Svetlana Cherepanoff

Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

Aim To determine the sub-macular Bruchs membrane (BrM) macrophage count and the choroidal and BrM macrophage immunophenotype in normal eyes and in eyes with early and advanced age-related macular degeneration (AMD). Methods BrM macrophages were counted in 125 human eyes (normal, normal aged, early AMD and geographical atrophy), and CD68 and inducible nitric oxide synthase (iNOS) immunohistochemistry was performed on 16 human eyes (normal, normal aged, early AMD, geographical atrophy and disciform scarring). All eyes were examined clinically ante mortem. Results were correlated with histopathological features, including basal laminar deposit and membranous debris, and with clinical fundus appearance. Results CD68+ macrophages were found in the choroid of normal human eyes, and did not express iNOS. Expression of iNOS by choroidal macrophages (as well as endothelial cells and pericytes) was associated with: (1) recruitment of macrophages to BrM in early AMD eyes with soft drusen or thick continuous basal laminar deposit, corresponding to clinically detectable soft drusen or pigment changes; and (2) active disciform scarring. iNOS expression was absent in BrM macrophages, suggesting immunomodulatory differences between the choroid and BrM. The highest BrM macrophage counts were found in eyes with subclinical choroidal neovascularisation. Conclusion The presence of extracellular deposits (soft drusen and thick continuous basal laminar deposit) is associated with macrophage recruitment to BrM and alteration in the immunophenotype of resident choroidal macrophages.

Retinal autoantibody profile in early age-related macular degeneration: preliminary findings from the Blue Mountains Eye Study.

Background:  To compare the retinal autoantibody profile in individuals with and without early age‐related macular degeneration (AMD) and to determine whether baseline autoantibodies are associated with progression to advanced AMD 5 and 10 years later.

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.

Aims To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Methods Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. Results On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. Conclusions This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.

Bilateral Diffuse Uveal Melanocytic Proliferation: Molecular Genetic Analysis of a Case and Review of the Literature

Purpose of the Study: To describe the clinicopathological features, mutational and chromosomal copy number analysis, and 8-year follow-up of a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with clear-cell carcinoma of the endometrium. Methods: Histological evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis and GNAQ/11 mutational analysis were performed in a 67-year-old female patient with the diagnosis of BDUMP. Results: Histological evaluation revealed proliferation of bland spindle cells, diffusely replacing the uveal tract, which showed a proliferation index of less than 1%. There was absence of mutations involving the codon 209 and 183 of GNAQ, and of GNA11. MLPA analysis showed disomy 3 with polysomy 8q for both eyes. The patient died 8 years later of an unrelated condition. Conclusions: Although BDUMP is considered to be a benign proliferative disease, copy number alterations of unknown significance may occur in these lesions.

Unusual limbal lesion in neurofibromatosis type 1.

Purpose: To describe an unusual limbal lesion clinically resembling pterygium in a young patient with neurofibromatosis type 1. Methods: Clinical case report with a review of the literature. Results: The lesion was excised, and histopathology was performed. Histopathology disclosed conjunctival mucosa with expansion of the substantia propria by dense and loose collagenous tissue, small nerves, and thin-walled blood vessels. No skin or skin appendages were seen, although a small amount of mature adipose was present. Focally, spindle cells with wavy nuclei were seen scattered within the collagenous areas and were positive on S100 immunohistochemistry. Mast cells were readily identifiable. There was no evidence of actinic elastosis, dysplasia, or malignancy. These histopathological features most resemble heterotopia with some features of neurofibroma. Conclusions: We report an unusual limbal lesion in a patient with neurofibromatosis type 1. Histopathological features resemble a heterotopia with some neurofibroma features. We suggest that all lesions excised from patients with neurofibromatosis, no matter how characteristic in appearance, be sent for histopathological confirmation of diagnosis.

Orbital Cellulitis and Secondary Angle Closure: A Rare Presentation of Choroidal Melanoma

We describe a case of choroidal melanoma initially presenting with orbital cellulitis, fulminant conjunctival swelling, and secondary angle closure. Despite treatment with intravenous antibiotics, the patients condition did not improve. With further investigations including ultrasound scan and magnetic resonance imaging, a high-density lesion was found within the globe. Characteristic imaging findings suggested a malignant origin and the lesion was found to be a melanoma on histopathological analysis.

