EFFECT OF PATIENTS' CLINICAL INFORMATION ON THE DIAGNOSIS OF AND DECISION TO TREAT RETINOPATHY OF PREMATURITY.

PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

Severe pediatric Graves orbitopathy in adolescents of African origin.

This article reports on two cases of severe pediatric Graves orbitopathy (GO) in two adolescents of African origin. Two black male adolescents presented with highly active GO and signs of beginning compressive optic neuropathy. Neither of them were smokers nor had a family history of GO. Besides urgent referral to pediatric endocrinologists, intravenous methylprednisolon pulse therapy was initiated. In spite of the fluctuating thyroid hormone levels in the initial phase of antithyroid therapy, intravenous steroid administration stopped the progression of malignant GO rapidly in both of our patients without any considerable side effects. Although the course of GO during childhood is considered to be mild, severe, sight threatening GO-requiring immunosuppression-may occur at young age, as in the reported adolescent patients of African descent.

Late Reconstruction of the Orbit With Patient-Specific Implants Using Computer-Aided Planning and Navigation.

PURPOSE: Reconstruction of orbital deformities is a challenging task. Virtual 3-dimensional (3D) planning and the use of patient-specific implants (PSIs) could improve anatomic and functional outcomes in the orbital region. MATERIALS AND METHODS: A retrospective study was performed of patients who underwent late orbital reconstruction from 2009 to 2013. To be included in the study, patients had a unilateral orbital deformity by involvement of at least 2 orbital wall defects. No orbital osteotomies could be used to correct the deformity. All patients underwent 3D virtual treatment planning. The unaffected orbit was mirrored onto the affected orbit. The PSI was fabricated according to this plan. Navigation was used to check the implant position. RESULTS: Six patients were included in this study. All patients had diplopia or motility limitations and enophthalmos. The ophthalmic parameters showed improvement in all patients. Enophthalmos was corrected adequately by the PSI. Four patients received a poly-ether-ether-ketone PSI. Two patients received a titanium mesh PSI. The position of the PSI was controlled by intraoperative navigation. Superimposition of the planned and postoperative positions of the PSI showed good correlation. CONCLUSION: PSIs placed with intraoperative navigation facilitate late or secondary correction of orbital deformities.

Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity.

PURPOSE: To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). DESIGN: Prospective intra- and inter-rater reliability analysis. METHODS: In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. RESULTS: Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0-5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). CONCLUSIONS: ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

Twin-twin transfusion syndrome as a possible risk factor for the development of retinopathy of prematurity.

PURPOSE: The objective of this study was to evaluate the correlation between twin-twin transfusion syndrome (TTTS) and the development of retinopathy of prematurity (ROP) in premature infants. METHODS: Fifty-one infants who were less than 32 postmenstrual gestational weeks at birth or with a birth weight less than 1,501grams were included in this longitudinal observational study. The infants were matched by gestational age and birth weight, and divided into three groups: multiples with TTTS, multiples without TTTS, and singletons. The primary outcome variable was the incidence of ROP in infants affected by TTTS versus infants not affected by TTTS. Secondary outcome variables were multiple pregnancy, gestational age, and birth weight. RESULTS: Infants affected by TTTS showed a significantly higher incidence of ROP than infants not affected by TTTS (p < 0.01). TTTS donors and TTTS recipients were both at greater risk of developing ROP. ROP occurred in infants with TTTS whose gestational age at birth was significantly higher than that of infants with ROP who were not affected by TTTS (p = 0.01). Multiple pregnancy itself was not a risk factor for ROP disease. CONCLUSIONS: Infants affected by TTTS during pregnancy are at high risk of developing ROP, even if they were born at an older gestational age. Special awareness in ROP screening is necessary for these infants.

Functional outcome after surgical treatment of orbital floor fractures.

In the present article, the authors want to present the results of a retrospectively evaluated consecutive series of patients with surgically treated isolated orbital floor fractures (OFF; "blow-out fractures") concerning the functional outcome after OFF and give detailed recommendations based on the clinical and radiological findings. A series of 60 patients with isolated OFF over a 5-year period needing surgically repair at the same institution were evaluated. Patient data were analysed in terms of preoperative and postoperative clinical parameters and radiological findings. The analysed parameters were type of fracture, diplopia, gaze restriction, enophthalmos, materials used for repair, surgical approach and timing of the surgical intervention. Burst type fractures were more often found than punched-out fractures. The most frequently used surgical approach was a preseptal transconjunctival approach. An overall decrease of gaze restriction (93%), diplopia (89%) and enophthalmos (86%) was observed. According to the fracture size, we used Ethisorb patches in smaller fractures and resorbable or titanium meshes or autologous bone in larger fractures in most cases. Patients who underwent surgery more than 7 days after the trauma showed better results with regard to an improvement of diplopia and motility disturbances than patients who were treated immediately. In indicated cases, the surgical repair of OFF leads to very good results if the anatomical and functional properties of the orbit and its contents are respected. The applied strategy and means presented in our study proved of value and can therefore be recommended.

