[The effect of central corneal thickness on tonometry]. / Einfluss der Hornhautdicke auf die Tonometrie.

Central corneal thickness (CCT) affects IOP measurements and is an independent risk factor for the development of glaucoma. IOP measurements of all common tonometers, such as the Goldmann applanation tonometer, non-contact tonometer and rebound tonometer, are affected by CCT. Nomograms to correct IOP measurements according to CCT have been established. These nomograms lead to a reduction of the measurement error caused by CCT in groups of patients. However, one has to be aware of the fact that, in individuals, the correction of IOP measurements can even increase the deviation of the IOP measurement from the actual IOP. The effect of CCT on dynamic contour tonometry and IOP (cc) measured by ORA is negligible. CCT is an important parameter in glaucoma management and needs to be considered when interpreting IOP measurements. This can be done by using nomograms or by implementing CCT in the calculation of the individual target pressure.

[Biomechanical condition of the cornea as a new indicator for pathological and structural changes]. / Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen.

AIM: Several methods permit the measurement of geometric parameters of the cornea, but until now biomechanical conditions of the cornea have been ignored (e.g. in refractive corneal surgery). Besides the geometric condition, biomechanical properties of the cornea have been shown to influence applanation measurement of intra-ocular pressure (IOP) and epidemiological studies have identified corneal thickness as an independent risk factor for the development and progression of glaucoma. The aim of this investigation was to characterize the biomechanical properties of the cornea using the ocular response analyzer (ORA). METHODS: The ocular response analyzer (ORA) is a new method available for non-contact measurement of the biomechanical properties of the cornea. We evaluated the reproducibility of measurements, the difference between static and dynamic factors and the impact of independent factors (e.g. IOP, age, CCT, swelling of the cornea) on 2,500 measurements of corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: In a large sample size we observed changes in CH and CRF after refractive surgery procedures (LASIK, UV-A cross-linking, keratoplasty) and in other corneal disorders (keratoconus, corneal dystrophies). CONCLUSIONS: CRF and CH changes may reflect structural changes of the cornea. Thus, the ORA provides valuable information for a better understanding and characterization of the biomechanical condition of the cornea, especially with regard to diseases such as keratoconus and glaucoma.

Effect of latanoprost and timolol on the histopathology of the human conjunctiva.

AIM: To investigate the effect of timolol and latanoprost on the extracellular matrix organisation, inflammatory infiltration, and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the human conjunctiva. METHODS: Conjunctival biopsies were obtained from the inferior fornix during routine cataract surgery from 20 patients with primary open-angle glaucoma, who had received a monotherapy either with timolol or latanoprost, and from 10 non-glaucomatous patients. Specimens were investigated by light microscopy, immunohistochemistry using antibodies against MMP-1,-3, TIMP-2,-3 and CD 68 antibodies and by quantitative transmission electron microscopy. RESULTS: The number of collagen fibres was significantly decreased in latanoprost-treated conjunctival specimens compared with timolol-treated eyes (p<0.01) but showed no difference to controls. Amorphous material was increased in both treated groups compared with controls (p<0.001) but was less in latanoprost-treated specimens compared with timolol-treated eyes (p<0.001). Optically clear spaces, probably containing glycosaminoglycans, were significantly reduced in both treated groups-with less of a reduction in latanoprost-compared with timolol-treated eyes (p<0.001). A marked upregulation of MMP-1 and MMP-3 and moderately increased staining for TIMP-2 and TIMP-3 was found in epithelial cells and subepithelial stromal cells of latanoprost-treated eyes. A moderate infiltration with macrophages and inflammatory cells was observed in timolol-treated eyes. CONCLUSIONS: Latanoprost-treated conjunctival specimens showed a decreased stromal collagen density and a less pronounced inflammatory infiltration. The upregulation of MMP-1 and MMP-3 in latanoprost-treated eyes might explain the reduced extracellular matrix accumulation in the conjunctival stroma. Therefore, latanoprost therapy might have a more favourable effect on the outcome of glaucoma filtering surgery.

[Measurement of the disc area by indirect ophthalmoscopy]. / Flächenbestimmung der Papille mittels indirekter Ophthalmoskopie.

