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The present study was conducted to assess the feasibility of laser Doppler velocimetry in young infants, as a prelude to ultimately undertaking such measurements in premature infants. A portable, unidirectional laser Doppler velocimeter was developed based on a Kowa RC-2 hand-held fundus camera. Six infants between 1 and 21 weeks of age were studied. Relative red blood cell velocity (δfmax) at the centre of retinal arteries was measured over approximately 10 heart cycles. A pulsatility parameter (P=1−δfmax.dia/δfmax.sys), a summary index of vascular status, was determined from the average diastolic and systolic values of δfmax. Velocity waveforms were obtained in four of the six infants. Arterial pulsatility for the group was 0.63±0.13. Precise non-invasive measurement of arterial red blood cell velocity waveforms in young infants was achieved. The high signal-to-noise ratio and temporal resolution of this data suggest that relative measurements of retinal blood flow may permit assessment of haemodynamic changes in premature infants.

AIMS--The effect of rebreathing into a bag (RB) on retinal macular blood velocity was evaluated in healthy volunteers. METHODS--Ten normal volunteers, whose ages ranged from 17 to 34 years, performed RB over 135 to 260 seconds (mean (SD) 193 (38) seconds) while retinal macular blood velocity was determined non-invasively using the blue field simulation technique. RESULTS--Leucocyte velocity significantly increased (p < 0.05) at 2 minutes and at the end of RB by 53% (42%) and 92% (65%), respectively (95% confidence interval of the mean (CIM)). All subjects observed an increase in the density of leucocytes. At the end of RB, mean systolic brachial arterial pressure and heart rate were significantly increased by 24% (11%) and 37% (15%) respectively (p < 0.01). At 2 minutes, end tidal oxygen concentration in the exhaled air was 47% (8%) (95% CIM) below and carbon dioxide was 41% (16%) above baseline (p < 0.001). The RB produces a large increase in macular leucocyte velocity, suggesting an increase in blood flow. CONCLUSION--Although RB has some systemic risk due to hypoxia and hypercapnia, RB for a short period of 1 or 2 minutes might be of help in the treatment of retinal arterial obstructive diseases in young patients without cardiovascular disorders if other treatments do not show any beneficial effects.

To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.Multicenter, randomized clinical trial.Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.Mean change in visual acuity.Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.Proprietary or commercial disclosure may be found after the references.

Patients with chronic kidney disease experience co-morbid illnesses, including cardiovascular disease (CVD) and retinopathy. The purpose of the present study was to assess the association between retinopathy and self-reported CVD in a subgroup of the participants in the Chronic Renal Insufficiency Cohort study. For this observational, ancillary investigation, 2,605 Chronic Renal Insufficiency Cohort participants were invited to participate in the present study, and nonmydriatic fundus photographs in both eyes were obtained for 1,936 subjects. The photographs were reviewed in a masked fashion at a central photograph reading center. The presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed using standard protocols by trained graders who were masked to the information about the study participants. A history of self-reported CVD was obtained using a medical history questionnaire. Kidney function measurements and traditional and nontraditional risk factors for CVD were obtained from the Chronic Renal Insufficiency Cohort study. A greater severity of retinopathy was associated with a greater prevalence of any CVD, and this association persisted after adjustment for the traditional risk factors for CVD. The presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relation between CVD prevalence and mean venular caliber. In conclusion, the presence of retinopathy was associated with CVD, suggesting that retinovascular pathology might indicate macrovascular disease, even after adjustment for renal dysfunction and traditional CVD risk factors. This would make the assessment of retinal morphology a valuable tool in CKD studies of CVD outcomes.

The effects of strict diabetic control on retinal haemodynamics were studied to elucidate whether such effects are associated with retinopathy changes. In 28 patients with poorly controlled insulin dependent diabetes mellitus and non-proliferative retinopathy, retinal haemodynamics were investigated at baseline, 5 days, 2 months, and 6 months after the institution of strict diabetic control using the bidirectional laser Doppler velocimetry technique and monochromatic fundus photography. Changes in retinal blood flow measured in a major retinal vein (Q) on the fifth day of strict diabetic control correlated significantly with changes in retinopathy level observed at the end of the 6 months of this study (rank correlation 0.65, p < 0.01). On the fifth day of strict diabetic control, 16 out of 20 eyes that showed no progression (NP) of retinopathy at the end of the study had decreases in Q, whereas six out of eight eyes that showed progression (P) had increases in Q. The difference in these changes in Q between P and NP eyes was statistically significant (one way analysis of variance, p = 0.001). No significant changes in Q were detected at 2 months or 6 months. Following the institution of strict diabetic control, no significant changes in time were detected in the regulatory response to 100% oxygen breathing characterised as the percentage decrease in Q at 4-6 minutes of oxygen breathing (analysis of variance, p = 0.36). Changes in Q following institution of strict diabetic control are associated with progression of retinopathy. Measurements described in this study may help identify diabetic patients at risk of progression when their metabolic control is improved.

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.

Background Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. Methods In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Results Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. Conclusions At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

Environmctital isonicrs are molccules of the sanic tnolccular spccics which are distinguishable bccause they exist in different liquid cagcs. This paper derives thc conditions for distinguishability whcn thc cagcs oxist in dynamic equilibrium. The approach is similar to tliat used in trcnting the coalcsccnce of spcctral lincs in dytiuiiic magnetic rcsonancc. For both water and benzciie there is evidence that the liquid might be a mixture of two niain cnvironmcntal isomers. By our criteria the suggested isomcrs for water would be casily distinguishable at ordinary T and P, while those for bcnzene would not be.

