Oman Journal of Ophthalmology

: 2013  |  Volume : 6  |  Issue : 4  |  Page : 5--7

Oxygen therapy and ophthalmology

Des Gorman 
 Professor of Medicine and Associate Dean, Faculty of Medical and Health Sciences, University of Auckland, NewZealand

Correspondence Address:
Des Gorman
Associate Dean Health Workforce, Ministry of Health, Level 17, West Plaza Building, Cnr Albert & Customs Streets, Auckland

How to cite this article:
Gorman D. Oxygen therapy and ophthalmology.Oman J Ophthalmol 2013;6:5-7

How to cite this URL:
Gorman D. Oxygen therapy and ophthalmology. Oman J Ophthalmol [serial online] 2013 [cited 2023 Jan 30 ];6:5-7
Available from:

Full Text


Oxygen as an element was discovered in the 17 th century. The importance of oxygen to combustion and then life was quickly determined. By contrast, conventional uses of oxygen in medicine did not occur until about 50 years ago. It is noteworthy that the almost simultaneous development of oxygen therapy, at elevated pressures (hyperbaric oxygen (HBO)), for decompression illnesses (the bends) in the US, [1] and for gas gangrene in Holland, [2] was almost 40 years after such oxygen therapy had been proposed as a panacea by practitioners who are now best described as charlatan.

The significance of this history of that HBO therapy has been bedeviled by such charlatanism and quackery, and even amongst conventional practitioners, by unsupportable claims of efficacy, such that many health providers regard such treatment pejoratively. [3] The downside of this cynicism is that many patients who would otherwise benefit from HBO therapy have been denied access to this treatment. In addition, many patients have been treated for barely plausible reasons, at both financial and personal cost.

The other salient point that arises from a consideration of the history of HBO therapy is that it is a new modality and that throughout its 50-year history, the standard of clinical research has been poor. As such, the available clinical database is of limited utility. In some instances, the lack of data arises from the nature of the illness. The sporadic and often life-threatening nature of decompression illness, and the spectacular life and limb-saving effects of HBO therapy are such that attempts to conduct a randomized controlled trial have not obtained ethical approval. Similarly, conditions such as clostridial gas gangrene is rare and otherwise lethal, making conventional study, at best, problematic.

Other conditions, such as carbon monoxide poisoning, have had extensive clinical study, although, with one exception, these clinical studies would not meet the higher level criteria for inclusion in a Cochrane Evaluation. [4] That single randomized controlled trial was conducted in Salt Lake City and showed a number needed to treat (NNT) of about five to avoid some form of sequelae. Despite the positive result of this single properly conducted study, many patients who have been poisoned by carbon monoxide are nevertheless not offered treatment. This is a difficult situation to understand given that the number needed to harm (NNH) for HBO therapy in this context is extremely high.

In modern clinical settings, the most common application of HBO therapy is for non-healing wounds in diabetics. [5] The effect of HBO on a diabetic wound is complex and multifactorial, and has advantages both in terms of financial and disease outcome. Attempts to use HBO to treat other forms of non-healing wound have been less successful, in part due to the reality that many of these arise in patients with essentially no useful peripheral circulation.

With regard to diseases and injuries of the eye, there are no useful clinical studies to validate the use of HBO; although, ironically, the first observation of the etiology of decompression illness was the observation of a bubble in a viper's eye. There are a number of case studies, which report good outcomes in patients with mucormycosis of the orbit, occlusive conditions of the retinal vasculature and in various degenerative illnesses and injuries of the eyes. [6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] Clearly, using HBO to treat an infection caused by an obligate anaerobe or as an adjunct in the treatment of conditions that involve hypoxia and/or ischemia, makes sense from a biological perspective. However, the biological effect of oxygen is very complex, and certainly dose-related, such that any treatment based on first principles would need to be conducted with careful consideration of dose intensity, duration, and frequency. [23]

As is true for all aerobic organisms, humans depend upon oxygen for normal biology. As the oxygen tension, which humans are subjected to is lowered from those present in the earth's atmosphere, conditions of hypoxia onset. Humans are very well-adapted to hypoxic conditions, [24] with short-term responses by way of relative increased perfusion of the brain and heart, and long-term responses in regard to oxygen-carrying capacity and transfer functions in blood. Nevertheless, a level of hypoxia is reached at which human biology fails.