Role of adenosine in the control of choroidal blood flow during changes in ocular perfusion pressure.

PURPOSE: The purpose of the present study was to investigate whether the nucleoside adenosine is involved in the regulatory processes of choroidal blood flow (ChBF) during an experimental decrease in ocular perfusion pressure (OPP). METHODS: In this randomized, double-masked, placebo-controlled, two-way crossover study, 14 subjects received either intravenous adenosine or placebo on two different study days. The suction cup method was used for a stepwise increase in intraocular pressure (IOP). Subfoveal ChBF was measured by laser Doppler flowmetry. Mean arterial pressure (MAP) and IOP were measured noninvasively. Ocular perfusion pressure was calculated as OPP = 2/3MAP - IOP. RESULTS: Adenosine increased ChBF significantly versus placebo before application of the suction cup (P < 0.05). When the suction cup was applied, a significant decrease in OPP was observed. This effect was comparable on all study days. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between -43% and -52%) which was less pronounced than the decrease in OPP (maximum between -62% and -64%). Neither placebo nor adenosine influenced the ChBF increase during suction cup-induced changes in OPP. CONCLUSIONS: The data of the present study confirm that the human choroid shows some regulatory capacity during a decrease in OPP. Adenosine influences basal vascular tone in the choroid but is not involved in the regulatory mechanisms during an increase in IOP. (ClinicalTrials.gov number, NCT00712764.).

Choroidal perfusion in eyes with untreated choroidal melanoma.

PURPOSE: Previous studies indicate that ocular blood flow is altered in eyes with choroidal melanoma. In the present study pulsatile ocular blood flow (POBF) was assessed to investigate whether there exists a correlation between tumour size and ocular blood flow parameters. METHODS: Twenty-two patients with unilateral untreated choroidal melanoma were studied using two measurement techniques: POBF was measured with a pneumotonometer and local foveal fundus pulsation amplitude (FPA) by laser interferometry, and results were correlated. Tumour volume was calculated using the ellipsoidal solid model and was correlated to POBF and FPA. RESULTS: Levels of POBF and FPAs tended to be higher in tumour eyes compared with unaffected eyes, but the differences did not reach the level of significance. Both methods showed a high degree of correlation in unaffected eyes. In tumour eyes the correlation was slightly less pronounced. There was no correlation between tumour and POBF or FPA. CONCLUSIONS: Our results do not indicate choroidal hyperperfusion in patients with choroidal melanoma. The clinical usefulness of measuring POBF in tumour patients may be limited.

Effects of dopamine on retinal and choroidal blood flow parameters in humans.

AIM: To investigate the effect of dopamine on retinal and choroidal blood flow in humans. METHODS: We investigated the effect of two doses of intravenous dopamine (5 and 10 microg/kg/min) via a randomised double-masked crossover study in 12 healthy subjects chosen from a total of 16. Blood flow parameters in retina, optic nerve head and choroid were assessed with bi-directional laser Doppler velocimetry, laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively. RESULTS: Intravenous dopamine dose-dependently increased retinal blood cell velocity and fundus pulsation amplitude (p<0.001). At the highest administered dose red blood cell velocity in retinal vessels increased by 37% and fundus pulsation amplitude by 24%. By contrast, optic nerve head blood flow did not change with dopamine administration. CONCLUSIONS: Our data indicate that dopamine has a pronounced enhancing effect on the retinal perfusion in humans. Further studies are required to establish the exact role of dopamine in the regulation of choroidal and optic nerve head blood flow.

Effects of pentoxifylline and alprostadil on ocular hemodynamics in healthy humans.

