[Acute Macular Neuroretinopathy]. / Akute makuläre Neuroretinopathie.

BACKGROUND: Acute macular neuroretinopathy (AMNR) is a rare unilateral or bilateral macular disorder. It typically occurs in young women presenting with sudden onset of central scotomas. They correspond to sharp reddish-brown areas in the macular region. The lesions often can only be observed with infrared reflectance imaging. These flat oval or wedge-shaped lesions are often grouped as a flower around the fovea. PATIENTS AND METHODS: Retrospective case series of 4 patients with AMNR. Clinical morphological features using different imaging techniques are presented. RESULTS: Four young women (26, 27, 28, 29 years of age) complained of seeing dark spots in the central visual field. In 3 patients, the scotomas occurred bilaterally. Three patients reported a history of preceding flu-like illness. In all 4 cases, visual acuity in both eyes was 1.0 with normal anterior and posterior segments. The corresponding retinal lesions were only noted in the infrared image of the optical coherence tomography (OCT). OCT images showed focal abnormalities in the photoreceptor outer segments. Follow-up periods varied between 9 and 36 months. In all patients, symptoms improved with at least partial recovery of the retinal architecture. CONCLUSIONS: Patients with AMNR suffer from acute onset of unilateral or bilateral central scotomas. Visual acuity is often only mildly affected. AMNR has a variable prognosis. In some cases, a self-limiting course with retinal recovery is observed while some patients have persistent reduction in visual acuity. Because there is no causative treatment for AMNR, an observational treatment approach is generally recommended.

[Congenital Simple Hamartoma of the Retinal Pigment Epithelium]. / Kongenitales einfaches Hamartom des retinalen Pigmentepithels.

BACKGROUND: Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE) is an uncommon benign lesion with characteristic clinical features. Ophthalmoscopically it appears as a small localized, well circumscribed, pigmented tumor in the foveal region. In contrast to the more common flat congenital hypertrophy of the RPE the CSHRPE has an elevated nodular appearance. PATIENTS AND METHODS: Retrospective case series of three patients with CSHRPE. Clinical morphological features using different imaging techniques are presented. RESULTS: A typical dark lesion was incidentally noted in the macula of two patients. Optical coherence tomography (OCT) demonstrated a nodular preretinal hyperreflectivity with shadowing of deeper structures. In one patient the CSHRPE was hypofluorescent throughout the angiogram. The third patient presented with a reduced visual acuity of 0.3. A characteristic lesion was found at the foveal center. OCT revealed a hyperreflective preretinal lesion with associated moderate disruption of the foveal architecture. Amblyopia treatment slightly improved visual acuity in this case. The lesions remained stationary in two patients (follow-up 8 - 14 months). CONCLUSIONS: CSHRPE are usually detected as an incidental finding. Given its benign character and typically asymptomatic presentation an observational treatment approach is generally recommended. The lesions generally remain stationary and are not known to grow. In cases with visual impairment due to foveal involvement amblyopia treatment should be initiated.

Effect of central corneal thickness on dynamic contour tonometry and Goldmann applanation tonometry in primary open-angle glaucoma.

OBJECTIVE: To compare the dependence of dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) on central corneal thickness (CCT) in primary open-angle glaucoma. METHODS: In a prospective study, the interocular (right vs left eye) difference in intraocular pressure measured by DCT and GAT was compared with the interocular CCT difference in 125 patients with primary open-angle glaucoma. RESULTS: Dynamic contour tonometry measurements (mean +/- SD, 19.4 +/- 4.1 mm Hg) were significantly (P=.004) higher than GAT measurements (mean +/- SD, 15.5 +/- 3.4 mm Hg), correlating significantly with each other (r(2)=0.82, P<.001). The interocular difference in intraocular pressure correlated significantly with the interocular CCT difference for GAT (r=0.30, P=.001) and DCT (r=0.23, P=.02) readings. Dynamic contour tonometry and GAT intraocular pressure differences significantly increased with older age (slope, 0.033 [95% confidence interval, 0.002-0.064] mm Hg/y; P=.03) but not with thicker CCT (slope, 0.006 [95% confidence interval, -0.003 to 0.017] mm Hg/mum; P=.22). CONCLUSIONS: In this series, GAT and DCT measurements were dependent on CCT in patients with primary open-angle glaucoma. Because intraocular pressure differences between DCT and GAT were independent of CCT, DCT and GAT are susceptible to similar measurement biases depending on CCT.