Aim We compared the regulatory responses induced by isometric exercise in control subjects and patients with age-related macular degeneration (AMD) to investigate choroidal vascular regulation in AMD. Methods Seventeen eyes of 17 patients with dry AMD in the study eye and 19 eyes of 19 controls were included in this study. Both groups were well matched for age, race and sex. Brachial artery blood pressure determinations and laser Doppler flowmetry (Oculix) measurements of relative foveolar choroidal blood velocity, volume and flow were obtained in the study eye of each subject during 30 s of baseline, and then during 3 min of isometric exercise consisting of squeezing a handgrip in each hand. Similar measurements were then also obtained during the 2 min following the cessation of exercise. Using non-paired, two-tailed t test, changes in circulatory parameters during exercise and following the end of exercise were compared between AMD patients and control subjects. The slope for the relationship between circulatory changes and perfusion pressure changes was calculated and compared between patients with AMD and controls using linear regression analysis. Analysis of data was performed in a masked fashion. Results There were no statistically significant differences between the changes in choriodal blood velocity, volume and flow observed in control subjects and patients with AMD during the isometric exercise phase and after exercise. Conclusions Our results suggest that the response of the choroidal circulation to this type of isometric exercise resulting in a moderate increase in blood pressure does not seem to be affected by AMD.

A new bidirectional laser Doppler velocimeter (LDV) is described for absolute measurement of the speed of red blood cells flowing in individual retinal vessels. The basic component of the instrument is a standard retinal camera that eliminates the need for a contact lens. The laser beam is delivered to the eye through the fundus illumination optical system of the camera. Target fixation is done with the eye under examination. The measurements are independent from the ocular refraction; only the axial length of the eye need be determined. The instrument markedly simplifies the technique of retinal blood flow measurement.

Background and objectives: The objective of this study was to describe the prevalence of ocular fundus pathology in the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter, longitudinal study of individuals with varying stages of chronic kidney disease (CKD). Design, setting, participants, & measurements: In this cross-sectional study, 45° digital photos of the disc and macula in both eyes were obtained by nonophthalmologic personnel using a nonmydriatic Canon CR-DGI fundus camera in 1936 individuals who participated in the CRIC study. Photographs were assessed in a masked manner by graders and a retinal specialist at a central photograph reading center. The purpose of this review was to inform participants quickly of conditions that warranted a complete eye examination by an ophthalmologist. Results: Among the 1936 participants who were photographed, 1904 (98%) had assessable photographs in at least one eye. Eye pathologies that required a follow-up examination by an ophthalmologist were identified in 864 (45%) of these 1904 participants. These eye pathologies included, among others, retinopathy (diabetic and/or hypertensive), a finding that was observed in 482 (25%) of these 1904 participants. Three percent (65 participants) of the 1904 participants had serious eye conditions that required urgent follow-up and treatment. Lower estimated GFR and cardiovascular disease were associated with greater eye pathology. Estimated GFR

To investigate the relationship between known risk factors for age-related macular degeneration (AMD) progression and foveolar choroidal circulation in eyes with nonexudative AMD.Cross-sectional study of nonexudative AMD.Laser Doppler flowmetry measurements of relative choroidal blood velocity, choroidal blood volume (ChBVol), and choroidal blood flow (ChBFlow) were obtained in the center of the fovea of 273 study eyes of 204 AMD patients investigated at the Scheie Eye Institute, University of Pennsylvania Medical School. All study eyes had visual acuity of 20/40 or better, good fixation, no other intraocular pathologic features, and no evidence of choroidal neovascularization. RPE hypertrophy was determined from color fundus photographs by trained masked graders at the Scheie Image Reading Center. Correlation analysis and multivariate linear regression analysis with adjustments for significant covariates were carried out.A significant inverse correlation was observed between age and ChBFlow (r = -0.36; P.0001), and ChBVol (r = -0.28; P.0001), but not for choroidal blood velocity. A significant inverse correlation was observed between spherical equivalent and ChBFlow (r = -0.21; P = .006) and ChBVol (r = -0.14; P = .04), but not for choroidal blood velocity. ChBFlow and ChBVol were significantly lower in patients with a history of hypertension (Por = .003) and in eyes with retinal pigment epithelium hypertrophy (Por = .04), respectively.All the above-described risk factors for AMD development and progression are associated with decreased choroidal circulatory parameters, suggesting that decreases in choroidal circulatory parameters may be involved in the development of AMD.

The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.

The development of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) often leads to a significant decrease in visual function. Several mechanisms have been proposed to explain the pathogenesis of CNV, and they include, among others, the presence of senescence changes in the RPE–Bruch’s membrane–photoreceptor complex, the accumulation of oxidative damage, and the development of ischemia of the outer retina. The purpose of our study was to investigate whether abnormalities of the foveolar choroidal circulation are associated with the development of CNV in AMD. Throughout the body, angiogenesis is often triggered by ischemia and hypoxia.1,2 Similarly, several ocular diseases, such as diabetic retinopathy, neovascular glaucoma, and vein occlusions, are associated with ocular ischemia and the development of neovascularization. A similar mechanism may also play a role in the development of CNV in AMD. Previous cross-sectional studies of patients with AMD performed in our laboratory3,4 have suggested that foveolar choroidal blood flow is decreased in patients with dry AMD and that eyes with more severe AMD features have lower foveolar choroidal blood flow, giving some support to the ischemia theory. We report the results of a prospective study in a cohort of patients with AMD at risk of development of CNV. Our purpose was to investigate in a longitudinal fashion whether foveolar choroidal blood flow decreases before the development of CNV and whether changes in blood flow precede the formation of CNV.

The American Society of Health-System Pharmacists (ASHP) and the Society for Hospital Medicine (SHM) believe that the rapidly emerging hospitalist model of inpatient care offers new and significant opportunities to optimize patient care through collaboration among hospitalists, hospital pharmacists

The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.

