A COVID-19-Related Retinopathy Case Report.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.

In a consanguineous Pakistani family with two affected individuals, a homozygous variant Gly399Val in the eighth transmembrane domain of the taurine transporter SLC6A6 was identified resulting in a hypomorph transporting capacity of ~15% compared with normal. Three-dimensional modeling of this variant has indicated that it likely causes displacement of the Tyr138 (TM3) side chain, important for transport of taurine. The affected individuals presented with rapidly progressive childhood retinal degeneration, cardiomyopathy and almost undetectable plasma taurine levels. Oral taurine supplementation of 100 mg/kg/day resulted in maintenance of normal blood taurine levels. Following approval by the ethics committee, a long-term supplementation treatment was introduced. Remarkably, after 24-months, the cardiomyopathy was corrected in both affected siblings, and in the 6-years-old, the retinal degeneration was arrested, and the vision was clinically improved. Similar therapeutic approaches could be employed in Mendelian phenotypes caused by the dysfunction of the hundreds of other molecular transporters.

Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.

Infantile and childhood-onset cataracts form a heterogeneous group of disorders; among the many genetic causes, numerous pathogenic variants in additional genes associated with autosomal-recessive infantile cataracts remain to be discovered. We identified three consanguineous families affected by bilateral infantile cataracts. Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271∗) in large family F385 (nine affected individuals; LOD score = 5.18 at θ = 0), frameshift deletion c.2947_2948del (p.Asp983∗) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs∗41) in family F3 (one affected individual). The phenotypes of all affected individuals include infantile-onset cataracts. RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells, and leads to a ∼50% reduction in electroretinography amplitudes in young flies. DNMBP regulates the shape of tight junctions, which correspond to the septate junctions in invertebrates, as well as the assembly pattern of E-cadherin in human epithelial cells. E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans. We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans.

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.

Surgical and visual outcome for recurrent retinal detachment surgery.

Purpose. To evaluate the anatomical and functional outcome of repeated surgeries for recurrent retinal detachment. Methods. We retrospectively reviewed 70 cases with refractory retinal detachment of various etiologies that required multiple operations. Anatomical success (attached retina) or failure (totally/partially-detached retina) was assessed biomicroscopically. The BCVA was used for the evaluation of the functional outcome, at presentation and at the end of follow-up. Various pre-, intra-, and postoperative factors were associated with anatomical success or failure as well as with final functionality. Results. The mean number of surgeries was 4 (range: 2 to 10). The anatomical success rate was 80% (56 attached cases, 14 detached cases). 29% of the attached cases had a BCVA better than 20/40 (Snellen chart). The number of operations doesn't seem to affect significantly the final visual acuity. The PVR was found to affect both the anatomical and functional outcome (P = 0.014 & P = 0.002, respectively). Conclusions. In the present study, it is suggested that multiple operations for refractory retinal detachment may result in successful anatomic results, with a fare functional outcome at the same time. Eventually, we verified that the existence of PVR worsens the prognosis.

Development of an intravitreal peptide (BQ123) sustained release system based on poly(2-hydroxyoctanoic acid) aiming at a retinal vasodilator response.

PURPOSE: Development of a novel formulation for intravitreal administration, in which the endothelinA receptor antagonist BQ123 is incorporated in a biodegradable and injectable polymer drug delivery system, poly(2-hydroxyoctanoic acid), aiming at a prolonged retinal vasodilator response. METHODS: BQ123 was incorporated in poly(2-hydroxyoctanoic acid), leading to an easily injectable, homogenous mixture. In vitro release profiles were obtained in porcine vitreous humor (n=6). The ex vivo biocompatibility was studied by placing the formulation in contact with porcine retinal tissues and performing histology. In a pilot in vivo study, the change in retinal vessel diameter of mini pigs (n=2) was followed over 3 h after an intravitreal injection of the formulation, as well as the release of BQ123 from the polymer system for approximately 7 days (n=6). RESULTS: In vitro, a constant release profile was obtained, releasing approximately 91% of BQ123 within 7 days. Histology on the porcine retinal tissues showed good ex vivo biocompatibility. In vivo, a vasodilative response was observed, with a retinal vessel diameter increase from 14% after 15 min, for approximately 39% after 3 h. At t=3 h, the BQ123 concentration in the vitreous humor was 0.7±0.2 µg/mL, followed by 1.5±1.0 and 1.1±0.8 µg/mL after 3 and 7 days, respectively. 39.9%±6.0% of BQ123 was still present in the polymer depot at t=7 days. CONCLUSIONS: The results show that an intravitreal injection of this drug delivery system leads to a prolonged vasodilative response and a BQ123 release over 7 days, suggesting its therapeutic potential in the management of retinal ischemic conditions.

