Orbital and conjunctival nontuberculous mycobacteria infection.

A 64-year-old female developed refractory red-eye with itching and watery discharge 2 weeks after being injured by a comb in the left eye. It presented as diffuse pinkish thickening of the bulbar conjunctiva. Biopsy and histological examinations revealed granulomatous inflammation with microgranuloma. Acid-fast-positive bacilli were found within the tissue, which was identified by culture 5 weeks later as Mycobacterium Abscessus. The orbital computed tomography with contrast medium showed irregular enhancement with an ill-defined margin along the inferior sclera. Due to symptomatic and recurrent bulbar conjunctival thickening and abscess-like lesion formations, wide excision of the conjunctival and orbital granuloma with amniotic membrane transplantation was performed twice. Conjunctiva inflammation subsided after the surgical treatment was combined with 4 months of topical and parenteral antimycobacterial treatment. The presentation, diagnosis, and treatment of ocular nontuberculous mycobacterial (NTM) infection will be discussed in this article. NTM can cause infections of all adnexal and ocular tissues in patients with ocular trauma or surgical history. The pathological findings were granulomatous inflammation without true caseating. Periocular cutaneous, adnexal, and orbital NTM infections remain rare and require surgical debridement and long-term parenteral antibiotic therapy.

Dermis-fat graft as treatment of early implant exposure in a postpenetrating keratoplasty patient with nontraumatic eyeball rupture.

Orbital implant exposure may be the most common complication after evisceration surgery with orbital implantation. Management of implant exposure is a vital issue for oculoplastic surgeons. We present the case of a patient with nontraumatic eyeball rupture receiving dermis-fat graft after early implant exposure. The present case with multiple penetrating keratoplasty history underwent emergent evisceration and silicon sphere implantation due to nontraumatic eyeball rupture with severe uvea prolapse. The surrounding corneal tissue of the rupture aperture was almost unidentified before the operation. Deep superior sulcus syndrome and orbital implant exposure developed 2 months after the operation; hence, orbital reconstruction and dermis-fat graft transplantation were performed. Orbital reconstruction and orbital implant exposure management are discussed in the content.

Risk of skin cancer in patients with pterygium: a nationwide population-based cohort study in Taiwan.

This study investigated the association between pterygium and skin cancer linking to ultraviolet (UV) radiation using claims data from 1997-2010, obtained from the Taiwan National Health Insurance Research Database. The study included 19,701 patients with pterygium and 78,804 sex- and age-frequency-matched comparison subjects. Multivariate Cox regression analyses were performed to assess the relationship between pterygium and risk of skin cancer by the end of 2010. The incidence rates of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) in two cohorts and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of the diseases were measured. Results showed that the incidences of MM and NMSC were both higher in the pterygium cohort than in the comparison cohort (5.5 vs 3.2 and 32.3 vs 15.0 per 100,000 person years, respectively). After adjusting for age, sex, UV index, occupation, and the other comorbidities, pterygium remained a significant predictor of NMSC (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42), but not MM (HR, 1.46; 95% CI, 0.59-3.65). These results suggest that pterygium patients are associated with an increased risk of NMSC, but not significant for MM.

Atypical Rosai-Dorfman disease with lacrimal gland involvement.

PURPOSE: Rosai-Dorfman disease is a rare, benign, idiopathic histocytic proliferative disorder that typically presents in young adults with painless cervical lymphadenopathy. Here we report an atypical case of Rosai-Dorfman disease involving orbit tissue and lacrimal gland, unilaterally. CASE: A 69-year-old Asian women developed a painless palpable mass with local edema over the left upper eyelid over several months. Computed tomography (CT) showed an orbital mass with homogenous soft tissue density over the left lacrimal gland and superior orbital area. The patient underwent complete excision of the orbital tumor. OBSERVATIONS: The histopathology revealed diffuse and nodular infiltrations of S-100 positive histiocytes, plasma cells and lymphocytes. Emperipolesis (lymphocytophagocytosis) was also noted. These findings were consistent with Rosai-Dorfman disease. Chest CT revealed hilar lymphadenopathy. Three months after excision of the orbital mass, the patient developed lymphadenopathy in the extremities that resolved spontaneously over a few weeks. There were no complications or recurrence without systemic treatment after the complete excision. CONCLUSIONS: Orbital Rosai-Dorfman disease is a rare disorder, especially in Asia. Though there is no consensus on therapeutic choices, including corticosteroids, chemotherapy, radiation therapy, and surgical excision, the complete surgical excision performed in this case was without complication and had a favorable outcome.

