A novel imaging approach to periocular basal cell carcinoma: in vivo optical coherence tomography and histological correlates.

PURPOSE: Optical coherence tomography (OCT) is a non-invasive imaging method widely used in ophthalmology. Recent developments have produced OCT devices for imaging the skin. The purpose of this study was to investigate Fourier Domain OCT morphological features of periocular basal cell carcinoma (BCC) in correlation with conventional histopathology. METHODS: Consecutive patients with periocular nodular BCC were prospectively examined with VivoSight OCT (Michelson Ltd) prior to surgical excision. OCT slice mode images were analysed using criteria defined for conventional and HD-OCT; the images were correlated to haematoxylin and eosin stained histology sections. RESULTS: A total of 15 patients with periocular BCC were recruited. Three categories of BCC morphological features were identified from slice mode OCT images: (1) Epidermal changes included epidermal thinning (15/15; 100%), ulceration and crusting (5/15, 33.3%) and decreased density of hair follicles (8/15; 53.3%); (2) Intralesional features included hyporeflective nodules (15/15; 100%), hyper-reflective edges (15/15; 100%) and hyporeflective central necrosis (3/15; 20%) (3) Perilesional features included hyporeflective borders (11/15; 73%), hypereflective margins (15/15; 100%) and dilated blood vessels (5/15; 33%). CONCLUSIONS: This study demonstrated that Fourier Domain OCT imaging offers additional information in the identification of morphological features of nodular BCC compared to conventional OCT diagnostic criteria. VivoSight produced fast, non-invasive imaging of skin lesions in the periocular region and high correlation with histology. Further studies are necessary to investigate OCT features of different histological subtypes of BCC.

Incidence and indications for pars plana vitrectomy following the treatment of posterior uveal melanomas in Scotland.

BACKGROUND: Globe-sparing treatments such as plaque brachytherapy, local or endoresection, and proton beam therapy (PBT) are the treatments of choice for posterior uveal melanoma. However, both early and late complications can arise from these techniques, including vitreous haemorrhage (VH) and retinal detachment (RD). Choroidal melanomas in Scotland are managed by a single unit, the Scottish Ocular Oncology Service (SOOS). METHODS: Indications and outcomes from surgery were analysed for patients undergoing vitrectomy following treatment for uveal melanoma in the SOOS between 1998 and 2013. RESULTS: Seventeen from 715 cases (2.4%) required vitrectomy, of which 8/445 (1.8%) followed plaque brachytherapy, 7/43 (16.3%) combined local resection and brachytherapy, and 2/227 (0.9%) PBT. Case notes were reviewed for 16/17 cases, with surgery indicated for VH in 10 (63%), RD in 5 (31%), and combined VH/RD in 1 (6%). The median interval from initial tumour treatment to vitrectomy was 5.8 months (range 10 days to 8.8 years). Ten (63%) required early vitrectomy (within 6 months), of which the majority (70%) followed combined resection/brachytherapy. Six (37%) required late vitrectomy (after 6 months), of which all were non-clearing VH following plaque brachytherapy, with proliferative retinopathy in 4/6 (67%), and tumour recurrence in 2/6 (33%). Overall vision improved in 8 eyes (50%), remained the same in 2 (12.5%), and deteriorated in 6 (37.5%). CONCLUSIONS: Early vitrectomy was most commonly indicated for RD following local resection, and late vitrectomy for VH due to radiation retinopathy. The majority of patients undergoing vitrectomy gained or maintained vision.

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas.

PURPOSE: To describe a cohort of patients with congenital eyelid coloboma, to identify associated ocular and craniofacial abnormalities, and to establish any correlation between the size and location of eyelid colobomas and the presence of such abnormalities. METHODS: An observational case series of 55 patients with eyelid coloboma treated by a single surgeon (JROC) between 1985 and 2005. RESULTS: Eyelid colobomas predominantly affected the upper lids (93%), and were typically unilateral (76%). About a third (29%) were an isolated finding, with the remainder associated with other ocular (62%) and/or craniofacial (53%) abnormalities. Of those with ocular abnormalities; 19 (56%) had conjunctival traction bands, 16 (47%) choristomas, and 8 (24%) an abnormal globe. Of those with craniofacial abnormalities; 13 (45%) had Goldenhar Syndrome, 10 (35%) clefting disorders, and 4 (14%) Fraser Syndrome. Clefting disorders were typically associated with more severe colobomas and a higher incidence of conjunctival traction bands, first arch syndromes with smaller colobomas and more choristomas. Overall large colobomas were significantly associated with the presence of other craniofacial defects compared with small colobomas (P<0.01, χ(2)), but coloboma size did not correspond with the presence of other ocular abnormalities. CONCLUSIONS: Coloboma size, location, and associations in this series are consistent with our current understanding of eyelid embryogenesis. It is likely that those colobomas associated with other craniofacial and ocular abnormalities are those which result from errors earlier in embryogenesis during eyelid specification, growth, and closure, whereas isolated colobomas arise later during eyelid separation, and after codependent structures have developed.