PURPOSE: The aim of this study was to assess the accuracy of measuring the optic disc area by indirect ophthalmoscopy. PATIENTS AND METHODS: In a prospective clinical trial, 57 eyes of 29 subjects (age 57.3+/-12.1 years) were examined. The refractive error was -0.67+/-2.69D (+3.75D to -8D).The vertical and horizontal disc diameters (DD) were measured using a Haag-Streit slit lamp and 60D-, 78D-, 90D-, and Super Field lenses (Volk Optical, Mentor, USA). Afterwards the disc area was calculated by an ellipse formula (horizontal DD x vertical DD x pi/4). The magnification factor given by the manufacturer was taken into account for each lens: 1.15x (60D lens), 0.93x (78D lens), 0.76x (90D lens), and 0.76x (Super Field lens), respectively. As reference for the disc size, the same eyes were examined by HRT II (Heidelberg Engineering, Heidelberg, Germany). Bland-Altman plots were used to assess the agreement between measurements obtained by indirect ophthalmoscopy and HRT. RESULTS: The results of the disc estimate compared with the HRT measurements were as follows: 0.119+/-0.51 mm(2) (60D lens), 0.224+/-0.57 mm(2) (78D lens), 0.10+/-0.51 mm(2) (90D lens), and -0.07 s+/-0.47 mm(2) (Super Field lens). Differences were not statistically significant for the 60D (p=0.083), 90D (p=0.147), or Super Field lenses (p=0.257). However, the difference between the 78D lens and HRT was statistically significant (Student's t-test; P=0.004). CONCLUSION: Measuring the disc size by indirect ophthalmoscopy is possible. The 90D lens showed the smallest and the 78D lens the largest deviation.

[Intraocular pressure measurement during the day and night for glaucoma patients and normal controls using Goldmann and Perkins applanation tonometry]. / Augeninnendruckmessungen im Tages- und Nachtverlauf bei Glaukompatienten und Normalprobanden mittels Goldmann- und Perkins-Applanationstonometrie.

OBJECTIVE: Our aim was to evaluate intraocular pressure (IOP) levels in primary open angle glaucoma (POAG) patients and healthy controls during both the day and night while measuring in an upright as well as in a supine position. METHODS: In a prospective clinical trial, 30 glaucoma patients on topical treatment and 50 healthy controls received IOP measurements every 4 h for a 24 h period starting at 8 am. Additionally, blood pressure and heart rate were measured and perfusion pressures were calculated. At 12 am IOP was initially measured in a sitting position and then, after 20 min, in a supine position. At midnight this was carried out conversely. At 4 am IOP was measured in a supine position; all other measurements were performed in a sitting position. Measurements in the sitting position were performed by Goldmann and Perkins tonometry and in a supine position by Perkins tonometry. RESULTS: IOP was 1 mmHg lower in Perkins tonometry measurements compared to Goldmann tonometry. There was no difference between the two patient groups. In a supine position, IOP measured by Perkins tonometry was higher than in an upright position. At 12 am the difference was 1.8 mmHg+/-2.7 mmHg (p=0.001) in healthy subjects and 1.3+/-2.7 mmHg (p=0.013) in the POAG patients. At 12 pm the increase of IOP in the supine position was even more pronounced with 2.4+/-3.4 mmHg in healthy subjects and 5.6+/-3.2 mmHg in the POAG patients (p=0.001). The blood pressure and the perfusion pressure were lowest during night measurements. CONCLUSIONS: During diurnal IOP measurements in an upright position there were no statistically significant differences in IOP changes between groups. However, in a supine position IOP was significantly higher than in a sitting position and increased more in the glaucoma patients than in healthy controls. This observation might be due to a faulty regulation of the fluid shift in glaucoma patients and could cause progression of glaucomatous damage.

[Comparative measurements of central corneal thickness with two ultrasound pachymeters]. / Vergleichende Messung der zentralen Hornhautdicke mit zwei Ultraschallpachymetern.