Polymorphisms in steroidogenesis genes, sex steroid levels, and high myopia in the Taiwanese population.

PURPOSE: To evaluate the relationship among single nucleotide polymorphisms (SNPs) in steroidogenesis enzyme genes, serum levels of sex steroids, and high myopia in Taiwanese male and female populations. METHODS: A campus-based sample of 283 cases (145 males and 138 females) with high myopia and 280 controls (144 males and 136 females) with low myopia or emmetropia was studied. Estradiol, progesterone, and testosterone levels were determined using enzyme-linked immunosorbent assay kits. We genotyped six SNPs within five steroidogenesis enzyme genes (17 alpha-hydroxylase/17,20 lyase [CYP17A1], 3 beta-hydroxysteroid dehydrogenase [HSD3B1], 17 beta-hydroxysteroid dehydrogenase 1 [HSD17B1], steroid-5-alpha-reductase, alpha polypeptide 2 [SRD5A2], and aromatase [CYP19A1]) using polymerase chain reaction-restriction fragment length polymorphism methods. Student's t-tests, χ(2) tests, logistic regression, multifactor dimensionality reduction (MDR) methods, and ANOVA were used to determine significance. RESULTS: An MDR analysis corroborated the synergistic genotype association and demonstrated that synergistic interaction between rs6203 (HSD3B1), rs10046 (CYP19A1), and sex might confer susceptibility to high myopia (p=0.019). In both male and female subjects, levels of testosterone were significantly higher in cases than in controls; in male subjects, the levels of estradiol were significantly higher and those of progesterone were significantly lower in cases (all p-values <0.001). The rs605059 (HSD17B1), with sex-gene interaction, showed association with estradiol levels in males (p=0.035) and testosterone levels in females (p=0.027). CONCLUSIONS: Testosterone levels correlate with high myopia, and interaction of steroidogenesis enzyme genes and sex may be a modulating factor in sex hormone metabolism and high-myopia risk.

Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema.

Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusions are complicated by neovascularization and macular edema. Multi-targeted kinase inhibitors that inhibit select growth factor receptor tyrosine kinases and/or components of their down-stream signaling cascades (such as Src kinases) are rationale treatment strategies for these disease processes. We describe the discovery and characterization of two such agents. TG100572, which inhibits Src kinases and selected receptor tyrosine kinases, induced apoptosis of proliferating endothelial cells in vitro. Systemic delivery of TG100572 in a murine model of laser-induced choroidal neovascularization (CNV) caused significant suppression of CNV, but with an associated weight loss suggestive of systemic toxicity. To minimize systemic exposure, topical delivery of TG100572 to the cornea was explored, and while substantial levels of TG100572 were achieved in the retina and choroid, superior exposure levels were achieved using TG100801, an inactive prodrug that generates TG100572 by de-esterification. Neither TG100801 nor TG100572 were detectable in plasma following topical delivery of TG100801, and adverse safety signals (such as weight loss) were not observed even with prolonged dosing schedules. Topical TG100801 significantly suppressed laser-induced CNV in mice, and reduced fluorescein leakage from the vasculature and retinal thickening measured by optical coherence tomography in a rat model of retinal vein occlusion. These data suggest that TG100801 may provide a new topically applied treatment approach for ocular neovascularization and retinal edema.

SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.

Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.

p21WAF-1/Cip-1 gene therapy as an adjunct to glaucoma filtration surgery.

Glaucoma is a blinding eye disease characterized by elevated intraocular pressure (IOP). Glaucoma filtration surgery (GFS) is designed to reduce IOP, but wound healing responses to the procedure can result in surgical failure. Anti-metabolites used in conjunction with GFS are commonly employed to control the wound healing response, but have unwanted side effects. This review describes the therapeutic potential of ocular gene therapy using an adenovirus vector containing the human p21WAF-1/Cip-1 gene (rAd-p21) to control unwanted wound healing post-GFS. Here, we summarize encouraging preclinical data in relevant models, and propose rAd-p21 gene therapy as an alternative to the currently used methods of wound healing modulation.