Case Reports Orbital Mucormycosis Following Periorbital Cutaneous Infection Harinder S. Chahal, M.D.*, Narine Abgaryan, B.S.*, Renuka Lakshminarayanan, M.D.†, and A. Tyrone Glover, M.D.* Abstract: Mucormycosis is an aggressive fungal infection characterized by rapidly progressive angioinvasion and tissue necrosis. When present in the orbit, mucormycosis can quickly lead to permanent visual loss and potentially fatal cerebral extension. Orbital involvement is almost universally preceded by infection of the paranasal sinuses. Secondary infection of the orbit via direct extension of neighboring cutaneous mucormycosis has not been previously described. The authors present a case of cutaneous mucormycosis with orbital extension in a poorly controlled diabetic patient.
“M
ucormycosis” is an umbrella term for infections caused by fungi from the order Mucorales, of which members of the genus Rhizopus and Mucor are responsible for most cases.1 These fungi are ubiquitous, found commonly in decaying matter including bread, air, soil, dust, plants, and animal excreta.1 Mucormycosis has several clinical presentations including rhino-orbito-cerebral (ROCM), pulmonary, cutaneous, gastrointestinal, and disseminated infections. Cutaneous mucormycosis is typically preceded by a history of trauma, surgery, or burns, and may be localized to skin, directly invade subcutaneous tissues, or disseminate hematogenously to distant organs.2,3 Orbital mucormycosis, in contrast, almost always results from infectious spread via the paranasal sinuses.2 To the best of the authors knowledge, orbital mucormycosis resulting from cutaneous disease has never been described. The authors present a case of traumatic injury to the face resulting in cutaneous mucormycosis, with subsequent orbito-cerebral involvement. This case report is in compliance with Health Insurance Portability and Accountability Act guidelines.
CASE REPORT A 48-year-old warehouse worker with poorly controlled insulin-dependent diabetes presented with progressive visual loss and total ophthalmoplegia of the right eye. Ten days prior, he sustained a 1 cm traumatic laceration to his right temporoparietal scalp from a tree branch. He immediately developed swelling and bruising in the right forehead and scalp area, with gradual progression to his right upper eyelid and left forehead region over several days. He was seen at an outside hospital 3 days after his initial injury for increased pain, swelling, and double vision. A CT scan was obtained at the outside hospital and was reported to be normal. The patient was subsequently discharged with pain medication and warm compresses.
*Department of Ophthalmology, University of California, Davis, Sacramento, California; and †Department of Pathology, The Kaiser Permanente Medical Group, Inc., Sacramento, California, U.S.A. Accepted for publication February 20, 2015. The authors have no financial or conflicts of interest to disclosure. Address correspondence and reprint requests to Harinder S. Chahal, M.D., Department of Ophthalmology, School of Medicine, University of California, Davis, 4860 Y St. Suite 2400, Sacramento, CA 95817. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000466
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
Two and a half weeks after his initial injury, his pain and swelling continued to progress with rapid visual decline, prompting his visit to our institution for a second evaluation. On examination, he was noted to be febrile with stable vital signs. The right and left forehead, temporal fossae, scalp, and eyelids were swollen and tender. The forehead rhytids were effaced. He was noted to have a thickened right brow, without fluctuance, and a normal appearing scar at the site of his previous laceration. He also had complete ptosis of the right upper eyelid, with significant proptosis of the right globe. The right eye was chemotic and injected, with complete loss of light perception and complete ophthalmoplegia. The right pupil was fixed and dilated, with a normal fundoscopic exam. The left eye was unaffected. The nasopharynx was clear and he denied any sinus symptoms or purulent rhinorrhea. Initial CT scan revealed marked preseptal soft tissue swelling on the right, with a clear orbital apex, and no evidence of orbital abscess or sinusitis (Fig. 1). Blood work revealed moderate leukocytosis and severe hyperglycemia and metabolic derangement consistent with diabetic ketoacidosis. Given concern for orbital cellulitis and mucormycosis, the patient was admitted and empirically treated with intravenous amphotericin B, vancomycin, and ceftriaxone. Despite initial treatment, the patient’s clinical picture remained unchanged after 24 hours. A subsequent MRI revealed soft tissue swelling in the right lateral and superior orbit, bilateral preseptal soft tissue swelling, and an ill-defined enhancement of the right orbital apex extending anteriorly along the optic nerve (Fig. 2). There were no fluid collections, and no evidence of sinus or brain abnormalities. Magnetic resonance venography revealed decreased flow within the right cavernous sinus. The patient was subsequently taken to the operating room for biopsies of the right eyelid and brow, along the site of his previous laceration, and also of his sinuses and orbit, for histopathologic analysis. Surgical specimens from the temporal brow subcutaneous tissues and orbit revealed fragmented hyphae highly suspicious for mucormycosis (Fig. 3). Of note, multiple biopsies sent from the sinonasal cavities including the cribiform plate, ethmoids, and nasal turbinates