Ocular rigidity and neuroretinal damage in patients with vasospasticity: a pilot study.

OBJECTIVE: Evidence suggests that ocular blood flow dysregulation in patients with vasospasticity could occur in response to biomechanical stimuli, contributing to optic nerve head susceptibility in glaucoma. We evaluate the role of vasospasticity in the association between ocular rigidity (OR) and neuroretinal damage, hypothesizing that low OR correlates with greater glaucoma damage in patients with vasospasticity. DESIGN: Cross-sectional study. PARTICIPANTS: Patients with open-angle glaucoma (OAG), suspect discs, or no glaucoma. METHODS: OR was measured using a noninvasive, validated method developed by our group. Retinal nerve fibre layer (RNFL) and ganglion cell complex thicknesses were acquired using spectral domain optical coherence tomography. Vasospasticity was assessed by a standardized questionnaire that was based on existing validated questionnaires and adapted to our requirements. Atherosclerosis was evaluated based on Broadway and Drance's (1998) cardiovascular disease score. Correlations between OR and structural parameters were assessed in patients with vasospasticity and those with atherosclerosis. RESULTS: Of 118 patients with either OAG (n = 67), suspect discs (n = 26), or no glaucoma (n = 25) who were recruited consecutively, 10 were classified as having vasospasticity, and 37 as having atherosclerosis. In the vasospastic group, significant correlations were found between OR and the minimum ganglion cell complex thickness (rs = 0.681, p = 0.030), the average RNFL thickness (rs = 0.745, p = 0.013), and the RNFL in the temporal quadrant (rs = 0.772, p = 0.009), indicating more damage with lower OR. Similar trends were maintained when applying multiple testing correction; however, only the eighth RNFL clock hour corresponding to the inferior-temporal peripapillary region remained significantly correlated with OR in the vasospastic group (p = 0.015). In contrast, no correlation was found in the atherosclerotic group (p > 0.05). CONCLUSIONS: The findings of the current pilot study indicate a trend for more neuronal structural damage in less-rigid eyes of patients with vasospasticity, meaning that OR may play a greater role in glaucoma in vasospastic patients than in patients with atherosclerosis. Although these results provide interesting insight into the pathophysiology of OAG, further investigation is needed to confirm our observations.

Correlation of ocular rigidity with intraocular pressure spike after intravitreal injection of bevacizumab in exudative retinal disease.

BACKGROUND/AIMS: To evaluate the non-invasive measurement of ocular rigidity (OR), an important biomechanical property of the eye, as a predictor of intraocular pressure (IOP) elevation after anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection (IVI). METHODS: Subjects requiring IVI of anti-VEGF for a pre-existing retinal condition were enrolled in this prospective cross-sectional study. OR was assessed in 18 eyes of 18 participants by measurement of pulsatile choroidal volume change using video-rate optical coherence tomography, and pulsatile IOP change using dynamic contour tonometry. IOP was measured using Tono-Pen XL before and immediately following the injection and was correlated with OR. RESULTS: The average increase in IOP following IVI was 19±9 mm Hg, with a range of 7-33 mm Hg. The Spearman correlation coefficient between OR and IOP elevation following IVI was 0.796 (p<0.001), showing higher IOP elevation in more rigid eyes. A regression line was also calculated to predict the IOP spike based on the OR coefficient, such that IOP spike=664.17 mm Hg·µL×OR + 4.59 mm Hg. CONCLUSION: This study shows a strong positive correlation between OR and acute IOP elevation following IVI. These findings indicate that the non-invasive measurement of OR could be an effective tool in identifying patients at risk of IOP spikes following IVI.

The Association Between Ocular Rigidity and Neuroretinal Damage in Glaucoma.

