Management of ocular thermal and chemical injuries, including amniotic membrane therapy Robert Fish and Richard S. Davidson Rocky Mountain Lions Eye Institute, University of Colorado School of Medicine, 1675 N. Aurora Court, MS F731, PO Box 6510, Aurora, CO 80045, USA Correspondence to Richard S. Davidson, MD, Associate Professor, Rocky Mountain Lions Eye Institute, University of Colorado, School of Medicine, 1675 N. Aurora Court, MS F731, PO Box 6510, Aurora, CO 80045, USA Tel: +1 720 848 2500; fax: +1 720 848 5014; e-mail: [email protected] Current Opinion in Ophthalmology 2010, 21:317–321 Purpose of review To provide a concise review of the literature regarding potential management strategies of ocular thermal and chemical injuries. Recent findings After experiencing a serious ocular surface burn, either thermal or chemical, the goal of therapy is to restore a normal ocular surface and corneal clarity. If extensive corneal scarring and/or limbal stem cell deficiency are present, techniques such as limbal stem cell grafting, amniotic membrane transplantation and possibly a keratoprosthesis can be employed to help restore vision. This article will review the literature available and discuss how these techniques have improved the prognosis of patients with serious thermal and chemical injuries. Summary Ocular thermal and chemical injuries are a true ocular emergency and require immediate and intensive evaluation and treatment. The sequelae of an ocular burn can be severe and particularly challenging to manage. Improvements in the understanding of the pathophysiology of a radiant energy or chemical injury as well as advancements in ocular surface reconstruction have provided hope for patients in whom would otherwise have a dismal visual prognosis. Keywords acid burn, alkali burn, amniotic membrane therapy, keratoprosthesis, ocular burn, thermal burn Curr Opin Ophthalmol 21:317–321 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 1040-8738 Introduction Burns to the eyelids, conjunctiva, cornea, or sclera, whether from radiant energy or a chemical cause, are a true ophthalmic emergency . The extent of the injury may vary but requires immediate evaluation and treatment. Ocular burns are classified based on their etiologies with radiant energy injuries (either thermal or ultraviolet) tending to carry a better prognosis compared with chemical exposures (acid or alkali). In general, the severity of the injury is directly related to the duration of exposure and the properties of the causative agent . Radiant energy injuries Radiant energy injuries may be divided into thermal or ultraviolet exposure. The cell death that occurs from a thermal injury is usually limited to the superficial epithelium, however, more extensive damage may sometimes occur. When a patient presents with a radiant energy injury it is important to thoroughly assess the extent of the ocular damage. Careful inspection of the eyelids and ocular surface is essential to determine the proper approach to 1040-8738 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins treatment. If the eyelids are injured as a result of the burn, it is important to determine whether or not the patient is able to adequately close the eye (s). If voluntary closure is not possible, then placement of a suture tarsorrhaphy may be helpful to protect the ocular surface. In addition to inspection of the eyelids, a complete ocular examination should also be performed. One should assess the status of the conjunctiva (both palpebral and bulbar) as well as the corneal surface. Corneal epithelial defects should be quantified and the presence or absence of an anterior chamber reaction should also be noted. Ultraviolet burns tend to result in a severe punctate keratitis. Although these injuries tend not to be vision threatening, they may be extremely painful. With frequent lubrication of the ocular surface they tend to resolve with minimal sequelae within 24–48 h. Treatment in the immediate period following thermal injury should consist of frequent lubrication of the ocular surface with a bland lubricating ointment (or artificial tears if damage to the ocular surface is minimal) and prevention of infection with the use of a topical DOI:10.1097/ICU.0b013e32833a8da2 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 318 Corneal and external disorders Figure 1 Photo of severe cicatricial changes following thermal injury (photo courtesy of Vikram D. Durairaj M.D.) antibiotic. If a significant amount of corneal edema is present then adding a topical steroid can be beneficial but if this is done prior to closure of the epithelium then one needs to observe the patient carefully for signs of