Clinical experience with pegaptanib sodium

Pegaptanib sodium (Macugen®) blocks the extracellular vascular endothelial growth factor (VEGF) isoform VEGF165, whose elevated levels are associated with the development of choroidal neovascularization (CNV). This selective inhibition prevents binding to the VEGF receptors and the development of the increased vascular permeability and the CNV associated with neovascular age-related degeneration (AMD). The VEGF Inhibition Study In Ocular Neovascularization (VISION) demonstrated that pegaptanib sodium confers clinically meaningful benefit in the treatment of all angiographic subtypes of neovascular AMD. It also has a favorable safety profile after 1 and 2 years of continuous treatment, and recent data suggest that the agent has a disease-modifying effect. Post hoc analysis of VISION suggests that treatment benefit may be greatest in patients with early lesions, in whom 80% achieved the primary endpoint of <15 letters lost, 47% maintained visual acuity (VA), and 20% gained ≥15 letters of vision. Similarly, our own clinical experience indicates that pegaptanib sodium achieves better outcomes in early lesions than in established lesions, particularly in patients with previously untreated minimally classic and occult lesions in whom VA improvement and lesion size stabilization has been recorded. Observations indicate that pegaptanib sodium has a slower mode of action than unselective VEGF inhibitors, resulting in an average of 3–4 injections being required to stabilize VA and lesion size. Pegaptanib sodium has good efficacy and safety profiles and represents a good treatment option for patients with early CNV membranes associated with neovascular AMD

Optical coherence tomography and optical coherence tomography angiography in uveitis : a review

Optical coherence tomography (OCT) has dramatically changed the understanding and management of uveitis and other ocular conditions. Currently, OCT angiography (OCTA) combines structural information with the visualization of blood flow within the imaged area. The aim of this review is to present the basic principles of OCT and OCTA interpretation and to investigate the role of these imaging techniques in the diagnosis and management of uveitis. Common complications of intraocular inflammation such as macular oedema and inflammatory choroidal neovascularization are often diagnosed and followed with OCT/OCTA scans. However, uveitis specialists can obtain much more information from tomographic scans. This review provides a comprehensive description of typical OCT/OCTA findings characterizing different ocular structures in uveitis, proceeding from the cornea to the choroid. A careful interpretation of OCT/OCTA images can help in the differential diagnosis, the prediction of clinical outcomes, and the follow-up of patients with uveitis

Comparison of wide field optical coherence tomography angiography with extended field imaging and fluorescein angiography in retinal vascular disorders

Purpose To compare swept source OCTA device, with and without the extended field imaging (EFI) technique, to standard fluorescein angiography (FA) in the clinical practice. Methods Consecutive patients with vascular disorder patients underwent FA with 55-degree lens (Spectralis Heidelberg Engineering, Heidelberg, Germany) and OCTA with the prototype PlexElite (Carl Zeiss Meditec, Dublin, CA) using a 12 mm x 12 mm volume scan pattern centered on the fovea and a prototype of + 20.00-diopter designed specifically by Zeiss. The imaging methods were compared for visible field of view, extension of non-perfused areas, presence and number of neovessels, vessel density (VD) and fractal dimension (FD). Results Forty-three eyes of 27 patients were included. The mean extension ratio of EFI SS-OCTA compared to SS-OCTA without EFI and FA were 1.97 \ub1 0.02 and 0.85 \ub1 0.01. The mean extension of non-perfused areas with EFI SS-OCTA (34.22 \ub1 33.4 mm 2 ) was significantly higher than SS-OCTA without EFI (20.46 \ub1 18.70 mm 2 ), and with FA (27.55 \ub1 4.4 mm 2 ). The mean VD and FD of EFI SS-OCTA were significantly different compared to SS-OCT without EFI. Conclusions EFI SS-OCTA captured larger areas than SS-OCTA without EFI and FA. OCTA in a single shot is able to obtain more information of the retina without the use of montage techniques. Despite the determination of retinal ischemia seems to be easier and more accurate using EFI SS-OCTA, FA offers more details of the perfusion status of the retina

In vivo diffuse correlation spectroscopy investigation of the ocular fundus

Diffuse correlation spectroscopy (DCS) measurements in vivo recorded from rabbits' ocular fundus are presented. Despite the complexity of these ocular tissues, we provide a clear and simple demonstration of the DCS abilities to analyze variations in physiological quantities of clinical interest. Indeed, the reported experimental activities demonstrate that DCS can reveal both choroidal-flow and temperature variations and detect nano- and microaggregates in ocular fundus circulation. Such abilities can be of great interest both in fundamental research and practical clinical applications. The proposed measuring system can be useful in: (a) monitoring choroidal blood flow variations, (b) determining the end-point for photo-dynamic therapy and transpupillary thermo therapy and, (c) managing the dye injection and determining an end-point for dye-enhanced photothrombosis. Moreover, it could allow both diagnoses when the presence of nano- and micro-aggregates is related to specific diseases and verifying the effects of nanoparticle injection in nanomedicine. Even though the reported results demonstrate the applicability of DCS to investigate ocular fundus, a detailed and accurate investigation of the limits of detection is beyond the scope of this article. \uc2\ua9 2013 Society of Photo-Optical Instrumentation Engineers

