Fluorescence lifetime imaging in retinal artery occlusion.

PURPOSE Fluorescence lifetime imaging ophthalmoscopy is a technique to measure decay times of endogenous retinal fluorophores. The purpose of this study was to investigate fluorescence lifetimes in eyes with central and branch retinal artery occlusion. METHODS Twenty-four patients with central or branch retinal artery occlusion were included in this study. The contralateral unaffected fellow eye was used as control. Measurements were performed using a fluorescence lifetime imaging ophthalmoscope based on a HRA Spectralis system. Fluorescence excitation wavelength was 473 nm, and mean lifetimes were measured in a short (498-560 nm) and in a long (560-720 nm) spectral channel. Fluorescence lifetimes in the area of retinal artery occlusion were measured and compared to corresponding areas in contralateral unaffected eyes. Additionally, findings were correlated to optical coherence tomography measurements. RESULTS Retinal lifetime images of 24 patients with retinal artery occlusion were analyzed. Mean retinal fluorescence lifetimes were prolonged by 50% in the short and 20% in the long spectral channel in ischemic retinal areas up to 3 days after retinal artery occlusion compared to the contralateral unaffected eyes. In the postacute disease stage there was no difference between the lifetimes of affected areas and unaffected fellow eyes. CONCLUSIONS Retinal artery occlusion leads to significantly longer fluorescence lifetimes of the retina in the acute phase and may serve as a useful indicator for acute ischemic retinal damage.

Spontanoeusly resolved macroaneurysm associated with a congenital anomalous retinal artery

Purpose: To report the outcome of retinal artery macroaneurysm associated with a congenital anomalous retinal artery. Methods: The patient was examined with ophthalmoscopy and fluorescein angiography. Results: A 60-year-old woman presented with visual acuity of 20/80 in her right eye. She was found to have an abnormal retinal vessel emerging from the optic disk, passing toward the center of the macula, and looping back toward the disk. The center of the loop had a leaking macroaneurysm, which was treated conservatively. At the 4-month follow-up visit, the visual acuity in the right eye had improved to 20/20 with resolution of most of the macular edema, exudates, and hemorrhage. Conclusion: This case demonstrates that retinal artery macroaneurysm can be successfully managed with a conservative approach, even when associated with a congenital anomalous retinal vessel.

Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma.

BACKGROUND: : Superselective ophthalmic artery chemotherapy (SOAC) has recently been proposed as an alternative to intravenous chemoreduction for advanced intraocular retinoblastoma. Preliminary results appear promising in terms of tumor control and eye conservation, but little is known regarding ocular toxicity and visual prognosis. In this study, we report on the vascular adverse effects observed in our initial cohort of 13 patients. METHODS: : The charts of 13 consecutive patients with retinoblastoma who received a total of 30 injections (up to 3 injections of a single agent per patient at 3-week interval) of melphalan (0.35 mg/kg) in the ophthalmic artery between November 2008 and June 2010 were retrospectively reviewed. RetCam fundus photography and fluorescein angiography were performed at presentation and before each injection. Vision was assessed at the latest visit. RESULTS: : Enucleation and external beam radiotherapy could be avoided in all cases but one, with a mean follow-up of 7 months. Sectoral choroidal occlusive vasculopathy leading to chorioretinal atrophy was observed temporally in 2 eyes (15%) 3 weeks to 6 weeks after the beginning of SOAC and retinal arteriolar emboli in 1 eye 2 weeks after injection. There was no stroke or other clinically significant systemic side effects except a perioperative transient spasm of the internal carotid artery in one patient. Vision ranged between 20/1600 and 20/32 depending on the status of the macula. CONCLUSION: : Superselective ophthalmic artery chemotherapy was effective in all patients with no stroke or other systemic vascular complications. Unlike intravenous chemoreduction, SOAC is associated with potentially sight-threatening adverse effects, such as severe chorioretinal atrophy secondary to subacute choroidal occlusive vasculopathy or central retinal artery embolism, not to mention the risk of ophthalmic artery obstruction, which was not observed in this series. Further analysis of the risks and benefits of SOAC will define its role within the therapeutic arsenal. Meanwhile, we suggest that SOAC should be given in one eye only and restricted to advanced cases of retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy.

Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma.

