Association of retinal microvascular caliber with blood pressure levels.

BACKGROUND: The most common ophthalmologic manifestation of hypertension is hypertensive retinopathy. Our study was designed to evaluate the factors that determine retinal vessel caliber in hypertensive subjects. METHODS: During a 6-month period, retinal photographs were taken of participants during a routine yearly check-up. The photographs were evaluated by an ophthalmologist and the diameters of the individual retinal vessels were measured and summarized by a computer program. Data including patient's medical history, physical examination and laboratory evaluations were collected. The findings of the ophthalmologic examinations were analyzed with respect to the relevant systemic data. RESULTS: We evaluated 285 subjects (43 women) with an average age of 62 ± 9 years (range 33-87). Hypertension was reported in 204 (71.6%) subjects and diabetes mellitus in 60 subjects (21%). The arteriolar calibers were inversely related to age (R = - 017; p = 0.01). Retinal arteriolar and venular calibers were wider in smokers and in subjects with dyslipidemia. History of hypertension was not associated with any vascular changes. However, retinal arteriolar caliber was inversely related to blood pressure levels. Diuretic treatment was associated with narrow retinal venular caliber. CONCLUSION: The association between different cardiovascular risk factors and hypertensive retinopathy is complex. Effective blood pressure control has a beneficial effect on the vascular changes in the retina.

The effect of latanoprost on ocular blood flow.

PURPOSE: To investigate the effect of latanoprost on ocular hemodynamics in healthy subjects. METHODS: In a randomized, double-masked, placebo-controlled crossover study, 12 healthy subjects received either placebo or latanoprost for 4 weeks in one randomly chosen eye. Following a 4-week washout period, each patient received the opposite treatment. Blood pressure, heart rate, logMar visual acuity, contrast sensitivity, iris photography, intraocular pressure (IOP), Heidelberg retinal flowmetry, and color Doppler imaging measurements were taken at baseline and post-treatment. Heidelberg retinal flowmetry images were analyzed using the pixel-by-pixel analysis. Color Doppler imaging measurements included peak systolic velocity and end diastolic velocities (cm/s), and the calculated resistance index. Pre- and post-treatment values were compared by Wilcoxon signed rank tests (P < 0.05 was considered to be statistically significant). RESULTS: There were no significant changes in heart rate, blood pressure, contrast sensitivity, or visual acuity with either treatment. Latanoprost demonstrated a significant reduction in both IOP (P = 0.005) and retinal blood flow at the 10th (P = 0.009) and 25th (P = 0.009) percentiles of Heidelberg retinal flowmetry measurements in the superior temporal region. Latanoprost, however, did not reduce blood flow in the inferior temporal region and did not significantly elevate the percentage of zero-flow pixels of the temporal peripapillary area. CONCLUSION: Latanoprost has mostly neutral effects on ocular circulation. These findings must be investigated in glaucoma patients who may respond differently than healthy subjects due to faulty vascular autoregulation.

Dye dependent differences in arteriovenous passage times: a comparison of indocyanine green and fluorescein sodium dye analysis.

BACKGROUND AND OBJECTIVE: To evaluate the difference in arteriovenous passage time calculated from retinal angiograms using indocyanine green and fluorescein sodium dye in healthy individuals. PATIENTS AND METHODS: Examinations of eight healthy individuals (mean age +/- standard deviation: 27.3 +/- 4.2 years) who had four consecutive ophthalmic visits that were 2 weeks apart were analyzed. Indocyanine green and fluorescein angiography were performed sequentially (with the indocyanine green angiography occurring first) using scanning laser ophthalmoscopy. Arteriovenous passage times were calculated offline using digital angiogram video analysis. RESULTS: Mean arteriovenous passage times calculated from indocyanine green angiography (1.417 +/- 0.136 seconds) recordings were significantly shorter than fluorescein sodium times (2.539 +/- 0.421 seconds) (P < .0001) and intra-group variability was similar. There were no significant correlations between indocyanine green and fluorescein sodium arteriovenous passage times. CONCLUSION: Arteriovenous passage times calculated using indocyanine green and fluorescein angiography are not interchangeable.

[An updated review of methods for human retinal oximetry measurements and current applications].

The concept of retinal oximetry is based on physical properties that have been recognized since the 18th century. Attempts to non-invasively quantify the oxygen saturation of blood within the retinal vasculature date back to the 1950's. There are different techniques in existence for the measurement of retinal oxygenation, the leading ones are: photographic, digital, spectroscopy and the pulse methods. Each method has its advantages and disadvantages. Current data from studies on retinal oximetry is presented, for both the healthy retina and in diseases such as glaucoma, diabetic retinopathy and age-related macular degeneration. It is clear that a thorough understanding of retinal oxygen tension is vital to our understanding of normal retinal physiology and the pathophysiology of degenerative eye diseases.

The relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration. PATIENTS AND METHODS: Thirteen patients with age-related macular degeneration were assessed by both color Doppler imaging and scanning laser ophthalmoscope indocyanine green (ICG) angiography. Color Doppler imaging was used to measure peak systolic and end diastolic velocity (from which the resistance index, a measure of the resistance to flow downstream, was calculated) in the retrobulbar vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area dilution analysis for quantitative choroidal fluorescence intensity assessment. Color Doppler imaging parameters were correlated with scanning laser ophthalmoscope ICG area dilution analysis parameters. RESULTS: A good correlation was found between the posterior ciliary arteries resistance index and scanning laser ophthalmoscope ICG area dilution analysis fluorescence duration. CONCLUSIONS: Scanning laser ophthalmoscope ICG area dilution analysis "duration" may serve as an alternative to color Doppler imaging in assessing the resistance to blood flow in the posterior ciliary arteries.

[An update on diabetic retinopathy].

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus. Research performed over the last several decades has demonstrated the benefit of systemic control and ocular treatments in reducing the risk of blindness. In the Western world, however, diabetic retinopathy remains the major cause of blindness in the working age population and its economical impact is the highest among the different ocular diseases. This review discusses the various aspects of diabetic retinopathy and includes an update on new research in the field.

Automatic retinal oximetry.

PURPOSE: To measure hemoglobin oxygen saturation (SO(2)) in retinal vessels and to test the reproducibility and sensitivity of an automatic spectrophotometric oximeter. METHODS: Specialized software automatically identifies the retinal blood vessels on fundus images, which are obtained with four different wavelengths of light. The software calculates optical density ratios (ODRs) for each vessel. The reproducibility was evaluated by analyzing five repeated measurements of the same vessels. A linear relationship between SO(2) and ODR was assumed and a linear model derived. After calibration, reproducibility and sensitivity were calculated in terms of SO(2). Systemic hyperoxia (n = 16) was induced in healthy volunteers by changing the O(2) concentration in inhaled air from 21% to 100%. RESULTS: The automatic software enhanced reproducibility, and the mean SD for repeated measurements was 3.7% for arterioles and 5.3% venules, in terms of percentage of SO(2) (five repeats, 10 individuals). The model derived for calibration was SO(2) = 125 - 142 . ODR. The arterial SO(2) measured 96% +/- 9% (mean +/- SD) during normoxia and 101% +/- 8% during hyperoxia (n = 16). The difference between normoxia and hyperoxia was significant (P = 0.0027, paired t-test). Corresponding numbers for venules were 55% +/- 14% and 78% +/- 15% (P < 0.0001). SO(2) is displayed as a pseudocolor map drawn on fundus images. CONCLUSIONS: The retinal oximeter is reliable, easy to use, and sensitive to changes in SO(2) when concentration of O(2) in inhaled air is changed.

A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma.

AIMS: The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal, choroidal, and retrobulbar hemodynamics and visual function in primary open-angle glaucoma (OAG) subjects. METHODS: Sixteen (16) OAG patients (age, 63.5 +/- 10.8 years; 9 male) were evaluated in a randomized, crossover, double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide. After randomization, 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study. Measurements included: adverse events check, visual acuity, contrast sensitivity, blood pressure, heart rate, intraocular pressure (IOP), and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry, color Doppler imaging, and scanning laser ophthalmoscopy. RESULTS: Both therapies were effective at lowering IOP, whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide (13.9% and 12.2% reduction, respectively; P = 0.5533). Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity (P = 0.0168) and lowered resistance to flow (P = 0.0279). Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide (P = 0.0125 and 0.0238, respectively). Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment. There were no statistically significant differences in adverse events, blood pressure, heart rate, visual acuity, contrast sensitivity scanning laser ophthalmoscopy, or Heidelberg Retinal Flowmeter for any treatment period. CONCLUSIONS: Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol. Visual function, however, was not different in this short-term comparison between the two treatments.

