Gábor Holló

Reproducibility of Retinal Nerve Fiber Layer and Macular Thickness Measurement with the RTVue-100 Optical Coherence Tomograph

PURPOSE To evaluate the reproducibility of peripapillary retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex (GCC) measurements made with the RTVue-100 Fourier-domain optical coherence tomography (OCT) device (Optovue, Inc., Fremont, CA) and to determine the influence of 4 factors: pupil dilation, subject age, experience in imaging examinations, and glaucoma severity. DESIGN Prospective study for evaluation of a diagnostic test. PARTICIPANTS Thirty-seven hospital-based participants (14 normal and ocular hypertensive subjects, 11 patients with moderate and 12 with severe glaucoma), all experienced in imaging examinations, and 40 consecutive screening trial participants lacking such experience. METHODS One eye of all participants was imaged 5 times. For the hospital-based participants, on the same day the measurement series was repeated after pupil dilation. For determination of intersession reproducibility, measurements were performed again 3 months later. MAIN OUTCOME MEASURES Intrasession and intersession coefficient of variation (CV), intraclass correlation coefficient (ICC), intratest variability, and test-retest variability. RESULTS For the average and quadrant RNFLT parameters and the GCC parameters, intrasession ICC varied between 93.9% and 99.0%, intrasession CV between 1.95% and 5.69%, and intratest variability varied between 3.11 and 9.13 microm. Most thickness values, all intrasession CV and intratest variability values, and the signal strength index were not changed significantly after pupil dilation. Intrasession CV of the 16 peripapillary RNFLT sectors varied between 4.90% and 11.66%. Most intrasession CV values increased significantly with increased disease severity, but intratest variability for average RNFLT and the quadrant RNFLT parameters, which are used for statistical comparison with the normative database, were unaffected by the severity of glaucoma. Patient age and experience in imaging examinations had no influence on intrasession CV. Intratest variability and intrasession CV represented 79.1% to 98.6% and 77.1% to 95.0% of test-retest variability and intervisit CV, respectively, for the average and quadrant RNFLT and the GCC parameters. CONCLUSIONS Intrasession and intersession reproducibility of RNFLT and GCC measurements with the RTVue-100 OCT are satisfactory for diagnostic purposes, both in normals and in patients with different glaucoma severity. Pupil dilation, age, and experience in imaging examinations did not influence reproducibility in a clinically significant manner. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Diagnostic accuracy of nerve fibre layer, macular thickness and optic disc measurements made with the RTVue-100 optical coherence tomograph to detect glaucoma.

PurposeTo evaluate the diagnostic accuracy of retinal nerve fibre layer thickness (RNFLT), ganglion cell complex (GCC), and optic disc measurements made with the RTVue-100 Fourier-domain optical coherence tomography (OCT) to detect glaucoma in a Caucasian referral population.MethodsOne randomly selected eye of 286 Caucasian patients (93 healthy, 36 ocular hypertensive, 46 preperimetric glaucoma, and 111 perimetric glaucoma eyes) was evaluated.ResultsUsing the software-provided classification, for the total population sensitivity did not exceed 73.6% for the optic nerve head parameters, and 62.7% for the other parameters. Specificity was high (94.6–100%) for most RNFLT and GCC parameters, but low (72.0–76.3%) for the optic disc parameters. Positive predictive value varied between 98.1 and 100% for the main RNFLT parameters, 92.6 and 100% for the 16 RNFLT sectors, 92.4 and 99.0% for the GCC parameters, but did not exceed 86.3% for any of the optic disc parameters. Positive likelihood ratio (PLR) was higher than 10 for average, inferior and superior RNFLT (25.5 to infinite), 12 of the 16 RNFLT sectors (12.6 to infinite), and three of the four GCC parameters (40.0 to 48.6). No optic disc parameter had a PLR higher than 3.0.ConclusionsRNFLT and GCC parameters of the RTVue-100 Fourier-domain OCT showed moderate sensitive but high specificity, positive predictive value and PLR for detection of glaucoma. The optic disc parameters had lower diagnostic accuracy than the RNFLT and GCC parameters.

The side effects of the prostaglandin analogues

In the last decade topically applied prostaglandin F2α analogues (bimatoprost, latanoprost, travoprost and unoprostone) have become widely used as a means to reduce elevated intraocular pressure in patients with glaucoma and ocular hypertension. These molecules all have similar side-effect profiles, which include both side effects that occur frequently (e.g., conjunctiva hyperaemia, increase of iris pigmentation and eyelash changes) and rare adverse reactions (e.g., periocular pigmentation, damage to the blood–aqueous barrier and cystoid macular oedema). Conjunctiva hyperaemia, eyelash changes and cystoid macular oedema are reversible, but certain other side effects, such as increased iris pigmentation, are not. However, the systemic side-effect profile is favourable for all the prostaglandin analogues, and some of the local side effects are only of cosmetic significance. Numerous clinical studies suggest that discontinuing treatment with prostaglandin analogues on account of their side effects is rare in clinical practice.