BACKGROUND:: Superselective ophthalmic artery chemotherapy (SOAC) has recently been proposed as an alternative to intravenous chemoreduction for advanced intraocular retinoblastoma. Preliminary results appear promising in terms of tumor control and eye conservation, but little is known regarding ocular toxicity and visual prognosis. In this study, we report on the vascular adverse effects observed in our initial cohort of 13 patients. METHODS:: The charts of 13 consecutive patients with retinoblastoma who received a total of 30 injections (up to 3 injections of a single agent per patient at 3-week interval) of melphalan (0.35 mg/kg) in the ophthalmic artery between November 2008 and June 2010 were retrospectively reviewed. RetCam fundus photography and fluorescein angiography were performed at presentation and before each injection. Vision was assessed at the latest visit. RESULTS:: Enucleation and external beam radiotherapy could be avoided in all cases but one, with a mean follow-up of 7 months. Sectoral choroidal occlusive vasculopathy leading to chorioretinal atrophy was observed temporally in 2 eyes (15%) 3 weeks to 6 weeks after the beginning of SOAC and retinal arteriolar emboli in 1 eye 2 weeks after injection. There was no stroke or other clinically significant systemic side effects except a peroperative transient spasm of the internal carotid artery in one patient. Vision ranged between 20/1600 and 20/32 depending on the status of the macula. CONCLUSION:: Superselective ophthalmic artery chemotherapy was effective in all patients with no stroke or other systemic vascular complications. Unlike intravenous chemoreduction, SOAC is associated with potentially sight-threatening adverse effects, such as severe chorioretinal atrophy secondary to subacute choroidal occlusive vasculopathy or central retinal artery embolism, not to mention the risk of ophthalmic artery obstruction, which was not observed in this series. Further analysis of the risks and benefits of SOAC will define its role within the therapeutic arsenal. Meanwhile, we suggest that SOAC should be given in one eye only and restricted to advanced cases of retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy.

Combined central retinal vein and cilioretinal artery occlusion

We present a case of combined central retinal vein and cilioretinal artery occlusion which, due to the absence of the temporal branch retinal artery, was initially misdiagnosed as a combined central retinal vein occlusion and temporal branch retinal artery occlusion. Given that - in contrast to cases of combined central artery and central retinal vein occlusion - the prognosis for cilioretinal artery occlusion with central retinal vein occlusion is quite good, this case illustrates the importance of suspecting an unusual condition in the presence of a combined occlusion.

Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia

Glutamate is the major excitatory neurotransmitter in the retina and is removed from the extracellular space by an energy-dependent process involving neuronal and glial cell transporters. The radial glial Muller cells express the glutamate transporter, GLAST, and preferentially accumulate glutamate. However, during an ischaemic episode, extracellular glutamate concentrations may rise to excitotoxic levels. Is this catastrophic rise in extracellular glutamate due to a failure of GLAST? Using immunocytochemistry, we monitored the transport of the glutamate transporter substrate, D-aspartate, in the retina under normal and ischaemic conditions. Two models of compromised retinal perfusion were compared: (1) Anaesthetised rats had their carotid arteries occluded for 7 days to produce a chronic reduction in retinal blood flow. Retinal function was assessed by electroretinography. D-aspartate was injected into the eye for 45 min, Following euthanasia, the retina was processed for D-aspartate. GLAST and glutamate immunocytochemistry. Although reduced retinal perfusion suppresses the electroretinogram b-wave, neither retinal histology, GLAST expression, nor the ability of Muller cells to uptake D-aspartate is affected. As this insult does not appear to cause excitotoxic neuronal damage, these data suggest that GLAST function and glutamate clearance are maintained during periods of reduced retinal perfusion. (2) Occlusion of the central retinal artery for 60 min abolishes retinal perfusion, inducing histological damage and electroretinogram suppression. Although GLAST expression appears to be normal. its ability to transport D-aspartate into Muller cells is greatly reduced. Interestingly, D-aspartate is transported into neuronal cells, i.e. photoreceptors, bipolar and ganglion cells. This suggests that while GLAST is vitally important for the clearance of excess extracellular glutamate, its capability to sustain inward transport is particularly susceptible to an acute ischaemic attack. Manipulation of GLAST function could alleviate the degeneration and blindness that result from ischaemic retinal disease. (C) 2001 Elsevier Science Ltd, All rights reserved.

