Factors associated with serum/plasma concentrations of vitamins A, C, E and carotenoids in older people throughout Europe: the EUREYE study.

PURPOSE: To report on plasma/serum levels of antioxidant vitamin and carotenoids in older adults resident in multiple countries in Europe and examine relationships with potential modifiers. METHODS: Population-based cross-sectional European Eye Study in 7 centres from northern to southern Europe. In total, 4,133 participants aged 65 years or over, collected by random sampling, were recruited. Questionnaires relating to diet, lifestyle and medical history were administered. Non-fasting blood samples were analysed in a single laboratory for vitamins A, C and E and a panel of carotenoids. Associations were analysed by bootstrapped multivariable regression analysis. RESULTS: Centre and season influenced the serum and plasma concentrations of all antioxidant vitamins and carotenoids. Gender, BMI, smoking, age, education, alcohol consumption and supplement use were also significantly associated with some, but not all, of the antioxidant vitamins and carotenoids examined. The proportion of variance explained ranged from 4.8 % for retinol to 25.2 % for zeaxanthin. CONCLUSIONS: In older people, antioxidant vitamin and carotenoid status varies by centre and season, but is also associated with other behavioural and lifestyle variables. Studies aiming to demonstrate an association between antioxidant vitamins and carotenoid status and chronic disease risk should consider these potential confounders.

Unusual toxoplasmic chorioretinitis in advanced age: a diagnostic problem.

PURPOSE: To raise awareness regarding presentation of toxoplasmic chorioretinitis late in life, and to discuss the invasive diagnostic options. PATIENTS/METHODS: Case report. RESULTS: A 62-year-old patient presenting with posterior vitritis and a focus of retinitis was misdiagnosed and treated with antivirals and corticosteroids. Relapse after initial stabilization justified a vitreous tap for culture and DNA detection of a number of infectious agents, leading to the correct diagnosis of T.gondii infection. CONCLUSIONS: Ocular sampling may be necessary to secure timely diagnosis and treatment of atypical retinitis. Acquired ocular toxoplasmosis may be under-recognized as a cause of infectious posterior uveitis and caution should be applied when administering steroids without a definite diagnosis.

Association of diabetes with age-related macular degeneration in the EUREYE study.

OBJECTIVE: To examine the association between self-reported diabetes history and early or late age-related macular degeneration (AMD) in the European population. METHODS: Participants aged 65 years and over in the cross-sectional population-based EUREYE study underwent an eye examination including digital retinal photography. The images were graded at a single centre. A structured questionnaire was administered by trained field workers for putative risk factors for AMD including history of diabetes mellitus. Logistic regression models were used to examine the association between diabetes and stages of AMD, taking account of potential demographic, behavioural, dietary and medical (history of cardiovascular disease) confounders. MAIN OUTCOME MEASURES: Photographic images were graded according to the modified International Classification System for AMD and stratified into five exclusive stages from no signs of AMD (AMD stage 0), early AMD (Stages 1-3) and late AMD (Stage 4). Late AMD was subdivided in neovascular AMD (NV-AMD) or geographic atrophy (GA). RESULTS: Data on diabetes history and potential confounders were available in 2117 control subjects without AMD, 2182 with early AMD, 49 with GA and 101 with NV-AMD. Of all participants, 13.1% reported a history of diabetes. After adjusting for potential confounders, subjects with neovascular AMD compared with controls had increased odds for diabetes (odds ratio 1.81; 95% confidence interval, 1.10 to 2.98, p = 0.02). Subjects with AMD grades 1 to 3 or GA had no increased odds for diabetes compared with those without AMD. CONCLUSIONS: In the EUREYE study, after multiple adjustments, positive association of diabetes mellitus with neovascular AMD was found. The hypothesis that diabetes is associated with neovascular AMD but not with geographic atrophy may suggest a different pathogenesis of the two advanced forms of the disease and needs to be further evaluated.

Biobanks and the importance of detailed phenotyping: a case study--the European Glaucoma Society GlaucoGENE project.

BACKGROUND: Dissecting complex diseases has become an attainable goal through large-scale collaborative projects under the term "biobanks." However, large sample size alone is no guarantee of a reliable genetic association study, and the genetic epidemiology of complex diseases still has many challenges to face. Among these, issues such as genotyping errors and population stratification have been previously highlighted. However, comparatively little attention has been given to accurate phenotyping. Study procedures of existing large-scale biobanks are usually restricted to very basic physical measurements and non-standardised phenotyping, based on routine medical records and health registry systems. DISCUSSION: Study procedures of existing large-scale biobanks are usually restricted. Considering that the objective of an association study is to establish genotype-phenotype correlations, it is doubtful how easily this could be achieved in the absence of accurate and reliable phenotype description. The use of non-specific or poorly defined phenotypes may partly explain the limited progress so far in glaucoma complex genetics. This report examines the European Glaucoma Society GlaucoGENE project, which is the only large multicentre glaucoma-specific biobank. Unlike previous biorepositories, this initiative focuses on detailed and standardised phenotyping and is expected to become a major resource for future studies on glaucoma.

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS: This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. RESULTS: Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant. CONCLUSIONS: Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.

Cigarette smoking and age-related macular degeneration in the EUREYE Study.

OBJECTIVE: To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population. DESIGN: Cross-sectional study. PARTICIPANTS: Four thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain). METHODS: Participants underwent an eye examination and digital retinal photography. The images were graded at a single center. Smoking history was ascertained by a structured questionnaire administered by trained fieldworkers. Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD, taking account of potential confounders and the multicenter study design. MAIN OUTCOME MEASURES: Photographic images were graded according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy (GA). RESULTS: One hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49 GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of neovascular AMD (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-4.8) or GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking. CONCLUSIONS: These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking. Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease.

Concurrent relapsing central nervous system and ocular involvement in a case of life-threatening Adamantiades-Behçet Disease (ABD).

Adamantiades-Behçet disease (ABD) is characterised by oral and genital ulcerations, skin lesions and ocular manifestations and, rarely, by central nervous system (CNS) involvement. Neuro-Behçet disease (NBD) is categorised to parenchymal or non-parenchymal, while combined CNS disease is rarely reported in the literature. A case of NBD, with severe relapsing ocular and neurological disease of combined pattern is presented. Neurological complications included brainstem manifestations, as well as neurovascular involvement, while ocular involvement consisted of bilateral uveitis and branch retinal vein occlusion. Manifestations responded to corticosteroid plus cyclophosphamide pulse therapy. Maintenance therapy included cyclosporine A, azathioprine and corticosteroids. Case individualities are discussed, focusing on scepticism concerning treatment of NBD relapses in the long term.

Effect of laser photocoagulation treatment for diabetic macular oedema on patient's vision-related quality of life.

PURPOSE: To evaluate the effect of laser photocoagulation for diabetic macular oedema (DME) on patients' Vision Related Quality Of Life (VR-QOL) and to investigate associations between changes in self reported VR-QOL and changes in visual acuity following application of laser treatment. METHODS: Prospective cohort study of 55 subjects who underwent laser treatment for DME. Eligible patients with no history of previous laser photocoagulation self-administered the 51-item field-test version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) prior to treatment and 3 months following the last session of laser application. Visual acuity was measured by means of the Early Treatment of Diabetic Retinopathy (ETDRS) chart. Multi-item scales rating different aspects of VR-QOL were compared prior and after photocoagulation and the change in questionnaire's composite score following treatment was correlated to change in visual acuity and other determinants previously reported as risk factors in the diabetic population. RESULTS: Scale scores associated with general vision, near vision, distance vision, peripheral vision, vision-specific social functioning, vision-specific mental health, expectations for visual function and dependency due to vision were significantly improved following laser treatment. Multivariate models revealed that improvement of the NEI-VFQ composite score was significant in subjects younger than 65 years of age (p = 0.04) who received more laser burns (p = 0.02) and had worse vision-related QOL prior to laser treatment as expressed by the baseline NEI- VFQ composite score (p = 0.03). There was no statistically significant association between change in the composite score following laser treatment and stage of diabetic retinopathy, duration of diabetes or laser settings used during photocoagulation. CONCLUSIONS: Photocoagulation for DME has a beneficial effect on patients' subjective perception of visual function. The use of vision-targeted health status questionnaires in conjunction with the clinical examination appears to provide a more comprehensive overview of individuals' daily well- being following laser treatment.