PURPOSE: Alprostadil, a prostaglandin (PG)E(1) analogue and pentoxifylline, an alkylxanthine derivate, have been shown to exert vasodilatory effects in several vascular beds. The purpose of the present study was to investigate the effect of PGE(1) and pentoxifylline on the ocular circulation. METHODS: A placebo-controlled, double-masked, three-way, crossover study was performed in 15 healthy male subjects. Subjects received pentoxifylline (300 mg), PGE(1) (alprostadil 60 mug), or placebo intravenously over 2 hours on three trial days. Choroidal red blood cell flow was assessed with laser Doppler flowmetry and pulsatile choroidal blood flow with laser interferometric measurement of fundus pulsation amplitude (FPA). Retinal blood cell flow was calculated based on the measurements of maximum erythrocyte velocity in a retinal vein assessed with bidirectional laser Doppler velocimetry, and diameter measurements of retinal vessels were obtained with a retinal vessel analyzer. RESULTS: Pentoxifylline increased FPA by 15.4% +/- 1.1% (P < 0.001 versus placebo and baseline). Alprostadil tended to increase FPA, but this effect did not reach the level of significance (P = 0.07 versus placebo). Choroidal blood flow as measured with laser Doppler flowmetry tended to increase during pentoxifylline and PGE(1) infusion by 8.9% +/- 2.9% (P = 0.062) and 4.5% +/- 6.2% (P = 0.29), respectively, but none of these effects was significant. The drugs under study had no effect on mean red blood cell velocity in retinal veins, on retinal vessel diameters, intraocular pressure, blood pressure, or pulse rate. CONCLUSIONS: PGE(1) did not alter the parameters of retinal or choroidal circulation in healthy subjects. Pentoxifylline increased FPA, but did not change choroidal blood flow as measured with laser Doppler flowmetry and did not affect retinal blood flow parameters. Accordingly, neither pentoxifylline nor PGE(1) appears to be suitable to improve ocular blood flow in healthy subjects. Whether long-term treatment with alprostadil would improve choroidal blood flow in patients with vascular disease remains to be established.

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia.

PURPOSE: Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. METHODS: We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. RESULTS: On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. CONCLUSIONS: Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Intravenously administered histamine increases choroidal but not retinal blood flow.

PURPOSE: To determine the effect of intravenously administered histamine on both retinal and choroidal blood flow in humans. METHODS: A randomized, double-masked, two-way crossover study was performed in 14 healthy volunteers. Placebo or histamine was administered intravenously in stepwise increasing doses (0.08 microg/kg/min, 0.16 microg/kg/min, and 0.32 microg/kg/min). Retinal vessel diameters were measured with a retinal vessel analyzer, and retinal venous blood speed was assessed by bi-directional laser Doppler velocimetry. Using these parameters retinal blood flow was calculated. Subfoveal and pulsatile choroidal blood flow were measured with laser Doppler flowmetry and laser interferometry, respectively. RESULTS: After infusion of histamine pulsatile choroidal blood flow increased by 5 +/- 3%, 9 +/- 8%, and 14 +/- 7% (P = 0.001, ANOVA) and subfoveolar choroidal blood flow by 8 +/- 11%, 13 +/- 11%, and 13 +/- 12% (P = 0.003, ANOVA). Retinal arterial and venous vessel diameter significantly increased by 3 +/- 4%, 2 +/- 4%, and 3 +/- 5% (P = 0.047, ANOVA) and 1 +/- 2%, 3 +/- 2%, and 3 +/- 2% (P = 0.015, ANOVA), respectively. Red blood cell velocity in major retinal veins tended to decrease by -9 +/- 12%, -9 +/- 20%, and -13 +/- 12%, but this effect did not reach levels of significance. Calculated retinal blood flow was not changed by administration of histamine (-7 +/- 14%, -4 +/- 20%, and -8 +/- 12%, P = 0.28, ANOVA). CONCLUSIONS: Intravenous histamine in the selected doses increased choroidal blood flow. Retinal vessels showed a small diameter increase, whereas red blood cell speed decreased, resulting in an unchanged total retinal blood flow. This may result from local differences in the receptor distribution in the posterior part of the eye.

Flicker light-induced vasodilatation in the human retina: effect of lactate and changes in mean arterial pressure.

