Konstantin Gugleta

Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage

PURPOSE To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation

Aims: To investigate the source of ocular blood flow alterations in glaucoma. Methods: In 56 patients with open angle glaucoma, blood flow parameters were obtained from both eyes in the ophthalmic and central retinal artery by means of colour Doppler imaging, as well as in the choroidal circulation and the neuroretinal rim of the optic nerve by means of laser Doppler flowmetry. Based on these haemodynamic parameters, a cluster analysis (two groups) was performed and differences with regard to risk factors were assessed between clusters. Results: Ocular blood flow data in the two clusters indicated that the two groups (cluster 1 = 26 patient with higher blood flow values; cluster 2 = 30 patients with lower blood flow values) differed mainly in choroidal and optic nerve blood flow. No differences in sex distribution, propensity to have normal tension glaucoma, age, endothelin-1 plasma levels, visual field damage, intraocular pressure, or systemic blood pressure parameters were observed between the two clusters. However, 12 patients (46%) from the cluster with high ocular blood flow values showed a vasospastic response in nailfold capillaroscopy, while such a response was observed in 24 patients (80%) of the cluster with low ocular blood flow values. This difference in vasospastic propensity was statistically significant (p = 0.0121). Conclusions: Ocular blood flow alterations in glaucoma patients seem, at least partly, to be related to a systemic vascular dysregulation.

Ocular perfusion pressure in glaucoma

This review article discusses the relationship between ocular perfusion pressure and glaucoma, including its definition, factors that influence its calculation and epidemiological studies investigating the influence of ocular perfusion pressure on the prevalence, incidence and progression of glaucoma. We also list the possible mechanisms behind this association, and discuss whether it is secondary to changes in intraocular pressure, blood pressure or both. Finally, we describe the circadian variation of ocular perfusion pressure and the effects of systemic and topical medications on it. We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage. However, prospective, longitudinal studies are needed to better define the role of ocular perfusion pressure in the development and progression of glaucoma.

Physiology of Perfusion as It Relates to the Optic Nerve Head

Blood flow in the optic nerve has been demonstrated to be autoregulated, and, thus, within certain limits, to be independent of the local perfusion pressure. As in the brain, a close coupling of neuronal activity and optic nerve head blood flow has been demonstrated. A number of regulatory systems and factors participate in the regulation of vascular tone in various organs, including the optic nerve. Metabolic and myogenic mechanisms keep local perfusion constant or adapted to the local metabolic needs. Such mechanisms seem to be involved in the regulation of optic nerve blood flow as well. In contrast, neuronal blood flow regulation is of minor importance in the optic nerve. Many of the regulatory modalities induce a response of vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer. Indeed, endothelial factors are of utmost importance in the regulation of optic nerve blood flow. The facts that there is a basal formation of nitric oxide, which leads to an active dilation of the ocular vasculature, and that endothelin-1 decreases blood flow to the anterior optic nerve in a dose-dependent manner suggest that alterations in these regulatory mechanisms might be relevant for optic nerve blood flow alterations as they relate to glaucomatous optic neuropathy. It is hoped that a detailed knowledge of blood flow regulation in the optic nerve might initiate new treatment modalities in optic neuropathies that are hemodynamic and vascular in nature.

Use of colour Doppler imaging in ocular blood flow research.

The main objective of this report is to encourage consistent quality of testing and reporting within and between centres that use colour Doppler imaging (CDI) for assessment of retrobulbar blood flow. The intention of this review is to standardize methods in CDI assessment that are used widely, but not to exclude other approaches or additional tests that individual laboratories may choose or continue to use.

Interocular difference in progression of glaucoma correlates with interocular differences in retrobulbar circulation

PURPOSE To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow. METHODS On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P <. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P <.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P <.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P <. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage. CONCLUSION Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.

Retrobulbar Blood Flow in Glaucoma Patients With Nocturnal Over-Dipping in Systemic Blood Pressure

PURPOSE To evaluate the relationship between the circadian blood pressure rhythm and the retrobulbar blood flow in glaucoma patients. DESIGN Cross-sectional study. METHODS Circadian blood pressure measurements and color Doppler imaging (CDI) in the ophthalmic artery as well as the central retinal artery of one randomly selected eye were obtained in 193 primary open-angle glaucoma patients. CDI parameters were compared by means of analysis of covariance between patients with a nocturnal decrease in mean systemic blood pressure (MBP) below 20% of the average daytime MBP (over-dippers), patients with a decrease between 10% to 20% (dippers), and patients with a decrease of less than 10% (nondippers), using age, intraocular pressure (IOP), and MBP during color Doppler measurement as covariates. RESULTS An analysis of covariance disclosed, after correcting for age, IOP, and MBP during color Doppler imaging, a significantly lower EDV (P =.0096) and a significantly higher RI (P =.033) in the central artery of over-dipping glaucoma patients compared with nondippers or dippers. This effect seemed independent of the use of vasoactive drugs . CONCLUSIONS Glaucoma patients with a marked drop in nocturnal systemic blood pressure seem to have altered retrobulbar blood flow parameters, suggesting that an abnormal systemic blood pressure profile may be the manifestation of some kind of systemic vascular dysregulation relevant for the ocular circulation.

