Letters
the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentation: This article was presented in part at the Atlantic Coast Retina Club 2015 Meeting; January 9, 2015; Boston, Massachusetts.
Figure 1. Clinical Appearance of the Patient A
1. Jia Y, Bailey ST, Wilson DJ, et al. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014;121(7):1435-1444. 2. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers in macular telangiectasia type 2 imaged by optical coherence tomographic angiography. JAMA Ophthalmol. 2015;133(1):66-73. 3. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50. 4. de Carlo TE, Bonini Filho MA, Chin AT, et al. Spectral domain optical coherence tomography angiography (OCTA) of choroidal neovascularization [published online March 17, 2015]. Ophthalmology. doi:10.1016/j.ophtha.2015.01.029. 5. Kotsolis AI, Killian FA, Ladas ID, Yannuzzi LA. Fluorescein angiography and optical coherence tomography concordance for choroidal neovascularisation in multifocal choroiditis. Br J Ophthalmol. 2010;94(11):1506-1508.
B
6. Moult E, Choi W, Waheed NK, et al. Ultrahigh-speed swept-source OCT angiography in exudative AMD. Ophthalmic Surg Lasers Imaging Retina. 2014; 45(6):496-505.
OBSERVATION
Facial Ulcers and Restrictive Strabismus From Delayed Periorbital Granuloma After Poly-L–Lactic Acid Injection Complications of injectable fillers are uncommon but potentially devastating. Most adverse events occur soon after injection and are mild, including redness, itching, blanching, and nodule formation.1 More severe outcomes include soft-tissue necrosis, blindness, and anaphylaxis.2 Recently, numerous patients with histories of filler injection have developed delayedonset granulomatous reactions and systemic inflammatory markers, a syndrome called autoimmune/inflammatory syndrome induced by adjuvants.3 Herein, we describe a patient with a nonhealing periorbital ulcer that progressed to orbital fibrosis. This presented a diagnostic dilemma owing to concurrent systemic inflammatory symptoms and a lack of reported history of facial fillers. Report of a Case | A 49-year-old woman presented to the oculoplastics clinic with healed ulcers of the lower lip and nasal dorsum and a nonhealing ulcer of the left lateral infraorbital area. She reported several years of facial ulcers described as “scratches” developing over weeks to months into red, indurated, tender ulcers that finally crusted and healed. Prior to presenting to our clinic, she had undergone a punch biopsy of the lip lesion and debridement of the nasal ulcer in separate procedures at outside institutions. The pathology department found granulomatous inflammation of unclear etiology. Our evaluation included consultations with the dermatology, otolaryngology, rheumatology, infectious diseases, gastroenterology, and psychiatry departments during which numerous diagnoses were considered, including scleroderma, granulomatosis with polyangiitis, polymyositisscleromyositis overlap syndrome, leprosy, and factitious disease. Our patient denied any history of facial surgery or exposures to foreign material or fillers. The patient’s review of systems was positive for dry mouth, Raynaud phenomenon, 1090
A, The saddle nose deformity (black arrowhead) and infraorbital ulcer (white arrowhead) seen at onset of the diplopia. B, Several months later after the diplopia had stabilized and with the patient’s daily dressings in place.
morning joint pain, mild hand and ankle swelling, and dysphagia. Maxillofacial computed tomography identified a nasal septal perforation, saddle nose deformity, clear paranasal sinuses, and the left infraorbital soft-tissue defect. Laboratory study results included positive findings for antinuclear antibodies (titer, 1:360; nuclear and cytoplasmic staining), mildly elevated angiotensin-converting enzyme level (78 U/L [to convert to nanokatals per liter, multiply by 16.667]), and mildly decreased C4 complement level. All other laboratory results were normal, including anti–proteinase 3, antimyeloperoxidase, anti–Scl-70, human immunodeficiency virus, antiphospholipid, C3 complement, anticitrullinated protein, human leukocyte antigen B27, T-SPOT.TB test for tuberculosis, syphilis, erythrocyte sedimentation rate, and C-reactive protein. Biopsies of the ulcer base showed foreign-body granulomas and scant polarizable material of uncertain diagnostic significance. Cultures were negative for infectious causes, including leishmaniasis and acidfast bacteria. The patient began treatment with oral prednisone and methotrexate to control inflammation. Several months later, the patient developed diplopia, a sense of fullness below the left eye, and extrusion of white fibrous material from the ulcer base. Repeated examination found restriction of the left eye into a hypotropic and exotropic position and a full-thickness defect through the lateral lower eyelid, exposing conjunctiva and bony orbital rim (Figure 1). Magnetic reso-
JAMA Ophthalmology September 2015 Volume 133, Number 9 (Reprinted)
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Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Figure 2. Histologic Evaluation of the Nonhealing Ulcer
Funding/Support: This work was supported in part by an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, Mayo Clinic. Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Correction: This article was corrected to fix an error in the text on July 29, 2015. 1. Daines SM, Williams EF. Complications associated with injectable soft-tissue fillers: a 5-year retrospective review. JAMA Facial Plast Surg. 2013;15(3):226-231. 2. Ozturk CN, Li Y, Tung R, Parker L, Piliang MP, Zins JE. Complications following injection of soft-tissue fillers. Aesthet Surg J. 2013;33(6):862-877. 3. Shoenfeld Y, Agmon-Levin N. “ASIA”: autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4-8. 20 µm
Biopsy tissue from the inferior orbit showing the acellular, eosinophilic foreign material with surrounding inflammation, including foreign-body granulomas (hematoxylin-eosin). The material was birefringent under polarized light, consistent with poly-L–lactic acid.
