2) Is a higher dose of ranibizumab (2.0 mg/0.05 mL) more effective in treating PCV than the current dose (0.5 mg/0.05 mL) approved for treatment of age-related macular degeneration? Methods: Retrospective evaluation of PCV in 104 eyes of 86 patients was accomplished with use of indocyanine green angiography plus optical coherence tomography to localize the branching vascular network and the polyps. Nineteen eyes of 19 patients with active leaking and exudation underwent a prospective open-label trial of monthly high-dose intravitreal ranibizumab (2.0 mg/0.05 mL). The primary outcome was prevention of major vision loss (≤15 ETDRS letters). Secondary outcomes included adverse events, improved vision, and changes in subretinal hemorrhage, subretinal fluid, macular edema, and polypoidal complexes at 6 months. Results: The PCV vessels were localized beneath the retinal pigment epithelium (RPE) and above Bruch’s membrane in 103 (99%) of 104 eyes. In the high-dose ranibizumab trial at 6 months, none of the patients lost ≥15 letters in visual acuity, and 5 (26%) of 19 gained ≥15 letters. Decreases were noted in subretinal fluid in 14 (82%) of 17 eyes, subretinal hemorrhage in 12 (100%) of 12, RPE detachment in 14 (88%) of 16, macular edema in 11 (92%) of 12, and polyps in 15 (79%) of 19 eyes. Conclusions: PCV vessels are a subtype of subretinal neovascularization located above Bruch’s membrane and below RPE. High-dose ranibizumab (2.0 mg/0.05 mL) decreased exudation and hemorrhage and resulted in significant polyp regression, although branching vascular networks persisted. PMID:25646029

  14. Segmentation of the macular choroid in OCT images acquired at 830nm and 1060nm

    NASA Astrophysics Data System (ADS)

    Lee, Sieun; Beg, Mirza F.; Sarunic, Marinko V.

    2013-06-01

    Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.

  15. Examining the Choroid in Ocular Inflammation: A Focus on Enhanced Depth Imaging

    PubMed Central

    Baltmr, Abeir; Lightman, Sue; Tomkins-Netzer, Oren

    2014-01-01

    The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT) is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation. PMID:25024846

  16. In vivo corneal neovascularization imaging by optical-resolution photoacoustic microscopy

    PubMed Central

    Liu, Wenzhong; Schultz, Kathryn M.; Zhang, Kevin; Sasman, Amy; Gao, Fengli; Kume, Tsutomu; Zhang, Hao F.

    2014-01-01

    Corneal neovascularization leads to blurred vision, thus in vivo visualization is essential for pathological studies in animal models. Photoacoustic (PA) imaging can delineate microvasculature and hemodynamics noninvasively, which is suitable for investigating corneal neovascularization. In this study, we demonstrate in vivo imaging of corneal neovascularization in the mouse eye by optical-resolution photoacoustic microscopy (OR-PAM), where corneal neovascularization is induced by deliberate alkali burn injuries in C57BL6/J inbred mice corneas on the left eye. We used OR-PAM to image five mice with corneal alkali burn injuries; the uninjured eyes (right eye) in these mice are then used as the controls. Corneal images acquired by OR-PAM with and without alkali burn injury are compared, clear signs of corneal neovascularization are present in the OR-PAM images of injured eyes; the OR-PAM results are also confirmed by postmortem fluorescence-labeled confocal microscopy. PMID:25013754

  17. Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis

    PubMed Central

    Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

    2015-01-01

    This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell & Green’s retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, –1, and –2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of –3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, −1, −2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

  18. Unsuspected Ganglioneuroma of the Choroid Diagnosed after Enucleation

    PubMed Central

    Mbagwu, Michael; Rahmani, Bahram; Srivastava, Arth; Burrowes, Delilah; Bryar, Paul J.

    2015-01-01

    We report a case of an unsuspected ganglioneuroma of the choroid in a patient with neurofibromatosis type 1. A 5-year-old girl presented from an outside institution with right proptosis and glaucoma since birth. Magnetic resonance imaging was obtained and showed a cavernous sinus mass extending into the right orbit and multiple orbital lesions. Additionally, increased signal in the posterior globe of the right eye was noted, but its etiology was unclear at the time. She was lost to follow-up for 3 years and later returned with a blind painful eye. Enucleation was performed, and histopathology was significant for diffuse choroidal ganglioneuroma and advanced glaucoma. We report the atypical history, examination findings, and histopathology to support the diagnosis. PMID:27171204

  19. [Histopathologic study of melanoma of the choroid after proton therapy].

    PubMed

    Devouassoux Shishe Boran, M; Grange, J D; Patricot, L M; Adeleine, P; Chauvel, P; Chiquet, C; Vitrey, D; Thivolet Béjui, F

    1997-07-01

    To evaluate irradiation effects on choroidal melanomas, histopathologic findings of 18 eyes whose primary treatment was enucleation were compared to 15 eyes enucleated after proton beam irradiation. Irradiated tumors showed more likely necrosis (p = 0.01) had balloon cells (p = 0.01), and inflammatory infiltrate (p = 0.05). In the irradiated group, the prevalence of tumor blood vessel damage was higher (p = 0.0002) and mitotic figures were fewer (p = 0.01). These findings suggest that proton beam irradiation damages tumor cells and alters the tumor's capacity for cellular reproduction. It damages blood vessels leading to tumor necrosis. It induces an inflammatory response of unknown effects. Radiosensitivity of choroidal melanomas cannot be assessed using conventional histologic methods. However, tumor necrosis, mitotic activity and rate of balloon cells can help to establish tumoral sensitivity to irradiation. PMID:9296578

  20. Bilateral choroidal excavation in best vitelliform macular dystrophy.

    PubMed

    Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Fasce, Francesco; Bandello, Francesco

    2014-01-01

    Focal choroidal excavation (FCE) has recently been described as one or more localized areas of choroidal excavation on spectral-domain optical coherence tomography (SD-OCT). The authors describe a case of bilateral FCE in Best vitelliform macular dystrophy (VMD). SD-OCT revealed FCE in both eyes characterized by interruption of the internal segment-outer segment junction and the presence of subretinal hyporeflective space. This is the first report describing bilateral FCE in a distinct macular disorder and specifically with VMD. Future investigations are warranted to ascertain the involvement of other macular dystrophies with atrophic evolution and the impact of FCE on the clinical course. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:e8-e10.]. PMID:24512759

  1. Uveal Melanoma in the Peripheral Choroid Masquerading as Chronic Uveitis

    PubMed Central

    Feng, Lei; Zhu, Jiang; Gao, Tao; Li, Baizhou; Yang, Yabo

    2014-01-01

    ABSTRACT Purpose To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes. Case Report A 36-year-old Chinese woman presented from an outside ophthalmologist with a 6-month history of unilateral chronic uveitis unresponsive to medical therapy in the left eye. She was found to have a uveal melanoma in the retinal periphery and underwent successful enucleation of her left eye. The histopathological diagnosis confirmed the clinical diagnosis. Conclusions When uveal melanoma presents in an atypical way, the diagnosis is more difficult. This case highlights the uncommon presentations of malignant melanoma of the choroid. It provides valuable information on how peripheral uveal melanoma can present with clinical signs consistent with an anterior uveitis. PMID:25036546

  2. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    SciTech Connect

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. )

    1991-05-01

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

  3. Quantitative polarization and flow evaluation of choroid and sclera by multifunctional Jones matrix optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Sugiyama, S.; Hong, Y.-J.; Kasaragod, D.; Makita, S.; Miura, M.; Ikuno, Y.; Yasuno, Y.

    2016-03-01

    Quantitative evaluation of optical properties of choroid and sclera are performed by multifunctional optical coherence tomography. Five normal eyes, five glaucoma eyes and one choroidal atrophy eye are examined. The refractive error was found to be correlated with choroidal birefringence, polarization uniformity, and flow in addition to scleral birefringence among normal eyes. The significant differences were observed between the normal and the glaucoma eyes, as for choroidal polarization uniformity, flow and scleral birefringence. An automatic segmentation algorithm of retinal pigment epithelium and chorioscleral interface based on multifunctional signals is also presented.

  4. Fundus Autofluorescence and Optical Coherence Tomography Findings in Choroidal Melanocytic Lesions

    PubMed Central

    Materin, Miguel A.; Raducu, Raluca; Bianciotto, Carlos; Shields, Carol L.

    2010-01-01

    Purpose: To establish the characteristics of secondary retinal and retinal pigment epithelial (RPE) changes associated with the presence of choroidal melanoma and choroidal nevus as documented by optical coherence tomography (OCT) and fundus autofluorescence (FAF). Materials and Methods: PubMed review of major English publications examining the correlation between clinical characteristics of choroidal melanoma and nevus with OCT and FAF findings. Results: The intrinsic properties of choroidal melanoma, as well as overlying RPE changes, drusen, and lipofuscin are best characterized by FAF, while OCT is more sensitive for the identification of subretinal and intraretinal fluid as well as atrophy, degeneration, and photoreceptor loss in the neurosensory retina. Conclusions: Secondary retinal changes associated with choroidal melanocytic lesions can be documented by OCT and FAF. OCT-evident changes are observed more often with choroidal melanoma than choroidal nevus. OCT is better suited to identify the overlying retinal detachment and edema, even before these findings are clinically apparent. FAF is most useful in documenting the presence of lipofuscin, a finding that represents one of the important criteria in differentiating small choroidal melanoma from benign choroidal nevus. PMID:20844674

  5. Choroidal Coloboma in a Case of Tay-Sachs Disease

    PubMed Central

    Ahmed, Nasreen Raees; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated. PMID:25295204

  6. Prognostic factors of choroidal melanoma in Slovenia, 1986–2008

    PubMed Central

    Budihna, Marjan; Drnovsek-Olup, Brigita; Andrejcic, Katrina Novak; Zupancic, Irena Brovet; Pahor, Dusica

    2016-01-01

    Introduction Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. Patients and methods From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Results Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. Conclusions It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation. PMID:27069456

  7. Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis

    PubMed Central

    Shao, Zhuo; Friedlander, Mollie; Hurst, Christian G.; Cui, Zhenghao; Pei, Dorothy T.; Evans, Lucy P.; Juan, Aimee M.; Tahir, Houda; Duhamel, François; Chen, Jing; Sapieha, Przemyslaw; Chemtob, Sylvain; Joyal, Jean-Sébastien; Smith, Lois E. H.

