Measuring hyperemic response to light flicker stimulus using continuous laser speckle flowgraphy in mice.

Alterations in neurovascular coupling have been associated with various ocular, cerebral, and systemic vascular disorders. In the eye, changes in vessel caliber by dynamic vessel analysis have been used to measure neurovascular coupling following a light flicker stimulus. Here, we present a new protocol for quantifying light-flicker induced hyperemia in the C57/Bl6J mouse retina using laser speckle flowgraphy (LSFG). Our protocol was adapted from protocols used in human subjects. By acquiring continuous time series data, we detected significant increase in blood flow. These responses are maintained with low variability over multiple imaging sessions, indicating these methods may be applied in serial studies of neurovascular coupling.

Plexus-specific effect of flicker-light stimulation on the retinal microvasculature assessed with optical coherence tomography angiography.

In neural tissues, the coupling between neural activity and blood flow is a physiological key principle in blood flow regulation. We used optical coherence tomography angiography to investigate stimulus-evoked hemodynamic responses in different microvascular layers of the human retina. Twenty-two healthy subjects were included. Vessel density before and during light stimulation was measured using optical coherence tomography angiography and assessed for the superficial, intermediate, and deep capillary plexus of the retinal circulation. Volumetric blood flow was measured using a custom-built Doppler optical coherence tomography system. Our results show that flicker stimulation induced a significant increase in the vessel density of +9.9 ± 6.7% in the superficial capillary plexus, +6.6 ± 1.7% in the intermediate capillary plexus, and +4.9 ± 2.3% in the deep capillary plexus. The hyperemic response of the superficial capillary plexus was significantly higher compared to the intermediate capillary plexus (P = 0.02) and deep capillary plexus (P = 0.002). Volumetric retinal blood flow increased by +39.9 ± 34.9% in arteries and by +29.8 ± 16.8% in veins. In conclusion, we showed a strong increase in the retinal microvascular density in response to light stimulation, with the most pronounced effect in the superficial capillary plexus. This is compatible with the hypothesis that the microvasculature exerts an important function in mediating functional hyperemia in humans.NEW & NOTEWORTHY We present vessel density alterations in response to flicker stimulation using optical coherence tomography angiography and identified the superficial capillary plexus as the layer with the most pronounced effect. This points out the physiological importance of the microvasculature in mediating functional hyperemia and suggests a fine-tuned plexus-specific mechanism to meet cellular metabolic demands.

In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects.

The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors. Established rodent models of ocular inflammatory diseases were used to determine therapeutic effects in living animals. The drugs were administered systemically after predetermination of their blood levels to ensure bioavailability at an appropriate dose level. Whereas compounds selective for a single prostanoid receptor typically exhibited modest but statistically significant inhibition, AGN 211377 profoundly inhibited S-antigen-induced uveitis and laser-induced retinal neovascularization. Consistent with previous polypharmacological studies on chemokine/cytokine release from human macrophages, the prostanoid EP1 receptor played a permissive role in suppressing neovascularization and inflammation in vivo Comparing AGN 211377 with a close structural congener lacking EP1 antagonism (AGN 197727), AGN 197727 was much less active than AGN 211377, but pronounced anti-inflammatory and angiostatic effects were achieved by adding the EP1 antagonist compound (SC-51322) to AGN 197727 in the systemic dosing regimen. Further, AGN 211377 produced superior anti-inflammatory activity compared with the nonsteroidal anti-inflammatory agent ketorolac. These results indicate the value of using a polypharmacological approach in the design of novel therapeutic agents in preference to compounds targeting a single receptor or enzyme. A compound such as AGN 211377 may represent more effective therapy than COX inhibitors in treating uveitis and ocular diseases where neovascularization is a significant part of the pathology.-Woodward, D. F., Wang, J. W., Ni, M., Bauer, A., Martos, J. L., Carling, R. W., Poloso, N. J. In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects.