The role of optic nerve blood flow in the pathogenesis of glaucoma.

Many theories have surfaced regarding the exact mechanisms behind glaucomatous damage, but the complex nature of the disease and the inaccessibility of the internal structures of the human eye have limited current knowledge. Increased intraocular pressure is the risk factor most often associated with glaucomatous optic neuropathy; ischemic insult to the optic nerve has also been suggested as a possible cause of cellular damage. The aim of this review is to cover the possible role of optic nerve head hemodynamics in the pathogenesis of glaucoma.

Pneumatic retinopexy: results in eyes with classic vs relative indications.

OBJECTIVE: To compare the results of pneumatic retinopexy in 3 groups of eyes with rhegmatogenous retinal detachment. METHODS: In this retrospective, consecutive study, 44 eyes of 44 patients who underwent pneumatic retinopexy were divided into 3 groups: eyes with vitreoretinal abnormalities (group A), pseudopakic or aphakic eyes (group B), and phakic eyes without vitreoretinal abnormalities (group C). RESULTS: Single retinopexy success was achieved in 10 (71%) of 14 eyes in group A, 7 (64%) of 11 eyes in group B, and 16 (84%) of 19 eyes in group C (P=.42). Final success after reoperation was achieved in 13 (93%) of 14 eyes in group A, 10 (91%) of 11 eyes in group B, and in all 19 eyes in group C (P=.44). In group B, the rate of single retinopexy success using cryotherapy was significantly higher (5/5; 100%) than when laser photocoagulation was used (1/5; 20%) (P=.015). The final visual outcome obtained in the 3 groups was similar. There were no significant intergroup differences in either early or late complications. CONCLUSIONS: The best results were achieved in eyes with classic indications for pneumatic retinopexy, though the differences between these results and those in the nonclassic indications were not significant. In pseudophakic or aphakic eyes, the rate of single operation success after cryopexy was significantly higher than the rate after laser photocoagulation.

Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome.

PURPOSE: To report the effects of intravitreal triamcinolone acetonide injections for subfoveal and juxtafoveal choroidal neovascularization (CNV) in ocular histoplasmosis syndrome. METHODS: In a retrospective analysis, the proportion of eyes that gained >or=5 or lost >or=5 and >or=15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, best-corrected visual acuity using ETDRS letter score (VA), greatest linear dimension (GLD), and treatment side effects were assessed. RESULTS: Ten patients (five subfoveal, five juxtafoveal CNV; median follow-up: 17 months; range, 6-41 months) were evaluated. Thirty percent gained >or=5 letters, 20% lost 5 to 14 letters, and 50% maintained stable VA. Overall, mean VA and GLD remained stable. Side effects were transient intraocular pressure elevation and mild cataract development. CONCLUSIONS: Intravitreal triamcinolone acetonide for CNV resulting from OHS was found to be relatively safe and showed good visual outcome for both subfoveal and juxtafoveal CNV. Further studies are warranted to evaluate this treatment.

Reduced cerebrovascular blood flow velocities and vasoreactivity in open-angle glaucoma.

PURPOSE: To compare cerebral blood flow velocities between open-angle glaucoma (OAG) patients and controls, at baseline and during hyperoxia. DESIGN: Observational cohort study. METHODS: A prospective study was conducted in a single institution. Sixteen OAG patients and 15 normal subjects, matched for age, were enrolled. Patients and controls were studied at baseline, while breathing room air, and during 100% oxygen breathing. The eye with the more severe visual field defect was chosen in glaucoma patients, while in controls, the study eye was chosen randomly. Subjects with history of diabetes, cardiovascular, or respiratory disease were excluded. Measurements included brachial arterial pressure, heart rate, intraocular pressure and transcranial Doppler (TCD). Mean and peak velocity and pulsatility index of the ipsilateral middle cerebral artery (MCA) were measured by TCD. RESULTS: At baseline, MCA mean and peak systolic blood flow velocities were significantly lower in glaucoma patients compared with controls velocities were significantly lower in glaucoma patients compared with controls (mean velocity: 50.2 vs 65.3 cm/s, P <.05; peak velocity: 74.2 vs 96.8 cm/s, P <.05). Additionally, while hyperoxia significantly decreased both mean and peak systolic velocities in MCA of controls (mean velocity: 65.3 vs 57.7 cm/s, P <.05; peak velocity 96.8 vs 87.9 cm/s, P <.05), it did not cause any significant change in OAG patients. CONCLUSIONS: Glaucoma patients were found to have lower MCA blood flow velocities and an absence of vasoreactivity to hyperoxia, compared with controls. The relationship of these cerebral hemodynamic abnormalities to glaucoma pathogenesis and progression remains to be explored.

