Empirical retinal venous pulse wave velocity using modified photoplethysmography.

OBJECTIVE: Using the novel imaging method of high-speed modified photoplethysmography we measured the retinal venous pulse wave velocity in a single case. RESULTS: A healthy 30-year-old subject underwent high-speed modified photoplethysmography (120 frames per second) with simultaneous ophthalmodynamometry at 26 Meditron units. A video of the optic nerve was analyzed using custom software. A harmonic regression model was fitted to each pixel in the time series and used to quantify the retinal vascular pulse wave parameters. Retinal venous pulsation at the optic disc was observed as a complex dynamic wall motion, whereas contraction commenced at a point in the vein at the center of the optic disc, and progressed centrifugally. The empirically estimated retinal venous pulse wave velocity at this segment was approximately 22.24694 mm/s. This measurement provides an estimate for future studies in the field.

Heart rate and age modulate retinal pulsatile patterns.

Theoretical models of retinal hemodynamics showed the modulation of retinal pulsatile patterns (RPPs) by heart rate (HR), yet in-vivo validation and scientific merit of this biological process is lacking. Such evidence is critical for result interpretation, study design, and (patho-)physiological modeling of human biology spanning applications in various medical specialties. In retinal hemodynamic video-recordings, we characterize the morphology of RPPs and assess the impact of modulation by HR or other variables. Principal component analysis isolated two RPPs, i.e., spontaneous venous pulsation (SVP) and optic cup pulsation (OCP). Heart rate modulated SVP and OCP morphology (pFDR < 0.05); age modulated SVP morphology (pFDR < 0.05). In addition, age and HR demonstrated the effect on between-group differences. This knowledge greatly affects future study designs, analyses of between-group differences in RPPs, and biophysical models investigating relationships between RPPs, intracranial, intraocular pressures, and cardiovascular physiology.

Comparison of Two Spectral-domain Optical Coherence Tomography Scan Modes for Measuring Retinal Vessel Diameter.

Purpose: To assess the agreement between Line 3-5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement.Methods: 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3-5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed.Results: There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p < .001; arterial: ICCs = 0.84, p < .001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p < .001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 µm - 1799 µm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p < .001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 µm/µm (p < .001) and 0.007 µm/µm (p = .02), respectively.Conclusion: Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used.

Downregulation of Retinal Connexin 43 in GFAP-Expressing Cells Modifies Vasoreactivity Induced by Perfusion Ocular Pressure Changes.

Purpose: Glia and their communication via connexin 43 (Cx43) gap junctions are known to mediate neurovascular coupling, a process driven by metabolic demand. However, it is unclear whether Cx43 mediated glial communication intermediates classical autoregulation. Here we used viral transfection and a glial fibrillary acidic protein (GFAP) promoter to downregulate glial Cx43 to evaluate its role in retinal vascular autoregulation to ocular perfusion pressure (OPP) reduction. Methods: Adult rats were intravitreally injected with the viral active construct or a control. Three weeks after the injection, eyes were imaged using confocal scanning laser ophthalmoscopy before and during a period of OPP decrease induced by blood draw to lower blood pressure or by manometric IOP elevation. Vessel diameter responses to the OPP decrease were compared between Cx43-downregulated and control-injected eyes. The extent of Cx43 downregulation was evaluated by Western blot and immunohistochemistry. Results: In control eyes, the OPP decrease induced dilatation of arterioles, but not venules. In Cx43-downregulated eyes, Cx43 expression in whole retina was decreased by approximately 40%. In these eyes, the resting diameter of the venules increased significantly, but there was no effect on arterioles. In Cx43-downregulated eyes, vasoreactivity evoked by blood pressure lowering was significantly compromised in both arterioles (P = 0.005) and venules (P = 0.001). Cx43 downregulation did not affect the arteriole responses to IOP elevation, whereas the responses of the venules showed a significantly greater decrease in diameter (P < 0.001). Conclusions: The downregulation of retinal Cx43 in GFAP-expressing cells compromises vasoreactivity of both arterioles and venules in response to an OPP decrease achieved via blood pressure lowering or IOP elevation. The results also suggest that Cx43-mediated glial communication actively regulates resting venular diameter.

