Purpose
To evaluate the effect of systemic oxygen therapy in the management of acute ocular chemical and thermal burns.
Design
Prospective, nonrandomized, comparative, interventional case series.
Methods
Twenty-four eyes of 22 patients with grade III to IV acute ocular chemical and thermal burns received conventional medical therapy. The oxygen therapy group (13 eyes) additionally received 100% oxygen using a simple mask at a flow rate of 10 L/minute for 1 hour twice daily. Main outcome measures were time for healing of the corneal epithelial defect and improvement in perilimbal ischemia. Secondary outcome measures included visual acuity, corneal transparency and vascularization, and complications.
Results
Corneal epithelial defects healed within 15.23 ± 3.94 days (range, 10 to 21 days) in the oxygen group versus 59.9 ± 23.33 days (range, 28 to 95 days) in controls ( P < .001). Vascularization of ischemic areas was complete in 14.54 ± 2.70 days (range, 10 to 21 days) in the oxygen group versus 45.09 ± 22.20 days (range, 25 to 105 days) in controls ( P = .001). In the oxygen group, the cornea was more transparent and less vascularized 3 and 6 months after injury. Mean final visual acuity (logarithm of the minimal angle of resolution) was 0.40 ± 0.52 (range, 0 to 1.3) versus 1.11 ± 0.83 (range, 0.1 to 3) in the oxygen and control groups, respectively ( P = .018). In the oxygen group, symblepharon or corneoscleral melting did not develop in any patient; however, in the control group, symblepharon developed in 3 eyes and corneoscleral melting developed in 1 patient.
Conclusions
In the acute phase of ocular chemical or thermal burns, oxygen therapy improves limbal ischemia, accelerates epithelialization, increases corneal transparency, and decreases corneal vascularization. It also may improve visual acuity and reduce complications.
Ocular chemical and thermal burns are true ophthalmic emergencies. The severity of the injury depends on the type of offending agent, its concentration, duration of exposure, and extent of contact. Limbal stem cells, which are the source of corneal epithelial regeneration, are believed to be the most important potential targets in acute chemical burns. The extent of limbal ischemia is considered to be the most important prognostic factor in determining final visual outcomes in these cases.
Improving perilimbal ischemia and controlling inflammation theoretically can preserve partially damaged limbal stem cells. Promotion of epithelial healing, control of inflammation, and prevention of tissue melting are the main objectives in the management of acute ocular burns. Persistent corneal epithelial defects may lead to tissue thinning or melting, perforation, and secondary infections. The de-epithelialized conjunctival surfaces tend to fuse and form symblepharon bands. Early conjunctival epithelial healing may prevent this complication.
With current medical therapies, smooth and complete conjunctivalization and vascularization of the cornea, without eyelid and adnexal structural abnormalities, are the optimal and acceptable goals in severe ocular burns. The ideal situation would be complete corneal conjunctivalization with minimal vascularization of the cornea. Conventional medical therapies, including steroids, ascorbate, citrates, tetracyclines, lubricants, and surgical procedures such as application of a glued-on hard contact lens, tenoplasty, amniotic membrane transplantation, have been used to achieve these goals.
The purpose of this study was to introduce systemic oxygen therapy as a novel therapeutic method in the acute phase of ocular chemical and thermal burns. By reducing perilimbal ischemia and decreasing inflammation, this method of therapy may facilitate epithelial healing and preserve partially damaged limbal stem cells.
Methods
This prospective, comparative, interventional case series was performed at the Department of Ophthalmology, Imam Khomeini Hospital, Ahvaz, Iran, and the Department of Ophthalmology, Labbafinejad Medical Center, Tehran, Iran. We included consecutive patients with grade III and IV (based on the Roper-Hall classification ) acute ocular chemical or thermal burns. Patients referred to the second study center served as the control group and received conventional medical therapy. The treatment group received systemic oxygen therapy in addition to conventional medical therapy on referral to the first study center, but no later than 3 weeks after injury. Oxygen was delivered at 100% concentration by a facial mask with flow rate of 10 L/minute for 1 hour twice daily in the sitting position. The 3-week window for giving oxygen was chosen arbitrarily to include more cases. Exclusion criteria included presentation later than 3 weeks after injury, inadequate treatment before presentation, history of ocular surgery or use of topical medications 1 month before injury, systemic immunosuppressive therapy, pregnancy, and contraindications to oxygen therapy, including chronic respiratory diseases such as chronic obstructive pulmonary disease. In the oxygen therapy group, potential advantages and risks of oxygen therapy were discussed thoroughly with the patients.