Autophagy induction does not protect retina against apoptosis in ischemia/reperfusion model.

The role played by autophagy after ischemia/reperfusion (I/R) in the retina remains unknown. Our study investigated whether ischemic injury in the retina, which causes an energy crisis, would induce autophagy. Retinal ischemia was induced by elevation of the intraocular pressure and modulation of autophagic markers was analyzed at the protein levels in an early and late phase of recovery. Following retinal ischemia an increase in LC3BII was first observed in the early phase of recovery but did not stay until the late phase of recovery. Post-ischemic induction of autophagy by intravitreal rapamycin administration did not provide protection against the lesion induced by the ischemic stress. On the contrary, an increase in the number of apoptotic cells was observed following I/R in the rapamycin treated retinas.

Safety of 20-gauge transconjunctival sutureless vitrectomy.

PURPOSE: To study the safety of 20-gauge transconjunctival sutureless vitrectomy. METHODS: Clinical data of patients who underwent 20-gauge transconjunctival sutureless vitrectomy for the first time, for various disorders, were reviewed retrospectively. The main outcome measures were the number of sclerotomies requiring suturing as well as the intra- and postoperative complications. RESULTS: A total of 179 operations were performed. Indications for vitrectomy included 68 idiopathic epiretinal membranes, 26 macular holes, 23 phakic and 16 pseudophakic retinal detachments, and 46 various other, less common etiologies. Of these 179 operations, 166 (93%) were sutureless. Of the 537 sclerotomies created, 25 (5%) received a single transconjunctival-scleral suture. Intraoperative complications included premature dislodging of the cannulas in 2 sclerotomies and an iatrogenic horseshoe tear at 1 sclerotomy site. Postoperative complications comprised transient hypotony in 14 cases, subconjunctival gas in 2 cases, and choroidal effusion in 1 case. No serious complications (such as endophthalmitis) were observed. CONCLUSION: 20-gauge transconjunctival sutureless vitrectomy can be considered safe, as the intra- and postoperative complications observed are neither numerous nor significant. Sclerotomies appear to be safe and relatively easy to perform, without compromising the advantages of sutureless surgery.

Long-term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration.

PURPOSE: To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). METHODS: Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow-up. RESULTS: A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3-10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = -0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow-up (p > 0.05). CONCLUSIONS: These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.

Design and in vitro assessment of L-lactic acid-based copolymers as prodrug and carrier for intravitreal sustained L-lactate release to reverse retinal arteriolar occlusions.

Ophthalmic conditions in which the retinal vasculature is obstructed generally lead to vision loss. Administration of the vasodilator L-lactate might offer a treatment strategy by restoring the blood flow, but unfortunately its effect after single intravitreal injection is short-lived. This study describes a concept in which the sustained release of L-lactic acid from a biodegradable copolymer system is investigated. The 50:50 (n/n) copolymer system, composed of L-lactic acid and L,D-2-hydroxyoctanoic acid, is a viscous injectable that will form an intravitreal drug depot. Hydrolysis of the copolymer will automatically lead to the release of L-lactic acid, which will convert to L-lactate at physiological pH, thereby providing a carrier and pro-drug in one. In vitro and ex vivo release studies demonstrate an L-lactic acid release over several weeks. Biocompatibility of the co-polymer and its degradation products is shown on a human retinal pigment epithelial cell line and on ex vivo retinal tissues. A low molecular weight copolymer (1200 g/mol) with low polydispersity has promising properties with a constant release profile, good biocompatibility and injectability.

Preretinal partial pressure of oxygen gradients before and after experimental pars plana vitrectomy.