were negative for invasive fungus. Based on the patient’s clinical picture, and magnetic resonance venography evidence suggestive of early cavernous sinus compromise, an exenteration of the right orbit was performed with wide excision of periorbital skin (Fig. 4). The supraorbital and supratrochlear neurovascular bundles, bridging the initial laceration site and orbit, were noted to be profoundly necrotic along their entire length. The patient also underwent a right maxillary antrostomy, right anterior and posterior ethmoidectomy, as well as right sphenoidotomy. The wound was subsequently managed with wet-to-dry dressings using amphotericin-soaked gauze, and was otherwise allowed to granulate without additional grafts or flaps. Postoperatively, the patient suffered stroke in the distribution of the right middle cerebral artery secondary to intracranial angioinvasion. Fortunately, no major neurologic sequelae were noted. He was hospitalized for 5 weeks, and required 1 additional surgical debridement his second week for persistent necrotic tissue. He was treated with high dose intravenous liposomal amphotericin B (5 mg/kg/daily) for 4 weeks, along with posaconazole (200 mg PO tid) for 12 months, and systemic anticoagulation for 6 months. Final culture results did not show growth, but characteristic histopathologic findings were felt to be diagnostic. He remains disease free and without significant neurologic deficits 2 years later.
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Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
Case Reports
FIG. 1. CT imaging of orbits and sinuses. A, Axial image demonstrating clear ethmoid and sphenoid sinuses with no intraorbital abnormality. B, Sagittal image with normal right orbit and maxillary sinus. Preseptal soft tissue swelling is noted superiorly (arrow).
FIG. 4. External postoperative photograph of the right orbit after exenteration, sinus debridement, and wide-margin skin and soft tissue excision.
FIG. 2. Contrast-enhanced axial MRI image. Periorbital soft tissue thickening is noted on the right. Enhancement and thickening of the right lateral rectus with perineural enhancement of the right optic nerve are also marked with arrows.
FIG. 3. Orbital soft tissue biopsy demonstrating nonseptate ribbon-like hyphal forms highlighted by gomori methenamine silver stain.
DISCUSSION Cutaneous mucormycosis, accounting for 11–19% of all cases, is the third most common form after ROCM and pulmonary mucormycosis.3,4 Direct fungal inoculation of the skin has been reported after wound trauma, lacerations, punctures by tree thorns, surgical injuries, burns, abrasions, insect bites, tattoos, contaminated adhesive tapes and dressings, and puncture sites from arterial lines and insulin injections.3–5 Patients may present
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with lesions localized to the skin (56%), deep extension into subcutaneous tissues (24%), or disseminated infection (20%).2,3 Mucormycosis rarely develops in immunocompetent hosts as spores are readily phagocytosed by neutrophils and macrophages.6,7 Immunocompromised patients, including those with acidosis, have impaired fungicidal activity resulting in spore germination and subsequent infection.6 Of note, however, mucormycosis has been reported in patients with no underlying systemic disease, and cutaneous mucormycosis is most common in these instances.2,6 Mucor is an angiotropic fungus with a predilection for the internal elastic lamina of the blood vessels, often invading neighboring tissues via direct extension along vessels and nerves.8,9 Orbital extension following cutaneous inoculation of the fungus has never been described, and likely occurred in this case via direct extension along the supratrochlear and supraorbital neurovascular bundles. Mortality from mucormycosis is estimated at 30% with cutaneous disease,3 and reaching as high as 80% or more in ROCM cases with cerebral involvement.7 In these cases, death usually results from intracerebral extension causing fatal cerebrovascular thrombosis or meningoencephalitis.10 The signs, symptoms, and radiographic findings of cutaneous and orbital mucormycosis are nonspecific, requiring histopathologic evidence or culture for diagnosis.1 The aggressive nature of this disease requires rapid diagnosis, early intervention with antifungal therapy, and the reversal of the underlying immunocompromising conditions—in this case strict glycemic control and underlying acidosis.5,9 The role of surgical debridement, and specifically the role of exenteration in ROCM, is considered controversial but may control extension and facilitate better penetration by antifungal medications.9 Existing systemic antifungal treatments include intravenous liposomal amphotericin B and oral Posaconazole.9,11As was done in this case, following debridement of necrotic tissue local amphotericin dressings may be applied.9 Other treatment modalities discussed in the literature include the use of hyperbaric oxygen, and treatment with 5-fluoro-cytosine therapy.6,9 Mucormycosis must remain on the differential of any immunocompromised or diabetic patient with nonspecific orbital findings,12,13 even in the absence of naso-canthal eschar and sinus disease. As demonstrated above, secondary orbital mucormycosis may occur via direct extension following periorbital cutaneous inoculation. We attribute our patient’s successful outcome to
© 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
aggressive surgical debridement, prompt antifungal administration, and rapid reversal of underlying ketoacidosis.
