Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.

Purpose: To develop a mouse model of human dry eye disease (DED) for investigation of sex differences in autoimmune-associated dry eye pathology. Methods: Ocular surface disease was assessed by quantifying corneal epithelial damage with lissamine green stain in the NOD.H-2h4,IFNγ-/-,CD28-/- (NOD.H-2h4 DKO) mouse model of Sjögren's syndrome (SS). Lacrimal gland function was assessed by tear volume quantification with phenol red thread and lacrimal gland inflammation (i.e., dacryoadenitis) was assessed by quantification of immune cell foci, flow cytometric analysis of immune cell composition, and expression of proinflammatory markers. Results: The NOD.H-2h4 DKO mouse model of SS exhibits greater age-dependent increases in corneal damage than in NOD.H-2h4 parental mice and demonstrates an earlier disease onset in females compared to males. The severity of ocular surface disease correlates with loss of goblet cell density, increased conjunctivitis, and dacryoadenitis that is more pronounced in NOD.H-2h4 DKO than NOD.H-2h4 mice. B cells dominate lacrimal infiltrates in 16-week-old NOD.H-2h4 and NOD.H-2h4 DKO mice, but T helper cells and macrophages are also present. Lacrimal gland expression of proinflammatory genes, including the P2X7 and P2Y2 purinergic receptors, is greater in NOD.H-2h4 DKO than NOD.H-2h4 mice and correlates with dacryoadenitis. Conclusions: Our results demonstrate for the first time that autoimmune dry eye disease occurs in both sexes of NOD.H-2h4 DKO and NOD.H-2h4 mice, with earlier onset in female NOD.H-2h4 DKO mice when compared to males of the same strain. This study demonstrates that both NOD.H-2h4 and NOD.H-2h4 DKO mice are novel models that closely resemble SS-related and sex-dependent DED.

Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring.

PURPOSE: To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS: Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS: An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS: Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.

Arteriovenous Malformation of the Eyelid: Surgical Management and Histologic Study.

A raised erythematous eyelid lesion that appeared in a 31-year-old man was diagnosed as an arteriovenous malformation (AVM), with confirmatory Doppler ultrasound demonstrating high arterial flow. Surgical excision, aided by electrocautery for extensive hemorrhage, resulted in an acceptable cosmetic result. Histopathology of the excised lesion showed collapsed capillary channels lined by endothelium. AVM is rarely encountered in the eyelid.

Aggressive esthesioneuroblastoma with divergent differentiation: A taxonomic dilemma.

The authors describe an esthesioneuroblastoma (olfactory neuroblastoma) that occurred within the nasal cavity and brain in a 31-year-old man. Following excision, the tumor recurred in the left orbit and in mediastinal lymph nodes. Treatment included orbital excision and systemic chemotherapy. Histopathology showed a high-grade neuroepithelial tumor with positive immunohistochemical markers for neuroendocrine and epithelial components, an unusual combination raising issues concerning taxonomy.

Effect of upper eyelid myectomy on subsequent chemodenervation in the management of benign essential blepharospasm.

PURPOSE: Some patients with severe benign essential blepharospasm (BEB) become clinically refractory to chemodenervation with botulinum toxin. In these patients, surgical myectomy is an effective additive treatment for the management of this disabling condition. The purpose of this study is to determine how myectomy for BEB alters subsequent botulinum toxin administration. METHODS: A retrospective chart review of 27 patients undergoing surgical myectomy for the treatment of refractory BEB was conducted. The frequency and dosage of botulinum toxin were compared between preoperative and postoperative treatments. Paired Student t tests were used to determine significance (α = 0.05). RESULTS: The mean interval between botulinum treatments was 10.1 weeks preoperatively and 15.7 weeks postoperatively (p < 0.001). The mean quantity of botulinum toxin administered was 68 units prior to myectomy and 64.9 units postoperatively (p = 0.227). When comparing the quantity of botulinum toxin injected into the upper eyelid region only (site of myectomy), there was a significant decrease in the dose administered preoperatively and postoperatively (46.8 units vs. 39.9 units, p = 0.00310). CONCLUSIONS: Upper eyelid myectomy is an effective treatment modality for BEB in those patients who are refractory to botulinum toxin injections. Myectomy for BEB decreases the morbidity, botulinum toxin treatment frequency, and long-term expense associated with this disabling condition.