Measurement of normal retinal vascular pulse wave attenuation using modified photoplethysmography.

Pulse wave attenuation characteristics reflect compliance and resistance properties of the vessel wall as well as initial pulse generation factors. Recently, it has become possible to measure and map the retinal vessel wall pulse wave amplitudes. Predictable pulse wave amplitude distribution may allow inferences to be made concerning vascular compliance and resistance. Twenty-eight eyes from sixteen subjects (8 male and 8 female) were examined using modified retinal photoplethysmography with simultaneous ophthalmodynamometry. This allowed the assessment of vessel wall pulsation amplitudes under a dynamic range of intraocular pressures. Pulse amplitudes were calculated using harmonic regression analysis. The pulse wave attenuation was measured under different ranges of ophthalmodynamometric force (ODF) as a function of distance along the vessel (VDist), which in turn was calculated in disc diameters (DD) from the center of the optic disc. A linear mixed-effects model with randomized slopes and intercepts was used to estimate the correlations between the logarithmically transformed harmonic regression wave amplitude (HRWa) and the Fourier trigonometric coefficients with the predictors (VDist and ODF). The retinal venous harmonic regression wave attenuation (coefficient value±standard error) -0.40±0.065/DD, (p-value < 0.00001, 95% confidence interval (CI) -0.53 to -0.27), which was approximately twice that of the arterial -0.17±0.048/DD, (p-value < 0.0004, 95% CI = -0.27 to -0.08). There was a positive correlation between attenuation of the harmonic regression wave and ophthalmodynamometric force in both vascular systems. The attenuation of all but the sine coefficient of the second Fourier harmonic (bn2) achieved statistical significance in the correlation with VDist. The cosine coefficient of the first Fourier harmonic an1 was the only coefficient to achieve statistical significance in the correlation with the predictors VDist and ODF in both vascular systems. The an1 coefficient value in the correlation with VDist was -3.79±0.78 and -1.269±0.37 (p < 0.0006), while this coefficient value in the correlation with ODF was 0.026±0.0099 and 0.009±0.04 (p < 0.01) in both the retinal veins and arteries respectively. The predictable attenuation characteristics in normal subjects suggest that this technique may allow the non-invasive quantification of retinal vascular compliance and other hemodynamic parameters.

Retinal vessel caliber and caliber responses in true normotensive black and white adults: The African-PREDICT study.

PURPOSE: Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults. METHODS: We included 112 black and 143 white healthy normotensive adults (20-30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected. RESULTS: The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ±â€¯11 vs. 164 ±â€¯11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ±â€¯2.1 vs. 3.3 ±â€¯1.8%; p < .001). CONCLUSIONS: Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation.

Association of Intracranial Pressure and Spontaneous Retinal Venous Pulsation.

Importance: A convenient and reliable method for noninvasive intracranial pressure assessments is desirable to reduce the need for invasive procedures (eg, intracranial pressure monitoring and lumbar punctures) and allow clinicians to identify and treat patients with intracranial hypertension in a timely manner. Objective: To determine whether infrared video assessment of spontaneous retinal venous pulsation is associated with intracranial pressure and is a valid tool to indicate the presence or absence of raised intracranial pressure in patients without papilledema. Design, Setting, and Participants: A single-center prospective study was conducted at a tertiary referral center between January 2017 and May 2018. Patients consecutively admitted for clinically indicated elective 24-hour invasive intracranial pressure monitoring had ophthalmic review including infrared video recording of their spontaneous venous pulsation. Two neuro-ophthalmologists, who were masked to the intracranial pressure monitoring results, independently graded the spontaneous venous pulsation (grade 0 to 3). Analysis began in June 2018. Main Outcomes and Measures: The association between simultaneously recorded intracranial pressure and spontaneous venous pulsation (binary variable: present/absent) assessed through retinal infrared video recordings was evaluated using a multiple linear regression model. Results: Of 105 patients, the mean (SD) age was 39 (14) years, and 79 (75%) were women. The mean (SD) simultaneous intracranial pressure was 1 (5) mm Hg for 91 patients (86.7%) with spontaneous venous pulsations and 13 (14) mm Hg for 14 patients (13.3%) without spontaneous venous pulsations. A multiple linear regression model adjusted for 7 potential confounders confirmed a statistically significant association between intracranial pressure and spontaneous venous pulsation (ß = -9.1; 95% CI, -13.7 to -4.6; P < .001; adjusted R2 = 0.42). Conclusions and Relevance: The absence of spontaneous venous pulsation on retinal infrared video recordings is significantly associated with higher levels of intracranial pressure and should raise the suspicion of intracranial hypertension.