ABNORMAL RETINAL REFLECTIVITY TO SHORT-WAVELENGTH LIGHT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia Type 2 (MacTel) is a bilateral, progressive, potentially blinding retinal disease characterized by vascular and neurodegenerative signs, including an increased parafoveal reflectivity to blue light. Our aim was to investigate the relationship of this sign with other signs of macular telangiectasia Type 2 in multiple imaging modalities. METHODS: Participants were selected from the MacTel Type 2 study, based on a confirmed diagnosis and the availability of images. The extent of signs in blue-light reflectance, fluorescein angiographic, optical coherence tomographic, and single- and dual-wavelength autofluorescence images were analyzed. RESULTS: A well-defined abnormality of the perifovea is demonstrated by dual-wavelength autofluorescence and blue-light reflectance in early disease. The agreement in area size of the abnormalities in dual-wavelength autofluorescence and in blue-light reflectance images was excellent: for right eyes: ρ = 0.917 (P < 0.0001, 95% confidence interval 0.855-0.954, n = 46) and for left eyes: ρ = 0.952 (P < 0.0001, 95% confidence interval 0.916-0.973, n = 49). Other changes are less extensive initially and expand later to occupy that area and do not extend beyond it. CONCLUSION: Our findings indicate that abnormal metabolic handling of luteal pigment and physical changes giving rise to increased reflectance are widespread in the macula throughout the natural history of the disease, precede other changes, and are relevant to early diagnosis.

Evaluation of Vascular Changes with Optical Coherence Tomography Angiography after Plaque Radiotherapy of Choroidal Melanoma.

AIM: The purpose of this paper was to evaluate whether optical coherence tomography angiography (OCT-A) can be used to quantify the vascular changes in radiation maculopathy, and changes in the tumor vasculature in eyes treated with plaque radiotherapy for choroidal melanoma. METHODS: In this prospective study, we evaluated 39 Caucasian patients with choroidal melanoma (39 eyes) treated with ruthenium-106 plaque radiotherapy. The patients underwent complete ophthalmic examination, bulbar echography, and OCT-A before and 1 year after treatment. RESULTS: At baseline, the mean best-corrected visual acuity (BCVA) in the affected eyes was 0.35 ± 0.40 logMAR, and the mean tumor thickness was 2.68 ± 0.25 mm at A-scan echography. After treatment, the mean BCVA increased to 0.41 logMAR, the mean tumor thickness decreased to 1.66 ± 0.23 mm, and the tumor basal diameter was significantly reduced (U = 108, p = 0.001). Moreover, the capillary vessel density was significantly lower in all Early Treatment of Diabetic Retinopathy Study sectors, and both the vessel and flow areas were significantly reduced (p = 0.030 and p = 0.001, respectively). CONCLUSIONS: OCT-A is a noninvasive, reliable method with which to quantify the vessel changes in radiation maculopathy and, given the association between vascularization and malignancy, this procedure may be an aid in treatment decision-making and in monitoring the efficacy of treatment.

The effect of simulated cataract light scatter on retinal vessel oximetry.

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p = 0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter.

Retinal neurovascular coupling in patients with glaucoma and ocular hypertension and its association with the level of glaucomatous damage.

PURPOSE: To analyze neurovascular coupling in the retina of untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. PATIENTS AND METHODS: Maximal vessel dilation in response to flicker light was analyzed with Retinal Vessel Analyzer (RVA) in temporal superior/inferior arterioles and veins in 51 POAG patients, 46 OHT and 59 control subjects. RVA parameters were compared between groups, between contralateral POAG eyes, and correlated to intraocular pressure, visual field mean defect and retinal nerve fiber layer thickness. RESULTS: POAG eyes demonstrated generally smaller response of all vessels to flicker light than the other two groups (ANOVA p=0.026; mean arterial flicker response in percent of baseline, averaged superior and inferior was 3.48 ± 2.22 % for controls , 2.35 ± 2.06 % for POAG patients , and 2.97 ± 2.35 % for OHT patients; corresponding values for venules were 3.88 ± 1.98 %, 2.89 ± 1.72 %, 3.45 ± 2.77 %). There was no difference in flicker response between the eye with more and less advanced damage in each patient of the POAG group (ANOVA p=0.79). Correlation of flicker response to intraocular pressure (IOP) was borderline at best, correlations to the level of glaucomatous damage were not significant. Correlation of flicker response of superior and inferior vessels of the same eye was significant for the arteries (Pearson r=0.23, p=0.004), as well as venules (r=0.52, p<0.001). CONCLUSION: General vessel response to flicker light was decreased in POAG patients, compared to normal controls and OHT patients. In contrast to significant correlation between the two contralateral eyes of the flicker response itself, only its borderline correlation to IOP was seen. There was no correlation to the level of damage, altogether indicating a systemic dysregulation phenomenon. GRANTS: Swiss National Foundation Grant 3200B0-113685, Velux Stiftung Grant, Freie Akademische Gesellschaft (FAG) Grant, Pfizer Inc. Grant CLINICAL TRIAL REGISTRATION REFERENCE NUMBER: ClinicalTrials.gov NCT00430209.

