Staged limbal stem cell transplantation and keratoplasty surgeries as a treatment for gelatinous drop-like corneal dystrophy.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive corneal dystrophy that has been associated with mutations in the TACSTD2 (M1S1) gene, which is normally expressed in corneal epithelial cells. GDLD is characterized by progressive deposition of amyloid in the corneal stroma with rapid recurrence in grafts after penetrating keratoplasty. We report of case of a patient with GDLD treated bilaterally with staged limbal stem cell transplantation and penetrating keratoplasty that resulted in long-term control of his disease. This case demonstrates that staged allogenic limbal stem cell transplantation, before or after penetrating keratoplasty, can be used to restore vision long-term in GDLD patients.

A Case of the Blues-Colored Pencil Orbitopathy in an 18-Month-Old Boy.

Orbital penetrating injuries from pencils are rare. This report describes a case of penetrating orbital injury in a young child with a retained blue-colored pencil core foreign body, which led to rapid onset of orbital abscess requiring surgical drainage. Intraoperatively, orbital tissues were stained a bright-blue color. Histopathological study of specimen also highlighted bright blue aggregates of foreign material infiltrating the orbital tissues. Cultures grew Streptococcus mitis and Exophiala jeanselmei , which are rare causes of orbital abscess. Unique properties of retained colored pencil core as compared to graphite pencil core are herein discussed. Due to differences in composition, colored pencil core foreign bodies may require more timely surgical intervention compared to noncolored graphite pencil core.

Delayed-Onset Inflammatory Optic Nerve Sheath Mass and Perineuritis Following Cessation of Ipilimumab and Nivolumab Therapy.

A 65-year-old male presented with headaches and painless episodes of unilateral vision loss. He had a history of renal cell carcinoma, in remission following surgery and immunotherapy with ipilimumab and nivolumab, discontinued 2 years and 3 months before presentation, respectively. MRI revealed an optic nerve sheath mass and perineuritis. After 1 month of corticosteroid therapy, there was a robust clinical and radiographic response, which relapsed dramatically following cessation. An optic nerve sheath biopsy showed chronic mild inflammation, and extensive work-up for alternative etiologies of orbital inflammation was negative. Following a prolonged taper of corticosteroids, he demonstrated complete response. In the setting of ocular immune privilege, ophthalmic immune-related adverse events (irAE) are rare, although multifarious. While on-treatment irAE are well-characterized, posttreatment irAE have become increasingly recognized across multiple organ systems. We report a case of a delayed-onset inflammatory optic nerve sheath mass and perineuritis after cessation of immunotherapy.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Immunoglobulin G4 Involvement in Lacrimal Sac Squamous Cell Carcinoma.

Lacrimal sac squamous cell carcinoma is a rare but life-threatening disease that is often a delayed diagnosis secondary to difficulty in differentiating from other causes of dacrocystitis and acquired nasolacrimal duct obstruction. Chronic inflammation, including that of an underlying autoimmune disease, prior instrumentation, and poor wound healing, may be risk factors in the development to lacrimal sac squamous cell carcinoma. The authors present the first case of lacrimal sac squamous cell carcinoma associated with antineutrophil cytoplasmic antibody-associated vasculitis and immunoglobulin G4 positivity. Rather than an overlap syndrome between antineutrophil cytoplasmic antibody-associated vasculitis and immunoglobulin G4-related disease, high immunoglobulin G4 positivity may be considered an inflammatory marker of disease severity in the setting of antineutrophil cytoplasmic antibody-associated vasculitis and underlying malignancy. Inflammation-mediated tumorangiogenesis should be considered in the development of malignancy and red flags of chronic uncontrolled inflammation should warrant a lower threshold for further workup.

Nodular fasciitis of the periorbital soft tissue in an adolescent confirmed by USP6 gene rearrangement.

Nodular fasciitis is a benign, idiopathic condition that can simulate both benign and malignant neoplasms. In adults, it generally occurs in the subcutaneous or superficial fascia of the trunk or upper extremities; occurrence in the periorbital region is far less common. We describe a case of a 16-year-old male with a 4-month history of a nodular, non-tender, progressively enlarging mass of the superotemporal periorbita. Histopathologic analysis of the excisional biopsy demonstrated nodular fasciitis, confirmed by molecular cytogenetic analysis that showed rearrangement of USP6.