An update on photodynamic therapy in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible loss of central vision in people aged > 50 years in the western world. Until recently, the only proven treatment to reduce the risk of vision loss from its more severe neovascular form was laser photocoagulation, but this treatment was suitable for only 15% of cases. Photodynamic therapy (PDT) with verteporfin was recently proposed to be effective in reducing the risk of visual loss for an estimated 20 - 30% of neovascular AMD patients. This review covers AMD epidemiology, the mechanism of PDT, the 2-year results of the two major clinical studies of PDT with verteporfin, the cost-effectiveness of PDT and the current research status of other drugs for PDT in AMD.

A review of methods for human retinal oximetry.

Attempts to noninvasively quantify the oxygen saturation of blood within the retinal vasculature date back to the 1950s. This article discusses the various approaches that have been taken to estimate the oxygen saturation in the retinal vasculature. Advantages and limitations of each are discussed. Data from human and animal subjects are also presented.

Comparison of ocular hemodynamics measured by a new retinal blood flowmeter and color Doppler imaging.

BACKGROUND AND OBJECTIVE: To compare measurements of a new retinal blood flow device with central retinal artery blood velocity. MATERIALS AND METHODS: One randomly selected eye from each of 13 subjects was examined. Blood flow was measured by laser blood flowmeter and velocity by color Doppler imaging. The correlation between measurements was analyzed using regression analysis where a P value of less than .05 and coefficient of regression values of greater than .5 were considered significant. RESULTS: The laser blood flowmeter produced vessel diameter measurements of 90.1 +/- 18.7 microm (mean +/- standard deviation), velocity of 19.7 +/- 8.06 mm/sec, and flow measurements of 4.24 +/- 2.41 microL/min. Central retinal artery peak systolic velocity, end diastolic velocity, and mean velocity correlated significantly with laser blood flowmeter velocity (P = .01, r = .66; P < .01, r = .77; and P = .003, r = .76, respectively) and flow (P = .01, r = .71; P = .03, r = .6; and P = .01, r = .69, respectively). CONCLUSIONS: The laser blood flowmeter produces retinal artery flow and velocity measurements that correlate with central retinal artery peak systolic velocity end diastolic velocity, and mean velocity measurements. Further validation of the laser blood flowmeter's accuracy in measuring real flow warranted and likely requires more invasive in vivo studies (in animal models). However, this study supports the ability of the laser blood flowmeter to measure retinal blood flow.

Intraocular pressure measurements and biomechanical properties of the cornea in eyes after penetrating keratoplasty.

PURPOSE: To compare intraocular pressure (IOP) measurements obtained using the Goldmann applanation tonometer (GAT; Haag-Streit), the Tono-Pen XL (Reichert, Inc), and the ocular response analyzer (ORA; Reichert Ophthalmic Instruments), and to determine the influence of corneal factors on IOP measurements in eyes that had undergone penetrating keratoplasty (PK). DESIGN: Consecutive, prospective study. METHODS: Study population. Sixty-one eyes that underwent PK were enrolled in this study. Intervention. IOP was measured using the GAT, Tono-Pen, and ORA. Corneal hysteresis and corneal resistance factor as provided by the ORA were recorded. Central corneal thickness was measured using an ultrasound pachymeter. Main outcome measures. IOP and corneal biomechanical factors. RESULTS: IOP measurements were obtained in an average of 65 months (range, 6 to 209 months) after PK surgery. ORA-derived IOP measurements (corneal-compensated IOP and Goldmann-correlated IOP) and Tono-Pen XL IOP all correlated in a significant manner to GAT IOP measurements. Corneal-compensated IOP and Tono-Pen XL IOP values were higher than GAT IOP (P < .001 and P = .001, respectively), whereas Goldmann-correlated IOP readings did not differ from GAT IOP readings (P = .054). Central corneal thickness did not correlate to any tonometry technique. In a regression analysis, corneal hysteresis and corneal resistance factor were found to play a role in IOP prediction. CONCLUSIONS: Central corneal thickness may be of less importance than corneal hysteresis and corneal resistance factor in IOP determination in eyes that have undergone PK, perhaps because of the lower modulus of elasticity in these eyes. GAT IOP seems to be lower than other tonometry techniques in eyes that have undergone PK.