BACKGROUND: The aim of this study was to compare two different ultrasound pachymeters based on measurements of central corneal thickness (CCT). METHODS: CCT of 1,070 eyes of 535 patients (glaucoma and glaucoma suspects) was determined using the ultrasound pachymeter IOPac (Heidelberg Engineering, Germany) and SP-3000 (Tomey Corporation, Japan). With the IOPac 8 measurements are averaged by the instrument and with the SP-3000 200 measurements, respectively. For statistical purposes intraclass correlation coefficients (ICC) and Bland-Altman analysis were calculated. RESULTS: The mean CCT was 561.3+/-35.6 microm (IOPac) and 561.8+/-35.6 microm (SP-3000). The mean difference between both pachymeters was 0+/-8 microm. ICC was 0.9746 (95% confidence interval: 0.9714-0.9774). CONCLUSIONS: The use of the two instruments tested has no influence on the determination of CCT. The measured CCT of glaucoma patients or suspects were slightly above the CCT of normals of other studies.

[Measurement of peripapillary nerve fiber layer thickness at different distances from the optic nerve head with OCT]. / Bestimmung der peripapillären Nervenfaserschichtdicke mit der optischen Kohärenztomographie (OCT) in verschiedenen Abständen zum Papillenrand.

PURPOSE: The aim of this study was to assess which distance to the optic nerve head is most favorable for circular measurements of retinal nerve fiber layer thickness (RNFLT) with OCT to detect differences between glaucoma and normal subjects. METHODS: A total of 98 eyes of 67 subjects (normal subjects and POAG patients) were examined by Stratus OCT (Zeiss, Model 3000, Software Version 2.0). Images were scanned in the "proportional circle" mode and analyzed with the "RNFL thickness analysis" protocol. For statistical analysis the Friedman test and the Mann-Whitney U test with Bonferroni correction were used. RESULTS: For 23 normal and 19 eyes of POAG patients a complete set of scans could be analyzed by the OCT software. RNFLT was statistically significantly different in scan diameters in both groups (P=0.000). Differences between the groups were statistically significant for the 1.0-fold (P=0.003), for the 1.4-fold (P=0.01), and for the 1.8-fold (P=0.002) disc diameter. CONCLUSION: Circular scans with a 1-fold and with a 1.8-fold disc diameter seem to be able to differentiate best between glaucoma and normal subjects.

[Applanation tonometry in "normal" patients and patients after LASIK]. / Applanationstonometrie bei Normalpatienten und Patienten nach LASIK.

BACKGROUND: Until now it was thought that morphological parameters of the eye such as corneal thickness, corneal curvature and axial length do not affect tonometry results. However, the aim of this study was to find out whether there actually is an influence of these parameters on applanation tonometry. PATIENTS AND METHOD: In this prospective study we examined 125 eyes of 125 normal patients with a corneal thickness of 568.8 +/- 43.79 microm, a corneal curvature of 7.72 +/- 0.27 mm and an axial length of 23.62 +/- 2.05 mm. Before performing a phacoemulsification, the anterior chamber was temporarily punctured. With a closed system the intraocular pressure (IOP) was manometrically set at 20, 35 and 50 mmHg using an H (2)O column. The IOP was then measured with a Perkins tonometer. With these patients we compared 102 eyes that had undergone LASIK due to a myopia of 6.3 +/- 2.17 D. Before and 6 months after surgery, IOD, k-values and central corneal thickness of these patients were measured. RESULTS: At all set pressure levels there was a highly significant correlation of measured IOP and corneal thickness. At all set pressure levels the measured IOP significantly depended on corneal thickness (r(2) = 0.78 - 0.83). After LASIK, IOP was reduced from 16.5 +/- 2.1 to 12.9 +/- 1.9 mmHg. There was a significant correlation between IOP and corneal curvature as well as corneal thickness (r(2) = 0.631; P < 0.001). The biomechanical characteristics of the cornea are changed so that the measured IOP has to be corrected by an additional 0.75 mmHg. CONCLUSION: Since corneal thickness does affect Goldmann applanation tonometry we recommend to use the "Dresden Correction Table" (Tab. ) to achieve the real IOP. Pressure measurements after LASIK are inaccurate because of a change in corneal biomechanics, corneal thickness and curvature and they should be corrected as follows: IOP (real) = IOP (measured) + (540 - CCT)/71 + (43 - K-value)/2.7 + 0.75 mmHg.