Clinical Assessment of Stereoscopic Optic Disc Photographs for Glaucoma: The European Optic Disc Assessment Trial

PURPOSE To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists. DESIGN Evaluation of diagnostic test and technology. PARTICIPANTS A total of 243 of 875 invited ophthalmologists in 11 European countries. METHODS We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers. MAIN OUTCOME MEASURES Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa). RESULTS The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRTs best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on average good (0.7). CONCLUSIONS In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome

Background/aim: The authors investigated the concentrations of 8-isoprostaglandin F2a, a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients with exfoliation syndrome (XFS) and cataract and compared the results with those in age matched patients with cataract, but without XFS, to determine whether XFS is associated with increased oxidative stress. Methods: Aqueous humour was aspirated at the beginning of phacoemulsification cataract surgery from 27 eyes of 27 cataract patients with XFS and 27 eyes of 27 age matched cataract patients without XFS. 8-Isoprostaglandin F2aconcentration in the aqueous was determined with a commercial immunoassay; ascorbic acid concentration was measured with a microplate assay method. Results:. The mean concentration of 8-isoprostaglandin F2ain the aqueous from patients with XFS (2429 (SD 2940) pg/ml; range 400–10500 pg/ml) was significantly higher than that measured in the aqueous of age matched control patients (529.1 (226.8) pg/ml; range 325–1000 pg/ml); (p = 0.0028). Furthermore, mean ascorbic acid concentration in XFS patients (0.75 (0.39) mM; range 0.28–1.70 mM) was significantly lower than that found in control patients (1.19 (0.47) mM; range 0.53–2.4 mM); (p = 0.0005). There was a reverse correlation between 8-isoprostaglandin F2aand ascorbic acid concentration. Conclusion: 8-Isoprostaglandin F2awas significantly increased in the aqueous of patients with XFS, and ascorbic acid was decreased, providing evidence of a role for free radical induced oxidative damage in the pathobiology of XFS.

Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome.

Background/aim: Endothelin 1 (ET-1) is considered the most potent vasoconstrictor in the body and the eye. This molecule may play a significant role in the pathobiology of exfoliation syndrome (XFS), a disorder characterised by a progressive iris vasculopathy. The purpose of this study was to investigate the concentration of ET-1 in the aqueous humour of cataract patients with and without XFS. Methods: Aqueous humour samples were obtained from 25 consecutive eyes of 25 cataract patients with XFS and an equal number of age matched controls during phacoemulsification cataract surgery. None of the subjects had elevated intraocular pressure or glaucoma. ET-1 concentration in the aqueous was measured using a specific immunoassay with 100% immunoreactivity for ET-1. Total aqueous humour protein concentration was measured with a microplate Coomassie blue based method and was correlated with ET-1 concentration. Results: Mean ET-1 concentration in the XFS aqueous samples (4.6 (SD 2.3) pg/ml) was significantly higher than that measured in the age matched control samples (2.8 (SD 1.71) pg/ml); (p = 0.006). Although total protein concentration was significantly elevated in the XFS samples (0.380 (SD 0.159) v 0.279 (SD 0.144) mg/ml in the controls); (p = 0.023), no correlation was found between aqueous ET-1 and total protein concentration (p = 0.730). Conclusion: The increased concentration of ET-1 in the aqueous humour of XFS patients suggests that ET-1 may play a role in the pathobiology of XFS.

Increase of carotid artery stiffness and decrease of baroreflex sensitivity in exfoliation syndrome and glaucoma

Aim: To investigate the distensibility of the common carotid artery (CCA), baroreflex sensitivity (BRS) and its relation to plasma homocysteine concentration in exfoliation syndrome or exfoliation glaucoma (XFS/XFG). Methods: Homocysteine concentrations were measured in 30 XFS/XFG patients and 18 age matched controls. In 21 patients and 17 controls the end diastolic diameter of the CCA and pulsatile distension were measured and BRS was calculated. Results: There was no significant difference between the groups in sex distribution, age, heart rate, blood pressure, systemic diseases, or medication. In XFS/XFG patients homocysteine concentration was significantly elevated (unpaired t test, p = 0.023), and CCA stiffness was higher (p<0.05), while strain, cross sectional compliance coefficient, distensibility, and BRS were significantly reduced compared to the controls (Mann-Whitney U test, p⩽0.013 for each parameter). In XFS/XFG patients a positive correlation was found between age and plasma homocysteine level (Pearson’s correlation, r = 0.490, p = 0.007), and a negative correlation between age and BRS (Kendall’s correlation r = −0.374, p = 0.021), as well as between homocysteine concentration and BRS (Kendall’s correlation r = −0.377, p = 0.024). No correlation was seen between these variables in the control group. Conclusions: These results suggest a pathological large artery function as well as altered parasympathetic vascular control in XFS/XFG which increases with age and with higher homocysteine concentration.

