Subretinal Neovascularization Research Articles

Association of Age-Related Macular Degeneration With Risk of All-Cause and Specific-Cause Mortality in the National Health and Nutrition Examination Survey, 2005 to 2008

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness in the United States if subretinal neovascularization is left untreated. Knowledge of the association between AMD and survival is informative for underlying mechanisms of AMD. To examine the association between AMD and risk of all-cause and specific-cause mortality in a representative US sample. This population-based prospective cohort study included 5603 participants 40 years or older who responded to the National Health and Nutrition Examination Survey (NHANES) in the 2005-2008 phase. Retinal photographs were graded as early, late, or no AMD. All analyses accounted for the complex and stratified design of NHANES with weighted data. Risks of all-cause mortality were assessed with Cox proportional hazards regression models; risks of specific-cause mortality, with Fine and Gray competing risks regression models. Time to death was counted from baseline to date of death or December 31, 2011, whichever came first. Data analysis was conducted from April 1 through 30, 2018. Age-related macular degeneration status as determined by digital fundus images. Mortality resulting from all causes and specific causes until December 31, 2011. Among the 5603 participants (52.6% female [n = 2793] and 77.1% white [n = 3017]; mean [SE] age, 56.4 [0.4] years), weighted prevalence of any AMD was 6.6%, with 386 (5.8%) having early AMD and 55 (0.8%) having late AMD. After a median follow-up of 4.5 years (interquartile range, 3.6-5.6 years), 433 (5.3%) died of all causes, of whom 361 (83.1%) had no AMD, 54 (11.5%) had signs of early AMD, 18 (5.4%) had signs of late AMD, and 72 (16.9%) had any AMD at baseline. Overall, unadjusted all-cause and specific-cause mortality rates were higher for those participants who had early, late, or any AMD compared with no AMD. However, after adjusting confounding factors, only late AMD was associated with more than a doubling of all-cause mortality (hazard ratio [HR], 2.01; 95% CI, 1.00-4.03) and more than a 3-fold higher risk of mortality due to causes other than cardiovascular disease and cancer (HR, 3.42; 95% CI, 1.38-8.49). No association was identified between AMD presence or early AMD and all-cause or specific-cause mortality. In this study's findings, only late AMD was independently associated with all-cause mortality and mortality due to causes other than cardiovascular disease and cancer, indicating that late AMD may be a marker of biological aging. Alternatively, this association may be due to unmeasured or inadequately assessed confounding factors for late AMD.

Monotherapy laser photocoagulation for diabetic macular oedema.

Monotherapy laser photocoagulation for diabetic macular oedema.

Étude du fond d’œil en fonction de l’âge dans le pseudoxanthome élastique chez 158 patients

To study the prevalence of fundus anomalies among patients with pseudoxanthoma elasticum as a function of their age. All patients have had a complete ophthalmologic examination in multidisciplinary consultation for PXE in a national reference center. Hundred and fifty-eight patients (60men and 98women aged from 10to 90years old, mean 45±17years) were included in a cross-sectional retrospective study. All fundus pictures were retrospectively reviewed over 9years. Peau d'orange (55.6%), was the first fundus feature observed in younger patients and disappeared with age. Angioid streaks (100%), appeared during the second decade of life: at first hypofluorescent and then hyperfluorescent after 40years old. Crystalline bodies (54.1%), optic nerve head drusen (19%) and peripheral pigmentation (39.9%) were found in the various age groups. Macular atrophy (33.5%) could have resulted from subretinal neovascularization (40.8%), pattern dystrophies (7.9%) or subretinal fibrosis (5.3%). The onset of neovascularization appeared during the fourth decade. Progressive centrifugal calcification of Bruch's membrane is the cause of the many fundus features observed in PXE patients. Knowledge of the natural history of PXE can help the clinician explain and reassure patients about the evolving risks of ophthalmological involvement, particularly the fact that neovascular complications arise from the fourth decade.

Sustained and targeted episcleral delivery of celecoxib in a rabbit model of retinal and choroidal neovascularization

BackgroundTo evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).MethodsNine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control.ResultsIn all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment.ConclusionIn this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.