    2013-01-01

    Angiogenesis of the microvasculature is central to the etiology of many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model of microvascular angiogenesis would be very valuable and enable access to a wide range of genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured in vitro are widely used, however, isolating pure vascular murine endothelial cells is technically challenging. A microvascular mouse explant model that is robust, quantitative and can be reproduced without difficulty would overcome these limitations. Here we characterized and optimized for reproducibility an organotypic microvascular angiogenesis mouse and rat model from the choroid, a microvascular bed in the posterior of eye. The choroidal tissues from C57BL/6J and 129S6/SvEvTac mice and Sprague Dawley rats were isolated and incubated in Matrigel. Vascular sprouting was comparable between choroid samples obtained from different animals of the same genetic background. The sprouting area, normalized to controls, was highly reproducible between independent experiments. We developed a semi-automated macro in ImageJ software to allow for more efficient quantification of sprouting area. Isolated choroid explants responded to manipulation of the external environment while maintaining the local interactions of endothelial cells with neighboring cells, including pericytes and macrophages as evidenced by immunohistochemistry and fluorescence-activated cell sorting (FACS) analysis. This reproducible ex vivo angiogenesis assay can be used to evaluate angiogenic potential of pharmacologic compounds on microvessels and can take advantage of genetically manipulated mouse tissue for microvascular disease research. PMID:23922736

  8. Choroidal coloboma in a case of tay-sachs disease.

    PubMed

    Ahmed, Nasreen Raees; Tripathy, Koushik; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated. PMID:25295204

  9. Focal choroidal excavation in patients with central serous chorioretinopathy

    PubMed Central

    Luk, F O J; Fok, A C T; Lee, A; Liu, A T W; Lai, T Y Y

    2015-01-01

    Purpose To evaluate the prevalence and clinical features of focal choroidal excavation (FCE) in patients presenting with central serous chorioretinopathy (CSC). Methods This is a retrospective consecutive case series of consecutive patients with CSC who were referred for spectral domain optical coherence tomography (SD-OCT) between January 2010 and December 2011. Medical records were reviewed and clinical features including presence of FCE in SD-OCT, fluorescence angiography (FA), and indocyanine green angiography (ICGA) were studied. Results Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%) patients. FCE was associated with subretinal fluid in six eyes of six patients and serous pigment epithelial detachment in three eyes of two patients. The mean central subfield retinal thickness of CSC eyes with FCE was 283.7 μm, compared with 377.5 μm for CSC eyes without FCE (Mann–Whitney U-test, P=0.020). Five FCE eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity of all 11 eyes with FCE remained stable or improved at the last follow-up. Conclusion FCE is not an uncommon feature in patients with CSC and might be associated with choroidal hemodynamic disturbances. PMID:25853402

  10. Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia.

    PubMed

    Marinescu, Ileana; Udriştoiu, I; Marinescu, D

    2013-01-01

    Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis. Neuroimaging shows that in patients with poor evolution, cognitive dysfunction and therapeutic resistance, the presence of choroid plexus calcification associated with hippocampal, frontal, temporoparietal and cerebellar atrophies. Antipsychotics with high capacity to block D2 dopamine receptors (haloperidol model) can aggravate apoptotic mechanisms of the brain areas involved in cognition and disrupts the functional integrity of the BBB due to decreased of choroid plexus blood flow because of the narrowing of cerebral small vessels. Choroid plexus calcification may be a predictive indicator of poor evolution or of a neurodegenerative type. PMID:23771083

  11. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma.

    PubMed

    Nakano, Satoko; Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro; Kubota, Toshiaki

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  12. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma

    PubMed Central

    Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  13. Vascular Guidance: Microstructural Scaffold Patterning for Inductive Neovascularization

    PubMed Central

    Muller, Daniel; Chim, Harvey; Bader, Augustinus; Whiteman, Matthew; Schantz, Jan-Thorsten

    2011-01-01

    Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examination of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept “vascular guidance,” whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology. PMID:21188080

  14. Accuracy of Corneal Power Measurements for Intraocular Lens Power Calculation after Myopic Laser In situ Keratomileusis

    PubMed Central

    Helaly, Hany A.; El-Hifnawy, Mohammad A. M.; Shaheen, Mohamed Shafik; Abou El-Kheir, Amr F.

    2016-01-01

    Purpose: To evaluate the accuracy of corneal power measurements for intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK). Methods: The study evaluated 45 eyes with a history of myopic LASIK. Corneal power was measured using manual keratometry, automated keratometry, optical biometry, and Scheimflug tomography. Different hypothetical IOL power calculation formulas were performed for each case. Results: The steepest mean K value was measured with manual keratometry (37.48 ± 2.86 D) followed by automated keratometry (37.31 ± 2.83 D) then optical biometry (37.06 ± 2.98 D) followed by Scheimflug tomography (36.55 ± 3.08). None of the K values generated by Scheimflug tomography were steeper than the measurements from the other 3 instruments. Using equivalent K reading (EKR) 4 mm with the Double-K SRK/T formula, the refractive outcome generated 97.8% of cases within ± 2 D, 80.0% of cases within ± 1 D, and 42.2% of cases within ± 0.5 D. The best combination of formulas was “Shammas-PL + Double-K SRK/T formula using EKR 4 mm.” Conclusion: Scheimflug tomography imaging using the Holladay EKR 4 mm improved the accuracy of IOL power calculation in post-LASIK eyes. The best option is a combination of formulas. We recommended the use the combined “Shammas-PL ± Double-K SRK/T formula using EKR 4 mm”h for optical outcomes. PMID:26957851

  15. Clinical Validation of Adjusted Corneal Power in Patients with Previous Myopic Lasik Surgery.

    PubMed

    Camps, Vicente J; Piñero, David P; Mateo, Veronica; García, Celia; Artola, Alberto; Pérez-Cambrodi, Rafael; Ruiz-Fortes, Pedro

    2015-01-01

    Purpose. To validate clinically a new method for estimating the corneal power (P c ) using a variable keratometric index (n kadj) in eyes with previous laser refractive surgery. Setting. University of Alicante and Medimar International Hospital (Oftalmar), Alicante, (Spain). Design. Retrospective case series. Methods. This retrospective study comprised 62 eyes of 62 patients that had undergone myopic LASIK surgery. An algorithm for the calculation of n kadj was used for the estimation of the adjusted keratometric corneal power (P kadj). This value was compared with the classical keratometric corneal power (P k ), the True Net Power (TNP), and the Gaussian corneal power (P cGauss). Likewise, P kadj was compared with other previously described methods. Results. Differences between P cGauss and P c values obtained with all methods evaluated were statistically significant (p < 0.01). Differences between P kadj and P cGauss were in the limit of clinical significance (p < 0.01, loA [-0.33,0.60] D). Differences between P kadj and TNP were not statistically and clinically significant (p = 0.319, loA [-0.50,0.44] D). Differences between P kadj and previously described methods were statistically significant (p < 0.01), except with P cHaigisL (p = 0.09, loA [-0.37,0.29] D). Conclusion. The use of the adjusted keratometric index (n kadj) is a valid method to estimate the central corneal power in corneas with previous myopic laser refractive surgery, providing results comparable to P cHaigisL. PMID:26528400

  16. Proinflammatory status in the aqueous humor of high myopic cataract eyes.

    PubMed

    Zhu, Xiangjia; Zhang, Keke; He, Wenwen; Yang, Jin; Sun, Xinghuai; Jiang, Chunhui; Dai, Jinhui; Lu, Yi

    2016-01-01

    High myopia has long been recognized as an inflammation-related disease, and high myopic eyes are thought to have a proinflammatory internal microenvironment, which might predispose to the occurrence of certain inflammation-related complications such as fibrotic capsular contraction syndrome after cataract surgery. Therefore, the purpose of this study was to detect inflammatory cytokines expressed in the aqueous humor (AH) of high myopic cataract (HMC) patients. The cytokines were screened using a RayBio Human Cytokine Antibody Array in AH samples from 15 age-related cataract (ARC) patients and 15 HMC patients. Those detected by the screening assays were verified using a Bio-Plex Suspension Array System in AH samples from 35 ARC patients and 45 HMC patients. The cytokine antibody array showed that the expression level of interleukin-1 receptor antagonist (IL-1ra) in the AH was higher in ARC than in HMC, whereas opposite trends were found for monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and presumably secreted (RANTES), IL-8, platelet-derived growth factor-BB, and IL-6 (all P < 0.05). In the verification assay using the suspension cytokine array, only the expression levels of IL-1ra and MCP-1 were significantly different between the ARC and HMC groups (P = 0.014 and 0.038, respectively); these results were confirmed by western blot assays. Our results demonstrated that the expression of IL-1ra was significantly lower and the expression of MCP-1 was significantly higher in the AH of HMC than in ARC, suggestive of a proinflammatory status in the anterior chamber of HMC eyes. PMID:25805322

  17. The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration

    PubMed Central

    Uehara, Hironori; Mamalis, Christina; McFadden, Molly; Taggart, Michael; Stagg, Brian; Passi, Samuel; Earle, Phillip; Chakravarthy, Usha; Hogg, Ruth E.; Ambati, Balamurali K.

