Choroidal volume variations during childhood

Purpose. We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. Methods. Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. Results. Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 \ub1 0.98 mm. Mean CV was 0.263 \ub1 0.068 mm3 for the foveal circle and 8.545 \ub1 1.822 mm3 for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm3 (2.5%) for every year, and decreased by 1.0 mm3 (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). Conclusions. The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present

Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1

Objective: To investigate in a large sample of consecutive patients with neurofibromatosis type 1 (NF1) the possibility of including the presence of choroidal abnormalities detected by near-infrared reflectance (NIR) as a new diagnostic criterion for NF1. Design: Cross-sectional evaluation of a diagnostic test. Participants and Controls: Ninety-five consecutive adult and pediatric patients (190 eyes) with NF1, diagnosed based on the National Institutes of Health (NIH) criteria. Controls included 100 healthy age- and gender-matched control subjects. Methods: Confocal scanning laser ophthalmoscopy was performed for each subject, investigating the presence and the number of choroidal abnormalities. Main Outcome Measures: Sensitivity, specificity, and diagnostic accuracy for the different cutoff values of the criterion choroidal nodules detected by NIR compared with the NIH criteria. Results: Choroidal nodules detected by NIR imaging were present in 79 (82%) of 95 of the NF1 patients, including 15 (71%) of the 21 NF1 pediatric patients. Similar abnormalities were present in 7 (7%) of 100 healthy subjects, including 2 (8%) of the 25 healthy pediatric subjects. The highest accuracy was obtained at the cutoff value of 1.5 choroidal nodules detected by NIR imagery. Sensitivity and specificity of the examination at the optimal cutoff point were 83% and 96%, respectively. Diagnostic accuracy was 90% in the overall population and 83% in the pediatric population. Both of these values were in line with the most common NIH diagnostic criteria. Conclusions: Choroidal abnormalities appearing as bright patchy nodules detected by NIR imaging frequently occurred in NF1 patients. The present study shows that NIR examination to detect choroidal involvement should be considered as a new diagnostic criterion for NF1

Purtscher-like retinopathy in septicemic disseminated intravascular coagulation associated with nephrotic syndrome

Purpose: To describe a case of severe Purtscher-like retinopathy during an episode of septicemic diffused intravascular coagulation (DIC) in a child with severe nephrotic syndrome. Methods: Case report. Results: A 5-year-old girl with a history of steroid-sensitive nephrotic syndrome was admitted for worsening symptoms of the systemic disease. Laboratory studies revealed evidence of DIC during an episode of septicemia. Ten days later, she had a sudden and severe bilateral visual loss. Her visual acuity was hand motion in either eye. Fundus examination showed ischemic retinal whitening and retinal hemorrhages. Fluorescein angiography revealed obstruction of arterioles and venules at the posterior pole. Three weeks later, ischemic retinal blanching and hemorrhages resolved in both eyes; visual acuity improved to 20/250 and 20/200 in right and left eye, respectively. No further functional improvement was noted after 3 months, due to diffuse thinning of the inner retina architecture as shown by optical coherence tomography. Conclusions: Purtscher-like retinopathy can occur in patients with septicemic DIC and nephrotic syndrome

Synthesis and antiplasmodial evaluation of new N-(imidazol-2-yl)-methyl-4-aminoquinolines

In order to develop new effective antimalarial agents, we have demonstrated that the replacement of the phenolic ring of amodiaquine-like compounds with an arylpyrrole nucleus is associated with a good antimalarial activity (M. Casagrande et al., Bioorg. Med. Chem. 2008, 16, 6813 and Bioorg. Med. Chem. 2010, 18, 6625). In addition, Chibale and co-workers recently reported a new potent antimalarial 4-aminoquinoline, termed phenylequine (PQ), characterized by a phenyl ring linked to 4-aminoquinoline nucleus through a methylenic group (M. A. L. Blackie et al., Bioorg. Med. Chem. Lett. 2010, 20, 1078). To test the effect on the antimalarial activity of the presence of other heterocyclic rings linked to the 7-chloro-4-aminoquinoline nucleus instead of the phenyl ring , a set of new 7-chloro-N-((1H-imidazol-2-yl)methyl)quinolin-4-amine and 7-chloro-N-((4-aryl-1H-imidazol-2-yl)methyl)quinolin-4-amine bearing at position 5 of imidazole a diethylaminomethyl or a pyrrolidinomethyl moiety as basic head, was synthesized and tested