Targeting Hif1a rescues cone degeneration and prevents subretinal neovascularization in a model of chronic hypoxia

BackgroundDegeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased choroidal blood flow, implicates reduced tissue oxygenation in AMD pathology and suggests a role of the cellular response to hypoxia in disease onset and progression. Such a chronic hypoxic situation may promote several cellular responses including stabilization of hypoxia-inducible factors (HIFs).MethodsTo investigate the consequence of a chronic activation of the molecular response to hypoxia in cones, von Hippel Lindau protein (VHL) was specifically ablated in cones of the all-cone R91W;Nrl-/- mouse. Retinal function and morphology was evaluated by ERG and light microscopy, while differential gene expression was tested by real-time PCR. Retinal vasculature was analyzed by immunostainings and fluorescein angiography. Two-way ANOVA with Šídák’s multiple comparison test was performed for statistical analysis.ResultsCone-specific ablation of Vhl resulted in stabilization and activation of hypoxia-inducible factor 1A (HIF1A) which led to increased expression of genes associated with hypoxia and retinal stress. Our data demonstrate severe cone degeneration and pathologic vessel growth, features that are central to AMD pathology. Subretinal neovascularization was accompanied by vascular leakage and infiltration of microglia cells. Interestingly, we observed increased expression of tissue inhibitor of metalloproteinase 3 (Timp3) during the aging process, a gene associated with AMD and Bruch’s membrane integrity. Additional deletion of Hif1a protected cone cells, prevented pathological vessel growth and preserved vision.ConclusionsOur data provide evidence for a HIF1A-mediated mechanism leading to pathological vessel growth and cone degeneration in response to a chronic hypoxia-like situation. Consequently, our results identify HIF1A as a potential therapeutic target to rescue hypoxia-related vision loss in patients.

Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum

BackgroundIn pseudoxanthoma elasticum (PXE), low pyrophosphate levels may cause ectopic mineralization, leading to skin changes, visual impairment, and peripheral arterial disease. ObjectivesThe authors hypothesized that etidronate, a pyrophosphate analog, might reduce ectopic mineralization in PXE. MethodsIn the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). The primary outcome was ectopic mineralization, quantified with 18fluoride positron emission tomography scans as femoral arterial wall target-to-background ratios (TBRfemoral). Secondary outcomes were computed tomography arterial calcification and ophthalmological changes. Safety outcomes were bone density, serum calcium, and phosphate. ResultsDuring 12 months of follow-up, the TBRfemoral increased 6% (interquartile range [IQR]: −12% to 25%) in the etidronate group and 7% (IQR: −9% to 32%) in the placebo group (p = 0.465). Arterial calcification decreased 4% (IQR: −11% to 7%) in the etidronate group and increased 8% (IQR: −1% to 20%) in the placebo group (p = 0.001). Etidronate treatment was associated with significantly fewer subretinal neovascularization events (1 vs. 9, p = 0.007). Bone density decreased 4% ± 12% in the etidronate group and 6% ± 9% in the placebo group (p = 0.374). Hypocalcemia (<2.20 mmol/l) occurred in 3 versus 1 patient (8.1% vs. 2.7%, p = 0.304). Eighteen patients (48.6%) treated with etidronate, compared with 0 patients treated with placebo (p < 0.001), experienced hyperphosphatemia (>1.5 mmol/l) and recovered spontaneously. ConclusionsIn patients with PXE, etidronate reduced arterial calcification and subretinal neovascularization events but did not lower femoral 18fluoride sodium positron emission tomography activity compared with placebo, without important safety issues. (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum; NTR5180)

Endocan Blockade Suppresses Experimental Ocular Neovascularization in Mice.

Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells under hypoxia, but the effect of endocan on ocular NV progression is largely unknown. In this study, we investigated the role of endocan in the ocular NV pathologic process and the possible mechanisms involved. In the eyes of mice with oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real-time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human retinal microvascular endothelial cell (HREC) tube formation was observed using a routine method. Endocan was significantly elevated in these three experimental mice models. Endocan blockade with the neutralizer intravitreal injection not only suppressed the area of retinal, choroidal and subretinal NV, but also resulted in a decrease in several angiogenesis-associated molecules. Recombinant endocan protein (rhEndocan) was found to induce tube formation on HRECs directly. The current data suggest that endocan is a potential therapeutic or an additional target for retinal and subretinal NV diseases.

