Päivi Ranta

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

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.

Retinal breaks and detachment after neodymium:YAG laser posterior capsulotomy: Five-year incidence in a prospective cohort

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.

Retinal detachment in pseudophakic eyes with and without Nd:YAG laser posterior capsulotomy

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 < 0.001). The mean number of retinal breaks was larger in the capsulotomy group (1.7 vs. 1.1, 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.

Retinal breaks before and after neodymium:YAG posterior capsulotomy.

PURPOSE To determine the frequency of asymptomatic retinal breaks before and after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS Of 350 consecutive patients referred for their first laser Nd:YAG posterior capsulotomy, 235 eligible eyes were enrolled and 220 eyes completed the study. A vitreoretinal surgeon looked for retinal breaks using binocular indirect ophthalmoscopy with scleral indentation. The eyes were examined 1 week before and 1 hour and 1 month after the posterior capsulotomy. The number, type, and location of retinal breaks were recorded. RESULTS The median age of eligible patients who did not participate in the study was higher than that of enrolled patients (79.6 versus 74.4 years; P =.0005). The mean axial length, median time from cataract surgery, and the course of cataract surgery were comparable in both groups. Before the posterior capsulotomy, an untreated retinal break was diagnosed in 4 of the 235 eyes (1.7%; 95% confidence interval [CI] 0 to 4) scheduled for surgery and an undiagnosed retinal detachment was present in 2 additional eyes (0.9%; 95% CI 0 to 3). An asymptomatic retinal break was also present in 4 fellow eyes (1.7%, 95% CI 0 to 4). No new breaks developed during Nd:YAG posterior capsulotomy using a median total energy of 51 mJ (range 10 to 901 mJ) and a median number of 22 applications (range 4 to 341 applications) and resulting in an opening with a median largest diameter of 3.4 mm (range 2.0 to 4.6 mm). In 1 treated eye (0.4%; 95% CI 0 to 2), a new retinal break had developed by 1 month postoperatively. CONCLUSIONS The observed 2.1% frequency of asymptomatic retinal breaks that had escaped the attention of the referring ophthalmologist or had developed by 1 month after Nd:YAG posterior capsulotomy can be contrasted with the 0.5% to 2.0% frequency of retinal detachment reported in the literature. However, it is not known which proportion of such asymptomatic breaks, if any, will progress to detachment after Nd:YAG laser posterior capsulotomy.

Functional and anatomic outcome of retinal detachment surgery in pseudophakic eyes

PURPOSE To determine the long-term anatomic and functional visual outcome of retinal detachment (RD) surgery in pseudophakic eyes after uncomplicated cataract surgery. DESIGN An interventional, retrospective noncomparative case series PARTICIPANTS One hundred thirty-eight consecutive patients who had undergone uncomplicated extracapsular cataract extraction and intraocular lens implantation followed by rhegmatogenous RD between 1990 and 1995. METHODS One hundred one eligible patients were examined (inclusion ratio, 73%) a median of 4.3 years after last RD surgery. The best-corrected visual acuity (BCVA), visual fields, retinal status, and patient-rated visual outcome were recorded, the latter by a questionnaire that included self-reported satisfaction, trouble with vision, a modified Cataract Symptom Score, and the VF-14 Visual Functioning Index. MAIN OUTCOME MEASURES BCVA, retinal attachment, diameter of visual field, modified Cataract Symptom Score, VF-14 score. RESULTS Baseline characteristics of enrolled and nonenrolled patients were comparable, except that nonenrolled patients were older. When RD developed, 55 eyes had an intact posterior capsule, and 46 had a laser posterior capsulotomy (LCT). The BCVAs before (median, logarithm of the minimum angle of resolution [-logMAR] 1.2 versus 1.1, Snellen equivalent 0.063 versus 0.08) and after retinal surgery (median, -logMAR 0.46 versus 0.4, Snellen equivalent 0.35 versus 0.4) were comparable for eyes with and without LCT (P = 0.86). The retina was reattached with one procedure in 75 eyes (74%), with two procedures in 98 eyes (97%), and with three to five procedures in all eyes. The retina remained attached long term in 92 eyes (91%). Redetachment rate (9% versus 9%, P = 1.0) and visual field diameters were comparable for eyes with and without LCT. Overall, 80% of patients were satisfied or very satisfied with their binocular vision, and 62% had no or only a little trouble with binocular vision. Visual performance was similar regardless of presence or absence of LCT (median Cataract Symptom Score, 3.0 versus 3.0, P = 0.76; and median VF-14 score, 87.5 versus 87.5, P = 0.81). CONCLUSIONS Nine in 10 pseudophakic retinal detachments remain attached long term, and 8 in 10 patients are satisfied with their binocular vision after surgery. Even though secondary cataract and posterior capsulotomy can cause problems for the retinal surgeon, the anatomic and functional outcomes of pseudophakic RD are not influenced by capsulotomy.

Complement factor H Y402H polymorphism and characteristics of exudative age‐related macular degeneration lesions

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.