infection. If the eyelids are significantly burned then a combination antibiotic/steroid (tobramycin/dexamethasone, Alcon Laboratories, Fort Worth, Texas, USA) ointment may also be beneficial in promoting healing and minimizing scar formation. These patients should be followed very closely for signs of infection and referral to an oculoplastics specialist may also be indicated if the patient shows signs of cicatricial eyelid changes as the eye is healing. Figs 1 and 2 demonstrate the severe cicatricial eyelid changes that may occur with a severe thermal injury (photos courtesy of Vikram D. Durairaj, M.D.). In situations where it appears that the limbal stem cells have been damaged then treatment should proceed as described below in the section on chemical injuries. Chemical injuries Like patients with a thermal injury, patients with a chemical injury will often present with the sudden onset of severe pain, epiphora, and blepharospasm after exposure to the inciting agent. Patients are often male Figure 2 Photo of same patient after surgical repair (photo courtesy of Vikram D. Durairaj M.D.) Figure 3 Grade 4 alkali burn 10 days after initial injury. Cornea is beginning to show some clearing centrally, however, a significant epithelial defect and ocular surface inflammation remains and work in an industrial setting, however, an acid or alkali injury can also occur within the domestic and/or assault setting. Eye protection (for those working with chemicals) is important to minimize the risk and severity of the exposure, but patients wearing eye protection may still encounter significant ocular contamination. Chemicals that may be implicated in alkali injuries include cleaning agents (sodium hydroxide), fertilizers (ammonium hydroxide), plaster (calcium hydroxide) and air bags (sodium hydroxide aerosol) [2,3]. Alkali substances are lipophilic and penetrate the eye more rapidly than acids. The basic substance can quickly deposit within the tissues of the ocular surface causing a saponification reaction within those cells. The damaged tissues then secrete proteolytic enzymes as part of an inflammatory response, which leads to further damage (a process called liquefactive necrosis). Alkali substances can penetrate into the anterior chamber as well causing cataract formation, damage to the ciliary body and damage to the trabecular meshwork. Due to the rapidity of this process, patients may experience irreversible intraocular damage in as little as 5–15 min (Fig. 3). Acid injuries tend to be less severe due to the fact that acids tend to cause protein coagulation in the epithelium, which limits further penetration into the eye. The one exception to this is hydrofluoric acid, which may rapidly pass through cell membranes and enter the anterior chamber of the eye . The damage to the corneal and conjunctival epithelium from an ocular burn may be so severe as to damage the pluripotent limbal stem cells causing a limbal stem cell deficiency (LSCD). This may lead to opacification and Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Management of thermal and chemical injuries Fish and Davidson 319 neovascularization of the cornea. An acute intraocular pressure rise occurrence due to shrinkage and contraction of the cornea and sclera is also possible . Longer term intraocular pressure rises can occur from accumulation of inflammatory debris within the trabecular meshwork as well as damage to the trabecular meshwork itself. Damage to the conjunctiva can cause extensive scarring, perilimbal ischemia, and contracture of the fornices. Loss of goblet cells and conjunctival inflammation can leave the ocular surface prone to dryness. This predisposition to dryness along with the possibility of lid malposition due to symblepharon formation or the formation of a cicatricial entropion or ectropion can be particularly problematic as well. Initial evaluation and initial treatment Patients suffering from a chemical injury will often initially present to the emergency department following exposure. Once a history of chemical exposure is obtained, the chemical should be identified if possible but this should not delay treatment of the patient. The local poison control center can be contacted if unsure of the nature of the chemical, www.aapcc.org, 1-800-2221222. The emergency department should be familiar with the necessity of prompt evaluation and treatment of this emergency and it should be triaged appropriately. Immediate treatment should include copious irrigation prior to ophthalmic evaluation. pH testing should be done in concert with this and familiarity with the testing strips with reference to the manufacturer’s specifications regarding interpretation, if