    2014-01-01

    Purpose To evaluate serum soluble Flt-1 (sFlt-1) in age-related degeneration (AMD) patients. Design Case control study. Methods Fifty-six non-AMD participants, fifty-three early AMD patients and ninety-seven neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS. Results Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8±2.9 pg/mL (±SEM), 88.2±2.6 pg/mL and 79.9±2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, p<0.01). For each 10 point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decreases by 27.8% OR=0.722 (95% CI: 0.588-0.888, p=0.002) and 27.0% OR=0.730 (95% CI: 0.594–0.898, p=0.003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD. Conclusions Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD. PMID:25284761

  18. The role of biomaterial properties in peri-implant neovascularization

    NASA Astrophysics Data System (ADS)

    Raines, Andrew Lawrence

    An understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is critical in the design of next generation implants to improve osseointegration and clinical success rates. Critical to the process of osseointegration is the rapid establishment of a patent neovasculature in the peri-implant space to allow for the delivery of oxygen, nutrients, and progenitor cells. The central aim of this thesis is to understand how biomaterials regulate cellular and host tissue response to elicit a pro-angiogenic microenvironment at the implant/tissue interface. To address this question, the studies performed in this thesis aim to (1) determine whether biomaterial surface properties can modulate the production and secretion of pro-angiogenic growth factors by cells, (2) determine the role of integrin and VEGF-A signaling in the angiogenic response of cells to implant surface features, and (3) to determine whether neovascularization in response to an implanted biomaterial can be modulated in vivo. The results demonstrate that biomaterial surface microtopography and surface energy can increase the production of pro-angiogenic growth factors by osteoblasts and that these growth factors stimulate the differentiation of endothelial cells in a paracrine manner and the results suggest that signaling through specific integrin receptors affects the production of angiogenic growth factors by osteoblast-like cells. Further, using a novel in vivo model, the results demonstrate that a combination of a rough surface microtopography and high surface energy can improve bone-to-implant contact and neovascularization. The results of these studies also suggest that VEGF-A produced by osteoblast-like cells has both an autocrine and paracrine effect. VEGF-A silenced cells exhibited reduced production of both pro-angiogenic and osteogenic growth factors in response to surface microtopgraphy and surface energy, and conditioned media from VEGF

  19. Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease

    PubMed Central

    Kur, Joanna; Newman, Eric A.; Chan-Ling, Tailoi

    2012-01-01

    We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored. PMID:22580107

  20. Automated three-dimensional choroidal vessel segmentation of 3D 1060 nm OCT retinal data

    PubMed Central

    Kajić, Vedran; Esmaeelpour, Marieh; Glittenberg, Carl; Kraus, Martin F.; Honegger, Joachim; Othara, Richu; Binder, Susanne; Fujimoto, James G.; Drexler, Wolfgang

    2012-01-01

    A fully automated, robust vessel segmentation algorithm has been developed for choroidal OCT, employing multiscale 3D edge filtering and projection of “probability cones” to determine the vessel “core”, even in the tomograms with low signal-to-noise ratio (SNR). Based on the ideal vessel response after registration and multiscale filtering, with computed depth related SNR, the vessel core estimate is dilated to quantify the full vessel diameter. As a consequence, various statistics can be computed using the 3D choroidal vessel information, such as ratios of inner (smaller) to outer (larger) choroidal vessels or the absolute/relative volume of choroid vessels. Choroidal vessel quantification can be displayed in various forms, focused and averaged within a special region of interest, or analyzed as the function of image depth. In this way, the proposed algorithm enables unique visualization of choroidal watershed zones, as well as the vessel size reduction when investigating the choroid from the sclera towards the retinal pigment epithelium (RPE). To the best of our knowledge, this is the first time that an automatic choroidal vessel segmentation algorithm is successfully applied to 1060 nm 3D OCT of healthy and diseased eyes. PMID:23304653

  1. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  2. Angiogenesis in glaucoma filtration surgery and neovascular glaucoma: A review.

    PubMed

    Kim, Megan; Lee, Chelsea; Payne, Rachael; Yue, Beatrice Y J T; Chang, Jin-Hong; Ying, Hongyu

    2015-01-01

    Angiogenesis may pose a clinical challenge in glaucoma, for example, during the wound healing phase after glaucoma filtration surgery and in the severe secondary glaucoma called neovascular glaucoma (NVG). Upregulation of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, occurs in eyes that have undergone glaucoma filtration surgery, as well as those with NVG. This has led investigation of the ability of anti-vascular endothelial growth factor therapy to improve outcomes, and we examine the findings with respect to the safety and efficacy of anti-vascular endothelial growth factor agents, mainly bevacizumab and ranibizumab, in eyes that have undergone glaucoma filtration surgery or have NVG. Combining conventional therapies-such as antimetabolites after filtration surgery and panretinal photocoagulation in NVG-and anti-vascular endothelial growth factor drugs may produce a synergetic effect, although further studies are required to evaluate the long-term efficacy of combination treatments. PMID:25980779

  3. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    PubMed

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats. PMID:26348484

  4. Choroidal malignant melanoma with no extraocular extension presenting as orbital cellulitis.

    PubMed

    Nalcaci, Serhad; Palamar, Melis; Yaman, Banu; Akalin, Taner; Mentes, Jale

    2016-10-01

    This report describes a patient with choroidal malignant melanoma presenting as orbital cellulitis without extraocular tumor extension. It is an interventional case report with histopathologic correlation. A 68-year-old male presented with a 3-day history of painful hyperemia and swelling in the right eye. The examination showed edematous eyelids, mechanical ptosis and chemosis with conjunctival injection. B-scan ultrasonography showed a mass with medium level echogenicity that filled the vitreous cavity. Magnetic resonance imaging showed a solid choroidal mass with hemorrhagic and inflammatory changes with no obvious extraocular extension. Due to these suggestive findings of choroidal melanoma the right eye was enucleated. A spindle cell choroidal melanoma including intense pigmentation and necrosis was confirmed by histopathological examination. Although rare; choroidal melanoma may present as orbital cellulitis, particularly when the tumor is necrotic. PMID:27463451

  5. Choroidal Blood-Flow Responses to Hyperoxia and Hypercapnia in Men with Obstructive Sleep Apnea

    PubMed Central

    Tonini, Matthieu; Khayi, Hafid; Pepin, Jean-Louis; Renard, Elisabeth; Baguet, Jean-Philippe; Lévy, Patrick; Romanet, Jean-Paul; Geiser, Martial H.; Chiquet, Christophe

    2010-01-01

    Study Objectives: Obstructive sleep apnea (OSA) impacts on macrovasculature and autonomic function and may therefore interfere with ocular microvascular regulation. We hypothesized that choroidal vascular reactivity to hyperoxia and hypercapnia was altered in patients with OSA compared with matched control subjects and would improve after treatment with continuous positive airway pressure (CPAP). Methods: Sixteen healthy men were matched 1:1 for body mass index, sex, and age with 16 men with newly diagnosed OSA without comorbidities. Subjects underwent sleep studies, 24-hour blood pressure monitoring, arterial stiffness measurements, and cardiac and carotid echography. Overall, patients were middle-aged, lean, and otherwise healthy except for having OSA with a limited amount of desaturation, with, at most, subclinical lesions of the cardiovascular system, stage 1 hypertension, or both. Choroidal laser Doppler flowmetry provides a unique opportunity to assess microvascular function by measuring velocity, (ChBVel), volume (ChBVol), and relative subfoveal choroidal blood flow (ChBF). Vascular choroidal reactivity was studied during hyperoxia and hypercapnia (8% CO2) challenges before and after treatment with nasal CPAP. Results: Patients with OSA and control subjects exhibited similar choroidal reactivity during hyperoxia (stability of choroidal blood flow) and hypercapnia (significant increases in ChBVel of 13.5% and in ChBF of 16%). Choroidal vasoreactivity to CO2 was positively associated with arterial stiffness in patients with OSA. Gas choroidal vasoreactivity was unchanged after 6 to 9 months of CPAP treatment. Conclusion: This study showed unimpaired choroidal vascular reactivity in otherwise healthy men with OSA. This suggests that patients with OSA, without comorbidities, have long-term adaptive mechanisms active in ocular microcirculation. Citation: Tonini M; Khayi H; Pepin JL; Renard E; Baguet JP; Lévy P; Romanet JP; Geiser MH; Chiquet C. Choroidal blood

  6. Three-dimensional choroidal segmentation in spectral OCT volumes using optic disc prior information

    NASA Astrophysics Data System (ADS)

    Hu, Zhihong; Girkin, Christopher A.; Hariri, Amirhossein; Sadda, SriniVas R.

    2016-03-01

    Recently, much attention has been focused on determining the role of the peripapillary choroid - the layer between the outer retinal pigment epithelium (RPE)/Bruchs membrane (BM) and choroid-sclera (C-S) junction, whether primary or secondary in the pathogenesis of glaucoma. However, the automated choroidal segmentation in spectral-domain optical coherence tomography (SD-OCT) images of optic nerve head (ONH) has not been reported probably due to the fact that the presence of the BM opening (BMO, corresponding to the optic disc) can deflect the choroidal segmentation from its correct position. The purpose of this study is to develop a 3D graph-based approach to identify the 3D choroidal layer in ONH-centered SD-OCT images using the BMO prior information. More specifically, an initial 3D choroidal segmentation was first performed using the 3D graph search algorithm. Note that varying surface interaction constraints based on the choroidal morphological model were applied. To assist the choroidal segmentation, two other surfaces of internal limiting membrane and innerouter segment junction were also segmented. Based on the segmented layer between the RPE/BM and C-S junction, a 2D projection map was created. The BMO in the projection map was detected by a 2D graph search. The pre-defined BMO information was then incorporated into the surface interaction constraints of the 3D graph search to obtain more accurate choroidal segmentation. Twenty SD-OCT images from 20 healthy subjects were used. The mean differences of the choroidal borders between the algorithm and manual segmentation were at a sub-voxel level, indicating a high level segmentation accuracy.