nance imaging revealed an amorphous mass of hypointense material in the inferior and temporal orbit. The patient underwent orbital exploration and aggressive biopsies, with histopathologic analysis revealing foreign-body granulomas with polarizable material consistent with poly-L–lactic acid (Figure 2). Following orbitotomy, the patient acknowledged having facial filler injections years before, having not recalled this event, as part of a variety of spa services received. She underwent reconstruction of the infraorbital defect and saddle nose deformity using a cervicofacial flap and paramedial forehead flap, respectively, in cooperation with the facial plastic surgery team. During recovery, the left cheek developed a seroma and delayed wound breakdown, requiring several wound revisions. Strabismus surgery has been performed. Discussion | To our knowledge, this is the first reported case of chronic granulomatous lesions leading to orbital fibrosis and strabismus after dermal filler injection. Extensive testing was unable to identify any alternative diagnosis, leading us to believe that this patient’s presentation fits the criteria for autoimmune/ inflammatory syndrome induced by adjuvants. Even in the absence of a confirmed history of soft-tissue filler use, it is important to keep this possibility on the diagnostic differential, as prompt intervention may decrease long-term complications. Molly L. Fuller, MD, PhD Elizabeth A. Bradley, MD Author Affiliations: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. Corresponding Author: Molly L. Fuller, MD, PhD, Department of Ophthalmology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (fuller [email protected]). Submitted for Publication: January 9, 2015; final revision received March 31, 2015; accepted April 5, 2015. Published Online: June 4, 2015. doi:10.1001/jamaophthalmol.2015.1666. jamaophthalmology.com
Zonular Dehiscence at the Time of Combined Vitrectomy and Cataract Surgery After Intravitreal Ocriplasmin Injection Ocriplasmin is a recombinant fraction of plasmin with nonspecific protease activity capable of cleaving fibronectin and laminin. It has recently been approved for the treatment of vitreomacular traction and associated macular holes (MHs). Clinical trials1 report good clinical results and safety profile. We report 2 cases that developed zonular dehiscence at the time of vitrectomy and intraocular lens (IOL) implantation after treatment with ocriplasmin. Report of Cases | Case 1. A woman in her mid-60s presented with an MH in her left eye. There was no history of eye disease, Marfan syndrome, or pseudoexfoliation syndrome. Bestcorrected visual acuity (BCVA) was 20/30 OD and 20/80 OS. Examination showed an MH with vitreomacular traction; the rest of the examination findings were unremarkable. She was given an intravitreal injection of 0.125 mg of ocriplasmin. A posterior vitreous detachment failed to develop and the MH remained. The patient did not experience any adverse symptoms. No phacodonesis was noticed. Seven weeks after the injection, the patient underwent phacoemulsification, 25-gauge pars plana vitrectomy, internal limiting membrane peel, lens implantation, and hexafluoroethane tamponade. An acrylic IOL was inserted (C-Flex 970C; Rayner), causing a zonular dialysis of more than 180°. The implant was replaced with an iris clip lens (Artisan; Ophtec) enclavated to the posterior iris surface. The patient recovered satisfactorily with MH closure evident 2 weeks postoperatively. After 6 months, the BCVA was 20/40 OS. Case 2. A woman in her late 60s was referred with an MH in her left eye. The eyes were otherwise normal. The BCVA was 20/30 OD and 20/100 OS. She was administered 0.125 mg of ocriplasmin intravitreally. A few hours later, she developed a posterior vitreous detachment with photopsia, vision loss, and photophobia. Electroretinography demonstrated marked dysfunction in all waveforms. Optical coherence tomography showed an increase of the base diameter of the MH, which failed to close after the fourth week. No phacodonesis was observed. (Reprinted) JAMA Ophthalmology September 2015 Volume 133, Number 9
Copyright 2015 American Medical Association. All rights reserved.
