Could Extension Into the Lacrimal Gland and Sac Thwart Topical Chemotherapy for Intraepithelial Sebaceous Carcinoma?

PURPOSE: To identify the frequency of intraepithelial (Pagetoid) spread beyond the ocular surface-namely beyond conjunctiva and cornea-in patients undergoing orbital exenteration for advanced periocular Sebaceous carcinoma (SC). DESIGN: A retrospective, noncomparative observational case series. SUBJECTS: Patients undergoing orbital exenteration for biopsy-proven SC, at Moorfields Eye Hospital between 1997 and 2013. METHODS: Review of clinical records and histological specimens, with particularly reference to involvement of conjunctiva and the extent of Pagetoid infiltration beyond the examinable ocular surface-here termed "hidden" disease. MAIN OUTCOME MEASURES: Histological evidence of intraepithelial SC within the lacrimal sac or lacrimal gland. RESULTS: Twenty-nine patients had clinical data and histological specimens adequate for review. Seventeen (59%) did not have a discrete mass (clinically or histologically) and, on clinical examination, were thought to only have extensive intraepithelial carcinoma; foci of microscopic invasion were, however, detected histologically in 11/17 (65%) of these specimens. Moreover, the in situ carcinoma was found to have invaded far in lacrimal gland ductules in 1/17 patients, in the lacrimal sac (in 2 patients; 12%) or in both the gland and sac (in 2 patients); these 5/17 (29%) cases all showed extensive poorly differentiated intraepithelial SC. Of the 12 other patients who had both Pagetoid spread and a clinically evident nodule, 3 had histological evidence of "hidden" disease. CONCLUSION: Although-due to their being operated in the era prior to the accepted usage of topical therapy for this condition-some of these exenterations might have had particularly advanced in situ SC, over a quarter of patients with periocular SC warranting orbital exenteration show "hidden" intraepithelial tumor within the lacrimal gland and sac. This important finding might significantly reduce the efficacy (particularly in the lacrimal gland) of the various topical therapies used for in situ SC of the ocular surface, and it also emphasizes the importance of excising both the lacrimal gland and sac in all orbital exenterations for this particular tumor.

Form, shape and function: segmented blood flow in the choriocapillaris.

The development of fluid transport systems was a key event in the evolution of animals and plants. While within vertebrates branched geometries predominate, the choriocapillaris, which is the microvascular bed that is responsible for the maintenance of the outer retina, has evolved a planar topology. Here we examine the flow and mass transfer properties associated with this unusual geometry. We show that as a result of the form of the choriocapillaris, the blood flow is decomposed into a tessellation of functional vascular segments of various shapes delineated by separation surfaces across which there is no flow, and in the vicinity of which the transport of passive substances is diffusion-limited. The shape of each functional segment is determined by the distribution of arterioles and venules and their respective relative flow rates. We also show that, remarkably, the mass exchange with the outer retina is a function of the shape of each functional segment. In addition to introducing a novel framework in which the structure and function of the metabolite delivery system to the outer retina may be investigated in health and disease, the present work provides a general characterisation of the flow and transfers in multipole Hele-Shaw configurations.

Recurrent ptosis due to myopathy of the levator palpebrae superioris.

The authors report the 10-year follow-up of a case with a recurrent ptosis affecting both eyelids independently. The histology of the levator palpebrae superioris and Müller's muscle was consistent with a localised myopathic process. A therapeutic response to acetazolamide suggests that ion-channel dysfunction may be the underlying cause for this new myopathy.

Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration.

BACKGROUND: Several studies indicate that age-related macular degeneration (AMD) and atherosclerosis may share common pathogenetic pathways. The aim of this study was to determine the role of systemic matrix metalloproteinases (MMPs) in AMD, given that MMPs are implicated in the pathogenesis of atherosclerosis. METHODS: This study determined the plasma matrix metalloproteinases (MMP-2 and MMP-9) levels in three groups of subjects: group 1 included subjects with age-related maculopathy (ARM), group 2 included subjects with choroidal neovascularization (CNV) owing to AMD and group 3 consisted of age-matched controls. RESULTS: The mean plasma levels of MMP-2 were not significantly different in the three groups. In contrast, the mean plasma MMP-9 levels were significantly higher in ARM and CNV groups compared to that of the control group. However, there was no significant difference in MMP-9 levels between ARM and CNV groups. CONCLUSION: This is the first study that reveals a link between raised plasma MMP-9 levels with AMD. Further studies are required to identify the factors that contribute to this association.

Outcome of retinoblastoma in east Africa.

