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author:("orin, Anton")
1.  Spectrum of Ocular Manifestations in CLN2-Associated Batten (Jansky-Bielschowsky) Disease Correlate with Advancing Age and Deteriorating Neurological Function 
PLoS ONE  2013;8(8):e73128.
Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of Batten’s disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described.
Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed.
Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic severity score was 2.6 (range 1 to 5). The mean neurological severity score was 6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03). A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.
Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.
PMCID: PMC3756041  PMID: 24015292
2.  Ultra-widefield fluorescein angiography of white without pressure 
To describe ultra-widefield fluorescein angiography (UWFA) findings in eyes with white without pressure (WWOP) and in eyes without any obvious peripheral chorioretinal disease, and to determine if a difference exists between these two groups.
A retrospective review of 379 eyes undergoing diagnostic UWFA using the Optos 200Tx imaging system. Eyes were excluded if the quality of the color photograph or UWFA prevented reliable evaluation. Eyes were also excluded if there was any evidence of peripheral retinal or choroidal disease, which was thought to have an effect on UWFA (eg, peripheral background diabetic or hypertensive retinopathy, vein occlusion, or any other peripheral vascular disorder). Eyes were determined to have WWOP, based on a dilated fundus examination and color fundus photography that contained areas of peripheral retinal whitening consistent with the diagnosis. UWFA was evaluated by trained masked graders, and determined to have or not have peripheral vascular leakage and/or staining.
Of the 379 eyes evaluated, 45 eyes were included in the study. Twelve eyes were determined to have peripheral WWOP; 33 eyes did not have WWOP on examination or color fundus photography. Three common UWFA peripheral patterns were visualized. Eyes with and without WWOP were grouped into one of three patterns. The majority of eyes without WWOP demonstrated UWFA pattern one (69.7%), while those in the WWOP group demonstrated pattern three (50%). The distribution of UWFA patterns is statistically different between those with and without WWOP (P = 0.002). In eyes without WWOP, in patients with no documented systemic microvascular disease (diabetes, hypertension), 71.4% of eyes had UWFA pattern one while 14.3% had both patterns two and three.
This study is one of the first to specifically evaluate peripheral vascular leakage/staining in eyes with WWOP as well as in eyes without any obvious peripheral chorioretinal disease. We demonstrate that a significant portion of WWOP eyes exhibit peripheral findings on UWFA (pattern one) compared to eyes without WWOP. Importantly, even in eyes that are apparently unremarkable in the periphery on exam and color photography, UWFA can still show peripheral vascular abnormalities. These results warrant further investigation.
PMCID: PMC3667996  PMID: 23737658
ocular imaging; ptos imaging; retina periphery
3.  Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies 
Human mutation  2011;32(12):1407-1416.
Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.
PMCID: PMC3217135  PMID: 21882290
age-related macular degeneration; AMD; apolipoprotein E; APOE; case-control association study
4.  Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People 
American Journal of Epidemiology  2011;173(12):1357-1364.
Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ2 for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ2 for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.
PMCID: PMC3145394  PMID: 21498624
aged; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4; apolipoproteins E; longevity; meta-analysis; multicenter study

Results 1-4 (4)