Multiple Genetically Distinct Uveal Melanomas Arise in the Same Eye of Two Patients with Melanosis Oculi.

PURPOSE: To determine whether unilateral multifocal uveal melanomas (UM) in the setting of ocular melanosis (melanosis oculi) represent genetically independent tumors. DESIGN: Clinical case series. METHODS: Two patients with unilateral multifocal UM in the setting of melanosis oculi were included. Tumors were evaluated for gene expression profile (GEP) and next generation sequencing (NGS) for uveal melanoma-associated mutations. Histopathologic analysis of enucleated specimens was also performed when available. RESULTS: Patients were both female, ages 73 and 83 years. In Patient #1, the tumors both exhibited Class 2 GEP but each harbored a unique BAP1 mutation. In Patient #2, one tumor was Class 1 and harbored an SF3B1 mutation, whereas the other tumor was Class 2 and harbored a BAP1 mutation. CONCLUSIONS: Unilateral multifocal UM in the setting of melanosis oculi can arise due to the development of genetically independent primary tumors, which is detectable based on the mutation profile of each tumor. This is the first report of genetically-confirmed independent primary tumors in the setting of unilateral multifocal UM.

Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate.

PURPOSE: To report the histological findings and clinical course of 2 patients with microcyst-like epithelial keratopathy (MEK) associated with antibody-drug conjugate, depatuxizumab mafodotin. METHODS: Case series. RESULTS: Two patients with glioblastoma multiforme participating in a phase 3 clinical trial of the antibody-drug conjugate, depatuxizumab mafodotin, presented with bilateral MEK. Confocal imaging showed multiple large, round, hyperreflective lesions in the epithelium. Epithelial debridement was performed for symptomatic relief in both patients. Along with aggressive lubrication, bandage contact lenses, and reduction in the chemotherapeutic dose to maintenance levels, both patients experienced symptomatic improvement. However, MEK lesions recurred after re-epithelialization. Immunohistochemistry of the diseased epithelium showed immunoglobulin (Ig)G-positive granular cytoplasmic inclusions and increased cell apoptosis. CONCLUSIONS: Depatuxizumab mafodotin accumulates in the basal corneal epithelium resulting in MEK because of increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

A Report of Intracranial Meningioma Recurring as Ectopic Orbital Meningioma Associated With Basal Encephalocele.

The authors describe a rare case of recurrent ectopic meningioma associated with sphenoid encephalocele in the medial anterior orbit of a 52-year-old man with a history of a resected intracranial meningioma. Typical features of ectopic meningioma are reviewed as well as potential etiologies of this very rare recurrence of intracranial meningioma in the orbit. Treatment is typically surgical excision.The authors report a rare case of recurrent orbital ectopic meningioma in the right medial canthus of a 52-year-old man.

ENDOGENOUS NOCARDIA ENDOPHTHALMITIS PRESENTING AS A MASS LESION IN A PATIENT WITH METATSTATIC NONSMALL CELL CARCINOMA OF THE LUNG.

PURPOSE: To report a case of Nocardia cyriacigeorgica endophthalmitis. METHODS: Case report. RESULTS: A 71-year-old man on long-term steroid therapy for poor respiratory function from lung carcinoma and presumed recent liver metastases presented with a four week history of blurry vision in the left eye. Ophthalmic examination revealed a white elevated mass in the macula with hemorrhage, concerning for metastasis. The patient was treated for presumed ocular metastases but had poor response to radiotherapy and was diagnosed four weeks later with N. cyriacigeorgica by retinal biopsy. Despite intravitreal and systemic antibiotics, the patient had progression of disease and died of respiratory involvement. CONCLUSION: Nocardia endogenous endophthalmitis can present as a mass retinal lesion in immunosuppressed patients with metastatic disease. Early vitreous and retinal biopsy may be required for definitive diagnosis and treatment. A pulmonary source of infection should be suspected and monitored closely.

Chronic inflammatory granulomata after use of GenTeal gel during strabismus surgery.