Medial conjunctival resection for tearing associated with conjunctivochalasis.

PURPOSE: Conjunctivochalasis is an age-dependent redundancy or laxity of the conjunctiva. It may result in epiphora (tearing) through mechanical disruption of the normal tear flow or exacerbate dry eye symptoms by disruption of an already unstable tear film. In this study, the authors performed a retrospective analysis of the benefits of a simple medial conjunctival resection for tearing associated with conjunctivochalasis. METHODS: A review of medical records identified 18 patients (25 eyes) who underwent a medial conjunctivoplasty for tearing between 2000 and 2012. The degree of epiphora was graded for each patient from 0 (no tearing) to 3 (persistent tearing requiring surgical correction). All patients were given an initial preoperative score of 3. Patients were excluded from the study if more than 1 eyelid procedure that would affect the lacrimal pump function was performed at the time of conjunctivoplasty or if clinically significant entropion, ectropion, or nasolacrimal duct obstruction was present at the time of conjunctivoplasty. RESULTS: At an average of 2.7 months post-conjunctivoplasty (range 4 weeks to 12 months), 80% of patients improved to a score of 2 or better and 60% improved to 1 or better. Six patients ultimately needed an additional surgical procedure for unresolved or recurrent tearing. CONCLUSIONS: The data suggest that conjunctivoplasty using a simple medial conjunctival resection is an effective treatment for patients with epiphora secondary to conjunctivochalasis.

Ophthalmic manifestations of rheumatologic disease: diagnosis and management.

Rheumatologic diseases are often associated with ophthalmic findings. Familiarity with and recognition of these ophthalmic presentations are important in the management of both the systemic and ocular manifestations of the disease. Identification of ocular signs and symptoms of rheumatologic disease will allow a more comprehensive approach to treatment of patients with rheumatic conditions.

Bacterial transcytosis across conjunctival M cells.

PURPOSE: Antigen-sampling M cells have been identified in conjunctival tissue overlying lymphoid follicles in rabbits and guinea pigs. Conjunctival M cells in the guinea pig display alpha(2-3) sialic acid on their surfaces, as evinced by selective labeling by Maackia amurensis leukoagglutinin (MAL)-I. Haemophilus influenzae strains OM12, which expresses the HMW1 adhesin for alpha(2-3) sialic acid, and Rd KW20, which lacks HMW1, were used to test the hypothesis that conjunctival M cells translocate large microbes. METHODS: Fluorescein-labeled bacteria were instilled into the conjunctival sac for up to 130 minutes. Confocal laser scanning microscopy and electron microscopy were used to visualize bacterial distribution. RESULTS: M cells, but not nonfollicular epithelial cells in the palpebral region, selectively bound and translocated bacteria. By 66 minutes, 423 +/- 165 bacteria/mm(2) of follicle-associated epithelial (FAE) surface were found in three-dimensional reconstructions extending 15.4 mum below the surface. By 127 minutes, the number of bacteria increased to 579 +/- 44/mm(2) of FAE surface and they had moved 50% deeper into the follicle. Coadministration with MAL-I reduced OM12 transport by 61%. Similarly, Rd KW20 uptake was 71% less at 63 minutes and 58% less at 121 minutes, indicating that OM12 uptake is at least partially mediated by binding to alpha(2-3) sialic acid. CONCLUSIONS: Conjunctival M cells are a port of entry for large microbes and may play a role in initiation of mucosal immune responses against commensal or transient ocular bacterial species and may allow the entry of pathogens.