The Oxygen Saturation in Vascular Abnormalities Depends on the Extent of Arteriovenous Shunting in Diabetic Retinopathy.

Purpose: Diabetic retinopathy is characterized by disturbances in retinal blood flow mediated by capillary occlusion, intraretinal microvascular abnormalities (IRMAs), neovascularizations, and omega loops and reduplications. It is likely that the study of oxygen saturation in these abnormalities can provide knowledge about their role in the development of diabetic retinopathy. Methods: The oxygen saturation in IRMA vessels and venous loops and reduplications were studied in 40 diabetic patients with severe nonproliferative or proliferative diabetic retinopathy. The saturation values in the studied vascular abnormalities were compared to those of the larger retinal arterioles and venules. Results: There was a similar oxygen saturation (mean ± SD) in IRMAs observed to connect arterioles with venules (78.6% ± 11.8%, n = 22) and IRMAs connecting venules with venules (79.2% ± 9.0%, n = 12; P > 0.999). The saturation in IRMAs was significantly lower (P < 0.0002) than in arterioles (97.4% ± 5.2%, n = 40) and significantly higher (P < 0.0001) than the saturation in omega loops and reduplications (54.2% ± 19.3%, n = 6), which in turn showed no significant difference from the saturation in the venules (61.8% ± 6.8%, n = 40, P = 0.4). Conclusions: The findings suggest that the oxygen saturation in vascular abnormalities in diabetic retinopathy depends on the extent of arteriovenous (A-V) shunting, with venous saturation due to no A-V shunting in venous loops and reduplications, and intermediate oxygen saturation due to moderate shunting in IRMAs. This may precede the development of neovascularizations with arterial oxygen saturation due to high A-V shunting.

Detection and characterization of tree shrew retinal venous pulsations: An animal model to study human retinal venous pulsations.

Spontaneous retinal venous pulsations (SRVPs), pulsations of branches of the central retinal vein, are affected by intraocular pressure (IOP) and intracranial pressure (ICP) and thus convey potentially-useful information about ICP. However, the exact relationship between SRVPs, IOP, and ICP is unknown. It is not easily feasible to study this relationship in humans, necessitating the use of an animal model. We here propose tree shrews as a suitable animal model to study the complex relationship between SRVPs, IOP, and ICP. Tree shrew SRVP incidence was determined in a population of animals. Following validation of a modified IOP control system to accurately and quickly control IOP, IOP and/or ICP were manipulated in two tree shrews with SRVPs and the effects on SRVP properties were quantified. SRVPs were present in 75% of tree shrews at physiologic IOP and ICP. Altering IOP or ICP produced changes in tree shrew SRVP properties; specifically, increasing IOP caused SRVP amplitude to increase, while increasing ICP caused SRVP amplitude to decrease. In addition, a higher IOP was necessary to generate SRVPs at a higher ICP than at a lower ICP. SRVPs occur with a similar incidence in tree shrews as in humans, and tree shrew SRVPs are affected by changes in IOP and ICP in a manner qualitatively similar to that reported in humans. In view of anatomic similarities, tree shrews are a promising animal model system to further study the complex relationship between SRVPs, IOP, and ICP.

Postural effects on spontaneous retinal venous pulsations in healthy individuals.

