Periocular tuberculous disease: experience from a UK eye hospital.

BACKGROUND/AIMS: To describe our experience of patients presenting to a tertiary referral adnexal department with orbital or periocular tuberculosis (TB) over a 10-year period. METHODS: We reviewed all patients with a diagnosis of orbital or periocular TB from 2001 to 2011 in Moorfields Eye Hospital. RESULTS: Nine patients were identified over the 10-year period. Three cases of cutaneous TB, two cases of TB dacryocystitis and four cases of diffuse orbital TB were identified. All patients lived in the UK, but were born in the African or Asian subcontinents. Three patients had known prior (and treated) pulmonary TB and all were immunocompetent.All patients presented with periocular discomfort. After tissue diagnosis, all patients were referred for triple antituberculous therapy (ATT); all patients completed their course of ATT, with resolution of all orbital and lacrimal masses. There were no recurrences at a median follow-up of 26 weeks (range 1 month-5 years). One patient, who required later evisceration, was the only case with loss of vision. CONCLUSIONS: Orbital and periocular TB can be difficult to diagnose and lead to diagnostic delays, with emphasis on clinical suspicion rather than a positive culture result; the management of such cases is not only surgical, but also medical and social. Although surgical intervention can alleviate symptoms and prevent visual loss, the use of a complete course of ATT is paramount for disease management and the patient and their family need to be counselled about the associated public health issues.

Wnt signalling in an in vitro niche model for conjunctival progenitor cells.

Mimicking an environment in vitro that is more similar to the stem cell niche in vivo, by co-culture of mitotically active conjunctival fibroblasts (HCF) with human conjunctival epithelial cells (HCECs), improves the maintenance of epithelial cells with progenitor cell characteristics during in vitro expansion. However, little is known about the pathways controlling the fate of the epithelial progenitor cells during in vitro culture. In this study, differences in gene expression between this in vitro 'niche' model and standard culture conditions, in which growth-arrested 3 T3 feeder cells and fetal calf serum are used, were explored using a genome level microarray platform, quantitative (q)RT-PCR and western blot. The microarray analysis revealed significant alterations of biological processes involved in cell proliferation, differentiation and cell death. The analysis of stem cell-related pathways indicated changes in expression of genes involved in the Wnt signalling pathway, and further investigation by qPCR revealed significant downregulation of the Wnt ligands Wnt3, Wnt4, Wnt7B and Wnt10A, Wnt receptor proteins FZD1, LRP5, LRP6, ß-catenin and TCF7L1 and important Wnt target genes, such as CCND1, also confirmed by western blot and immunocytochemistry. The results indicate that epithelial cell expansion in the HCEC-HCF co-culture system is accompanied by significant changes in expression of genes involved in the Wnt signalling pathway. This altered pathway activation might be involved in the enhanced maintenance of epithelial progenitor cells in this in vitro 'niche' model.

Discoid lupus erythematosus of the periorbita: clinical dilemmas, diagnostic delays.

PURPOSE: Untreated periocular discoid lupus erythematosus (DLE), though very rare, may lead to significant morbidity with lid deformities, trichiasis, and symblepharon formation. We present the largest reported cohort of patients with biopsy-proven DLE solely affecting the periorbital region. METHODS: Observational case series of patients managed over a 7-year period (2004-10). RESULTS: Seven patients (one male) presented to the Adnexal Service at Moorfields Eye Hospital at a median age of 47 years (range 23-71 years); median interval from symptom onset to biopsy-proven diagnosis was 38 months (range 6-86 months). Changes in peripheral skin were present in 1 patient (occurring after the initial eyelid presentation) and the presenting periocular features were dissimilar across the group, these included: chronic blepharo-conjunctivitis, madarosis, atypical chalazia, depigmentation of the eyelid margin, or marked, persistent periocular oedema with dacryoadenitis.Two cases settled spontaneously, but five required systemic hydroxychloroquine or intralesional corticosteroid injections. CONCLUSION: Periorbital DLE is rare and very varied in its presentation, the protean manifestations often resulting in significant diagnostic delay. All patients with unusual periocular skin disease and those with a refractory inflammatory dermopathy, should undergo biopsy of involved tissue(s), thus leading to earlier diagnosis and prevention of permanent cicatricial periocular changes.

Conjunctival epithelial cells maintain stem cell properties after long-term culture and cryopreservation.