Purpose: Ocular rigidity (OR) is an important biomechanical property, thought to be relevant in the pathophysiology of open-angle glaucoma (OAG). This study aims to evaluate the relationship between OR and neuroretinal damage caused by glaucoma. Methods: One hundred eight subjects (22 with healthy eyes, 23 with suspect discs, and 63 with OAG) were included in this study. OR was measured using a noninvasive optical coherence tomography (OCT)-based method developed by our group. We also measured central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Pearson and partial correlations were performed to evaluate the relationship between OR and glaucomatous damage represented by ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and neuroretinal rim area. Results: Significant positive correlations were found between OR and minimum GCC thickness (r = 0.325, P = 0.001), average GCC thickness (r = 0.320, P = 0.002), rim area (r = 0.344, P < 0.001), and RNFL thickness in the superior (r = 0.225, P = 0.023), and inferior (r = 0.281, P = 0.004) quadrants. These correlations were generally greater than those found for CCT, CH, and CRF. Furthermore, no correlation was found between OR and corneal biomechanical parameters. After adjusting for age, sex, and ethnicity, significant correlations were found between OR and minimum and average GCC thickness (r = 0.357, P = 0.001 and r = 0.344, P = 0.001, respectively), rim area (r = 0.327, P = 0.001), average RNFL thickness (r = 0.331, P = 0.001), and RNFL thickness in the superior (r = 0.296, P = 0.003) and inferior (r = 0.317, P = 0.001) quadrants. Conclusions: In this study, we found a positive correlation between structural OCT-based parameters and OR, indicating more neuroretinal damage in eyes with lower OR. These findings could provide insight into the pathophysiology of OAG.

Relationship between central corneal thickness and changes of optic nerve head topography and blood flow after intraocular pressure reduction in open-angle glaucoma and ocular hypertension.

OBJECTIVES: To investigate changes in optic nerve head topography and blood flow after therapeutic intraocular pressure reduction and to correlate them with central corneal thickness. METHODS: Sixteen patients with open-angle glaucoma and 16 patients with ocular hypertension underwent Heidelberg retina tomography and scanning laser Doppler flowmetry in 1 eye before and at least 2 months after a mean 35% sustained therapeutic reduction in intraocular pressure. Patients were assigned to a thin or thick group based on their median central corneal thickness. RESULTS: Compared with 16 patients with thick corneas (mean +/- SD central corneal thickness, 587 +/- 31 microm), the 16 patients with thin corneas (518 +/- 32 microm) had greater reductions in mean (36 +/- 32 vs 4 +/- 36 microm, P = .003) and in maximum cup depth (73 +/- 107 vs 4 +/- 89 microm, P = .02). These changes were not statistically significantly different between the patients with open-angle glaucoma and those with ocular hypertension. Smaller mean +/- SD improvements in neuroretinal rim blood flow were seen in patients with thinner corneas compared with those with thicker corneas (35 +/- 80 vs 110 +/- 111 arbitrary units, P = .04). CONCLUSION: Patients with open-angle glaucoma and ocular hypertension with thinner corneas show significantly greater shallowing of the cup, a surrogate marker for lamina cribrosa displacement (compliance), and smaller improvements of neuroretinal rim blood flow after intraocular pressure reduction.

Correlation between finger blood flow and changes in optic nerve head blood flow following therapeutic intraocular pressure reduction.

PURPOSE: To correlate finger blood flow and changes in optic nerve head (ONH) blood flow following therapeutic intraocular pressure (IOP) reduction in open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: Seventeen open-angle glaucoma patients and nineteen ocular hypertension patients underwent therapeutic IOP reduction followed by a minimum of 4 weeks of follow-up. Optic nerve head blood flow measurements were obtained by scanning laser Doppler flowmetry using full-field perfusion image analysis. Finger blood flow was measured using the Transonic laser Doppler Flowmeter. Finger blood flow was measured at baseline, after immersion in warm water (40 degrees C) for 2 minutes (Flow Max), and after immersion in cold water (4 degrees C) for 10 seconds (Flow Min). Patients were identified as vasospastic if their Flow Max/Flow Min >7. Statistical comparisons were performed using two-tailed distribution paired T-test and Pearson's correlation factor. RESULTS: For similar mean percentage intraocular pressure reduction, vasospastic patients had greater improvements in rim blood flow than did non-vasospastic patients [+35% versus +13%] (P = 0.01). While there was no difference in rim blood flow changes in the vasospastic versus the non-vasospastic OAG group, the vasospastic ocular hypertension group showed 18% increase in rim blood flow whereas the non-vasospastic ocular hypertension group showed an 8% decrease. A significant negative correlation was also found in the open-angle glaucoma group between rim blood flow change and Flow Max (-0.681, P = 0.003). In contrast, no such correlation was found in the ocular hypertension group (+0.144, P = 0.556). CONCLUSION: OAG patients had a significant negative correlation between changes in rim blood flow and maximum finger Doppler flow. Among ocular hypertension patients, increased rim blood flow was only found in the vasospastic group, though this increase was not statistically significant. These results suggest that open-angle glaucoma and ocular hypertension patients with the most severe vasospastic disease may show the greatest improvements in rim blood flow after sustained intraocular pressure reduction.