Scanning laser polarimetry of the retinal nerve fibre layer in primary open angle and capsular glaucoma

AIMS To evaluate the clinical value of scanning laser polarimetry with the nerve fibre analyser type II in primary open angle glaucoma (POAG) and capsular glaucoma. METHODS Scanning laser polarimetry was performed on one eye of 30 patients suffering from POAG, 25 patients suffering from capsular glaucoma, and on 35 healthy control subjects. The retinal nerve fibre layer (RNFL) thickness values were compared among the groups. Reproducibility of the measurements was calculated and the influence of pilocarpine induced miosis on the results was investigated. RESULTS RNFL thickness in the superior and inferior sectors, as well as along the total circumference was significantly lower in both glaucoma groups than in the control eyes (p<0.05). None of the thickness values differed between the two glaucoma groups. Reproducibility was comparable in all groups; the coefficient of variation varied between 3.0% and 8.9% for the different sectors investigated. Miosis had no significant impact either on the thickness values or on the reproducibility (p>0.05). CONCLUSION The results suggest that scanning laser polarimetry is a useful method for nerve fibre layer analysis in glaucoma, and that it is not influenced by the pupil size.

Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer‐masked, three‐centre study

Aim: To evaluate the diurnal intraocular pressure (IOP) control and safety of bimatoprost versus latanoprost in exfoliative glaucoma (XFG). Methods: One eye of 129 consecutive patients with XFG (mean (SD) age 66.5 (8.3) years) was included in this prospective, observer-masked, three-centre, crossover comparison. After a 4–6 week medicine-free period patients were randomised to bimatoprost or latanoprost monotherapy for 3 months. Patients were then switched to the opposite treatment for another 3 months. At the end of the washout and the treatment periods diurnal IOP was measured at 0800, 1300, and 1800. Results: At baseline the IOP (mean (SD)) was 28.0 (4.0), 26.9 (3.6), and 25.9 (3.6) mm Hg, at the three time points, respectively. Both treatments significantly reduced mean diurnal IOP at month 3. Mean diurnal IOP was 26.9 (3.5) mm Hg at baseline, 17.6 (3.3) mm Hg with bimatoprost, and 18.6 (3.6) mm Hg with latanoprost (p<0.0001). Furthermore, lower IOP values were obtained with bimatoprost at all time points (17.9 (3.4), 17.3 (3.3), and 17.6 (3.5) mm Hg, respectively) compared with latanoprost (18.7 (3.6), 18.5 (3.6), and 18.6 (4.1) mm Hg, respectively). The corresponding mean differences (0.8, 1.1, and 1.0 mm Hg, respectively) were all significant (p<0.001 for each comparison). Significantly more patients with XFG obtained a target diurnal IOP <17 mm Hg with bimatoprost than with latanoprost, 55/123 (45%) v 34/123 (28%); (p = 0.001), and significantly fewer patients were non-responders with bimatoprost than with latanoprost (5 v 13, p = 0.021). More patients reported at least one adverse event with bimatoprost than with latanoprost (58 v 41 at 3 months; p = 0.0003). Conclusion: This crossover study suggests that better diurnal IOP control is obtained with bimatoprost than with latanoprost in patients with XFG.

Twenty-four-hour intraocular pressure control with bimatoprost and the bimatoprost/timolol fixed combination administered in the morning, or evening in exfoliative glaucoma

Aim To compare 24 h intraocular pressure (IOP) control of morning and evening administered bimatoprost/timolol fixed combination (BTFC) and evening administered bimatoprost in exfoliative glaucoma (XFG). Methods One eye of 60 XFG patients was included in this prospective, observer-masked, crossover comparison. Following wash-out, all patients received bimatoprost monotherapy for 6 weeks. They were then randomised to morning, or evening, administered BTFC for 3 months and then switched to the opposite therapy. Results At baseline, mean 24 h pressure was 29.0 mm Hg. Bimatoprost reduced the mean IOP by 8.1 mm Hg (27.8%, p<0.001). The evening administration of BTFC reduced 24 h IOP to a statistically lower level than morning administration (10.2 mm Hg (35.3%) vs 9.8 mm Hg (33.8%); p=0.005). Both dosing regimens reduced IOP significantly more than bimatoprost (p≤0.006, for all time points). A 24 h IOP reduction ≥30% was seen in 43 patients (72%) with evening BTFC compared with 39 patients (65%) with morning BTFC (p=0.344) and only 24 patients (40%) with bimatoprost monotherapy (p<0.001 vs both BTFC regimens). Conclusion Both BTFC dosing regimens significantly reduce 24 h IOP in XFG compared with bimatoprost monotherapy. The evening dosing gives rise to statistically better 24 h IOP control and could be considered in these patients.