Ocular Oxygen Research Articles

Exposure to persistent hemodynamically significant patent ductus arteriosus is associated with retinopathy of prematurity

BackgroundHemodynamically significant patent ductus arteriosus (hsPDA) shunt may predispose infants to retinopathy of prematurity (ROP) because of its higher preductal cardiac output and blood oxygen content, which may augment ocular oxygen delivery. MethodsA retrospective cohort study of preterm infants, born at <27 weeks’ gestation and admitted at <24h postnatal age to a large quaternary referral was conducted. The primary composite outcome was death at <32 weeks or moderate-to-severe ROP (≥stage 2 or requiring treatment) in either eye. Secondary outcomes included ROP requiring treatment, and any ROP. Univariate analysis of patient characteristics and outcomes was performed as well as logistic regression. A receiver operating characteristics curve was generated for the outcome of ROP ≥stage 2 or requiring treatment. ResultsA total of 91 patients were screened, of whom 86 (54 hsPDA, 32 controls) were eligible for inclusion. hsPDA patients were younger and lighter at birth and had a higher burden of hyperglycemia and respiratory illness. The rates of the composite outcome (death <32 weeks or moderate-to-severe ROP) and of any ROP were more frequent in the hsPDA group. hsPDA shunt exposure was independently associated with development of any ROP among survivors to assessment (P = 0.006). PDA cumulative exposure score of 78 (clinical equivalent = 7 days high-volume shunt exposure) predicts moderate-to-severe ROP with 80% sensitivity and 78% specificity. ConclusionsAmong infants <27 weeks, hsPDA shunt is associated with increased risks of a composite outcome of death or moderate-to-severe ROP, as well as ROP of any stage. Shunt modulation as a strategy to reduce ROP represents a biologically plausible avenue for investigation.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Acute uveitic phase of Vogt-Koyanagi-Harada disease: optic nerve head swelling, ocular blood flow and retinal oxygen metabolism.

To investigate the association of optic nerve head (ONH) swelling in the acute uveitic phase of Vogt-Koyanagi-Harada (VKH) disease with blood flow velocity in the choroid and ONH and oxygen saturation and diameter of retinal vessels. In this prospective study, 25 patients (50 eyes) were studied. Thirteen patients (26 eyes) had ONH swelling and 12 patients (24 eyes) had no ONH swelling. Laser speckle flowgraphy (LSFG) and retinal oximetry measurements were performed at presentation. In the ONH, mean blur rate (MBR)-vessel, representing blood flow velocity in retinal vessels, was significantly lower in the eyes affected by ONH swelling, while choroidal MBR was not significantly different. Eyes with ONH swelling had a significantly lower oxygen saturation in retinal venules, a significantly higher arteriovenous oxygen saturation difference and a significantly smaller calibre of retinal arterioles compared with eyes without ONH swelling. There were significant positive correlations between the MBR-vessel of the ONH and venular oxygen saturation and calibre of retinal arterioles. In addition, MBR-vessel of the ONH had a significant negative correlation with arteriovenous oxygen saturation difference. The occurrence of ONH swelling in the acute uveitic phase of VKH disease is associated with lower retinal blood flow velocity and smaller calibre of retinal arterioles as well as lower oxygen saturation in retinal venules and higher arteriovenous difference in oxygen saturation.

A review of ocular perfusion pressure and retinal thickness: A case for the role of systemic hypotension in glaucoma