All patients had received ocular irrigation with 1 to 2 L lactated Ringer solution after the injury. Conventional medical therapy included topical antibiotics, steroids, cycloplegics, lubricating ointments, artificial tears, vitamin C 500 mg every 6 hours, and systemic tetracycline 250 mg every 6 hours tapered over 2 to 3 months according to the degree of ocular surface inflammation. All patients were recommended forcefully to perform eyelid blinking, manually to separate the eyelids from the globe, and frequently to perform ductions and versions to decrease the risk of symblepharon formation. Irrigation of the ocular surface with balanced salt solution was performed 4 times daily to reduce ocular surface inflammation. Fibrinous bands and membranes in the upper and lower fornices were removed by gentle movement of the end of a thermometer at each follow-up visit. Patients in the oxygen therapy group were examined by a pulmonologist (E.I.) to rule out any contraindication to oxygen therapy. The main outcome measures were improvement of ischemia and healing of corneal epithelial defects; secondary outcome measures included corneal transparency and vascularization, improvement of visual acuity, and complications.
Corneal transparency and vascularization were graded subjectively and independently from 1+ to 4+ by two examiners (F.S. and M.Z.) 3 and 6 months after surgery. If the cornea was severely opacified and iris details were not visible, it was graded as 1+. If the cornea was clear and iris details were clearly identifiable, transparency was graded as 4+. If there was only 1 vascularized quadrant, vascularization was graded as 1+. If all 4 corneal quadrants were vascularized, it was graded as 4+. For greater accuracy, both slit-lamp findings and digital corneal photographs were used for grading. Mean gradings by the two examiners were considered as the final grade.
Patients were visited daily during the first week, every other day during the second week, and twice weekly thereafter until complete healing. At each follow-up visit, a complete eye examination was performed with special attention to perilimbal ischemia and the extent of corneal and conjunctival epithelial defects. Photographic documentation of slit-lamp findings was performed once or twice weekly.
Results
Twenty-four eyes of 22 patients (all male) were included. Twenty eyes had chemical burns (14 alkaline and 6 acidic) and 4 had thermal burns. Thirteen eyes were included for oxygen therapy and 11 eyes served as controls. Mean age was 27.58 ± 14.29 years (range, 6 to 49 years) in the oxygen therapy and 30.3 ± 10.3 years (range, 19 to 49 years) in the control group ( P = .510). Mean follow-up period was 18.0 ± 9.27 months (range, 6 to 42 months) in the oxygen group and 18.36 ± 8.33 months (range, 7 to 37 months) in the control group ( P = .734). Oxygen therapy was initiated at a mean of 9.15 ± 6.91 days (range, 2 to 21 days) after injury. Corneal epithelial defects healed within 15.23 ± 3.94 days (range, 10 to 21 days) after oxygen therapy versus 59.91 ± 23.33 days (range, 28 to 95 days) in the control group (95% confidence interval of the difference, −58.27 to −31.09 days; P < .001). Vascularization of ischemic regions began 4 days after oxygen therapy. Vascularization was complete after 14.54 ± 2.70 days (range, 10 to 21 days) in the oxygen therapy group versus 45.09 ± 22.20 days (range, 25 to 105 days) in the control group (95% confidence interval of the difference, −43.38 to −17.73; P = .001). Three and 6 months after the injury, corneal transparency was 2.8 + versus 1.4 + and 2.6 + versus 1.3 + in the oxygen therapy and control groups, respectively. Corresponding values for corneal vascularization were 2.0 + versus 3.4 + and 2.0 + versus 3.2 + in the oxygen therapy and control groups, respectively. At the end of follow-up, mean visual acuity (logarithm of the minimal angle of resolution) was 0.40 ± 0.52 (0 to 1.3) versus 1.11 ± 0.83 (0.1 ± 3) in the oxygen therapy and control groups ( P = .018). In the oxygen group, 9 of 13 eyes (0.69%) had useful vision (>20/200) without need for surgery; this situation occurred in 4 (0.36%) of 11 eyes in the control group.