PURPOSE: To evaluate preretinal partial pressure of oxygen (PO2) gradients before and after experimental pars plana vitrectomy. METHODS: Arteriolar, venous, and intervascular preretinal PO2 gradients were recorded in 7 minipigs during slow withdrawal of oxygen-sensitive microelectrodes (10-µm tip diameter) from the vitreoretinal interface to 2 mm into the vitreous cavity. Recordings were repeated after pars plana vitrectomy and balanced salt solution (BSS) intraocular perfusion. RESULTS: Arteriolar, venous, and intervascular preretinal PO2 at the vitreoretinal interface were 62.3 ± 13.8, 22.5 ± 3.3, and 17.0 ± 7.5 mmHg, respectively, before vitrectomy; 97.7 ± 19.9, 40.0 ± 21.9, and 56.3 ± 28.4 mmHg, respectively, immediately after vitrectomy; and 59.0 ± 27.4, 25.2 ± 3.0, and 21.5 ± 4.5 mmHg, respectively, 2½ hours after interruption of BSS perfusion. PO2 2 mm from the vitreoretinal interface was 28.4 ± 3.6 mmHg before vitrectomy; 151.8 ± 4.5 mmHg immediately after vitrectomy; and 34.8 ± 4.1 mmHg 2½ hours after interruption of BSS perfusion. PO2 gradients were still present after vitrectomy, with the same patterns as before vitrectomy. CONCLUSION: Preretinal PO2 gradients are not eliminated after pars plana vitrectomy. During BSS perfusion, vitreous cavity PO2 is very high. Interruption of BSS perfusion evokes progressive equilibration of vitreous cavity PO2 with concomitant progressive return of preretinal PO2 gradients to their previtrectomy patterns. This indicates that preretinal diffusion of oxygen is not altered after vitrectomy. The beneficial effect of vitrectomy in ischemic retinal diseases or macular edema may be related to other mechanisms, such as increased oxygen convection currents or removal of growth factors and cytokines secreted in the vitreous.

Retinal blood flow evaluation.

Much of our basic knowledge of retinal blood flow regulation is based on data obtained from animal experiments through the use of invasive techniques. However, during the last decades, major developments in the field of optics and lasers have led to a variety of noninvasive techniques, which have been applied to the human eye for the investigation of retinal hemodynamics, and more specifically the regulation of retinal blood flow in response to a number of physiological and pharmacological stimuli. The Retinal Vessel Analyzer has markedly simplified the measurement of the diameter of retinal vessels, as well as the change in this diameter evoked by various physiological stimuli (dynamic measurements). Bidirectional laser Doppler velocimetry allows the measurement of absolute red blood cell centerline velocity, which, when combined with the diameter allows the calculation of retinal blood flow in the main retinal vessels. Laser Doppler flowmetry and laser speckle flowgraphy are techniques that measure the velocities of blood in discrete areas of the retinal tissue microcirculation. Adding a scanning capability, a spatial map of velocities across the retinal tissue is obtained. The blue-field simulation technique allows the quantification of the velocity, number and velocity pulsatility of leukocytes moving in the retinal capillaries of the macular region. With color Doppler imaging, the peak systolic and end-diastolic values of blood velocity in the ophthalmic and central retinal artery are measured, from which a resistivity index is obtained. These techniques may help better understand the role of altered retinal blood flow and its regulation in the pathogenesis of retinal diseases of vascular origin.

Choroidal hemodynamic in myopic patients with and without primary open-angle glaucoma.

PURPOSE: To investigate the change in subfoveal choroidal blood flow in patients with glaucoma and to assess the effect of myopia, as one of the vascular risk factors for glaucoma on this flow. METHODS: Subfoveal choroidal blood flow in groups of 12 myopic and glaucomatous eyes has been investigated by means of the laser Doppler flowmetry (LDF), comparing the results with those of 17 myopic eyes without glaucoma, 34 non-myopic glaucomatous eyes and of 50 control eyes. The subfoveal choroidal LDF parameters, that is, blood velocity (ChBVel), volume (ChBVol), and flow (ChBF), as well as the vascular resistance were studied in each group. Statistical analysis was performed by means of anova and t-test according to the Bonferroni procedure for multiple comparisons. Pearson correlation was used to establish the correlations between the hemodynamic parameters and the degree of myopia in dioptres. RESULTS: All LDF parameters (ChBVel, ChBVol and ChBF) were significantly reduced in glaucomatous patients (1.3 ± 0.4, 0.14 ± 0.06 and 4 ± 2 respectively) and myopic patients with primary open-angle glaucoma (POAG) (1.3 ± 0.4, 0.08 ± 0.04 and 2 ± 0.7 respectively) and without POAG (1.2 ± 0.3, 0.11 ± 0.08 and 2 ± 1 respectively) in comparison with age-matched controls (1.5 ± 0.4, 0.27 ± 0.1 and 8 ± 2 respectively). On the other hand, the choroidal vascular resistance (Rm) was increased in the previously described studied patients groups (16 ± 7, 26 ± 9 and 24 ± 9 respectively) compared with controls (7 ± 2). The LDF parameters did not differ significantly between myopic subjects without and with POAG (p = 0.09, p = 0.09, p = 0.2, p = 0.08 and p = 0.9 respectively). Compared to patients with emmetropic glaucomatous, significant reduction in the ChBVol and ChBF and increased Rm were recorded in patients with glaucomatous myopia (p = 0.05, p = 0.04 and p = 0.04 respectively). Pearson correlation demonstrated a significant correlation between the degree of myopia in dioptres and the ChBF (p = 0.012). CONCLUSIONS: The subfoveal choroidal LDF parameters were reduced in patients with POAG and myopia. Theses alterations are more in glaucomatous patients with myopia in comparison with age-matched glaucomatous patients without myopia. These data suggest that the impaired choroidal circulation caused by myopia might be an important additional risk factor involved in the glaucomatous damaging process.

