Rosa M. Coco

Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss

PURPOSE To describe fundus autofluorescence (AF) patterns and their change over time in patients with age-related macular degeneration (AMD) and high risk of visual loss participating in the drusen laser study (DLS). DESIGN Randomized clinical trial. METHODS The study population consisted of 29 patients (35 eyes) participating in the DLS, which is a prospective, randomized, controlled clinical trial of prophylactic laser therapy in patients with AMD and high risk of neovascular complications. The intervention consisted of 16 eyes having prophylactic laser and 19 receiving no treatment. The main outcome measures were changes in the distribution of drusen and AF. Patients were reviewed for a median follow-up or 24 months (range 12-36 months). RESULTS At baseline, four patterns of fundus AF were recognized: focal increased AF (n = 18), reticular AF (n = 3), combined focal and reticular AF (n = 2), and homogeneous AF (n = 12). At last follow-up, fundus AF remained unchanged in 15 untreated (78%) and in seven treated (43%) eyes. In only one untreated eye, focal areas of increased AF returned to background levels and were no longer detectable at last follow-up, compared with six treated eyes. This difference was statistically significant (P =.03). Only large foveal soft drusen (drusenoid pigment epithelium detachments) consistently corresponded with focal changes in AF, whereas no obvious correspondence was found between small soft drusen located elsewhere and changes in AF. CONCLUSION The lack of obvious correspondence between the distribution of drusen and of AF found in this study appears to indicate that drusen and AF represent independent measures of aging in the posterior pole.

Surgical outcomes for primary rhegmatogenous retinal detachments in phakic and pseudophakic patients: the Retina 1 Project—report 2

Aims: To compare anatomical and functional outcomes for 546 phakic and pseudophakic primary rhegmatogenous retinal detachments (RDs) treated by pars plana vitrectomy or scleral buckling. Methods: Prospective, non-randomised, interventional study in 15 centres in Spain and Portugal, with data from RDs consecutively treated from January 2005 to May 2007. Cases with preoperative proliferative vitreoretinopathy grade C-1 or higher and perforating trauma were excluded. Minimum follow-up was 3 months. Twenty-seven pre-, intra- and post-surgical variables for each patient were analysed. Multivariate analysis was carried out by logistic regression analysis with stepwise selection of variables. Results: Data from 546 patients were analysed. Global anatomical success was 94.7%. Logistic regression analysis showed that only the development of postoperative proliferative vitreoretinopathy was associated with a poor anatomical outcome. The poorest functional results were associated with macular involvement, extension of RD, previous RD surgery, time of evolution of RD, and age of patient. Hierarchical log-linear analysis showed no effect of the lens status (phakic versus pseudophakic) on the functional results. However, pars plana vitrectomy was most often performed in pseudophakic eyes and resulted in a worse final visual acuity (p<0.001). Conclusions: No differences in anatomical success between phakic and pseudophakic eyes were found in this series. Pars plana vitrectomy was most often performed in pseudophakic eyes and had a greater probability of a worse final visual acuity than scleral buckling.

A Strong Genetic Association between the Tumor Necrosis Factor Locus and Proliferative Vitreoretinopathy: The Retina 4 Project

OBJECTIVE To assess the genetic contribution to proliferative vitreoretinopathy (PVR) and report the strong association observed in the tumor necrosis factor (TNF) locus. DESIGN As a component of The Retina 4 Project, a case-controlled, candidate gene association study in the TNF locus was conducted. PARTICIPANTS AND CONTROLS Blood from 450 patients with (138 cases) and without (312 controls) post-rhegmatogenous retinal detachment (RD) PVR was genotyped to determine polymorphisms located in the TNFα gene. METHODS Single nucleotide polymorphisms (SNPs) with correlation coefficients of ≥ 0.8 and a minor allelic frequency of ≥ 10% were studied. Functional SNPs or SNPs previously described in association with other inflammatory diseases were also added for analysis. The SNPlex Genotyping System (Applied Biosystems, Foster City, CA) was used for genotyping. Single nucleotide polymorphism and haplotype analyses were performed. Bioinformatic tools were used to evaluate those SNPs that were significantly associated. MAIN OUTCOME MEASURES Single and haplotypic significant associations with PVR. RESULTS A total of 11 common tag SNPs in the following genes were analyzed: lymphotoxin alpha (LTA), TNFα, leukocyte-specific transcript 1 (LST1), and the activating natural killer receptor p30 (NCR3). After permutation, there was a significant association in the non-synonymous polymorphism rs2229094(T→C) in the LTA gene (P = 0.0283), which encodes a cysteine to arginine change in the signal peptide. This marker was also present in all significant haplotypic associations and was not observed in any nonsignificant associations. When this SNP was analyzed using bioinformatic tools, the hydropathy profile changed, as well as the transmembrane region and the splicing site predictions. CONCLUSIONS The strong association found in the rs2229094(T→C) of the LTA gene may indicate an important role of this polymorphism in the development of PVR. If supported in extended studies, the rs2229094(T→C) may have significant implications regarding the genetic risk of the retinal repairing process.