Choroidal Blood Flow Response to Isometric Exercise in Glaucoma Patients and Patients with Ocular Hypertension

PURPOSE To analyze submacular choroidal blood flow (ChBF) response to isometric exercise in untreated patients with glaucoma and ocular hypertension. METHODS ChBF was examined by means of confocal laser Doppler flowmetry during 5 minutes of baseline, during 90 seconds of isometric exercise with a Martins vigorimeter and during 15 minutes of recovery. Values from one randomly chosen eye of 45 healthy subjects, the eye with more advanced damage in 45 primary open-angle glaucoma (POAG) patients, and the eye with higher native intraocular pressure in 45 patients with ocular hypertension (OHT) were acquired, and parameters of ChBF as well as blood pressure response were analyzed. RESULTS Healthy eyes demonstrated higher ChBF at baseline than did the eyes in both the other groups (5126 ± 1487, 4186 ± 1011, and 4437 ± 1372 arbitrary units, ANOVA P = 0.003). Both mean and diastolic arterial blood pressures at baseline were lower in POAG patients than in those with OHT and healthy controls (P < 0.03); however, the response of mean blood pressure to isometric exercise was comparable across groups (P = 0.79). The ChBF response to exercise was stronger in the POAG group (ANOVA P = 0.02), it was twice as high as in the controls (+8.1% ± 8.0% vs. +3.7% ± 6.7%; P = 0.007) and borderline higher than in the OHT patients (+5.0% ± 8.0%; P = 0.051). CONCLUSIONS Baseline ChBF was lower in both the POAG and the OHT patients, compared with that in the controls. The stronger increase in ChBF in POAG patients in the face of an exercise-induced blood pressure increase indicates less active regulatory capacity in glaucoma patients.

Rigidity of retinal vessel in untreated eyes of normal tension primary open-angle glaucoma patients.

BackgroundTo analyze pulse wave propagation in the ocular circulation and vessel stiffness in untreated eyes of normal tension primary open-angle glaucoma (NTG) patients. MethodsInferotemporal retinal vessels of 22 NTG eyes and 25 controls were examined with a Retinal Vessel Analyzer. Inferotemporal peripapillary retinal nerve fiber layer thickness was measured by ocular coherence tomography. Phase delay between venous trough and arterial peak was assessed at 3 sites centrifugal from the disc and a choroid-to-retina pulse delay was calculated as an estimation of vessel rigidity. ResultsThere was choroid-to-retina pulse delay of 0.26±0.08, 0.30±0.11, and 0.33±0.11 seconds, respectively, in NTG eyes at proximal, middle, and distal sites; in control eyes, the corresponding values were 0.28±0.10, 0.35±0.12, and 0.40±0.17 seconds. Average choroid-to-retina pulse delay was shorter in NTG eyes (P=0.028). Retinal nerve fiber layer (inferotemporal) showed an opposite correlation with choroid-to-retina pulse delay in controls (r=−0.48, P=0.019) and in NTG eyes (r=0.47, P=0.032 ). ConclusionsUntreated NTG eyes show stiffer retinal vessels. Vessel rigidity correlates with level of glaucomatous damage.

Experience with Cosopt, the fixed combination of timolol and dorzolamide, after switch from free combination of timolol and dorzolamide, in Swiss ophthalmologists’ offices

SUMMARY Purpose: To analyse a response to the therapy switch from the concomitant application of β-blocker and topical carbonic anhydrase inhibitor to the fixed combination of timolol and dorzolamide (Cosopt*) in glaucoma/ocular hypertensive patients under everyday, office-practice conditions. * Cosopt is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA Patients and methods: The data source was a survey among practising ophthalmologists in Switzerland assessing their experience with glaucoma patients/ocular hypertensives put for the first time on the fixed combination of timolol and dorzolamide. A total of 98 patients underwent the therapy switch in at least one eye. The intraocular pressure (IOP) change between the baseline visit before switch to the timolol-dorzolamide fixed combination occurred, and the first follow-up control after the switch, served as an indicator of compliance. Results: The IOP decreased on average from 19.43 ± 5.64 mmHg to 17.97 ± 3.58 mmHg (p < 0.01). The time to the follow-up visit ranged from 4 to 354 days, and the magnitude of IOP change demonstrated a significant dependence on the time to the follow-up visit, also when corrected for baseline IOP level. A total of 87 (85.3%) continued on the timolol-dorzolamide fixed combination therapy after the first control visit. In 68 of these 98 patients the contralateral eyes underwent the same therapy switch, and their IOP followed an identical pattern of behaviour. Conclusion: The average I OP decrease of 1.5 mmHg upon therapy switch to the timolol-dorzolamide fixed combination suggests a better efficacy due to improved compliance. Short-term compliance benefit seems to be more pronounced. The high timolol-dorzolamide fixed combination therapy continuation rate reflects an improvement in compliance and subjectively-perceived convenience.