Unfavorable effect of photodynamic therapy for late subretinal neovascularization with chorioretinal anastomoses associatedwith idiopathic multiple serous detachments of the retinal pigment epithelium.

To describe a case of a 46-year-old woman with an asymptomatic history of unilateral multiple serous detachments of the retinal pigment epithelium (PED) in the right eye, treated with photodynamic therapy (PDT) with verteporfin for recent onset of subfoveal choroidal neovascularization (CNV) with chorioretinal anastomoses (CRA). Fluorescein and indocyanine green (ICG) angiography, performed with a Heidelberg scanning laser ophthalmoscope (SLO), demonstrated a predominantly classic foveal choroidal neovascular membrane associated with a PED and 1 one retinal and 2 two venous chorioretinal anastomoses. The left fundus was normal. PDT therapy was performed according to standard techniques. Three PDT treatments were performed at an interval of 3 months. Three months after the second PDT, visual acuity dropped to 20/200, with an en-largement of the neovascular network. One month after the third treatment, visual acuity deteriorated further and the CRA appeared enlarged, associated with a dense fibrotic re-action in the centere of the lesion. This clinical observation demonstrates that idiopathic serous detachments of the retinal pigment epithelium may represent predisposing changes to CNV development, and in the case CNV is associated with CRA, PDT may be unsuccessful. (Eur J Ophthalmol 2004; 14: 568-71).

Plexus-Specific Detection of Retinal Vascular Pathologic Conditions with Projection-Resolved OCT Angiography

To evaluate the projection-resolved (PR) optical coherence tomography angiography (OCTA) algorithm in detecting plexus-specific vascular abnormalities in retinal pathologies. Cross-sectional observational clinical study. Patients diagnosed with retinal vascular diseases and healthy volunteers. Eyes were imaged using an OCT system operating at 840 nm and employing the split-spectrum amplitude decorrelation algorithm. A novel algorithm suppressed projection artifacts inherent to OCTA. The volumetric scans were segmented and visualized on different plexuses. Qualitative observation of vascular abnormalities on both cross-sectional and en face PR-OCTA images. Eight illustrative cases are reported. In cases of diabetic retinopathy, retinal vessel occlusion, and retinitis pigmentosa, PR-OCTA detected retinal nonperfusion regions within deeper retinal plexuses not visualized by conventional OCTA. In age-related macular degeneration, cross-sectional PR-OCTA permitted the classification of choroidal neovascularization, and, in a case of retinal angiomatous proliferation, identified a vertical vessel contiguous with the deep capillary plexus. In macular telangiectasia, PR-OCTA detected a diving perifoveal vein and delineated subretinal neovascularization. Application of PR-OCTA promises to improve sensitive, accurate evaluation of individual vascular plexuses in multiple retinal diseases.

The efficacy of cryotherapy in one case of retinal vasoproliferative tumor.

Retinal vasoproliferative tumor (VPT) is uncommon retinal lesion, classified as primary (idiopathic) or secondary. Retinal VPT has a predilection for the peripheral inferior temporal quadrant of the retina and may be unilateral or bilateral. It can lead to decrease vision due to intraretinal or subretinal exudation, neovascularization, retinal detachment, vitreous hemorrhage, preretinal fibrosis, macular edema and epiretinal membrane formation. Different modalities have been used to treat this tumor including clinical observation, pars plana vitrectomy, cryotherapy, laser photocoagulation, brachytherapy and radiotherapy. The authors describe a case of idiopathic retinal VPT associated with extensive serous retinal detachment and point out the importance of diagnosis and the effectiveness of cryotherapy.

The Role of Hypoxia, Hypoxia-Inducible Factor (HIF), and VEGF in Retinal Angiomatous Proliferation.

