Corneal Injuries and Wound Healing – Review of Processes and Therapies

Research Article

Austin J Clin Ophthalmol. 2014;1(4): 1017.

# Corneal Injuries and Wound Healing – Review of Processes and Therapies

Benjamin D Ashby, Qian Garrett and Mark DP Willcox*

Department of Optometry and Vision Science, University of New South Wales, Australia

*Corresponding author: Mark Willcox, School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia

Received: February 14, 2014; Accepted: March 12, 2014; Published: March 21, 2014

Wounds in the cornea are usually self–limiting, but are common and a major reason for visits to hospital emergency departments. Although most heal without permanent visual impairment and do not require hospitalisation, in Australia these injuries are conservatively estimated to cost $155 million per year when lost working days and medical expenses are both taken into consideration. There is also some limited evidence that these injuries have a longer term impact on quality of life. This paper describes the impact of corneal injuries, the structure of the cornea, the cellular processes involved in corneal wound healing, and review the current and future therapies to treat this condition. ## Introduction and Background ## Epidemiology Eye injuries are the most common reason for attendance at an emergency department, accounting for 14% of eye department presentations and 8% of eye department hospitalisations [1,2]. These figures are reflected in an annual incidence of 0.315% (CI 0.266– 0.363%) based on over 800,000 patients treated in the United States for eye injuries in emergency departments in the year 2000 [3]. This is of a similar magnitude to the findings of most other large studies of urban populations in developed countries over the last 40 years although reported values are approximately three times higher for Australian and Italian populations [4–7]. These numbers increase in rural locations [6] and developing [8] or newly industrialised countries[7]. Approximately three quarters of these emergency ocular trauma assessments are for corneal foreign bodies or an abrasion indicating the primary site of injuries is most commonly the corneal epithelium.[2,3,6]. Less common but with far greater likelihood of sight threatening sequelae are chemical burns which account for 5–22% of eye injuries [3,6,9,10]. Based on hospital admissions the majority, 30–80%, of burns are from alkaline substances. These come into contact with the eye from either accidental exposure or assaults [9,11]. The most common sources of alkali chemicals involved in ocular burns are readily available building products and household cleaners such as ammonia, sodium hydroxide, plaster and cement [9,12,13]. Rarer still and also of a severe nature is corneal compromise associated with microbial keratitis (MK), that is a particular concern in contact lens wearing populations. The incidence in Australia has recently been reported at 4.2 per 10,000 (CI 3.4–5.5) [14] a figure comparable to the 4–5 per 10,000 found in most international studies in developed countries over the last 30 years [15–17]. This problem is however not limited to contact lens wears as the remaining 78% of hospital treated MK have no association with lens use, although this only represents an incidence of 5–11 per 100,000 in the general population [13,18]. The problem is much greater in developing countries where the incidence is higher by a factor of 10 [19]. There is also corneal compromise occurring as part of elective procedures, primarily the incisions and ablations created for refractive and cataract surgeries. Since gaining regulatory approval in the US in 1998 over a million patients a year are undergoing laser assisted in–situ keratomileusis (LASIK) procedures, with smaller numbers undergoing the more invasive photorefractive keratectomy (PRK) and the increasingly rarer radial keratotomy [20, 21]. While cataract extractions require a smaller epithelial wound they are performed much more frequently than refractive surgeries with an increasing majority of incisions positioned over the clear cornea rather than the limbus [21]. According to World Health Organisation data most developed countries have a cataract surgery rate of over 4,000 per year per 100,000 population with Australia approximately 50% higher based on data reported in the Blue Mountains Eye Study [22]. ## Morbidity Although ocular traumas account for almost 2% of emergency hospital presentations, most heal without permanent visual impairment and do not require hospitalisation [1]. Those of working age are consistently reported to be at more than double the risk for these eye injuries with an average of three lost days of productivity [2]. This is a considerable economic burden that is only increased by the additional care required for the 5–11% of cases that will need hospitalisation [2,3,6]. In Australia these injuries are conservatively estimated to cost$155 million per year when lost working days and medical expenses are both taken into consideration [6].