PURPOSE: To assess amplitudes of spontaneous retinal venous pulsations (SVP) in three various postures (sitting, supine and lateral decubitus) in healthy individuals. METHODS: Thirty participants (28 ± 8 years, 25 females) were included in the study. Intraocular pressure (IOP), blood pressure (BP) and SVP's were measured at three different postures using a calibrated Tono-Pen applanation tonometer, a digital sphygmomanometer, and a custom-built handheld video ophthalmoscope, respectively. Retinal venous pulsations (SVP) amplitudes were extracted from the retinal videos using a custom written MATLAB algorithm. Mean arterial pressure (MAP = (systolic + 2diastolic)/3) and mean ocular perfusion pressure (MOPP = (2/3 MAP)-IOP) were also calculated at each posture. A one-way ANOVA was applied to each parameter to determine any significant difference for the various postural changes. RESULTS: Mean IOP increased (p < 0.0001) and mean SVP decreased (p < 0.0001) from sitting to supine. The mean IOP (mmHg) and SVP (MU; measuring units) in sitting, supine and lateral decubitus were 16.2 ± 2, 19.4 ± 4, 19.8 ± 2 mmHg and 5.8 ± 2, 4.5 ± 2, and 4.7 ± 2 MU, respectively. Mean arterial pressure (MAP) and MOPP also decreased significantly from sitting to supine (p < 0.001, p < 0.001) and sitting to lateral decubitus (p < 0.05, p < 0.01). There were no significant differences between IOP, SVP, MAP or MOPP during a postural modification from supine to lateral decubitus. CONCLUSIONS: In this study, we showed a significant reduction in SVP amplitudes and a significant increase in IOP from sitting to supine position in a healthy young cohort. This supports the rationale to further study such phenomenon in ocular conditions such as glaucoma to determine whether relative SVP change, for a similar postural change, can reveal early signs of vascular dysfunction.

Blood Flow in Monocular Retinoblastoma Assessed by Color Doppler and Correlations With High-Risk Pathologic Features.

Purpose: To use color Doppler to analyze blood flow in the retrobulbar central retinal artery (CRA) and central retinal vein (CRV) in monocular retinoblastoma. Methods: This prospective study included patients with group D and E retinoblastomas managed with only enucleation. Peak blood velocities were assessed in the CRA and CRV of tumor-containing eyes (CRAv and CRVv, respectively). The resistivity index in the CRA (RIa) and pulse index in the CRV (PIv) were calculated and related to optic nerve invasion (ONi), choroid invasion (mCHi), and tumor volume. RIa and PIv were also calculated for healthy eyes. Results: In total, 25 patients with a mean age of 30.8-months old were included. The means (SD) for CRAv, CRVv, RIa, and PIv were 26.94 (12.32) cm/s, 16.2 (9.56) cm/s, 0.88 (0.12) and 0.79 (0.29), respectively. Tumor volume was significantly correlated with CRAv (P = 0.025) and RIa (P = 0.032). ONi was present in 19 eyes and correlated with a smaller PIv (P < 0.001). A PIv less than 0.935 had a sensitivity of 89.5% and specificity of 83.3% for predicting ONi. mCHi was not correlated with flow values. Healthy eyes had a significantly lower RIa (P < 0.001) and lower PIv than eyes with (P = 0.009) and without (P < 0.001) ONi. Conclusions: In advanced-stage monocular retinoblastoma, tumor volume was directly correlated with CRAv and RIa, and lower PIv was correlated with optic nerve invasion when a predictive cut-off value of less than 0.935 was applied. Comparisons with healthy eyes showed that tumor-containing eyes were associated with higher RIa and PIv values.

Constriction of Retinal Venules to Endothelin-1: Obligatory Roles of ETA Receptors, Extracellular Calcium Entry, and Rho Kinase.