Increased electroretinogram a-wave amplitude after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

PURPOSE: To assess the effect of bevacizumab (Avastin), a vascular endothelial growth factor inhibitor, on retinal function by full-field electroretinography (ERG) in patients with neovascular age-related macular degeneration (AMD). DESIGN: A prospective, nonrandomized, controlled interventional clinical trial. METHODS: Twelve patients (aged 50)85) with neovascular AMD each received one unilateral intravitreal injection of bevacizumab 1.25 mg/ 0.05 ml as part of the standard management for choroidal neovascular AMD. Before and 1 month after injection, all patients underwent bilateral full-field ERG scanning by a masked technician according to the ISCEV protocol, and their wave amplitudes were recorded. Untreated eyes served as controls. Scotopic responses were recorded at four incremental light intensities and photopic responses at two incremental light intensities. Changes in ERG-amplitude responses were calculated. Repeated-measures ANOVA was used for data analysis. RESULTS: Mean pre- and postinjection differences in a-wave amplitudes between the incremental light intensities in injected eyes were significantly higher than in controls (15.92 versus 1.33 lV for scotopic responses and 4.97 versus )1.06 lV for photopic responses; p = 0.057 and p = 0.01, respectively). Mean b-wave amplitudes in injected eyes were significantly higher than in controls for photopic responses (p = 0.048), but for scotopic responses, the difference between treated and untreated eyes was not significant (p = 0.23). CONCLUSIONS: Intravitreally injected bevacizumab improves both rod and cone functioning in patients with neovascular AMD, as demonstrated by the increase in the ERG a-wave responses of these patients. Other measured ERG parameters yielded no significant photoreceptor toxicity.

The effect of intravitreal bevacizumab (Avastin) on ocular pulse amplitude in neovascular age-related macular degeneration.

PURPOSE: To evaluate the effect of intravitreal (IVT) bevacizumab in neovascular age-related macular degeneration (AMD) on global choroidal hemodynamics, as measured by ocular pulse amplitude (OPA). METHODS: This was a two-center prospective study (Sheba Medical Center, Israel, and University Hospitals Leuven, Belgium). AMD patients who required IVT bevacizumab (1.25 mg/0.05 mL; first or repeated) were examined three times: at days 0 (prior to injection), 7 (±3), and 28 (±7) postinjection. At each visit, OPAs of both eyes were measured using the Pascal dynamic contour tonometer (DCT). A paired t-test between preoperative and postoperative OPA was conducted. Pearson correlation was used to evaluate the influence of various measured parameters on DCT-OPA. RESULTS: A total of 38 neovascular AMD patients were recruited, and 30 patients were included in the final analysis (18 females and 12 males; age 78.8 ± 5.82 years [mean ± standard deviation]). A good correlation was found throughout the study between the DCT-intraocular pressure (IOP) and Goldmann IOP and between DCT-IOP and DCT-OPA. No change in OPA of bevacizumab-treated eyes was found between the visits (2.24 ± 0.73, 2.2 ± 0.86, and 2.23 ± 0.73 mm Hg at visits 1, 2, and 3, respectively; paired t-test: P = 0.77 between visits 1 and 2, P = 0.98 between visits 1 and 3). No correlations were found between DCT-OPA and age, heart rate, systemic blood pressure, axial length, keratometry readings, and central corneal thickness. CONCLUSIONS: OPA, an indirect measure of global choroidal hemodynamics, remains unchanged following IVT off-label bevacizumab. This finding adds to the growing evidence regarding the safety profile of bevacizumab in AMD treatment.