Periphere okklusive Vaskulopathie bei einer Patientin mit kombinierter Präeklampsie und Alpha-Thalassämie minor [Peripheral occlusive retinal vasculopathy in a woman with combined preeclampsia and alpha thalassemia minor].

Normalerweise eine Störung der ersten Schwangerschaft, ist die Präeklampsie charakterisiert durch eine arterielle Hypertonie (> 140 mmHg systolisch oder > 90 mmHg diastolisch), die in der Regel nach der 20. Schwangerschaftswoche auftritt und von einer Proteinurie begleitet wird [1]. Die Präeklampsie wird als ,,schwer" bezeichnet, wenn sie mit einer wesentlichen Erhöhung des Blutdrucks (> 160 mmHg systolisch oder > 110 mmHg diastolisch), schwerer Proteinurie, Oligurie, Lungenödem, abdominalen Schmerzen, Leberfunktionsstörungen, Thrombozytopenie und visuellen oder zerebralen Symptomen einhergeht. Eine Eklampsie wiederum ist durch die Entwicklung von tonisch-klonischen Anfällen bei einer präeklamptischen Patientin charakterisiert. Bei der Alpha-Thalassämie tritt ein Defekt von 2 oder mehr der 4 Alpha-Globin-Gene auf. Von einer Alpha-Thalassämie minor spricht man, wenn 2 Alpha-Ketten-Gene deletiert sind. Sie tritt häufig bei Menschen aus Afrika, Südostasien, dem westindischen und mediterranen Raum auf. Die Alpha-Thalassämie minor verursacht eine milde bis moderate mikrozytäre Anämie. Wir berichten über eine Patientin mit peripherer okklusiver Vaskulopathie im Rahmen einer kombinierten Präeklampsie und Alpha-Thalassämie minor.

The vasodilatory effect of juxta-arteriolar microinjection of endothelinA receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas.

Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.

Retinal vessel oxygen saturation and its correlation with structural changes in retinitis pigmentosa.

PURPOSE: To study the influence of retinal structural changes on oxygen saturation in retinitis pigmentosa (RP) patients. METHODS: Oximetry measurements were performed on 21 eyes of 11 RP patients and compared to 24 eyes of 12 controls. Retinal oxygen saturation was measured in all major retinal arterioles (A-SO₂) and venules (V-SO₂) with an oximetry unit of the retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Oximetry data were compared with morphological changes measured by Cirrus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA, USA, macular thickness protocol). RESULTS: In RP patients, the retinal A-SO₂ and V-SO₂ levels were higher at 99.3% (p = 0.001, anova based on mixed-effects model) and 66.8% (p < 0.001), respectively, and the difference between the two (A-V SO₂) was lower at 32.5% (p < 0.001), when compared to the control group (92.4%; 54.0%; 38.4%, respectively). With the RP group, the A-V SO₂ correlated positively, not only with central macular thickness, but also with retinal thickness, in zones 2 and 3 (p = 0.006, p = 0.007, p = 0.014). CONCLUSION: These data indicate that oxygen metabolism was altered in RP patients. Based on our preliminary results, retinal vessel saturation correlated with structural alterations in RP. This method could be valuable in monitoring disease progression and evaluating a potential therapeutic response.

Occlusion postcontusionnelle de l'artère et de la veine centrale de la rétine [Post-concussion occlusion of the central artery and vein of the retina]

BACKGROUND: Combined simultaneous occlusion of the central retinal artery and central retinal vein occurs very rarely and has been observed in patients with systemic disorders such as leukaemia. CASE REPORT: We report a case of a young man who suffered a combined retinal vascular occlusion with occlusion of the posterior ciliary arteries following blunt trauma to the face with massive haematoma of the lids. To our knowledge, this is the first time that such a sequence of events has been recorded.