The effect of compression on clinical diagnosis of glaucoma based on non-analyzed confocal scanning laser ophthalmoscopy images.

BACKGROUND AND OBJECTIVE: To evaluate the effect of different image compression formats of non-analyzed Heidelberg Retina Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) images on the diagnosis of glaucoma by ophthalmologists. MATERIALS AND METHODS: Thirty-three topographic and reflectance images taken with the HRT representing different levels of disease were transformed using nine different compression formats. Three independent ophthalmologists, masked as to contour line and stereometric parameters, classified the original and compressed HRT images as normal, suspected glaucoma, or glaucoma, and Kappa agreement coefficients were calculated. RESULTS: The Tagged Image File Format had the largest file size and the Joint Photographic Experts Group (JPEG) 2000 format had the smallest size. The highest Kappa coefficient value was 1.00 for all ophthalmologists using the Tagged Image File Format. Kappa values for JPEG formats were all in the range of good to excellent agreement. Kappa values were lower for Portable Network Graphic and Graphics Interchange Format compression formats. CONCLUSION: Image compression with JPEG 2000 at a ratio of 20:1 provided sufficient quality for glaucoma analysis in conjunction with a relatively small image size format, and may prove to be attractive for HRT telemedicine applications. Further clinical studies validating the usefulness of interpreting non-analyzed HRT images are required.

The heritability of glaucoma-related traits corneal hysteresis, central corneal thickness, intraocular pressure, and choroidal blood flow pulsatility.

PURPOSE: The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. METHODS: Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined using the Reichert Ocular Response Analyser. Central corneal thickness was measured with an ultrasound pachymeter. Three measures of intraocular pressure were obtained: Goldmann-correlated and corneal compensated intraocular pressure using the Ocular Response Analyser, and Pascal intraocular pressure using the Pascal Dynamic Contour Tonometer. The pulsatility of choroidal blood velocity and flow were measured in the sub-foveolar choroid using single-point laser Doppler flowmetry (Oculix). We estimated heritability using maximum-likelihood variance components methods implemented in the SOLAR software. RESULTS: No significant heritability was detected for the pulsatility of choroidal blood flow or velocity. The Goldman-correlated, corneal compensated, and Pascal measures of intraocular pressure measures were all significantly heritable at 0.94, 0.79, and 0.53 after age and sex adjustment (p = 0.0003, p = 0.0023, p = 0.0239). Central corneal thickness was significantly heritable at 0.68 (p = 0.0078). Corneal hysteresis was highly heritable but the estimate was at the upper boundary of 1.00 preventing us from giving a precise estimate. CONCLUSION: Corneal hysteresis, central corneal thickness, and intraocular pressure are all heritable and may be suitable as glaucoma endophenotypes. The pulsatility of choroidal blood flow and blood velocity were not significantly heritable in this sample.

Estimation of ocular rigidity in glaucoma using ocular pulse amplitude and pulsatile choroidal blood flow.