Similarly, and as well shown by sentinel experiments conducted during World War II, as oxygen tensions are raised above those present in the earth's atmosphere, oxygen becomes injurious; [25] largely through the production of a range of free radicals which exceed the body's scavenging and clearance capacity. Prolonged breathing of oxygen at greater than 60 kilopascals results in interstitial lung injury. By contrast, breathing oxygen at greater than 100 kilopascals, and more particularly at greater than 160 kilopascals, results in significant disruption of normal brain biology and eventually convulsions.

This overview of hypoxia, normoxia, and hyperoxia at a whole of organism level, is also true for almost every cellular and subcellular function in the human body. For example, as was shown over 30 years ago, [26] PMNL motility and killing capacity of microorganisms is inhibited under conditions of hypoxia, stimulated in normoxic conditions, and again inhibited at extreme hyperoxia. The use of oxygen therapy then in this context would be to convert a hypoxic tissue, where PMNL function is inhibited, to a normoxic tissue, in which such function is restored.

By contrast, in decompression illness and carbon monoxide poisoning, where neutrophil diapedesis from the cerebral circulation induces lipid injury, changes in the antigenicity of myelin basic protein, and in turn precipitates an immune mediated neuropathy, [27] the use of oxygen as a treatment is at deliberately "poisonous levels" to inhibit neutrophil function. In particular, the cyclic guanosine monophosphate (GMP) regulation of neutrophil binding to endothelial cells is inhibited at high levels of oxygen such that activated neutrophils are "trapped" within the circulation.

Another illustration of the complexity of oxygen's biology and the importance of dose in medical applications, is in wound healing, [5] and where collagen maturation and cross-linking is inhibited at low oxygen tensions. Consequently, in chronically hypoxic tissue, where there is no meaningful oxygen tension gradient across the edge of the wound, there is little or no release or angiogenesis factor by macrophages, and similarly little or no collagen formation to provide the template for consequent wound healing. In these circumstances, judicious use of oxygen, to restore normal oxygen tensions in adjacent tissues, and to create an oxygen gradient across the wound edge, can provide significant stimulation of wound healing. That is, new blood vessels form or bud from existing vessels and grow into the wound, collagen is formed, laid down, and cross linked. Interestingly, as the wound revascularizes, the dose of oxygen that the patient has to be subjected to, to achieve the desired level of tissue oxygen tension decreases and often quite dramatically.

All of this argument is not only to illustrate that the dose of oxygen needs to be selected to achieve the desired tissue tension, but that the dose will change as treatment progresses.

In regard to diseases and injuries of the eyes then, the biology of oxygen, and the medical applications of this, clearly has great appeal for a range of hypoxic and ischemic conditions. However, the measurement of intraocular and periocular tensions in response to different oxygen doses and the effect that these have on these diseases, is yet to be determined. Clearly, it is possible to postulate mechanisms of action by which oxygen therapy may positively influence the outcome for patients with "epidemic" diseases in modern societies such as glaucoma and macular degeneration. Ironically, most of the current interface between ophthalmology and optometry, and HBO, is the large number of elderly patients who are being treated with HBO for non-healing wounds and who commonly develop reversible changes in visual refraction and or experience an acceleration of preexisting cataract. [28]

It follows that HBO is a potential as compared to a proven therapy for any illness of injury of the eye. It is also self-evident that there is a need for careful evaluation of the potential utility of HBO in such injuries and illnesses. The return on this research investment may well be significant given the huge social and financial cost of degenerative and other eye diseases in ageing communities.