REFERENCES 1. Dan M. Mucormycosis of the head and neck. Curr Infect Dis Rep 2011;13:123–31. 2. Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53. 3. Skiada A, Petrikkos G. Cutaneous mucormycosis. Skinmed 2013;11:155–9; quiz 159–60. 4. Arnáiz-García ME, Alonso-Peña D, González-Vela Mdel C, et al. Cutaneous mucormycosis: report of five cases and review of the literature. J Plast Reconstr Aesthet Surg 2009;62:e434–41. 5. Hicks WL, Jr, Nowels K, Troxel J. Primary cutaneous mucormycosis. Am J Otolaryngol 1995;16:265–8. 6. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004;10(Suppl 1):31–47.
Case Reports
7. Gamaletsou MN, Sipsas NV, Roilides E, et al. Rhino-orbitalcerebral mucormycosis. Curr Infect Dis Rep 2012;14: 423–34. 8. Adam RD, Hunter G, DiTomasso J, et al. Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 1994;19:67–76. 9. Wali U, Balkhair A, Al-Mujaini A. Cerebro-rhino orbital mucormycosis: an update. J Infect Public Health 2012;5:116–26. 10. Gass JD. Ocular manifestations of acute mucormycosis. Arch Ophthalmol 1961;65:226–37. 11. Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009;48:1743–51. 12. DiBartolo MA, Kelley PS. Rhino-orbital-cerebral mucormycosis (ROCM): a comprehensive case review. Aviat Space Environ Med 2011;82:913–6. 13. Walsh TJ, Gamaletsou MN, McGinnis MR, et al. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis 2012;54(Suppl 1):S55–60.
© 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
“M
ucormycosis” is an umbrella term for infections caused by fungi from the order Mucorales, of which members of the genus Rhizopus and Mucor are responsible for most cases.1 These fungi are ubiquitous, found commonly in decaying matter including bread, air, soil, dust, plants, and animal excreta.1 Mucormycosis has several clinical presentations including rhino-orbito-cerebral (ROCM), pulmonary, cutaneous, gastrointestinal, and disseminated infections. Cutaneous mucormycosis is typically preceded by a history of trauma, surgery, or burns, and may be localized to skin, directly invade subcutaneous tissues, or disseminate hematogenously to distant organs.2,3 Orbital mucormycosis, in contrast, almost always results from infectious spread via the paranasal sinuses.2 To the best of the authors knowledge, orbital mucormycosis resulting from cutaneous disease has never been described. The authors present a case of traumatic injury to the face resulting in cutaneous mucormycosis, with subsequent orbito-cerebral involvement. This case report is in compliance with Health Insurance Portability and Accountability Act guidelines.
CASE REPORT A 48-year-old warehouse worker with poorly controlled insulin-dependent diabetes presented with progressive visual loss and total ophthalmoplegia of the right eye. Ten days prior, he sustained a 1 cm traumatic laceration to his right temporoparietal scalp from a tree branch. He immediately developed swelling and bruising in the right forehead and scalp area, with gradual progression to his right upper eyelid and left forehead region over several days. He was seen at an outside hospital 3 days after his initial injury for increased pain, swelling, and double vision. A CT scan was obtained at the outside hospital and was reported to be normal. The patient was subsequently discharged with pain medication and warm compresses.