PURPOSE: Theoretical models and animal studies have suggested that scleral rigidity plays an important role in the pathogenesis of glaucoma. The aim of this study was to present a noninvasive technique for estimating ocular rigidity (E) in vivo, and to compare the estimated rigidity between patients with open-angle glaucoma (OAG); ocular hypertension (OHT); suspect glaucomatous disc (GS); and normal subjects (N). We hypothesized that OHT patients would have higher rigidity. METHODS: All patients underwent measurements of ocular pulse amplitude (OPA) using dynamic contour tonometry, pulsatile choroidal blood flow (ChBFP) using laser Doppler flowmetry; axial length (AL); and assessment of automated visual field mean deviation (MD). The ratio between OPA and ChBFP was calculated according to the Friedenwald's equation of ocular rigidity. The calculated ratio is denoted as (ER). The average ER values of the four diagnostic groups were compared using nonparametric tests. The relationship between ER and other ocular and systemic factors was examined using correlation and regression analysis. RESULTS: A total of 257 subjects were included in the study (56 N, 108 OAG, 48 GS, and 45 OHT). ER correlated negatively with AL and positively with MD, signifying that a lower rigidity was associated with a longer eye and a worse (more negative) MD. ER was also found to be highest in OHT (0.235 ± 0.16) and lowest in OAG (0.188 ± 0.14; P = 0.01). CONCLUSIONS: Estimated coefficient of ocular rigidity by OPA and ChBFP suggested that glaucoma patients had the lowest rigidity and OHT the highest. It supports the idea that a more compliant ocular shell may predispose the optic nerve head to intraocular pressure (IOP)-related damage.

Pulsatile movement of the optic nerve head and the peripapillary retina in normal subjects and in glaucoma.

PURPOSE: To measure the pulsatile movement of neuroretinal tissue at the optic nerve head synchronous with the cardiac cycle. METHODS: We used a noninvasive imaging device based on Fourier domain low-coherence interferometry to measure the pulsatile movements of the optic nerve head, peripapillary retina, and cornea with submicron accuracy along a line across the fundus. We also measured the change in the Axial Distance between the peripapillary Retina and the base of the optic disc Cup (ADRC) during the cardiac cycle. Twelve normal subjects and 20 subjects with open-angle glaucoma were tested. RESULTS: In normal subjects, the mean fundus pulsation amplitude (defined as the fundus movement minus the simultaneous corneal movement) were 13.0 ± 2.5 µm, 9.0 ± 2.1 µm, and 8.7 ± 2.9 µm at the base of the optic nerve head cup, the nasal peripapillary retina, and the temporal peripapillary retina, respectively, compared with 16.7 ± 6.8 µm, 17.3 ± 10.9 µm, and 12.7 ± 6.2 µm for the corresponding values in the glaucoma group (P = 0.26, P = 0.008, and P = 0.12, respectively). The mean changes in ADRC during the cardiac cycle in normal subjects were 10.7 ± 2.1 µm and 11.6 ± 1.8 µm for the nasal and temporal side of the optic disc, respectively, compared to 14.9 ± 5.6 µm and 14.0 ± 4.9 µm in glaucoma subjects (P = 0.03 and P = 0.10, respectively). CONCLUSIONS: There was an approximately 11-µm pulsatile change in the ADRC in normal subjects, and on the nasal side of the disc, this amount was significantly greater in glaucoma patients.

The effect of intravitreal injection of bevacizumab on retinal circulation in patients with neovascular macular degeneration.

PURPOSE: Intravitreal (ITV) injection of anti-VEGFs like bevacizumab are widely used to treat neovascular AMD. However, VEGF is essential for biologic functions such as blood pressure regulation. Indeed, anti-VEGF intravenous administration is associated with hypertension. Therefore, the effect of ITV bevacizumab on retinal circulation was examined. METHODS: Twenty-three patients with neovascular AMD treated with three repeat ITV injections of bevacizumab were recruited. Blood arteriolar diameter and flow measurements were performed with a bidirectional laser Doppler flowmeter at baseline, 1 week after the first injection, just before the second injection, and 5 weeks after the third injection. Scanning laser Doppler flowmetry was used to assess the effect of bevacizumab on tissue perfusion at the first and fourth visits. RESULTS: Arteriolar diameter significantly decreased from 122.5 ± 14.5 µm to 118.9 ± 14.0 µm (P = 0.03) during the first week to reach a mean value of 117.2 ± 13.7 µm at the end of the study (P < 0.01). Arterial blood flow did not change significantly. Neuroretinal rim perfusion decreased from 181.1 ± 84.1 arbitrary flow units to 167.7 ± 76.5 arbitrary flow units, which was borderline significant (P = 0.06). No significant change was observed in the peripapillary retina. CONCLUSIONS: Arteriolar diameter decreased significantly after the first injection and persisted until the end of the study suggesting a long-term effect of bevacizumab on vascular tone. However, the blood flow change is not significant. A borderline significant decrease in neuroretinal rim perfusion was observed and suggests that the neuroretinal rim may be more sensitive than the peripapillary retina to the effects of bevacizumab.