Effects of dopamine on retinal and choroidal blood flow parameters in humans.

AIM: To investigate the effect of dopamine on retinal and choroidal blood flow in humans. METHODS: We investigated the effect of two doses of intravenous dopamine (5 and 10 microg/kg/min) via a randomised double-masked crossover study in 12 healthy subjects chosen from a total of 16. Blood flow parameters in retina, optic nerve head and choroid were assessed with bi-directional laser Doppler velocimetry, laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively. RESULTS: Intravenous dopamine dose-dependently increased retinal blood cell velocity and fundus pulsation amplitude (p<0.001). At the highest administered dose red blood cell velocity in retinal vessels increased by 37% and fundus pulsation amplitude by 24%. By contrast, optic nerve head blood flow did not change with dopamine administration. CONCLUSIONS: Our data indicate that dopamine has a pronounced enhancing effect on the retinal perfusion in humans. Further studies are required to establish the exact role of dopamine in the regulation of choroidal and optic nerve head blood flow.

Effects of pentoxifylline and alprostadil on ocular hemodynamics in healthy humans.

PURPOSE: Alprostadil, a prostaglandin (PG)E(1) analogue and pentoxifylline, an alkylxanthine derivate, have been shown to exert vasodilatory effects in several vascular beds. The purpose of the present study was to investigate the effect of PGE(1) and pentoxifylline on the ocular circulation. METHODS: A placebo-controlled, double-masked, three-way, crossover study was performed in 15 healthy male subjects. Subjects received pentoxifylline (300 mg), PGE(1) (alprostadil 60 mug), or placebo intravenously over 2 hours on three trial days. Choroidal red blood cell flow was assessed with laser Doppler flowmetry and pulsatile choroidal blood flow with laser interferometric measurement of fundus pulsation amplitude (FPA). Retinal blood cell flow was calculated based on the measurements of maximum erythrocyte velocity in a retinal vein assessed with bidirectional laser Doppler velocimetry, and diameter measurements of retinal vessels were obtained with a retinal vessel analyzer. RESULTS: Pentoxifylline increased FPA by 15.4% +/- 1.1% (P < 0.001 versus placebo and baseline). Alprostadil tended to increase FPA, but this effect did not reach the level of significance (P = 0.07 versus placebo). Choroidal blood flow as measured with laser Doppler flowmetry tended to increase during pentoxifylline and PGE(1) infusion by 8.9% +/- 2.9% (P = 0.062) and 4.5% +/- 6.2% (P = 0.29), respectively, but none of these effects was significant. The drugs under study had no effect on mean red blood cell velocity in retinal veins, on retinal vessel diameters, intraocular pressure, blood pressure, or pulse rate. CONCLUSIONS: PGE(1) did not alter the parameters of retinal or choroidal circulation in healthy subjects. Pentoxifylline increased FPA, but did not change choroidal blood flow as measured with laser Doppler flowmetry and did not affect retinal blood flow parameters. Accordingly, neither pentoxifylline nor PGE(1) appears to be suitable to improve ocular blood flow in healthy subjects. Whether long-term treatment with alprostadil would improve choroidal blood flow in patients with vascular disease remains to be established.

On pulse-wave propagation in the ocular circulation.