Flow of energy in the outer retina in darkness and in light.

Structural features of neurons create challenges for effective production and distribution of essential metabolic energy. We investigated how metabolic energy is distributed between cellular compartments in photoreceptors. In avascular retinas, aerobic production of energy occurs only in mitochondria that are located centrally within the photoreceptor. Our findings indicate that metabolic energy flows from these central mitochondria as phosphocreatine toward the photoreceptor's synaptic terminal in darkness. In light, it flows in the opposite direction as ATP toward the outer segment. Consistent with this model, inhibition of creatine kinase in avascular retinas blocks synaptic transmission without influencing outer segment activity. Our findings also reveal how vascularization of neuronal tissue can influence the strategies neurons use for energy management. In vascularized retinas, mitochondria in the synaptic terminals of photoreceptors make neurotransmission less dependent on creatine kinase. Thus, vasculature of the tissue and the intracellular distribution of mitochondria can play key roles in setting the strategy for energy distribution in neurons.

Novel versus traditional risk markers for diabetic retinopathy.

AIMS/HYPOTHESIS: To explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR). METHODS: A clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously. RESULTS: There were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p < 0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively). CONCLUSIONS/INTERPRETATION: ApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.

Retinal compensatory changes after light damage in albino mice.

PURPOSE: To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. METHODS: BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. RESULTS: Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. CONCLUSIONS: In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function.

Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration.

PURPOSE: To analyze the damage produced by light in mydriatic and miotic albino retinas under two different sources of light. METHODS: Albino Sprague Dawley female rats were exposed to 3,000 lx during 48 h under two different light sources: linear and circular bulbs. Before exposure, their left pupils were dilated. Before and at different times after light exposure (ALE), electroretinographic signals were recorded. One week before processing, retinal ganglion cells (RGCs) were traced by applying fluorogold on the superior colliculi. Just before processing, some animals were intravenously injected with horseradish peroxidase to analyze retinal vascular leakage. At different times ALE, animals were sacrificed and their retinas dissected as whole mounts or cross-sections. Cross-sections were used to study the retinal degeneration and to detect apoptotic nuclei by the transferase dUTP nick end labeling (TUNEL) technique. Whole mounts were used to analyze vascular leakage; investigate the nerve fiber layer, identified by immunodetection of neurofilaments; and quantify the whole population of RGCs identified by fluorogold tracing and Brn3a immunodetection. With the quantitative data, detailed isodensity maps were generated to study the spatial loss of RGCs. RESULTS: Phototoxicity causes an immediate and permanent abolishment of the electroretinographic response. Early ALE, photoreceptors degenerate by apoptosis and this death is more severe in mydriatic conditions and under circular bulbs. Photoreceptor loss starts in an arciform dorsomedial retinal area, but at 3 months ALE has spread to the whole retina and there are no differences related to either pupil dilation or light source. Three months ALE, RGC axons show distorted trajectories and abnormal expression of neurofilaments. Six months or more ALE, there is significant death of RGCs caused by axonal strangulation by displaced inner retinal vessels. Topography of the surviving RGCs shows that their loss is not uniform throughout the retina. CONCLUSIONS: Light damage to photoreceptors depends on pupil dilation and light source, but affects all retinal layers with time. These deteriorative events are also observed in light-induced and inherited retinal degenerations in pigmented animals, but occur differently. Thus, the role of ocular pigmentation and the etiology of photoreceptor degeneration on retinal remodelling deserve further investigation.