Objective To assess the predictive value of early retinal vascular diameter measurements for the development of severe retinopathy of prematurity (ROP) in high-risk preterm infants. Methods Digital fundus images were taken of 78 eyes at risk for ROP with a noncontact camera during fundoscopic examination when infants were 31 to 34 weeks of postconception age. Vessel diameters were measured for the major superior and inferior temporal arteries and veins with the use of VesselMap software. Mean vessel diameters from eyes that developed severe ROP requiring treatment were compared with those that developed less severe ROP not requiring treatment or no ROP. Results All 4 major temporal retinal vessels showed significantly larger average diameters in the group of eyes that developed severe ROP requiring treatment. Multivariate analysis adjusted by birth weight, gestational age, and chronologic age showed similar results. Early retinal vessel diameter measurements showed good predictive value for the progression to severe ROP requiring treatment (area under the receiver operating characteristic curve, 0.75-0.94). Conclusions At 31 to 34 weeks of postconception age, average retinal vessel diameter measurements were significantly larger in infants who developed severe ROP requiring treatment than in infants who developed less severe ROP or no ROP.

The Beck Depression Inventory-II (BDI-II) is frequently used to evaluate bariatric patients in clinical and research settings; yet, there are limited data regarding the factor structure of the BDI-II with a bariatric surgery population. Exploratory factor analysis (EFA) using principal axis factoring with oblimin rotation was employed with data from 1228 consecutive presurgical bariatric candidates. Independent t tests were used to examine potential differences between sexes. Confirmatory factor analysis (CFA) was conducted with the next 383 consecutive presurgical patients to evaluate the proposed model based on EFA results. EFA revealed three factors: negative perceptions, diminished vigor, and cognitive dysregulation, each with adequate internal consistency. Six BDI-II items did not load significantly on any of the three factors. CFA results largely supported the proposed model. Results suggest that dimensions of depression for presurgical bariatric candidates vary from other populations and raise important caveats regarding the utility of the BDI-II in bariatric research.

To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a multicenter randomized clinical trial.CATT patients with neovascular age-related macular degeneration (AMD).Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA.Morphologic features and VA at 1 and 2 years.The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P0.001), total lesion size was greater (4.55 vs 2.31 DA; P0.001), total retinal thickness was greater (524 vs 455 μm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years.In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of50% blood can be managed similarly to those with less or no blood.

Purpose To determine the feasibility of using semiautomated analysis of digital fundus images to quantify the differences in retinal vascular diameter between retinopathy of prematurity (ROP) patients with and without plus disease. Design Case-control study. Methods Thirty eyes of 15 patients with ROP were included in this study. Fourteen eyes of seven patients had plus disease and 16 eyes of eight patients had no evidence of plus disease. Digital fundus images were captured using an NM200D (Nidek, Inc, Aichi, Japan) camera. Vessel diameters were determined using VesselMap software (Imedos, Jena, Germany). The Student t test analysis was used to compare diameters of vessels with and without plus disease. Results We found that the average venous diameter is significantly larger by 15% in the group with plus disease. Conclusions VesselMap analysis of digital images is feasible. This method is able to distinguish between veins with and without plus disease, and may be useful in telemedicine screening strategies.

Niacin is a B vitamin well-known for causing vasodilation and flushing. The purpose of this study was to investigate its effect on the retinal vasculature of patients with age-related macular degeneration (AMD).Twelve patients with AMD were enrolled in a double-blind, randomized, placebo-controlled, crossover trial. Fundus photographs of the posterior pole were taken at baseline, 30 min, and 90 min after a single dose of niacin or placebo. The protocol was repeated after a washout period using the alternate study drug. The diameters of two veins and one artery on each image were measured.An analysis of variance for repeated measures comparing the effects of niacin with those of placebo demonstrated a significant increase in the inferior temporal retinal artery diameter (p = 0.01), with a 5.3 +/- 7.7% increase at 30 min (p = 0.05) and 5.8 +/- 5.0% increase at 90 min (p = 0.003). No significant changes were observed in the temporal retinal veins.Our results suggest that niacin produces vasodilatation of retinal arterioles. Further studies are needed to ascertain whether niacin treatment may be beneficial in retinal ischemic diseases.

The aim of the present study was to investigate the effect of sildenafil citrate (viagra) on retinal venous diameter in patients with age-related macular degeneration (AMD). We investigated 14 male patients in a double-masked, randomized, placebo-controlled, crossover study. In each subject, one eye with typical non-exudative AMD fundus features was studied. Each of the subjects received 100 mg dose of sildenafil or matching placebo on two separate study visits. Monochromatic fundus photographs were obtained in the study eye before dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of the major retinal veins from digitized negatives were carried out using "Vessel map" static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical analysis of the data comparing the effect of sildenafil and placebo on venous diameters was performed using analysis of variance (ANOVA) for repeated measures. An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal vein diameters showed a significant interaction between time and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a statistically significant vasodilatation of major retinal veins of 4.7% at 90 min (P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30 min there was a 2.2% difference, which was not statistically significant (P=0.14). Our results suggest that in patients with age-related macular degeneration, sildenafil citrate (viagra) produces a statistically significant vasodilatation of major retinal veins that is similar to what has been reported in normal subjects. Whether this vasodilatation is associated with changes in retinal blood flow needs to be further investigated.

