Denise Descovich

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.

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°C) for 2 minutes (Flow Max), and after immersion in cold water (4°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 Pearsons 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 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.

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.

Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging.

We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology.

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

PurposeTo 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 (&Dgr;IOP=DCTIOP− GATIOP). MethodsTwo 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 &Dgr;IOP was evaluated using correlation analysis and analysis of variance (ANOVA). Right (OD) and left eyes (OS) were analyzed separately. Results&Dgr;IOP was higher in eyes with longer axial lengths (OD: r=0.142, P=0.02; OS: r=0.233, P<0.001). &Dgr;IOP also correlated with CH (OD: r=−0. 127, P=0.04; OS: r=−0.169, P=0.01), in which the &Dgr;IOP increased as CH decreased (corresponding to less rigid corneas). OPA also correlated negatively with &Dgr;IOP, 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 &Dgr;IOP significantly. ConclusionsGAT underestimated IOP more compared with DCT in patients with longer axial length and in patients with lower corneal hysteresis.

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 Friedenwalds 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.