Purpose: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in retinal venous pathologies such as diabetic retinopathy and retinal vein occlusion. However, underlying mechanisms contributing to venular constriction remain unknown. Thus, we examined the roles of ET-1 receptors, extracellular calcium (Ca2+), L-type voltage-operated calcium channels (L-VOCCs), Rho kinase (ROCK), and protein kinase C (PKC) in ET-1-induced constriction of retinal venules. Methods: Porcine retinal venules were isolated and pressurized for vasoreactivity study using videomicroscopic techniques. Protein and mRNA were analyzed using molecular tools. Results: Retinal venules developed basal tone and constricted concentration-dependently to ET-1. The ETA receptor (ETAR) antagonist BQ123 abolished venular constriction to ET-1, but ETB receptor (ETBR) antagonist BQ788 had no effect on vasoconstriction. The ETBR agonist sarafotoxin S6c did not elicit vasomotor activity. In the absence of extracellular Ca2+, venules lost basal tone and ET-1-induced constriction was nearly abolished. Although L-VOCC inhibitor nifedipine also reduced basal tone and blocked vasoconstriction to L-VOCC activator Bay K8644, constriction of venules to ET-1 remained. The ROCK inhibitor H-1152 but not PKC inhibitor Gö 6983 prevented ET-1-induced vasoconstriction. Protein and mRNA expressions of ETARs and ETBRs, along with ROCK1 and ROCK2 isoforms, were detected in retinal venules. Conclusions: Extracellular Ca2+ entry via L-VOCCs is essential for developing and maintaining basal tone of porcine retinal venules. ET-1 causes significant constriction of retinal venules by activating ETARs and extracellular Ca2+ entry independent of L-VOCCs. Activation of ROCK signaling, without involvement of PKC, appears to mediate venular constriction to ET-1 in the porcine retina.

Ultra-Wide-Field Fluorescein Angiography-Guided Normalization of Ischemic Index Calculation in Eyes With Retinal Vein Occlusion.

Purpose: The purpose of this study was to compare the use of central and montaged ultra-wide-field fluorescein angiography (UWFFA) images for calculating the area of nonperfusion (NP) and ischemic index (ISI) in patients with retinal vein occlusion (RVO) and macular edema (ME) and to correlate these measurements with best-corrected visual acuity (BCVA) and central macular thickness (CMT). Methods: Thirty eyes of 30 RVO patients with recurrent ME were enrolled. Baseline UWFA images were sent to the Doheny Image Reading Center for quantitative analysis by certified graders. The association between ISI from the various zones and BCVA and CMT was examined by Spearman rank correlation and compared. Generalized linear models (GLMs) were used to analyze associations between BCVA and disease status. Results: The NP area and ISI for central and montaged images were not significantly different for any retinal zone. A modest but statistically significant negative linear correlation was observed between BCVA and ISI, ranging from r = -0.3825 in the perimacular area (PMA) to r = -0.584 in the far peripheral area (FPA). On GLM analysis, both PMA (ß = -1.059; 95% confidence interval: -1.74 to -0.378) and FPA (ß = -0.505; 95% confidence interval: -0.988 to -0.021) were significant independent predictors of BCVA. We found no correlation between ISI from the various zones and CMT in this cohort. Conclusions: Montaging of UWFFA images may not be required to adequately quantify and represent areas of NP in eyes with RVO. NP in both the PMA and peripheral retina appear relevant to visual function, highlighting the importance of evaluating the retinal periphery in these individuals.

Association between optical coherence tomography based retinal microvasculature characteristics and myocardial infarction in young men.

Incident myocardial infarction (MI) is a leading cause of adult mortality in the United States. However, because MI has a relatively low incidence in the young population, little information exists on the disease in younger adults. Because the retina has the unique quality that its vasculature is readily and noninvasively visible, the retina is frequently studied to evaluate correlations between vessels and cardiovascular diseases. In the current study, we evaluated the retinal microvasculature of patients who had experienced an MI before 50 years of age (n = 53 subjects) and age- and sex-matched patients who had not experienced an MI (n = 53 patients). We used circular optical coherence tomography (OCT) scans to image peripapillary venules and arterioles. The diameter of each vessel was measured and the respective arterial-venous ratio (AVR) was calculated. We did not detect any significant differences between MI and control subjects in retinal vessel calibre or AVR.

Correlation Between Ischemic Index of Retinal Vein Occlusion and Oxygen Saturation in Retinal Vessels.