Purpose To determine whether laser treatment applied according to the complications of age-related macular degeneration prevention trial (CAPT) has an effect on the choroidal circulation. Design Randomized controlled trial. Methods This study included 30 CAPT patients with bilateral drusen. Laser Doppler flowmetry was used to measure relative choroidal blood flow (Ch flow ) in the fovea. Measurements were obtained through dilated pupils in both eyes of each patient before photocoagulation was applied in one eye. Measurements were repeated at three months (30 patients) and 28 months (23 patients). Results Average Ch flow at baseline, three months, and 28 months was 7.2 ± 2.1 (±1 SD), 7.3 ± 2.5, and 6.8 ± 2.7 arbitrary units (AU) in the control eyes and 6.6 ± 1.6, 7.0 ± 2.3, and 7.8 ± 3.0 AU in the treated eyes. In comparison to control eyes, there was no significant change in Ch flow in the treated eyes at three months after treatment. At 28 months, however, there was a 5.6% drop in Ch flow in control eyes and an 18.2% increase in Ch flow in treated eyes from baseline. The average difference of 23.8% between the percentage changes in Ch flow observed in the control and treated eyes was statistically significant (paired two-tailed Student t test; P = .05). Conclusions Our results suggest an increase in choroidal blood flow 28 months after laser treatment according to the CAPT protocol. This increase may play a role in the mechanism leading to the disappearance of drusen after photocoagulation. Whether removal of drusen after photocoagulation is beneficial to the patients is not known at this time.

To evaluate the relationship between extent of glaucoma damage and optic nerve blood flow, we investigated optic nerve head bloodflow in patients with asymmetric glaucoma damage between their two eyes and also in glaucomatous eyes with asymmetric damage inferiorly versus superiorly.From our institutional practice, 16 subjects with asymmetric glaucoma damage between their two eyes and 25 eyes of 20 patients with asymmetric damage superiorly versus inferiorly were included in the study. Determinations of relative optic nerve head blood flow, velocity, and volume were obtained with laser Doppler flowmetry in the superotemporal and inferotemporal neuroretinalrim and in the cup. Means of flow (Flow(3)), velocity (Vel(3)), and volume (Vol(3))were calculated from these three measurement sites, and eyes or hemidisks with greater glaucomatous damage were compared to eyes or hemidisks with less damage.For subjects with asymmetric glaucoma damage between eyes, Flow(3) and Vel(3) were significantly lower in the eyes with worse glaucoma damage(mean difference = 2.09, p = 0.005, and mean difference = 0.05, p = 0.002,respectively). When comparing optic disks displaying within-eye asymmetry, the hemidisk with greater damage showed significantly lower blood velocity than the hemidisk with less damage (mean difference = 0.05, p = 0.013); however,no difference in blood flow or volume was detected.This study provides additional evidence that impaired optic nerve circulation is associated with the extent of glaucomatous pathology.

PURPOSE. In an earlier study, the authors reported that foveolar choroidal blood flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the choroidal circulatory changes in patients with AMD, the relationship between ChBFlow and fundus features associated with increased risk of choroidal neovascularization (CNV) were investigated. METHODS. The study included 26 control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of 123 patients with AMD. The AMD study eyes were divided into three groups according to increasing risk for development of CNV: (1) drusen 63 m, no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; (2) drusen 63 m, RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory parameters were assessed by analysis of variance (ANOVA) and test of linear trend. RESULTS. Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk for CNV (linear trend, P 0.05). The lowest circulatory parameters were observed in the eyes with the highest risk for CNV development. Trends for ChBVel and ChBFlow were still significant after adjustment for multiple factors. CONCLUSIONS. There is a systematic decrease in choroidal circulatory parameters with an increase in the severity of AMD features associated with risk for the development of CNV, suggesting a role for ischemia in the development of CNV. (Invest Ophthalmol Vis Sci. 2005;46:1033‐1038) DOI:10.1167/ iovs.04-1050

Purpose: We studied the choroidal circulation in patients with proliferative diabetic retinopathy (PDR) to assess whether choroidal hemodynamic abnormalities may exist in PDR. Methods: Eighteen eyes of 18 patients with PDR and high-risk characteristics for visual loss were included in this study. Mean duration of diabetes was 20 ± 9 years (mean ± SD), hemoglobin A1c was 8.9 ± 2.3%, and blood glucose at the time of blood flow measurement was 188 ± 90 mg/dl. Choroidal circulatory parameters obtained in these patients were compared to those of 35 eyes of 35 age and blood pressure matched, healthy controls using a Wilcoxon rank sum test. Laser Doppler flowmetry (Oculix) was used to calculate relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the center of the foveola. Results: No significant differences in average age, mean blood pressure (BPm), or perfusion pressure (PP) were observed between diabetic patients and control subjects. In diabetic patients, Chvol was 0.29 ± 0.08 (mean ± 1 SD) arbitrary units (AU); this value was 15% lower than that of control subjects, 0.34 ± 0.10 AU (p = 0.04). In contrast, average Chvel was not significantly different between subjects with PDR (0.39 ± 0.07 AU) and control subjects (0.41 ± 0.07 AU). The average Chflow in subjects with PDR (9.4 ± 2.9 AU) was 27% lower than that of control subjects (12.8 ± 4.2 AU; p = 0.003). No significant correlation was detected between the circulatory measurements and age, BPm, or PP. There was a statistically significant negative correlation between duration of diabetes and Chvel (R = −0.55; p = 0.03). Conclusions: Our results suggest that Chvol and Chflow are significantly reduced in patients with PDR.