  7. The choroid plexus response to a repeated peripheral inflammatory stimulus

    PubMed Central

    2009-01-01

    Background Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid. Results In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection. Conclusion These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated. PMID:19922669

  8. Studies on the human choroid plexus in vitro.

    PubMed

    Redzic, Zoran B

    2013-01-01

    The role of human choroid plexus (CP) epithelium in the transport of solutes between the blood and the cerebrospinal fluid and/or in secretion processes may be studied by employing several experimental approaches. There are a number of in vitro techniques for human CP epithelium (CPE) and all have limitations that do not exclude them a priori, but that should be carefully taken into consideration. Developmental and morphological studies have been largely performed on human choroid plexus samples of either embryonic or post-mortem origin. Functional uptake studies may be performed on pathologically unaltered CP samples obtained during surgical removal of choroid plexus tumors. This approach can be used to explore transport processes mainly across the apical side of the CPE, but cannot be used to study vectorial transport across the CPE. Also, these samples have limited viability. A monolayer of CPE in culture, grown on permeable supports, provides the best available tool to study transport processes or polarized secretion by the CP, but thus far only limited attempts to culture these cells have been published and they mainly include data from neoplastic CPE. A study that used a human papilloma-derived cell line in culture showed that it forms a monolayer with barrier properties, although the cells express pleomorphic and neoplastic features and lack contact inhibition. Other cell cultures express some CPE markers but do not develop tight junctions/barrier properties. This article reviews the main characteristics and limitations of available in vitro methods to study human CPE, which could help researchers choose an appropriate experimental approach for a particular study. PMID:23391221

  9. Choriocapillaris and Choroidal Microvasculature Imaging with Ultrahigh Speed OCT Angiography

    PubMed Central

    Choi, WooJhon; Mohler, Kathrin J.; Potsaid, Benjamin; Lu, Chen D.; Liu, Jonathan J.; Jayaraman, Vijaysekhar; Cable, Alex E.; Duker, Jay S.; Huber, Robert; Fujimoto, James G.

    2013-01-01

    We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning ∼32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and ∼6 mm nasal to the fovea at the depths of the choriocapillaris and Sattler's layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging. PMID:24349078

  10. Efficacy and Acceptability of Orthokeratology for Slowing Myopic Progression in Children: A Systematic Review and Meta-Analysis

    PubMed Central

    Wen, Daizong; Huang, Jinhai; Chen, Hao; Bao, Fangjun; Savini, Giacomo; Calossi, Antonio; Chen, Haisi; Li, Xuexi; Wang, Qinmei

    2015-01-01

    Background. To evaluate the efficacy and acceptability of orthokeratology for slowing myopic progression in children with a well conducted evidence-based analysis. Design. Meta-analysis. Participants. Children from previously reported comparative studies were treated by orthokeratology versus control. Methods. A systematic literature retrieval was conducted in MEDLINE, EMBASE, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The included studies were subjected to meta-analysis using Stata version 10.1. Main Outcome Measures. Axial length change (efficacy) and dropout rates (acceptability) during 2-year follow-up. Results. Eight studies involving 769 subjects were included. At 2-year follow-up, a statistically significant difference was observed in axial length change between the orthokeratology and control groups, with a weighted mean difference (WMD) of −0.25 mm (95% CI, −0.30 to −0.21). The pooled myopic control rate declined with time, with 55, 51, 51, and 41% obtained after 6, 12, 18, and 24 months of treatment, respectively. No statistically significant difference was obtained for dropout rates between the orthokeratology and control groups at 2-year follow-up (OR, 0.79; 95% CI, 0.52 to 1.22). Conclusions. Orthokeratology is effective and acceptable for slowing myopic progression in children with careful education and monitoring. PMID:26221539

  11. Comparison of Astigmatic Correction after Femtosecond Lenticule Extraction and Small-Incision Lenticule Extraction for Myopic Astigmatism

    PubMed Central

    Kobashi, Hidenaga; Kamiya, Kazutaka; Ali, Mohamed A.; Igarashi, Akihito; Elewa, Mohamed Ehab M.; Shimizu, Kimiya

    2015-01-01

    Purpose To compare postoperative astigmatic correction between femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) in eyes with myopic astigmatism. Methods We examined 26 eyes of 26 patients undergoing FLEx and 26 eyes of 26 patients undergoing SMILE to correct myopic astigmatism (manifest astigmatism of 1 diopter (D) or more). Visual acuity, cylindrical refraction, the predictability of the astigmatic correction, and the astigmatic vector components using Alpin’s method, were compared between the two groups 3 months postoperatively. Results We found no statistically significant difference in manifest cylindrical refraction (p=0.74) or in the percentage of eyes within ± 0.50 D of their refraction (p=0.47) after the two surgical procedures. Moreover, no statistically significant difference was detected between the groups in astigmatic vector components, namely, surgically induced astigmatism (0.80), target induced astigmatism (p=0.87), astigmatic correction index (p=0.77), angle of error (p=0.24), difference vector (p=0.76), index of success (p=0.91), flattening effect (p=0.79), and flattening index (p=0.84). Conclusions Both FLEx and SMILE procedures are essentially equivalent in correcting myopic astigmatism using vector analysis, suggesting that the lifting or non-lifting of the flap does not significantly affect astigmatic outcomes after these surgical procedures. PMID:25849381

  12. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  13. Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma

    PubMed Central

    Béliveau-Nadeau, Dominic; Callejo, Sonia

    2016-01-01

    Radiotherapy has a long history in the organ-sparing management of choroidal melanoma. Joining plaque radiotherapy and proton irradiation, stereotactic robotic photon irradiation is a new tool in the radiation oncologist’s armamentarium for ocular tumors. The non-coplanar fields with steep dose gradients are well suited to spare uninvolved retina, anterior chamber, and the optic nerve. In our practice, it is the preferred treatment for melanomas that are non-amenable to standard plaque brachytherapy. Since late 2010, we have treated more than 40 patients with our robotic linear accelerator. This case-based technical note outlines the technique used at the University of Montreal, Montreal, Canada. PMID:27226942

  14. Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

    PubMed Central

    Kondo, Tatsuya; Vicent, David; Suzuma, Kiyoshi; Yanagisawa, Masashi; King, George L.; Holzenberger, Martin; Kahn, C. Ronald

    2003-01-01

    Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell–specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process. PMID:12813019

  15. Ten-Year Changes in Fusional Vergence, Phoria, and Nearpoint of Convergence in Myopic Children

    PubMed Central

    Anderson, Heather; Stuebing, Karla K.; Fern, Karen D.; Manny, Ruth E.

    2013-01-01

    Purpose To identify longitudinal changes in fusional vergence ranges and their relationship to other clinical measures in young myopic subjects. Methods Measurements were collected annually for 10 years on 114 subjects from the University of Houston Correction of Myopia Evaluation Trial cohort. Subject age was 7 to 13 years at year 1 of follow-up. Measurements included refractive error, distance and near phoria, interpupillary distance (IPD), prism bar fusional vergence ranges, and nearpoint of convergence (NPC). Multilevel modeling was used to determine baseline and rate of change for fusional vergence ranges and the impact of phoria, IPD, and NPC on these measures. Results Year 1 mean distance base-out (BO) break was 20 prism diopters (pd) and decreased 5.6 pd over 10 years (p <0.001). Mean near BO break was 30 pd at year 1 and decreased 9.4 pd over 10 years (p < 0.001). Greater esophoria was significantly related to greater BO break (p < 0.02) and receded NPC was significantly related to lower magnitude BO break at near (p < 0.001). Distance IPD increased 3 mm over 10 years (p < 0.001) but was unrelated to the magnitude of the BO ranges (p > 0.2). Mean distance base-in (BI) break was 7 pd at year 1 and increased 0.5 pd in 10 years (p = 0.04). Mean near BI break was 13 pd at year 1 and did not significantly change. Mean distance phoria was 0.1 pd exophoria at year 1 and did not change, whereas near phoria was 2.4 pd esophoria at year 1 and became more exophoric (4 pd in 10 years, p < 0.001). Conclusions These results suggest that for myopic children convergence ranges decrease for both distance and near viewing during the school years as near phoria becomes more exophoric. These findings could have clinical implications given that compensating convergence ranges decrease as near phoria becomes more divergent. PMID:21623250

  16. Analysis of Normal Peripapillary Choroidal Thickness via Spectral Domain Optical Coherence Tomography

    PubMed Central

    Ho, Joseph; Branchini, Lauren; Regatieri, Caio; Krishnan, Chandrasekharan; Fujimoto, James G.; Duker, Jay S.

