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Purpose Photodynamic therapy (PDT) has been widely used in the treatment of age-related macular degeneration (AMD). The complement cascade has an important role in the tissue reactions occurring after PDT. The Y402H polymorphism of the complement factor H (CFH) gene has been identified as a risk factor for AMD. Since CFH is central in the regulation of the complement system the authors wanted to analyze whether the CFH Y402H polymorphism modifies the PDT outcome in AMD. Methods A total of 88 patients having been treated with PDT and without further scheduled PDT sessions were analyzed. Depending on the situation at their final PDT session the patients were classified retrospectively as PDT-responders or PDT-nonresponders. All patients were genotyped for the CFH Y402H polymorphism. Results The proportion of PDT-responders was 18/26 (69.2%) in patients homozygous for the CFH Y402H risk allele, 34/50 (68.0%) in heterozygous, and 7/12 (58.3%) in patients with the normal genotype (p=0.520). The median number of PDT treatments of the PDT-responders was three for all the genotypes. Conclusions The dysfunction of the CFH related to the risk of AMD and caused by the Y402H polymorphism does not modify the outcome of PDT. Genotyping for CFH Y402H cannot be used to select patients for this treatment.

The formation of glycohemoglobin, especially the hemoglobin A1c (HbA1c) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970s it has been known that diabetics display higher values OF HbA1C because they have elevated blood glucose concentrations. Thus HbA1c has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement OF HbA1C, numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple mini-column technique to the very accurate automated high-pressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for HbA1c varied extensively between laboratories, therefore in United States and Canada working groups (WG) of the Diabetes Controls and Complications Trial (DCCT) were set up to standardize the HbA1c assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990s, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) appointed a new WG to plan a reference preparation and method for the HBA1c measurement. When the reference procedures were established, in 2004 IFCC recommended that all manufacturers for equipment used in HbA1c assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation (CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the HbA1c assays, analytical problems, problems with the units in which HbA1c values are expressed, reference values, quality control aspects, target requirements for HbA1c, and the relationship of the plasma glucose values to HbA1c concentrations. We also note that the acceptance of the mmol/mol system for HbA1c as recommended by IFCC, i.e., the new unit and reference ranges, are becoming only slowly accepted outside of Europe where it seems that expressing HbA1c values either only in per cent units or with parallel reporting of percent and mmol/mol will continue. We believe that these issues should be resolved in the future and that it would avoid confusion if mmol/mol unit for HbA1c were to gain worldwide acceptance.

Background We evaluated the Iris iQ200 Automated Urine Microscopy Analyzer to find out if the instrument performed better than traditional visual bright field microscopy in detecting basic urine particles, as assessed against reference phase contrast microscopy. Methods The HUSLAB quality system was followed in planning and completing the evaluation process. The iQ200 instrument results from 167 mid-stream, uncentrifuged urine specimens were compared to those obtained with phase contrast reference microscopy, and to those with routine bright field microscopy. Linearity, carry-over and precision were tested according to well-established protocols. Results The iQ200 counted erythrocytes (RBC) at r = 0.894 ( R 2 = 0.799) with Automated Particle Recognition (APR) software alone and at r = 0.948 ( R 2 = 0.898) after re-classification. The performance for leukocytes (WBC) was r = 0.885 with APR and r = 0.978 after re-classification. The correlations of counting after user re-classification were r = 0.927 for squamous epithelial cells (SQEP), r = 0.856 for casts, and r = 0.706 for non-squamous epithelial cells. The iQ200 showed good linearity and precision and no carry-over was detected. Conclusions The Iris iQ200 was capable to count reliably RBC, WBC, and SQEP cells and to identify a fraction of bacteria and renal elements. Counting results equalled or exceeded that of routine bright field microscopy or earlier flow cytometric technology. The instrument eliminates manual sample preparation but requires a well-trained technologist for re-grouping of findings.

Objective This study aimed to determine whether the characteristics of pseudophakic retinal detachment (RD) differ in eyes with and without a neodymium (Nd):YAG laser capsulotomy to identify features that might help to treat capsulotomy patients better. Design The study design was a retrospective cohort study of 129 consecutive eyes, 61 with a capsulotomy and 68 control eyes with an intact posterior capsule, in which a primary rhegmatogenous RD developed after a strictly uncomplicated extracapsular cataract extraction and intraocular lens implantation. Setting The study was conducted in a primary referral center. Main outcome measures Number, type, and location of retinal breaks and type and extent of RD were measured. Results Risk factors predisposing to RD did not differ between the capsulotomy and control group. The median interval from cataract surgery to RD was expectedly longer in the capsulotomy group (4.1 years vs. 1.5 years, P P = 0.05), especially in upper quadrants (82 of 103 vs. 48 of 77, P = 0.024). Capsulotomy eyes also had a trend to have more atrophic holes that caused detachment relative to horseshoe breaks (34 of 103 vs. 15 of 77, P = 0.062). The type and extent of RD were similar in the two groups. Conclusions This pilot study suggests that atrophic holes, particularly in the superior quadrants, may lead to RD preferentially after posterior capsulotomy. Early identification and treatment of such breaks might decrease the number of pseudophakic detachments after capsulotomy.