This study investigated retinal hemodynamic changes associated with different pathologic features observed on fundus color and fluorescein angiography in patients with proliferative diabetic retinopathy.Retinal circulatory characteristics were investigated in 25 eyes of 23 diabetic patients with proliferative retinopathy using a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography.Eyes with severe capillary nonperfusion had 32% less average volumetric blood flow rate (Q) than eyes with less severe nonperfusion (P = 0.0005). In addition, eyes with severe vessel staining with fluorescein had 20% less average Q than eyes without staining (P = 0.0508). Eyes with severe fluorescein leakage in the macula had a 17% larger total venous cross-section than eyes with milder leakage (P = 0.027). Eyes with clinically significant macular edema had 11% larger average venous diameter than eyes without this feature (P = 0.0085).Severe capillary nonperfusion and vessel staining with fluorescein are associated with decreased retinal blood flow rates. Vasodilatation may be an important factor for increased vascular permeability and macular edema in proliferative diabetic retinopathy.

Aim: To perform a preliminary assessment of the relation between optic nerve circulatory parameters and glaucomatous visual field progression. Methods: This study included 29 eyes of 23 patients with open angle glaucoma that had typical glaucomatous nerve fibre bundle visual field defects and increased cup to disc ratios. Laser Doppler flowmetry (Oculix) was used to measure relative optic nerve blood volume (Vol), velocity (Vel) and flow in the superior temporal (ST) and inferior temporal (IT) neuroretinal rim of the optic nerve. After blood flow measurements patients were followed for 6–62 months (mean 33 (SD 17) months) and 2–11 Humphrey visual fields (4.7 (2.6) fields) were obtained. Progression of glaucoma was assessed by the slope of the corrected pattern standard deviation (CPSD) values versus time, which was calculated manually for each eye using regression analysis. Results: A significant negative correlation was observed between Vol in the IT rim and the CPSD slope ( r = −0.56, p = 0.002); patients with lower Vol tended to show faster progression of glaucomatous field damage than those with higher Vol. When the eyes were arbitrarily divided into two groups according to lower Vol (0.32 (0.06) arbitrary units, AU, n = 15) or higher Vol (0.49 (0.06) AU, n = 14), those with lower Vol had significantly worse mean CPSD slopes (0.50 (0.48) dB/year) than those with higher Vol (−0.67 (1.38) dB/year; Student’s t test, p = 0.009). Conclusions: In the IT rim, the area most prone to develop glaucomatous field damage, lower Vol is associated with subsequently faster CPSD progression. These measurements suggest that circulatory abnormalities may have a role in the development of glaucoma.

PURPOSE: The present investigation was conducted to evaluate the effect of sildenafil citrate (Viagra, Pfizer Inc., New York, NY) on retinal blood vessel diameter. DESIGN: Double-blind randomized, placebo-controlled, cross-over study. METHODS: Fifteen healthy male volunteers (mean age 39 years) received 100-mg doses of sildenafil or matching placebo on 2 separate days. Monochromatic fundus photography was obtained in one eye, and brachial artery blood pressure and intraocular pressure were measured at baseline, 1 hour, and 5 hours after dosing. The diameters of two major temporal veins and one artery were measured in a masked fashion from digitized photographic negatives. RESULTS: In comparison with placebo, no statistically significant change in average venous diameter was observed for the superior (analysis of variance [ANOVA], P = .97), inferior retinal temporal vein (ANOVA, P = .73), or the retinal temporal artery (ANOVA, P = .89) after sildenafil treatment. In comparison to placebo, there was no significant difference in the percentage change from baseline in venous or arterial diameter at 1 or 5 hours after sildenafil. The power to detect a 6.5% change in retinal vascular diameter following sildenafil was approximately 80% ( P = .05). CONCLUSIONS: These data suggest that at the maximum therapeutic dose used clinically (100 mg), sildenafil does not have a significant effect on retinal vascular caliber.

PURPOSE: To assess the acute effects of sildenafil citrate (VIAGRA) on the intraocular pressure (IOP) of patients with chronic open-angle glaucoma. DESIGN: This was a double-blind, randomized, placebo-controlled, crossover study, in which 15 patients received a single oral dose of sildenafil 100 mg or matching placebo on two separate occasions. METHODS: Fifteen subjects aged 63 ± 14 years (mean ± SD) with bilateral chronic open-angle glaucoma were administered a single oral dose of sildenafil 100 mg or matching placebo on two separate occasions at least 3 days apart. IOP was measured in both eyes by Goldmann ap-planation tonometry at baseline and then at 1–5 hours after dosing. Brachial artery systolic and diastolic blood pressures were determined by sphygmomanometry, and heart rate was also monitored at baseline and 1–5 hours after dosing. RESULTS: Compared with placebo, no statistically or clinically significant change in IOP was detected after a single dose of sildenafil 100 mg ( P = .20). Moreover, no significant change in mean systemic blood pressure ( P = .12) or heart rate ( P = .72) was detected after treatment with sildenafil. CONCLUSION: At the maximum therapeutic dose of 100 mg, sildenafil did not produce any significant acute change in IOP in men with chronic open-angle glaucoma. This information is of importance for patients with glaucoma receiving sildenafil for treatment of erectile dysfunction.

To evaluate the effects of felodipine, a calcium channel blocker, on ocular circulation.In a double blind, randomized, crossover design, 10 volunteers received placebo or felodipine on 2 separate days. Bidirectional laser Doppler velocimetry (BLDV), laser Doppler flowmetry (LDF), and monochromatic fundus photography (MFP) were employed to assess retinal, choroidal, and optic nerve rim circulatory parameters. Measurements were obtained at baseline, 1.5, and 3 hours after dosing. Blood pressure, intraocular pressure (IOP), and heart rate were monitored, and perfusion pressure (PP) was calculated.In comparison to placebo, significant average percentage decreases in diastolic blood pressure (BPd; p = 0.001), mean blood pressure (BPm; p = 0.003), and perfusion pressure (PP; p = 0.003) were observed 1.5 hours following felodipine. No significant differences were observed following placebo. Retinal, choroidal and optic nerve rim circulatory parameters showed no significant changes after placebo or felodipine. A significant positive correlation between BPd and optic nerve velocity (ONve1) was observed 3 hours following felodipine (R = +0.654; p = 0.040). In contrast, no significant correlation between BPd and ONve1 was noted (R = +0.198; p = 0.583) following placebo.No significant change in retinal, optic nerve rim, or foveolar choroidal blood flow were observed, a factor that may be important in the treatment of systemic hypertension in patients with glaucoma.

