Julia Lamparter

Diagnostic ability of retinal ganglion cell complex, retinal nerve fiber layer, and optic nerve head measurements by Fourier-domain optical coherence tomography

PurposeTo evaluate the diagnostic ability of Fourier-domain optical coherence tomography (FD-OCT) measurements in glaucoma patients, patients with ocular hypertension, and normal subjects.MethodsNinety-three participants with open-angle glaucoma (OAG), 58 patients with ocular hypertension (OHT), and 60 healthy control subjects were included in the study. All study participants underwent FD-OCT imaging. Retinal ganglion cell complex (GCC), macular thickness, peripapillary retinal nerve fiber layer thickness (RFNL), and optic nerve head parameters (ONH) were measured in each participant. The diagnostic ability was evaluated using area under the receiver operating characteristics curves (AUROC).ResultsGlaucoma patients showed a significant reduction in GCC and macular retinal thickness compared to patients with OHT and normal subjects. No differences in GCC were found between the patients with OHT and normal subjects. The best diagnostic ability in the comparison between glaucoma and normal subjects after adjusting for age was found for cup-to-disc ratio (AUROCu2009=u20090.848), RNFL average thickness (AUROCu2009=u20090.828), and GCC global loss volume (AUROCu2009=u20090.805). The diagnostic power of the best GCC, RNFL, and ONH parameter did not show differences beyond random variation (pu2009>u20090.05).ConclusionsImaging of the GCC using FD-OCT (RTVue-100) has a comparable diagnostic ability to RNFL and ONH measurements in distinguishing between glaucoma patients and healthy subjects. No differences were found between patients with OHT and normal subjects with regard to ONH, RNFL, and GCC parameters.

The influence of intersubject variability in ocular anatomical variables on the mapping of retinal locations to the retinal nerve fiber layer and optic nerve head.

PURPOSEnTo investigate the influence of intersubject variation in ocular parameters on the mapping of retinal locations to the retinal nerve fiber layer and optic nerve head.nnnMETHODSnOne hundred retinal nerve fiber layer (RNFL) bundle photographs from 100 subjects were optimized digitally and single RNFL bundles manually traced back to the ONH where their entry point was noted. A 24-2 visual field (VF) grid pattern was superimposed onto the photographs in order to relate VF test points to intersecting RNFL bundles and their entry angles into the ONH. Axial length, spherical equivalent, the position of the ONH in relation to the fovea, size, orientation, tilt, and shape of the ONH were assessed. Multilevel linear models were generated for predicting the entry angle of RNFL bundles, based on ocular parameters.nnnRESULTSnA total of 6388 RNFL bundles were traced. The influence of ocular parameters could be evaluated for 33 out of 52 VF locations. The position of the ONH in relation to the fovea was the most prominent predictor for variations in the mapping of retinal locations to the ONH, followed by disc area, axial length, spherical equivalent, disc shape, disc orientation, and disc tilt.nnnCONCLUSIONSnMapping of retinal locations to the optic nerve head varies between patients according to a given patients ocular parameters. By considering these parameters, patient-tailored, structure-function maps can be built and structural and functional measurements can be correlated more accurately. Individualized maps may assist clinicians detecting glaucoma and monitoring glaucomatous progression.

Structure-function relationship between FDF, FDT, SAP, and scanning laser ophthalmoscopy in glaucoma patients.

PURPOSEnFlicker defined form perimetry (FDF) and frequency doubling technology perimetry (FDT) are alleged to detect glaucoma at an earlier stage than standard automated perimetry (SAP). It is the purpose of this study to investigate the structure-function relationship between FDF, FDT, SAP, and confocal scanning laser ophthalmoscopy (cSLO) in patients with glaucoma.nnnMETHODSnSeventy-six patients with glaucoma were included in the study. Patients were tested with SAP, Matrix-FDT, FDF perimetry, and cSLO. Structure-function relationships between global and sectoral cSLO parameters and global and sectoral mean sensitivity (MS) of SAP, Matrix-FDT, and FDF were calculated using Spearmans rank correlation and linear regression.nnnRESULTSnOverall, FDF perimetry showed the strongest structure-function relationship (GLOBAL correlation with rim area: 0.44; range of significant sectoral FDF values: 0.23-0.69), followed by FDT (global correlation with rim area: 0.35; range of significant sectoral FDT values: 0.25-0.60). SAP presented with the weakest structure-function relationship and fewer statistically significant results (global correlation with rim volume: 0.32; range of significant sectoral SAP values: 0.23-0.58). Sector-by-sector, the structure-function relationship was greatest in the superotemporal and inferotemporal regions. Weakest correlations were found in the inferonasal and nasal sectors.nnnCONCLUSIONSnThe correlation between structure and function is stronger in FDF and FDT compared with SAP. Correlations are strongest in temporal areas where glaucomatous damage tends to occur first. A better understanding of the structure-function relationship should allow for improved detection and management of glaucoma patients.

Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study

Objective Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany. Research Design and Methods The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases. Results Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955–0.992]; p = 0.006) arterial hypertension (1.90 [1.190–3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504–7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068–1.114]; p<0.0001 and 1.18 [1.137–1.222]; p<0.0001, respectively). Conclusions Our calculations suggest that more than a quarter-million persons have vision-threatening diabetic retinal disease in Germany. Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus.

Prevalence and associations of diabetic retinopathy in a large cohort of prediabetic subjects: The Gutenberg Health Study

AIMSnTo evaluate the prevalence of diabetic retinopathy/maculopathy (DR/DMac) and its associations with cardiovascular risk factors (CRF) in participants with prediabetes (PwPD) in a large European cohort within the population-based Gutenberg Health Study (GHS).nnnMETHODSnThe study was based on a sub-cohort of the GHS (n=5,000, age: 35-74 y). Prediabetes was diagnosed according to HbA1c levels (5.7-6.4%). DR/DMac was graded from fundus photographs. Blood samples and comprehensive questionnaires served for evaluation of laboratory results and CRF.nnnRESULTSnThe prevalence of prediabetes was 22.4%, and of DR/DMac 8.1%/0.2%, respectively. The majority of participants had mild DR (7.2%). A percentage of 0.5 of PwPD presented with moderate and 0.3% with severe non-proliferative disease. None of the subjects had proliferative DR. No independent association was found between any of the analyzed CRF [hypertension, smoking, (family) history of myocardial infarction, congestive heart failure, coronary heart disease, stroke, obesity, dyslipidemia, chronic obstructive pulmonary disease, peripheral artery disease and chronic kidney disease] and DR.nnnCONCLUSIONSnAlthough prevalences of prediabetes and DR in this Caucasian cohort are considerable, retinopathy findings are mainly mild, and no association was found for DR/DMac and CRF.

Distribution of central corneal thickness and its association with ocular parameters in a large central European cohort: the Gutenberg health study.

Main objective To evaluate the distribution of central corneal thickness (CCT) in a large German cohort and to analyse its relationship with intraocular pressure and further ocular factors. Design Population-based, prospective, cohort study. Methods The Gutenberg Health Study (GHS) cohort included 4,698 eligible enrollees of 5,000 subjects (age range 35–74 years) who participated in the survey from 2007 to 2008. All participants underwent an ophthalmological examination including slitlamp biomicroscopy, intraocular pressure measurement, central corneal thickness measurement, fundus examination, and were given a questionnaire regarding glaucoma history. Furthermore, all subjects underwent fundus photography and visual field testing using frequency doubling perimetry. Results Mean CCT was 557.3±34.3 µm (male) and 551.6±35.2 µm in female subjects (Mean CCT from right and left eyes). Younger male participants (35–44 years) presented slightly thicker CCT than those older. We noted a significant CCT difference of 4 µm between right and left eyes, but a high correlation between eyes (Wilcoxon test for related samples: p<0.0001). Univariable linear regression stratified by gender showed that IOP was correlated with CCT (p<0.0001). A 10 µm increase in CCT led to an increase in IOP between 0.35–0.38 mm Hg, depending on the eye and gender. Multivariable linear regression analysis revealed correlations between gender, spherical equivalent (right eyes), and CCT (p<.0001 and pu200a=u200a0.03, respectively). Conclusions We observed positive correlations between CCT and IOP and gender. CCT was not correlated with age, contact lens wear, positive family history for glaucoma, lens status, or iris colour.

Learning Curve and Fatigue Effect of Flicker Defined Form Perimetry

PURPOSEnTo evaluate the learning curve and fatigue effect of flicker defined form (FDF) perimetry.nnnDESIGNnProspective cross-sectional study.nnnMATERIAL AND METHODSnOne hundred forty-one eyes of 75 healthy subjects were included in the study. Every subject was measured 3 times on 3 different days within 3 months. Differences among the tests were analyzed for mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), reliability indices, test duration, and test points <5% and <0.5% in 75 right eyes on the basis of linear mixed models for repeated measurements. To assess the effect of fatigue, differences of MS, MD, and PSD values between 66 left and right eyes were evaluated regarding alterations between these 3 examinations.nnnRESULTSnAfter 3 test sessions, significant improvements were found in MS and MD among all 3 tests (P ≤ .01), and in PSD between test 1 and test 3 (P = .02). Test duration decreased significantly between tests 1 and 3 (P = .01); fixation-loss errors decreased significantly between tests 2 and 3 and between tests 1 and 3 (P = .02, respectively). Test points with p < 0.5% decreased significantly between tests 1 and 2 (P = .04) and 1 and 3 (P = .01) When comparing both eyes, MS, MD, and PSD were significantly better in first than in second eyes examined.nnnCONCLUSIONSnThere exist significant learning and fatigue effects for repeated flicker defined form perimetry. For good and reliable results on FDF perimetry, at least 3 tests should be performed in an individual. Between the tests of both eyes, a rest should be offered.