Background Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. Methods/Principal Findings We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75×10−9; non-AMD controls and OR 2.79, p = 2.78×10−19, blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. Conclusions/Significance Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

Purpose: The Y402H polymorphism of the complement factor H (CFH) gene is associated with age-related macular degeneration (AMD) in many populations. The reported genotype)phenotype correlations in the CFH Y402H polymorphism have not been pronounced and no studies on the effect of the polymorphism on the subgroups within wet AMD have been performed. In this study, we wanted to evaluate whether the CFH Y402H polymorphism has an effect on clinical variables in recent exudative AMD lesions. Methods: The study included 172 patients with exudative AMD. The size of AMD lesions and the presence and area of other AMD lesion variables were recorded in fluorescein angiography (FA) and analysed in relation to the Y402H genotypes. Results: The median lesion size (classic + occult choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] + haemorrhage, if present) was 8.15 mm 2 in patients homozygous for the CFH risk allele (CC), 7.50 mm 2 in heterozygous patients (CT), and 7.05 mm 2 in those with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV, combined, without serous PED or haemorrhage were 6.37 mm 2 , 5.00 mm 2 and 5.18 mm 2 , respectively (p = 0.407). There was a trend for CC patients to have more frequently minimally classic and less frequently predominantly classic lesion composition than CT or TT subjects. Conclusions: We detected no clear impact of the CFH Y402H polymorphism on recent exudative AMD lesion characteristics. Although the complement cascade is implicated in CNV formation and scarring processes in the retina, the Y402H polymorphism appears relatively neutral in these functions.

A strong association of a Tyr402His polymorphism in the complement factor H (CFH) gene and a Met299Val polymorphism in the elongation of very long chain fatty acids-like 4 (ELOVL4) gene with age-related macular degeneration (AMD) has been identified in Caucasian populations in the United States. Earlier a Gln5345Arg variant in the hemicentin 1 (HMCN1) gene was reported in a large AMD family in the United States. We wanted to investigate whether the polymorphisms of the CFH and the ELOVL4 genes or the mutation of the HMCN1 gene are associated with AMD in patients originating from the Finnish population with characteristics of a genetic isolate.The material consisted of familial (n=181) and sporadic cases (n=154) with AMD, a control group with no AMD (non-AMD controls, n=105), and a control group of anonymous blood donors (blood donor controls, n =350). The DNA of the subjects was sequenced to analyze the variants of the three genes.We detected a strong association between the C/C-genotype compared to the T/T-genotype of Tyr402His polymorphism (first base of the Tyr-codon changes) of the CFH gene and AMD in the AMD cases compared to the non-AMD (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)). The frequency of the C/C genotype was significantly increased in both familial cases compared to non-AMD controls with non-adjusted odds ratio (OR) 10.1 (confidence intervals [CI] 95% 4.64-22.2) or compared to blood donor controls with non-adjusted OR 5.50 (CI 95% 3.17-9.55) and in sporadic cases with non-adjusted OR 9.33 (CI 95% 4.10-21.3; non-AMD-controls), OR 5.06 (CI 95% 2.75-9.28; blood donor controls). Frequency of C allele differed significantly between cases and controls (p=1.32x10(-11); non-AMD-controls and p=3.94x10(-14); blood donor controls). No association with AMD was detected with Met299Val polymorphism in the ELOVL4 gene in the familial or sporadic cases compared to non-AMD or blood donor controls. None of our subjects (258 AMD cases, 72 non-AMD controls) had the Gln5345Arg variant in the HMCN1 gene.The CFH gene polymorphism seems to be an important etiologic factor for AMD also in the isolated Finnish population.

Purpose: To determine the 5-year incidence of retinal breaks and retinal detachment (RD) after neodymium:YAG (Nd:YAG) laser posterior capsulotomy and the prophylactic treatment of perioperative retinal breaks. Setting: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. Methods: This study design was stage 2 of a prospective nonrandomized interventional case series. Of 341 patients (350 eyes) referred for a first Nd:YAG laser posterior capsulotomy between October 1994 and February 1996, 211 (220 eyes) were examined for retinal breaks before and after capsulotomy (stage 1 of study). Asymptomatic breaks were prophylactically photocoagulated. Of the 211 patients, 106 (113 eyes) were examined at stage 2 a median of 4.9 years after Nd:YAG capsulotomy. The charts of all 341 patients were reviewed for development of RD and retinal breaks. The proportion of patients developing RD was estimated by Kaplan-Meier survival analysis, and the risk for RD was modeled by Cox proportional hazard regression. Results: By 5 years, the overall cumulative proportion of RD in the 341 patients was 2.0% (95% confidence interval [CI], 1.0-4.0). Of the 211 eyes enrolled in stage 1, 2 (1.2%) developed an RD (95% CI, 0.3-4.7). Of 51 fellow eyes that had a capsulotomy and 120 eyes that had a capsulotomy but were not enrolled in stage 1 and were not prophylactically treated, RD occurred in 6 eyes (5.8%; 95% CI, 2.6-13). By univariate Cox regression, the axial length, whether modeled as a continuous variable (hazard ratio [HR] 1.51 for each millimeter increase) or categorized using 25.0 mm as a cutoff (HR 11.1), had the strongest association with RD after Nd:YAG posterior capsulotomy (P = .0002 and P = .0016, respectively). Conclusions: In addition to the capsulotomy, other known risk factors predicted RD after Nd:YAG laser posterior capsulotomy. Close follow-up and prophylactic photocoagulation of preexisting retinal breaks are worth considering, especially in high-risk eyes.