We estimated the proportion of patients reaching a pediatric ophthalmology unit (Comprehensive Community Based Rehabilitation for Tanzania Disability Hospital, CCBRT) or an oncology unit (ORCI) in east Africa and investigated presentation, histology, and treatment outcomes of patients with retinoblastoma. A 5-year retrospective study identified 91 patients, representing approximately 18% of the nationwide total. Mean lag time was 10 months (standard deviation (SD) = 17) and mean follow-up was 8 months (SD = 11, range 0-40, n = 91). Thirty months disease-free survival probability was 0.23 (standard error = 0.07). Outcomes for retinoblastoma in Africa remain poor. The data presented here suggest strategies for improving the outcomes, including encouraging earlier presentation and establishment of multi-disciplinary treatment centers.

Macular pigment in the human retina: histological evaluation of localization and distribution.

PURPOSE: Clinical investigations have demonstrated variation in both the peak optical density and the spatial distribution of macular pigment. To confirm these impressions histologically, the present study examined the distribution of macular pigment in the human retina. MATERIALS AND METHODS: The macular retina of 11 donor eyes of different ages (28-91 years) were examined histologically on 100 microm vibratome sections directly, without further staining. Measurements were made in two dimensions: (1) adding the number of macular sections with visible macular pigment, and (2) direct measurement of the extension of macular pigment in the foveolar section, which visibly contained the most macular pigment. RESULTS: The measurements with two methods demonstrated good correlation. The macula demonstrated a variation in the spatial extension of the visible macular pigment between 200 and 900 microm diameter around the centre of the fovea, which was also found when direct measurements were taken. There was no correlation with the donor age. The main location of macular pigment was in the layer of the fibres of Henle in the fovea and in the inner nuclear layer at the parafoveal site. CONCLUSIONS: Histologically, a wide variation of the spatial distribution of macular pigment was found that confirms clinical observations. The primary localization of human macular pigment is in the inner retinal layers.

Epibulbar osseous choristoma: benign pathology simulating an intraorbital foreign body.

Epibulbar osseous choristomas typically present, in the young, as a supero-temporal subconjunctival nodule and radiographic imaging often shows a densely radio-opaque fleck on the sclera--this often being misinterpreted as a parabulbar foreign body. Four illustrative cases are presented.

Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration.

BACKGROUND: Several studies indicate that age-related macular degeneration (AMD) and atherosclerosis may share common pathogenetic pathways. The aim of this study was to determine the role of systemic matrix metalloproteinases (MMPs) in AMD, given that MMPs are implicated in the pathogenesis of atherosclerosis. METHODS: This study determined the plasma matrix metalloproteinases (MMP-2 and MMP-9) levels in three groups of subjects: group 1 included subjects with age-related maculopathy (ARM), group 2 included subjects with choroidal neovascularization (CNV) owing to AMD and group 3 consisted of age-matched controls. RESULTS: The mean plasma levels of MMP-2 were not significantly different in the three groups. In contrast, the mean plasma MMP-9 levels were significantly higher in ARM and CNV groups compared to that of the control group. However, there was no significant difference in MMP-9 levels between ARM and CNV groups. CONCLUSION: This is the first study that reveals a link between raised plasma MMP-9 levels with AMD. Further studies are required to identify the factors that contribute to this association.

Masked orbital abscess in Wegener's granulomatosis.

Two patients with chronic Wegener's granulomatosis presented with worsening proptosis and visual acuity. Both patients had been maintained on long-term corticosteroids, which led to masking of the signs of orbital sepsis with potentially life-threatening implications.

Legeais BioKpro III keratoprosthesis implantation: long term results in seven patients.

AIMS: The long term results of the Legeais BioKpro III keratoprosthesis are presented for seven patients with severe corneal scarring. METHODS: The study took place at Moorfields Eye Hospital, London. Patients had either end stage ocular surface disease or corneal opacification after multiple failed graft surgery, with the potential for significant visual improvement. After insertion the device was covered with a conjunctival flap or buccal mucous membrane graft, which was later opened to expose the optic. The outcome measures were vision, complications, and retention of the device. RESULTS: The BioKpro III was inserted into seven patients with severe corneal scarring: ocular cicatricial pemphigoid, measles keratitis, thermal injury, Stevens-Johnson syndrome, aniridia, chemical injury, and congenital rubella. The follow up was 18-48 months. The keratoprosthesis failed in six, because of extrusion occurring 2-28 months postoperatively. Retroprosthetic membranes occurred in three patients, and endophthalmitis in one. Vision improved from hand movements to 6/12 in the only patient who retained the KPro; however he was troubled by mucus accumulation on the optic. CONCLUSIONS: The one success has been in a patient with thermal burns. The remaining results have been poor, with the KPro extruding in six of the seven patients.

Biopsy-confirmed spontaneous resolution of orbital langerhans cell histiocytosis.