[The risk of glaucoma and corneal thickness]. / Glaukomrisiko und Hornhautdicke.

Intraocular pressure is still the most important risk factor for the development of glaucomatous optic nerve damage. There is growing evidence that corneal thickness is a risk factor for the development of glaucoma. This might be caused by the effect of corneal thickness on intraocular pressure (IOP) measurements. Goldmann applanation tonometry measurements are correlated with corneal thickness. Thick corneas lead to false high readings whereas thin corneas lead to false low readings. If corneal thickness as a risk factor for glaucoma is only related to the dependency of IOP measurements on corneal thickness or is related to possible different biomechanical tissue properties in glaucomatous eyes is not known. However, a large proportion of the corneal thickness effect seems to be related to the effect on IOP readings by applanation tonometry. Neglecting corneal thickness can lead to false measurements of IOP with consequent misdiagnosis and false treatment. Therefore, measurements of corneal thickness should be performed in glaucoma patients and suspects.

[Evaluation of focal arteriolar narrowing of retinal arterioles in glaucoma]. / Fokale Verengungen retinaler Arteriolen beim Glaukom.

PURPOSE: Vascular risk factors seem to play a role in the pathogenesis of glaucoma. This study was performed to compare the prevalence of focal arteriolar narrowing in glaucoma patients and normals. MATERIAL AND METHODS: Stereoscopic optic disc photographs of 40 normal subjects and 14 primary open-angle glaucoma (POAG) patients were reviewed independently in a masked fashion by two graders. Focal arteriolar narrowing within one disc diameter from the rim edge was evaluated based on two different methods: narrowing present if (1) the arteriole was wider distal to the narrowing and (2) if the arteriole was wider both distal and proximal to the narrowing. RESULTS: With both methods, focal arteriolar narrowing was significantly higher in glaucoma versus normal eyes. Focal arteriolar narrowing was observed with definition 1 in 35.0% of normals and 71.4% of POAG patients and with definition 2 in 12.5% of normals and 42.9% of POAG patients. CONCLUSIONS: Focal arteriolar narrowing is more frequent in glaucoma patients than in normals. Independent of the method for assessing arteriolar narrowing, however, the diagnostic value of arteriolar narrowing seems limited due to the high incidence in normals.

[Papillary hemodynamics in patients with normal pressure glaucoma and hemorrhage of the optic papilla circumference]. / Papilläre Hämodynamik bei Patienten mit Normaldruckglaukom und Papillenrandblutungen.

BACKGROUND: Optic disc hemorrhages in patients with normal-pressure glaucoma (NPG) are usually regarded as a sign of vascular dysfunction and as an indicator for glaucoma damage progression. METHODS: Optic nerve head blood flow was measured in 21 patients suffering from NPG with acute optic disc hemorrhages by scanning laser Doppler flowmetry at various locations of the optic disc. Intraocular pressure and mean deviation of the visual field were also monitored. Two groups served as control: 21 patients with NPG matched for age, sex, and stage of the disease and in addition the contralateral eye without any hemorrhages. RESULTS: Optic nerve head blood flow as a mean of several locations was significantly lower in eyes with optic disc hemorrhages than in controls and differed significantly from the contralateral eye. CONCLUSION: Optic nerve blood flow was lower in NPG eyes with optic disc hemorrhages than in the contralateral eye and in controls.

[Ocular hemodynamics and visual field in glaucoma treated with dorzolamide]. / Okuläre Hämodynamik und Gesichtsfeld beim Glaukom unter Dorzolamid-Therapie.