There is also some limited evidence that these injuries have a longer term impact on quality of life. A study of 47 patients conducted 2 years after an ocular trauma found twice the level of physiological morbidity expected in the normal population. A fear of blindness was reported by 87% of patients and according to the authors the experience caused “considerable and sustained distress many months after the trauma”. This is disproportionate to the outcome as only 17% of participants had a final vision of less than 6⁄60 in the injured eye [23]. The psychological impact may be explained by the considerable pain, photophobia and sudden reduction in vision associated with corneal injuries. A study of 88 consecutive patients presenting to casualty with corneal abrasions rated their pain, photophobia and visual blur as 3.7, 3.5 and 2.8 out of 5, respectively, on a visual analogue scale where 0 is no pain⁄photophobia⁄blur and 5 is the worst pain⁄ photophobia⁄blur imaginable [24]. At the time of presentation half of these patients required both oral analgesia in addition to topical ocular pain control measures such as lubricants and cycloplegia. The pain is then reported to diminish as epithelialisation takes place [24– 27]. Thus initially corneal injury is associated with appreciable pain and reduced vision that then improved as healing takes place. Even after the eye has recovered there may still be a prolonged period of anxiety.

Chemical injuries represent a much more serious threat to the eye with 8–12% requiring hospital admission for a week followed by 3–6 months of treatment [6]. For non–admitted cases the majority still need medical reviews for 1–7 days [9]. Of the corneal traumas the prognosis is poorest for alkali burns with 20% resulting in a final visual acuity of less than 6⁄12 [11,28].

Corneal compromise from microbial invasion is a rare but serious event with an incidence in the world developed countries of 2 million every year [29]. Mild microbial keratitis associated with contact lens use has been estimated to cost AU$1228 (US$1353) per case. This includes both the cost of treatment and lost working days [30]. The economic impact of microbial keratitis in non–contact lens wearers from developed economies has not been reported. In developing countries, using India as an example, microbial keratitis results in an average of one month lost productivity, a cost of treatment that exceeds the average monthly income and a final visual outcome of less than 6⁄60 in almost half of cases [31]. A lower cost may be anticipated for non–contact lens wearers as they would not incur the \$150 expense for new spectacles [32]. Also the incidence of the more aggressive Pseudomonas aeruginosa pathogen is much lower [13]. owever a higher cost in the non–contact lens wearing population is more likely as the average disease severity is greater, with longer hospital stays and more medical re–examinations required [13]. More than half of those cases of a severity requiring hospital admission result in a permanent reduction in vision [33].

Cataract surgery in the current era is a safe procedure with severe, sight threatening, adverse events occurring in no more than 0.4% of cases [34]. Of these complications endophthalmitis accounts for 1⁄3rd with a proposed link to the corneal incision that is supported by double the rate of infection for the more popular clear corneal incisions versus scleral incisions [34–36]. For refractive surgery LASIK is currently preferred over PRK due to the faster visual recovery and lower level of postoperative pain [21,37,38]. Both of these disadvantages to PRK can be attributed to the increased healing time required by a largerarea of cornea to reepithelialise after the procedure. PRK is however suitable for a wider range of patients and is reported to provide a better visual outcome with fewer complications [39]. This is however not universally agreed upon with a pre–2005 meta–analysis of the literature by Shortt et al. tentatively suggesting LASIK may be safer but of similar efficacy [40].

## Corneal Wound Healing

Corneal Structure: The cornea is the transparent anterior segment of the globe of the eye that refracts light onto the retina. It is the first element in the eye’s optical system, contributing 2⁄3rd of the eye’s total focusing power and must remain essentially clear for optimal vision to be achieved. To maintain transparency the cornea must remain a vascular, unscarred and preserve its highly regular organised internal structure. The cornea is also the most sensitive tissue in the body.

A normal cornea consists of three well defined layers (Figure 1).