PURPOSE: Diffuse luminance flicker light increases retinal and optic nerve head blood flow in animals and humans, but the exact mechanisms that mediate increased flow have yet to be identified. In the current study, the effect of increased plasma lactate levels on flicker-induced vasodilatation in the retina was investigated in three independent studies in healthy humans. METHODS: In the first study, plasma lactate concentrations were increased by bicycle exercise in 12 volunteers, and the change in retinal vessel diameter to 8-Hz square-wave flicker stimulation was measured with the Zeiss Retinal Vessel Analyzer (Carl Zeiss Meditec, Oberkochen, Germany). In a different study, sodium lactate was administered intravenously, and flicker responses were measured in 12 subjects. As a control experiment accounting for pressure increases induced by exercise, the effect of elevated ocular perfusion pressure on the flicker response was investigated during tyramine infusion (n = 12). RESULTS: The increase in plasma lactate concentration during intravenous infusion from 1.3 +/- 0.4 to 6.3 mmol/L and during dynamic exercise from 1.2 +/- 0.3 to 9.4 mmol/L decreased flicker responses in retinal arteries from 5.3% +/- 0.9% to 1.7% +/- 0.6% (P < 0.001) and from 3.6% +/- 0.6% to 2.0% +/- 0.8% (P = 0.03), respectively. In contrast, an increase of mean blood pressure from 81 +/- 3 to 92 +/- 3 mm Hg after tyramine infusion had no significant effect on flicker-induced vasodilatation in retinal arteries and veins. CONCLUSIONS: The signaling between neuronal activity and flow response in the human retina is sensitive to changes in blood lactate levels, whereas changes in systemic blood pressure have no major effect. Whether an increased cytosolic redox impairment contributes to flicker-induced vasodilatation has yet to be clarified.

Effects of adrenomedullin on ocular hemodynamic parameters in the choroid and the ophthalmic artery.

PURPOSE: Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo. METHODS: The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days. RESULTS: Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion. CONCLUSIONS: Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.

Effect of intravenous administration of sodium-lactate on retinal blood flow in healthy subjects.

PURPOSE: The present study was designed to investigate the effect of intravenously administered sodium lactate on ocular blood flow. METHODS: Twelve healthy male volunteers received either sodium lactate (0.6 mol/L) or physiologic saline solution in a randomized, double-masked, two-way crossover study. Sodium lactate or placebo were administered at an infusion speed of 500 and 1000 mL/h for 30 minutes each. Blood flow measurements were performed in the last 10 minutes of the infusion periods. Retinal blood flow was calculated based on the measurement of maximum erythrocyte velocity, assessed with bidirectional laser Doppler velocimetry, and retinal vessel diameter obtained with a retinal vessel analyzer. Choroidal blood flow was assessed with laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. RESULTS: Administration of lactate increased blood lactate concentration from 1.3 +/- 0.4 to 3.9 +/- 0.7 mmol/L (P < 0.001) and to 7.1 +/- 1.4 mmol/L (P < 0.001) at infusion speeds of 500 and 1000 mL/h, respectively. At these blood lactate concentrations, retinal blood flow increased by 15% +/- 20% and by 24% +/- 37% (ANOVA, P = 0.01). Fundus pulsation amplitude increased by 3% +/- 6% and 10% +/- 5% (ANOVA, P = 0.04) at the two plasma lactate concentrations. Subfoveal choroidal blood flow measured with laser Doppler flowmetry tended to increase by 10% +/- 15% and 13% +/- 20% (ANOVA, P = 0.19), but this effect was not significant. Infusion of sodium lactate induced alkalosis in arterial blood taken from the earlobe (7.41 +/- 0.03 at baseline; 7.50 +/- 0.03 during lactate infusion; P = 0.001). CONCLUSIONS: The data indicate that intravenously administered sodium lactate increases retinal blood flow. Whether this is related to a cytosolic redox impairment or to other hitherto unidentified mechanism remains to be clarified. Further studies are needed to determine whether lactate plays a role in regulation of choroidal blood flow.

The ocular hemodynamic response to nitric oxide synthase inhibition is unaltered in patients with early type I diabetes.

BACKGROUND: An impaired ocular hemodynamic response to systemic nitric oxide synthesis inhibition has been demonstrated in patients with long-standing insulin-dependent diabetes mellitus. It is unclear whether this altered responsiveness is already detectable in early uncomplicated type I diabetes. METHODS: The effect of the nitric oxide synthase inhibitor N(G)-monomethyl- l-arginine (L-NMMA) was studied in 10 male patients with early type I diabetes under euglycemic conditions and 10 healthy matched control subjects in a single (analyst) blinded cohort study design. Changes in ocular hemodynamics (fundus pulsation amplitude, mean flow velocity in the ophthalmic artery) and in pulse rate and mean blood pressure were measured in response to systemic intravenous doses of 1.5, 3, and 6 mg/kg L-NMMA. RESULTS: L-NMMA dose-dependently and significantly decreased fundus pulsation amplitude (-21.0% vs -23.3% in diabetics and controls, respectively), mean flow velocity in the ophthalmic artery (-12.3% vs -10.8%) and pulse rate (-15.4% vs -16.6%) and increased mean arterial pressure (+19.5% vs +14.7%). The ocular and systemic hemodynamic effects of L-NMMA were not different between patients with diabetes and controls. CONCLUSION: The responsiveness of the choroidal vasculature and the ophthalmic artery to L-NMMA is not altered in early type 1 diabetes. An impaired hemodynamic response to nitric oxide synthesis inhibition in diabetes is therefore not caused by a primary defect but rather due to altered vascular responsiveness secondary to long-standing disease.