In industrialized countries, age-related macular degeneration (AMD) is the leading cause of blindness in elderly people. Hallmarks of the non-neovascular (dry) form of AMD are the formation of drusen and geographic atrophy, whereas the exudative (wet) form of the disease is characterized by invading blood vessels. In retinal angiomatous proliferation (RAP), a special form of wet AMD, intraretinal vessels grow from the deep plexus into the subretinal space. Little is known about the mechanisms leading to intraretinal neovascularization, but age-related changes such as reduction of choroidal blood flow, accumulation of drusen, and thickening of the Bruch's membrane may lead to reduced oxygen availability in photoreceptors. Such a chronic hypoxic situation may induce several cellular response pathways including the stabilization of hypoxia-inducible factors (HIFs) and the production of angiogenic factors, such as vascular endothelial growth factor (VEGF). Here, we discuss the potential contribution of hypoxia and HIFs in RAP disease pathology and in some mouse models for subretinal neovascularization.

Optical Coherence Tomography Angiography Findings in Type-2 Macular Telangiectasia.

Objectives:To evaluate the vascular changes of idiopathic macular telangiectasia type 2 (MacTel 2) patients with optical coherence tomography angiography (OCTA) and correlate these changes with the findings of spectral domain optical coherence tomography (SD-OCT).Materials and Methods:Simultaneous SD-OCT and OCTA images of 10 eyes of 6 patients who were diagnosed as MacTel 2 in Ankara University Faculty of Medicine, Department of Ophthalmology were obtained and graded according to the OCTA grading system for MacTel 2.Results:Ten eyes of 6 patients were included. Four (66%) patients were female and 2 (34%) were male. The disease was grade 0 in 2 eyes, grade 1 in 2 eyes, grade 2 in 3 eyes, grade 3 in 1 eye, grade 4 in 1 eye, and grade 5 in 1 eye. The most common findings in grade 1, 2, and 3 non-proliferative disease were thinning of the outer retinal layers, presence of intraretinal hyporeflective layers and inner limiting membrane draping. In cases with subretinal choroidal neovascularisation (CNV) in OCTA, CNV or CNV scar was present in the B-scan SD-OCT images. In a case in which OCT was within normal limits, vascular changes consistent with grade 1 disease were observed in OCTA. On the contrary, 2 patients with significant foveal atrophy and macular hole in B-scan showed changes of early disease in OCTA. In some of the eyes, OCTA revealed an intact superficial vascular layer despite visible changes in the deep layer and the presence of neovascularisation.Conclusion:OCTA yields findings which are important for understanding the pathogenesis of the disease and providing better follow-up. Contrary to fundus fluorescein angiography, changes in the deep arterial plexus in the early disease and CNV can be clearly observed with OCTA. To achieve the best results in clinical practice, en face flow maps should be evaluated together with B-scan SD-OCT images.

Therapeutic Effects of PPARα Agonist on Ocular Neovascularization in Models Recapitulating Neovascular Age-Related Macular Degeneration.

PurposeThis study was designed to evaluate effects of fenofibric acid (Feno-FA), a peroxisome proliferator–activated receptor-alpha (PPARα) agonist, on ocular neovascularization (NV) in models recapitulating neovascular age-related macular degeneration (AMD), and to explore whether the effects are PPARα dependent.MethodsLaser-induced choroidal NV (CNV) in rats and very low-density lipoprotein receptor knockout (Vldlr−/−) mice received daily intraperitoneal injections of Feno-FA or vehicle. Vascular leakage was examined by fundus fluorescein angiography and permeability assay using Evans blue as tracer. In CNV rats, severity of CNV was evaluated by CNV areas and CNV volume. In Vldlr−/− mice, subretinal NV (SRNV) and intraretinal NV (IRNV) were quantified in choroid flat mount and retina flat mount, respectively. Inflammatory factors were measured using Western blotting and retinal leukostasis assay. Further, Pparα−/− mice and age-matched wild-type (WT) mice were used for laser-induced CNV and treated with Feno-FA to explore the underlying mechanism.ResultsFeno-FA significantly reduced vascular leakage in CNV rats and Vldlr−/− mice, reduced CNV volume in laser-induced CNV rats, and suppressed SRNV and IRNV in Vldlr−/− mice. In addition, Feno-FA downregulated the expression of inflammatory factors, including VEGF, TNF-α, and intercellular cell adhesion molecule-1 (ICAM-1), in the eyecups of CNV rats and decreased adherent retinal leukocytes in Vldlr−/− mice. Furthermore, Pparα−/− mice developed more severe CNV compared with WT mice, and PPARα knockout abolished the beneficial effects of Feno-FA on CNV.ConclusionsFeno-FA has therapeutic effects on ocular NV in models recapitulating neovascular AMD through a PPARα-dependent mechanism.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHANGES IN EARLY TYPE 3 NEOVASCULARIZATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