Background: Ocular perfusion pressure (OPP) is defined as blood pressure (BP) minus intraocular pressure (IOP). Low OPP may result in decreased ocular blood flow (OBF) and oxygen to the optic nerve head (ONH) and retina.Aim: To review the role of systemic hypotension and similar conditions in OPP and its influence on retinal nerve fibre layer (RNFL) thickness and the ganglion cell complex (GCC).Method: A literature search was conducted using the following search terms: ‘systemic hypotension’; ‘glaucoma’; ‘retinal nerve fibre layer’; ‘optic nerve’; ‘ocular blood flow’ and ‘ocular perfusion pressure’.Results: The Los Angeles Eye Study and Barbados Eye Study found that decreased OPP and BP increased the risk of glaucoma development by up to six times. Reduced retinal perfusion with resultant thinning of the RNFL in conditions with a similar mechanism, such as obstructive sleep apnoea syndrome, has indicated the importance of reduced OPP in retinal thickness. In the absence of any study directly showing the effect of systemic hypotension on OPP and retinal thickness, a working hypothesis proposes that reduced BP with or without normal-to-raised IOP will reduce OPP. The reduced OPP and OBF in those with systemic hypotension may result in oxidative stress and hypoxia which may then cause retinal ganglion cell death and the resultant retinal thinning.Conclusion: The increased risk of glaucoma development and progression relating to decreased BP and OPP has been proven to be of importance. Monitoring patients with systemic hypotension and evaluating the macula, ONH RNFL and GCC thickness may alert clinicians to possible glaucomatous changes.

Hyperoxic myopia: a case series of four divers

Hyperoxic myopia is a phenomenon reported in individuals who have prolonged exposure to an increased partial pressure of oxygen (PO2) and subsequently have a myopic (nearsighted) change in their vision. To date, there are numerous accounts of hyperoxic myopia in dry hyperbaric oxygen treatment patients; however, there have been only three confirmed cases reported in wet divers. This case series adds four confirmed cases of hyperoxic myopia in wet divers using 1.35 atmospheres (ATM) PO2 at the Navy Experimental Diving Unit (NEDU). The four divers involved were the first author's patients at NEDU. Conditions for two divers were confirmed via record review, whereas the other two divers were diagnosed by the first author. All subjects were interviewed to correlate subjective data with objective findings. Each subject completed five consecutive six-hour hyperoxic (PO2 of 1.35 ATM) dives with 18-hour surface intervals. Each individual was within the U. S. Navy Dive Manual's standards for general health. Visual acuity was measured prior to diving. Within three to four days after diving, the individuals reported blurry vision with an associated myopic refraction shift. Each diver had spontaneous resolution of his myopia over the next two to three weeks, with no significant residual symptoms. The divers in this case series were exposed to an increased PO2 (1.35 ATM for 30 hours over five days), a lesser exposure than that in other reports of hyperoxic myopia in wet divers diagnosed with hyperoxic myopia (1.3-1.6 ATM for 45-85 hours in 12-18 days). Furthermore, this pulse of exposure was more concentrated than typically seen with traditional hyperbaric oxygen therapy. Hyperoxic myopia continues to be a risk for those conducting intensive diving with a PO2 between 1.3-1.6 ATM. Additional investigation is warranted to better define risk factors and PO2 limits regarding ocular oxygen toxicity.

Hypoxia impairs visual acuity in snapper (Pagrus auratus)

We investigated the effect of environmental hypoxia on vision in snapper (Pagrus auratus). Juvenile snapper inhabit estuarine environments where oxygen conditions fluctuate on a seasonal basis. Optomotor experiments demonstrated that visual acuity is impaired by environmental hypoxia, but not until levels approach the critical oxygen tension (P crit) of this species (around 25% air-saturated seawater). In 100, 80, and 60% air-saturated seawater, a positive optomotor response was present at a minimum separable angle (M SA) of 1°. In 40% air-saturated seawater, vision was partially impaired with positive responses at M SAs of 2° and above. However, in 25% air-saturated seawater, visual acuity was seriously impaired, with positive responses only present at M SAs of 6° and above. Snapper were found to possess a choroid rete, facilitating the maintenance of high ocular oxygen partial pressures (PO2) during normoxia and moderate hypoxia (PO2, between 269 and 290 mmHg). However, at 40 and 25% water oxygen saturation, ocular PO2 was reduced to below 175 mmHg, which is perhaps linked to impairment of visual acuity in these conditions. The ability to preserve visual function during moderate hypoxia is beneficial for the maintenance of a visual lifestyle in the fluctuating oxygen environments of estuaries.