Reproducibility of the Heidelberg retinal flowmeter in determining low perfusion areas in peripapillary retina.

AIM: To evaluate the interobserver variability and retest reproducibility of confocal scanning laser Doppler flowmeter in measuring capillary perfusion of the peripapillary retina. METHODS: Blood flow measurements were performed in one eye of 10 normal subjects by two investigators on two different days (visits). Five separate measurements of the peripapillary blood flow parameters were recorded by each observer at each visit. The Heidelberg retina flowmeter was used to record capillary perfusion in a 2560x640 microm area of the superotemporal peripapillary region and pixel by pixel analysis was done from an area adjacent to the optic disc, with a minimum of 1600 pixels. The percentage of pixels with less than 1 arbitrary unit of flow (no flow) and 10, 25, 50, 75, 90th percentiles of flow values was calculated. Interobserver measurements were compared by paired t test. Intraclass correlations (ICC) were used to determine the interobserver variability and retest reproducibility of the measurements. Intrasession coefficients of variations (CV) were also calculated. RESULTS: There were no statistically significant differences between the two observers for all measurements and between visits for the percentage of pixels with no flow. ICC was 66% (range 57.09%-77.1%) for pixels with no flow. For the 10, 25, 50, 75, 90th percentiles of flow the ICC was 63.07% (53.91%-77.81%), 71.3% (64.23%-80.85%), 72.61% (66.02%-78.96%), 65.86% (58.53%-74.77%), and 60.05% (54.34%-70.06%), respectively. CV was 16.59%, 11.47%, 9.32%, 9.03%, 11.58%, and 16.05% for the percentage of no flow pixels and the 10, 25, 50, 75, 90th percentiles of flow, respectively. CONCLUSIONS: The Heidelberg retinal flowmeter allows reproducible measurements of all levels of capillary perfusion areas when pixel by pixel analysis is used.

Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma.

PURPOSE: To evaluate the efficacy and safety of brimonidine 0.2% two or three times daily versus timolol maleate 0.5% solution twice daily. METHODS: Patients with primary open-angle glaucoma were randomized by Latin square technique to one of the three treatment sequences in this crossover, prospective double-masked trial. Each treatment period consisted of 6 weeks of chronic dosing followed by a diurnal curve for the intraocular pressure measured at 08:00, 10:00, 16:00, 18:00, 20:00, 22:00, and 24:00 hours. Intraocular pressure was measured by applanation tonometry. RESULTS: Thirty patients completed this trial. The average diurnal intraocular pressures in the trial were measured for timolol maleate (17.7 +/- 2.7 mm Hg), brimonidine given three times daily (18.0 +/- 2.2 mm Hg), and brimonidine given twice daily (19.2 +/- 2.4 mm Hg). There was a statistical difference between groups (P <.005). When groups were compared by pairs, three times daily dosing with brimonidine and timolol maleate both reduced the pressure more than twice daily brimonidine at every time point past 10:00 hours and for the diurnal curve (P <.05). In contrast, three times daily brimonidine and timolol maleate were statistically similar for the diurnal pressure, and each time point, except timolol maleate, decreased the pressure more at 16:00 (P =.042). Safety was similar between groups. CONCLUSIONS: This study demonstrated that both timolol maleate twice daily and brimonidine three times daily provide a similar intraocular pressure reduction to each other. Timolol maleate twice daily and brimonidine three times daily provide a greater decrease in pressure in the late afternoon and nighttime hours, compared with brimonidine twice daily.

Hypothyroidism and glaucoma. A study of 100 hypothyroid patients.

