ATM Gene Variants in Patients with Idiopathic Perifoveal Telangiectasia

PURPOSE. To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major agerelated macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT). METHODS. Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism. RESULTS. Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population. CONCLUSIONS. At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly diseaseassociated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease. (Invest Ophthalmol Vis Sci. 2008; 49:3806 -3811

A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

Comprehensive Analysis of the Candidate Genes CCL2, CCR2, and TLR4 in Age-Related Macular Degeneration

PURPOSE. To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD). METHODS. This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.S. study. Quantitative (q)PCR reactions were performed to evaluate expression of these genes in laserdissected retinal pigment epithelium from 13 donor AMD and 13 control eyes. RESULTS. Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show a significant association between D299G or T399I and AMD, nor did haplotypes containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did not demonstrate an association with AMD. For CCR2, haplotype frequencies were not significantly different between cases and controls. For CCL2, one haplotype containing the minor allele of C35C was significantly associated with AMD (P ϭ 0.03), but this did not sustain after adjustment for multiple testing (q ϭ 0.30). Expression analysis did not demonstrate altered RNA expression of CCL2 and CCR2 in the retinal pigment epithelium from AMD eyes (for CCL2 P ϭ 0.62; for CCR2 P ϭ 0.97). CONCLUSIONS. No evidence was found of an association between TLR4, CCR2, and CCL2 and AMD, which implies that the common genetic variation in these genes does not play a significant role in the etiology of AMD. (Invest Ophthalmol Vis Sci

Ocular Involvement in Patients with Fungemia in an Urban Tertiary Care Center

<p><i>Purpose</i>: To illustrate the rate of endogenous endophthalmitis associated with fungemia and evaluate the importance of screening in a public city hospital.</p> <p><i>Methods</i>: A retrospective review was performed on all inpatient ophthalmology consults for fungemia from 2010 to 2015. Clinical histories, ocular examinations, and microbial cultures were reviewed.</p> <p><i>Results</i>: Of 95 patients (mean age 51.6 years, 75% male) with fungemia, 9/95 (9.5%) demonstrated intraocular involvement. Of these nine patients, two were unable to participate in the ophthalmic exam due to intubation, while the remaining seven reported no changes in their vision. Two patients had their antifungal medications adjusted to optimize intraocular penetration and one patient progressed to develop vitreous involvement but died before further escalation of care occurred.</p> <p><i>Conclusion</i>: All involved individuals in this study were either non-communicative or without visual complaints. This suggests that routine screening should still be recommended, especially in a public hospital setting.</p

A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

Background: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. Methods: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). Results: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. Conclusions: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

Elastin rs2301995 Polymorphism is not Associated with Polypoidal Choroidal Vasculopathy in Caucasians

Methods: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the ELN locus in fifty-six patients with PCV, 368 patients with advanced age-related macular degeneration (AMD) and 368 age- and ethnically-matched unaffected controls.Results: the ELN rs2301995 SNP was not statistically significantly associated with the PCV phenotype (P == 0.9). the frequency of the minor allele of the rs2301995 SNP was practically identical in the PCV, AMD and control groups (6.3% vs. 5.4% vs. 7.1%).Conclusion: the PCV phenotype in European-American patients is not associated with rs2301995 SNP in the ELN locus.Columbia Univ, Eye Inst Res Addit, Dept Pathol & Cell Biol, New York, NY 10032 USAManhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retina Res Ctr, New York, NY USAMacula Consultants New York, Vitreous, Retina, New York, NY USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilColumbia Univ, Dept Ophthalmol, New York, NY 10032 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Expanded clinical spectrum of enhanced S-cone syndrome

New funduscopic findings in patients with enhanced S-cone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy. To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene. Retrospective, noncomparative case series of 31 patients examined between 1983 and 2012. Academic and private ophthalmology practices specialized in retinal dystrophies. A cohort of patients diagnosed with ESCS and harboring known NR2E3 mutations. Patients had ophthalmic examinations including visual function testing that led to the original diagnosis. New fundus features captured with imaging modalities. New clinical observations in ESCS include (1) torpedo-like, deep atrophic lesions with a small hyperpigmented rim, variably sized and predominantly located along the arcades; (2) circumferential fibrotic scars in the posterior pole with a spared center and large fibrotic scars around the optic nerve head; and (3) yellow dots in areas of relatively normal-appearing retina. Enhanced S-cone syndrome has more pleiotropy than previously appreciated. While the nummular type of pigmentation at the level of the retinal pigment epithelium and cystoid or schisis-like maculopathy with typical functional findings remain classic hallmarks of the disease, changes such as circumferential fibrosis of the macula or peripapillary area and "torpedo-like" lesions along the vascular arcades may also direct the clinical diagnosis and focus on screening the NR2E3 gene for a molecular diagnosi