To investigate the morphologic changes on optical coherence tomography angiography (OCTA) of treatment-naive Type 3 neovascularization secondary to exudative age-related macular degeneration after 1 year of anti-vascular endothelial growth factor therapy. Consecutive patients diagnosed with treatment-naive early-stage Type 3 neovascularization were enrolled in this retrospective study. All patients underwent color fundus photographs/MultiColor (Heidelberg Engineering) imaging, fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCTA Optovue RTVue XR Avanti (Optovue) at baseline, and repeated OCTA and structural spectral domain OCT at Month 12. Qualitative analysis of the 3 × 3 OCTA examinations at baseline and Month 12 was then compared, to assess changes after anti-vascular endothelial growth factor therapy. A total of 15 treatment-naive eyes of 15 consecutive patients were included in the analysis. At 12-month follow-up after pro-re-data anti-vascular endothelial growth factor therapy (5.75 ± 1.48 injections of ranibizumab, and injections of 6.33 ± 1.21 of aflibercept), OCTA demonstrated persistence of the deep capillary plexus abnormalities in 13/15 eyes. In the outer retina and choriocapillaris, the initial lesion became undetectable in 7/15 cases, accompanied by choriocapillaris atrophy. The abnormal vascular complex persisted in the form of a tuft-shaped lesion in the outer retinal segmentation in 9/15 eyes, which in the choriocapillaris segmentation was associated with sub-retinal pigment epithelium neovascularization in 8 cases. Optical coherence tomography angiography showed that the tuft-shaped abnormal outer retinal lesion, frequently associated with a small clew-like flow signal in the choriocapillaris, after 1 year of anti-vascular endothelial growth factor therapy, either becomes undetectable or develops sub-retinal pigment epithelium neovascularization.

MicroRNA-155 Inhibits Polarization of Macrophages to M2-Type and Suppresses Choroidal Neovascularization.

Arg-1+Ym-1+ M2-type macrophages play essential roles in the development of choroidal neovascularization (CNV). Thus, inhibition of M2-type macrophages may be effective in suppressing CNV. However, the potential mechanisms of macrophage polarization during development of CNV remain unclear. In this study, we report that microRNA-155 (miR-155) inhibited M2 polarization by targeting C/EBPβ in CNV model mice and in bone marrow-derived primary macrophages. Moreover, our data show that intravitreous injection of miR-155 mimics suppressed subretinal leakage and neovascularization. Therefore, we conclude that C/EBPβ plays a significant role in M2 macrophage polarization in CNV model, while miR-155 mimics could suppress CNV by inhibiting C/EBPβ activity and M2 macrophage polarization.

Macular Telangiectasia Type 2 With Spontaneous Resolution of Intraretinal/Sub-Internal Limiting Membrane Hemorrhage in the Absence of Neovascularization

Purpose: To describe a case of macular telangiectasia type 2 (MacTel) presenting with decreased vision due to intraretinal/sub-internal limiting membrane (ILM) hemorrhage in the absence of neovascularization. Method: Clinical examination and multimodal imaging were performed. Results: A 65-year-old female presented with blurred left vision, recording 20/160 in that eye. There was intraretinal hemorrhage at the left macula centrally, with sub-ILM hemorrhage superiorly and inferiorly. Optical coherence tomography (OCT) showed no evidence of subretinal neovascularization. Imaging of the right macula was consistent with MacTel. The blood spontaneously cleared and the left visual acuity gradually improved to 20/25 by 4 months. Fluorescein angiography confirmed MacTel, and once the hemorrhage resolved, both inner and outer retinal cavitation was identified on OCT of the left macula. The left best-corrected visual acuity remained at 20/25 at 2-year follow-up. Conclusion: Spontaneous resorption of hemorrhage was accompanied by visual improvement.

Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia.