    2011-01-01

    PURPOSE To analyze the normal peripapillary choroidal thickness utilizing a commercial spectral domain optical coherence tomography (OCT) device and determine the inter-grader reproducibility of this method. DESIGN Retrospective, non-comparative, non-interventional case series. PARTICIPANTS Thirty-six eyes of 36 normal patients seen at the New England Eye Center between April and September 2010. METHODS All patients underwent high-definition scanning with the Cirrus HD-OCT. Two raster scans were obtained per eye, a horizontal and a vertical scan, both of which were centered at the optic nerve. Two independent graders individually measured the choroidal thickness. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500 μm intervals away from the optic nerve in the superior, inferior, nasal and temporal quadrants. Statistical analysis was conducted to compare mean choroidal thicknesses. Inter-grader reproducibility was assessed by intraclass correlation coefficient and Pearson’s correlation coefficient. Average choroidal thickness in each quadrant was compared to retinal nerve fiber layer (RNFL) thickness in their respective quadrants. MAIN OUTCOME MEASURES Peripapillary choroidal thickness, intraclass coefficient, Pearson’s correlation coefficient. RESULTS The peripapillary choroid in the inferior quadrant was significantly thinner compared to all other quadrants (p< 0.001). None of the other quadrants were significantly different from each other in terms of thickness. The inferior peripapillary choroid was significantly thinner compared to all other quadrants at all distances measured away from the optic nerve (p< 0.001). Generally, the peripapillary choroid increases in thickness the farther it was away from the optic nerve and eventually approaching a plateau. Intraclass correlation coefficient ranged from 0.62 to 0.93 and Pearson’s correlation coefficient ranged from 0.74 to 0.95 (p

  17. Myopia and Inflammation

    PubMed Central

    Herbort, Carl P.; Papadia, Marina; Neri, Piergiorgio

    2011-01-01

    The correlation between myopia and intraocular inflammation has rarely been explored. The aim of this article is to review myopic changes induced by inflammatory diseases and inflammatory diseases related to myopia, followed by a discussion on inflammatory choroidal neovascularization. Clinical cases are used to illustrate these conditions. The review does not include inflammatory conditions caused by surgical interventions employed for treatment of myopia. Uveitic conditions that can induce a myopic shift include sclero-choroidal inflammation, lens induced myopia due to steroid cataracts, juvenile idiopathic arthritis (JIA) induced myopia, and transient drug induced myopia due to sulfonamides and acetazolamide used for treatment of ocular toxoplasmosis and inflammatory cystoid macular edema, respectively. Most inflammatory conditions related to myopia are conditions involving the choriocapillaris. These include multifocal choroiditis and/or punctate inner choroiditis, multiple evanescent white dot syndrome and acute idiopathic blind spot enlargement. It can be hypothesized that fragility of the choriocapillaris due to particular anatomic changes due to myopia, together with unknown immunogenetic factors predispose myopic eyes to primary inflammatory choriocapillaropathies. PMID:22454750

  18. Myopia and inflammation.

    PubMed

    Herbort, Carl P; Papadia, Marina; Neri, Piergiorgio

    2011-10-01

    The correlation between myopia and intraocular inflammation has rarely been explored. The aim of this article is to review myopic changes induced by inflammatory diseases and inflammatory diseases related to myopia, followed by a discussion on inflammatory choroidal neovascularization. Clinical cases are used to illustrate these conditions. The review does not include inflammatory conditions caused by surgical interventions employed for treatment of myopia. Uveitic conditions that can induce a myopic shift include sclero-choroidal inflammation, lens induced myopia due to steroid cataracts, juvenile idiopathic arthritis (JIA) induced myopia, and transient drug induced myopia due to sulfonamides and acetazolamide used for treatment of ocular toxoplasmosis and inflammatory cystoid macular edema, respectively. Most inflammatory conditions related to myopia are conditions involving the choriocapillaris. These include multifocal choroiditis and/or punctate inner choroiditis, multiple evanescent white dot syndrome and acute idiopathic blind spot enlargement. It can be hypothesized that fragility of the choriocapillaris due to particular anatomic changes due to myopia, together with unknown immunogenetic factors predispose myopic eyes to primary inflammatory choriocapillaropathies. PMID:22454750

  19. Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy

    PubMed Central

    Zhou, Yedi; Yoshida, Shigeo; Kubo, Yuki; Kobayashi, Yoshiyuki; Nakama, Takahito; Yamaguchi, Muneo; Ishikawa, Keijiro; Nakao, Shintaro; Ikeda, Yasuhiro; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2016-01-01

    Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization. PMID:27312090

  20. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

    SciTech Connect

    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra; Sasaki, Ken-ichiro; Bruhl, Thomas; Hofmann, Wolf K.; Peters, Christoph; Reinheckel, Thomas; Pennacchio, Len A.; Abolmaali, Nasreddin D.; Chavakis, Emmanouil; Zeiher, Andreas M.; Dimmeler, Stefanie

    2004-01-15

    Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sites of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.

  1. Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy.

    PubMed

    Zhou, Yedi; Yoshida, Shigeo; Kubo, Yuki; Kobayashi, Yoshiyuki; Nakama, Takahito; Yamaguchi, Muneo; Ishikawa, Keijiro; Nakao, Shintaro; Ikeda, Yasuhiro; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2016-01-01

    Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization. PMID:27312090

  2. Femtosecond laser-assisted selective reduction of neovascularization in rat cornea.

    PubMed

    Sidhu, Mehra S; Choi, Min-Yeong; Woo, Suk-Yi; Lee, Hyun-Kyu; Lee, Heung-Soon; Kim, Kyu-Jin; Jeoung, Sae Chae; Choi, Jun-Sub; Joo, Choun-Ki; Park, Il-Hong

    2014-07-01

    Nonlinear multiphoton absorption induced by focusing near infrared (NIR) femtosecond (fs) laser pulses into a transparent cornea allows surgery on neovascular structures with minimal collateral damage. In this report, we introduce an fs laser-based microsurgery for selective treatment of rat corneal neovascularizations (in vivo). Contiguous tissue effects are achieved by scanning a focused laser pulse below the corneal surface with a fluence range of 2.2-8.6 J/cm(2). The minimal visible laser lesion (MVL) threshold determined over the corneal neovascular structures was found to be 4.3 J/cm(2). Histological and optical coherence tomography examinations of the anterior segment after laser irradiations show localized degeneration of neovascular structures without any unexpected change in adjacent tissues. Furthermore, an approximately 30 % reduction in corneal neovascularizations was observed after 5 days of fs laser exposure. The femtosecond laser is thus a promising tool for minimally invasive intrastromal surgery with the aid of a significantly smaller and more deterministic photodisruptive energy threshold for the interaction between the fs laser pulse and corneal neovascular structures. PMID:24570086

  3. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

    PubMed Central

    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Chárthaigh, Róisín-Ana Ní; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2016-01-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease. PMID:25894826

  4. Decreased choroidal thickness in eyes with secondary angle closure glaucoma. An aetiological factor for deep retinal changes in glaucoma?

    PubMed Central

    Kubota, T.; Jonas, J. B.; Naumann, G. O.

    1993-01-01

    A decreased count of retinal photoreceptors all over the fundus and a loss of retinal pigment epithelium cells mainly in the parapapillary region have been reported to be associated with glaucoma. This study addressed the question whether this cell loss in the deep retinal layers may be connected with a change of the choroidal thickness in glaucomatous eyes. Histological sections of 12 eyes with secondary angle closure glaucoma due to a malignant melanoma of the ciliary body and 20 eyes with a malignant choroidal melanoma and normal intraocular pressure were histomorphometrically evaluated. Before enucleation the intraocular pressure was significantly higher in the glaucoma group compared with the control group. Thickness of the choroid was measured at 12 locations from the posterior pole to the fundus periphery. The choroid was significantly thinner in the glaucoma group than in the control group. The decreased choroidal thickness was mainly due to a diminished choroidal vessel diameter. The differences were more marked at the optic disc border than in the fundus periphery. The decreased choroidal thickness in the glaucomatous eyes suggests a reduced choroidal perfusion. It fits with the reported lack of autoregulation of the choroidal blood circulation. Considering the diminished choroidal thickness especially in the parapapillary region, it may be one among other factors explaining the changes of the deep retinal layers in eyes with glaucoma. It indicates that thinning of the choroid, besides the chorioretinal atrophy in the parapapillary region, should be added to the panoply of histological changes in glaucoma. Images PMID:8343472

  5. Accuracy of Intraocular Lens Power Calculation Formulas for Highly Myopic Eyes.

    PubMed

    Zhang, Yichi; Liang, Xiao Ying; Liu, Shu; Lee, Jacky W Y; Bhaskar, Srinivasan; Lam, Dennis S C

    2016-01-01

    Purpose. To evaluate and compare the accuracy of different intraocular lens (IOL) power calculation formulas for eyes with an axial length (AL) greater than 26.00 mm. Methods. This study reviewed 407 eyes of 219 patients with AL longer than 26.0 mm. The refractive prediction errors of IOL power calculation formulas (SRK/T, Haigis, Holladay, Hoffer Q, and Barrett Universal II) using User Group for Laser Interference Biometry (ULIB) constants were evaluated and compared. Results. One hundred seventy-one eyes were enrolled. The Barrett Universal II formula had the lowest mean absolute error (MAE) and SRK/T and Haigis had similar MAE, and the statistical highest MAE were seen with the Holladay and Hoffer Q formulas. The interquartile range of the Barrett Universal II formula was also the lowest among all the formulas. The Barrett Universal II formulas yielded the highest percentage of eyes within ±1.0 D and ±0.5 D of the target refraction in this study (97.24% and 79.56%, resp.). Conclusions. Barrett Universal II formula produced the lowest predictive error and the least variable predictive error compared with the SRK/T, Haigis, Holladay, and Hoffer Q formulas. For high myopic eyes, the Barrett Universal II formula may be a more suitable choice. PMID:27119018

  6. Accuracy of Intraocular Lens Power Calculation Formulas for Highly Myopic Eyes

    PubMed Central

    Zhang, Yichi; Liang, Xiao Ying; Liu, Shu; Lee, Jacky W. Y.; Bhaskar, Srinivasan; Lam, Dennis S. C.