Non-complicated retinal detachment management: variations in 4 years. Retina 1 project; report 1

Aims: To assess variations in the characteristics and management of two series of non-complicated rhegmatogenous retinal detachments (RD) carried out 4 years apart in Spain. Methods: Prospective, multicentric, non-randomised comparative study. 339 consecutive cases of RD treated in five hospitals were included. Group 1 (G1) (n = 186) included cases operated on from 1999 to 2001; group 2 (G2) (n = 153) included cases from 2004 to 2006. 83 variables related to preoperative characteristics of RD, surgical management and postoperative evolution were recorded. Surgeons were allowed to treat patients following their personal criteria. Differences in preoperative characteristics, rate of vitrectomy and anatomical outcome were studied. Quantitative variables were compared by Mann–Whitney U test and qualitative variables by standard contingency tables. Multivariate analysis was carried out by logistic regression analysis. Results: G1 showed a significantly longer delay in performing surgery, since the first symptoms appeared (G1: 29 (SD 50) days; G2: 22 (55); p<0.001) and more RD without visible retinal break than G2 (G1: 17.4%; G2: 9.2%; p = 0.028). In G2, cases with multiple retinal breaks (G1: 31.6%; G2: 44.6%) were more frequent (p = 0.022). No significant differences in other preoperative variables were observed. Vitrectomy was performed in 30.1% in G1 and in 78.4% in G2 as a primary surgical approach (p<0.001). Regardless of the characteristics of the RD, the rate of vitrectomy was higher in G2. The reattachment rate was over 94% in both groups (p = 0.833). Pseudophakic RD showed better anatomical outcomes in G2 (G1: 83.9%; G2: 96.4%; p = 0.028). Conclusion: There is an increasing tendency to treat RD with primary vitrectomy, which is related to neither a higher complexity of cases nor better anatomical results.

Pathology associated with optical coherence tomography macular bending due to either dome-shaped macula or inferior staphyloma in myopic patients.

Purpose: To evaluate the prevalence of and describe the pathology associated with macular bending (MB) defined as a smooth macular elevation found in optical coherence tomography (OCT) of patients with high myopia related to either dome-shaped macula (DSM) or the border of an inferior staphyloma. Procedures: We reviewed the 330 files of all highly myopic patients in our database that had had an OCT performed in the last 5 years. Main outcome measures were MB prevalence and its associated pathology. Results: Sixty-eight eyes from 45 patients (13.63%) presented MB; 23 bilateral, 40 in a posterior pole or macular staphyloma and 21 in an inferior staphyloma. Eighteen eyes presented choroidal neovascularization (CNV), 7 subretinal fluid without CNV, 11 retinoschisis and 3 a macular hole which had been stable for years. No differences were found in the rate of complications between patients with DSM or inferior staphyloma. Conclusions: MB is not an uncommon clinical feature. Associated pathology prevalence in MB was elevated and similar in posterior and inferior staphylomas.

Intraretinal immunohistochemistry findings in proliferative vitreoretinopathy with retinal shortening.

To report the major intraretinal pathological changes in retinas with proliferative vitreoretinopathy (PVR) and retinal shortening, 13 human retinal samples from postoperative PVR after primary surgery for retinal detachment were immunostained for vimentin, glial fibrillary acidic protein (GFAP), cytokeratins, and CD68. One more sample was studied with electron microscopy. Retinal disorganization, neuronal loss, and gliosis were observed in 12 out of 13 samples, but all 13 were positive for GFAP. Müller cell processes showed different degrees of intermediate filament hyperplasia. CD68-positive cells were present in 11 of 13 retinal samples. Conclusion: A gliotic response plays a major role in retinal shortening in PVR. In addition, the presence of macrophage-like cells in retinal tissues suggests a possible role of these cells in the pathogenesis of this variety of PVR.