PURPOSE: To assess the short-term effects of sildenafil citrate on intraocular pressure in healthy male volunteers and participants in clinical trials. METHODS: Intraocular pressure and pupil diameter were measured in two placebo-controlled studies. Oral doses of sildenafil citrate (VIAGRA; Pfizer Inc, New York, New York) ranged from 10 mg to 150 mg. RESULTS: No major changes in intraocular pressure or pupillometry were detected at any time (1.0–24 hours) after administration of sildenafil. Additionally, of 36 subjects with a medical history of increased intraocular pressure in the sildenafil safety database, none were reported to have a clinically significant increase of their intraocular pressure. During clinical trials, two glaucoma cases were listed as serious adverse events, but were not considered treatment related. CONCLUSION: No clinical abnormalities were observed in intraocular pressure or pupil diameter in subjects receiving sildenafil. Currently, no evidence suggests that long-term treatment with sildenafil has an effect on intraocular pressure or is associated with the development or worsening of glaucoma.

The purpose of this randomized double-masked cross-over study was to determine the effects of 20 mg of 5-isosorbide mononitrate (ISMO) on the retinal hemodynamics of young healthy subjects.Monochromatic fundus photography and bidirectional laser Doppler velocimetry (BLDV) were used to determine vascular diameters (D), and blood velocity (V(max)) and flow (Q) in retinal veins, respectively. The diameter of the vein [D((vein))] at the same location where BLDV measurements were made, and the diameter of a neighboring artery [D((art) )], were determined from the fundus photographs. Measurements were carried out one and three hours after ISMO dosing, on twelve and six subjects, respectively. Mean blood pressure (BP(m)) and intraocular pressure (IOP) were also monitored, and ocular perfusion pressure (PP) was calculated. Results are expressed in percentage changes (+/- the standard error of the mean).On average, we observed a moderate increase of Q one hour after ISMO dosing (+8.2 +/- 5.4%), but not after placebo (+2.7 +/- 1.6%). This effect of ISMO, which displayed remarkable interindividual variability (95% confidence interval: -3.9%, +20.4%), did not attain statistical significance. D((vein)) and D((art)) were not appreciably affected. No effect was observed three hours after either ISMO or placebo dosing. PP was reduced one hour following ISMO administration, mainly as a function of reduced BP(m), although this variation was not statistically significant. IOP did not change appreciably throughout the duration of the study.Our findings suggest that, in contrast to the optic nerve head, in which we previously documented consistent and significant increases in blood flow following ISMO administration at both one and three hours, retinal hemodynamics are not equally responsive to a single dose of ISMO at these time points. Marked interindividual variability to the effects of this long-acting nitric oxide donor was documented one hour after administration, but not at three hours. This study further suggests that distinct vascular tissues of the ocular microcirculation respond differently to identical pharmacological challenges.

PURPOSE: To describe the clinical features and complications of diabetic retinopathy, visual acuity, and number of repeat treatments after panretinal photocoagulation for proliferative diabetic retinopathy in a tertiary care center. METHODS: A cohort study was conducted with data collection from medical records of patients undergoing panretinal photocoagulation between 1985 and 1995 at the Scheie Eye Institute; 297 eyes of 186 patients were eligible for study. RESULTS: The presence of neovascularization of the disk at baseline, an earlier onset of diabetes, and a shorter duration of disease before panretinal photocoagulation were the strongest risk factors for needing an additional panretinal photocoagulation treatment. Sixty-two percent of eyes with poor visual acuity (≤20/200) at baseline still had poor visual acuity at 1 year, and 76% with good visual acuity (≥20/40) at baseline maintained good visual acuity at 1 year. Poor vision at baseline was the only risk factor for having poor vision at 1 year. Vitreous hemorrhage was present in 44% of eyes at baseline. New vitreous hemorrhage developed in 37% of eyes during the first year after panretinal photocoagulation. A traction retinal detachment was present in 4% of eyes at baseline and newly developed in 6% of eyes during follow-up. A repeat panretinal photocoagulation treatment was performed in 39% of eyes after initial treatment. A vitrectomy was performed in 10% of eyes from baseline through the 1-year follow-up visit. CONCLUSIONS: The data from this study are useful for counseling patients with respect to likely visual outcome, possibility of major complications from proliferative diabetic retinopathy, and the chance of undergoing additional laser treatment after panretinal photocoagulation.

Cyclic nucleotide-gated channels are ion channels the gating of which is directly controlled by cyclic nucleotides. The most well-known of these are non-selective cation channels that require the binding of cyclic nucleotide in order to open (cyclic nucleotide-activated channels). These channels pass not only monovalent cations, but divalent cations even better. They are prominently present in retinal photoreceptors and olfactory receptor neurons, where they play crucial roles in visual and olfactory transductions (for reviews, see

The action of calmodulin (CaM) on target proteins is important for a variety of cellular functions. We demonstrate here, however, that the presence of a CaM-binding site on a protein does not necessarily imply a functional effect. The α-subunit of the cGMP-gated cation channel of human retinal cones has a CaM-binding site on its cytoplasmic N-terminal region, but the homomeric channel that it forms is not functionally modulated by CaM. Mutational analysis based on comparison to the highly homologous olfactory cyclic nucleotide-gated channel α-subunit, which does form a CaM-modulated channel, indicates that residues downstream of the CaM-binding domain on these channels are also important for CaM to have an effect. These findings suggest that a CaM-binding site and complementary structural features in a protein probably evolve independently, and an effect caused by CaM occurs only in the presence of both elements. More generally, the same may be true for other recognized binding sites on proteins for modulators or activators, so that a demonstrated physical interaction does not necessarily imply functional consequence.