Understanding Medline indexing

Editor, T hank you for the thoughtful editorial on ‘The ingredients of a good paper’ in the September issue of Acta Ophthalmologica (Stefansson & Kivela 2010). I particularly appreciate your words on choosing text for titles and abstracts. These sections of the article are incorporated verbatim into the Medline record and provide key access points for those searching Medline. However, I believe it is important to clarify the role of author-selected keywords in Medline indexing. The National Library of Medicine maintains a website with information on the indexing process. The page at http:// www.nlm.nih.gov/bsd/disted/mesh/pro cess.html discusses the use of author keywords by the indexers as a guide to what concepts may be discussed in the article itself, but as the subsequent pages make clear, the indexer uses only terms found in MeSH, a controlled vocabulary or taxonomy, in selecting the subject indexing terms that appear in the Medline record. For instance, the recent article, ‘Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: the addition of dorzolamide to timolol monotherapy’ Siesky et al. (2010), has the following keywords in the text:

Ocular oxygen consumption: estimates using vitreoperfusion in the cat.

Little is known about the ocular oxygen consumption rate (QO2) in human diseases. Alterations in QO2 must occur in many conditions, such as retinal ischemia. We present a method of estimating QO2 that eventually could be used in patients during vitrectomy surgery. We performed vitreoperfusion (i.e., perfusion of the vitreous cavity after vitrectomy) in 14 cat eyes with no ocular blood flow. The solution contained nutrients at a high partial pressure of oxygen (PO2). In eight eyes, the retinas were undisturbed (Group 1), and in six eyes, we excised the retinas (Group 2). We estimated QO2 in both groups on the basis of the temporal decline of PO2 in the vitreoperfusion solution according to a pharmacokinetic model. The mean and standard deviation of QO2 was 3.2 +/- 0.8 microL/min in Group 1 and 0.4+/- 0.7 microL/min in Group 2, with the difference being the retinal contribution, 88%. In Group 1, metabolism, bulk flow, and diffusion accounted for 82, 13, and 5%, respectively, of the oxygen loss from the vitreoperfusion solution. We estimated ocular oxygen consumption by means of vitreoperfusion. Eventually, the pathophysiology of human diseases may be clarified by similar measurements during vitrectomy.

The role of pseudobranch and choroid rete for ocular oxygen supply

The role of pseudobranch and choroid rete for ocular oxygen supply

Quantification of erythrocyte flow in the choroid of the albino rat.

Choroidal blood flow is one of the highest in the body on a global volume basis. Little is known, however, about flow through individual vessels, which has important consequences for ocular blood delivery and oxygen transport. The purpose of this study was to use a new epifluorescent technique to view, record, and quantify erythrocyte (RBC) flow in individual rat choroidal vessels through the intact sclera. With the Sprague-Dawley rats under urethan anesthesia, rhodamine-labeled liposomes were injected intravenously and served as a plasma marker. Rat RBC were labeled ex vivo with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate and then infused intravenously. The flow of the fluorescent RBC through 69 choroidal vessels with diameters between 12 and 52 microm in six rats was recorded on videotape, and the images were used to determine vascular diameter, RBC flux and velocity, and microvessel hematocrit (Hct). RBC flux and RBC velocity were positively correlated with vessel diameter (r = 0.67, P < 0.001 and r = 0.29, P = 0.016, respectively). Microvascular Hct ranged between 4 and 32% (8 and 67% of systemic Hct) and was negatively correlated with diameter (r = -0.28, P = 0.018). The relationships of RBC flux and RBC velocity with vessel diameter were the same as found in other tissues. However, in other vascular beds, microvascular Hct and diameter are positively correlated. Because microvascular Hct is a determinant of relative viscosity and oxygen delivery, this relatively high Hct in small choroidal vessels could have significant implications for local blood flow and oxygen transport.

Ocular oxygen measurement.