At final follow-up, in the oxygen therapy group, 3 (23%) of 13 eyes had corneal vascularization. Complete vascularization of the cornea developed in 2 eyes (grade IV burns), and in 1 eye (grade III burn), vascularization involved 1 quadrant. Oxygen therapy had been started during the third week after injury in all 3 of these cases. In the control group, complete corneal vascularization developed in all eyes with grade IV burns. In at least 1 quadrant of each eye with grade III burns, corneal vascularization developed. In 3 eyes with grade IV burns in the control group, symblepharon developed in at least 1 quadrant. Symblepharon and corneal thinning did not occur in any eye in the oxygen group. One patient in the oxygen therapy group (Patient 2), in whom corneoscleral thinning or melting previously had developed before oxygen therapy, regained near-normal corneal thickness within 10 days after oxygen therapy. In the control group, corneoscleral thinning developed in one patient that was corrected with tenoplasty and amniotic membrane transplantation. Patient characteristics in the oxygen therapy group are summarized in the Table .
| Patient No. | Age (yrs) | Eye | Chemical Agent | Grade of Burn a | Beginning of Oxygen Therapy b | Epithelial Healing c | Improvement of Ischemia c | Follow-up (mos) | Final Snellen BCVA (logMAR) |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 16 | Right | Alkali | IV | 4 | 14 | 14 | 42 | 20/30 (0.18) |
| 2 | 6 | Right | Thermal | III | 20 | 10 | 10 | 30 | 20/20 (0) |
| 3 | 13 | Left | Thermal | IV | 21 | 21 | 21 | 18 | 20/400 (1.3) |
| 4 | 40 | Right | Alkali | IV | 6 | 16 | 16 | 24 | 20/25 (0.1) |
| 5 | 44 | Right | Acid | III | 8 | 14 | 14 | 12 | 20/25 (0.1) |
| 6 | 15 | Left | Thermal | IV | 21 | 20 | 15 | 6 | 20/400 (1.3) |
| 7 | 32 | Right | Alkali | IV | 4 | 17 | 17 | 10 | 20/25 (0.1) |
| 8 | 21 | Right | Alkali | IV | 7 | 12 | 14 | 12 | 20/30 (0.18) |
| 9 | 38 | Right | Acid | III | 3 | 10 | 12 | 16 | 20/20 (0) |
| 10 | 18 | Right | Thermal | III | 5 | 10 | 12 | 12 | 20/25 (0.1) |
| 11 | 39 |
| Alkali |
| 9 |
|
| 14 |
|
| 12 | 49 | Left | Alkali | IV | 2 | 16 | 14 | 12 | 20/30 (0.18) |
a Based on Roper-Hall classification.
b Number of days after injury.
Case Reports
Patient 1
A 16-year-old worker with unilateral ammonia injury in his right eye was referred 4 days after injury. Initial examination revealed visual acuity of hand movements, 360-degree limbal ischemia, large bulbar and palpebral conjunctival epithelial defects, and total corneal epithelial defect with severe edema. A gray inflammatory membrane covered the entire ocular surface with multiple fibrinous bands. One day after oxygen therapy, corneal edema decreased significantly, allowing detection of severe anterior chamber reaction with heavy pigment dispersion and a dense anterior subcapsular cataract, indicating intraocular penetration of the chemical agent. Four days after oxygen therapy, the gray membrane totally disappeared, small vessels began to grow in the inferonasal and inferotemporal quadrants, and early healing of the corneal epithelium was evident. Progressive vascularization of ischemic areas and healing of the corneal epithelium occurred. Fourteen days later, epithelial defects healed with significant vascularization in most parts of the ischemic conjunctiva. Six months later, the eye was quiet, the cornea was opaque with minimal vascularization, and there was no symblepharon formation. Penetrating keratoplasty together with cataract extraction and intraocular lens implantation was performed 2 years after injury. Final best-corrected visual acuity (BCVA) was 20/30.
Patient 2
A 6-year-old boy with a grade III unilateral thermal burn in his right eye was referred 20 days after injury ( Figure ). According to his physician, refractory and progressive corneoscleral thinning or melting started 10 days after the burn. BCVA was 20/80 in his right eye. Corneal thickness had decreased to less than one third. Four days after oxygen therapy, small vessels began to grow into the ischemic area. Ten days later, complete healing with fibrovascular tissue replacement occurred and the cornea regained near normal thickness (Figure). Final BCVA was 20/20.