The rationale of retinal endovascular fibrinolysis in the treatment of retinal vein occlusion: from experimental data to clinical application.

PURPOSE: We describe a retinal endovascular fibrinolysis technique to directly reperfuse experimentally occluded retinal veins using a simple micropipette. METHODS: Retinal vein occlusion was photochemically induced in 12 eyes of 12 minipigs: after intravenous injection of 10% fluorescein (1-mL bolus), the targeted retinal vein segment was exposed to thrombin (50 units) and to Argon laser (100-200 mW) through a pars plana approach. A beveled micropipette with a 30-µm-diameter sharp edge was used for micropuncture of the occluded vein and endovascular microinjection of tissue plasminogen activator (50 µg/mL) in 11 eyes. In one control eye, balanced salt solution was injected. The lesion site was examined histologically. RESULTS: Retinal vein occlusion was achieved in all cases. Endovascular microinjection of tissue plasminogen activator or balanced salt solution led to reperfusion of the occluded retinal vein in all cases. Indicative of successful reperfusion were the following: continuous endovascular flow, unaffected collateral circulation, no optic disk ischemia, and no venous wall bleeding. However, balanced salt solution injection was accompanied by thrombus formation at the punctured site, whereas no thrombus was observed with tissue plasminogen activator injection. CONCLUSION: Retinal endovascular fibrinolysis constitutes an efficient method of micropuncture and reperfusion of an experimentally occluded retinal vein. Thrombus formation at the punctured site can be prevented by injection of tissue plasminogen activator.

Retinal vessel diameter can reliably be determined in minipigs using Retinal Vessel Analyser with a microscope-mounted fundus camera.

PURPOSE: Retinal Vessel Analyser (RVA) is a validated instrument to measure retinal vessel diameter in humans. The purpose of this study was to assess the reproducibility (inter-observer reliability) and the repeatability (test-retest reliability) of RVA with a microscope-mounted fundus camera to determine retinal vessel diameter in minipigs. METHODS: Ocular fundus image from five anaesthetized minipigs was recorded in a digital videotape for approximately 5 min, under stable systemic arterial pressure and gas conditions. To evaluate the reproducibility, each one of two investigators used RVA to measure the diameter of the superior temporal retinal artery on five separate 30-second video sequences from each minipig, which were the same video sequences for both investigators. To evaluate the repeatability, one investigator performed five measurements on a single, randomly selected, 30-second video sequence from each minipig. The reproducibility was determined using the intra-class correlation coefficient (ICC), and the repeatability was assessed using the coefficient of variation (COV). Bland-Altman plots were also used to assess agreement between the two investigators. RESULTS: Retinal arteriolar diameter measurements with RVA in minipigs were highly reproducible. Differences between the two investigators were lower than 0.7%. The ICC was 1.00, indicating perfect reproducibility, and the mean COV was 0.18%, reflecting excellent repeatability of the measurements with RVA. CONCLUSION: Retinal vessel diameter can reliably be determined not only in humans, but also in minipigs, using the commercially available RVA apparatus and a microscope-mounted fundus camera.

Vision impairment during cardiac surgery and extracorporeal circulation: current understanding and the need for further investigation.

The aim of this article was to provide a comprehensive review of current knowledge regarding ocular hemodynamic alterations affecting the retinal neuroglial cells and optic nerve head (ONH) function during cardiac surgery. Literature indicates that visual loss after heart surgery is a rare but devastating complication provoked by two main causes of optic ischaemia and infarction during on-pump cardiac procedures: microembolism and/or hypoperfusion. Retinal ischaemia and ischaemic optic neuropathy are two possible major consequences of extracorporeal circulation in cardiac surgery. The hemodynamic modifications within the vascular beds of retina and ONH during cardiovascular operations have been incompletely studied. Consequently, it is of great interest to investigate the hemodynamic changes during cardiopulmonary bypass within the choroidal, retinal and optic nerve microcirculations as well as other potential causes of vaso-occlusion. Maintaining stable hemodynamic parameters during cardiovascular surgery seems to be the key to prevent visual impairment.