*Department of Ophthalmology, University of California, Davis, Sacramento, California; and †Department of Pathology, The Kaiser Permanente Medical Group, Inc., Sacramento, California, U.S.A. Accepted for publication February 20, 2015. The authors have no financial or conflicts of interest to disclosure. Address correspondence and reprint requests to Harinder S. Chahal, M.D., Department of Ophthalmology, School of Medicine, University of California, Davis, 4860 Y St. Suite 2400, Sacramento, CA 95817. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000466
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
Two and a half weeks after his initial injury, his pain and swelling continued to progress with rapid visual decline, prompting his visit to our institution for a second evaluation. On examination, he was noted to be febrile with stable vital signs. The right and left forehead, temporal fossae, scalp, and eyelids were swollen and tender. The forehead rhytids were effaced. He was noted to have a thickened right brow, without fluctuance, and a normal appearing scar at the site of his previous laceration. He also had complete ptosis of the right upper eyelid, with significant proptosis of the right globe. The right eye was chemotic and injected, with complete loss of light perception and complete ophthalmoplegia. The right pupil was fixed and dilated, with a normal fundoscopic exam. The left eye was unaffected. The nasopharynx was clear and he denied any sinus symptoms or purulent rhinorrhea. Initial CT scan revealed marked preseptal soft tissue swelling on the right, with a clear orbital apex, and no evidence of orbital abscess or sinusitis (Fig. 1). Blood work revealed moderate leukocytosis and severe hyperglycemia and metabolic derangement consistent with diabetic ketoacidosis. Given concern for orbital cellulitis and mucormycosis, the patient was admitted and empirically treated with intravenous amphotericin B, vancomycin, and ceftriaxone. Despite initial treatment, the patient’s clinical picture remained unchanged after 24 hours. A subsequent MRI revealed soft tissue swelling in the right lateral and superior orbit, bilateral preseptal soft tissue swelling, and an ill-defined enhancement of the right orbital apex extending anteriorly along the optic nerve (Fig. 2). There were no fluid collections, and no evidence of sinus or brain abnormalities. Magnetic resonance venography revealed decreased flow within the right cavernous sinus. The patient was subsequently taken to the operating room for biopsies of the right eyelid and brow, along the site of his previous laceration, and also of his sinuses and orbit, for histopathologic analysis. Surgical specimens from the temporal brow subcutaneous tissues and orbit revealed fragmented hyphae highly suspicious for mucormycosis (Fig. 3). Of note, multiple biopsies sent from the sinonasal cavities including the cribiform plate, ethmoids, and nasal turbinates were negative for invasive fungus. Based on the patient’s clinical picture, and magnetic resonance venography evidence suggestive of early cavernous sinus compromise, an exenteration of the right orbit was performed with wide excision of periorbital skin (Fig. 4). The supraorbital and supratrochlear neurovascular bundles, bridging the initial laceration site and orbit, were noted to be profoundly necrotic along their entire length. The patient also underwent a right maxillary antrostomy, right anterior and posterior ethmoidectomy, as well as right sphenoidotomy. The wound was subsequently managed with wet-to-dry dressings using amphotericin-soaked gauze, and was otherwise allowed to granulate without additional grafts or flaps. Postoperatively, the patient suffered stroke in the distribution of the right middle cerebral artery secondary to intracranial angioinvasion. Fortunately, no major neurologic sequelae were noted. He was hospitalized for 5 weeks, and required 1 additional surgical debridement his second week for persistent necrotic tissue. He was treated with high dose intravenous liposomal amphotericin B (5 mg/kg/daily) for 4 weeks, along with posaconazole (200 mg PO tid) for 12 months, and systemic anticoagulation for 6 months. Final culture results did not show growth, but characteristic histopathologic findings were felt to be diagnostic. He remains disease free and without significant neurologic deficits 2 years later.
e1
Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
Case Reports
FIG. 1. CT imaging of orbits and sinuses. A, Axial image demonstrating clear ethmoid and sphenoid sinuses with no intraorbital abnormality. B, Sagittal image with normal right orbit and maxillary sinus. Preseptal soft tissue swelling is noted superiorly (arrow).
FIG. 4. External postoperative photograph of the right orbit after exenteration, sinus debridement, and wide-margin skin and soft tissue excision.
FIG. 2. Contrast-enhanced axial MRI image. Periorbital soft tissue thickening is noted on the right. Enhancement and thickening of the right lateral rectus with perineural enhancement of the right optic nerve are also marked with arrows.
FIG. 3. Orbital soft tissue biopsy demonstrating nonseptate ribbon-like hyphal forms highlighted by gomori methenamine silver stain.