PURPOSE: To evaluate the relationship between the ischemic index and the oxygen saturation in retinal vessels in patients with retinal vein occlusion. DESIGN: Prospective, cross-sectional study. METHODS: We performed a prospective study. The cohort consisted of 43 eyes of 43 patients with retinal vein occlusions (RVO), 23 of whom had central retinal vein occlusions (CRVO) and 20 who had branch retinal vein occlusions (BRVO). We evaluated the retinal vessel saturation using an automatic retinal oximetry device. The retinal ischemic index (ISI) was determined using ultra-widefield fluorescein angiography. RESULTS: Mean arterial saturation (±SD) was 100% ± 11%, mean vein saturation was 52% ±13%, and mean A-V difference was 48% ± 16% in eyes with BRVO. The average ISI in the same group was 0.48 (range 0-1). There was no statistically significant correlation between the retinal ischemic index and retinal saturation in the BRVO group. The affected eye in the CRVO group had a mean arterial saturation of 101% ± 6%, vein saturation of 44% ± 11 % and A-V difference of 58% ± 10%. The average ISI in the CRVO group was 0.54 (range 0-1). A statistically significant negative correlation between ISI and vein saturation was found in the CRVO group (r = -0.686; P =.0003). A significant positive correlation between ISI and the A-V difference was found in the CRVO group (r = 0.893; P <.0001). CONCLUSIONS: Oxygen saturation in the retinal vein and the arteriovenous difference correlated with the ischemic index in CRVO patients. No correlation was found for BRVO patients.

Changes in retinal venular oxygen saturation predict activity of proliferative diabetic retinopathy 3 months after panretinal photocoagulation.

BACKGROUND/AIMS: Proliferative diabetic retinopathy (PDR) is a severe blinding condition. We investigated whether retinal metabolism, measured by retinal oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP). METHODS: We performed a prospective, interventional, clinical study of patients with treatment-naive PDR. Wide-field fluorescein angiography (OPTOS, Optomap) and global and focal retinal oximetry (Oxymap T1) were performed at baseline (BL), and 3 months (3M) after PRP. Angiographic findings were used to divide patients according to progression or non-progression of PDR after PRP. We evaluated differences in global and focal retinal oxygen saturation between patients with and without progression of PDR after PRP treatment. RESULTS: We included 45 eyes of 37 patients (median age and duration of diabetes were 51.6 and 20 years). Eyes with progression of PDR developed a higher retinal venous oxygen saturation than eyes with non-progression at 3M (global: +5.9% (95% CI -1.5 to 12.9), focal: +5.4%, (95% CI -4.1 to 14.8)). Likewise, progression of PDR was associated with a lower arteriovenular (AV) oxygen difference between BL and 3M (global: -6.1%, (95% CI -13.4 to -1.4), focal: -4.5% (95% CI -12.1 to 3.2)). In a multiple logistic regression model, increment in global retinal venular oxygen saturation (OR 1.30 per 1%-point increment, p=0.017) and decrement in AV oxygen saturation difference (OR 0.72 per 1%-point increment, p=0.016) at 3M independently predicted progression of PDR. CONCLUSION: Development of higher retinal venular and lower AV global oxygen saturation independently predicts progression of PDR despite standard PRP and might be a potential non-invasive marker of angiogenic disease activity.

Regulation of oxygen saturation in retinal blood vessels in response to dynamic exercise.

PURPOSE: To evaluate the impact of dynamic exercise on retinal vessel oxygen saturation in healthy individuals. METHODS: Twenty-six healthy participants underwent moderate dynamic exercise (modified Master's two-step exercise). In all subjects, intraocular pressures (IOP), systolic and diastolic blood pressures (SBP and DBP), retinal vessel calibres and retinal arterial and venous oxygen saturation were measured at baseline, immediately following exercise and 15 min postexercise. RESULTS: Moderate dynamic exercise increased SBP and DBP immediately postexercise (SBP: 116 (±13) mmHg to 150 (±21) mmHg; p < 0.001 and DBP: 69 (±10) mmHg to 74 (±10); p < 0.001), while IOP decreased by an average of 2 mmHg (baseline: 13 (±3) mmHg)) immediately postexercise (11 (±2) mmHg). Oxygen saturation in retinal arteries remained unchanged (baseline = 93 ± 8%; immediately postexercise = 94 ± 9% and 15 min postexercise = 96 ± 8%; p = 0.069), but increased in retinal veins immediately postexercise and did not return to baseline values within 15 min postexercise (baseline = 54 ± 12%; immediately postexercise = 56 ± 15%; 15 min postexercise=57 ± 12%; p = 0.036). CONCLUSION: There is a mild increase in retinal venous oxygen saturation and there is a trend towards an increase in arterial saturation in otherwise healthy individuals following dynamic exercise.

