How an ocular burn damages the eye
The cornea is the transparent window of the eye that helps focus light to form an image of the outside world. For the cornea to remain transparent, it must have a healthy surface layer of epithelium, a stable tear film, and an absence of blood vessels. The epithelium is the moist cellular layer that covers the cornea, the white part of the eye, and the inside of the eyelids. The epithelium that covers the cornea is different from the epithelium of the conjunctiva. It is maintained in this state by a population of specialised stem cells found at the margin of the cornea (the limbus). In the normal eye, corneal epithelial cells slowly migrate from the limbus towards the centre of the cornea.
A burn to the eye initially damages the surface epithelial layer, but it can also damage the deeper structures of the eye and the eyelids. A characteristic of an acute burn is an epithelial defect. This defect can fully recover after a minor burn. However, if the burn damages the stem cells of a segment of the limbus, the normal epithelium central to that area may not recover. The cornea is then covered by a functionally different type of epithelium derived from the peripheral conjunctiva, which may take weeks or months, and the cornea can become hazy and vascularised. In the absence of any epithelial covering, an additional risk is that the deeper tissues of the exposed cornea (stroma) may become progressively thinner and eventually perforate. The more extensive the damage to the limbus (measured in clock hours), the worse the outcome. The abnormal surface of the cornea, as well as haze and damage to structures within the eye (iris, lens, retina, optic nerve), can all lead to loss of vision.
Treatments for ocular burns
A burn to the surface of the eye is an emergency, and the eye must be washed immediately with water or saline to remove any chemical agents. The amount of damage to the epithelium (an epithelial defect) and the blood vessels at the edge of the cornea are measured, estimating the risk of future complications. The eye is then treated with medicines to reduce the risk of further complications and help the epithelial layer recover. Some doctors also use an amniotic tissue membrane placed over the surface of the eye. The amniotic membrane is the sac that surrounds a baby as it develops inside its mother.
Why we did this Cochrane Review
We wanted to know whether using an amniotic membrane with medicines is better than just medicines.
What did we do?
We looked for studies in which an amniotic membrane was used to treat eyes that had been burned. We then looked for studies comparing eyes treated with medicines and an amniotic membrane patch with eyes treated using only medicines. We looked for randomised controlled trials, in which the treatment that people received was decided at random because these studies give the most reliable evidence about the effect of treatment. We assessed the treatment of moderate burns and severe burns separately, because they have different outcomes. We measured whether the treatment worked by comparing the proportion of eyes in which the epithelium over the cornea had failed to recover 21 days after the injury, visual function at the end of treatment, the presence of abnormal new blood vessels on the cornea, scarring between the cornea and the lids, the time taken for the epithelium to heal and adverse events in the intervention and control groups. We assessed the risk of bias in the randomised controlled study findings across pre-specified domains. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to evaluate certainty of evidence include risk of bias, imprecision, inconsistency, indirectness, and publication bias.
What we found
We found two randomised controlled studies comparing the effect of medicines with the addition of an amniotic membrane patch inserted within seven days of the injury against medicines alone. One study suggested that treatment with amnion may be beneficial in moderate burns, but we found the certainty of the evidence to be low due to a high risk of bias and serious imprecision. For severe burns, there were no important differences between eyes that received an amniotic membrane and eyes that did not.
There is only uncertain evidence from randomised controlled studies of an important difference in healing between eyes treated with medicines and an amniotic membrane within seven days of an ocular burn and eyes that are treated only with medicines. Further research is needed to identify the best treatment for acute burns to the eye to reduce the risk of potentially devastating consequences and visual loss.
How up to date is this review?
Searches were last done in September 2021.
There is uncertain evidence to support the treatment of moderate acute ocular surface burns with AMT in addition to standard medical therapy as a means of preventing failure of epithelialisation by day 21, improving visual outcome and reducing corneal neovascularisation, symblepharon formation and time-to-epithelialisation. For severe burns, the available evidence does not indicate any significant benefit of treatment with AMT.