PURPOSE: To measure the oscillation phase delay between retinal arterioles and venules in order to analyze pulse wave propagation in the ocular circulation of vasospastic and nonvasospastic subjects and a change thereof during the cold pressor test in another group of healthy subjects. METHODS: Twenty-four young, healthy women, 12 vasospastic and 12 nonvasospastic, were analyzed. A retinal vessel analyzer was used to obtain 1-minute recordings of the ocular fundus. A phase delay between the arteriole and venule pulsations was assessed at three sites, one (proximal) in the close retinal vicinity of the disc, one (middle) 1 to 2 disc diameters away from the disc, and a third (distal) 3 to 4 disc diameters away from the disc; and, assuming that venules are counterphased to the choroidal circulation, a choroid-to-retina pulse delay was calculated. In addition, the change in these parameters was analyzed during the modified cold-pressor test in 10 healthy subjects (five women, five men). RESULTS: Pulse oscillations in arterioles led those in venules by 95.0 degrees +/- 39.0 degrees , 60.5 degrees +/- 57.5 degrees , and 47.5 degrees +/- 64.0 degrees in vasospastic subjects, and 76.0 degrees +/- 58.0 degrees , 31.5 degrees +/- 60.0 degrees , and 2.5 degrees +/- 80.5 degrees in nonvasospastic subjects in the proximal, middle, and distal measuring sites, respectively. Calculated choroid-to-retina pulse delays in vasospastic subjects were 0.20 +/- 0.10, 0.28 +/- 0.14, and 0.30 +/- 0.11 seconds and in nonvasospastic subjects 0.25 +/- 0.15, 0.35 +/- 0.11, and 0.43 +/- 0.2 seconds at the proximal, middle, and distal measuring sites, respectively. The difference was significant between vasospastic and nonvasospastic subjects (P = 0.033) and among the measuring sites (P = 0.0023). During exposure to cold, the choroid-to-retina pulse delays changed from 0.31 +/- 0.08, 0.40 +/- 0.16, and 0.51 +/- 0.26 seconds to 0.26 +/- 0.12, 0.30 +/- 0.10, and 0.33 +/- 0.14 seconds at the proximal, middle, and distal measuring sites, respectively (P = 0.024 for the change from baseline to cold exposure, and P = 0.022 for measuring sites). CONCLUSIONS: Retinal vessels in vasospastic subjects demonstrate an altered pattern of oscillation phase delay between arterioles and venules. Vessels in vasospastic subjects seem to conduct pulse waves faster and are thus stiffer than those in nonvasospastic subjects. The pattern of oscillation demonstrates changes during the cold pressor test in healthy subjects, indicating faster pulse-wave propagation.

Short-term retinal vessel diameter variability in relation to the history of cold extremities.

PURPOSE: To test whether the regularity and short-term changes of retinal vessel diameter are related to the history of cold hands and feet and to nailfold circulatory response to cooling. METHODS: In 13 vasospastic and 13 nonvasospastic young healthy women (based on their history of cold extremities and nailfold capillaroscopy) 20- to 30-second recordings of the ocular fundus was obtained with a retinal vessel analyzer. The spatial regularity of arterioles and venules was analyzed by means of the coefficient of variation of vessel diameter and by exploratory Fourier analysis of spatial frequencies. Temporal variability was analyzed as excursion amplitude of the vessel diameter, as a correlation of means and standard deviations of vessel diameter within a defined time period, and by Fourier analysis of temporal diameter change in the heartbeat frequency range. RESULTS: Mean diameters of selected segments of arterioles (129.9 +/- 15.3 and 124.4 +/- 24.4 microm) and venules (150.8 +/- 14.6 and 149.3 +/- 19.6 microm) were not different between the vasospastic and nonvasospastic groups, respectively. Spatial variability: The coefficient of variation in arterioles was 8.8% +/- 2.8% and 6.1% +/- 1.7%, in venules 3.8% +/- 1.4%, and 3.6% +/- 0.9% in the vasospastic and nonvasospastic groups, respectively (difference by ANOVA, P = 0.017). Fourier analysis revealed differences between arterioles in the two groups, with relative Fourier power spectrum amplitudes of spatial frequencies higher in vasospastic eyes (Mann-Whitney P = 0.029). Temporal variability: The excursion amplitudes of vessel diameters were comparable in the two groups. Individual coefficients of correlation of successive means and standard deviations of the vessel diameter were 0.11 +/- 0.23 and 0.09 +/- 0.23 in the nonvasospastic group, and 0.25 +/- 0.40 and 0.24 +/- 0.22 in the vasospastic group, in the arterioles and venules, respectively (ANOVA: vasospastic versus nonvasospastic; P = 0.038). Fourier analysis in the heartbeat frequency range revealed differences in relative power spectrum amplitudes of temporal frequencies between arterioles in the two groups (higher in the vasospastic group, Mann-Whitney P = 0.029). CONCLUSIONS: Retinal arterioles in healthy vasospastic women show higher spatial irregularity and an increased vessel diameter variation within the temporal frequency of the heartbeat than do arterioles in nonvasospastic women.

Analysis of retinal vasodilation after flicker light stimulation in relation to vasospastic propensity.

PURPOSE: To explore the maximum retinal vasodilation in response to repeated flicker light stimulation in relation to vasospastic propensity in healthy subjects. METHODS: Twenty-four young healthy women were grouped as vasospastic and nonvasospastic, based on their history of cold extremities and on the results of nailfold capillaroscopy. A retinal vessel analyzer was used to obtain recordings of the ocular fundus during still illumination and three flicker light stimulations. Retinal vessels were analyzed in the immediate vicinity of the optic nerve head and 2 to 3 disc diameters away from the disc. The maximum dilatory amplitudes were always the highest 1-second mean vessel diameter in response to each of the three flicker light stimuli. RESULTS: Maximum dilatory amplitude (in percent) was, in the proximal measurement site in the arterioles, 6.2 +/- 2.6, 4.8 +/- 2.1, and 6.6 +/- 3.9 in the vasospastic group, and 7.9 +/- 3.2, 8.6 +/- 4.1, and 9.1 +/- 4.7 in the nonvasospastic group in three repeated flicker stimulations. Corresponding values for distal measurement sites were 6.7 +/- 2.5, 4.8 +/- 3.4, and 4.7 +/- 4.4 and 9.0 +/- 3.7, 11.0 +/- 5.2, and 12.3 +/- 7.7. The maximum amplitude was significantly lower in the vasospastic group (P = 0.001). The maximum venule dilation was also significantly lower in the vasospastic group (P = 0.037). Vessel diameters failed to stabilize at the original baseline level during the 80-second recovery period, and this baseline offset had opposite signs in the arterioles in the vasospastic (remained below the original baseline) and nonvasospastic (remained above the original baseline) groups. CONCLUSIONS: The maximum dilatory amplitude was significantly lower in vessels in the vasospastic group. An augmentation of the maximum vasodilation was observed in the nonvasospastic group after repeated flicker stimulations, a phenomenon that was missing in arterioles of vasospastic subjects. It seems that such different behavior is due to the opposite baseline offsets in interflicker periods in the two groups.

Intravenous administration of diphenhydramine reduces histamine-induced vasodilator effects in the retina and choroid.

PURPOSE: Intravenous administration of histamine causes an increase in choroidal blood flow (ChBF) and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. The present study was undertaken to clarify whether H1 receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina. METHODS: A randomized, double-masked, placebo-controlled, two-way crossover study was performed in 18 healthy, male, nonsmoking subjects. Histamine (0.32 microg/kg per minute over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H1 blocker diphenhydramine (1.0 mg/min over 50 minutes). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo, and after co-infusion of histamine. Subfoveal ChBF and fundus pulsation amplitude (FPA) were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser Doppler velocimetry. RESULTS: Administration of histamine caused a decrease in mean arterial pressure by -4% +/- 9% (ANOVA P = 0.01). This effect was blunted by coadministration of diphenhydramine (ANOVA, P = 0.04). Histamine significantly increased FPA and subfoveal ChBF. Coadministration of diphenhydramine significantly reduced this effect (ANOVA; FPA P = 0.001, ChBF P = 0.049). Histamine significantly increased retinal arterial diameter by +3.5% +/- 4.5% and retinal venous diameter by +3.7% +/- 2.8%. Again, coadministration of diphenhydramine significantly reduced the vasodilative effect to +0.3% +/- 5.5% in retinal arteries (ANOVA, P = 0.00006) and to +0.9% +/- 2.5% in retinal veins (ANOVA, P = 0.004). CONCLUSIONS: The present data confirm that histamine increases ChBF and retinal vessel diameters in healthy subjects. Administration of the H1 receptor blocker diphenhydramine significantly reduced histamine-induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H1 receptors are involved in the histamine-mediated hemodynamic effects in vivo.

Retinal vascular diameter in young subjects with a vasospastic propensity.

PURPOSE: Retinal vascular diameters have recently been shown not to be related to an increased risk of open-angle glaucoma. Because vasospastic propensity has been suggested to represent a risk factor for various ocular diseases, especially glaucoma, the steady-state retinal vascular diameter in subjects with a propensity for systemic vascular dysregulation was compared with a group of age-matched gender-matched controls. METHODS: Thirty healthy non-smoking individuals [female/male 26/4; mean +/- SD age 22.8+/-3.4 (range 18-31) years] were enrolled into the study. Subjects were classified as having vasospasm (15 subjects) if they related a clear history of frequently cold hands and as healthy subjects (15 subjects) if they denied such a history. Vasospastic propensity or the absence of it had to be confirmed by nail-fold capillaroscopy. Vascular diameter of retinal vessels was measured repeatedly on two days with the retinal vessel analyser and corrected for perfusion pressure, age, and refraction. RESULTS: Neither retinal arteriole diameter (P=0.30) or retinal venule diameter (P=0.49), nor retinal arteriole-to-venule ratio (P=0.96), differed between the two experimental groups. CONCLUSIONS: Although vasospastic propensity has been suggested to represent a risk factor in various ocular diseases, the steady-state retinal vessel diameters are not altered in healthy vasospastic subjects. It is probable that the steady-state retinal vessel diameters are no adequate risk indicators for the haemodynamic risk in diseases such as glaucoma.

Therapeutic strategies for normal-tension glaucoma.

Treatment of normal-tension glaucoma has been a subject of debate for several years. Glaucomatous damage cannot be influenced directly, and current treatment modalities in normal-tension glaucoma are aimed at the control of risk factors. Intraocular pressure is a widely accepted risk factor and its reduction can improve the prognosis in normal-tension glaucoma patients. The repeated demonstration of the importance of hemodynamic factors in normal-tension glaucoma has, however, not been paralleled by a comparable progress in the development of therapeutic modalities capable of influencing favorably ocular blood flow. Today, calcium channel blockers seem to be the most promising adjunctive treatment to be considered in patients with glaucomatous optic neuropathy without increased intraocular pressure.

Inhaled carbon monoxide increases retinal and choroidal blood flow in healthy humans.

PURPOSE: It has been hypothesized that carbon monoxide (CO) acts as an important vascular paracrine factor and plays a role in blood flow regulation in several tissues. The present study investigated the effect of inhaled CO on retinal and choroidal blood flow. METHODS: Fifteen healthy male volunteers were studied in a randomized, double-masked, placebo-controlled design with washout periods of at least 1 week between study days. CO in a dose of 500 ppm or placebo (synthetic air without CO) was inhaled for 60 minutes. Ocular hemodynamics were measured at baseline and at 30 and 60 minutes after start of inhalation. Retinal vessel diameters were measured with a retinal vessel analyzer. RBC velocity was assessed using bidirectional laser Doppler velocimetry. Retinal blood flow was calculated based on retinal vessel diameters and RBC velocity. Fundus pulsation amplitude (FPA) was measured using laser interferometry, and submacular choroidal blood flow using laser Doppler flowmetry. RESULTS: Breathing of CO significantly increased carboxyhemoglobine, from 1.2 +/- 0.5% to 8.5 +/- 0.9% and 9.4 +/- 0.6% at the two time points, respectively (P < 0.01). The diameter of retinal arteries increased by +3.5 +/- 3.8% and +4.2 +/- 3.9% (P < 0.01) in response to CO inhalation. In retinal veins, CO also induced an increase in diameter of +4.3 +/- 3.0% and +4.8 +/- 5.0%, respectively (P < 0.01). By contrast, placebo did not influence retinal vessel diameter. RBC velocity tended to increase during CO inhalation (+8 +/- 22%), but this effect did not reach the level of significance (P = 0.1). Calculated retinal blood flow increased significantly by +12 +/- 5% (P < 0.02). FPA increased after breathing CO by +20 +/- 20% and +26 +/- 21% at the two time points, respectively (P < 0.01). Subfoveal choroidal blood flow increased by +14 +/- 9% and +15 +/- 9% during breathing of CO (P < 0.01). CONCLUSIONS: This experiment demonstrated that retinal and choroidal blood flow increase during inhalation of CO. Whether this increase is caused by tissue hypoxia or a yet unknown mechanism has to be clarified.

Effect of histamine and cimetidine on retinal and choroidal blood flow in humans.

Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameter in healthy subjects. The mechanism underlying this effect remains to be elucidated. In the present study, we hypothesized that H2 receptor blockade alters hemodynamic effects of histamine in the choroid and retina. Eighteen healthy male nonsmoking volunteers were included in this randomized, double-masked, placebo-controlled two-way crossover study. Histamine (0.32 microg.kg(-1).min(-1) over 30 min) was infused intravenously in the absence (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50 min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of cimetidine or placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal blood flow (+14 +/- 15%, P < 0.001), fundus pulsation amplitude (+11 +/- 5%, P < 0.001), retinal venous diameter (+3.0 +/- 3.6%, P = 0.002), and retinal arterial diameter (+2.8 +/- 4.2%, P < 0.01) but did not change retinal blood velocity. The H2 antagonist cimetidine had no significant effect on ocular hemodynamic parameters. In addition, cimetidine did not modify effects of histamine on choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and retinal arterial diameter compared with placebo. The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. This ocular vasodilator effect of histamine is, however, not altered by administration of an H2 blocker. Whether the increase in blood flow is mediated via H1 receptors or other hitherto unidentified mechanisms remains to be elucidated.

Prevalence of patients presenting with neovascular age-related macular degeneration in an urban population.

PURPOSE: To determine the number and type of new cases of neovascular age-related macular degeneration (AMD) present in a defined urban population and to establish the proportion that would be recommended for treatment with verteporfin or laser photocoagulation. METHODS: Patients referred to an ophthalmic center in Vienna during a 10-week period because of recent deterioration in vision caused by newly diagnosed neovascular AMD were included. RESULTS: Neovascular AMD was diagnosed in 168 eyes in 153 patients. One hundred one eyes (60.1%) had lesions that were occult with no classic choroidal neovascularization (CNV); of these, 70 were subfoveal, 19 were juxtafoveal, and 12 were extrafoveal. Thirty-five eyes (20.8%) had predominantly classic lesions; of these, 27 were subfoveal, 6 were juxtafoveal, and 2 were extrafoveal. Thirty-two eyes (19.0%) had minimally classic lesions, of which 31 were subfoveal and 1 was extrafoveal. In accordance with consensus guidelines from a panel of experts and with American Academy of Ophthalmology's Preferred Practice Pattern guidelines, 33 lesions (17%) would be considered for treatment with verteporfin therapy. A further 37 subfoveal lesions with occult with no classic CNV and 7 juxtafoveal lesions with occult with no classic CNV might also benefit from verteporfin therapy if there is evidence of presumed recent disease progression. Five lesions (3.0%) could have been treated with laser photocoagulation according to Macular Photocoagulation Study criteria. CONCLUSIONS: These results suggest that verteporfin therapy substantially increases the number of patients with treatable neovascular AMD.

Intravenously administered histamine increases choroidal but not retinal blood flow.

PURPOSE: To determine the effect of intravenously administered histamine on both retinal and choroidal blood flow in humans. METHODS: A randomized, double-masked, two-way crossover study was performed in 14 healthy volunteers. Placebo or histamine was administered intravenously in stepwise increasing doses (0.08 microg/kg/min, 0.16 microg/kg/min, and 0.32 microg/kg/min). Retinal vessel diameters were measured with a retinal vessel analyzer, and retinal venous blood speed was assessed by bi-directional laser Doppler velocimetry. Using these parameters retinal blood flow was calculated. Subfoveal and pulsatile choroidal blood flow were measured with laser Doppler flowmetry and laser interferometry, respectively. RESULTS: After infusion of histamine pulsatile choroidal blood flow increased by 5 +/- 3%, 9 +/- 8%, and 14 +/- 7% (P = 0.001, ANOVA) and subfoveolar choroidal blood flow by 8 +/- 11%, 13 +/- 11%, and 13 +/- 12% (P = 0.003, ANOVA). Retinal arterial and venous vessel diameter significantly increased by 3 +/- 4%, 2 +/- 4%, and 3 +/- 5% (P = 0.047, ANOVA) and 1 +/- 2%, 3 +/- 2%, and 3 +/- 2% (P = 0.015, ANOVA), respectively. Red blood cell velocity in major retinal veins tended to decrease by -9 +/- 12%, -9 +/- 20%, and -13 +/- 12%, but this effect did not reach levels of significance. Calculated retinal blood flow was not changed by administration of histamine (-7 +/- 14%, -4 +/- 20%, and -8 +/- 12%, P = 0.28, ANOVA). CONCLUSIONS: Intravenous histamine in the selected doses increased choroidal blood flow. Retinal vessels showed a small diameter increase, whereas red blood cell speed decreased, resulting in an unchanged total retinal blood flow. This may result from local differences in the receptor distribution in the posterior part of the eye.

Incidence of laser photocoagulation and photodynamic therapy with verteporfin at a tertiary retinal center.

PURPOSE: To examine the influence of photodynamic therapy (PDT) with verteporfin on the indication and frequency of conventional thermal krypton laser photocoagulation in choroidal neovascularization. METHODS: A retrospective chart review was performed comparing laser indication and frequency 1 year before and 2 years after PDT started to be used routinely following the guidelines of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group and the Verteporfin in Photodynamic Therapy Study Group. RESULTS: Similar frequencies of laser treatment were seen in the year before and during the first year after PDT was commenced (301 [7.1% of all patients] to 281 [6.9%]). In the year thereafter, however, there was a marked decrease in laser treatments (174 [3.9%]). Interestingly, there was a steady increase in the relative frequency of laser treatments of extrafoveal and parapapillary lesions in the years after PDT was commenced (29.2%, year 1; 30.6%, year 2; and 39.6%, year 3). CONCLUSION: PDT has led to a decrease in conventional laser photocoagulation at one large tertiary retinal center in Austria. Moreover, it is our belief that patients are now referred at earlier stages of the disease, which has resulted in a shift in thermal laser indications.

Dopaminergic vasodilation in the choroidal circulation by d1/d5 receptor activation.

PURPOSE: To test whether exogenous dopamine can cause choroidal vasodilation and to identify the mediating receptors in anesthetized rabbits. METHODS: Mean arterial pressure (MAP), intraocular pressure (IOP), and orbital venous pressure (OVP) were measured by direct cannulation of the central ear artery, the vitreous, and the orbital venous sinus, respectively. Laser Doppler flowmetry was used to measure choroidal blood flow (ChorBF) while MAP was manipulated mechanically with occluders on the aorta and vena cava, thus changing perfusion pressure (PP) over a wide range. In the first group of animals (n = 11), pressure-flow (PF) relationships were performed at control and in response to 40 micro g/kg per minute intravenous (IV) dopamine (D40) and D40+SCH-23390 (0.5 mg/kg, bolus injection IV). In the second group of animals (n = 6), PF relationships were recorded at control and during infusion of SKF-38393 (80 micro g/kg per minute). RESULTS: D40 lowered IOP and caused an upward shift in the choroidal PF relationship, which was blocked by the D1/D5 antagonist SCH-23390 suggesting the involvement of the dopamine D1/D5 receptors. Stimulation of the D1/D5 receptors by infusion of the selective agonist SKF-38393 also lowered IOP and caused an upward shift in the PF relationship. Dopamine and SKF-38393 tended to decrease OVP, but the effect was not significant. CONCLUSIONS: Dopamine can cause choroidal vasodilation in anesthetized rabbits. Because SCH-23390 was able to block the response and SKF-38393 caused a similar vasodilation, we conclude that the vasodilation is caused by a D1/D5-receptor-mediated mechanism.