Retinal venous pressure is higher than the airway pressure and the intraocular pressure during the Valsalva manoeuvre.

PURPOSE: The aims of this prospective experimental study were to explore the influence of the Valsalva manoeuvre (VM) on retinal venous pressure (RVP) in human volunteers in a university setting and to establish correlations for RVP with the increase in airway pressure (∆AirP) and in intraocular pressure (∆IOP). METHODS: In total, 31 healthy young volunteers (age: 24 ± 1.7 years) were investigated. The instruments used included a dynamic contour tonometer, a contact lens dynamometer (Imedos) and an electronic pressure transducer for measuring airway pressure. The following measurements were successively performed in left eyes: tonometry, dynamometry, repeated simultaneous dynamometry and airway pressure measurement during the VM and tonometry during the VM. The pressures obtained during the VM were determined at 10, 20 and 30 seconds after onset of the VM by linear interpolation. RESULTS: The pressures (in mmHg) at baseline and during the VM (median and range with outliers) were as follows: ∆AirP: 10 seconds: 10.0 (7.5); 20 seconds: 12.5 (11.0); and 30 seconds: 11.0 (10.0); and RVP: Start: 17.1 (2.4); 10 seconds: 26.0 (7.5); 20 seconds: 25.0 (6.5); and 30 seconds: 24.0 (6.0). During the VM, the RVP was significantly increased compared with the ∆AirP (p = 0.0017). The IOP during the VM was 13.5 (2.7), and the increase in IOP (∆IOP) was 0.8 (5.6). CONCLUSION: During the VM, the RVP was increased compared with the ∆AirP. The increase in RVP (∆RVP) was significantly greater than the ∆IOP. During the VM, the calculated retinal perfusion pressure may be more strongly reduced by the ∆RVP than by the ∆IOP. These properties may influence retinal and optic nerve head pathophysiology.

The 3D Retinal Capillary Circulation in Pigs Reveals a Predominant Serial Organization.

Purpose: To establish a model of the retinal capillary circulation in pigs, which in many aspects is close to the human retina. Methods: Using high density confocal microscopy image stacks of immunolabeled porcine retinal whole mounts, microvessels close to the optic nerve head were traced in three dimensions. The direction of flow of individual capillaries was deduced from their arteriolar and/or venous connections. Results: From major arteries, second-order arteries traversed the nerve fiber layer and resolved exclusively into the superficial vascular plexus (SVP), which dichotomized the blood flow between radial peripapillary capillaries (RPCs) on one side and the intermediate (IVP) and deep vascular plexus (DVP) on the other. Each RPC was supplied by one or several capillaries from the SVP and drained to the IVP or DVP. The DVP was a mosaic of approximately 300 to 600 µm wide anastomotic watersheds, each drained by one or two venules connected to major veins. A presumptive direction of flow could be determined for >90% of capillaries. These results suggest a model of the capillary circulation in which the three microvessel layers are serially organized with RPCs are in parallel between the SVP and IVP or DVP. Conclusions: In the peripapillary retina of pigs, microvascular layers have a serial arrangement, with RPCs emerging from the SVP and draining to the IVP or DVP; hence, connected in parallel of this scheme. The bulk of flow, therefore, traverses the SVP and DVP successively. This organization contributes to the higher oxygen saturation in the SVP and RPCs than in the DVP. Physiopathologic implications of this model regarding retinal diseases are discussed.