Eye casualty services in London.

The combined pressures of the European Working Time Directive, 4 h waiting time target, and growing rates of unplanned hospital attendances have forced a major consolidation of eye casualty departments across the country, with the remaining units seeing a rapid increase in demand. We examine the effect of these changes on the provision of emergency eye care in Central London, and see what wider lessons can be learned. We surveyed the managers responsible for each of London's 8 out-of-hours eye casualty services, analysed data on attendance numbers, and conducted detailed interviews with lead clinicians. At London's two largest units, Moorfields Eye Hospital and the Western Eye Hospital, annual attendance numbers have been rising at 7.9% per year (to 76 034 patients in 2010/11) and 9.6% per year (to 31 128 patients in 2010/11), respectively. Using Moorfields as a case study, we discuss methods to increase capacity and efficiency in response to this demand, and also examine some of the unintended consequences of service consolidation including patients travelling long distances to geographically inappropriate units, and confusion over responsibility for out-of-hours inpatient cover. We describe a novel 'referral pathway' developed to minimise unnecessary travelling and delay for patients, and propose a forum for the strategic planning of London's eye casualty services in the future.

Patient-reported benefit from oculoplastic surgery.

PURPOSE: It is vital that surgeons undertaking oculoplastic procedures are able to show that the surgery they perform is of benefit to their patients. Not only is this fundamental to patient-centred medicine but it is also important in demonstrating cost effectiveness. There are several ways in which benefit can be measured, including clinical scales, functional ability scales, and global quality-of-life scales. The Glasgow benefit inventory (GBI) is an example of a patient-reported, questionnaire-based, post-interventional quality-of-life scale that can be used to compare a range of different treatments for a variety of conditions. METHODS: A cross-sectional study was undertaken using the GBI to score patient benefit from four commonly performed oculoplastic procedures. It was completed for 66 entropion repairs, 50 ptosis repairs, 41 ectropion repairs, and 41 external dacryocystorhinostomies (DCR). The GBI generates a scale from -100 (maximal detriment) through zero (no change) to +100 (maximal benefit). RESULTS: The total GBI scores of patients undergoing surgery for entropion, ptosis, ectropion, and external DCR were: +25.25 (95% CI 20.00-30.50, P<0.001), +24.89 (95% CI 20.04-29.73, P<0.001), +17.68 (95% CI 9.46-25.91, P<0.001), and +32.25 (95% CI 21.47-43.03, P<0.001), respectively, demonstrating a statistically significant benefit from all procedures. CONCLUSION: Patients derived significant quality-of-life benefits from the four most commonly performed oculoplastic procedures.

Expressive language disorder after infarction of left lentiform nucleus.

A 53 year old bilingual woman presented with apraxia of speech and writing in English and German after ischaemic infarction of the left posterior lentiform nucleus. Detailed language assessment revealed impairments of articulation, verbal fluency, auditory repetition, interpretation of complex semantic relationships, formulation of definitions and verbal short-term memory. The case illustrates the role of the basal ganglia in speech planning, word retrieval and verbal short-term memory.

The heat sink and its relationship to reducing heat during pin-reduction procedures.

When self-threading pins are used in the restoration of teeth, the heat generated by cutting these pins to the correct length may traumatize the pulp. This study evaluated cotton forceps and a mosquito hemostat used as a heat sink and at different positions on the pin to determine any change in heat transferred to the tooth. Three hundred self-threading pins (Whaledent TMS System: 100 each of the Regular, Minim, and Minikin sizes) were inserted into freshly extracted teeth and sectioned. The temperature change at the apical end of the pin was measured using a thermistor probe. The results indicated that metal supporting instruments can be effective in reducing heat transferred to the apical aspect of the pin during pin reduction.