The influence of selenium (Se) restriction on disposition in plasma and urine fractions of infused (74)Se (selenite) was studied when adult males (Enshi City, Hubei Province, PRC) whose habitual daily Se intake is approximately 480 microg per day were transferred to Lichuan County, where the daily intake is approximately 30 microg. The subjects received an infusion (106 microg Se) on the day before consuming foods low in Se and a second infusion (113 microg Se) 63 days later. Blood and 24-hour urine samples were collected each day for 7 days after the first infusion and on days 22, 43, and 62 following the first infusion. Urine and blood were also collected daily for the next 7 days after the second infusion. Plasma total Se concentration increased for 7 days after each of the two infusions and urine Se decreased exponentially following both the first and second infusions. The excretion of trimethylselenonium followed the same pattern as the total urinary Se. Surprisingly, there was not a significant difference in selenite retention between the two infusion periods, and the data indicated that, regardless of the chemical form of Se present in various organs, its catabolism leading to excretion in urine followed the same pathway as that of selenite. Labeled Se was incorporated predominantly in the plasma selenoprotein P fraction and the half-life of Se in this fraction was determined to be 1.9 to 2.9 days. Thus, a longer depletion period is required in these subjects to obtain more significant changes.

To investigate the circulation of the optic nerve head and choroid in patients with glaucoma.Laser Doppler flowmetry was used to determine optic nerve head relative blood velocity (ONVel), volume (ONVol), and flow (ONFlow) in 19 primary open-angle glaucoma patients and 15 age-matched healthy control subjects. In each subject, determinations were obtained from four sites on the neuroretinal tissue and from the center of the cup. A mean of the ONVel, ONVol, and ONFlow for these five measurement sites were calculated for each subject and defined as ONVel5, ONVol5, and ONFlow5. Circulatory parameters were correlated with measures of disease progression such as cup-to-disc ratio and Humphrey visual field indices. Measurements of relative choroidal blood velocity, volume, and flow were also obtained from the foveola.In glaucoma patients, mean ONFlow5 was significantly lower than in control subjects (24%; P = 0.001; independent, two-tailed Student's t-test). This decrease was caused by a significant decrease in ONVol5 (15%; P = 0.04) and a nonsignificant decrease in ONVel5 (10%; P = 0.07). In glaucomatous eyes, mean ONFlow was significantly reduced from normal, by 28% in the inferior temporal neuroretinal rim location (P = 0.001) and by 24% in the superior temporal location (P = 0.001). Although mean ONFlow was also decreased by 33% in the cup, the difference was not statistically significant after a Bonferroni correction was applied. No significant differences from normal were observed in the superior and inferior nasal rim tissues. In glaucoma patients, ONFlow5 was significantly and inversely correlated with the corrected pattern standard deviation (R = -0.53; P = 0.02) and with the cup-to-disc ratio (R = -0.65; P = 0.002). Choroidal blood flow measurements obtained in the foveola of glaucomatous eyes showed no statistically significant differences from normal.ONFlow5 is reduced by approximately 24% in glaucoma patients. In the inferior temporal rim, the area in which nerve bundle defects most commonly occur, blood flow is reduced by 28%. Patients with more advanced glaucomatous damage, as detected by visual field corrected pattern standard deviation and measurement of the cup-to-disc ratio, tend to have lower ONFlow5. These results suggest a decrease in optic nerve blood flow that is correlated with functional and morphologic measures of glaucomatous progression. However, from these results we cannot conclude whether this decrease in flow has a primary role in the etiology of glaucoma or whether it is the result of the loss of neural components caused by this disease.

To compare measurements of the foveolar choroidal blood circulation in subjects with nonexudative, age-related macular degeneration (AMD) with those of control subjects.Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the center of the fovea. Measurements were obtained in 20 eyes of 20 subjects with 10 or more large drusen, visual acuity of 20/32 or better, and no evidence of choroidal neovascularization. Findings obtained in these subjects were compared with those of 10 eyes of 10 age- and blood pressure-matched control subjects with no large drusen. Foveolar choroidal blood flow measurements were obtained by asking the study participants to fixate on a probing laser beam.No significant differences in average age, blood pressure, or intraocular pressure were observed between subjects with AMD and control subjects. In subjects with AMD, average ChBVol was 0.24 +/- 0.08 (+/- 1 SD) arbitrary units (AU); this value was 33% lower than that of control subjects (0.36 +/- 0.11 AU; two-tailed, independent Student's t-test, P = 0.005). Average ChBVel, conversely, was not significantly different from normal (0.44 +/- 0.07 AU) in subjects with AMD (0.44 +/- 0.10 AU). Average ChBFlow in subjects with AMD (8.7 +/- 3.1 AU) was 37% lower than that of control subjects (13.7 +/- 3.5 AU) (P = 0.0005). Average blood flow pulsatility was 6% higher in subjects with AMD (0.71 +/- 0.15) than in control subjects (0.66 +/- 0.14), but this difference was not statistically significant (P = 0.42).Average ChBFlow in the nonexudative stages of AMD is lower than that of age-matched controls, and the effect is caused mainly by a decrease in ChBVol. Further studies are needed to elucidate whether decreased ChBFlow plays a role in the development of choroidal neovascularization, and whether ChBFlow measurements may help identify subjects with AMD at risk for developing choroidal neovascularization.