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the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentation: This article was presented in part at the Atlantic Coast Retina Club 2015 Meeting; January 9, 2015; Boston, Massachusetts.
Figure 1. Clinical Appearance of the Patient A
1. Jia Y, Bailey ST, Wilson DJ, et al. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014;121(7):1435-1444. 2. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers in macular telangiectasia type 2 imaged by optical coherence tomographic angiography. JAMA Ophthalmol. 2015;133(1):66-73. 3. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50. 4. de Carlo TE, Bonini Filho MA, Chin AT, et al. Spectral domain optical coherence tomography angiography (OCTA) of choroidal neovascularization [published online March 17, 2015]. Ophthalmology. doi:10.1016/j.ophtha.2015.01.029. 5. Kotsolis AI, Killian FA, Ladas ID, Yannuzzi LA. Fluorescein angiography and optical coherence tomography concordance for choroidal neovascularisation in multifocal choroiditis. Br J Ophthalmol. 2010;94(11):1506-1508.
B
6. Moult E, Choi W, Waheed NK, et al. Ultrahigh-speed swept-source OCT angiography in exudative AMD. Ophthalmic Surg Lasers Imaging Retina. 2014; 45(6):496-505.
OBSERVATION
Facial Ulcers and Restrictive Strabismus From Delayed Periorbital Granuloma After Poly-L–Lactic Acid Injection Complications of injectable fillers are uncommon but potentially devastating. Most adverse events occur soon after injection and are mild, including redness, itching, blanching, and nodule formation.1 More severe outcomes include soft-tissue necrosis, blindness, and anaphylaxis.2 Recently, numerous patients with histories of filler injection have developed delayedonset granulomatous reactions and systemic inflammatory markers, a syndrome called autoimmune/inflammatory syndrome induced by adjuvants.3 Herein, we describe a patient with a nonhealing periorbital ulcer that progressed to orbital fibrosis. This presented a diagnostic dilemma owing to concurrent systemic inflammatory symptoms and a lack of reported history of facial fillers. Report of a Case | A 49-year-old woman presented to the oculoplastics clinic with healed ulcers of the lower lip and nasal dorsum and a nonhealing ulcer of the left lateral infraorbital area. She reported several years of facial ulcers described as “scratches” developing over weeks to months into red, indurated, tender ulcers that finally crusted and healed. Prior to presenting to our clinic, she had undergone a punch biopsy of the lip lesion and debridement of the nasal ulcer in separate procedures at outside institutions. The pathology department found granulomatous inflammation of unclear etiology. Our evaluation included consultations with the dermatology, otolaryngology, rheumatology, infectious diseases, gastroenterology, and psychiatry departments during which numerous diagnoses were considered, including scleroderma, granulomatosis with polyangiitis, polymyositisscleromyositis overlap syndrome, leprosy, and factitious disease. Our patient denied any history of facial surgery or exposures to foreign material or fillers. The patient’s review of systems was positive for dry mouth, Raynaud phenomenon, 1090
A, The saddle nose deformity (black arrowhead) and infraorbital ulcer (white arrowhead) seen at onset of the diplopia. B, Several months later after the diplopia had stabilized and with the patient’s daily dressings in place.
morning joint pain, mild hand and ankle swelling, and dysphagia. Maxillofacial computed tomography identified a nasal septal perforation, saddle nose deformity, clear paranasal sinuses, and the left infraorbital soft-tissue defect. Laboratory study results included positive findings for antinuclear antibodies (titer, 1:360; nuclear and cytoplasmic staining), mildly elevated angiotensin-converting enzyme level (78 U/L [to convert to nanokatals per liter, multiply by 16.667]), and mildly decreased C4 complement level. All other laboratory results were normal, including anti–proteinase 3, antimyeloperoxidase, anti–Scl-70, human immunodeficiency virus, antiphospholipid, C3 complement, anticitrullinated protein, human leukocyte antigen B27, T-SPOT.TB test for tuberculosis, syphilis, erythrocyte sedimentation rate, and C-reactive protein. Biopsies of the ulcer base showed foreign-body granulomas and scant polarizable material of uncertain diagnostic significance. Cultures were negative for infectious causes, including leishmaniasis and acidfast bacteria. The patient began treatment with oral prednisone and methotrexate to control inflammation. Several months later, the patient developed diplopia, a sense of fullness below the left eye, and extrusion of white fibrous material from the ulcer base. Repeated examination found restriction of the left eye into a hypotropic and exotropic position and a full-thickness defect through the lateral lower eyelid, exposing conjunctiva and bony orbital rim (Figure 1). Magnetic reso-
JAMA Ophthalmology September 2015 Volume 133, Number 9 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Central Michigan University User on 09/15/2015
jamaophthalmology.com
Letters
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Figure 2. Histologic Evaluation of the Nonhealing Ulcer
Funding/Support: This work was supported in part by an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, Mayo Clinic. Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Correction: This article was corrected to fix an error in the text on July 29, 2015. 1. Daines SM, Williams EF. Complications associated with injectable soft-tissue fillers: a 5-year retrospective review. JAMA Facial Plast Surg. 2013;15(3):226-231. 2. Ozturk CN, Li Y, Tung R, Parker L, Piliang MP, Zins JE. Complications following injection of soft-tissue fillers. Aesthet Surg J. 2013;33(6):862-877. 3. Shoenfeld Y, Agmon-Levin N. “ASIA”: autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4-8. 20 µm
Biopsy tissue from the inferior orbit showing the acellular, eosinophilic foreign material with surrounding inflammation, including foreign-body granulomas (hematoxylin-eosin). The material was birefringent under polarized light, consistent with poly-L–lactic acid.
nance imaging revealed an amorphous mass of hypointense material in the inferior and temporal orbit. The patient underwent orbital exploration and aggressive biopsies, with histopathologic analysis revealing foreign-body granulomas with polarizable material consistent with poly-L–lactic acid (Figure 2). Following orbitotomy, the patient acknowledged having facial filler injections years before, having not recalled this event, as part of a variety of spa services received. She underwent reconstruction of the infraorbital defect and saddle nose deformity using a cervicofacial flap and paramedial forehead flap, respectively, in cooperation with the facial plastic surgery team. During recovery, the left cheek developed a seroma and delayed wound breakdown, requiring several wound revisions. Strabismus surgery has been performed. Discussion | To our knowledge, this is the first reported case of chronic granulomatous lesions leading to orbital fibrosis and strabismus after dermal filler injection. Extensive testing was unable to identify any alternative diagnosis, leading us to believe that this patient’s presentation fits the criteria for autoimmune/ inflammatory syndrome induced by adjuvants. Even in the absence of a confirmed history of soft-tissue filler use, it is important to keep this possibility on the diagnostic differential, as prompt intervention may decrease long-term complications. Molly L. Fuller, MD, PhD Elizabeth A. Bradley, MD Author Affiliations: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. Corresponding Author: Molly L. Fuller, MD, PhD, Department of Ophthalmology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (fuller [email protected]). Submitted for Publication: January 9, 2015; final revision received March 31, 2015; accepted April 5, 2015. Published Online: June 4, 2015. doi:10.1001/jamaophthalmol.2015.1666. jamaophthalmology.com
Zonular Dehiscence at the Time of Combined Vitrectomy and Cataract Surgery After Intravitreal Ocriplasmin Injection Ocriplasmin is a recombinant fraction of plasmin with nonspecific protease activity capable of cleaving fibronectin and laminin. It has recently been approved for the treatment of vitreomacular traction and associated macular holes (MHs). Clinical trials1 report good clinical results and safety profile. We report 2 cases that developed zonular dehiscence at the time of vitrectomy and intraocular lens (IOL) implantation after treatment with ocriplasmin. Report of Cases | Case 1. A woman in her mid-60s presented with an MH in her left eye. There was no history of eye disease, Marfan syndrome, or pseudoexfoliation syndrome. Bestcorrected visual acuity (BCVA) was 20/30 OD and 20/80 OS. Examination showed an MH with vitreomacular traction; the rest of the examination findings were unremarkable. She was given an intravitreal injection of 0.125 mg of ocriplasmin. A posterior vitreous detachment failed to develop and the MH remained. The patient did not experience any adverse symptoms. No phacodonesis was noticed. Seven weeks after the injection, the patient underwent phacoemulsification, 25-gauge pars plana vitrectomy, internal limiting membrane peel, lens implantation, and hexafluoroethane tamponade. An acrylic IOL was inserted (C-Flex 970C; Rayner), causing a zonular dialysis of more than 180°. The implant was replaced with an iris clip lens (Artisan; Ophtec) enclavated to the posterior iris surface. The patient recovered satisfactorily with MH closure evident 2 weeks postoperatively. After 6 months, the BCVA was 20/40 OS. Case 2. A woman in her late 60s was referred with an MH in her left eye. The eyes were otherwise normal. The BCVA was 20/30 OD and 20/100 OS. She was administered 0.125 mg of ocriplasmin intravitreally. A few hours later, she developed a posterior vitreous detachment with photopsia, vision loss, and photophobia. Electroretinography demonstrated marked dysfunction in all waveforms. Optical coherence tomography showed an increase of the base diameter of the MH, which failed to close after the fourth week. No phacodonesis was observed. (Reprinted) JAMA Ophthalmology September 2015 Volume 133, Number 9
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Central Michigan University User on 09/15/2015
1091
