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PURPOSE: This study examined the effects of normobaric oxygen in patients diagnosed with either a Central Retinal Vein Occlusion (CRVO) or Branched Retinal Vein Occlusion (BRVO) who had previously undergone treatment via Anti-VEGF or PRP treatment. The investigation looked into the changes in Macular Thickness (MT) and Visual Acuity (VA). METHODS: This pilot study analyzed patient data from Beth Israel Deaconess Medical Center (Boston, MA) that had been diagnosed with Retinal Vein Occlusions. The patients were brought in and given 3 hours of normobaric oxygen via an oxygen concentrator with imaging and vision checked both before and after the therapy. RESULTS: Eighty-eight percent of our patients in this pilot study saw a decrease in macular thickness after 3-hour oxygen therapy. The mean change in Maximal Macular Thickness was a decrease of 7.1% which was statistically significant when compared to healthy eyes (p<0.001). Additionally, 44% of patients saw an increase in visual acuity, the primary measure of vision. Visual acuity showed a statistically significant change when compared to changes in healthy eyes (p=0.015). No statistical significance was found in the testing of contrast sensitivity nor intraocular pressure. CONCLUSION: Our study showed improvement in central macular thickness and quality of life for individuals using noninvasive normobaric hyperoxia as a treatment for retinal vein occlusions. However, further research is needed to improve the impact of the study and a full randomized control trial should be implemented to further understand the potential impacts of a noninvasive normobaric hyperoxia treatment as a means to alleviate symptoms in retinal vein occlusions. In addition, in the future oxygen supplementation in conjunction with periodic injections of Anti- VEGF could be investigated as a treatment regimen with potential benefits beyond individual therapy. / 2020-06-17T00:00:00Z

Exposure to hyperoxia has been shown to have detrimental effects on newborn hemodynamics and antioxidant activities in males. These effects are unknown in the newborn female, despite clinical data showing that in children undergoing surgery females have poorer outcomes. This thesis explored whether newborn females respond worse than males to hyperoxia, specifically in hemodynamics and antioxidant activity. Hemodynamic results showed continual decreases in DBP and MAP, increases in HR, decreases in SBP, and increases in PP, which were experienced earlier and to a greater degree in the female. Additionally, reduced antioxidant activity seen in newborns was worse in females in both the heart and skeletal muscle. These results suggest that in response to hyperoxia, newborn females are at a hemodynamic disadvantage when compared to males, which may be a contributing factor for why female children are at a higher risk during surgery or medical management involving hyperoxia.

Exposure to hyperoxia has been shown to have detrimental effects on newborn hemodynamics and antioxidant activities in males. These effects are unknown in the newborn female, despite clinical data showing that in children undergoing surgery females have poorer outcomes. This thesis explored whether newborn females respond worse than males to hyperoxia, specifically in hemodynamics and antioxidant activity. Hemodynamic results showed continual decreases in DBP and MAP, increases in HR, decreases in SBP, and increases in PP, which were experienced earlier and to a greater degree in the female. Additionally, reduced antioxidant activity seen in newborns was worse in females in both the heart and skeletal muscle. These results suggest that in response to hyperoxia, newborn females are at a hemodynamic disadvantage when compared to males, which may be a contributing factor for why female children are at a higher risk during surgery or medical management involving hyperoxia.

This study determines effects of oxygen levels on morphology and VEGF expression of developing chicken lungs following incubation in normoxia (21% O2), hypoxia (15% O2) or hyperoxia (30% O2), until developmental days 16 or 18. Lung morphology was assessed using light microscopy, while VEGF expression was determined with ELISA. In hypoxia, the proportion of parabronchial tissue and parabronchi including lumina increased from day 16 to 18 (61 to 68% and 74.2 to 82.2%, respectively). Non-parabronchial tissue was higher in hypoxia than in hyperoxia on day 16 (26 to 20%). However, by day 18, there were no differences between groups. VEGF expression was 33% higher in hypoxia than in hyperoxia on day 16 (736 vs. 492 pg/ml). On day 18, VEGF expression was 43% higher in hyperoxia than in normoxia (673 to 381pg/ml), and remained elevated by 40% in hypoxia over normoxia (631 pg/ml). VEGF may be a mechanism by which parabronchial tissue is stimulated from day 16 to 18 following exposure to chronic hypoxia.