Ocular surface burns can be caused by chemicals (alkalis and acids) or direct heat. One effect of the burn is damage to the limbal epithelial stem cells of the ocular surface with delayed re-epithelialisation, stem cell failure, and conjunctivalisation of the cornea. Amniotic membrane transplantation (AMT) performed in the acute phase (day 0 to day 7) following an ocular surface burn is claimed to reduce pain and accelerate healing. The surgery involves securing a layer of amniotic membrane (AM) to the eyelid margins as a patch to cover the entire ocular surface. However, there is debate about the severity of an ocular burn that may benefit from AMT and uncertainty of whether AMT improves outcomes.
To compare the effect of AMT with medical therapy in the first seven days after an ocular surface burn, compared to medical therapy alone.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 9); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 September 2021.
We included randomised trials that compared an AMT applied in the first seven days following an ocular surface burn in addition to medical therapy with medical therapy alone. The outcome measures were failure of re-epithelialisation by day 21 post injury, visual acuity at final follow-up, corneal neovascularisation, symblepharon, time to re-epithelialisation and adverse effects.
Two review authors independently screened search results, assessed the included studies for risk of bias and extracted relevant data. We contacted trial investigators for missing information. We summarised data using risk ratios (RRs) and mean differences (MDs) as appropriate.
We analysed two RCTs, but excluded individual patients who had been treated outside the acute phase in one of the studies (data provided by study authors). In total, 36 moderate burns from one RCT and 92 severe burns from two RCTs were evaluated separately. For both categories, the certainty of the evidence was downgraded principally as a result of high risks of performance and detection biases, and because of imprecision indicated by very wide confidence intervals. In addition, follow-up was insufficiently frequent to calculate time-to-epithelialisation precisely.
Moderate severity ocular burns (Roper-Hall classification II-III)
The relative risk of AMT on failure of epithelialisation by day 21 was 0.18 (0.02 to 1.31), and LogMAR visual acuity was 0.32 lower (0.55 to 0.09 lower) in the treatment group (i.e. better), suggesting a possible benefit of AMT. The GRADE assessment for failure of epithelialisation by day 21 was downgraded to very low due to the risk of bias and imprecision (very wide confidence intervals including no effect). The GRADE assessment for visual acuity at final follow-up was downgraded to low due to the risk of bias and imprecision (optimal information size not met). The relative effects of AMT on corneal neovascularisation (RR 0.56; 0.21 to 1.48), symblepharon (RR 0.41; 0.02 to 9.48) and time-to-epithelialisation (13 days lower; 26.30 lower to 0.30 higher) suggest possible benefit of AMT, but the wide confidence intervals indicate that both harm and benefit are possible. GRADE assessments for these outcomes were once again downgraded to very low due to the risk of bias and imprecision. Since adverse effects are rare, the small sample would have fewer occurrences of rare but potentially important adverse effects. The GRADE assessment for adverse effects was therefore considered to be low.
Severe ocular burns (Roper-Hall classification IV)
The relative risk of AMT on failure of epithelialisation by day 21 was 1.03 (0.94 to 1.12), and LogMAR visual acuity was 0.01 higher (0.29 lower to 0.31 higher) in the treatment group (i.e, worse), indicating no benefit of AMT. GRADE assessments for failure of epithelialisation by day 21 and final outcomes were downgraded to low. The relative effects of AMT on corneal neovascularisation (RR 0.84; 0.66 to 1.06), symblepharon (RR 0.89; 0.56 to 1.42) and time-to-epithelialisation (1.66 days lower; 11.09 lower to 7.77 higher) may include both benefit and harm. GRADE assessments for corneal neovascularisation, symblepharon and time-to-epithelialisation were downgraded to low due to risk of bias and imprecision. For adverse effects, the GRADE assessment was downgraded to low, reflecting the small sample sizes in the RCTs.