    2016-01-01

    Purpose. To evaluate and compare the accuracy of different intraocular lens (IOL) power calculation formulas for eyes with an axial length (AL) greater than 26.00 mm. Methods. This study reviewed 407 eyes of 219 patients with AL longer than 26.0 mm. The refractive prediction errors of IOL power calculation formulas (SRK/T, Haigis, Holladay, Hoffer Q, and Barrett Universal II) using User Group for Laser Interference Biometry (ULIB) constants were evaluated and compared. Results. One hundred seventy-one eyes were enrolled. The Barrett Universal II formula had the lowest mean absolute error (MAE) and SRK/T and Haigis had similar MAE, and the statistical highest MAE were seen with the Holladay and Hoffer Q formulas. The interquartile range of the Barrett Universal II formula was also the lowest among all the formulas. The Barrett Universal II formulas yielded the highest percentage of eyes within ±1.0 D and ±0.5 D of the target refraction in this study (97.24% and 79.56%, resp.). Conclusions. Barrett Universal II formula produced the lowest predictive error and the least variable predictive error compared with the SRK/T, Haigis, Holladay, and Hoffer Q formulas. For high myopic eyes, the Barrett Universal II formula may be a more suitable choice. PMID:27119018

  7. [Refractive development and form-deprivation induced myopic refractive error in CBA/CaJ mice].

    PubMed

    Li, Yun-Yun; Qian, Kang-Wei; Wu, Xiao-Hua; Zhou, Wei; Zhong, Yong-Mei; Weng, Shi-Jun

    2016-04-25

    Due to the advantages in genetic manipulation, mice have become one of the most commonly used mammalian models for the study of mechanisms underlying myopia development. However, the vast majority of laboratory mouse strains are incapable of synthesizing melatonin, a neurohormone that may play an important role in myopia generation in humans. The present study investigated refractive development profiles in the CBA/CaJ mouse, a strain proficient in melatonin, and determined whether and how its refractive development could be affected by form-deprivation. Eccentric infrared photoretinoscopy revealed that this animal could be stably refracted, and the refractive error underwent developmental changes, which increased with age in the hyperopic direction and eventually got stable approximately 9 weeks after birth. The absolute values of refractive error in CBA/CaJ mice were larger than those of age-matched C57BL/6 mice, whereas the time points when refractive error reached steady state were similar between the two strains. Five weeks of form-deprivation applied to 3-week-old CBA/CaJ mice by translucent occluder wear caused a significant myopic shift in refractive error, indicating that this strain could be adequately used as a myopia model. PMID:27108899

  8. The Myopic-Ubpy-Hrs nexus enables endosomal recycling of Frizzled

    PubMed Central

    Pradhan-Sundd, Tirthadipa; Verheyen, Esther M.

    2015-01-01

    Endosomal trafficking of signaling proteins plays an essential role in cellular homeostasis. The seven-pass transmembrane protein Frizzled (Fz) is a critical component of Wnt signaling. Although Wnt signaling is proposed to be regulated by endosomal trafficking of Fz, the molecular events that enable this regulation are not completely understood. Here we show that the endosomal protein Myopic (Mop) regulates Fz trafficking in the Drosophila wing disk by inhibiting the ubiquitination and degradation of Hrs. Deletion of Mop or Hrs results in endosomal accumulation of Fz and therefore reduced Wnt signaling. The in situ proximity ligation assay revealed a strong association between Mop and Hrs in the Drosophila wing disk. Overexpression of Hrs rescues the trafficking defect caused by mop knockdown. Mop aids in the maintenance of Ubpy, which deubiquitinates (and thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is dispensable. These findings support a previously unknown role for Mop in endosomal trafficking of Fz in Wnt-receiving cells. PMID:26224310

  9. The p75 neurotrophin receptor localization in blood-CSF barrier: expression in choroid plexus epithelium

    PubMed Central

    2011-01-01

    Background The presence of neurotrophins and their receptors Trk family has been reported in the choroid plexus. High levels of Nerve Growth Factor (NGF), Neurotrophin-4 (NT-4) and TrkB receptor were detected, while nothing was know about p75 neurotrophin receptor (p75NTR) in the choroid plexus epithelial cells. In neurons, p75NTR receptor has a dual function: promoting survival together with TrkA in response to NGF, and inducing apoptotic signaling through p75NTR. We postulated that p75NTR may also affect the survival pathways in the choroid plexus and also undergoes regulated proteolysis with metalloproteases. Results Here, we demonstrated the presence of p75NTR receptor in the choroid plexus epithelial cells. The p75NTR receptor would be involved in cell death mechanisms and in the damaged induced by amyloid beta (Aβ) in the choroid plexus and finally, we propose an essential role of p75NTR in the Aβ transcytosis through out choroid plexus barrier. Conclusions The presence analysis reveals the new localization of p75NTR in the choroid plexus and, the distribution mainly in the cytoplasm and cerebrospinal fluid (CSF) side of the epithelial cells. We propose that p75NTR receptor plays a role in the survival pathways and Aβ-induced cell death. These data suggest that p75NTR dysfunction play an important role in the pathogenesis of brain diseases. The importance and novelty of this expression expands a new role of p75NTR. PMID:21569322

  10. CHOROIDAL THICKNESS IN PATIENTS WITH DIABETIC RETINOPATHY ANALYZED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    REGATIERI, CAIO V.; BRANCHINI, LAUREN; CARMODY, JILL; FUJIMOTO, JAMES G.; DUKER, JAY S.

    2012-01-01

    Purpose This study was designed to examine choroidal thickness in patients with diabetes using spectral-domain optical coherence tomography. Methods Forty-nine patients (49 eyes) with diabetes and 24 age-matched normal subjects underwent high-definition raster scanning using spectral-domain optical coherence tomography with frame enhancement software. Patients with diabetes were classified into 3 groups: 11 patients with mild or moderate nonproliferative diabetic retinopathy and no macular edema, 18 patients with nonproliferative diabetic retinopathy and diabetic macular edema, and 20 patients with treated proliferative diabetic retinopathy and no diabetic macular edema (treated proliferative diabetic retinopathy). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-μm intervals up to 2,500 μm temporal and nasal to the fovea. Results Reliable measurements of choroidal thickness were obtainable in 75.3% of eyes examined. Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and thinning again temporally in normal subjects and patients with diabetes. Mean subfoveal choroidal thickness was thinner in patients with diabetic macular edema (63.3 μm, 27.2%, P < 0.05) or treated proliferative diabetic retinopathy (69.6 μm, 30.0%, P < 0.01), compared with normal subjects. There was no difference between nonproliferative diabetic retinopathy and normal subjects. Conclusion Choroidal thickness is altered in diabetes and may be related to the severity of retinopathy. Presence of diabetic macular edema is associated with a significant decrease in the choroidal thickness. PMID:22374157

  11. Photodynamic therapy for diffuse choroidal hemangioma in a child with Sturge-Weber syndrome.

    PubMed

    Nugent, Ryan; Lee, Lawrence; Kwan, Anthony

    2015-04-01

    Sturge-Weber syndrome is a rare neurocutaneous disorder involving the leptomeninges, skin of the face, and, in 40% of cases, diffuse choroidal hemangioma. We report the case of a 6-year-old girl with Sturge-Weber syndrome and a large diffuse choroidal hemangioma with retinal detachment involving the majority of the retina. The patient underwent photodynamic therapy. The retinal detachment resolved completely within 3 months of treatment. This case represents the youngest patient in the literature to undergo successful treatment with photodynamic therapy for Sturge-Weber syndrome-associated diffuse choroidal hemangioma. PMID:25828818

  12. Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus

    SciTech Connect

    Muccioli, G.; Guardabassi, A.; Pattono, P. )

    1990-03-01

    The occurrence of prolactin binding sites in some brain structures (telencephalon, ventral hypothalamus, myelencephalon, hypophysis, and choroid plexus) from Xenopus laevis (anuran amphibian) was studied by the in vitro biochemical technique. The higher binding values were obtained at the level of the choroid plexus and above all of the hypothalamus. On the bases of hormonal specificity and high affinity, these binding sites are very similar to those of prolactin receptors of classical target tissues as well as of those described by us in other structures from Xenopus. To our knowledge, the present results provide the first demonstration of the occurrence of prolactin specific binding sites in Xenopus laevis choroid plexus cells.

  13. [The use of aflibercept (Eylea) in the treatment of polypoidal choroidal vasculopathy--case report].

    PubMed

    Glasner, Paulina; Raczyńska, Dorota; Glasner, Leopold

    2015-01-01

    The paper presents a case of a 25-year-old woman referred to the Outpatient Clinic at the Department of Ophthalmology, University Clinical Centre in Gdansk, with sudden vision impairment in her right eye. Clinical manifestation and diagnostic tests gave a basis for the preliminary diagnosis of polypoidal choroidal vasculopathy. Polypoidal choroidal vasculopathy is a type of choroidal neovascularisation, frequently confused with age-related macular degeneration. Standard treatment includes photodynamic therapy and intravitreal injections of anti-vascular endothelial growth factor agents. 2.0 miligrams of aflibercept was administered as an intravitreal injection, causing a rapid, significant improvement of visual function and proper anatomical relationships within the retina. PMID:26999944

  14. Efficacy and Safety of Topical Timolol Eye Drops in the Treatment of Myopic Regression after Laser In Situ Keratomileusis: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Xiaochen; Zhao, Guiqiu; Lin, Jing; Jiang, Nan; Wang, Qian; Xu, Qiang

    2015-01-01

    Aims. The aim of this study was to assess the efficacy and safety of timolol in the treatment of myopic regression after laser in situ keratomileusis (LASIK). Methods. We searched MEDLINE, CENTRAL, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) from the inception to July 2015 for relevant randomized controlled trials that examined timolol therapy for myopic regression. The methodological quality of the studies included was assessed using the Revman 5.3 software. Results. We included six clinical trials involving 483 eyes in this review, including 246 eyes in treated group and 237 eyes in controlled group. We observed statistically significant improvements on the postoperative SE in the 3 months. However, the change of CCT was not statistically different between the control group and the experimental group. There were fewer cases of IOP, UDVA, and CDVA in treated group having significant difference from the controlled group. Conclusions. Topical timolol could be an effective treatment for reduction of myopic regression especially the spherical errors after myopic LASIK. Further RCTs with larger sample sizes for these trials are warranted to determine the efficacy and limitation for myopic regression after LASIK. PMID:26798507