Neuroprotection of medical IOP-lowering therapy

Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α2-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α2-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α2-adrenergic receptor agonist, brimonidine.

The Prevalence of Amblyopia in Germany: Data From the Prospective, Population-Based Gutenberg Health Study

BACKGROUNDnAmblyopia is due to insufficient development of the visual system in early childhood and is a major source of lifelong impairment of visual acuity. Too little is known about the prevalence of amblyopia in Germany and the frequency of its various causes.nnnMETHODSnThe Gutenberg Health Study of the University of Mainz Faculty of Medicine is an ongoing population-based, prospective, monocentric cohort study with 15 010 participants aged 35 to 74. All participants are examined for the presence of ocular, cardiovascular, neoplastic, metabolic, immunologic, and mental diseases. 3227 participants aged 35 to 44 underwent ophthalmological examination from 2007 to 2012. Amblyopia was defined as impaired visual acuity in the absence of any organic pathology capable of explaining the condition, and in the presence of a known risk factor for amblyopia.nnnRESULTSnAmblyopia, when defined as a visual acuity less than or equal to 0.63, was present in 182 participants (5.6%, 95% confidence interval [CI] 4.9-6.5%), 120 of whom had a visual acuity less than or equal to 0.5 (3.7%, 95% CI 3.3-5.2%). A narrower definition of amblyopia requiring, in addition, an interocular difference in acuity of at least two lines yielded slightly lower prevalence figures: 5.0% (95% CI 4.2-5.8%) and 3.7% (95% CI 3.1-4.4%), respectively. The causes of amblyopia (visual acuity ≤ 0.63) were anisometropia (different refractive strengths of the two eyes) in 49% of participants, strabismus (a squint) in 23%, both of these factors in 17%, and visual deprivation in 2%. 3 patients (2%) had relative amblyopia due to a traumatic cataract sustained in early childhood. 7% of the participants with amblyopia had binocular amblyopia.nnnCONCLUSIONnThis study yielded a prevalence figure of 5.6% for amblyopia in Germany-a higher figure than in other, comparable population-based studies, which have generally yielded figures of ca. 3% for visual acuity ≤ 0.63. The distribution of the causes of amblyopia is similar across studies.

Prevalence of Diabetic Retinopathy in Screening-detected Diabetes mellitus: Results from the Gutenberg Health Study (GHS)

Aims/hypothesisIndividuals with type 2 diabetes mellitus may experience an asymptomatic period of hyperglycaemia, and complications may already be present at the time of diagnosis. We aimed to determine the prevalence of diabetic retinopathy in patients with newly diagnosed (screening-detected) type 2 diabetes.MethodsThe Gutenberg Health Study is a population-based study with 15,010 participants aged between 35 and 74xa0years. We determined the weighted prevalence of diabetic retinopathy by assessing fundus photographs. Screening-detected type 2 diabetes was defined as an HbA1c concentration of 6.5% (47.5xa0mmol/mol) or more, no medical diagnosis of diabetes and no intake of insulin or oral glucose-lowering agents.ResultsOf 14,948 participants, 1377 (9.2%) had diabetes mellitus. Of these, 347 (25.2%) had newly diagnosed type 2 diabetes detected by the screening. Overall, the weighted prevalence of screening-detected type 2 diabetes was 2.1%. Fundus photos were evaluable for 285 (82.1%) participants with newly diagnosed diabetes. The weighted prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13.0%; 12% of participants had a mild non-proliferative diabetic retinopathy and 0.6% had a moderate non-proliferative diabetic retinopathy. Diabetic retinopathy was proliferative in 0.3%. No cases of severe non-proliferative diabetic retinopathy or diabetic maculopathy were found. Thirty (14.9%) of 202 and six (7.2%) of 83 individuals with and without concomitant arterial hypertension, respectively, had diabetic retinopathy (OR 2.54, 95% CI 1.06, 7.14). Visual acuity did not differ between individuals with and without diabetic retinopathy .Conclusions/interpretationIn this large European study, the prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13%. Only a very small proportion of participants with detected diabetic retinopathy needed treatment.