Multimodal Imaging of Vitreoretinal Lymphoma

Purpose: To assess the characteristics and prevalence of fundus abnormalities in vitreoretinal lymphoma (VRL) using multimodal imaging. Methods: We retrospectively reviewed chart and imaging studies of patients diagnosed with VRL. Results: All 10 VRL patients (14 eyes) included in the study showed vitreitis, hyperreflective lesions on near-infrared reflectance imaging, and hypoautofluorescent lesions on fundus autofluorescence. Other findings included hypofluorescent lesions on fluorescein angiography (79%), hypocyanescent lesions on indocyanine green angiography (77%), small retinal pigment epithelium detachments (PEDs) (71%) and large PEDs (36%) on optical coherence tomography (OCT). Outer retinal layer nodularity was identified on OCT in 93% of cases. Small PEDs corresponded to hyperreflective, hyperautofluorescent, hypofluorescent, hypocyanescent lesions. Conclusion: Multiple signs were present on multimodal imaging in VRL eyes. Lymphomatous infiltration created focal PEDs showing abnormal imaging signals. Outer retinal layer nodularity could represent an additional sign of infiltration. Multimodal imaging may guide physicians in the early diagnosis of VRL

MULTIMODAL IMAGING IN DEFEROXAMINE RETINOPATHY

PURPOSE: To describe macular lesions in patients with deferoxamine (DFO) retinopathy, and to follow their clinical course using multimodal imaging. METHODS: The authors retrospectively reviewed charts and multimodal imaging of 20 patients with \u3b2-thalassemia diagnosed with DFO retinopathy (40 eyes) after a minimum of 10 years of DFO treatment. Imaging included fundus photography, near-infrared reflectance and fundus autofluorescence imaging on confocal laser scanning ophthalmoscope, and spectral domain optical coherence tomography. RESULTS: Mean age of the 20 patients was 45 years, and mean duration of subcutaneous DFO therapy was 32 years (range, 20-52 years). Ten patients (50%) showed different types of pattern dystrophy-like fundus changes, including butterfly shaped-like (n = 3), fundus flavimaculatus-like (n = 3), fundus pulverulentus-like (n = 3), and vitelliform-like (n = 1) changes. Ten patients (50%) presented only minimal changes in the macula; these patients were significantly younger than patients presenting other patterns (P = 0.023). Confocal laser scanning ophthalmoscope and spectral domain optical coherence tomography showed that these abnormalities were more diverse and widespread than expected by ophthalmoscopy. Abnormal fundus autofluorescence and/or near-infrared reflectance signals corresponded to accumulation of material located within the outer retina or in the Bruch membrane-retinal pigment epithelium (RPE) complex on spectral domain optical coherence tomography. Follow-up examinations during a 40-month period revealed progressive development of RPE atrophy in areas of pattern dystrophy-like changes. CONCLUSION: DFO retinopathy included a variety of pattern dystrophy-like changes or minimal changes affecting the RPE-Bruch membrane-photoreceptor complex. Multimodal imaging demonstrated that fundus changes were more diverse and widespread than expected from ophthalmoscopy. Consistently with previous histologic description of DFO retinopathy, multimodal imaging confirmed that photoreceptor outer-derived retinoids, various fluorophores, and RPE displacement or clumping are involved in DFO retinopathy, finally leading to frank RPE atrophy in most cases of pattern dystrophy-like changes

Abnormal fundus autofluorescence results of patients in long-term treatment with deferoxamine

PURPOSE:To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with \u3b2-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN:Prospective, cross-sectional, case-control study. PARTICIPANTS:A total of 197 consecutive patients with \u3b2-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS:All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES:Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS:Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS: Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DF

Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

Brown adipocytes are unique in that they expend energy and produce heat to maintain euthermia through expression of uncoupling protein-1 (UCP1). Given their propensity to stimulate weight loss and promote resistance to obesity, they are a compelling interventional target for obesity-related disorders. Here, we tested whether an optogenetic approach could be used to activate UCP1-dependent thermogenesis in brown adipocytes. We generated brown adipocytes expressing a bacterial-derived photoactivatable adenylyl cyclase (bPAC) that, upon blue light stimulation, increases UCP1 expression, fuel uptake and thermogenesis. This unique system allows for precise, chemical free, temporal control of UCP1-dependent thermogenesis, which can aid in our understanding of brown adipocyte biology and development of therapies that target obesity-related disorders