Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.

Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.

Venous blood flow alterations in glaucoma patients.

PURPOSE: To evaluate the correlation between retinal venous blood flow parameters and glaucomatous visual field damage in a retrospective analysis. METHODS: Fifty-five (24 male, 31 female) glaucoma patients, under intraocular pressure (IOP) reducing treatment, aged (mean ± SD) 69 ± 10 years, 29 with primary open-angle and 26 with normal-tension glaucoma, were evaluated with regard to the correlation between IOP, color Doppler retinal venous blood flow velocity and glaucomatous damage. RESULTS: Univariate regression analysis disclosed statistically significant correlations of the visual field index MD with age, IOP and venous blood flow (p ≤ 0.026 for each parameter). A mixed linear effects model disclosed a significant correlation of MD with age, IOP and venous blood flow (p ≤ 0.002 for each parameter), but not with sex, side (right eye versus left eye) and diagnosis (primary open-angle glaucoma versus normal-tension glaucoma). Finally, interocular difference (right eye vs. left eye of the same patient) in MD correlated with interocular differences in venous blood flow velocities (p < 0.001), but not with interocular differences in IOP. CONCLUSIONS: Glaucomatous damage correlated negatively with retinal venous blood flow velocity, be it between subjects or between eyes within individuals. This study is limited by its cross-sectional design, and it is not possible to draw any conclusion with regard to the origin of the correlations.

Incidence of severe rise in intraocular pressure after intravitreous injection of aflibercept with prefilled syringes.

Our aim was to analyze the intraocular pressure (IOP) changes following different intravitreous injection (IVI) procedures with or without prefilled syringes (PFS) and to elaborate their possible causes. Clinical study and laboratory assessment. 173 eyes of 141 patients. The IOP was prospectively measured pre- and postoperatively in three groups of patients receiving IVI either with ranibizumab (RP), aflibercept PFS (AP) or aflibercept vials (AV). The AP emptying volume (EV) was assessed using 40 aflibercept PFS vials: the plunger was aligned precisely (normal volume, NV) or right below the indication line (high volume, HV) and the drug was ejected with (wP) or without forced pressure (nP). Primary outcome was post-treatment IOP with type of IVI and pre-treatment IOP as fixed factors. Secondary outcome was identification of possibly confounding factors (age, sex, pathology, presence of pseudophakia, spherical error, and number of injections) and IOP > 30 mmHg post-treatment. An IOP rise above 30 mmHg was observed in 8/38 (22%), 16/51 (31%) and 35/86 (41%) cases in the RP, AV and AP groups, respectively (p = 0.129). Pre-treatment IOP was the only predictive variable for IOP rise (p < 0.001). The EV values in the NVnP, NVwP, HVnP and HVwP groups were 56.06 ± 10.32, 70.69 ± 4.56, 74.22 ± 7.41 and 81.63 ± 3.67 µl, respectively (p < 0.001). We observed a marked, although not significantly higher incidence of IOP elevations with the aflibercept PFS. One possible reason may be the error-proneness of administering the correct volume with the AP. Caution should be taken when using the aflibercept PFS in order to prevent potential optic nerve damage in cases with marked elevation in IOP.

Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population.

BACKGROUND: The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population. METHODS: In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis. RESULTS: A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs. CONCLUSIONS: Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

Short-term variability of systemic blood pressure and submacular choroidal blood flow in eyes of patients with primary open-angle glaucoma.

PURPOSE: To analyse short-term variability of systemic blood pressure and choroidal blood flow in glaucoma patients, and compare them with ocular hypertensive patients and controls. SUBJECTS AND METHODS: Thirty untreated patients with primary open-angle glaucoma (POAG), 25 untreated patients with ocular hypertension (OHT) and 50 healthy controls without local therapy were included in the study. Continuous 5-minute measurements of arterial systemic blood pressure (SBP) by Finometer and choroidal blood flow (CBF) by laser Doppler flowmetry were obtained. Variability of SBP and CBF was analysed by means of coefficient of variation and analyzed in ANOVA model. Linear regression analysis was performed on parameters of morphological (nerve fiber layer thickness) and functional glaucomatous damage (visual field) on one side, and between SBP and CBF on the other side. RESULTS: ANOVA model demonstrated significant differences in variability between the groups (p = 0.003); post-hoc analysis specified a significantly higher short-term variability of both the blood pressure and choroidal blood flow in POAG patients (coefficients of variation: 3.33% +/- 1.05% and 3.90% +/- 2.17% respectively) than in healthy controls (coefficient of variation: 2.57% +/- 0.80% and 2.94% +/- 1.52% respectively). No significant differences were found for OHT patients. CONCLUSIONS: POAG patients without local therapy demonstrate an increased short-term BP and CBF variability.

Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes.

PURPOSE: There is growing evidence that vasospatic individuals could be predisposed to develop glaucoma. Vasospastic deregulation is ensuing in activation of circulating leukocytes. In previous studies using "gene-hunting" strategies, we demonstrated stable alterations in gene expression profiles of circulating leukocytes isolated from glaucoma patients with vascular deregulation when compared to healthy individuals with no history of glaucomatous damage. The goal of this study was to look for possible similarities in gene expression profiles of circulating leukocytes in vasospastic individuals and glaucoma patients. METHODS: Normal-tension (NTG) and high-tension (HTG) glaucoma patients as well as individuals with vascular deregulation (VD) and healthy controls were recruited for the gene expression analysis. The methodology of comparative Expression Array analysis followed by highly sensitive quantitative real-time PCR has been used. RESULTS: Compared to the control group the expression of 146, 68, and 60 genes was found to be altered in NTG, HTG, and VD groups respectively. Thirty-four genes demonstrated similar expressional alterations in NTG, HTG, and VD groups versus controls, and only 21 genes demonstrated similar expressional alterations in NTG and HTG groups, having no overlap with the VD group. CONCLUSIONS: This result indicates a potential predisposition of vasospastic individuals to glaucomatous optic nerve atrophy. The targeted expression profiles might be further considered for early/predictive glaucoma diagnosis.

Strategies for reducing variance in laser Doppler flowmetry measurements.

BACKGROUND: Scattering of blood flow data as assessed with laser Doppler flowmetry (LDF) in humans is a problem in many studies using this technique. We set out to reduce variability in LDF data by eliminating the effect of the total returning light level (DC) on LDF parameters in the choroid through partial regression analysis. METHODS: In 20 healthy subjects, choroidal blood flow parameters were measured at different DC values using a portable confocal LDF device. We used two different strategies to reduce scattering of data eliminating the effect of yield, which is defined as DC/gain. On the one hand, we used a previously described method based on a third-order polynomial fit, which combines all obtained data. On the other hand, we applied a new method based on a linear fit for each individual subject. RESULTS: Variability of data during changes in DC is higher for LDF parameters volume and flow than for velocity. Both methods were successful in reducing scattering of LDF parameters with varying DC. CONCLUSIONS: The present study indicates that both methods to correct for changes in yield were successful in reducing the variability of LDF measurements. When systematic changes in DC occur after an intervention, one needs to be careful in interpreting the obtained data and it remains to be shown if either of the two techniques is capable of correcting for this effect. The approach presented here may, however, represent an effective, easily applicable and valid approach to reduce scattering of data from using LDF to assess blood flow in the posterior pole of the human eye.

Optical coherence tomography angiography (OCTA) as a new diagnostic tool in uveitis.