Measuring Dynamics of Scattering Centers in the Ocular Fundus

The study is focused on the analysis of the diffusing-wave-spectroscopy signalrecorded invivo on the ocular fundus of a rabbit eye. The motion of the scattered sites wasmeasured as a function of the pressure exerted by a Goldmann contact lens and during themoderate temperature increase induced by a therapeutic laser diode. Temporal fluctuations ofthe signal revel motion of molecules and thus changes in tissues temperature andchorioretinal blood velocity. Experimental results show the ability of the system to detectmotion of the scattering sites in the ocular fundus layers during variations of the ocularpressure and laser heating

In-vivo diffusing-wave-spectroscopy measurements of the ocular fundus

We present what is to our knowledge the first observation of a diffusing-wave-spectroscopy signal recorded in-vivo on the ocular fundus. A modified ophthalmic microscope was developed which can acquire diffusing-wave-spectroscopy signal from the eye fundus. The diffusing-wave-spectroscopy signal was recorded in-vivo on a rabbit eye during transpupillary thermotherapy. Experimental results show the ability of the system to detect motion of the scattering sites in the ocular fundus layers during laser thermal heating. (c) 2007 Optical Society of America

The dark atrophy with indocyanine green angiography

PURPOSE. To evaluate differences in fluorescein angiography (FA) and indocyanine green angiography (ICGA), findings between subjects affected by Stargardt disease (STGD) and atrophic AMD. METHODS. This was a consecutive, cross-sectional case series. A total of 24 eyes of 12 patients with STGD and 23 eyes of 14 patients with atrophic AMD were enrolled in the study. Patients underwent dynamic simultaneous FA and ICGA using a dual beam confocal scanning system. Images were recorded from the initial filling of choroidal and retinal vessels throughout all the phases of the angiogram. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence were also executed. FA and ICGA findings in the two groups were evaluated. RESULTS. In 92% (22/24) of eyes affected by STGD, ICGA showed hypocyanescence from the areas of atrophy, more evident in the late phases. This finding, defined as ICGA-imaged &apos;&apos;dark atrophy,&apos;&apos; was present in only 13% (3/23) of the eyes affected by atrophic AMD. The remaining eyes in both groups showed iso-or mild hypercyanescence from the areas of atrophy. Eyes with ICGA-imaged dark atrophy, both in STGD and in atrophic AMD groups, did not show early obscuration of the choroidal vessels by FA. SD-OCT revealed morphologically intact choroid in STGD patients with ICGA-imaged dark atrophy. In atrophic AMD eyes with ICGA-imaged dark atrophy, SD-OCT revealed a severely thinned choroid. CONCLUSIONS. Hypocyanescence by ICGA from the areas of atrophy was more frequent in STGD compared with atrophic AMD. This finding, along with SD-OCT evidence of intact choroid, suggests a possible selective damage of the choriocapillaris in STGD. (Invest Ophthalmol Vis Sci. 2012;53:3999-4004) DOI:10.1167/iovs.11-9258 R ecessive Stargardt disease (STGD) and age-related macular degeneration (AMD) lead to progressive and severe visual acuity loss. STGD is one of the most common inherited retinal dystrophies, while AMD is the most important cause of central visual acuity loss in western countries. STGD typically appears before age 20. It exhibits simple Mendelian transmission and is caused by mutations in the ABCA4 gene. A reduction in ABCA4 activity in the photoreceptors results in the increased production and accumulation of A2E and related bisretinoids within RPE cells. 1,2 These compounds cannot be readily metabolized and have negative effects on RPE cell function and viability. 3,4 RPE cell loss might originate from several mechanisms, including photooxidative stress, 5 vascular alterations, 6,7 and deposition of toxic lipofuscin material under RPE. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) are important tools for diagnostic and pathogenetic evaluation of the two diseases. In STGD, FA is helpful because it allows for the identification of the dark choroid. This finding is characterized by the absence of normal background fluorescence mainly due to the presence of RPE lipofuscin that absorbs the blue excitatory light. 8 Also, ICGA may provide useful information, in particular about the alterations of the choroid and the choriocapillaris. 10 In addition, partial absorption by retinal pigment epithelial melanin occurs. In contrast, indocyanine green absorbs and emits light in the near-infrared spectrum, and allows better penetration. Furthermore, indocyanine green is predominantly bound to plasma protein (98% compared with 60%-80% for fluorescein), and this limits its diffusion through the fenestrations of the choriocapillaris. 11 Moreover, AMD may be characterized by a presumed macular choroidal watershed filling. 12 ICGA showed diminished choroidal arterial perfusion of the macula and enlargement of choroidal veins in the pathogenesis of AMD. 13 The combination of FA and ICGA facilitates interpretation of the exam and provides more information than either FA or ICGA alone. 10 Therefore, in this study, simultaneous FA and ICGA were used to evaluate possible differences in the pathogenesis of the two clinical entities. METHODS Twenty-six consecutive patients affected by STGD and atrophic AMD

Oxidized cholesterol as the driving force behind the development of Alzheimer&#8217;s disease

Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis