CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD

Age-related macular degeneration (AMD) is a prevalent cause of blindness in Western societies. Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age-related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown. Here, we analyzed association between variants in CFH, C3 and ARMS2 and disease progression of geographic atrophy (GA) due to AMD. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P = 1.6x10(-9), 3.2x10(-3), and P = 2.6x10(-12), respectively) when compared to 612 unrelated healthy control individuals. In cases, median progression rate of GA over a mean follow-up period of 3.0 years was 1.61 mm(2)/year with high concordance between fellow eyes. No association between the progression rate and any of the genetic risk variants at the three loci was observed (P>0.13). This study confirms that variants at CFH, C3, and ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression

Anaplasma phagocytophilum Ats-1 Is Imported into Host Cell Mitochondria and Interferes with Apoptosis Induction

Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. Bacterial factors involved in this process are unknown. In the present study, we screened a genomic DNA library of A. phagocytophilum for effectors of the type IV secretion system by a bacterial two-hybrid system, using A. phagocytophilum VirD4 as bait. A hypothetical protein was identified as a putative effector, hereby named Anaplasma translocated substrate 1 (Ats-1). Using triple immunofluorescence labeling and Western blot analysis of infected cells, including human neutrophils, we determined that Ats-1 is abundantly expressed by A. phagocytophilum, translocated across the inclusion membrane, localized in the host cell mitochondria, and cleaved. Ectopically expressed Ats-1 targeted mitochondria in an N-terminal 17 residue-dependent manner, localized in matrix or at the inner membrane, and was cleaved as native protein, which required residues 55–57. In vitro-translated Ats-1 was imported in a receptor-dependent manner into isolated mitochondria. Ats-1 inhibited etoposide-induced cytochrome c release from mitochondria, PARP cleavage, and apoptosis in mammalian cells, as well as Bax-induced yeast apoptosis. Ats-1(55–57) had significantly reduced anti-apoptotic activity. Bax redistribution was inhibited in both etoposide-induced and Bax-induced apoptosis by Ats-1. Taken together, Ats-1 is the first example of a bacterial protein that traverses five membranes and prevents apoptosis at the mitochondria

Wanted : Camille Turner and Camal Pirbhai

"In the captivating photo series Wanted, artists Camal Pirbhai and Camille Turner repurpose authentic 18th-century fugitive slave ads printed in Canada, which featured detailed descriptions of the clothing worn by people who had resisted enslavement by stealthily running away. Descriptions of these outfits are reinterpreted in this photo series as high-fashion spreads that wouldn’t look out of place in a glossy magazine or on a billboard." -- Publisher's website

Eyelid tattoo blow-out: a case of pigment migration from cosmetic eyelid tattoo

Abstract P49David IT Sia, Adnan Pirbhai, Shyamala Huilgol, Dinesh Selv

Sebaceous carcinoma in Japanese patients: clinical presentation, staging and outcomes

This article has a correction, please see: Br J Ophthalmol 2014;98:286AIM: To describe the clinical features, management and correlation of the American Joint Committee on Cancer tumour node metastasis (TNM) staging for eyelid carcinoma with outcomes in Japanese patients with sebaceous carcinoma. METHODS: Multicentre retrospective review of 63 Japanese patients. Tumours were staged using the American Joint Committee on Cancer 7th edition TNM criteria. RESULTS: A distinct mass was the initial presentation in 94% and correct initial diagnosis made in 57% patients. Most tumours (60%) presented at stage T2aN0M0. The remaining TNM stages were: T2bN0M0 (25%); T3aN0M0 (9%); T3bN0M0 (2%); T2bN1M0 (2%); T3bN1M1 (2%). Frozen section controlled excision was performed in 81%. One patient required an orbital exenteration. Median follow-up was 4.2 years. Local recurrence occurred in four patients treated with frozen section controlled excision. Five patients had regional nodal metastases, two of which had T2aN0M0 lesions. T3a tumours and greater were significantly associated with local recurrence but not regional nodal metastasis. One patient died due to disease. One patient is alive with disease, and remaining patients were alive without disease at last follow-up. CONCLUSIONS: In this Japanese cohort, an eyelid mass was the main clinical presentation of sebaceous carcinoma. Contrary to previous reports, T2a tumours smaller than 10 mm were associated with regional nodal metastases.Akihide Watanabe, Michelle T Sun, Adnan Pirbhai, Kosuke Ueda, Nobutada Katori, Dinesh Selv

Hepatocellular carcinoma metastasis to sphenoid wing

We present a case report where hepatocellular carcinoma metastasis to the sphenoid wing was the initial presentation of an occult primary.Adnan Pirbhai, Shyalle Kahawita, Garry Davis, Tom Dodd, Josephine Thomas, and Dinesh Selv

The radiological spectrum of lacrimal gland pleomorphic adenoma

Abstract P33Nicholas Andrew, Akihide Watanabe, Kosuke Ueda, Shigeru Kinoshita, Nobutada Katori, Michael Reid, Adnan Pirbhai, Dinesh Selv

Mucus extravasation into the orbit during frontal sinus irrigation

During minitrephination and irrigation of the frontal sinus, mucus extravasated into the orbit through a defect in the sinus floor. The mucus incited a foreign body reaction and became encapsulated within the orbit necessitating excision via an anterior orbitotomy