BACKGROUND: The broad spectrum of uveitis disorders requires a multimodal imaging approach in the daily practice of an ophthalmologist. As inflammatory conditions, they have in common an alteration in leukocyte migration. In this context, optical coherence tomography angiography (OCTA) might be of great value for diagnosing or following up patients with these disorders. To date, OCTA has rather been used as an additional tool besides the well-established diagnostic imaging tools, but its complementary diagnostic features become increasingly relevant, to follow disease activity and treatment response and for the understanding of pathomechanisms of various uveitis types. This review summarizes the possible applications of OCTA and its advantages and disadvantages as opposed to dye-based angiographies in uveitic diseases. MAIN BODY: Hitherto gold standards in the diagnostic workup of posterior or intermediate uveitis have been angiography on a dye-based method, which is fluorescein or indocyanine green. It gives information about the status of the blood-retinal barrier and the retinal and choroidal vasculature by visualizing diffuse leakage as a state of inflammation or complications as an ischemia or choroidal neovascularization. As noninvasive methods, fundus autofluorescence depicts the status of metabolic activity of the retinal pigment epithelium and OCT or enhanced depth imaging OCT, respectively, as a depth-resolving imaging method can supply additional information. OCTA as a non-invasive, depth-resolution imaging tool of retinal and choroidal vessels adds detailed qualitative and quantitative information of the status of retinal and choroidal vessels and bridges the gap between the mentioned conventional diagnostic tools used in uveitis. It is important, though, to be aware of its limitations, such as its susceptibility to motion artifacts, limited comparability among different devices, and restricted contribution of information regarding the grade of disease activity. CONCLUSION: OCTA as a non-invasive, depth-resolution imaging tool can give qualitative and quantitative information about the status of retinal and choroidal vessels, but also has certain limitations. Employing OCTA as a complementary rather than exclusive tool, it can give important additional information about the macro- and microvasculature under inflammatory circumstances. Thereby, it also contributes to the understanding of the pathophysiology of various uveitis entities.

Statistical framework for validation without ground truth of choroidal thickness changes detection.

Monitoring subtle choroidal thickness changes in the human eye delivers insight into the pathogenesis of various ocular diseases such as myopia and helps planning their treatment. However, a thorough evaluation of detection-performance is challenging as a ground truth for comparison is not available. Alternatively, an artificial ground truth can be generated by averaging the manual expert segmentations. This makes the ground truth very sensitive to ambiguities due to different interpretations by the experts. In order to circumvent this limitation, we present a novel validation approach that operates independently from a ground truth and is uniquely based on the common agreement between algorithm and experts. Utilizing an appropriate index, we compare the joint agreement of several raters with the algorithm and validate it against manual expert segmentation. To illustrate this, we conduct an observational study and evaluate the results obtained using our previously published registration-based method. In addition, we present an adapted state-of-the-art evaluation method, where a paired t-test is carried out after leaving out the results of one expert at the time. Automated and manual detection were performed on a dataset of 90 OCT 3D-volume stack pairs of healthy subjects between 8 and 18 years of age from Asian urban regions with a high prevalence of myopia.

Cold extremities and difficulties initiating sleep: evidence of co-morbidity from a random sample of a Swiss urban population.

Difficulties initiating sleep (DIS) can frequently occur in psychiatric disorders but also in the general population. The primary vasospastic syndrome is a functional disorder of vascular regulation in otherwise healthy subjects complaining of thermal discomfort from cold extremities (TDCE). Laboratory studies have shown a close relationship between long sleep onset latency and increased distal vasoconstriction in healthy young subjects. Considering these findings, the aims of the Basel Survey were to assess the prevalence rates for DIS and TDCE and to determine whether both symptoms can be associated in the general population. In a random population sample of Basel-Stadt, 2800 subjects (age: 20-40 years) were requested to complete a questionnaire on sleep behavior and TDCE (response rate: 72.3% in women, n = 1001; 60.0% in men, n = 809). Values of DIS and TDCE were based on questionnaire-derived scores. In addition, TDCE was externally validated in a separate group of subjects (n = 256) by finger skin temperature measurements--high TDCE values were significantly associated with low finger skin temperature. A total of 31.1% of women and 6.9% of men complain of TDCE. In contrast, prevalence rates of DIS were only slightly higher in women in comparison to men (9.3% versus 6.7%, P < 0.1). Irrespective of gender, each seventh subject complaining of TDCE had concomitant DIS and the relative risk in these subjects was approximately doubled. Therefore, a thermophysiological approach to DIS may be relevant for its differential diagnosis and its treatment.

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

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

Is neurovascular coupling of relevance in glaucoma?

Rapid development of functional neuroimaging techniques have brought about a growing interest for neurovascular coupling in neuroresearch, which, in turn, has prompted similar research in ophthalmology. There are now hints that neurovascular coupling is disturbed in glaucoma. The contact of the nerve terminals to the cortical blood vessels is mostly realized through astrocytes. A major defining property of glaucoma, cupping of the optic disk, implies tissue remodeling of the optic nerve head and involves an astrocytic responses. A malfunction of the astrocytes in glaucoma may lead not only to the hallmark of glaucoma-cupping and death of retinal ganglion cells-but also to an accompanying or even preceding disturbance in ocular neurovascular coupling. This article is a short overview of research published in this field so far.

