L. Kagemann

Ocular haemodynamic responses to induced hypercapnia and hyperoxia in glaucoma

Aim: To determine the ocular haemodynamic response to gas perturbations in glaucoma. Methods: Intraocular pressure (IOP), systemic systolic and diastolic blood pressure (SBP and DBP), and retrobulbar blood flow velocities, measured by colour Doppler imaging (CDI), were recorded at two visits. CDI was used to measure peak systolic and end diastolic velocities (PSV and EDV) and resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). At the first visit, measurements were taken at baseline (B1: breathing room air) and during isoxic hypercapnia (end tidal PCO2 increased 15% above baseline) in 16 normal subjects and 12 patients with glaucoma. On another day, measurements were repeated at a second baseline (B2) and during hyperoxia (100% oxygen breathing) for 15 normal subjects and 13 glaucoma patients. Baseline systemic data were compared using paired t tests; REANOVA was performed to compare group differences at baseline and to determine the vessel response to each condition. Fisher’s LSD was used for post hoc comparison. Results: Baseline OA PSV was lower for the glaucoma than for the normal group (p = 0.047); the groups were otherwise similar at baseline. IOP demonstrated no response to hypercapnia, but reduced during hyperoxia for both the normal subjects (p<0.0001) and glaucoma patients (p = 0.04). During hypercapnia, SBP increased in normal subjects (p = 0.03) and glaucoma patients (p = 0.01); DBP increased in normal subjects (p = 0.021). There was a corresponding increase in ocular perfusion pressure (OPP) for normal subjects (p = 0.01) and glaucoma subjects (p = 0.028), and as a result OPP was included as a covariate in the REANCOVA model. Hypercapnia resulted in increased PSV in the CRA of normal subjects (p = 0.035) and increased PSV and EDV in the SPCAs of glaucoma patients (p = 0.041 and p = 0.030 respectively). Hyperoxia resulted in reduced PSV and EDV in the ophthalmic arteries of normal subjects only (p = 0.001 and 0.031 respectively). Conclusions: These findings suggest the presence of relative vasoconstriction in glaucoma patients, which is at least partially reversed by hypercapnia.

The first technique for non-invasive measurements of volumetric ophthalmic artery blood flow in humans

Aim: To validate the first non-invasive measurements of volumetric ophthalmic artery blood flow in humans. Methods: The ophthalmic arteries of healthy normal adults were examined by Advanced Technology Laboratories (ATL, a subsidiary of Phillips Medical Systems Inc) high definition imaging (HDI) 5000 colour Doppler imaging ultrasound with a 5–12 MHZ probe. A group of 14 subjects for experiment 1 and a group of 10 subjects for experiments 2 and 3 were selected, with the examined eye chosen randomly. Peak systolic velocities (PSV) and end diastolic velocities (EDV) of the ophthalmic artery and central retinal artery were measured and recorded. Cineloops (cinegraphic videos) of the ophthalmic arteries were then recorded with the ATL HDI 5000 and values for ophthalmic artery blood flow were produced offline using experimental analysis software. Multiple regression analysis was used to compare blood flow measurements with PSV and EDV measurements in the ophthalmic artery. In two follow up experiments, intraobserver variation in obtaining cineloops and the interanalyser variability in cineloop analysis were studied. Results: Volumetric flow correlated with ophthalmic artery PSV and EDV (p = 0.02, r2 = 0.5). There was no correlation with the cental retinal artery. The intraobserver coefficient of variation in obtaining cineloops was 29.89% for blood flow, 19.07% for diameter, and 22.27% for velocity. The coefficients of variation of the measurements of the two cineloop analysers were 40.21% for blood flow, 22.71% for diameter, and 26.34% for velocity. Conclusion: Cineloop analysis produces ophthalmic artery flow measurements which correlate with PSV and EDV, suggesting validity. The intraobserver variation and cineloop analyser variation were found to be in the acceptable range.

Reproducibility of the Heidelberg retinal flowmeter in determining low perfusion areas in peripapillary retina

Aim: To evaluate the interobserver variability and retest reproducibility of confocal scanning laser Doppler flowmeter in measuring capillary perfusion of the peripapillary retina. Methods: Blood flow measurements were performed in one eye of 10 normal subjects by two investigators on two different days (visits). Five separate measurements of the peripapillary blood flow parameters were recorded by each observer at each visit. The Heidelberg retina flowmeter was used to record capillary perfusion in a 2560×640 μm area of the superotemporal peripapillary region and pixel by pixel analysis was done from an area adjacent to the optic disc, with a minimum of 1600 pixels. The percentage of pixels with less than 1 arbitrary unit of flow (no flow) and 10, 25, 50, 75, 90th percentiles of flow values was calculated. Interobserver measurements were compared by paired t test. Intraclass correlations (ICC) were used to determine the interobserver variability and retest reproducibility of the measurements. Intrasession coefficients of variations (CV) were also calculated. Results: There were no statistically significant differences between the two observers for all measurements and between visits for the percentage of pixels with no flow. ICC was 66% (range 57.09%–77.1%) for pixels with no flow. For the 10, 25, 50, 75, 90th percentiles of flow the ICC was 63.07% (53.91%–77.81%), 71.3% (64.23%–80.85%), 72.61% (66.02%–78.96%), 65.86% (58.53%–74.77%), and 60.05% (54.34%–70.06%), respectively. CV was 16.59%, 11.47%, 9.32%, 9.03%, 11.58%, and 16.05% for the percentage of no flow pixels and the 10, 25, 50, 75, 90th percentiles of flow, respectively. Conclusions: The Heidelberg retinal flowmeter allows reproducible measurements of all levels of capillary perfusion areas when pixel by pixel analysis is used.

Color doppler imaging of the central retinal artery in premature infants undergoing examination for retinopathy of prematurity.

PURPOSE Recent attempts have been made to quantify blood flow velocity in the central retinal artery (CRA) of adults using color Doppler imaging (CDI). Although retinal vascular abnormalities are the hallmark of severe retinopathy of prematurity (ROP), normal values have not been established for CRA blood flow velocity in premature infants. METHODS CDI of the CRA was successfully performed on 43 eyes in 22 infants (postconceptional ages 32 to 39 weeks) before the infants underwent examination for ROP. Peak systolic velocity (PSV) and end diastolic velocity were recorded from at least 1 eye of each patient. Pourcelots resistive index was then calculated for each eye studied. RESULTS Mean PSV for patients with no ROP (n = 6) was 7.2 +/- 1.5 cm/s, whereas those with any degree of ROP excluding plus disease (n = 9) had a mean PSV of 8.9 +/- 1.8 cm/s. Of the patients with ROP and plus disease (n = 7), the mean PSV was 7.0 +/- 1.6 cm/s. There were no statistically significant differences among these 3 groups (P= .08). CONCLUSIONS CDI can be successfully performed on preterm infants and yields values lower than those previously reported in healthy adult subjects. PSV in the CRA may be higher in subjects with ROP in the absence of plus disease; however, further study is needed to determine whether these differences are significant.

The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration

Aim: To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD). Methods: In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months. Results: Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19). Conclusions: Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Effect of intravenous droperidol on intraocular pressure and retrobulbar hemodynamics

Purpose Topically-applied dopamine antagonists reduce intraocular pressure (IOP) and increase retinal blood flow in animal models. We examined the acute effects of intravenous infusion of a dopamine blocker (droperidol) on these parameters in healthy humans. Methods Sixteen subjects free from ocular or systemic disease (mean age 33 ± 10 yrs) received either 5 mg iv droperidol over 5 minutes, or iv saline placebo in double-masked fashion. IOP was determined 30 and 60 minutes later, while color Doppler imaging was used to determine flow velocities in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries 60 minutes after drug infusion. Results 30 minutes after drug infusion, IOP was reduced 6.0 mmHg as compared with baseline (p<0.001); after 60 minutes, IOP remained reduced by 3.7 mmHg (p<0.001). Placebo had no effect on IOP. While droperidol slightly elevated blood pressure and increased the calculated ocular perfusion pressure, the drug reduced visual acuity and contrast sensitivity (p<0.05). Droperidol elevated peak systolic velocity in the central retinal and nasal posterior ciliary arteries, without changing end-diastolic velocity or the resistance index in either of these vessels. Droperidol had no effect on flow velocities in the ophthalmic artery or the temporal posterior ciliary artery. Conclusions The rapid and marked ocular hypotension resulting from intravenous droperidol suggests that this agent may prove useful in the management of acute ocular hypertension. The retrobulbar changes consequent to the ocular tension reduction likely represent autoregulatory responses to altered ocular perfusion pressure.

Central retinal artery occlusion in pediatric patients secondary to anomalous retinal vasculature

been estimated at less than 1 in 50,0001. •Retinal artery occlusions in children are exceedingly rare and are seen in the setting of systemic conditions that predispose to embolic disease. These include trauma, coagulopathies, collagen vascular disease, fibromuscular dysplasia, neoplastic disease, and cardiac disease2. •Congenital prelaminar bifurcation of the central retinal artery (CRA) is a unique variant rarely described in the literature. These hemi-trunks are at much greater risk for acute occlusion and may predispose patients with other underlying risk factors to permanent vision loss2. Central retinal artery occlusion in pediatric patients secondary to anomalous retinal vasculature Dante Sorrentino1,3 MD, Lea Ann Lope1,3 DO, Ellen Mitchell1,3 MD, Larry Kagemann1,3 PhD, Marie Restori2 PhD, Kanwal ‘Ken’ Nischal1,3 MD, FRCOphth