Thinking 3D: Leonardo to the Present

The Portrait of Luca Pacioli with a Student (1495), reproduced on the first wall of the exhibition space, sets the mood and the intellectual climate of Thinking 3D: Leonardo to the Present, an exhibition held at the Bodleian Libraries in Oxford from March 21, 2019 until February 9, 2020. In the painting, Pacioli, a mathematician and teacher of Leonardo da Vinci and Albrecht Dürer, stands in a dimly lit study with one hand on an open book and the other holding a stick, pointing to a geometric ..

A comparison of retrokeratoprosthetic membrane and conjunctival inflammatory responses to silicone oil

Silicone oil continues to be an important aid in retinal detachment surgery. We report a case in which disparate responses to silicone oil were noted in the conjunctiva and intraocularly. Intraocularly, the oil permeated a fibrous membrane that formed behind a keratoprosthesis, the first example of this phenomenon. We detail the histological response to the oil at this site as well as a distinctly different reaction present to oil in the conjunctiva of the same eye. The divergence of histological responses provides a demonstration of the eye's apparent retained capacity to protect against intraocular inflammation, despite multiple previous surgeries

Coagulation Factor XIII-A Subunit Missense Mutation in the Pathobiology of Autosomal Dominant Multiple Dermatofibromas

Dermatofibromas are common benign skin lesions, the etiology of which is poorly understood. We identified two unrelated pedigrees in which there was autosomal dominant transmission of multiple dermatofibromas. Whole exome sequencing revealed a rare shared heterozygous missense variant in F13A1 gene encoding factor XIII subunit A, a transglutaminase involved in hemostasis, wound healing, tumor growth, and apoptosis. The variant (p.Lys679Met) has an allele frequency of 0.0002 and is predicted to be a damaging mutation. Recombinant human Lys679Met FXIII-A demonstrated reduced fibrin crosslinking activity in vitro. Of note, treatment of fibroblasts with media containing Lys679Met FXIII-A led to enhanced adhesion, proliferation and type I collagen synthesis. Immunostaining revealed co-localization between FXIII-A and α4β1 integrins, more prominently for Lys679Met FXIII-A than wild-type. In addition, both the α4β1 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine-Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may leads to a conformational change in the FXIII-A protein that enhances α4-integrin binding and provide insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma

Biocompatibility and biofilm inhibition of N,N-hexyl,methyl-polyethylenimine bonded to Boston Keratoprosthesis materials

The biocompatibility and antibacterial properties of N,N-hexyl,methyl-polyethylenimine (HMPEI) covalently attached to the Boston Keratoprosthesis (B-KPro) materials was evaluated. By means of confocal and electron microscopies, we observed that HMPEI-derivatized materials exert an inhibitory effect on biofilm formation by Staphylococcus aureus clinical isolates, as compared to the parent poly(methyl methacrylate) (PMMA) and titanium. There was no additional corneal epithelial cell cytotoxicity of HMPEI-coated PMMA compared to that of control PMMA in tissue cultures in vitro. Likewise, no toxicity or adverse reactivity was detected with HMPEI-derivatized PMMA or titanium compared to those of the control materials after intrastromal or anterior chamber implantation in rabbits in vivo.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract DAAD-19-D-0002

Unusual Involvement of IgG4-Related Sclerosing Disease in Lacrimal and Submandibular Glands and Extraocular Muscles

Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject

Primary Sebaceous Carcinoma of the Corneaoscleral Limbus With Pagetoid Recurrence

We report a sebaceous carcinoma confined to the corneoscleral limbus without involvement of the eyelid. A 60-year-old man, who showed multiple masses on the corneaoscleral limbus and limbal ulceration but with normal eyelids, underwent surgical en-bloc excision of the masses. Histopathologic examination revealed a sebaceous carcinoma. Three weeks after excision, multiple pagetoid recurrences were found along the bulbar conjunctiva 2 mm away from the limbus. After the application of topical mitomycin C, the pagetoid spread regressed completely. After a 2 year follow-up, no other local or systemic recurrences were observed. This report shows that the ulcerative mass which is confined to only the corneoscleral limbus may be a sebaceous carcinoma even without eyelid involvement. Topical mitomycin C may be effective for treating pagetoid spread of sebaceous carcinoma of limbal origin

A Drug Delivery System for Administration of Anti–TNF-α Antibody

Purpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results: Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions: Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy