Characterization of Ocular Biomechanics in Pellucid Marginal Degeneration.

PURPOSE: This study sought to investigate the diagnostic capacity of corneal biomechanical response parameters in a group of patients with pellucid marginal degeneration (PMD) using the Ocular Response Analyzer (ORA) and Corvis ST devices. METHODS: In this prospective clinical study, we used the Corvis ST and ORA devices to investigate the ocular biomechanics of patients with PMD. Eighty-one eyes were included, and 2 study groups were formed: the PMD group (the study group, n = 29) and the control group (n = 52). We focused on 13 biomechanical parameters. Statistical analysis was performed using SPSS. Biomechanical parameters for the 2 groups were compared using analysis of covariance. RESULTS: The ORA results demonstrated that the Keratoconus Match Index was significantly lower in the PMD group than in the control group (0.031 ± 0.37 vs. 0.79 ± 0.33; P = 0.001). The 2 groups did not significantly differ with respect to intraocular pressure- and central corneal thickness-adjusted values for corneal hysteresis or corneal resistance factor. Regarding the Corvis parameters, differences between the control and PMD groups were detected for CorWmax amp (control 1.01 ± 0.01, PMD 1.06 ± 0.01; P = 0.020) and CorA2 t (control 21.78 ± 0.03, PMD 21.66 ± 0.04; P = 0.0003). CONCLUSIONS: We identified 2 Corvis parameters that could be used to characterize PMD and differentiate PMD corneas from normal corneas. These parameters support the hypothesis that there is significantly less deformation of the central cornea in PMD corneas than in healthy corneas. However, because useful "first-line" diagnostic devices for diagnosing PMD (such as Pentacam and the ORA) exist, the Corvis ST serves as an additional diagnostic tool that can also be used for long-term monitoring after diagnosis confirmation.

Diameter of retinal vessels in patients with diabetic macular edema is not altered by intravitreal ranibizumab (lucentis).

PURPOSE: To investigate the effect(s) of intravitreally injected ranibizumab on retinal vessel diameter in patients with diabetic macular edema. METHODS: Participants of this prospective study were 14 men and 16 women (30 eyes) aged 60 ± 11 years (mean ± standard deviation), all with clinically significant diabetic macular edema. Treatment comprised 3 intravitreal injections of ranibizumab given at 4-week intervals. Examinations were conducted before the first (baseline), before the second (Month 1), before the third (Month 2) injections, and 3 months after baseline (Month 3). Measured parameters included systemic blood pressure, static retinal vessel analysis (central retinal artery equivalent and central retinal vein equivalent), and dynamic retinal vessel analysis, as measured by the change in vessel diameter in response to flicker stimulation during three measurement cycles. Flicker stimulation was accomplished using a 50-second baseline recording, followed by an online measurement during 20-second flicker stimulation and 80-second online measurements in both arteriolar and venular vessel segments. RESULTS: Static retinal vessel analysis showed a reduction of central retinal artery equivalent from 186.25 ± 51.40 µm (baseline) to 173.20 ± 22.2 µm (Month 1), to 174.30 ± 27.30 µm (Month 2), and to 170.56 ± 22.89 µm (Month 3), none of which was statistically significant (P = 0.23, 0.12, and 0.14, respectively). Central retinal vein equivalent was reduced from 216.21 ± 25.0 µm (baseline) to 214.48 ± 25.4 µm (Month 1), to 214.80 ± 24.30 µm (Month 2), and to 211.41 ± 24.30 µm (Month 3), revealing no statistically significant differences between examination time points (P = 0.54, 0.06, and 0.24, respectively). Dynamic vessel analysis yielded a mean retinal arterial diameter change of +1.47% ± 2.3 (baseline), +1.91% ± 2.5 (Month 1), +1.76% ± 2.2 (Month 2), and +1.66% ± 2.1 (Month 3), none of which showed statistically significant differences (P = 0.32, 0.49, and 0.70, respectively). Mean retinal venous diameter changes were +3.15% ± 1.7 (baseline), +3.7% ± 2.3 (Month 1), +4.0% ± 2.0 (Month 2), and +4.95% ± 1.9 (Month 3), none of which showed statistically significant differences (P = 0.12, 0.17, and 0.14, respectively). Central retinal thickness, as measured by spectral domain optical coherence tomography, decreased significantly from 435.2 ± 131.8 µm (baseline) to 372.3 ± 142.8 µm (Month 3), P = 0.01. Regression analysis of arteriolar and venular diameters indicated that there was no significant correlation between these 2 parameters (r = 0.053; P = 0.835 and r = 0.06; P = 0.817, respectively). Also, no significant correlation was observed between the difference in the central retinal thickness and change in arteriolar or venular dilatation (r = 0.291, P = 0.241 and r = 0.06, P = 0.435, respectively). CONCLUSION: Intravitreally applied ranibizumab did not significantly affect retinal vessel diameter in patients with diabetic macular edema. Decline in the central foveal thickness after ranibizumab therapy, as measured by spectral domain optical coherence tomography, was not linked to any change in retinal vessel diameter or dilatatory response, neither for arterioles nor venules.

Enhanced pressure in the central retinal vein decreases the perfusion pressure in the prelaminar region of the optic nerve head.

PURPOSE: The pressure in the central retinal vein (CRVP) has been shown to be higher in glaucoma patients than in controls. Until now, these measurements have been performed in arbitrary units or in units of ophthalmodynamometric force. In our study, a contact lens dynamometer, calibrated in mm Hg, was used to calculate the retinal perfusion pressure. METHODS: A total of 27 patients with primary open angle glaucoma (POAG) and 27 healthy control subjects were included in the study. The IOP measurement included Goldmann applanation tonometry, whereas the pressure enhancement measurement consisted of contact lens dynamometry. results: the pressures are given in mm hg, and are expressed as the mean ± SD for the control subjects versus the POAG patients: IOP 14.4 ± 2.7 vs. 15.4 ± 2.9, systolic blood pressure 141 ± 20.1 vs. 153 ± 16.5 (P = 0.013), central retinal vein threshold pressure (CRVTP) 11.9 ± 3.8 vs. 16.8 ± 5.0, CRVP 15.0 ± 2.7 vs. 17.9 ± 4.2, and retinal perfusion pressure (PPret) standard 84 ± 12.2 vs. 94 ± 9.1 and new 83 ± 12.2 vs. 91 ± 9.6. The differences in PPret between using the new versus the standard method are 0.55 ± 1.33 vs. -2.5 ± 3.89 (P = 0.041 and P = 0.002, respectively). The PPret was at least 5.0 mm Hg lower in 5 of the 27 POAG patients when the new calculation method was used. CONCLUSIONS: The perfusion pressure in the retina and prelaminar region of the optic nerve head (ONH) may be lower than expected because the CRVP may be higher. The pressure measurement in the central retinal vein may be a step toward a better understanding of ONH pathophysiology.

Morphological and functional differences between normal-tension and high-tension glaucoma.

PURPOSE: To compare visual field (VF) and nerve fibre loss in patients with normal-tension (NTG) and high-tension glaucoma (HTG) at an equal level of glaucomatous structural damage of the optic nerve head (ONH). METHODS: In a retrospective, pair-matched, comparative study, 126 eyes with NTG and 126 eyes with HTG were matched according to the same glaucomatous ONH damage based on rim volume, rim area and disc size measured by the Heidelberg Retina Tomograph (HRT III). Visual field by Humphrey perimetry and nerve fibre layer thickness measured by scanning laser polarimetry (GdxVCC) were compared between both groups. RESULTS: Based on the HRT, NTG and HTG displayed comparable structural damage of the ONH without a statistically significant difference between both groups (mean, NTG/HTG: disc area 2.32/2.32 mm², p =0.342; rim area 1.03/1.00 mm², p = 0.279; rim volume 0.2/0.19 mm³; p = 0.274). Eyes with NTG had significantly less VF damage than eyes with HTG (mean, NTG/HTG: mean deviation (MD) -3.69/-9.77 dB, p = 0.0001; pattern standard deviation (PSD) 4.80/7.17 dB, p = 0.0001). The nerve fibre layer of NTG patients was thicker than that of HTG patients (mean, NTG/HTG: GDx total: 46.9/44.0 µm, p = 0.073; GDx superior: 57.2/49.9 µm, p = 0.0001; GDx inferior: 54.9/49.7 µm, p = 0.001). CONCLUSIONS: At an equal level of glaucomatous structural damage of the ONH indicated by cupping, rim area and rim volume, NTG patients seem to have a less affected visual field and a better preserved nerve fibre layer than HTG patients.

The effect of acetazolamide on different ocular vascular beds.

PURPOSE: To assess the effect of acetazolamide (AZ) on different ocular vascular beds. METHODS: In a prospective study, 32 healthy volunteers (16 male, 16 female) with a mean age of 23.9 ± 3.3 years (20-39 years) were included. Before and after intravenous administration of 1,000 mg AZ (single dose), ocular microcirculation parameters were measured every 20 min for 2 h. Retinal vessel diameters (VD) were measured by the retina vessel analyzer, blood flow (BF) in the neuroretinal rim by the laser doppler flowmeter according to Riva, and the parapapillary retinal BF by the scanning laser Doppler flowmeter. Additionally, the Langham ocular blood flow system was used to determine the ocular pulse amplitude (OPA) and the pulsatile ocular blood flow (pOBF). The measurements were correlated with systemic blood pressure (BP), ocular perfusion pressure (OPP), capillary base excess parameters and serum AZ levels. RESULTS: Arterial and venous VD were significantly increased by about 4-5% each. Papillary BF increased significantly about 40%. Parapapillary retinal flow dropped significantly about 19% (120 min). OPA and pOBF showed no statistically significant changes. BP showed no significant changes, and OPP was significantly increased. There were no correlations with pH or systemic perfusion parameters. CONCLUSIONS: AZ leads to a dilatation of retinal VD, to an increase of BF in the optic nerve head, and to a decrease of parapapillary retinal BF. The different BF changes in different vascular beds might be due to different regulatory mechanisms, steal effects, or different distributions of the carbonic anhydrase.

Identification of biomechanical properties of the cornea: the ocular response analyzer.

PURPOSE: Several methods have been devised for measuring geometric parameters of the cornea but, until now, the biomechanics of the cornea have been largely ignored. The relatively new Ocular Response Analyzer (ORA) provides such biomechanical information. In order to correctly interpret the underlying biomechanics of ORA data, we review reported ORA measurements and provide a compendium of factors influencing these measurements, with discussion of possible explanations for ORA measurement results. METHODS: This review comprised a literature search using "ocular response analyzer" and "ocular response analyser" as keywords. We reviewed and compared reported results from recent ORA studies so obtained, with an eye to understanding corneal biomechanics. RESULTS: Several ORA biomechanical parameters of the cornea - corneal hysteresis (CH) and corneal resistant factor (CRF) - characterize the viscoelastic properties of the cornea, especially those of the ground substance. The impact on CH and CRF values of various independent factors, e.g. intraocular pressure (IOP), age, central corneal thickness (CCT), and corneal swelling, are discussed. The impact on CH and CRF of treatment-related structural changes of the cornea, i.e. those occurring after refractive surgical procedures, placement of intracorneal rings, and collagen crosslinking (CXL), as well as pathological changes of the cornea, e.g. those resulting from keratoconus, edema, and glaucoma, are discussed. CONCLUSIONS: Changes in CRF and CH may be reflective of structural changes in the ground substance of the cornea. Thus, ORA provides invaluable information for delineating biomechanical conditions pertaining to the cornea, with special regard to ocular diseases, e.g. keratoconus and glaucoma.

Biomechanical and morphological differences between the sclera canal ring and a peripheral sclera ring in the porcine eye.

AIM: To investigate a possible association between the biomechanical load and unload behaviour and the elastin content of the sclera canal ring (SCR) and a superiorly localized sclera ring (SPS) in the porcine eye. METHODS: Two sclera rings were trephined from each of 40 porcine eyes, one containing the SCR and the other an SPS. The load and the unload curves were measured in the extension range of 0-2.0 mm by a biomaterial tester. Hysteresis was determined from the area enclosed by the loading and unloading curve. Histochemical staining with resorcin-fuchsin and morphometric analysis of paraffin-embedded sections of both rings were performed to detect the area occupied by elastin fibres. RESULTS: At 1 mm extension, the mean load of the SCR was 0.89 ± 0.22 N and that of the SPS 1.13 ± 0.19 N, which was not significantly different between both rings (p > 0.05). Mean hysteresis in the SCR was 1.55 ± 0.30 N × mm and 1.90 ± 0.18 N × mm in the SPS, which was significantly different between both rings (p = 0.01). Mean sclera thickness was 986 µm in the SCR (range: 900-1,060 µm) and 971 µm in the SPS (range: 800-1,200 µm) without a statistically significant difference between both sclera rings (p = 0.78). The area occupied by elastin fibres was 15.5 ± 3.4% in the SCR and 4.5 ± 1.5% in the SPS, which was significantly different between both rings (p = 0.0001). CONCLUSION: Hysteresis in the SCR was significantly lower than in the SPS, indicating a higher elasticity of the SCR in the porcine eye. This effect could be explained by a higher content of elastin in the surrounding ring of the peripapillary optic nerve head providing reversible contraction in cases of intra-ocular pressure variations.

Diabetes mellitus affects biomechanical properties of the optic nerve head in the rat.

BACKGROUND: To investigate the effect of diabetes on the biomechanical behavior of the optic nerve head (ONH) and the peripapillary sclera (ppSc) in streptozocine-induced diabetic rats. METHODS: Diabetes mellitus was induced in 20 Wistar rats using streptozocine. Twenty-five nondiabetic rats served as controls. Eyes were enucleated after 12 weeks and 2 strips of one eye were prepared containing ONH or ppSc. The stress-strain relation was measured in the stress range of 0.05-10 MPa using a biomaterial tester. RESULTS: At 5% strain the stress of the ONH in diabetic rats was 897±295 kPa and in the control group it was 671±246 kPa; there was a significant difference between both groups (p=0.011). The stress of the diabetic ppSc (574±185 kPa) increased compared to that of the nondiabetic ppSc (477±171 kPa), but this did not reach statistical significance (p=0.174). The calculated tangent modulus at 5% strain was 11.79 MPa in the diabetic ONH and 8.77 MPa in the nondiabetic ONH; there was a significant difference between both groups (p=0.006). The calculated tangent modulus at 5% strain was 7.17 MPa in the diabetic ppSc and 6.12 MPa in the nondiabetic ppSc, without a statistically significant difference (p=0.09). CONCLUSION: In contrast to the ppSc, the ONH of diabetic rats showed a significant increase in stiffness compared to nondiabetic rats, which might be explained by nonenzymatic collagen cross-linking mediated by advanced glycation end products due to high blood glucose levels in diabetes. Further studies are needed to investigate if these biomechanical changes represent a detrimental risk factor for intraocular pressure regulation in diabetic glaucoma patients.

Statins affect ocular microcirculation in patients with hypercholesterolaemia.

PURPOSE: To investigate the effect of statins on ocular microcirculation in patients with hypercholesterolaemia. METHODS: Ten patients with hypercholesterolaemia were included in this study. The diameter of retinal vessels was measured continuously with the retinal vessel analyser (RVA) before and 4 weeks after statin therapy. After baseline assessment, a monochromatic luminance flicker was applied to evoke retinal vasodilation. Flicker response was then analysed after 50, 150 and 250 seconds after baseline measurement. Additionally, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride levels were obtained to find a possible correlation between retinal vessel diameter changes and lipid metabolism before and after statin therapy. RESULTS: The mean diameter of the arterioles before statin therapy at baseline was 106.3 ± 1.5 µm and the mean diameter of the venules at baseline was 127.3 ± 2.5 µm. The mean diameter of the arterioles 4 weeks before statin therapy was 107.3 ± 1.8 µm after 50 seconds, 107.9 ± 1.8 µm after 150 seconds and 108.0 ± 1.8 µm after 250 seconds (p = 0.01). The mean diameter of the venules 4 weeks before statin therapy was 128.0 ± 2.6 µm after 50 seconds, 128.2 ± 2.5 µm after 150 seconds and 128.2 ± 2.3 µm after 250 seconds (p = 0.01). The mean diameter of the arterioles 4 weeks after statin therapy at baseline was 107.1 ± 1.6 µm and the mean diameter of the venules at baseline was 127.7 ± 2.3 µm which was significantly different from measurements before statin therapy (p = 0.004). The diameter of the arterioles 4 weeks after statin therapy increased to 109.2 ± 2.1 µm after 50 seconds, to 110.6 ± 2.6 µm after 150 seconds and to 111.8 ± 2.3 µm after 250 seconds with statistical significance at all time points (p = 0.001). The mean diameter of the venules after statin therapy increased to 130.6 ± 2.7 µm after 50 seconds, to 132.1 ± 2.6 µm after 150 seconds and to 133.5 ± 3.0 µm after 250 seconds with statistical significance at all time points (p = 0.001). CONCLUSIONS: The present study demonstrated a significant increase in vasodilatation of retinal arterioles and venules 4 weeks after statin therapy in patients with hypercholesterolaemia indicating pleiotropic effects of statins on the retinal microcirculation which seem to be mediated by the endothelium-dependent, NO-mediated pathway.

The effect of low-density lipoprotein apheresis on ocular microcirculation in patients with hypercholesterolaemia: a pilot study.

AIM: To investigate the effect of low-density lipoprotein (LDL) apheresis on ocular microcirculation in patients with hypercholesterolaemia. METHODS: Six patients with hypercholesterolaemia were included in this study. The diameter of retinal vessels was measured continuously with the retinal vessel analyser before and after LDL apheresis. After baseline assessment a monochromatic luminance flicker was applied to evoke retinal vasodilation. Flicker response was then analysed 50, 70 and 120 s after baseline measurement. In addition, cholesterol, high-density lipoprotein, LDL and triglyceride levels were obtained to find a possible correlation between changes in retinal vessel diameter and lipid metabolism before and after apheresis. RESULTS: The mean diameter of the arterioles at baseline was 107.6±2.1 µm and the mean diameter of the venules at baseline was 132.8±3.2 µm. The diameter of the arterioles after apheresis increased to 111.2±2.3 µm after 50 s, 113.2±2.6 µm after 70 s and 113.7±2.6 µm after 120 s, showing a trend to statistical significance at all time points (p=0.046, p=0.028 and p=0.028, respectively). The mean diameter of the venules after apheresis increased to 138.8±5.9 µm after 50 s, 139.8±6.3 µm after 70 s and 141.2±6.0 µm after 120 s, showing a trend to statistical significance at all time points (all p=0.028). CONCLUSIONS: Changes in retinal vascular diameter seem to be associated with the systemic effect of a single LDL apheresis. Vasodilatation of the arterioles and the venules improved after LDL apheresis, indicating an improvement of ocular perfusion in patients with hypercholesterolaemia.

Comparison of Travoprost and Bimatoprost plus timolol fixed combinations in open-angle glaucoma patients previously treated with latanoprost plus timolol fixed combination.

PURPOSE: To compare the ocular hypotensive effect of bimatoprost plus timolol and travoprost plus timolol fixed combinations in glaucoma patients whose disease was controlled but had not reached their target intraocular pressure (IOP) with the fixed combination of latanoprost plus timolol. DESIGN: A 2 × 3-month, multicenter, prospective, randomized, double-masked, cross-over clinical trial. METHODS: Eighty-nine open-angle glaucoma (OAG) patients were included. After a 6-week run-in period with latanoprost plus timolol, patients were randomized to either travoprost plus timolol or bimatoprost plus timolol for 3 months. Patients then switched to the opposite therapy for 3 additional months. The primary end point was the comparison of mean daily IOP after 3 months of each treatment. RESULTS: At baseline, mean IOP was 16.5 mm Hg (95% confidence interval, 16.0 to 17.0 mm Hg) with treatment with latanoprost plus timolol. Both bimatoprost plus timolol and travoprost plus timolol statistically significantly reduced the mean IOP from baseline (P < .0001). Mean IOP at month 3 was statistically significantly lower in the bimatoprost plus timolol group compared with the travoprost plus timolol group (14.7 mm Hg [95% confidence interval, 14.3 to 15.3 mm Hg] vs 15.4 mm Hg [95% confidence interval, 15.0 to 15.9 mm Hg]; P = .0041). IOP was lower during bimatoprost plus timolol treatment at all time points and statistical significance was reached at 8 am, 11 am, and 5 pm, but not at 2 pm and 8 pm. Both treatments showed similar tolerability profile. CONCLUSIONS: Bimatoprost plus timolol and travoprost plus timolol can provide additional IOP-lowering effect in patients not fully controlled with latanoprost plus timolol. The observed additional IOP reduction was greater with bimatoprost plus timolol with a similar tolerability profile.

Contact lens dynamometry: the influence of age.

PURPOSE: To examine the influence of age on systolic (systOAP) and diastolic (diastOAP) blood pressure in the ophthalmic artery (OA) measured by a new contact lens dynamometer (CLD). METHODS: In a prospective cross-sectional clinical trial, 106 eyes of 106 patients (58 women, 48 men) were examined. A nearly uniform age distribution was achieved by recruiting subjects in seven age groups, with at least 12 in each decade. Blood pressure in the OA was measured with a new CLD. Arterial blood pressure at the upper arm was measured by cuff, according to the Riva-Rocci (RR) METHOD: Main outcome measures were: SystOAP and diastOAP in the OA and systolic (systRR) and diastolic (diastRR) pressures in the subclavian artery. RESULTS: The blood pressures showed the following linear regression equations in association with age: systRR (mm Hg) = 115 + 0.45 × age (years) (R = 0.50; P < 0.00001); diastRR (mm Hg) = 72 + 0.28 × age (years) (R = 0.42; P < 0.00001); systOAP (mm Hg) = 61 + 0.93 × age (years) (R = 0.74; P < 0.0001); and diastOAP (mm Hg) = 44 + 0.37 × age (years) (R = 0.57; P < 0.0001). CONCLUSIONS: The relative slopes of the regression lines relating age to diastolic and systolic pressures are steeper in the ophthalmic than in the subclavian artery, indicating that the pressures in the ophthalmic artery increase faster with age than do the associated pressures in the subclavian artery, as measured by the standard sphygmomanometry. This phenomenon may be explained by progressive stiffening of the walls in the carotid and ophthalmic arteries. The effect of age should be taken into account whenever interpreting ophthalmodynamometric measurements for clinical diagnostic purposes.