Dynamic retinal vessel response to flicker in obesity: A methodological approach.

Obesity and related metabolic disorders affect vascular endothelial function. The use of the Dynamic Vessel Analyzer (DVA) represents a modern methodological approach to analyze vascular function in the retinal microcirculation. Whether the dynamic reaction to flicker stimulation in retinal vessels is altered in obese subjects is investigated. Retinal vessel reactions to flicker stimulation were examined by DVA in 46 obese individuals (49.6±10.0years) and 46 age- and gender-matched healthy controls. The clinical examination included anthropometry, blood pressure measurements and blood sampling. Mean maximal arteriolar dilation in response to flicker was reduced in the obese group (3.2±1.8%) compared to controls (4.1±2.0%, p<0.05) and the time to maximal arteriolar dilation was prolonged (18.0±9.4s vs. 14.6±3.8s, p=0.03). In addition, mean maximal venular dilation was reduced in obese subjects (3.9±1.7% vs. 4.7±1.8%, p<0.05). Among the microvascular parameters, the most significant correlation with waist circumference was found for the "area under the reaction curve 50-80s after stimulation" in arterioles (r=-0.40; p<0.001). Functional retinal arteriolar reactivity to flicker stimulation differs between obese and healthy lean subjects. Time course analysis of retinal vessel response and its quantitative parameters can comprehensively characterize alterations of retinal vessel reactivity in metabolic disease.

Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice.

PURPOSE: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. MATERIALS AND METHODS: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a (137)Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. RESULTS: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P<0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P<0.05), indicating that pathological angiogenesis was intact. CONCLUSIONS: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone marrow cells are involved in the pathology or severity of retinal angiogenic diseases.

Wide-Field (15â€Š× 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

PURPOSE: The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA). DESIGN: Single-centre retrospective review. METHODS: Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA). RESULTS: At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P < 0.001, and 46% vs 48%, P = 0.001, respectively), peripapillary region (66% vs 77%, P < 0.001, and 66% vs 72%, P = 0.001, respectively), and papillomacular bundle (60% vs 68%, P < 0.001, and 61% vs 64%, P = 0.03, respectively). Comparison (no CERR vs controls) revealed nonsignificant foveal avascular zone enlargement (1.20 vs 0.23 mm, P = 0.16) and reduction of CVD in the superficial plexus (46% vs 47%, P = 0.008), and not the deep plexus (48% vs 48%, P = 0.42) of the total wide-field. Comparison of irradiated eyes (CERR vs no CERR) showed reduction of CVD in the superficial and deep plexus of the total wide-field (43% vs 46%, P < 0.006, and 46% vs 48% P < 0.02, respectively), peripapillary region (66% vs 74%, P < 0.001, and 66% vs 72% P < 0.01, respectively), and superficial plexus in the papillomacular bundle (60% vs 65%, P = 0.03). CONCLUSIONS: Following plaque radiotherapy for choroidal melanoma, wide-field swept-source optical coherence tomography angiography demonstrates retinal microvascular abnormalities in the CVD in eyes with and without CERR. These findings are important in early detection and monitoring of radiation retinopathy.

Low power laser treatment of the retina ameliorates neovascularisation in a transgenic mouse model of retinal neovascularisation.