necessary, should be sought if unfamiliar with how to interpret the results. The initial ocular examination should include a basic ophthalmic examination with attention being paid to the examination of the fornices to ensure that there is no remaining alkaline material such as lime or plaster present. Sweeping the fornices with a glass rod can sometimes aid with this assessment. Irrigation with isotonic saline or lactated Ringer’s solution should be performed and sometimes irrigating volumes up to 20 liters or more is required to change the pH to a physiologic level. The longer irrigation is delayed, the more irrigation volume that will likely be required as the chemical can deposit within the tissue making it somewhat recalcitrant to irrigation. A topical anesthetic to provide the patient with some degree of comfort may be helpful. One study comparing isotonic saline, lactated ringer’s solution, normal saline with bicarbonate, and balanced saline solution plus (BSS Plus, Alcon Laboratories, Fort Worth, Texas, USA) noted no difference in normalization of pH but did note more tolerance and comfort with BSS plus . A Morgan lens may also be employed to allow more direct irrigation of the ocular surface, thereby limiting a patient’s involuntary blepharospasm from preventing irrigation of the ocular surface. Once copious irrigation has been achieved and the pH is neutralized, the ocular examination should proceed with attention being paid to visual acuity, intraocular pressure, perilimbal blanching/ischemia (paying attention to clock hours of involvement of blanching, as well as overall health and appearance of the corneal epithelium). Initial pH testing should involve both eyes even if the patient claims to only have unilateral ocular pain/irritation so that a contralateral injury is not neglected. Classification Classification schemes regarding the extent of the initial injury were initially developed in the mid 1960’s, first by Ballen  and then further modified by Roper-Hall . The Roper-Hall classification system was largely based on the degree of corneal haze and the amount of perilimbal blanching/ischemia noted on a grading scale of I (good prognosis) to IV (poor prognosis) (Table 1). Pfister subsequently made a classification system varying from mild, mild-moderate, moderate to severe, severe and very severe based upon pictures and photographs demonstrating corneal haze and perilimbal ischemia . Dua proposed a classification scheme based upon clock hour limbal involvement (as opposed to ischemia) as well as percentage of bulbar conjunctival involvement . The important thing in the clinical setting is to note the amount of limbal, corneal and conjunctival involvement at the time of initial injury and to document changes in the examination as the patient is followed, however, grading the severity may provide the patient with a general idea of the prognosis. Subacute medical management Once the pH has been neutralized and the patient has been more thoroughly examined, attention should be directed toward treating the injuries the patient has received. This treatment includes promoting healing of Table 1 Classification of severity of ocular surface burns by Roper–Hall  Grade Prognosis Cornea Conjunctiva/limbus I II III IV Good Good Guarded Poor Corneal epithelial damage Corneal haze, iris details visible Total epithelial loss, stromal haze, iris details obscured Cornea opaque, iris and pupil details obscured No limbal ischemia <1/3 limbal ischemia 1/3–1/2 limbal ischemia >1/2 limbal ischemia Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 320 Corneal and external disorders the corneal epithelium and treating the intraocular pressure if elevated. If the extent of the injury is minor, preservative free artificial tears may be adequate to promote reepithelization. A bandage contact lens may provide the patient with more comfort as well. Studies have demonstrated that oral or topical ascorbate, and topical citrate can promote epithelial healing and limit stromal necrosis . A topical steroid may also be employed to limit the ensuing inflammatory infiltrate and promote healing. Use of topical steroids alone can potentially lead to a further increase in corneoscleral melt . Davis et al.  evaluated patients with topical prednisolone 0.5% in conjunction with topical ascorbate 10% and concluded that there was not an associated increase in corneoscleral melt if topical steroids were used until reepithelization. If there is a large epithelial defect, use of a topical antibiotic such as a fourth generation fluoroquinolone for antimicrobial prophylaxis is indicated. If there is extensive damage and necrosis, the patient may be