Subconjunctival granulomata developed in 2 patients after use of GenTeal gel to lubricate the cornea during strabismus repair. We report the clinical findings and histopathology of the subconjunctival nodules. These lesions are similar to those previously reported following use of GenTeal gel in retinal surgery and use of similar large polymers in nonocular surgeries. Copious irrigation should be considered when conjunctival wounds are exposed to GenTeal gel, and alternative corneal wetting agents should be considered for use during strabismus surgery.

Orbital implant exposure after Acanthamoeba panophthalmitis.

PURPOSE: Acanthamoeba is a protozoa that can lead to severe ocular disease and sequelae. Although intraocular Acanthamoeba infection is rare, the following case demonstrates an unusual presentation of recurrent Acanthamoeba infection in a 30 year old contact lens wearing male. OBSERVATIONS: After presenting with recurrent Acanthamoeba keratitis and undergoing various treatments, the patient developed nodular scleritis, which evolved into panophthalmitis, and ultimately, required enucleation. Eight months post-operatively, the patient developed orbital implant exposure secondary to persistent Acanthamoeba infection and underwent removal of the implant and aggressive, systemic treatment involving a multispecialty care team. He then underwent placement of a dermis fat graft and had no signs of persistent infection at the time of last follow-up, which was 24 months after placement of the dermis fat graft. CONCLUSIONS: and Importance: To the authors' knowledge, this is the first known case of Acanthamoeba infection causing orbital implant exposure. Persistent infection should be considered in Acanthamoeba patients who have undergone enucleation and have orbital implant exposure. Better knowledge regarding the pathogenesis and extracorneal complications of this challenging disease may improve patient care and outcomes.

Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate: [RETRACTED].

PURPOSE: To report the first histological characterization of microcyst-like epithelial keratopathy (MEK) associated with depatuxizumab mafodotin (ABT-414). METHODS: Case report. RESULTS: A 35-year-old man with glioblastoma multiforme participating in a phase III trial of the antibody-drug conjugate ABT-414 developed a large corneal abrasion from complications of MEK. Confocal imaging showed multiple large, round, hyperreflective lesions. Epithelial debridement was performed. Immunohistochemistry of the diseased epithelium showed IgG-positive granular cytoplasmic inclusions and increased cell apoptosis. With discontinuation of topical steroids, frequent lubrication, bandage contact lenses, and reduction in dose to maintenance therapy, the patient experienced symptomatic improvement. However, the MEK lesions recurred after debridement. CONCLUSIONS: ABT-414 accumulates in the basal corneal epithelium resulting in MEK due to increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

Osseous and Adipocytic Differentiations in the Intraocular Lens and Vitreous.

PURPOSE: To analyze 3 unusual mesenchymal transformations within the eye: adipose or osseous metaplasia of the lens and adipose tissue in the vitreous cavity. DESIGN: Observational case series. METHODS: Reevaluation of clinicopathologic diagnoses and histopathologic findings in sections stained with hematoxylin-eosin, periodic acid-Schiff (PAS) reaction, and Masson trichrome method. RESULTS: The 3 cases of mesenchymal transformation occurred in microphthalmic eyes with persistent hyperplastic primary vitreous (more recently termed persistent fetal vasculature). In 1 case there was total lens replacement with lamellar bone; in another, total replacement of the crystalline lens by adipose tissue; and in a third, an anomalous pocket of adipose tissue in the central vitreous. Multifocal remnants of the lens capsule were seen in the osseous case but were absent from the adipocytic cases. The vitreous adipose tissue was surrounded by an elaborate capillary plexus with an empty, collapsed PAS-positive lens capsule in the pupillary region. Anterior pigmented neuroectodermal disorganization, dysgenesis of angle structures, and a hypoplastic or disorganized iris were also observed in the 3 cases. CONCLUSIONS: After review of the literature, it appears that lenticular osseous replacement occurs more often than adipocytic. In addition to vascularization of the lens through a capsular dehiscence, other causes are explored, including direct epithelial-mesenchymal transformations of the lens epithelium or, less likely, of the disorganized adjacent neuroectoderm. The focus of vitreous adipose tissue may represent a transformed luxated lens extruded from its capsule, which was left behind in the pupillary zone.

Giant Cell Tumor of the Frontal Bone Presenting as an Orbital Mass.