Ocular oxygen measurement.

Quantitative Mapping of Ocular Oxygenation Using Magnetic Resonance Imaging

Retinal hypoxia is hypothesized to initiate angiogenesis, a leading cause of blindness in developed countries. Attempts to test this hypothesis suffer from the need to use highly invasive oxygen electrodes. In this communication, noninvasive and quantitative mapping of ocular oxygenation using magnetic resonance imaging is demonstrated for the first time.

Ocular oxygenation: the effect of phenylephrine on anterior chamber oxygen tension.

Phenylephrine preparations are widely used in medicine for their vasoconstrictive and mydriatic effects. The effect of phenylephrine, a powerful alpha-receptor stimulant, on anterior chamber oxygen tension (Po2) was studied using a polarographic electrode inserted into the mid anterior chamber of cats. A commercial 10% solution was applied topically. A decrease in anterior chamber Po2 was usually observed in 8-24 minutes and declined steadily thereafter. Prior to treatment, the mean anterior chamber Po2 was 26 +/- 3 torr; 1/2 hour after treatment it decreased to 20 +/- 7 torr. After 1 hour it dropped to 13 +/- 8 torr and was further reduced to 11 +/- 6 torr by 2 hours. By 90 minutes, the drug had caused a 58% reduction in anterior chamber oxygen tension. This drop is similar to that reported for epinephrine. It is suggested that the mechanism for most of this decrease is reduced blood flow, mediated by the direct vasoconstrictive effect of the drug in addition to compression of the iris vasculature induced by dilation. The resulting change (reduction) in caliber of the iris arteries produces a parallel change (reduction) in blood volume and flow resulting in a diminished Po2. The clinical implications of this conclusion in disorders where hypoxia is felt to play a causal role such as neovascular glaucoma, diabetes, pregnancy and hyphema in sickle cell disease are explored.

Ocular oxygen toxicity: The effect of hyperbaric oxygen on retinal Na +−K + ATPase

A comparative study was conducted of the effect of hyperbaric oxygen on Na+−K+ ATPase activity in the retina. Isolated retinas of rainbow trout (Salmo gairdneri), frogs (Rama pipiens) and rats (Long-Evans strain) were exposed, in tissue culture medium, to hyperbaric oxygen at 3800–11600 mmHg or air at 740 mmHg (control) for 4 hr. Exposure of trout retinas to hyperbaric oxygen at 14°C had no effect on Na+−K+ ATPase activity, while an increase in temperature to 23°C resulted in a 10–20% decrease in enzyme activity compared to control. Na+−K+ ATPase activity of frog retinas was not affected by exposure to hyperbaric oxygen at 22 or 37°C. Exposure of rat retinas to hyperbaric oxygen at 37°C resulted in a 50–60% inhibition of Na+−K+ ATPase activity. These results are in agreement with previous studies of oxidative metabolism, lactate dehydrogenase activity and the electroretinogram which indicate that the teleost retina is resistant to oxygen toxicity, while the mammalian retina is highly susceptible to oxygen toxicity. It is concluded that inhibition of Na+−K+ ATPase is involved in the toxicity of oxygen to the mammalian retina and that the inhibition of this enzyme may be a contributing factor in the attenuation of the electroretinogram which has been observed during exposure of retinas to hyperbaric oxygen.

Ocular oxygen toxicity: The effect of hyperbaric oxygen on the in vitro electroretinogram

1. 1. Electroretinograms (ERG) were recorded from isolated eyecups of frogs, rats, goldfish, and trout during exposure to hyperbaric oxygen. 2. 2. Hyperbaric oxygen is toxic to the frog and rat retinas as indicated by attenuation of the ERG. 3. ]3. Electroretinographic evidence indicates that the teleost retina is resistant to oxygen toxicity.

Short circuiting the ocular oxygen concentrating mechanism in the teleost Salmo gairdneri using carbonic anhydrase inhibitors.