  15. Overload and neovascularization of shoulder tendons in volleyball players

    PubMed Central

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  16. Smart social adaptation prevents catastrophic ecological regime shifts in networks of myopic harvesters

    NASA Astrophysics Data System (ADS)

    Donges, Jonathan; Lucht, Wolfgang; Wiedermann, Marc; Heitzig, Jobst; Kurths, Jürgen

    2015-04-01

    In the anthropocene, the rise of global social and economic networks with ever increasing connectivity and speed of interactions, e.g., the internet or global financial markets, is a key challenge for sustainable development. The spread of opinions, values or technologies on these networks, in conjunction with the coevolution of the network structures themselves, underlies nexuses of current concern such as anthropogenic climate change, biodiversity loss or global land use change. To isolate and quantitatively study the effects and implications of network dynamics for sustainable development, we propose an agent-based model of information flow on adaptive networks between myopic harvesters that exploit private renewable resources. In this conceptual model of a network of socio-ecological systems, information on management practices flows between agents via boundedly rational imitation depending on the state of the resource stocks involved in an interaction. Agents can also adapt the structure of their social network locally by preferentially connecting to culturally similar agents with identical management practices and, at the same time, disconnecting from culturally dissimilar agents. Investigating in detail the statistical mechanics of this model, we find that an increasing rate of information flow through faster imitation dynamics or growing density of network connectivity leads to a marked increase in the likelihood of environmental resource collapse. However, we show that an optimal rate of social network adaptation can mitigate this negative effect without loss of social cohesion through network fragmentation. Our results highlight that seemingly immaterial network dynamics of spreading opinions or values can be of large relevance for the sustainable management of socio-ecological systems and suggest smartly conservative network adaptation as a strategy for mitigating environmental collapse. Hence, facing the great acceleration, these network dynamics should

  17. One-Step Transepithelial Topography-Guided Ablation in the Treatment of Myopic Astigmatism

    PubMed Central

    Stojanovic, Aleksandar; Chen, Shihao; Chen, Xiangjun; Stojanovic, Filip; Zhang, Jia; Zhang, Ting; Utheim, Tor Paaske

    2013-01-01

    Purpose To evaluate one-step topography-guided transepithelial ablation in the treatment of low to moderate myopic astigmatism using a 1KHz excimer laser. Methods Retrospective study of 117 consecutive eyes available for evaluation 12 months after surgery. Pre- and post-operative visual and refractive data as well as post-operative pain and haze were analyzed. A novel technique integrating custom refractive- and epithelial- ablation in a single uninterrupted procedure was used. Results The mean pre-operative spherical equivalent (SE) and the mean cylinder were: –3.22 diopters (D) ±1.54 (SD) (range –0.63 to –7.25 D) and –0.77 D ±0.65 (range 0 to –4.50 D), respectively. At 12 months after surgery: no eyes lost ≥2 lines of corrected distant visual acuity (CDVA). Safety and efficacy indexes were 1.27 and 1.09, respectively. Uncorrected distant visual acuity (UDVA) was ≥20/20 in 96.6% of the eyes. Manifest refraction spherical equivalent was within ±0.5 D of the desired refraction in 93.2% of the eyes. Average root mean square (RMS) wavefront error measured at central 6 mm, increased from 0.38 pre-operatively to 0.47 µm post-operatively. Refractive stability was achieved and sustained 1 month after surgery. No visually significant haze was registered during the observation period. Post-operative pain was reported in 4.5% of patients. Conclusions One-step transepithelial topography-guided treatment for low to moderate myopia and astigmatism performed with a 1 KHz laser, provided safe, effective, predictable and stable results with low pain and no visually significant haze. PMID:23799124

  18. A critical role for pannexin-1 in activation of innate immune cells of the choroid plexus

    PubMed Central

    Maslieieva, Valentyna; Thompson, Roger J

    2014-01-01

    Epiplexus cells are a population of innate immune cells in the choroid plexus of the brain ventricles. They are thought to contribute to the immune component of the blood-cerebrospinal-fluid-barrier (BCSFB). Here we have developed a novel technique for studying epiplexus cells in acutely isolated, live and intact choroid plexus. We show that epiplexus cells are potently activated by exogenous ATP, increasing their motility within the tissue. This ATP-induced chemokinesis required activation of pannexin-1 channels, which are expressed by the epithelial cells of the choroid plexus and not the epiplexus cells themselves. Furthermore, ATP acts at least in part through the P2X4 ionotropic purinergic receptor. Thus, the resident immune cells of the choroid plexus appear to be in communication with the epithelial cells through pannexin-1 channels. PMID:24418937

  19. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    PubMed

    Bloch, Sara Brandi

    2013-11-01

    The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

  20. Failure of choroidal melanoma to respond to helium ion therapy

    SciTech Connect

    Char, D.H.; Crawford, J.B.; Castro, J.R.; Woodruff, K.H.

    1983-02-01

    Helium ion irradiation is a promising alternative therapy for choroidal melanoma. In short-term follow-up (less than 5 years), more than 90% (18/19) of treated patients demonstrated tumor regression. Researchers had to enucleate five eyes after helium ion therapy either because of continued tumor growth (four patients) or other complications (one patient). Two melanomas continued to grow and seemed to be radioresistant. In two other tumors it retrospectively seemed that the entire lesion was not inside the radiation field. In one patient total retinal detachment and glaucoma developed; enucleation was performed because of a painful eye. Metastatic disease developed in no patients. The treatment failures emphasize that there are a number of unresolved issues regarding the use of charged-particle irradiation in the treatment of melanoma. Further studies must be performed to answer these questions and better delineate the use of these newer forms of therapy.

  1. [Magnetic resonance tomography in ophthalmology. I. Choroid melanoma].

    PubMed

    Seiler, T; Bende, T; Schilling, A; Wollensak, J

    1987-09-01

    The value of magnetic resonance tomography (MRT) for the diagnosis of choroidal melanomas is illustrated with reference to 26 cases. The geometric dimensions of the tumors are in good agreement with findings obtained by ultrasonography. The relaxation time T2 varies between 85 and 120 msec in contrast to 145-210 msec in subretinal hemorrhages and 190-400 msec in secondary retinal detachments. In contrast to A-scan a differential diagnosis is possible even with lesions less than 1.5 mm in prominence. In solutions of melanin the relaxation time T2 decreases with increasing melanin concentration. This leads to an interpretation that the pigment content of the melanoma is responsible for the relatively short relaxation times. Thus, the relaxation time T2 is a useful factor in predicting metastasis. PMID:3316814

  2. Evaluation of choroidal thickness changes after phacoemulsification surgery

    PubMed Central

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Muhafiz, Ersin; Kırboğa, Kadir; Gürdal, Canan

    2016-01-01

    Purpose The aim of the study was to analyze the effects of uneventful phacoemulsification surgery on choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT). Methods In this prospective study, 38 eyes of 38 patients having phacoemulsification surgery were included. All patients underwent detailed ophthalmologic examination, including preoperative axial length (AXL) measurement with optical biometry and intraocular pressure (IOP) measurement preoperatively and 1 month postoperatively. The CT was measured perpendicularly at the fovea and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal using SD-OCT preoperatively and 1 month postoperatively. Changes in the CT after surgery and correlation of this change with age, AXL, preoperative IOP, and IOP change were evaluated. Results There was a statistically significant increase in the CT at all regions evaluated. This increment was more prominent in the nasal and subfoveal regions. The IOP decreased significantly 1 month after surgery (16.14±4.94 mmHg vs 13.91±4.86 mmHg; P<0.001). The change in IOP was correlated with the CT changes at all regions, whereas age, AXL, and preoperative IOP had no significant correlations with the changes in CT. Conclusion Phacoemulsification surgery may cause significant increase in CT, which is correlated with surgery-induced IOP change in the short term. Long-term follow-up of eyes having phacoemulsification surgery may provide further insight into the effects of cataract surgery on the choroid. PMID:27307699

  3. The association between neovascular age-related macular degeneration and regulatory T cells in peripheral blood

    PubMed Central

    Madelung, Christopher Fugl; Falk, Mads Krüger; Sørensen, Torben Lykke

    2015-01-01

    Purpose To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). Patients and methods Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were recruited from our outpatient retinal clinic. Control individuals were typically spouses. The diagnosis of neovascular AMD was confirmed using fluorescein and indocyaningreen angiography. Fresh venous blood was analyzed by flow cytometry using fluorochrome-conjugated antibodies to the Treg surface antigens CD4, CD25, CD127, CD45RA, and CD31. Main outcome measures were the percentage of CD25highCD127low Tregs, the percentage of CD45RA+ naïve Tregs, and the percentage of CD31+ recent thymic emigrant Tregs. Results Comparing patients with neovascular AMD to controls, no significant differences were found in the percentages of CD4+ lymphocytes, CD25highCD127low Tregs, CD45RA+ naïve Tregs, or CD31+ recent thymic emigrant Tregs. Conclusion Our data does not indicate an altered state of systemic Treg cells in neovascular AMD. PMID:26170606

  4. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia

    PubMed Central

    Al-Zahrani, Yahya A.; Al-Dhibi, Hassan A.; Al-Abdullah, Abdulelah A.

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  5. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia.