A 10-year-old male was referred for evaluation of a right orbital mass present for 3 weeks with associated tenderness to palpation. Magnetic resonance imaging (MRI) and computed tomography imaging (CT) revealed a solid mass centered in the frontal bone with extension into the orbit. Surgical excision and histologic analysis of the lesion was consistent with a diagnosis of a Giant Cell Tumor (GCT) of the frontal bone. The patient tolerated the procedure without complication and is doing well upon follow-up.

Immunopathology and histopathology of conjunctival biopsies in patients with presumed idiopathic punctal stenosis.

BACKGROUND/AIMS: Numerous processes have been implicated as causes of punctal stenosis. Recent studies have highlighted inflammation in punctoplasty specimens in patients with punctal stenosis. Conjunctival biopsy has been suggested as a means to determine underlying aetiologies, although little is known regarding what conjunctival pathologies are associated with punctal stenosis. Our objective is to examine the pathological and immunological findings in conjunctival biopsy specimens in patients with presumed idiopathic punctal stenosis. METHODS: A retrospective chart review was performed at a single institution over a 5 year period of patients with presumed idiopathic punctal stenosis who underwent conjunctival biopsy for histopathological and/or direct immunofluorescence (DIF) examination. Patients with known aetiologies of punctal stenosis were excluded. RESULTS: 23 patients met inclusion criteria. Conjunctival biopsies (n=36) from all 23 patients underwent histological examination. 35 specimens (97.2%) showed lymphocytic infiltrates. Two patients (8.7%) had findings suggestive of sarcoidosis. Conjunctival biopsies from 18 of the 23 patients were also evaluated by DIF. Nine patients (50.0%) had fibrinogen characteristics suggestive of lichen planus. There were no complications related to the conjunctival biopsy procedures. CONCLUSIONS: Conjunctiva appears to be an excellent proxy in evaluating patients with presumed idiopathic punctal stenosis. The biopsy is safe and provides ample tissue. Clinically, abnormal tissue should be targeted, if available. 11 of the 23 patients in this study demonstrated findings consistent with underlying immunological disorders, suggesting that conjunctival biopsy may play a role in identifying underlying aetiologies of punctal stenosis. Knowledge of these underlying conditions impacted treatments for several patients.

A Unique Ocular Presentation of Extragenital Lichen Sclerosus.

Lichen sclerosus is a chronic, debilitating, and recurring disease that is most commonly seen affecting the anogenital region. Extragenital locations of lichen sclerosus has been well documented, frequently seen in the shoulders, neck, trunk, breasts, and arms, however, infrequently of the face. Specifically, extragenital lichen sclerosus has been reported in several cases to be involving the infraorbital region, but to our knowledge it has never been found affecting the adnexa of the eye. To our understanding, this is the first documented report of a patient with extragenital lichen sclerosus of an eyelid.

Chronic anophthalmic socket pain treated by implant removal and dermis fat graft.

AIMS: To report the outcome of orbital implant removal and dermis fat graft (DFG) implantation in patients with chronic anophthalmic socket pain (ASP), in whom all detectable causes of pain had been ruled out and medical management had failed. METHODS: Retrospective, multicentre case series. A review of all cases undergoing orbital implant replacement with DFG between 2007 and 2013 was conducted at the University of Iowa Hospitals and Clinics (UIHC), USA, and St. Erik Eye Hospital, Sweden. Inclusion criteria included (1) chronic ASP >2 years and unresponsive to treatment, (2) absence of pathological or structural cause for pain established by socket examination and orbital imaging, and (3) minimum 12-month post-surgical follow-up. RESULTS: Six cases with chronic ASP were identified, four were post-enucleation and two were eviscerated at an average age of 45 years. The incidence of chronic ASP among enucleations at UIHC over a 6-year period was 0.7%. Indications for enucleation and evisceration included tumours and glaucoma. Intractable ASP had been present for an average of 11 years and persisted despite medical management. All patients were free of pain within 3 months of implant removal and DFG placement and remained pain free at an average 24 months following surgery. CONCLUSIONS: Orbital implant replacement with DFG was effective at relieving chronic ASP, and pain resolution was sustained in all cases. This surgical intervention may be a useful management option for patients in whom all detectable causes of chronic pain have been excluded and have failed medical pain management.