Incidence of patients presenting with exudative maculopathy and neovascular retinal disease in an urban population.

PURPOSE: To determine the incidence of exudative macular and neovascular retinal disease presenting within a defined urban population. STUDY DESIGN: prospective, observational, consecutive case series. PATIENTS AND METHODS: Patients referred to ten ophthalmic centers within a defined 10-week period with a newly diagnosed exudative macular and/or neovascular retinal disease were examined fundoscopically, angiographically and quantified according to age and underlying disease. RESULTS: A total of 527 eyes of 426 patients were referred. The most frequent disease was neovascular age-related macular degeneration (AMD, 199/527, 37.8%, 184 patients), followed by diabetic maculopathy and/or proliferative diabetic retinopathy (199/527, 37.8%, 128 patients) and venous occlusive disease (67/527, 12.7%, 67 patients). The majority of neovascular AMD consisted of occult without classic choroidal neovascularization (CNV, 115/ 199, 57.8%); predominantly classic CNV was seen more often than minimally classic CNV (43/199, 21.6% vs. 27/ 199, 13.6%). The overwhelming majority of the diabetic cases had diabetic macular edema (179/199, 89.9%); only 10.1% had vasoproliferative disease. All other causes of CNV, macular edema/exudation, and retinal neovascularization were observed in < 5% of all patients. CONCLUSION: The main causes of exudative maculopathy are CNV due to neovascular AMD and diabetic macular edema. Proliferative diabetic retinopathy is the main cause of retinal neovascularization. The number of patients with neovascular AMD presents a future challenge for ophthalmologists.

Flicker light-induced vasodilatation in the human retina: effect of lactate and changes in mean arterial pressure.

PURPOSE: Diffuse luminance flicker light increases retinal and optic nerve head blood flow in animals and humans, but the exact mechanisms that mediate increased flow have yet to be identified. In the current study, the effect of increased plasma lactate levels on flicker-induced vasodilatation in the retina was investigated in three independent studies in healthy humans. METHODS: In the first study, plasma lactate concentrations were increased by bicycle exercise in 12 volunteers, and the change in retinal vessel diameter to 8-Hz square-wave flicker stimulation was measured with the Zeiss Retinal Vessel Analyzer (Carl Zeiss Meditec, Oberkochen, Germany). In a different study, sodium lactate was administered intravenously, and flicker responses were measured in 12 subjects. As a control experiment accounting for pressure increases induced by exercise, the effect of elevated ocular perfusion pressure on the flicker response was investigated during tyramine infusion (n = 12). RESULTS: The increase in plasma lactate concentration during intravenous infusion from 1.3 +/- 0.4 to 6.3 mmol/L and during dynamic exercise from 1.2 +/- 0.3 to 9.4 mmol/L decreased flicker responses in retinal arteries from 5.3% +/- 0.9% to 1.7% +/- 0.6% (P < 0.001) and from 3.6% +/- 0.6% to 2.0% +/- 0.8% (P = 0.03), respectively. In contrast, an increase of mean blood pressure from 81 +/- 3 to 92 +/- 3 mm Hg after tyramine infusion had no significant effect on flicker-induced vasodilatation in retinal arteries and veins. CONCLUSIONS: The signaling between neuronal activity and flow response in the human retina is sensitive to changes in blood lactate levels, whereas changes in systemic blood pressure have no major effect. Whether an increased cytosolic redox impairment contributes to flicker-induced vasodilatation has yet to be clarified.

Effects of adrenomedullin on ocular hemodynamic parameters in the choroid and the ophthalmic artery.

PURPOSE: Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo. METHODS: The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days. RESULTS: Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion. CONCLUSIONS: Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.