PURPOSE: To determine whether glaucoma is associated with hypothyroidism, as has previously been suggested. METHODS: This is a cross-sectional study and a noncomparative interventional case series. One hundred consecutive patients with newly diagnosed hypothyroidism were referred for complete ophthalmologic examination, including automated perimetry and examination of the optic disks, to identify the presence of glaucoma. After correction of the hypothyroidism, reexamination was performed. RESULTS: No patient had glaucoma and no correlation was found between intraocular pressure and either thyroid stimulating hormone or free tri-iodothyronine. No statistically significant difference was found between intraocular pressure levels before and after treatment of the hypothyroidism. CONCLUSION: This study does not demonstrate an association between hypothyroidism and glaucoma.

Follow-up of the original cohort with the Ahmed glaucoma valve implant.

PURPOSE: To study the long-term results of the Ahmed glaucoma valve implant in patients with complicated glaucoma in whom short-term results have been reported. METHODS: In this multicenter study, we analyzed the long-term outcome of a cohort of 60 eyes from 60 patients in whom the Ahmed glaucoma valve was implanted. Failure was characterized by at least one of the following: intraocular pressure greater than 21 mm Hg at both of the last two visits less than 6 mm Hg at both of the last two visits, loss of light perception, additional glaucoma surgery, devastating complications, and removal or replacement of the Ahmed glaucoma valve implant. Devastating complications included chronic hypotony, retinal detachment, malignant glaucoma, endophthalmitis, and phthisis bulbi; we also report results that add corneal complications (corneal decompensation or edema, corneal graft failure) as defining a devastating complication. RESULTS: The mean follow-up time for the 60 eyes was 30.5 months (range, 2.1 to 63.5). When corneal complications were included in the definition of failure, 26 eyes (43%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 76%, 68%, 54%, and 45%, respectively. When corneal complications were excluded from the definition of failure, 13 eyes (21.5%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 87%, 82%, 76%, and 76%, respectively. Most of the failures after 12 months of postoperative follow-up were because of corneal complications. CONCLUSIONS: The long-term performance of the Ahmed glaucoma valve implant is comparable to other drainage devices. More than 12 months after the implantation of the Ahmed glaucoma valve implant, the most frequent adverse outcome was corneal decompensation or corneal graft failure. These corneal problems may be secondary to the type of eyes that have drainage devices or to the drainage device itself. Further investigation is needed to identify the reasons that corneal problems follow drainage device implantation.

Longitudinal changes in optic disc topography of adult patients after trabeculectomy.

OBJECTIVE: To study longitudinal changes in optic disc topography after trabeculectomy in adult patients. DESIGN: Prospective case series. PARTICIPANTS: Twenty-five eyes of 25 patients undergoing trabeculectomy were enrolled. INTERVENTION: Images of the optic disc were obtained preoperatively and approximately 2 weeks, 4 months, and 8 months after surgery by use of a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph). MAIN OUTCOME MEASURES: The topographic optic disc parameters (cup volume, cup area, rim volume, rim area, cup-disc area ratio, mean cup depth, maximum depth, cup shape, and height variation contour) were measured automatically for each image with the Heidelberg Retina Tomograph Software (version 1.11). RESULTS: Approximately 2 weeks after surgery, the mean preoperative intraocular pressure (IOP) of 19.3 mmHg (SD, 6.4 mmHg) decreased to 6.0 mmHg (SD, 3.6 mmHg), cup volume and mean cup depth decreased, height variation contour increased, and the cup shape parameter became more negative. Approximately 4 months after surgery, mean IOP was 9.7 mmHg (SD, 4.2 mmHg), and the only statistically significant change from preoperative values of optic disc parameters was in the cup shape measure. Approximately 8 months after surgery, there was no statistically significant change in any of the optic disc parameters compared with preoperative values, although IOP was 10.4 mmHg (SD, 5.9 mmHg). CONCLUSIONS: Changes in the optic disc that may be present 2 weeks after a trabeculectomy do not appear to persist 4 and 8 months later in eyes with advanced glaucomatous optic nerve damage, except for cup shape, which was different from preoperative values at 4 months but not at 8 months.