DISCUSSION Cutaneous mucormycosis, accounting for 11–19% of all cases, is the third most common form after ROCM and pulmonary mucormycosis.3,4 Direct fungal inoculation of the skin has been reported after wound trauma, lacerations, punctures by tree thorns, surgical injuries, burns, abrasions, insect bites, tattoos, contaminated adhesive tapes and dressings, and puncture sites from arterial lines and insulin injections.3–5 Patients may present
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with lesions localized to the skin (56%), deep extension into subcutaneous tissues (24%), or disseminated infection (20%).2,3 Mucormycosis rarely develops in immunocompetent hosts as spores are readily phagocytosed by neutrophils and macrophages.6,7 Immunocompromised patients, including those with acidosis, have impaired fungicidal activity resulting in spore germination and subsequent infection.6 Of note, however, mucormycosis has been reported in patients with no underlying systemic disease, and cutaneous mucormycosis is most common in these instances.2,6 Mucor is an angiotropic fungus with a predilection for the internal elastic lamina of the blood vessels, often invading neighboring tissues via direct extension along vessels and nerves.8,9 Orbital extension following cutaneous inoculation of the fungus has never been described, and likely occurred in this case via direct extension along the supratrochlear and supraorbital neurovascular bundles. Mortality from mucormycosis is estimated at 30% with cutaneous disease,3 and reaching as high as 80% or more in ROCM cases with cerebral involvement.7 In these cases, death usually results from intracerebral extension causing fatal cerebrovascular thrombosis or meningoencephalitis.10 The signs, symptoms, and radiographic findings of cutaneous and orbital mucormycosis are nonspecific, requiring histopathologic evidence or culture for diagnosis.1 The aggressive nature of this disease requires rapid diagnosis, early intervention with antifungal therapy, and the reversal of the underlying immunocompromising conditions—in this case strict glycemic control and underlying acidosis.5,9 The role of surgical debridement, and specifically the role of exenteration in ROCM, is considered controversial but may control extension and facilitate better penetration by antifungal medications.9 Existing systemic antifungal treatments include intravenous liposomal amphotericin B and oral Posaconazole.9,11As was done in this case, following debridement of necrotic tissue local amphotericin dressings may be applied.9 Other treatment modalities discussed in the literature include the use of hyperbaric oxygen, and treatment with 5-fluoro-cytosine therapy.6,9 Mucormycosis must remain on the differential of any immunocompromised or diabetic patient with nonspecific orbital findings,12,13 even in the absence of naso-canthal eschar and sinus disease. As demonstrated above, secondary orbital mucormycosis may occur via direct extension following periorbital cutaneous inoculation. We attribute our patient’s successful outcome to
© 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015
aggressive surgical debridement, prompt antifungal administration, and rapid reversal of underlying ketoacidosis.
REFERENCES 1. Dan M. Mucormycosis of the head and neck. Curr Infect Dis Rep 2011;13:123–31. 2. Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53. 3. Skiada A, Petrikkos G. Cutaneous mucormycosis. Skinmed 2013;11:155–9; quiz 159–60. 4. Arnáiz-García ME, Alonso-Peña D, González-Vela Mdel C, et al. Cutaneous mucormycosis: report of five cases and review of the literature. J Plast Reconstr Aesthet Surg 2009;62:e434–41. 5. Hicks WL, Jr, Nowels K, Troxel J. Primary cutaneous mucormycosis. Am J Otolaryngol 1995;16:265–8. 6. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004;10(Suppl 1):31–47.
Case Reports
7. Gamaletsou MN, Sipsas NV, Roilides E, et al. Rhino-orbitalcerebral mucormycosis. Curr Infect Dis Rep 2012;14: 423–34. 8. Adam RD, Hunter G, DiTomasso J, et al. Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 1994;19:67–76. 9. Wali U, Balkhair A, Al-Mujaini A. Cerebro-rhino orbital mucormycosis: an update. J Infect Public Health 2012;5:116–26. 10. Gass JD. Ocular manifestations of acute mucormycosis. Arch Ophthalmol 1961;65:226–37. 11. Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 2009;48:1743–51. 12. DiBartolo MA, Kelley PS. Rhino-orbital-cerebral mucormycosis (ROCM): a comprehensive case review. Aviat Space Environ Med 2011;82:913–6. 13. Walsh TJ, Gamaletsou MN, McGinnis MR, et al. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis 2012;54(Suppl 1):S55–60.
© 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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Copyright © 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
