Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Changes in tarsal plate fibrillar collagens and elastic fibre phenotype in floppy eyelid syndrome.

BACKGROUND: The aims of this study are to investigate the expression of the main structural components of the tarsal extracellular matrix (ECM) in floppy eyelid syndrome (FES) focusing on elastic fibres and collagen types I and III, and also to identify possible cell-mediated inflammatory mechanisms in the pathogenesis of this condition. METHODS: A histopathological case control study was conducted using 30 upper lid specimens from patients with FES and 15 undiseased upper lid control specimens. Structural ECM components were assessed using a combination of immunctorial ataining ohistochemical and techniques including antibodies to collagens I and III, Verhöeff's iron haematoxylin, Gomori's aldehyde fuchsin and Lillie's oxidised aldehyde fuchsin. The contribution of different cellular components of the inflammatory response was investigated by immunohistochemical techniques using antibodies to CD3, CD20, CD68. Slide scoring was performed using a semiquantitative technique on an ordinal scale. Statistical analysis was performed using matched ordinal regression analysis. RESULTS: FES tarsal plate tissue demonstrated a decreased abundance of mature elastic fibres (P ≤ 0.001) and an increased abundance of oxytalan fibres (P = 0.006). Intensity of staining for collagens I (P = 0.012) and III (P < 0.001) was increased. No significant difference in the abundance of CD3, CD20 and CD68 expressing cells was identified. CONCLUSIONS: The findings of altered elastic fibre phenotype and collagen accumulation are consistent with an adaptive response to cyclic mechanical loading of the tarsal plate, rather than an aetiological feature. These findings are important in understanding how the tarsal ECM responds to mechanical loading.

Immunopathology of intraocular silicone oil: enucleated eyes.

AIMS: To characterise the distribution of silicone oil in ocular tissues in globes enucleated after complicated retinal detachment, and to document the distribution and nature of any associated inflammatory response. METHOD: 9 enucleated globes that had previously undergone retinal detachment surgery with silicone oil and 7 control globes that had undergone enucleation after retinal detachment surgery (n = 2) or ocular trauma (n = 5) were studied. Sections were histologically examined using light microscopy to document the distribution of silicone oil in ocular tissues. Immunohistochemical analysis was carried out using the ABC technique and a panel of monoclonal and polyclonal antibodies. Electron microscopy was undertaken to observe the penetration of silicone oil in the trabecular meshwork of the anterior chamber drainage angle. RESULTS: Silicone oil was distributed throughout the globes-notably in the iris, ciliary body, retina, trabecular meshwork and epiretinal membranes. Focal areas of intraretinal silicone were associated with disorganised retinal architecture, retinectomy sites or subretinal oil. The distribution of macrophages was closely related to the distribution of silicone oil. T and B lymphocytes were not associated with silicone oil unless additional pathology was also present-for example, cyclitic membrane or uveitis. One of the nine eyes had silicone oil present in the optic nerve. In the control globes, the inflammatory response was mediated primarily by macrophages and T lymphocytes, and was less marked than that observed in the silicone oil globes. CONCLUSION: This study shows that silicone oil may be sequestered in varied ocular tissues and is associated with localised inflammation mediated by macrophages.

Immunopathology of intraocular silicone oil: retina and epiretinal membranes.

AIMS: To determine the inflammatory response in retina and epiretinal membranes after intraocular silicone oil tamponade. METHODS: 14 proliferative vitreoretinopathy (PVR) epiretinal membranes, 33 retro-oil epiretinal membranes, 19 retinectomies, 14 retro-oil retinectomies and 37 idiopathic epiretinal membranes (controls) underwent immunohistochemical analysis using the avidin-biotin complex technique and a panel of monoclonal and polyclonal antibodies. The number of positive cells counted in five 0.5 mm diameter fields of immunohistochemical sections was graded on a score of 1-4. RESULTS: Macrophage cell counts were significantly greater in membranes with a history of exposure to silicone oil (p<0.001). An inflammatory response could be observed within 1 month of silicone oil exchange, and the intensity seemed to be unrelated to the duration of exposure. Macrophages were confined to epiretinal membranes on the surface of retinectomy specimens in 10 of 14 cases and intraretinal macrophages were observed only in specimens with gliotic retina. T and B lymphocytes were rarely seen in the specimens examined. Marked glial cell up regulation was observed in 11 of 16 retinectomy specimens and in 8 of 11 retro-oil retinectomies. Glial cell content was variable in the membranes, but there was a trend of increased presence after exposure to silicone oil. CONCLUSION: This study has shown that the use of silicone oil is accompanied by an inflammatory reaction, primarily mediated by bloodborne macrophages. This response can be observed within 1 month of silicone oil injection and continues after silicone oil removal. Retinal surgeons should be aware of the potential secondary effects of intraocular silicone oil when they are considering its use (and removal) in vitreoretinal surgery.

Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active-controlled clinical trial.

INTRODUCTION: Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation. METHODS AND ANALYSIS: This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naïve or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non-ocular adverse events will also be reported over 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects' regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR. TRIAL REGISTRATION NUMBER: ISRCTN 32207582.

In vivo confocal microscopy and histopathology of the conjunctiva in trachomatous scarring and normal tissue: a systematic comparison.

AIM: To compare in vivo confocal microscopy (IVCM) with the histopathological examination of tissue and cellular changes in normal and diseased conjunctiva. METHODS: Participants underwent clinical examination and IVCM of the tarsal conjunctiva. A biopsy of the upper tarsal conjunctiva was collected and stained with tinctorial stains and by immunohistochemical staining for CD45 and CD83. Connective tissue scarring, inflammatory cell density and the presence of dendritiform cells were quantitatively assessed in a masked manner by both IVCM and histological assessments for comparative analysis. RESULTS: Thirty-four participants with severe trachomatous conjunctival scarring and 33 participants with healthy conjunctiva were recruited. The IVCM connective tissue scarring score was strongly associated with the histological grading of scarring (p<0.001). There was limited evidence of an association between the IVCM inflammatory cell infiltrate and the histological inflammatory cell grade (p=0.05). We did not find any evidence to support the hypothesis that dendritiform cells seen with IVCM are mature, conventional dendritic cells. CONCLUSIONS: The results show that IVCM can be used to robustly quantitate connective tissue scarring and also has a role in measuring the inflammatory cell infiltrate. The discordance between IVCM dendritiform cells and immunohistochemical dendritic cells may be a result of study limitations or may be because these dendritiform structures represent another cell type, such as fibroblasts, rather than dendritic cells.

Keratectasia as a presentation of surgically induced necrotizing sclerokeratitis (SINS).

PURPOSE: A case of keratectasia is reported as a severe presentation of surgically induced necrotizing sclerokeratitis (SINS). METHODS: A 72-year-old white woman had a painful, raised lesion on the superior cornea of her right eye 3 years after uncomplicated extracapsular cataract extraction with intraocular lens implantation. Examination showed a large ectatic area of the superior cornea with inflamed sclera adjacent to the surgical wound, which was diagnosed as SINS. RESULTS: No underlying systemic autoimmune condition or vasculitis was identified on investigation. Progressive painful keratectasia necessitated enucleation, which confirmed on histopathologic examination features of chronic nodular episcleritis and nongranulomatous scleritis with evidence of keratitis and fibrovascular scarring. CONCLUSION: The predominant inflammatory response in the cornea represents surgically induced necrotizing keratoscleritis (SINK) as a new variant presentation of SINS. Oral corticosteroids and immunosuppressive agents should not be delayed to prevent progressive tissue destruction and poor outcome.

A non-invasive pigmented nodule arising within primary acquired melanosis--an unusual phenomenon.

We report a case of a raised pigmented nodule that arose within conjunctival primary acquired melanosis (PAM). This nodule showed no histological features of invasive disease.

Renal cell carcinoma metastasis masquerading as recurrent orbital haematoma.

A 70 year old man developed orbital haemorrhage after retrobulbar anaesthesia for cataract surgery and biopsy of a persistent lateral rectus mass suggested organising haematoma. Subsequent progression of the mass was shown, on repeated biopsy, to be due to metastatic renal cell carcinoma--a tumour recognised for its angiogenic and haemorrhagic potential.

Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.

Pleomorphic lipoma of the orbit: a case series and review of literature.

OBJECTIVE: Pleomorphic lipomas are rare benign tumors that can resemble a variety of malignant soft tissue tumors on histologic examination. Six cases of patients with orbital pleomorphic lipoma, one of which was proven to be bilateral, are presented. DESIGN: Retrospective, noncomparative, interventional case series with clinicopathologic correlation. METHODS: Clinical and histologic review of 6 patients with pleomorphic lipomas of the orbit and histologic review of fat from 22 exenteration specimens and 20 other orbital procedures. MAIN OUTCOME MEASURES: Evidence of histologic abnormalities in histologic specimens. RESULTS: Pleomorphic spindle cells and multinucleated cells with nuclei arranged in a floret-like pattern were present in 7 specimens from 6 patients presenting with a clinical diagnosis of orbital fat prolapse, but there were no similar cell types present in the adipose tissue of 22 exenteration or 20 other orbital specimens. CONCLUSION: Pleomorphic lipoma may arise in the orbit, presenting as what was hitherto considered to be age-related epibulbar prolapse of orbital fat.