Purine nucleoside phosphorylase. 1. Structure-function studies.

To probe the catalytic mechanism of human purine nucleoside phosphorylase (PNP), 13 active-site mutants were constructed and characterized by steady-state kinetics. In addition, microtiter plate assays were developed for both the phosphorolytic and synthetic reactions and used to determine the kinetic parameters of each mutant. Mutations in the purine binding site exhibited the largest effects on enzymatic activity with the Asn243Ala mutant resulting in a 1000-fold decrease in the kcat for inosine phosphorolysis. This result in combination with the crystallographic location of the Asn243 side chain suggested a potential transition state (TS) structure involving hydrogen bond donation by the carboxamido group of Asn243 to N7 of the purine base. Analogous to the oxyanion hole of serine proteases, this hydrogen bond was predicted to aid catalysis by preferentially stabilizing the TS as a consequence of the increase in negative charge on N7 that occurs during glycosidic bond cleavage and the associated increase in the N7-Asn243 hydrogen bond strength. Two residues in the phosphate binding site, namely His86 and Glu89, were also predicted to be catalytically important based on their alignment with phosphate in the X-ray structure and the 10-25-fold reduction in catalytic activity for the His86Ala and Glu89Ala mutants. In contrast, catalytic efficiencies for the Tyr88Phe and Lys244Ala mutants were comparable with wild-type, indicating that the hydrogen bonds predicted in the initial X-ray structure of PNP [Ealick, S. E., et al. (1990) J. Biol. Chem. 265, 1812-1820] were not essential for catalysis. These results provided the foundation for studies reported in the ensuing two manuscripts focused on the PNP catalytic mechanism [Erion, M. D., et al. (1997) Biochemistry 36, 11735-11748] and the use of mutagenesis to reverse the PNP substrate specificity from 6-oxopurines to 6-aminopurines [Stoeckler, J. D., et al. (1997) Biochemistry 36, 11749-11756].

Intraosseous chondroid syringoma of the hallux.

A 25-year-old black woman had a deformed right great toe. X-ray examination revealed extensive lytic change in the distal phalanx, to which technetium uptake was limited. The amputation specimen revealed a benign chondroid syringoma in the subungual tissue that penetrated and permeated the bone. Chondroid syringoma is rare in the foot, and we present what we believe is the first such immunohistochemically confirmed case involving bone.

Demonstration of a functional requirement for the carbamate nitrogen of ribulosebisphosphate carboxylase/oxygenase by chemical rescue.

Ribulosebisphosphate carboxylase/oxygenase is reversibly activated by the reaction of CO2 with a specific lysyl residue (Lys191 of the Rhodospirillum rubrum enzyme) to form a carbamate that coordinates an essential Mg2+ cation. Surprisingly, the Lys191----Cys mutant protein, in the presence of CO2 and Mg2+, exhibits tight binding of the reaction intermediate analogue 2-carboxyarabinitol bisphosphate [Smith, H. B., Larimer, F. W., & Hartman, F. C. (1988) Biochem. Biophys. Res. Commun. 152, 579-584], a property normally equated with effective coordination of the Mg2+ by the carbamate. Catalytic ineptness of the Cys191 mutant protein, despite its ability to coordinate Mg2+ properly, might be due to the absence of the carbamate nitrogen. To investigate this possibility, we have evaluated the ability of exogenous amines to restore catalytic activity to the mutant protein. Significantly, the Cys191 protein manifests ribulose bisphosphate dependent fixation of 14CO2 when incubated with aminomethanesulfonate but not ethanesulfonate. This novel activity reflects a Km value for ribulose bisphosphate which is not markedly perturbed relative to wild-type enzyme, a Km for Mg2+ which is in fact decreased 10-fold, and rate saturation with respect to aminomethanesulfonate (Kd = 8 mM). Chromatographic and spectrophotometric analyses reveal the product of CO2 fixation to be D-3-phosphoglycerate, while turnover of [1-3H]ribulose bisphosphate into [3H]phosphoglycolate confirms oxygenase activity. We conclude that aminomethanesulfonate restored ribulosebisphosphate carboxylase/oxygenase activities to the Cys191 mutant protein by providing a nitrogenous function which satisfies a catalytic demand normally met by the carbamate nitrogen of Lys191.