1Moon RE, Gorman DF. Treatment of the decompression disorders. In: Bennett PB, Elliott DH, Editors. The Physiology and Medicine of Diving. 4 th ed. London: Balliere-Tindall; 1993. p. 506-11.
2BrummelkampWH, Hogendijk J, Boerema I. Treatment of anaerobic infections (clostridial myositis) by drenching the tissues with oxygen under high atmospheric pressure. Surg 1961;49:299-302.
3Gorman DF. Hyperbaric oxygen therapy: A future perspective. In: Shields TG, editor. Diving and hyperbaric medicine. Eur Undersea Biomed Soc Aberdeen 1988.
4Weaver LK, Hopkins RO, Chan KJ, Churchill S, Elliott CG, Clemmer TP, et al., Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057-67.
5Gorman DF. Oxygen therapy in the diabetic foot. In: Frykberg R, editor. The High Risk Foot in Diabetes Mellitus. New York: Churchill Livingstone; 1990. p. 441-7.
6Bojiæ L, Kovaceviæ H, Andriæ D, Romanoviæ D, Petri NM. Hyperbaric oxygen dose of choice in the treatment of glaucoma. Arh Hig Rada Toksikol 1993;44:239-47.
7Bojiæ L, Racic G, Gosoviæ S, Kovaceviæ H. The effect of hyperbaric oxygen breathing on the visual field in glaucoma. Acta Ophthalmol 1993: 71:315-9.
8Gismondi A, Colonna S, Micalella F, Metrangolo C. Hyperbaric oxygen therapy in thrombotic occlusion of the central retinal vein. Minerva Med 1981;31:72:1413-5.
9Jansen EC, Nielsen NV. Promising visual improvement of cystoids macular oedema by hyperbaric oxygen therapy. Acta Ophthalmol Scand 2004;82:485-6.
10Johnson GP. Cases from the aerospace medicine residents′ teaching file. Case #38. A navigator with nonischemic central retinal vein occlusion progressing to ischemic central retinal vein occlusion. Aviat Space Environ Med 1990;61:962-5.
11Kiryu J, Ogura Y. Hyperbaric oxygen treatment for macular edema in retinal vein occlusion: Relation to severity of retinal leakage. Ophthalmologica 1996;210:168-70.
12Krott R, Heller R, Heimann K. Adjuvant hyperbaric oxygen therapy (HBO) in cystoid macular edema-preliminary results. Klin Monbl Augenheilkd 1999;215:144.
13Miyamoto H, Ogura Y, Honda Y. Hyperbaric oxygen treatment for macular edema after retinal vein occlusion-fluorescein angiographic findings and visual prognosis. Nippon Ganka Gakkai Zasshi 1995;99:220-5.
14Miyake Y, Awaya S, Takahashi H, Tomita N, Hirano K. Hyperbaric oxygen and acetazolamide improve visual acuity in patients with cystoid macular edema by different mechanisms. Arch Ophthalmol 1993;111:1605-6.
15Miyamoto H, Ogura Y, Wakano Y, Honda Y. The long term results of hyperbaric oxygen treatment for macular edema with retinal vein occlusion. Nippon Ganka Gakkai Zasshi 1993;97:1065-9.
16Ogura Y, Kiryu J, Takahashi K, Honda Y. Visual improvement in diabetic macular edema by hyperbaric oxygen treatment. Nippon Ganka Gakkai Zassh 1988;92:1456-60.
17Ogura Y, Takahashi M, Ueno S, Honda Y. Hyperbaric oxygen treatment for chronic cystoid macular edema after branch retinal vein occlusion. Am J Ophthalmol 1987;104:301-2.
18Pfoff DS, Thom SR. Preliminary report on the effect of hyperbaric oxygen on cystoid macular edema. J Cataract Refract Surg 1987;13:136-40.
19Roy M, Bartow W, Ambrus J, Fauci A, Collier B, Titus J. Retinal leakage in retinal vein occlusion: Reduction after hyperbaric oxygen. Ophthalmologica 1989;198:78-83.
20Suttorp-Schulten MS, Riemslag FC, Rothova A, van der Kley AJ, Riemslag FC. Long-term effect of repeated hyperbaric oxygen therapy on visual acuity in inflammatory cystoid macular oedema. Br J Ophthalmol 1997;81:329.
21Weiss JN. Hyperbaric oxygen therapy and age-related macular degeneration: Undersea Hyperb Med 2010;37:101-5.
22Xu YN, Huang JG. Hyperbaric oxygen treatment for cystoid macular edema secondary to retinal vein occlusion. Zhonghua Yan Ke Za Zhi 1991;27:216-8.
23Indications for hyperbaric oxygen therapy. Undersea Hyperbaric Medical Society. Available from: [Last accessed on 2011 Sept 20].
24Bunn HF, Poyton RO. Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 1996;76:839-85.
25Donald KW. Oxygen Poisoning in Man: Part I. Br Med J 1947;1:667-72.
26Mader JT, Brown GL, Guckian JC, Wells CH, Reinarz JA. A mechanism for the amelioration of hyperbaric oxygen therapy of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 1980;42:915-22.
27Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613-29.
28Available from: [Last accessed on 2013 Oct 13].