Relationship between retinal glial cell activation in glaucoma and vascular dysregulation.

PURPOSE: To investigate the possible relationship between presumed activated retinal astrocytes and Müller cells (ARAM) and primary vascular dysregulation (PVD) in patients with primary open-angle glaucoma (POAG). PATIENTS AND METHODS: One hundred eighty-six eyes of 93 patients with POAG were included in the study. Presumed ARAM was defined as patchy, discrete glittering but transparent changes of the retina. The diagnosis of PVD was based on both the patient's history and an abnormal circulatory behavior. Frequency tables were used to describe categorical variables, and differences were compared by means of chi test. A generalized linear mixed model was applied to determine the influence of vascular dysregulation, mean visual defect, and age on ARAM. RESULTS: ARAM was found to be bilateral in 26.8% of patients (50 eyes), and unilateral in 11.8% (11 eyes). Patient's mean age was 68.6 (SD+/-8.1) years in the group with ARAM and 65.6 (SD+/-13.6) years in the group without (P=0.56). In the generalized linear mixed model, ARAM was significantly associated with vascular dysregulation [odds ratios (OR): 4.4, confidence intervals (CI): 1.7-11.3, P=0.002] but not with greater age (OR: 1.1 per decade of years, 0.7-1.6, P=0.48) and eye side (OR: 1.1, CI: 0.8-1.6, P=0.52). An increase of mean visual defect of 5.5 dB doubled the risk for ARAM (OR: 2.0; CI: 1.5-2.7, P<0.001). CONCLUSIONS: Presumed retinal glial cell activation in POAG is clearly related to vascular dysregulation and to some extent to the stage of glaucomatous damage.

On pulse-wave propagation in the ocular circulation.

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

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

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

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

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

Effect of hospitalization on intraocular pressure in patients with high tension and normal tension glaucoma.

PURPOSE: To determine the effect of hospitalization on intraocular pressure (IOP) in glaucoma patients. DESIGN: Prospective case series. METHODS: IOP was measured on three consecutive days in 26 high-tension (HTG) and 13 normal-tension (NTGwm) glaucoma patients under IOP-lowering treatment, and in 28 normal-tension glaucoma patients without IOP-lowering treatment (NTGnm), and change was compared by analysis of variance. RESULTS: IOP decreased significantly, but comparably, in the three groups and between right and left eyes, although, the relative change to IOP on day 1 was significantly less pronounced in the group without treatment on day 2 and 3 compared with the treated groups. CONCLUSIONS: Glaucoma patients showed a significant decrease in IOP during hospitalization. Although this decrease was more pronounced among the treated patients, it was also present in nontreated patients. Consequently, other factors than improved compliance during hospitalization must play a role in this phenomenon.

The prognostic value of retinal vessel analysis in primary open-angle glaucoma.

PURPOSE: To analyse a prognostic value of initial retinal vessel flicker response for the 3-year development of functional (visual field) and morphological (nerve fibre layer thickness) damage progression in primary open-angle glaucoma patients. PATIENTS AND METHODS: Initially, 70 patients were recruited, and flicker response was measured by standardized procedure with the retinal vessel analyser (RVA). Ocular coherence tomography of retinal nerve fibre layer (OCT RNFL) and a visual field testing were performed at beginning and every 6 months for 3 years; 56 patients completed the study. RESULTS: No correlation was found between the progression of visual field (VF) mean defect and retinal nerve fibre layer (RNFL) thinning over 3 years on one and the maximal flicker reaction in arteries and veins on the other side (all p > 0.1). However, the calculated difference of examined parameters in the superior versus inferior retinal halves correlated significantly between the RNFL thinning and the initial maximal flicker response for arteries (p = 0.01) and veins (p = 0.003). CONCLUSION: This longitudinal study did not find a general correlation between initial retinal vessel response to flicker light and the glaucoma damage progression measured by OCT and VF, hence limiting the relevance of the RVA device as a predictor of future glaucomatous damage.

High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light.

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.