Assessment of factors affecting the difference in intraocular pressure measurements between dynamic contour tonometry and goldmann applanation tonometry.

PURPOSE: To determine if the difference in intraocular pressure (IOP) measurements between dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) is correlated with axial length (AL), and to assess the possible influence of age, sex, central corneal thickness (CCT), corneal hysteresis (CH), ocular pulse amplitude (OPA), and glaucoma status on the difference in IOP measurements between the 2 instruments (ΔIOP=DCTIOP- GATIOP). METHODS: Two hundred sixty-oneparticipants (509 eyes) in these 4 groups were included: 53 normal individuals (N; 106 eyes), 112 glaucoma patients (OAG; 212 eyes), 52 glaucoma suspects (GS; 103 eyes), and 44 patients with ocular hypertension (OHT; 88 eyes). The patients who had had an incisional ocular surgery were excluded. All participants underwent IOP evaluation with DCT and GAT and AL, CCT, and CH measurements. The influence of age, sex, AL, CCT, CH, OPA, and glaucoma diagnostic status on ΔIOP was evaluated using correlation analysis and analysis of variance (ANOVA). Right (OD) and left eyes (OS) were analyzed separately. RESULTS: ΔIOP was higher in eyes with longer axial lengths (OD: r=0.142, P=0.02; OS: r=0.233, P<0.001). ΔIOP also correlated with CH (OD: r=-0. 127, P=0.04; OS: r=-0.169, P=0.01), in which the ΔIOP increased as CH decreased (corresponding to less rigid corneas). OPA also correlated negatively with ΔIOP, but the correlation was only statistically significant in left eye (OD: r=-0.112, P=0.08; OS: r=-0.124, P=0.05). Age, CCT, sex, and diagnostic status did not influence ΔIOP significantly. CONCLUSIONS: GAT underestimated IOP more compared with DCT in patients with longer axial length and in patients with lower corneal hysteresis.

Postmenopausal hormone therapy increases retinal blood flow and protects the retinal nerve fiber layer.

PURPOSE: To investigate whether postmenopausal hormone therapy (HT) increases retinal and ONH blood flow (BF) and protects ONH topography and the function of retinal ganglion cells in postmenopausal women (PMW). The effect of estradiol (E(2)) treatment on retinal tissue perfusion was also investigated in ovariectomized rats, an animal model for menopause. METHODS: Sixty-four healthy PMW were recruited, 29 of whom never used HT ( HT) and 35 of whom had used HT (+HT) continuously since the onset of menopause. Blood flow of the inferotemporal retinal artery (ITRA), peripapillary retina, and ONH rim were measured in one eye. The ONH stereometric parameters and the pattern electroretinogram (PERG) were also measured. In ovariectomized rats, the retinal tissue perfusion was assessed using the BF tracer N-isopropyl-p-[(14)C]-iodoamphetamine ([(14)C]-IMP) in rats treated with either E(2) (n = 7) or placebo (n = 5). RESULTS: Compared with the HT group, the +HT group presented significantly greater BF of the ITRA (P = 0.006), greater rim volume for the entire ONH region (P = 0.032), and greater rim volume (P = 0.042), height variation contour (P = 0.011), mean thickness (P = 0.033), and cross-sectional area (P = 0.020) of the retinal nerve fiber layer for the inferotemporal region of the ONH when adjusted for age, ocular perfusion pressure, and age at menarche. In ovariectomized rats, E(2) treatment significantly increased retinal perfusion in a range of 22% to 45%. CONCLUSIONS: These findings indicate that estrogens and HT increase retinal blood flow and protect the retinal nerve fiber layer.