23-gauge transconjunctival sutureless vitrectomy: visual outcomes and complications.

PURPOSE: To report results and complications of 23-gauge transconjunctival sutureless pars plana vitrectomy for a variety of vitreoretinal diseases. METHODS: A prospective consecutive case series study was performed in 66 eyes of 66 patients. Indications for surgery were epiretinal membrane (n = 20), rhegmatogenous retinal detachment (n = 19: 14 pseudophakic, 5 phakic), macular hole (n = 16), vitreous hemorrhage (n = 5), cyclodialysis (n = 1), intraocular lens luxation (n = 1), asteroid hyalosis (n = 1), congenital retinoschisis (n = 1), and endophtalmitis (n = 2). Main outcome measures included visual acuity, intraocular pressure, and intra- and post-operative complications. RESULTS: Mean patient age at time of operation was 68 ± 12 years. Overall, visual acuity improved from 1.03 ± 1.00 logMAR preoperatively to 0.32 ± 0.33 logMAR postoperatively (p < 0.01) after a mean follow-up time of 9.3 ± 4.7 months. Mean preoperative intraocular pressure was 13.9 ± 3.5 mmHg, and mean postoperative intraocular pressure was 17.9 ± 9.6 mmHg on day 1 (p < 0.01) and 14.7 ± 2.8 mmHg (p = 0.05) at final visit. Concerning complications, 2 cases of hypotony and 7 of hypertony occurred on day 1, a macular hole reopened some weeks later, and a retinal detachment recurred in one case. CONCLUSION: 23-gauge transconjunctival sutureless vitrectomy is an effective and safe technique for a variety of vitreoretinal diseases.

Idiopathic macular epiretinal membrane surgery and ILM peeling: anatomical and functional outcomes.

PURPOSE: Evaluation of the visual and anatomical outcomes following idiopathic macular epiretinal membrane (ERM) removal, with or without internal limiting membrane (ILM) peeling, and review of the literature. METHODS: A retrospective study of 39 eyes operated for idiopathic ERM was conducted. Pars plana vitrectomy was combined with ERM removal and Indocyanine green (ICG) assisted ILM peeling in 24 eyes. RESULTS: In Group A (without ILM peeling), mean preoperative BCVA was 0.48 logMAR (0.3 in decimal units), whereas mean postoperative BCVA was 0.37 logMAR (0.4 in decimal units). In Group B (with ILM peeling), mean preoperative BCVA was 0.58 logMAR (0.25 in decimal units), whereas mean postoperative BCVA was 0.31 logMAR (0.5 in decimal units). No statistically significant difference was observed between Groups A and B regarding preoperative or postoperative BCVA (p>0.1, Student's t-test). OCT measurement of postoperative foveal thickness reveled a significant decrease in thickness in both groups; however, no correlation was observed between postoperative BCVA and postoperative foveal thickness (Pearson's correlation coefficient = 0.139; p>0.1). CONCLUSIONS: In spite of final visual acuity improvement following idiopathic ERM removal, recovery of a normal foveal thickness is not achieved in the majority of the cases. ICG assisted ILM peeling does not affect the functional outcome of idiopathic ERM removal.

Blood flow measurements within optic nerve head during on-pump cardiovascular operations. A window to the brain?

This observational study is conducted to demonstrate optic nerve head (ONH) blood flow alterations during extracorporeal circulation (ECC) in routine on-pump cardiovascular operations in order to evaluate the perfusion status of important autoregulatory tissue vascular beds during moderate hypothermia. Twenty-one patients free from eye disease were prospectively enrolled in our database. Perioperative ONH blood flow measurements were performed using a hand-held portable ocular laser Doppler flowmeter just after administration of general anesthesia and during cardiopulmonary bypass (CPB) upon the lowest temperature point of moderate hypothermia. Important operative flow variables were correlated to optic nerve blood flow during surgical phases. Statistical analysis showed significant reduction of 32.1 ± 14.5% of mean ONH blood flow in phase 2 (P < 0.0001) compared to the reference flow values of phase 1. A negative univariate association between ECC time and ONH blood flow in phase 2 (P = 0.031) is noted. This angiokinetic approach can detect changes of flow within autoregulatory vascular tissue beds like ONH, thus creating a 'window' on cerebral microvasculature. ONH blood flow is reduced during CPB. Our data suggest that it is of paramount importance to avoid extracorporeal prolongation even in moderate hypothermic cardiovascular operations.