Hyperbaric Oxygen Therapy in Ophthalmology: A Narrative Review

**Background** The retina has the highest oxygen consumption rate of any organ, making it vulnerable to hypoxic-ischemic damage. Hyperbaric oxygen therapy (HBOT) involves breathing nearly 100% oxygen inside a chamber pressurized to 1 atmosphere absolute (ATA), increasing dissolved oxygen in tissues. During HBOT, nitrogen in the vitreous is replaced with oxygen, which acts as an oxygen reserve for the first 2 days of treatment, and tissue oxygen levels remain elevated for up to 4 hours after therapy. HBOT has been used for conditions such as decompression sickness and wound healing for over 50 years, but its use in ophthalmology remains off-label. This narrative review provides an updated overview of HBOT's indications, effectiveness, and safety in treating ophthalmic disorders.

**Methods** A systematic search of EMBASE, PubMed, ScienceDirect, Web of Science, The Cochrane Library, Google Scholar, and Ovid MEDLINE was conducted using keywords such as "HBOT and CRAO/BRAO," "HBOT and retina," "HBOT and eye," "HBOT and macula," "HBOT and diabetic retinopathy," "HBOT and cornea," and "HBOT and optic neuropathy." The latest search was performed on 11 September 2023. Inclusion criteria comprised original studies, case reports, systematic reviews, and meta-analyses published in English. Exclusions included self-standing abstracts, duplicated data, and articles lacking original data or clear methods. Two independent authors extracted data on country, first author, publication year, study population, intervention, study design, and follow-up duration.

**Key Results** - **Healthy Retinas**: Studies on HBOT's effect on healthy retinas show contradictory results. Sayin et al. found no changes in retinal layer thickness after 10 HBOT sessions, while Tukenmez Dikmen et al. reported a statistically significant change in central macular thickness after 20 sessions. Çevik et al. observed decreased vascular density in superficial and deep capillary plexuses but no effect on the foveal avascular zone. - **Diabetic Retinopathy and Diabetic Macular Edema**: Evidence is mixed. Sellman et al.'s randomized, double-blind, placebo-controlled trial with 50 patients found no differences in visual acuity, retinopathy stage, or macular edema between HBOT and placebo groups over 2 years. In contrast, Maalej et al. reported reduced central macular thickness and stabilized DR lesions in 25 NPDR patients after 6 weeks of HBOT. Kaldırım et al. observed macular thickening on SD-OCT in NPDR patients after 30 HBOT sessions, with choroidal thinning suggesting vasoconstriction. Gün et al. found no acute effects on macular or choroidal thickness after a single session. Two case reports described vitreous hemorrhage following HBOT in patients with proliferative diabetic retinopathy. - **Central Retinal Artery Occlusion (CRAO) and Branch Retinal Artery Occlusion (BRAO)**: The strongest evidence supports HBOT for RAO. In animal models, HBOT reduced apoptosis from 58% to 30% cell loss. Rozenberg et al. compared HBOT plus standard care versus standard care alone in adults with CRAO symptoms within 24 hours; the HBOT group showed significantly improved final vision after adjusting for age, sex, and symptom duration. Masters et al. reported 72% of patients experienced visual acuity improvement for up to 30 months, with greatest benefit when treated within 12 hours. Bagli et al. found average logMAR visual acuity improved from 3.0 to 1.8 after 20 HBOT sessions. Elder et al. identified 31 patients with acute retinal artery occlusion; all nine with permanent improvement were treated within 10 hours. A standardized protocol study (28 patients) achieved ≥0.3 logMAR improvement in 50% at 1 month. Schmidt et al. reported final visual acuity in BRAO patients was 0.69 ± 0.29 with HBOT versus 0.32 ± 0.23 with hemodilution alone. Menzel-Severing et al. found mean visual acuity improvement of three lines with HBOT versus one line with hemodilution alone, though not statistically significant (p < 0.0001). Wu et al.'s meta-analysis of seven RCTs (251 individuals) showed oxygen therapy, especially HBOT, led to statistically significant visual acuity improvement, with median treatment duration of 10.5 hours and three sessions being most effective. - **Central Corneal Thickness**: Ayata et al. found central corneal thickness decreased in non-diabetic patients after a single HBOT session, but not in diabetics, possibly due to impaired Na+/K+-ATPase activity. - **Optic Neuropathy**: Malik et al. reported that HBOT combined with oral corticosteroids preserved visual acuity in four patients with radiation optic neuropathy. A case of traumatic optic neuropathy showed improvement from hand motion to 6/60 after 61 HBOT sessions. Another case of postoperative posterior ischemic optic neuropathy showed vision improvement close to baseline after HBOT. - **Choroidal Neovascularization**: Malerbi et al. studied seven patients receiving 10 daily HBOT sessions; five also received intravitreal bevacizumab. After a mean follow-up of 150 days, CNV area and diameter decreased in five patients, remained stable in one, and increased in one. - **Other Case Reports**: HBOT was beneficial in mumps retinitis (40 sessions, visual acuity improved to 20/100 and 20/320), orbital emphysema (35 sessions), carbon monoxide poisoning (50 sessions, visual acuity improved from 0.2 to 0.5), and acute macular neuroretinopathy in systemic lupus erythematosus (12 cycles, maintained improvement over 1 year). - **Disadvantages**: HBOT can cause dry eye, cataracts (after >150 total hours), reversible myopic shift (up to −4.50 diopters), keratoconus, otic barotrauma, bronchopulmonary toxicity, and seizures. Oxidative stress may exacerbate age-related macular degeneration and glaucoma. One case reported acute macular edema after seven HBOT sessions.

**Clinical Implications** HBOT shows promise as a safe, low-cost, and moderately effective treatment for acute retinal artery occlusion, especially when initiated early (within 12–24 hours). However, the evidence is largely from case reports and observational studies, with few high-quality randomized controlled trials. The review emphasizes the need for standardized protocols, larger patient cohorts, and rigorous methodologies to establish evidence-based guidelines. HBOT is not approved by regulatory authorities for ophthalmic indications, and careful risk assessment is required due to potential side-effects, including oxidative stress and cataract formation. The average cost per HBOT session is approximately USD 500, making it a cost-effective intervention compared to other treatments.