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

A consensus definition for lamellar macular hole

Background: A consensus on an optical coherence tomography (OCT) definition of lamellar macular hole (LMH) and similar conditions is needed. Methods: The panel reviewed relevant peer-reviewed literature to reach a consensus on LMH definition and to differentiate LMH from other similar conditions. Results: The panel reached a consensus on the definition of 3 clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on 3 mandatory criteria and 3 optional anatomical features. The 3 mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges, and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a foveal bump and the disruption of the ellipsoid line. ERM foveoschisis definition is based on 2 mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle’s fiber layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness, and the presence of retinal wrinkling. MPH definition is based on 3 mandatory criteria and 2 optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness. Conclusions: The use of the proposed definitions may provide uniform language for clinicians and future research

Optical coherence tomography-based consensus definition for lamellar macular hole.

BackgroundA consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.MethodsThe panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.ResultsThe panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.ConclusionsThe use of the proposed definitions may provide uniform language for clinicians and future research

The Relationship Between Blue-Fundus Autofluorescence and Optical Coherence Tomography in Eyes With Lamellar Macular Holes

PURPOSE. The purpose of this study was to evaluate the relationship between blue-fundus autofluorescence (B-FAF) and optical coherence tomography (OCT) in eyes with lamellar macular holes (LMHs). METHODS. this was a multicenter, observational case series. Ninety-two eyes with LMH associated with the standard epiretinal membrane (ERM) or lamellar hole-associated epiretinal proliferation (LHEP) were evaluated. The eyes must also present an area of increased autofluorescence on B-FAF. RESULTS. The ERM-alone group and the LHEP group differed with respect to the following variables: logarithm of the minimum angle of resolution best-corrected visual acuity (0.13 +/- 0.13 vs. 0.25 +/- 0.17;P < 0.001), central foveal thickness (218.74 +/- 52.4 mu m vs. 187.28 +/- 50.29 mu m;P = 0.008), FAF diameter (400.78 +/- 189.36 mu m vs. 503.37 +/- 214.25 mu m;P = 0.014), outer plexiform layer (OPL) diameter (382.10 +/- 157.34 mu m vs. 550.79 +/- 228.05 mu m;P = 0.0001), and disruption of external limiting membrane and ellipsoid zone, which was noted in only 1 and 3 eyes with ERM alone, respectively, and in 18 and 23 eyes with LHEP, respectively (P < 0.0001 for both observations). No difference was found for diameters measured at the level of the inner limiting membrane and schisis/cavitation. In both the ERM-alone group and the LHEP group, a strong correlation was found between the diameters measured on B-FAF and diameters measured at the OPL level on OCT images (P < 0.0001 for both groups). CONCLUSIONS. In eyes with LMHs, a strong correlation exists between the diameters of the holes measured with B-FAF and those measured at the OPL level with OCT. This may indicate that the loss or displacement of retinal cells containing macular pigment at the OPL level, specifically photoreceptors and/or Muller cells, is involved in this vitreomaculopathy

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

Fundus Autofluorescence in Lamellar Macular Holes and Pseudoholes: A Review

Macular pseudoholes (MPHs) and lamellar macular holes (LMHs) have been recently defined according to spectral domain optical coherence tomography (SD-OCT) criteria. A major feature for differentiating an MPH from an LMH remains the loss of foveal tissue. The anatomy of the foveola is peculiar with the macular pigment (MP) embedded in a very thin layer of tissue underlying the internal limiting membrane and mainly constituted of a specialized group of Müller cells and Henle’s fibers. Despite the near microscopic resolution (≈5–7 μm) and the capability to visualize the outer retina in detail, SD-OCT may fail to ascertain whether a very small loss of this foveolar tissue has occurred. Blue-fundus autofluorescence (B-FAF) imaging is useful in this respect because even very small loss of MP can be identified, suggesting a corresponding localized loss of the innermost layers of the foveola. A definition of MP loss would help differentiating an LMH from an MPH where B-FAF imaging will be negative

AN MCSCF AB INITIO STUDY OF C-CL BOND CLEAVAGE IN H3C-Cl

The thermal, photochemical and reductive dehalogenations of methyl chloride (H3C-Cl) are studied with the ab initio MCSCFmethod using three different basis sets (3-2 lG*, 6-31G* and 6-31 +G*). It has been found that both thermal and photochemicaldecomposition produce a methyl and a chlorine radical. The photochemical decomposition involves excitation of the H3C-Clmolecule from the singlet ground state to a singlet or triplet n-u* state which dissociates directly to these products. The reductivedehalogenation involves the formation of a metastable anion (resulting from electron transfer to the chloromethane) which dissociatesimmediately to a methyl radical and chloride anion. While for the thermal and photochemical decomposition the resultsobtained at the various computational levels do not significantly differ, for a reliable description of the reductive dehalogenation,it is essential to use a basis set, such as 6-31 +G*, which includes appropriate sp-type diffuse function