To determine the effect of one week of topical treatment with levobunolol HCl 0.5% on the retinal circulation of normal subjects.Fifteen healthy volunteers with no history of ocular disease were included in this study. In a double-masked, randomized, cross-over design, one eye of each subject was treated, for one week, with one drop of either levobunolol or placebo, administered twice daily. Following a washout period of at least three weeks, the same eye received the alternate treatment for one week. Before the beginning of therapy and then two hours after the last drop, vessel diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow rate (Q) were determined in one major retinal vein of the treated eye, using bidirectional laser Doppler velocimetry and monochromatic fundus photography. Statistical analysis was performed using two-tailed, paired Student's t-test, linear regression, and correlation analysis.The average percentage change from baseline in intraocular pressure was statistically significant following levobunolol (-15% +/- 13% (+/-1 SD), P.001), but not following placebo (-3% +/- 11%, P.05). No significant changes in average D, Vmax, or Q were observed after levobunolol treatment (-1% +/- 4%, 5% +/- 11%, 4% +/- 15%, respectively) or placebo treatment (-1% +/- 4%, -2% +/- 9%, -5% +/- 10%, respectively). The average difference between the changes in Q from baseline after levobunolol and placebo treatments (9% +/- 17%) achieved a significance level of P = 0.06. Furthermore, following levobunolol treatment, Q was 7% +/- 14% higher than following placebo treatment (P = 0.05).A comparison of the effects of placebo and levobunolol treatments suggests that levobunolol has a variable effect on the retinal circulation with a tendency to show an overall slight increase in flow.

Purpose: The effect of topical levobunolol HCl 0.5% on the retinal circulation was studied on 15 normal volunteers aged 21-54 years (32 ± 10 years). Methods: In a double-masked, randomised design, one eye of each subject received a drop of levobunolol HCl 0.5% (LEV) and the fellow eye received a drop of artificial tears (TEAR). Leucocyte velocity (VBFS) and density in the retinal macular microcirculation were measured by the blue-field simulation technique. Venous diameter (D), maximum erythrocyte velocity (Vmax) and volumetric blood flow rate (Q) were measured in a major temporal vein by laser Doppler velocimetry and monochromatic fundus photography. Results: The following average changes from baseline were observed 2 hours after treatment: heart rate, −4.6 ± 8.3% (p = 0.04); intraocular pressure, −31.7 10.6% (p = 0.0001); and perfusion pressure, 15.4 14.4% (p = 0.02) in LEV eyes; no statistically dgnificant changes in IOP and perfusion pressure were seen in TEAR eyes. When each eye was compared with its own baseline, there were no significant changes in VBFS, density, D, Vmax and Q in LEV eyes. In TEAR eyes, there were no significant changes in VBFS, density, Vmax and Q, but a significant change in D (−1.8 ± 2.6%; P = 0.02) was observed. A significant average percentage increase in Q of 10.9 ± 19.2% (paired t-test between the change after LEV and the Aange after TEAR, p = 0.044) was seen in LEV eyes when compared with TEAR eyes. Twelve of the 15 subjest demonstrated a relative increase in Q in the LEV eyes in comparison with the TEAR eyes, while 3 subjects showed the opposite. Conclusion: A significant difference in the effect of levobunolol between the two eyes was detected, even though there was no statistically significant effect when each eye was compared with its baseline.

In its intermediate hosts, infection with Taxoplasma gondii is characterized by an early phase when the tachyzoites (the rapidly multiplying stage of the parasite) can be found in different tissues accompanied by a mononuclear inflammatory reaction in small necrotic foci. Parasite multiplication during this stage of disease is most rapid in the liver, lymphoid tissues, lung, and brain. With development of immunity, the tachyzoites are cleared from the host tissues, the necrotic foci regenerate and bradyzoites (the dormant stage of T. gondii) form inside cysts mainly in the central nervous system without causing inflammatory reactions and necrosis (Frenkel 1988). This strong cell-mediated immunity (CMI) induced by T. gondii is maintained by Type 1 CD4+CD8- (Th1) and CD4-CD8+ T lymphocytes, as well as interferon (IFN)-γ and protects the host against rapid parasite growth and consequent pathology (Gazzinelli et al. 1993a). However, immunity is not able to eliminate the infection since the bradyzoites inside cysts can resist protective cell-mediated response. Nevertheless, spontaneous release of parasites from cysts occurs and may boost immunologic memory, thereby explaining the long-lasting immunity induced by this infection. In immunocompetent hosts, these released bradyzoites elicit a strong inflammatory response and are eventually destroyed by the immune system. However, in immunocompromised hosts, the bradyzoites released from cysts can transform into tachyzoites, resulting in rapid parasite proliferation, severe tissue damage, and a disease, toxoplasmic encephalitis, which, if left untreated, is usually fatal. In fact, T. gondii has emerged as the major opportunistic infection of parasitic origin in the current acquired immunodeficiency syndrome (AIDS) epidemic (Canning 1990; Kreiss and Castro 1990).

An ion channel directly activated by cGMP was first discovered about ten years ago. Since then, a number of ion channels with the same property (cyclic nucleotide-activated channels) have been reported that are involved in a variety of cell functions. In addition, other channels have been found that are not primarily controlled by cyclic nucleotides but are modulated by them (cyclic nucleotide-modulated channels). These channels likewise have diverse functions and tissue distributions. Both channel classes are reviewed here. Coverage includes the cyclic-nucleotide binding site on these channels, ion permeation, pharmacological blockers, channel gating and modulation, and physiological functions of the channels.