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A letter to the editor in response to the article "The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis," by A. Thakkinstain et al, in a previous issue is presented.

The article reports that seven genetic loci in the pathogenesis of age-related macular degeneration (AMD) have been identified by the AMD Gene Consortium. It is hope that the development will help identify individuals at risk of developing severe disease, with the number of loci implicated in AMD totaled 19. Sudha K. Iyengar of Case Western reserve University School of Medicine describes some features of the seven new loci.

The article discusses the study that found four well-documented single-nucleotide polymorphisms within four different genes associated with age-related macular degeneration (AMD) did not predict response to anti- vascular endothelial growth factor (VEGF) treatment in patients with neovascular AMD. According to principal investigator Stephanie A. Hagstrom, Doctor of Philosophy (PhD), a difference in response to therapy was seen in the clinic and in Comparison of AMD Treatments Trials (CATT).

This study will examine whether certain polymorphisms (small gene variances) predispose people to develop Age-related macular degeneration. AMD affects people older than 50 years of age and can cause permanent loss of central vision. The study will examine and compare the frequency of polymorphisms in patients with AMD to that of individuals without AMD. This information will help identify genetic risk factors for AMD and may lead to the development of more effective treatments. [ABSTRACT FROM AUTHOR]

The article presents a survey question to eye specialists/ophthalmologists whether they would administer the genetic tests if the tests were readily available in their office.

The article reports that the StarGen gene therapy clinical test for Stargadt's disease has occurred at Oregon Health and Science University in Portland, Oregon. The therapy is created by British pharmaceutical Oxford Biomedica with financial aid from the Foundation Fighting Blindness. StarGen seeks to apply injection of a synthetic virus that carries as healthy replica of the ABCA4 gene into retinal cells to treat blindness caused by the disease.

Purpose: To determine if genetic variants that have been associated with age-related macular degeneration (AMD) have a differential effect on the risk of choroidal neovascularization (CNV) and geographic atrophy. Design: Genetic association study. Methods: setting: Multicenter study. study population: Seven hundred forty-nine participants with geographic atrophy and 3209 participants with CNV were derived from 4 AMD studies with similar procedures from Tufts Medical Center, the Age-Related Eye Disease Study, University of Utah, and Hopital Intercommunal de Creteil. procedures: AMD grade was assigned based on fundus photography and examination using the clinical age-related maculopathy staging system. All samples were genotyped for single nucleotide polymorphisms (SNPs) previously associated with AMD. Allele frequencies were compared between participants with CNV and geographic atrophy using PLINK within each cohort and Mantel-Haenszel meta-analysis was performed to combine odds ratios (OR). main outcome measures: Differences in allele frequencies between participants with geographic atrophy and CNV. Results: The frequency of the T allele of ARMS2/HTRA1 rs10490924 was significantly higher in participants with CNV than in those with geographic atrophy (OR, 1.37; 95% confidence interval, 1.21–1.54; P value = 4.2 × 10−7). This result remained statistically significant when excluding individuals who had geographic atrophy in 1 eye and CNV in the contralateral eye (P = 2.2 × 10−4). None of the other SNPs showed a significant differential effect for CNV vs geographic atrophy, including CFH, C2/CFB, C3, CFI, LIPC, and TIMP3. Conclusions: Genetic variation at the ARMS2/HTRA1 locus confers a differential risk for CNV vs geographic atrophy in a well-powered sample. [ABSTRACT FROM AUTHOR]

The article focuses on a study which assessed the role of the hepatic lipase gene in age-related macular degeneration (AMD) risk. The study included 979 unrelated advanced AMD patients and 1,709 unrelated controls. Study authors discovered that a genetic link exists between a gene related to high-density lipoprotein or good cholesterol and a risk of AMD. They claimed that their study showed alternative hallmark of wet AMD and sign of dry AMD.

Purpose: To report the first use of in vitro fertilization (IVF) and preimplantation genetic diagnosis to achieve an unaffected pregnancy in an autosomal-recessive retinal dystrophy. Design: Case report. Methods: An affected male with Stargardt disease and his carrier wife underwent IVF. Embryos obtained by intracytoplasmic sperm injection underwent single-cell DNA testing via polymerase chain reaction and restriction enzyme analysis to detect the presence of ABCA4 mutant alleles. Embryos were diagnosed as being either affected by or carriers for Stargardt disease. A single carrier embryo was implanted. Results: Chorionic villus sampling performed during the first trimester verified that the fetus possessed only 1 mutant paternal allele and 1 normal maternal allele, thus making her an unaffected carrier of the disease. A healthy, live-born female was delivered. Conclusion: IVF and preimplantation genetic diagnosis can assist couples with an affected spouse and a carrier spouse with recessive retinal dystrophies to have an unaffected child. [Copyright &y& Elsevier]

The article presents the author's views on the role of genetics in age-related macular degeneration (AMD). According to the author, at least 15 genes with a large number of single nucleotide polymorphisms (SNPs) on them are associated with the development of AMD. The author says that these SNPs play an important role in the development of both AMD and polypoidal choroidal vasculopathy (PCV).