Ocular oxygen concentration by the process of counter current multiplication in rainbow trout (Salmo gairdneri) was rapidly suppressed after intraperitoneal injections of the carbonic anhydrase inhibitor CL-11,366. The rapidity with which this drug acted suggested a short circuiting of the choroidal rete mirabile. A comparison was made between the time after injection of inhibitor at which oxygen concentrating ability was lost to the time after injection of inhibitor at which its presence in red blood cells, choroidal rete, pseudobranch, and retinal tissue was first noted. A scheme for the possible role of carbonic anhydrase from each of these tissues in the process of ocular oxygen concentration is given.

Effect of acetazolamide on some hematological parameters and ocular oxygen concentration in rainbow trout

1. 1. Values for several hematological parameters are given for control and acetazolamide treated rainbow trout. 2. 2. Analyses of blood obtained 24 hr after acetazolamide treatment indicates that this carbonic anhydrase inhibitor had no effect on the O 2 dissociation curve for whole blood. 3. 3. Acetazolamide did cause an increase in red blood cell (RBC) volume and a significant decrease in the amount of oxygen carried per g of hemoglobin. 4. 4. The Root effect was observed in trout blood even in the presence of a pO 2 of 450 mm Hg and the absence of functional carbonic anhydrase. 5. 5. It was concluded that the rapid depletion of ocular pO 2 in trout eyes following acetazolamide treatment is not due to a decrease in the supply of oxygen to the counter current multiplier via the blood.

Teleost retinal metabolism as affected by acetazolamide.

SummaryTrout retinas were incubated in air–tight syringes at 15°. Values for the Po2 of the incubation medium and the Qo2 of retinal tissue varied independently indicating that Po2 was not a rate–limiting factor for Qo2. When compared to controls, retinas from trout treated with acetazolamide had a decreased Qo2 an increase in aerobic glycolysis, and an over–all increase in production of acid metabolites. Retinas treated with the drug in vitro showed a decrease in Qo2, decrease in aerobic glycolysis, and a decline in glucose utilization but no decrease in total production of acid metabolites. The relationship between the effects of acetazolamide on retinal metabolism and the depletion of ocular oxygen tensions after administration of the drug are discussed.The technical assistance of Mrs. Esther Brenke is acknowledged.

Ocular oxygen concentrations accompanying severe chronic ophthalmic pathology in the lake trout ( Salvelinus namaycush)

1. 1. Ocular oxygen tensions of 359± 31·9 (37) mm Hg were found in normal lake trout eyes while those eyes showing gross pathology had a significantly lower PO 2 of 219 ± 34·4 (27). 2. 2. The progression of the ocular histopathology is described in relationship to pseudobranch degeneration. 3. 3. The maintenance of elevated intraocular PO 2 even in the presence of chronic ophthalmic pathology is noted.

The dependence of the oxygen-concentrating mechanism of the teleost eye (Salmo gairdneri) on the enzyme carbonic anhydrase.

Microoxygen polarographic electrodes were constructed and used to measure oxygen tension (P(OO2)) in the eyes of rainbow trout (Salmo gairdneri). The values obtained are compared with arterial blood and environmental water P(OO2) and indicate that there is an oxygen-concentrating mechanism in the eye supplying oxygen to the avascular retina. Anatomically similar retes suggest that the mechanism is similar to the one which exists in the swim bladder. Elimination of the arterial blood supply to the choroidal gland rete mirabile of the eye (through pseudobranchectomy) and the consequent lowering of ocular oxygen tensions implicate the choroidal gland as one of the major components of the oxygen-concentrating mechanism. After pseudobranchectomy the presence of ocular P(OO2) above that of arterial blood is indicative of a secondary structure in the eye capable of concentrating oxygen. Inhibition of carbonic anhydrase, using acetazolamide, is shown to result in complete suppression of the oxygen-concentrating mechanism. A hypothesis is advanced for the participation of retinal-choroidal and erythrocyte carbonic anhydrase in the oxygen-concentrating mechanism.