AIM: Transplantation of tissue-engineered conjunctival epithelial cell sheets has proven to be a promising technique for conjunctival reconstruction. The ability to cryopreserve conjunctival epithelial cells and maintain their stem cell population would improve their availability for clinical use. The aim of this study was to evaluate whether cryopreservation and long-term in vitro culture has an effect on the proliferative capacity and the progenitor-like cell characteristics of conjunctival epithelial cells. METHOD: Human conjunctival cells from bulbar biopsies were isolated and expanded on a growth arrested 3T3 feeder layer. The cells were evaluated for cytokeratin (CK4/CK19) expression by immunostaining. An aliquot with half of the cells from the initial culture was frozen in liquid nitrogen and stored for 14 days and, in addition, donor cells were cryopreserved for more than 6 months (202.7 +/- 13.0 days). Both cryopreserved and noncryopreserved cells were serially cultivated over four passages. For each passage the colony-forming efficiency and the cell population doubling rates were evaluated, and expression of putative progenitor cell markers, p63alpha and ABCG2, was assessed by immunostaining and reverse transcription PCR. RESULTS: Both noncryopreserved and cryopreserved cells demonstrated a high colony-forming capacity that decreased with passage. Cells from both groups underwent approximately 20 cell population doublings before senescence. Immunoreactivity to p63alpha and ABCG2 was found in both groups until passage 4 and their presence was also confirmed by reverse transcription PCR. No difference in cell viability, colony-forming efficiency and immunoreactivity to p63alpha and ABCG2 was observed between cells cryopreserved for 14 days, and more than 6 months (202.7 +/- 13.0 days). CONCLUSION: Conjunctival epithelial cells with progenitor cell-like characteristics can be efficiently cryopreserved and can subsequently maintain their function in vitro over several culture passages. The option to cryopreserve conjunctival cells prior to in vitro expansion would be an advantage when cells have to be cultivated for clinical transplantation.

Subspecialty adnexal ophthalmological examination using telemedicine.

We studied the clinical outcome of examination of a group of patients with adnexal (eyelid and orbit) conditions. Seventeen patients with adnexal problems were assessed by an ophthalmologist at a distance using telemedicine, and then subsequently by an ophthalmologist in a face-to-face consultation. Measurements such as palpebral aperture, levator muscle function and eyelid skin crease position were recorded. The clinical outcomes from both consultations were recorded independently by the consultants and then compared. The study showed that certain adnexal conditions, such as congenital and involutional ptosis, could be accurately assessed using telemedicine, but that other conditions, such as socket problems in patients who had a previous enucleation or those with non-specific ocular pain with less clear-cut features, were better assessed in a face-to-face consultation. Overall, teleconsultations appeared to be suitable for the assessment of uncomplicated ptosis but not for less well defined conditions. Other factors, such as family dynamics and language problems, also limited the usefulness of the technique.

Visual development in the blepharophimosis syndrome.

One hundred and one cases of the blepharophimosis syndrome presenting over a decade are reviewed with particular attention to the factors influencing their visual development. Three distinct clinical patterns emerge--severe bilateral ptosis, moderate bilateral ptosis, and asymmetric ptosis--and their differing incidence of amblyopia and strabismus is discussed. The risk of amblyopia is much higher than previously believed (56.4% in our series) and preventive management is discussed.

CT findings in orbital tumours of nerve sheath origin.

The clinical and CT features of orbital nerve sheath tumours (13 neurofibromas and 17 neurilemmomas, including one malignant neurilemmoma) have been reviewed. The commonest clinical findings were proptosis, mild impairment of visual acuity and disorders of eye movements. No significant correlation with intra- or extraconal location and these symptoms was found. The two types of tumour were morphologically similar, most being smooth retrobulbar masses, elongated in the long axis of the orbit; lobulation was slightly more common with neurofibromas. The neurilemmomas were generally larger than the neurofibromas. The distribution of neurilemmomas in the retrobulbar space, and in its intra- and extraconal compartments appeared random, but most neurofibromas occurred in the upper orbit and three quarters lay extraconally. The apex of the orbit was seen to be clear of tumour in all intraconal neoplasms (except the one case of malignant neurilemmoma); this observation may be useful in differentiation from intrinsic optic nerve tumours and pseudotumour. Focal or generalised enlargement of the bony orbit was common, being seen in four-fifths of neurilemmomas and three-quarters of neurofibromas. Tumour density was homogeneous for all the neurilemmomas and in the majority of neurofibromas: attenuation coefficients were slightly higher for the neurofibromas. Subcutaneous extension was more common in neurofibromas, occurring in approximately one third of cases but was observed in about a tenth of the neurilemmomas. Enhancement with intravenous contrast medium was variable; contrast medium was helpful in showing intracranial extension. Although the CT findings did not allow unequivocal presurgical diagnosis, they were suggestive in many cases and facilitated biopsy.