Tumour Expression of Histone Deacetylases in Uveal Melanoma

Purpose: To determine the expression of histone deacetylase enzymes in uveal melanoma tumour cells. Procedures: This is an observational immunohistochemical study of 16 formalin-fixed, paraffin-embedded eyes enucleated for uveal melanoma between January 2001 and March 2002. Haematoxylin and eosin paraffin sections were reviewed for histopathological parameters according to the American Joint Committee on Cancer 7th edition. Sections were then immunohistochemically stained for histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2 using an automated Leica Bond II platform and Fast Red chromogen, then digitally scanned using Aperio software before assessment of staining. Results: Nuclear expression of histone deacetylases 1, 2, 3, 4 and 6 and of sirtuin 2 was confirmed in uveal melanoma tumour cells. In addition, the tumour cells showed cytoplasmic expression of histone deacetylases 4 and 6 and sirtuin 2. Nuclear and cytoplasmic immunostaining was also seen in intraocular tissues uninvolved by the tumour. Conclusion: Uveal melanoma tumour cells express histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2, confirming potential tissue targets for histone deacetylase inhibitors.

Invasive Fungal Sinusitis Presenting as Acute Posterior Ischemic Optic Neuropathy

ABSTRACT Invasive fungal sinusitis causes painful orbital apex syndrome with ophthalmoplegia and visual loss; the mechanism is unclear. We report an immunocompromised patient with invasive fungal sinusitis in whom the visual loss was due to posterior ischaemic optic neuropathy, shown on diffusion-weighted MRI, presumably from fungal invasion of small meningeal-based arteries at the orbital apex. After intensive antifungal drugs, orbital exenteration and immune reconstitution, the patient survived, but we were uncertain if the exenteration helped. We suggest that evidence of acute posterior ischaemic optic neuropathy should be a contra-indication to the need for orbital exenteration in invasive fungal sinusitis.

Successful treatment of HCV-related glomerulonephritis with sofosbuvir and daclatasvir

tion of the VEGF receptor, which drives angiogenesis, leading to improvement of the survival rate and tumour shrinkage in patients with non-small-cell lung cancer. VEGF is indispensable for the proliferation, differentiation, and survival of mesangial and endothelial cells. Local, ongoing VEGF production by podocytes is necessary for the functioning of the adult glomerular filtration barrier. The use of VEGF inhibitors in cancer treatment has been associated with an increased incidence of proteinuria (21–63%). In our case, bevacizumab was effective for treating lung cancer but proteinuria progressed. We considered that not only drug withdrawal but also additional therapy, such as with angiotensin receptor blockers, might be needed for treating severe proteinuria resulting from bevacizumab. In recent years, various molecular-targeted drugs and biological agents have been on the market, and some of them induce kidney damage at high rates. Clinicians should carefully evaluate whether to continue therapy when there are concurrent positive and negative effects of a medication, with a priority on quality of life prognosis.

Corneal biopsy for diagnosis of recalcitrant microbial keratitis

PurposeTo document the findings of corneal biopsies for progressive microbial keratitis in a large tertiary referral institution.MethodsA retrospective medical records review of all patients who underwent at least one corneal biopsy for the diagnosis of microbial keratitis at Sydney Eye Hospital, Australia between January 1, 2010 and December 31, 2016 was performed.ResultsThirty-eight patients (18 men and 20 women) underwent a corneal biopsy for progressive microbial keratitis unresponsive to broad-spectrum topical antimicrobials. Risk factors for microbial keratitis included contact lens wear in 8 (21%), recent intraocular surgery in 5 cases (13%), recent agricultural trauma in 3 cases (8%), exposure keratopathy due to Graves’ orbitopathy in 1 case (3%), and profound systemic immunosuppression due to chemotherapy for leukaemia in 1 case (3%). The remaining 20 patients had no identifiable risk factors. Fifteen patients (39%) had a positive biopsy result, which identified bacteria in 6 cases and Mycobacteria in 1 case, both by culture of the biopsy specimen. Three cases of fungus were identified on culture of biopsy specimen, two of which were also confirmed on histopathology and an additional case was identified from histopathology alone. A single case of Acanthamoeba was diagnosed by culture and histopathology, and an additional 3 cases were diagnosed on histopathology alone. A corneal biopsy yielded new organisms in 73% (11/15) cases where the culture results of biopsy specimens were positive.ConclusionCorneal biopsy is an important tool in the diagnosis of progressive keratitis, often identifying causal organisms not found on corneal scraping alone.