A 17-year-old boy presented with a left upper lid swelling, headaches and diplopia. An orbital computerized tomography (CT) scan showed a mass in the left lacrimal fossa eroding bone and extending into the temporalis fossa and intracranially. An urgent biopsy without curettage was carried out and showed Langerhans cell histiocytosis. He was otherwise well and no other lesion was found. He was therefore observed and reviewed regularly. During follow-up it was noted that the mass was reducing in size. Five months after the initial biopsy a further procedure, involving curettage and an intralesional steroid, was carried out at a tertiary referral center. Histology of the material obtained showed no remaining evidence of Langerhans cell histiocytosis. Spontaneous resolution of orbital Langerhans cell histiocytosis has been described clinically and radiologically. This is the first case of spontaneous resolution to be confirmed histologically.

Effect of steroidal and non-steroidal drugs on the microglia activation pattern and the course of degeneration in the retinal degeneration slow mouse.

BACKGROUND: In hereditary retinal degeneration, microglia cells become activated, migrate through the outer nuclear layer (ONL) and accumulate in the subretinal space. Although this inflammatory process is not likely to be responsible for the onset of photoreceptor apoptosis, cytotoxic substances secreted by activated microglia could potentially accelerate and perpetuate the degenerative process. Anti-inflammatory drugs have been shown to modulate the microglia response in neurodegenerative disorders and potentially ameliorate the disease progression in various animal model systems. In this study we wanted to test the impact of the most commonly used anti-inflammatory drugs (acetylsalicylate and prednisolone) on the microglia activation pattern, the rate of caspase-3-dependent photoreceptor apoptosis and the course of the degeneration in the retinal degeneration slow (rds) mouse retina. METHODS: 169 pigmented rds mice and 30 CBA wild-type mice were used for this study. The treatment groups were injected daily with either acetylsalicylate (200 mg/kg) or prednisolone (2 mg/kg) i.p. from day 0 up to 3 months. Animals were sacrificed at days 10, 14, 16, 18, 20, 30, 40, 60 and 90. Cryoprotected frozen sections were immunostained with F4/80 and cleaved caspase-3 antibodies. The main outcome measures were the total microglia count in the subretinal space, the total cleaved caspase-3-positive cells in the ONL and the averaged number of photoreceptor rows in the midperipheral retina. RESULTS: Neither acetylsalicylate nor prednisolone reduced subretinal microglia accumulation in the rds mouse degeneration model. Moreover, they aggravated migration and accumulation in the early time course. The apoptotic cascade started earlier and was more pronounced in both treatment groups compared to the control group. The pace of retinal degeneration was not reduced in the treatment groups compared to the untreated control. In contrast, acetylsalicylate did significantly accelerate the photoreceptor cell degeneration in comparison to the prednisolone (p < 0.001) and to the control group (p < 0.001). CONCLUSIONS: Acetylsalicylate and prednisolone do not decrease the microglia response in the rds mouse and are not neuroprotective. More research is needed to clarify the molecular mechanisms which lead to photoreceptor cell death and to elucidate the complex role of microglia in inherited retinal degeneration.

Ultrastructure of vitreomacular traction syndrome associated with persistent hyaloid artery.

AIM: To demonstrate the ultrastructure of vitreomacular traction associated with persistent hyaloid artery. METHODS: Pars plana vitrectomy was performed in a 66-year-old man with progressive vitreomacular traction associated with a persistent hyaloid artery. Epimacular tissue was peeled and processed for transmission electron microscopy. RESULTS: Ultrastructural analysis revealed multiple sheets of cellular and collagenous components. Myofibroblasts and newly formed collagen were the predominant features. Fibrous astrocytes, fibroblasts, macrophages, and basement membrane were also present. CONCLUSION: The cellular composition of the epimacular tissue and high cellular activity suggest that persistence of the hyaloid artery may contribute to the development of vitreomacular traction.

Why do histology on retinal haemorrhages in suspected non-accidental injury?

The detailed documentation of ocular pathology has become an important component in the autopsy investigation of suspected cases of non-accidental injury in infants and young children. Careful histological examination of retinal haemorrhages is of critical importance, but there remains debate about the significance of some findings. This issue has been thrown into sharper relief by recent neuropathological studies questioning the mechanisms of some CNS findings. To discuss the importance of histological findings in the retina and their potential significance and specificity, we have invited contributions from authors in the USA and UK.

Minimising the risk of prion transmission by contact tonometry.

AIMS: The unknown prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the UK population has led to fears of horizontal transmission through routine medical procedures. The potential risk of transmission via contact tonometry was examined. METHODS: The total amount of protein carried over by tonometer tips after applanation of patients was assessed. RESULTS: Tonometer tips had an inherent ability to carry proteinaceous material. There was a large variability in the load carried over between individual patients. Rinsing tonometer tips in water reduced protein carryover. Wiping the tonometer tips also reduced carriage, though less dramatically. CONCLUSION: There is a small theoretical risk of transmission of vCJD by contact tonometry through reuse, but this should be reduced if the prisms are washed and wiped. In the light of these findings a protocol for the management of reusable tonometer prisms is recommended.