Photodynamic Therapy for Subfoveal and Juxtafoveal Choroidal Neovascularization Associated with Punctate Inner Choroidopathy

Purpose: To evaluate the treatment of subfoveal and juxtafoveal choroidal neovascularization (CNV) using verteporfin photodynamic therapy (vPDT) in patients affected by punctate inner choroidopathy (PIC). Methods: A chart review of 8 patients with CNV associated with PIC treated with vPDT was done. Results: The 8 patients (8 eyes) included 4 men and 4 women with a mean age of 30.9 years. Six of them presented juxtafoveal CNVs, and two had subfoveal CNVs, at presentation. Mean follow-up time was 22.7 months. The VA improved in five eyes, and three eyes declined. One patient developed a new CNV a few days after vPDT, and one had multiple CNVs at presentation. Two of the 3 patients with longer follow-up period presented late recurrences. Conclusions: vPDT is a beneficial resource in stabilizing and also improving VA in PIC patients affected with subfoveal and juxtafoveal CNV, although one third of the patients retain poor visual acuity.

High-performance liquid chromatographic determination of vancomycin in rabbit serum, vitreous and aqueous humour after intravitreal injection of the drug

A high-performance liquid chromatographic method for the determination of vancomycin in rabbit serum, vitreous and aqueous humour has been developed. No clean-up step was necessary for vitreous and aqueous humour samples. For serum samples liquid-liquid and solid-phase extraction were tested and the best results were achieved using C18 cartridges. The extracts were analyzed on a C18 reversed-phase column, using a mixture of 0.05 M phosphate buffer (pH 4) with 10% of acetonitrile as mobile phase. The detection was carried out at 198 nm, which allows higher sensitivity. The average quantitation limit obtained was 0.03 micrograms/ml. The method has been applied to the study of the residual quantities of vancomycin in serum and rabbit eyes after intravitreal administration of the drug in endophthalmitis treatment.

Burden of illness of bilateral neovascular age-related macular degeneration in Spain

ABSTRACT Background: The burden of illness, including health resource utilization and costs associated with bilateral neovascular age-related macular degeneration (Nv-AMD), was assessed in Spain. Patients and methods: As part of an international prospective, case-controlled study, 89 Spanish patients with bilateral Nv-AMD were recruited by retina specialists and 96 Spanish control subjects were recruited by general practitioners and ophthalmologists. Physicians recorded clinical data and visual acuity (VA). In a subsequent telephone interview, Nv-AMD patients and controls completed the National Eye Institute Visual Function Questionnaire (NEI VFQ)-25, the EuroQol (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS) questionnaire. Annual vision-related and non-vision-related medical costs and non-medical-related costs were calculated from study-specific questions. Results: The mean age was 76.2 years for Nv-AMD patients and 61.9 years for control subjects. The adjusted mean (95% CI) NEI VFQ-25 summary score was 51.9 (48.5; 55.4) for Nv-AMD patients and 87.7 (85.5; 89.9) for control subjects (p < 0.05). The summary score of Nv-AMD patients decreased significantly with VA declination. Mean direct vision-related medical and non-medical-related costs were significantly greater for Nv-AMD patients than the control subjects, whereas non-vision-related medical costs were similar between groups. The total mean annual resource utilization cost was €5733 for Nv-AMD patients compared to €1070 for control subjects (p < 0.0001). Conclusions: Although the study design is subject to a number of limitations, patients with Nv-AMD in Spain have worse quality of life outcomes, greater depression, and higher healthcare costs as compared with similarly-aged individuals who are not affected by this disease.

Oct findings in torpedo maculopathy.

BACKGROUND Torpedo maculopathy, also called solitary hypopigmented nevus, is a rare though benign disorder. To our knowledge, there are no previous optical coherence tomography (OCT) descriptions in the literature. METHODS Results of ophthalmologic examinations (including retinography, OCT, and visual field testing) for 2 girls aged 12 years and 13 years throughout 5 years of follow-up were reviewed. RESULTS In both cases, anterior and posterior segment evaluation was unremarkable except for the presence of a flat, fishtail-shaped, hypopigmented lesion temporal to the macula, pointing to the fovea. In case 1, OCT disclosed faint thinning of the retina above the lesion especially in the outer retina and hyperreflectivity of the retinal pigment epithelium (RPE) associated with a posterior hyperreflective signal deep in the choroids. In case 2, OCT showed an atrophic retina with reduced thickness probably due to the absence of the photoreceptor layer. Shallow serous neurosensory detachment, increased RPE reflectivity, and higher penetration of light to the choroid were also evident. CONCLUSION In both cases of torpedo maculopathy studied by OCT, we found a variable amount of retinal degeneration, and a serous retinal detachment was found in one case.