    PubMed

    Al-Zahrani, Yahya A; Al-Dhibi, Hassan A; Al-Abdullah, Abdulelah A

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  6. Association between choroidal thickness and anterior chamber segment in eyes with narrow or open-angle

    PubMed Central

    Li, Song-Feng; Wu, Ge-Wei; Chen, Chang-Xi; Shen, Ling; Zhang, Zhi-Bao; Gao, Fei; Wang, Ning-Li

    2016-01-01

    AIM To investigate the relationship between choroidal thickness and anterior chamber segment in subjects with eyes with narrow or open-angle. METHODS The subfoveal choroidal thickness was measured with enhanced depth-imaging optical coherence tomography and anterior chamber parameters were measured with ultrasound biomicroscopy in one eye of 23 subjects with open-angle eyes and 38 subjects with narrow-angle eyes. The mean age was 59.52±7.04y for narrow-angle subjects and 60.76±7.23y for open-angle subjects (P=0.514). Multivariate linear regression analysis was performed to assess the association between choroidal thickness and narrow-angle parameters. RESULTS There were no differences in subfoveal choroidal thickness between open- and narrow-angle subjects (P=0.231). Anterior chamber parameters, including central anterior chamber depth, trabecular iris angle, iris thickness 500 µm from the scleral spur (IT500), and ciliary body thickness at 1 mm and 2 mm from the scleral spur (CBT1, CBT2) showed significant differences between the two groups (P<0.05). Subfoveal choroidal thickness showed negative correlation (β=-0.496, P=0.016) only with anterior chamber depth in the open-angle group and with age (β=-0.442, P=0.003) and IT500 (β=-0.399, P=0.008) in the narrow-angle group. However, subfoveal choroidal thickness was not correlated with trabecular iris angle, anterior chamber depth, ciliary body thickness, or central corneal thickness in the narrow-angle group. CONCLUSION Choroidal thickness does not differ in the two groups and has not correlated with anterior chamber parameters in narrow-angle subjects, suggesting a lack of relationship between choroidal thickness and primary angle-closure glaucoma. PMID:27588269

  7. Expression of connexin 43 and E-cadherin in choroidal melanoma

    PubMed Central

    Mou, Ying-Ying; Zhao, Gui-Qiu; Lin, Jin-Yong; Zhao, Jie; Lin, Hong; Hu, Li-Ting; Xu, Qiang; Wang 1, Qing; Sun, Wei-Rong

    2011-01-01

    AIM To investigate the expression of connexin 43 and epithelial cadherin (E-cadherin) in choroidal melanoma, to explore the clinical and pathological implications of expression of these proteins, and to determine their relations with malignant features. METHODS The expression of connexin 43 and E-cadherin in choroidal melanoma were detected by immunohistochemistry and correlated with clinicopathological features. RESULTS Positive rates of connexin 43 in choroidal melanomas and benign pigmented nevus tissues were 75% and 40% respectively with significant differences between the two groups (χ2=5.607, P=0.009). Positive rates of E-cadherin in choroidal melanomas and benign pigmented nevus tissues were 40% and 75% respectively with significant differences between the two groups (χ2=5.214, P=0.010). Significant overexpression of connexin 43 and reduction of E-cadherin expression was associated with the invasion to the sclera, and there were respectively significant differences between without and with scleral invasion groups (χ2=2.880, P=0.040; χ2=2.778, P=0.046). Overexpression of connexin 43 were correlated with tumor cell types and the expression of connexin 43 and E-cadherin may be correlated with each other. CONCLUSION The increased expression of connexin 43 and the decreased expression of E-cadherin may be involved in the process of invasion of choroidal melanoma. The overepression of connexin 43 and reduction of E-cadherin may contribute to the development of choroidal melanoma. PMID:22553632

  8. Choroidal changes observed with enhanced depth imaging optical coherence tomography in patients with mild Graves orbitopathy.

    PubMed

    Özkan, B; Koçer, Ç A; Altintaş, Ö; Karabaş, L; Acar, A Z; Yüksel, N

    2016-07-01

    PurposeTo evaluate the choroidal thickness in patients with Graves orbitopathy (GO) using enhanced depth imaging-optical coherence tomography (EDI-OCT).MethodsThirty-one patients with GO were evaluated prospectively. All subjects underwent ophthalmologic examination including best-corrected visual acuity, intraocular pressure measurement, biomicroscopic, and fundus examination. Choroidal thickness was measured at the central fovea. In addition, visual evoked potential measurement and visual field evaluation were performed.ResultsThe mean choroidal thickness was 377.8±7.4 μ in the GO group, and 334±13.7 μ in the control group. (P=0.004). There was a strong correlation between the choridal thickness and the clinical activity scores (CAS) of the patients (r=0.281, P=0.027). Additionally, there was a correlation between the choroidal thickness and the visual-evoked potential (VEP) P100 latency measurements of the patients (r=0.439, P=0.001).ConclusionsThe results of this study demonstrate that choroid is thicker in patients with GO. The choroidal thickness is also correlated with the CAS and VEP P100 latency measurements in these patients. PMID:27315349

  9. Investigating the choriocapillaris and choroidal vasculature with new optical coherence tomography technologies.

    PubMed

    Ferrara, Daniela; Waheed, Nadia K; Duker, Jay S

    2016-05-01

    The body of knowledge of in vivo investigation of the choroid has been markedly enhanced by recent technological advances in optical coherence tomography (OCT). New insights elucidating the morphological features of the choriocapillaris and choroidal vasculature, in both physiological and pathological conditions, indicate that the choroid plays a pivotal role in many posterior segment diseases. In this article, a review of the histological characteristics of the choroid, which must be considered for the proper interpretation of in vivo imaging, is followed by a comprehensive discussion of fundamental principles of the current state-of-the-art in OCT, including cross-sectional OCT, en face OCT, and OCT angiography using both spectral domain OCT and swept source OCT technologies. A detailed review of the tomographic features of the choroid in the normal eye is followed by relevant findings in prevalent chorioretinal diseases, focusing on major causes of vision loss such as typical early and advanced age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, pachychoroid spectrum disorders, diabetic choroidopathy, and myopia. PMID:26478514

  10. Evaluation of Choroidal Thickness in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

    PubMed Central

    Ozec, Ayse Vural; Dogan, Oznur; Dursun, Feyza Gulac; Toker, Mustafa Ilker; Topalkara, Aysen; Arici, Mustafa Kemal; Erdogan, Haydar

    2016-01-01

    Purpose. To compare the macular and peripapillary choroidal thickness in eyes with pseudoexfoliation (PEX) syndrome and PEX glaucoma with the normal eyes of healthy controls. Materials and Methods. In this prospective study, 30 eyes of 30 patients with PEX syndrome, 28 eyes of 28 patients with PEX glaucoma, and 30 eyes of 30 age-matched healthy subjects were enrolled. Choroidal thicknesses in the macular and peripapillary areas were measured by using spectral domain optical coherence tomography. Results. Gender, age, and axial length did not significantly differ between the groups (all, p > 0.05). The mean values of choroidal thickness in the macular and peripapillary areas (except the superior quadrant) in the patients with PEX syndrome and PEX glaucoma were lower compared with controls (all p < 0.05). The mean values of the macular and peripapillary choroidal thickness in the PEX glaucoma group were lower compared with PEX syndrome group; however this difference was not significant. Conclusions. The findings of this study revealed that macular and peripapillary choroidal thicknesses were decreased in PEX syndrome and PEX glaucoma cases. The role of choroid in the development of glaucomatous damage in patients with PEX syndrome remains unclear. PMID:27403338

  11. Defining the proteome of human iris, ciliary body, retinal pigment epithelium, and choroid.

    PubMed

    Zhang, Pingbo; Kirby, David; Dufresne, Craig; Chen, Yan; Turner, Randi; Ferri, Sara; Edward, Deepak P; Van Eyk, Jennifer E; Semba, Richard D

    2016-04-01

    The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2959, 2867, and 2755 nonredundant proteins with peptide and protein false-positive rates of <0.1% and <1%, respectively. Forty-three unambiguous protein isoforms were identified in iris, ciliary body, and RPE/choroid. Four "missing proteins" were identified in ciliary body based on ≥2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194. PMID:26834087

  12. Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy

    PubMed Central

    Jo, Hyoung; Jung, Sang Hoon; Kang, Jun; Yim, Hye Bin; Kang, Kui Dong

    2014-01-01

    Sulodexide is a mixed glycosaminoglycan composed of heparin and dermatan sulfate. In this study, the anti-angiogenic effect of sulodexide was investigated using an oxygen-induced retinopathy (OIR) mouse model. The retinas of sham-injected OIR mice (P17) had a distinctive central area of nonperfusion, and this area was significantly decreased in sulodexide-injected mice. The number of neovascular tufts measured by SWIFT_NV and mean neovascular lumen number were significantly decreased in sulodexide-injected mice. Hyperbaric oxygen exposure resulted in increased levels of VEGF, MMP-2 and MMP-9, and when mice were treated with sulodexide, a dose-dependent reduction in VEGF, MMP-2 and MMP-9 levels was observed. Our results clearly demonstrate the anti-angiogenic effect of sulodexide and highlight sulodexide as a candidate supplementary substance to be used for the treatment of ocular pathologies that involve neovascularization. [BMB Reports 2014; 47(11): 637-642] PMID:24602608

  13. Correlation of Aging and Segmental Choroidal Thickness Measurement using Swept Source Optical Coherence Tomography in Healthy Eyes

    PubMed Central

    Wakatsuki, Yu; Shinojima, Ari; Kawamura, Akiyuki; Yuzawa, Mitsuko

    2015-01-01

    Purpose To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattler's (CS) layer and/or the large vessel layer in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm. Methods We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan. Results Total choroidal thicknesses at each of the five sites were related to subject age (P<0.0001). The choroid was thinnest at the nasal site, followed by the temporal, inferior, superior and finally the subfoveal site itself. The total choroidal thickness at the nasal site was significantly less than those at the other four sites (p<0.05). The CS layer showed thinning which correlated with age (P<0.0001). The thickness of the choroidal large vessel layer also decreased with age (p = 0.02). Subfoveal choroidal thickness was calculated as follows: 4