This study was designed to determine if low power laser therapy can achieve amelioration of vasoproliferation yet preserve useful vision in the treated area in a transgenic mouse model of retinal neovascularisation. The mice were anaesthetised and the pupils dilated for ERG and fundus fluorescein angiography on postnatal day 32. The left eyes were treated with approximately 85 laser spots (532 nm, 50 ms, 300 microm diameter) at a power level of 20 mW at the cornea. The eyes were examined using ERG and fluorescein angiography, one, four and six weeks later. Flat mounts of FITC-dextran infused retinas, retinal histology and PEDF immunohistochemistry was studied one or six weeks after laser treatment. In untreated eyes the expected course of retinal neovascularisation in this model was observed. However, retinal neovascularisation in the laser treated eye was significantly reduced. The laser parameters chosen produced only mild lesions which took 10-20 s to become visible. ERG responses were comparable between the treated and untreated eyes, and histology showed only partial loss of photoreceptors in the treated eyes. PEDF intensity corresponded inversely with the extent of neovascularisation. Low power panretinal photocoagulation can inhibit retinal neovascularisation and yet preserve partial visual function in this transgenic mouse model of retinal neovascularisation.

[Response of retinal vessel diameter to flicker-light in vasospastics compared to healthy controls]. / Flickerlichtprovokation bei Vasospastikern verglichen mit gesunden Kontrollpersonen.

BACKGROUND: Vascular dysregulation is considered to be a risk factor in several ophthalmic diseases. The purpose of this study was to evaluate the reaction of retinal vessels to flicker light in otherwise healthy subjects with a vasospastic propensity. PATIENTS AND METHODS: Thirty healthy Caucasians, aged between 18-35 years were recruited for this study and grouped into vasospastics, based on a history of frequent cold hands, even in summer, with concordant findings in nailfold capillary microscopy, or as controls, if such a history was absent. The reaction of the retinal vascular diameter to flicker light was observed in a distance of two to three discs diameters away from the optic nerve head with the retinal vessel analyser. Three phases of flicker light of twenty seconds followed by baseline light phases of eighty seconds were recorded. The maximal vasodilatory amplitude of each flicker phase was determined and the results averaged. RESULTS: The maximal average dilatory amplitude at the arterial side reached (mean +/- SD) 2.9 +/- 1.7 % and 4.8 +/- 2.6 % of the baseline amplitude respectively in vasospastic subjects and in healthy controls (t = 2.34; p = 0.025). The reaction at the venous side was statistically comparable in both groups. CONCLUSIONS: Otherwise healthy, vasospastic subject disclosed an altered reaction of the retinal vasculature to flicker light in this study.

[Cataract extraction and blue light--impact on the retina]. / Kataraktextraktion und Blaulicht--Wirkung auf die Netzhaut.

This review focuses on the scientific background for the use of "yellow artificial lenses". We will address the fact that numerous basic scientific publications point to a rationale for this practice although it is often difficult to derive clear-cut evidence from clinical epidemiological studies for the preventive use of yellow artificial lenses. In the first part we refer to studies showing that especially the shortwave part of the visible spectrum of light can be harmful for the retina and optic nerve. For this, we have screened the literature for the major sources of radical production and for the targets of oxidative stress after impingement of "blue light" on the retina. Furthermore, we can show that many studies in cell and molecular biology, animal experiments and first clinical trials point to a preferential use of yellow-tinted lenses especially in the elderly and AMD patients.

Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors.

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

Adaptation of retinal ganglion cell function during flickering light in the mouse.

Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina. Little is known about flicker-induced changes of activity of retinal neurons themselves. We non-invasively investigated flicker-induced changes of retinal ganglion cell (RGC) function in common inbred mouse strains using the pattern electroretinogram (PERG), a sensitive measure of RGC function. Flicker was superimposed on the pattern stimulus at frequencies that did not generate measurable flicker-ERG and alter the PERG response. Transition from flicker at 101 Hz (control) to flicker at 11 Hz (test) at constant mean luminance induced a slow reduction of PERG amplitude to a minimum (39% loss in C57BL/6J mice and 52% loss in DBA/2J mice) 4-5 minutes after 11 Hz flicker onset, followed by a slow recovery to baseline over 20 minutes. Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse. This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease. The non-contact flicker-PERG method opens the possibility of combined assessment of neural and vascular response dynamics.

Microvascular abnormalities secondary to radiation therapy in neovascular age-related macular degeneration: findings from the INTREPID clinical trial.

PURPOSE: To report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites. METHODS: Two hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. INTERVENTIONS: 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment. RESULTS: The frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3. CONCLUSION: Treatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.