better served undergoing debridement of the necrotic tissue. Following debridement there may be a role in amniotic membrane grafting to promote epithelial regeneration whilst suppressing perilimbal inflammation (see below surgical management). If the patient has an elevated intraocular pressure, aqueous suppression is the first choice. Oral aqueous suppression if the patient has no other contraindications may be preferable to avoid further toxicity to the epithelium from the preservatives in the drops. This method of treatment may also be more comfortable to the patient as well. Cycloplegia may also improve the patient’s comfort following the injury. These patients will require close follow up after the initial injury for management of possible sequelae including potential corneal ulceration/perforation, secondary open angle glaucoma, corneal scarring, limbal stem cell deficiency, conjunctival scarring/symblepharon, dry eye, and exposure due to lid malposition from cicatricial changes. Surgical management of ocular surface damage Surgical management of an ocular burn is directed towards the initial debridement of necrotic material and, if necessary, the application of topical adhesives or tectonic grafting (in the setting of a perforated corneal ulcer), replacing devitalized limbal stem cells, restoring the corneal clarity and transparency, and addressing lid malposition/lagophthalmos as well as treating glaucoma. The surgical management of lid malposition and glaucoma extend beyond the scope of this article. In recent years, advancements have been made in limbal stem cell transplantation, adjunctive usage of amniotic membrane and, in severe cases, placement of a keratoprosthesis. The improvements made in these areas have provided patients with hope of visual rehabilitation in cases that would have previously been given a very poor prognosis dooming them to a life of disability and dependency. Amniotic membrane transplantation (AMT) helps to restore the conjunctival surface and reduce limbal stromal inflammation and can be used in both the acute and chronic setting following a chemical or thermal injury [12–14] Meller et al.  reported on 13 eyes of 11 patients receiving AMT within 2 weeks following conventional medical therapy. They noted epithelialization in 11 of 13 eyes, and only those eyes with grade IV burns experienced limbal stem cell deficiency (LCSD). AMT can be used in the clinical setting of ocular surface reconstruction, healing an epithelial defect, improving limbal stem-cell function (disruption of the limbal barrier with irregular epithelial surface or visually significant corneal scarring), and symptomatic pain relief. Tejwani reported a 92.9% success in healing epithelial defects, 84.6% success in symptomatic relief, 63.5% success in ocular surface reconstruction and 63.3% success in improving limbal stem cell function in a retrospective case review of patients with alkali injuries undergoing AMT either in the acute or chronic setting after the initial injury . Tseng et al.  reported four patients with mild LCSD due to chemical burns and showed significant postoperative improvement following AMT. In patients with total LCSD, there were eight patients undergoing staged AMT followed by autologous limbal stem cell transplantation (ALT) and penetrating keratoplasty (PKP) of which seven out of eight experienced an improvement in visual acuity, whereas one experienced a worsened visual acuity. Gomes et al.  reported the usage of AMT alone in patients with partial LCSD and in concert with ALT for those with total LSCD in patients with chemical burn. They reported 90% of patients showed an improvement in their visual acuity. Ocular surface restoration with AMT has the advantage of creating an environment with reduced perilimbal inflammation; promoting healthy epithelium with reduced corneal neovascularization and may set the patient up for successful future ALT and/or PKP if stromal scarring remains. The downside of autologous limbal stem cell transplantation is the need for systemic immunosuppression. In those patients in whom it ultimately does not become possible to restore corneal clarity and a normal ocular surface, a keratoprosthesis remains a viable option. A long Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Management of thermal and chemical injuries Fish and Davidson 321 discussion preoperatively regarding the risks of this procedure and the need for regular follow up and adherence to an intensive daily eye drop regimen should take place prior to performing the surgery. A patient with unilateral ocular involvement may not be ready for or motivated to undergo such a procedure, and may be setting