OBJECTIVE: It has been shown that oral carbonic anhydrase inhibitors improve visual function in glaucoma. Furthermore topical dorzolamide might improve ocular hemodynamics, as was demonstrated previously. This study was undertaken to evaluate whether topical dorzolamide affects visual function and ocular hemodynamics in glaucoma. METHODS: In a retrospective, open clinical trial, dorzolamide eye drops were administered to 28 patients with confirmed primary open angle glaucoma (POAG) in both eyes, 3 times daily for a mean follow up of 9 months. One eye was randomly chosen for evaluation. IOP, blood pressure, heart rate, pulsatile ocular blood flow (POBF) and Humphrey 30-2 visual fields were measured at baseline and after the start of the therapy. POBF was determined by pneumotonography. For statistical analysis the Wilcoxon-matched-paired test and the Bonferoni-Holm adjustment were used. RESULTS: In dorzolamide-treated patients the IOP dropped from 18 mmHg to 15.5 mmHg after 9 months therapy (p < 0.01) and the visual field improved significantly by 18% (p < 0.05). A statistically significant change was found for POBF from 543 microliters/min to 675 microliters/min (p < 0.05). CONCLUSIONS: The results showed the expected drop in intraocular pressure. Visual function and pulsatile ocular blood flow improved significantly which might be explained by an analogous, vasodilatory effect as was observed in orally applied carbonic anhydrase inhibitors.

[Retinal nerve fiber layer thickness and peripapillary blood flow in glaucoma patients and healthy probands]. / Retinale Nervenfaserschichtdicke und peripapillärer Blutfluss bei Glaukompatienten und Gesunden.

BACKGROUND: In progressive glaucoma there is increasing loss of retinal nerve fibers and therefore decreasing nerve fiber layer thickness. As measurements of capillary blood flow have been reported to depend on nerve fiber layer thickness, this could result in incorrectly high blood flow measurements in patients with advanced glaucoma. METHODS: In 33 healthy controls and 59 glaucoma patients we measured retinal nerve fiber layer thickness by laser polarimetry and relative capillary blood flow by scanning laser doppler flowmetry three times on the nasal and temporal peripapillary retina. For statistical analysis a regression analysis was used. RESULTS: The correlation coefficients for volume, velocity, and flow with nerve fiber layer thickness at the same location were 0.02/-0.03/-0.02 in the temporal retina and -0.22/-0.07/-0.19 in the nasal retina (all correlations nonsignificant). CONCLUSION: No correlation was found between nerve fiber layer thickness and capillary blood flow. Measurement of capillary blood flow in glaucoma patients thus does not appear to be affected by decreasing nerve fiber layer thickness.

Effect of topical dorzolamide on optic nerve head blood flow.

PURPOSE: The topical carbonic anhydrase inhibitor dorzolamide has proven effective in lowering intraocular pressure in glaucoma patients. Because an impaired blood supply of the optic nerve has to be regarded as a major pathogenic risk factor it seems important to examine the effect of this new antiglaucomatous drug on capillary optic nerve head blood flow. METHODS: In a double-masked, randomized clinical trial, dorzolamide eye drops were applied to both eyes of 15 healthy subjects (8 female, 7 male, mean age 30.6 years) three times daily for 3 days. The control group (15 healthy volunteers, 9 female, 6 male, mean age 30.8 years) received a placebo preparation according to the same protocol. Intraocular pressure (IOP), blood pressure, heart rate, capillary optic nerve head blood flow and retinal blood flow were measured at baseline (1D0), 90 min after single instillation (1D90), and after 3 days of therapy (3D). Scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter) and laser Doppler flowmetry according to Riva (Oculix 4000) were used to measure optic nerve head blood flow. RESULTS: IOP dropped in dorzolamide-treated subjects from 12.5 mmHg to 11.0/10.5 mmHg (1D0, 1D90, 3DO) and in the control group from 13.0 mmHg to 12.5/12.5 mmHg. Optic nerve blood flow as measured by scanning laser Doppler flowmetry showed no significant changes in dorzolamide-treated volunteers (temporal 310/329/315 AU, nasal 387/402/399 AU) or in the placebo group (temporal 238/306/276 AU, nasal 356/382/379 AU). Also as measured by laser Doppler flowmetry optic nerve head blood flow did not show significant changes in dorzolamide-treated volunteers (temporal 12.98/12.6/11.7 AU, nasal 16.6/16.9/15.7 AU) or in the placebo group (temporal 11.9/12.4/12.4 AU, nasal 16.1/15.8/17.7 AU). The systemic parameters blood pressure and heart rate remained unchanged during the treatment period. CONCLUSION: The results showed the expected drop in IOP. However, capillary optic nerve head blood flow, measured by two different techniques, did not change during therapy. This may be due to the effective autoregulation in human optic nerve head circulation, which seems not to be affected by dorzolamide.