Purpose: To describe fundus autofluorescence (FAF) in carriers of choroideremia (CHM), and to compare FAF findings with ophthalmoscopy and electrophysiologic and psychophysical data. Design: Prospective, observational case series and systematic review. Participants: Six unrelated carriers of CHM. Methods: Clinical examination included a comprehensive ophthalmic examination, fundus photography, FAF, kinetic perimetry, 2-color threshold perimetry (2CTP), full-field electroretinography (ERG), and multifocal ERG (mfERG). All 6 carriers (33–60 years of age) were screened for mutations in the coding region of Rab Escort Protein 1 gene (REP1) including close flanking intronic sequence and deletions within 2160 bp of 5′ untranslated sequence. Main Outcome Measures: Intensity and distribution of FAF, rod sensitivity loss, cone sensitivity loss in 2CTP, amplitude and latency in full-field ERG, amplitude in mfERG, and correlation of all 3 parameters. Results: Mutations in the coding region of REP1 were identified in 3 of 6 carriers. All 6 carriers had good visual acuity. Three carriers complained of photophobia and 1 of impaired vision in dim light. Ophthalmoscopy revealed peripapillary atrophy and retinal pigment epithelium (RPE) mottling mainly in the macular region, and additional RPE clumping and flecks of atrophy in the periphery. A very irregular pattern of low- and high-density FAF speckles was seen. Low-density FAF surrounding the optic nerve head corresponded with the peripapillary atrophy. In areas of major FAF changes, mfERG was deteriorated. The 2CTP images revealed functional disturbances in rods and cones. No general pattern was observed. On MfERG, reduced amplitudes in areas with normal cone sensitivity in 2CTP were seen. Conclusions: All 6 carriers of CHM showed a characteristic FAF pattern that can guide mutation analysis. Even when other functional testing is inconspicuous, FAF is a rapid, noninvasive indicator. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Objective: To identify any mutation of the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) gene in Japanese patients with Schnyder''s crystalline corneal dystrophy (SCCD) and to investigate in vivo microstructural phenotype and genotype correlations using laser scanning confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module; Heidelberg Engineering GmbH, Dossenheim, Germany). Design: Small, comparative case series. Participants: Three patients from 3 pedigrees (3 males) with clinically diagnosed SCCD and their relatives (2 males, 1 female) participated in this study. Testing: All participants were examined genetically and by slit-lamp biomicroscopy and in vivo laser confocal microscopy. Main Outcome Measures: Genomic DNA from the patients and 100 unrelated healthy volunteers (200 chromosomes) was isolated from blood samples and used for mutation screening of the UBIAD1 gene. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of deposits. Results: Novel mutations in the UBIAD1 gene (Y174C, K181R, and N233H) were identified. Additionally, cosegregation of the mutation (Y174C) and SCCD was confirmed in 1 pedigree, indicating that the mutation of the UBIAD1 gene is causative for SCCD. The 3 mutations were absent in all 200 control chromosomes. In vivo laser confocal microscopy demonstrated subepithelial highly reflective crystals in 4 cases; the shapes of the crystals were needle-shaped (3 cases) or rectangular (1 case). A phenotype and genotype correlation was demonstrated in 1 pedigree, and phenotypic heterogeneity (SCCD with or without crystals caused by a same mutation of Y174C in the UBIAD1 gene) also was demonstrated in 1 pedigree. Conclusions: Nonsynonymous novel mutations in the UBIAD1 gene were detected in 3 unrelated Japanese pedigrees with SCCD, confirming the genetic heterogeneity of this disorder. In vivo laser confocal microscopy is capable of identifying characteristic corneal microstructural changes related to genetically mapped SCCD with high resolution, and phenotypic heterogeneity was presented. Further confocal and mutational analysis using a larger number of patients with SCCD is required to elucidate in vivo microstructural phenotype and genotype correlations. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]