PURPOSE: Diabetic macular edema (DME) is the most common cause of vision loss in patients with diabetic retinopathy. This study aims to approach diabetic macular edema and diabetic retinopathy as ischemic conditions and explores a potential treatment through hyperoxia. The study measured changes in retinal thickness, visual acuity, and contrast sensitivity in subjects receiving normobaric oxygen. METHODS: Fifty-one patients with diabetic macular edema at Beth Israel Deaconess Medical Center Eye Clinic (Boston, MA) received oxygen via a face mask at 5 liters per minute for 3 hours. Retinal thickness at the central subfield and maximal retinal thickness were measured using optical coherence tomography. Contrast sensitivity, best corrected visual acuity, and intraocular pressure were measured before and after oxygen as well. RESULTS: Macular thickness from diabetic macular edema decreased by an average of 2.09% (p < .05) at the point of maximal thickness, and by 0.88% (p < .05) at the central subfield. Vision also improved by an average of 0.043 LogMAR units (p < .05). Changes in macular thickness and visual acuity were non-significant in healthy control eyes that received oxygen. The results of hyperoxia on contrast sensitivity were indeterminate. CONCLUSIONS: We found that normobaric hyperoxia for 3 hours reduces macular thickness from diabetic macular edema and improves visual acuity. This study offers additional evidence that diabetic macular edema is an ischemic disorder and suggests that oxygen therapy may serve as an alternate or complimentary treatment of DME. / 2020-06-17T00:00:00Z

Inflammation and oxidative stress are increasingly recognised as important independent mediators of preterm brain injury and have been implicated in the pathogenesis of cerebral palsy and cognitive impairment. Such exposures are common for the premature infant in whom infection and inflammatory morbidities occur in around 60%. Furthermore, many preterm infants require oxygen therapy and respiratory support due to lung immaturity. Epidemiological and experimental studies indicate that in addition to the independent effects of inflammation and extreme hyperoxia on the developing brain, inflammation preconditions the developing brain resulting in variable injury when exposed to subsequent hypoxia-ischaemia. However experimental studies employing exposure to more modest oxygen fluctuations are lacking. This thesis characterises a clinically relevant model of prematurity where the developing brain is exposed to low grade inflammation and oxygen fluctuation around a hyperoxic mean. We hypothesise that antenatal inflammation and postnatal oxygen fluctuation, both alone and in combination, have detrimental effects on developing white matter. Pregnant dams received intraperitoneal lipopolysaccharide (LPS) or saline on G18 and G19. Dams and their pups were then reared in room air or fluctuating hyperoxia (circa 10kPa) for seven days. We measured longitudinal brain and body growth in different experimental groups to 12 weeks. Whole brains were examined for mRNA expression of inflammatory cytokines (TNFα, IL-1β, IL-6 and IL-10) and markers of oxidative injury (iNOS, SOD2). To determine the effect of perinatal insults on developing white matter, we analysed the expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the internal and external capsule. We also examined white matter tracts for differences in microglia (CD68), oligodendrocyte progenitor cells (NG2), oligodendroglial cells (Olig2) and cell death (cleaved caspase3). Behavioural studies (Morris Watermaze Test, Elevated Plus Test and Open Field Test) were undertaken at 12 weeks of age to detect any long-term functional difference between the groups. Antenatal inflammation reduces both brain and body growth at P7. This normalises by P14 unless this inflammatory insult has been followed by postnatal oxygen fluctuation, where brain and body growth restriction persists until P14. We defined our inflammatory response at P1 following antenatal inflammation and did not observe elevation of mRNA at P1. We demonstrated increased SOD2 at this time point, indicating a reparative process. At P7 we observed a significant reduction in the oxidative response following combined exposure to antenatal inflammation and postnatal oxygen fluctuation, indicating a potential limit to, or suppression of, the reparative process. In terms of white matter injury, antenatal inflammation reduces myelination at P7. There is no synergistic effect of inflammation and oxygen fluctuation on MBP immunohistochemistry at P7. However, MBP mRNA expression is increased in pups exposed to both insults compared to those exposed to inflammation alone suggesting that the oxygen fluctuation may stimulate MBP production in response to oxidative injury. MBP mRNA levels and protein expression have all normalised by P14. We observed a reduction in total cell number in the external capsule and corpus callosum in the dual insult group, without an increase in caspase. In keeping with other studies we detected no effect of our perinatal insults on NG2+ve oligodendrocytes. Olig2+ve cell numbers were also consistent between experimental groups. In further characterisation of the cellular response, antenatal inflammation followed by postnatal oxygen fluctuation resulted in a decrease in GFAP mRNA at P7, an effect which was reversed and significantly increased by P14 suggesting delayed activation of the innate immune system. No difference was observed in microglial numbers between experimental groups. There was however, increased microglial cell death (CD68 + caspase) in the group exposed to antenatal inflammation. When this insult was combined with postnatal oxygen fluctuation there was a comparative decrease in microglial cell death, which may reflect an earlier peak of microglial cell death, due to an increased and sustained inflammatory stimulus. Morris Watermaze testing demonstrated that pups exposed to both insults took longer than controls to locate the hidden platform on day 1, which is a measure of spatial learning. The Elevated Plus Test and Open Field Test demonstrated that pups exposed to both insults were less anxious and took more risks than pups exposed to single insults. In conclusion, within a clinically relevant preterm model, antenatal inflammation transiently disrupts both brain and body growth and myelination of the motor tracts of the developing brain. Moreover, when combined with postnatal oxygen fluctuation, detrimental effects on growth are amplified and sustained. Decreased cell numbers are also observed within white matter tracts. In terms of long term functionality, these pups display disinhibition of behaviour as young adults. Collectively, this thesis demonstrates that synergistic actions of common low-grade perinatal insults may alter normal neurodevelopment, and that this may carry a risk of neurodevelopmental sequelae for preterm infants.

Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

Oxygen is a necessary part of our everyday lives and is important for normal eye function. Blood flow through the retinal vasculature supplies oxygen to the inner retina. The resistance of the retinal vessels can change, increasing and decreasing blood flow by dilation and constriction of the vessel. The response of retinal hemodynamics to vasoactive stimuli is termed vascular reactivity. To investigate vascular reactivity characteristics, a system that prospectively targets a certain level of oxygen is employed. We characterize how the retinal vessels respond over time to hypoxia as well as define vascular reactivity to different oxygen concentrations in healthy participants. We demonstrate that the vessels increase diameter fully after 6 minutes and flow after 10 minutes. The relationship between retinal hemodynamics and arterial partial pressure of oxygen (PaO2) is demonstrated in healthy humans. Future studies should investigate these changes in diseased models to better understand when the retinal vasculature response may be insufficient.

PURPOSE: Age-related macular degeneration (AMD) is a complex, progressive ocular disorder that results in outer retinal ischemia and severe vision loss. Dry AMD, the most common form of AMD, is characterized by the build-up of extracellular drusen deposits, dysfunction of the outer retinal layers and degeneration of photoreceptors. This study aimed to examine the anatomic and physiologic effects of short-term normobaric hyperoxia in patients at different stages of dry AMD. METHODS: Twenty-two eyes from 16 patients diagnosed with dry AMD (11 females, 5 males) were used in this study. Eyes were categorized as having either small drusen or drusenoid pigment epithelial detachments (DPEDs) through optical coherence tomography (OCT) imaging. Eyes associated with small drusen received 3-hours of 40% fraction of inspired oxygen (FiO2) normobaric hyperoxia (NBH), whereas eyes associated with DPEDs received either 3-hour NBH or 3-hours of 20% FiO2 normobaric normoxia (NBN). Visual acuity and OCT images of the macula were taken before and after oxygen treatment. Anatomic outcomes consisted of foveal thickness, foveal volume, macular volume and maximum drusen height; visual acuity was the functional outcome. The relationship between maximum drusen height and visual acuity was then examined to determine if these outcomes were associated. RESULTS: Eyes associated with DPED treated with 3-hour NBH had the largest decreases in foveal thickness, foveal volume, macular volume and maximum drusen height. The macular layers were then divided into inner and outer layers. The outer layers, comprised of Bruch’s membrane, drusen and the retinal pigment epithelium, had significant decreases in anatomic outcomes, whereas the inner layers showed no changes. DPED patients treated with 3-hour NBH also had the largest increase in visual acuity following treatment. There was a significant negative correlation between baseline drusen height and baseline visual acuity. For patients with small drusen treated with 3-hour NBH, there were no significant changes to anatomic or functional outcomes. CONCLUSION: The current study demonstrates the efficacy of short-term administration of normobaric hyperoxia in high-risk dry AMD patients with associated DPEDs. Normobaric hyperoxia appears to be a novel and promising treatment that requires further investigation.