Changing antiglaucoma therapy from timolol to betaxolol: effect on ocular blood flow.

The aim of the present study was to investigate the effect of a therapy change from timolol to betaxolol on ocular blood flow in patients with open-angle glaucoma. This randomized double-blind study comprised 34 consecutive patients with open-angle glaucoma, already treated with either timolol alone or in combination with other antiglaucoma agents. The patients were randomly allocated to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Ocular blood flow measurement as well as systemic hemodynamic and intraocular pressure (IOP) measurements were performed at baseline and 1 week and 1 and 3 months after the therapy change. Visual field testing was performed at baseline and at 3 months. After 3 months of treatment with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal blood flow were significantly altered. The power to detect a 9% change in pulsatile choroidal blood flow and a 20% change in retinal blood flow in the present study was 90%. The IOP was not significantly altered in either group. In contrast, visual fields slightly improved after betaxolol treatment compared to baseline (p = 0.047), but this effect was not significant versus timolol. Changing therapy from timolol to betaxolol has no effect on ocular blood flow in patients with open-angle glaucoma.

Nitric oxide regulates retinal vascular tone in humans.

The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects.

Flickering light stimulation of retinal photoreceptors induces retinal vessel dilation in humans. In the present study the effect of high blood glucose levels on this neuro-vascular mechanism was investigated in 12 healthy young male subjects. Blood glucose levels were consecutively increased during 30 min to 100, 200 and 300 mg/dl and kept at the respective level for the following 30 min using hyperglycemic insulin clamps. Eight Hertz flickering light was applied to the fundus at the end of each glucose plateau during continuous retinal vessel diameter measurements with the Zeiss retinal vessel analyser (RVA). During normoglycemia (100 mg/dl) flickering light induced a significant vasodilation of retinal arteries (+2.8+/-0.4%, p<0.0001) and veins (+2.6+/-0.4%, p<0.0001). At 300 mg/dl blood glucose the flicker response in retinal veins was significantly decreased by 55% (p=0.015 versus 100 mg/dl). The modified RVA employed in the present study provides high sensitivity and is capable of studying flicker-induced retinal vasodilation. Using this technique the present study confirms that flickering light stimulation of the human retina induces vasodilation in retinal vessels in healthy subjects. In addition, our data indicate that the retinal vessel response to flickering light stimulation is significantly reduced during hyperglycemia in humans. The relevance of this finding for diabetes-related eye disease remains to be shown.

Ocular surface changes and tear film alterations associated with sun gazing during a solar eclipse.

PURPOSE: A solar eclipse occurred in central Europe on August 11th, 1999. Following the eclipse, patients with ocular symptoms were investigated. Gazing at the sun without protection is liable to damage the retina. Our attention was focused on changes of the ocular surface and the tear film. METHODS: Forty-three patients were investigated within one week after the solar eclipse as baseline. 33 of them were followed up one year later. Visual acuity and the central visual-field were measured, and the ocular surface and the fundus were examined using a slit lamp. The quality of the lacrimal tear film was examined using Schirmer's test for the aqueous layer, break-up time for the mucous layer and interference observation for the lipid layer, measured by a slit lamp and a tearoscope. RESULTS: At the baseline 19 patients had non-specific visual problems. Pathological alterations of the tear film were seen in all three tear-film layers: Schirmer's test was pathological in 87%, break-up time decreased in 85%, the interference pattern of the lipid layer changed in 67% and there were changes in 87% using the tearoscope. One year later the non specific visual disorders had disappeared. Schirmer's test did not reveal much change from the baseline: 51% pathological, 24% remained pathological in break-up-time and the lipid layer was normalized except in 9%. Using the tearoscope, lipids were better than grade 3 in all patients. CONCLUSION: After gazing at a solar eclipse the ocular surface and tear film changed. While the aqueous layer remained pathological in many patients, the lipid layer and the mucous layer recovered spontaneously.