Objectives:To evaluate the effectiveness of intravitreal bevacizumab (IVB) in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.Materials and Methods:Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab). Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT) and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT). Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment.Results:The mean age of patients was 66.0±7.0 years (56-75). The mean follow-up time was 54.7±16.0 month (24-72). The mean BCVA was 0.62±0.35 (0.00-1.00) logMAR at baseline and 0.54±0.35 (0.00-1.00) logMAR at final exam (p=0.03). The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01). Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases.Conclusion:IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

FAK phosphorylation plays a central role in thrombin-induced RPE cell migration

The migration of retinal pigment epithelial (RPE) cells is an important step in various pathologic conditions including subretinal neovascularization (SRN), proliferative vitreoretinopathy (PVR) and, importantly, as a consequence of retinal surgery. Therefore, the elucidation of the mechanisms underlying RPE trans-differentiation and migration is essential for devising effective treatments aimed to the prevention of these disorders. A common event in these pathologies is the alteration of the blood-retina barrier (BRB), which allows the interaction of RPE cells with thrombin, a pro-inflammatory protease contained in serum. Our previous work has demonstrated that thrombin induces RPE cell cytoskeletal remodeling and migration, hallmark processes in the development of PVR; however, the molecular mechanisms involved are still unclear. Cell migration requires the disassembly of focal adhesions induced by Focal Adhesion Kinase (FAK) phosphorylation, together with the formation of actin stress fibers. The aim of the present work was to identify thrombin-activated signaling pathways leading to FAK phosphorylation and to determine FAK participation in thrombin-induced RPE cell migration. Results demonstrate that the activation of PAR1 by thrombin induces FAK autophosphorylation at Y397 and the subsequent phosphorylation of Y576/577 within the activation loop. FAK phosphorylation was shown to be under the control of c/nPKC and PI3K/PKC-ζ, as well as by Rho/ROCK, since the inhibition of these pathways prevented thrombin-induced FAK phosphorylation and the consequent disassembly of focal adhesions, in parallel to FAK-dependent actin stress fiber formation and RPE cell migration. These findings demonstrate, for the first time, that thrombin stimulation of RPE cell transformation and migration are regulated by FAK tyrosine phosphorylation. Thus, targeting FAK phosphorylation may provide a strategical basis for PVR treatment.

Sema3f Protects Against Subretinal Neovascularization In Vivo

Pathological neovascularization of the outer retina is the hallmark of neovascular age-related macular degeneration (nAMD). Building on our previous observations that semaphorin 3F (Sema3f) is expressed in the outer retina and demonstrates anti-angiogenic potential, we have investigated whether Sema3f can be used to protect against subretinal neovascularization in two mouse models. Both in the very low-density lipid-receptor knockout (Vldlr−/−) model of spontaneous subretinal neovascularization as well as in the mouse model of laser-induced choroidal neovascularization (CNV), we found protective effects of Sema3f against the formation of pathologic neovascularization. In the Vldlr−/− model, AAV-induced overexpression of Sema3f reduced the size of pathologic neovascularization by 56%. In the laser-induced CNV model, intravitreally injected Sema3f reduced pathologic neovascularization by 30%. Combined, these results provide the first evidence from two distinct in vivo models for a use of Sema3f in protecting the outer retina against subretinal neovascularization.

The vitreomacular interface in different types of age-related macular degeneration.

To evaluate the vitreomacular interface in cases with wet age-related macular degeneration (AMD) and to compare them to eyes with dry AMD and normal eyes. This was a cross-sectional comparative study that included 87 eyes with wet AMD, 42 eyes with dry AMD and 40 eyes without AMD as a control group. Optical coherence tomography (OCT) examination was performed for all patients to assess the vitreomacular interface. In the wet AMD group, 34.5% of cases had vitreomacular adhesion (VMA). Only 14.3% of dry AMD cases and 10% of control cases had VMA. There was a significant difference between the control group and the wet AMD group (P=0.004) as well as the dry and wet AMD group (P=0.017). There was also a significant difference between the incidence of VMA in patients with subretinal choroidal neovascularization (CNV, type 1) and intraretinal CNV (type 2 or type 3) (P=0.020). There is an association between posterior vitreous attachment and AMD. There is also an increased incidence of VMA with intra-retinal CNV.