A Genome-Wide Association Study of Optic Disc Parameters

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72 x 10(-19)) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67 x 10(-33)) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15610 211) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93 x 10(-10)) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origi

No evidence for a saccadic range effect for visually guided and memory-guided saccades in simple saccade-targeting tasks

International audienceSaccades to single targets in peripheral vision are typically characterized by an undershoot bias. Putting this bias to a test, Kapoula [1] used a paradigm in which observers were presented with two different sets of target eccentricities that partially overlapped each other. Her data were suggestive of a saccadic range effect (SRE): There was a tendency for saccades to overshoot close targets and undershoot far targets in a block, suggesting that there was a response bias towards the center of eccentricities in a given block. Our Experiment 1 was a close replication of the original study by Kapoula [1]. In addition, we tested whether the SRE is sensitive to top-down requirements associated with the task, and we also varied the target presentation duration. In Experiments 1 and 2, we expected to replicate the SRE for a visual discrimination task. The simple visual saccade-targeting task in Experiment 3, entailing minimal top-down influence, was expected to elicit a weaker SRE. Voluntary saccades to remembered target locations in Experiment 3 were expected to elicit the strongest SRE. Contrary to these predictions, we did not observe a SRE in any of the tasks. Our findings complement the results reported by Gillen et al. [2] who failed to find the effect in a saccade-targeting task with a very brief target presentation. Together, these results suggest that unlike arm movements, saccadic eye movements are not biased towards making saccades of a constant, optimal amplitude for the task

Switching to preservative-free latanoprost: impact on tolerability and patient satisfaction

Francisco José Muñoz Negrete,1 Hans G Lemij,2 Carl Erb3 1Ophthalmology Service, Hospital Ramón y Cajal, Madrid, Spain; 2Glaucoma Service, Rotterdam Eye Hospital, Rotterdam, the Netherlands; 3Augenklinik Wittenbergplatz, Berlin, Germany Abstract: Patient satisfaction with glaucoma treatment has been poorly studied to date. Because glaucoma is a chronic condition in which the therapeutic response is dependent on adherence to treatment, patient acceptability is an important factor in achieving satisfactory outcomes. This multicenter, international (Belgium, the Netherlands, and Spain), epidemiological convenience sample survey among patients commencing treatment with preservative-free latanoprost collected data on patient satisfaction with particular regard to tolerability. A total of 1,541 patients were recruited who were predominantly elderly (74% were over 60 years of age) and female (61%). Most of the patients had previously received preserved topical glaucoma medication (69%), 6.7% had previously received preservative-free medication, whereas 24% had not previously been treated for glaucoma. The great majority of patients (>95%) were satisfied with the preservative-free latanoprost treatment. Among the patients who had previously received preserved medication, 73% of patients found preservative-free latanoprost to be better tolerated and 89% found it at least as easy to use as their prior treatment. Patient satisfaction (determined by a 0–100 mm visual analog scale) was improved by 47% on a switch from preserved treatment to preservative-free latanoprost. Intraocular pressure was similar in patients who had previously received preserved (18.3 mmHg), preservative-free (17.8 mmHg) glaucoma medication or who were naïve to treatment (20.3 mmHg). Preservative-free latanoprost provided effective reduction of intraocular pressure with better tolerability and patient satisfaction than preserved glaucoma medication. This tolerability profile can be expected to improve adherence to treatment in glaucoma patients. Keywords: prostaglandins analogs, glaucoma therapy, preservative, patient satisfaction, tolerability, persistence, tear substitute

Patient satisfaction with glaucoma therapy: reality or myth?

Hans G Lemij,1 Juliette GMM Hoevenaars,2 Cees van der Windt,3 Christophe Baudouin4 On behalf of the GOAL Study Investigators 1Glaucoma Service, Rotterdam Eye Hospital, Rotterdam, 2VieCuri Medisch Centrum, Venlo, 3Ziekenhuis Rivierenland, Tiel, the Netherlands; 4Quinze-Vingts National Hospital and Vision Institute, Paris, France Abstract: While safe and effective treatments for glaucoma exist, their effectiveness is compromised by poor compliance. Patients who have problems with their topical glaucoma medication are acknowledged to be at higher risk for poor compliance, frequent medication switching, and surgery. Patient satisfaction with therapy and its associated benefits have until recently taken second place to efficacy. The present study is a transverse cross-sectional epidemiological survey among glaucoma patients receiving therapy with prostaglandin analogs. The primary objective was to determine and characterize patient satisfaction with glaucoma therapy, and the secondary objective was to identify factors that may contribute to poor patient satisfaction. Ophthalmologists in the Netherlands included 199 patients and 164 were analyzed. Patients were predominantly elderly with early, primary, open angle glaucoma. Eighty-nine percent of them stated they were satisfied or very satisfied with their treatment. However, signs of ocular surface disorder on ophthalmological examination were evident in 44% of patients, corneal fluorescein staining was positive in 28% of patients, and 38% of patients were using tear substitutes. The prevalence of blepharitis/meibomian gland dysfunction and dry eye was more than twice as high after the commencement of therapy compared with before therapy. Univariate analysis revealed that patient dissatisfaction with their glaucoma therapy was statistically significantly (P<0.001) associated with the presence of ocular surface disease, hyperemia, ocular signs, symptoms upon and between instillation, and the use of tear substitutes. Apparently, patients in the present study are satisfied with their treatment; 89% expressed satisfaction compared with only 11% who professed dissatisfaction. The results suggest that even if local adverse events and ocular surface disease, in particular, contribute to glaucoma patient dissatisfaction, only a minority of patients expressed such dissatisfaction. At the time of the study, most (94%) of the patients included were receiving preserved preparations. Further studies should evaluate the influence of preservative on patient satisfaction. Keywords: prostaglandin analogs, cross-sectional study, compliance, adherence, ocular surface disease, dry eye, meibomian gland dysfunctio

Global Visit Effects in Point-Wise Longitudinal Modeling of Glaucomatous Visual Fields

PURPOSE: One of the difficulties in modeling visual field (VF) data is the sometimes large and correlated measurement errors in the point-wise sensitivity estimates. As these errors affect all locations of the same VF, we propose to model them as global visit effects (GVE). We evaluate this model and show the effect it has on progression estimation and prediction. METHODS: Visual field series (24-2 Full Threshold; 15 biannual VFs per patient) of 125 patients with primary glaucoma were included in the analysis. The contribution of the GVE was evaluated by comparing the fitting and predictive ability of a conventional model, which does not contain GVE, to such a model that incorporates the GVE. Moreover, the GVE's effect on the estimated slopes was evaluated by determining the absolute difference between the slopes of the models. Finally, the magnitude of the GVE was compared with that of other measurement errors. RESULTS: The GVE model showed a significant improvement in both the model fit and predictive ability over the conventional model, especially when the number of VFs in a series is limited. The average absolute difference in slopes between the models was 0.13 dB/y. Lastly, the magnitude of the GVE was more than three times larger than the measureable factors combined. CONCLUSIONS: By incorporating the GVE in the longitudinal modeling of VF data, better estimates may be obtained of the rate of progression as well as of predicted future sensitivities.status: publishe