himself or herself up for a complicated and undesirable postoperative course. In the proper setting, however, keratoprosthesis placement can be a truly vision-saving procedure. The Boston Type I keratoprosthesis study group found 89% (17/19) anatomical retention in patients with a chemical burn, results similar to those patients who experienced multiple graft rejections, with slightly improved visual acuity results – 94% BCVA more than 20/200 (16/19) . Bradley et al.  reported similar results with three alkali burn patients experiencing 100% anatomical retention and 100% visual acuity more than 20/200. The complications of a keratoprosthesis placement include infection, corneal melt, glaucoma, as well as formation of a retroprosthetic membrane. Monitoring for postoperative glaucoma has proved particularly challenging with no reliable way of checking intraocular pressure to date. Some surgeons will place a tube shunt at the time of keratoprosthesis placement in anticipation of this problem. We currently will keep our patients on a topical antibiotic drop regimen indefinitely. We choose to use a fourth generation fluoroquinolone and reserve vancomycin or other fortified antibiotic drops for cases of infectious ulcerative keratitis/melt should they arise. Acknowledgement Management of ocular thermal and chemical injuries, including amniotic membrane transplantation are done by R.F. and R.S.D. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 324). 1 Tuft SJ, Shortt AJ. Surgical rehabilitation following severe ocular burns. Eye (Lond.) 2009; 23:1966–1971. The Tuft and Shortt article is a concise review of the appropriate treatment options in both the acute and long-term setting for ocular surface burns. It explores the various ocular surface reconstruction techniques available such as limbal stem cell grafting and keratoprosthesis placement. 2 Pfister R, Pfister D. Alkali injuries of the Eye, Chapter 103 1285–1293. Cornea, 2nd ed. In: Krachmer JH, Mannis MJ, and Holland EJ, editors. Philadelphia, Elsevier Mosby, 2005. 3 Stein JD. ‘Air bags and ocular injuries.’ Transactions of the American Ophthalmological Society (0065-9533), 1999; 97, p. 59. 4 Paterson CA, Pfister RR. Intraocular pressure changes after alkali burns. Arch Ophthalmol 1974; 91:211–218. 5 Herr RD, White GL, Bernhisel K, Mamalis N, et al. Clinical comparison of ocular irrigation fluids following chemical injury. Am J Emerg Med 1991; 9:228–231. 6 Ballen PH. Treatment of chemical burns of the eye. Eye, Ear, Nose and Throat Monthly 1964; 43:57–58. 7 Roper-Hall MJ. Thermal and chemical burns. Trans Ophthalmol Soc UK 1965; 85:631–653. 8 Pfister RR. Chemical injuries of the eye. Ophthalmology 1983; 90:1246– 1253. 9 Dua HS, King AJ, Joseph A. A new classification of ocular surface burns. Br J Ophthalmol 2001; 85:1379–1383. 10 Donshik PC, Berman MB, Dohlman CH, et al. Effect of topical corticosteroids on corneal ulceration in alkali-burned corneas. Arch Ophthalmol 1978; 96:2117–2120. 11 Davis AR, Ali QH, Aclimandos WA, Hunter PA. Topical steroid use in the treatment of ocular alkali burns. Br J Ophthalmol 1997; 81:732–734. Conclusion Overall, patients experiencing an ocular burn will need a thorough and immediate evaluation and intensive treatment. Advances in understanding of the pathophysiology of the injury have led to improvements in treatment in the acute setting such as employment of topical ascorbate and citrate, as well as surgical treatment in the subacute and chronic settings with AMT, ALT with or without PKP and ultimately keratoprosthesis placement, if necessary. The goal of treatment is restoration of the normal ocular surface anatomy and lid position, control of glaucoma, and restoration of corneal clarity once this has been achieved. 12 Tejwani S, Kolari RS, Sangwan VS, Rao GN. Role of amniotic membrane graft for ocular chemical and thermal injuries. Cornea 2007; 26:21–26. 13 Tseng SC, Prabhasawat P, Barton K, et al. Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol 1998; 116:431–441. 14 Meller D, Pires RTF, Mack RJS, Figueiredo F, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000; 107:980–990. 15 Gomes JAP, Santos MS, Cunha MC, et al. Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn. Ophthalmology 2003; 110:466–473. 16 Zerbe BL, Belin MW, Ciolino JB, Boston Type I Keratoprosthesis Study Group. Results from the Multicenter Boston Type I Keratoprosthesis Study. Ophthalmology 2006; 113:1779–1784. 17 Bradley JC, Hernandez EG, Schwab IR, Mannis MJ. Boston type I keratoprosthesis: The University of California Davis Experience. Cornea 2009; 28:321–327. Copyright © Lippincott Williams & Wilkins. 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