Phosphene Thresholds Elicited by Transcorneal Electrical Stimulation in Healthy Subjects and Patients with Retinal Diseases

PURPOSE. To evaluate electrically evoked phosphene thresholds (EPTs) in healthy subjects and in patients with retinal disease and to assess repeatability and possible correlations with common ophthalmologic tests. METHODS. In all, 117 individuals participated: healthy subjects (n = 20) and patients with retinitis pigmentosa (RP, n = 30), Stargardt's disease (STG, n = 14), retinal artery occlusion (RAO, n = 20), nonarteritic anterior ischemic optic neuropathy (NAION, n = 16), and primary open-angle glaucoma (POAG, n = 17). EPTs were determined at 3, 6, 9, 20, 40, 60, and 80 Hz with 5+5-ms biphasic current pulses using DTL electrodes. Subjects were examined twice (test-retest range: 1-6 weeks). An empirical model was developed to describe the current-frequency relationship of EPTs. Visual acuity, visual field (kinetic + static), electrophysiology (RP, RAO, STG: Ganzfeld-electroretinography [ERG]/multifocal-ERG; POAG: pattern-ERG; NAION: VEP), slit-lamp biomicroscopy, fundus examination, and tonometry were assessed. RESULTS. EPTs varied between disease groups (20 Hz: healthy subjects: 0.062 +/- 0.038 mA; STG: 0.102 +/- 0.097 mA; POAG: 0.127 +/- 0.09 mA; NAION: 0.244 +/- 0.126 mA; RP: 0.371 +/- 0.223 mA; RAO: 0.988 +/- 1.142 mA). In all groups EPTs were lowest at 20 Hz. In patients with retinal diseases and across all frequencies EPTs were significantly higher than those in healthy subjects, except in STG at 20 Hz (P = 0.09) and 40 Hz (P = 0.17). Test-retest difference at 20 Hz was 0.006 mA in the healthy group and 0.003-0.04 mA in disease groups. CONCLUSIONS. Considering the fast, safe, and reliable practicability of EPT testing, this test might be used more often under clinical circumstances. Determination of EPTs could be potentially useful in elucidation of the progress of ophthalmologic diseases, either in addition to standard clinical assessment or under conditions in which these standard tests cannot be used meaningfully. (ClinicalTrials.gov number, NCT00804102.) (Invest Ophthalmol Vis Sci. 2012; 53: 7440-7448) DOI:10.1167/iovs.12-9612

Comparison of subjective and objective methods to determine the retinal arterio-venous ratio using fundus photography

Purpose: To assess the inter and intra observer variability of subjective grading of the retinal arterio-venous ratio (AVR) using a visual grading and to compare the subjectively derived grades to an objective method using a semi-automated computer program. Methods: Following intraocular pressure and blood pressure measurements all subjects underwent dilated fundus photography. 86 monochromatic retinal images with the optic nerve head centred (52 healthy volunteers) were obtained using a Zeiss FF450+ fundus camera. Arterio-venous ratios (AVR), central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated on three separate occasions by one single observer semi-automatically using the software VesselMap (ImedosSystems, Jena, Germany). Following the automated grading, three examiners graded the AVR visually on three separate occasions in order to assess their agreement. Results: Reproducibility of the semi-automatic parameters was excellent (ICCs: 0.97 (CRAE); 0.985 (CRVE) and 0.952 (AVR)). However, visual grading of AVR showed inter grader differences as well as discrepancies between subjectively derived and objectively calculated AVR (all p < 0.000001). Conclusion: Grader education and experience leads to inter-grader differences but more importantly, subjective grading is not capable to pick up subtle differences across healthy individuals and does not represent true AVR when compared with an objective assessment method. Technology advancements mean we no longer rely on opthalmoscopic evaluation but can capture and store fundus images with retinal cameras, enabling us to measure vessel calibre more accurately compared to visual estimation; hence it should be integrated in optometric practise for improved accuracy and reliability of clinical assessments of retinal vessel calibres. © 2014 Spanish General Council of Optometry.

Retinal microvascular dysfunction occurs similarly in Alzheimer's disease and primary open angle glaucoma patients

Purpose: The exact nature of the relationship between Alzheimer’s disease (AD) and primary open angle glaucoma (POAG) is still the subject of debate. One factor attributed to the aetiology of both conditions is vascular dysfunction. This study aimed to investigate the similarities and differences in retinal microvascular function between mild AD patients, early stage POAG patients and healthy controls Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 22 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p=0.014), which was not replicated in the healthy age and cardiovascular risk matched controls (p>0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p=0.001) Conclusions: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. These comparable signs may reflect similarities in the pathophysiological processes that occur in the development of both conditions