Factors associated with elevated rates of adverse outcomes after cyclodestructive procedures versus drainage device procedures.

OBJECTIVE: To identify factors associated with an increased risk of adverse outcomes after cyclodestructive or drainage device procedures. DESIGN: Retrospective, cohort analysis. PARTICIPANTS: A total of 5570 Medicare patients who were older than 65 years of age and who underwent cyclodestructive or drainage device procedures in 1994 participated. INTERVENTION: The authors identified cyclodestructive and drainage device procedures from claims to the Health Care Finance Administration (HCFA) by International Classification of Diseases (ICD-9) procedure codes, Current Procedural Terminology procedure codes, and HCFA Common Procedural Classification System codes. The authors analyzed adverse outcome rates using hierarchical logistic regression. Race, age group, gender, length of observed follow-up, state in which surgery took place, ocular procedures performed before and at the same time as the index surgery, and ocular diagnosis were included as covariates in the model. MAIN OUTCOME MEASURES: The authors defined an adverse outcome as the occurrence after the index surgery of at least one of the following: repeat cyclodestructive or drainage device procedure, retinal hole-tear repair, retinal detachment repair, surgery for endophthalmitis, vitrectomy, enucleation, evisceration, surgery for ocular hypotony, and/or extrusion or revision of drainage device. Adverse outcomes were also defined without the inclusion of repeat cyclodestructive or drainage device procedures. RESULTS: When repeat cyclodestructive or drainage device procedures were not included in the definition of an adverse outcome, eyes with a drainage device procedure were 3.8 times more likely to have an adverse outcome than eyes with a cyclodestructive procedure (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.07, 4.67). Subjects with concurrent corneal transplant had increased odds of an adverse outcome compared to subjects without a concurrent corneal transplant (OR, 2.00; 95% CI, 1.27, 3.15). When the definition of an adverse outcome included repeat cyclodestructive or drainage device procedures, the odds of an adverse outcome were similar for both cyclodestructive and drainage device procedures (OR, 0.94; 95% CI, 0.79, 1.13). CONCLUSIONS: Cyclodestructive procedures need to be repeated more frequently than drainage device procedures. However, if the patient has a drainage device procedure, then that patient is more likely to have other types of adverse ophthalmic events than if he or she had a cyclodestructive procedure. Because the average follow-up of subjects in this study is 5 months (range, 0-12 months), outcomes that might take longer to manifest themselves would be excluded from this study.

Contrast sensitivity evaluation in eyes predisposed to age-related macular degeneration and presenting normal visual acuity.

In order to test the validity of contrast sensitivity (CS) measurements in the early detection of visual impairment in age-related macular degeneration (AMD), we have evaluated the findings of CS in patients with drusen and normal visual acuity (17 eyes), as well as in the contralateral 'healthy' eye of patients with AMD (14 eyes). We also tried to estimate the validity of CS measurements in the prognosis of neovascular macular degeneration. The CS findings were evaluated in comparison to the findings of CS measurements in age-matched controls (32 eyes). CS loss is a constant finding in eyes with drusen and normal visual acuity. CS loss is more important at the middle range and high spatial frequencies. CS loss and degree of CS loss are not prognostic indicators of neovascular macular degeneration.

[Surgical decompression of the optic nerve in intracanal injuries. Indications and results]. / Décompression chirurgicale du nerf optique lors des traumatismes intracanalaires. Indications et résultats.

Fifteen patients with traumatic optic neuropathy (anatomical section excluded) underwent surgical anterior decompression of the optic nerve, via the trans ethmoid-sphenoid approach. Improvement of visual function assessed by visual acuity and visual field measurements, was obtained in 10 patients. Results remained stable for a follow-up period of at least 6 months. There was a delay of several weeks before improvement in some of the patients. Thus a long follow-up period seems recommended. Trans ethmoid-sphenoid optic nerve decompression is a reliable procedure with low morbidity, and represents a promising therapy for indirect injuries of the optic nerve.