Academic literature on the topic 'RB Pathology ; RE Ophthalmology'

Purpose Accurate identification of the factors contributing to epiphora is essential in directing appropriate management and treatment strategies. The authors applied a methodical strategy of assessment for epiphora to patients who were already on the waiting list for dacryocystorhinostomy (DCR). The findings were compared to the original findings. Methods Forty-four eyes of 35 patients listed for DCR were re-examined. All canaliculi were examined using four tests: dye disappearance, Jones 1 (dye retrieval), probing using Bowman probes, and syringing of the nasolacrimal duct (NLD) under local anesthesia. Some patients were examined using an endocanalicular mini-endoscope. Patients with NLD obstruction underwent DCR and those with canalicular and NLD stenosis underwent intubation of the lacrimal system-canaliculus, lacrimal sac, and nasolacrimal duct-using silicone stents. The authors refer to this as canaliculodacryocystoplasty (CDCP). The patients were assessed for symptoms of epiphora at 12 months. Forty-four eyes had been listed for DCR. They had been originally diagnosed, by means of lacrimal syringing, as NLD obstruction (24 eyes) or stenosis (12 eyes), and functional blocks (8 eyes). Results Four out of the original 44 planned DCR surgeries were performed after re-evaluation. After re-examination, 28 lacrimal systems were found to have canalicular stenosis, 4 NLD stenosis, 4 NLD obstruction, 4 punctal phimosis, 3 ocular surface disease, and 1 patient was asymptomatic. Twenty-eight lacrimal systems underwent CDCP, 4 underwent DCR, 4 had punctoplasty, and 4 had probing alone. Three had treatment for ocular surface disease and one patient required no treatment. After a follow-up of 12 months, 41 (93%) systems had improvement or were free of their epiphora. Conclusions Syringing of the lacrimal apparatus may result in a high false positive diagnosis of NLD obstruction. Canalicular pathology is not uncommon in this cohort of patients and may be underdiagnosed.

345 Background: Bladder cancer is a rare entity in the pediatric population making it difficult to define surveillance protocols and long term outcomes. Notably, most pediatric tumors are low grade and non-muscle invasive and do not recur. In order to determine the source of the different natural history between pediatric population and adults, we hypothesized that pediatric bladder cancer may potentially stem from different molecular pathways than its adult form. Our main objective was to study the molecular pathogenesis in this rare disease using immunohistochemical (IHC) and mutational analysis of the main known genes involved in bladder cancer. Methods: Paraffin-embedded tissue slides of bladder tumors from three pediatric patients were retrospectively identified from our institution's pathology archives (1990-present) and re-evaluated. Clinical data was reviewed. FGFR3, H-RAS, and PI3K mutational analysis of the most well-known mutated spots was conducted by PCR amplification and Sanger sequencing. IHC analysis was conducted using antibodies against p53, Pten, Rb, EGFR, Her2Neu and ki-67. Results: Two patients had low-grade Ta disease, whereas the other tumor was classified as a Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP). None of the lesions recurred. Two patients were female and one was male. The ages at diagnosis were 13, 11, and 17, with a mean follow-up of 5.2 years (Range: 1.5-8.0 years). All specimens showed H-RAS G12V mutation, whereas they were characterized by wild-type FGFR3 and PI3K. Nuclear p53 was not detected, whereas PTEN and Rb expression were maintained. EGFR was homogenously expressed in the three cases, and Her2Neu was negative. The proliferation rate analyzed by Ki-67 expression was very low in all cases (<5%). Conclusions: Pediatric tumors may arise from a pathway that is not initiated by FGFR3 or p53 mutations, but by H-RAS mutations. This distinction may explain the relatively few recurrences seen in the pediatric population. Molecular investigation of larger series of pediatric tumors is warranted, and will aid in determining the surveillance and the clinical follow up, if any, needed in this rare entity.

Bloody tears (Haemolacria) are a rare symptom that can be caused by local or systemic pathology. It is one of the most alarming symptom in ophthalmology. Besides those, idiopathic cases have been reported. A case of hyperthyroidism where haemolacria was secondary to the condition has also been reported. Haemolacria are also reported as secondary to epistaxis. Psychogenic causes are described including Munchausen Syndrome by proxy. Here we describe a series of four cases of haemolacria along with bleeding from other sites, found as associated features of dissociative disorders. In this series, patients with age ranging from 14-17 years, three of them are female and one male have been included. Examination excluded local ocular and nasal pathology, coagulopathy and hyperthyroidism. In course of their illness, two of these cases met the DSM 5 criteria for both dissociative disorders and conversion disorders, rest of them have been diagnosed as mixed dissociative disorders. After appropriate intervention, three patients recovered completely and in one patient symptoms (also bleeding) recurred on re-exposure to the previous stress factors. We report three cases of Dissociative disorders and one with both dissociative and conversion disorder where bloody tears were one of the feature. To the best of our knowledge this is the first official report of its kind in Bangladesh.J Bangladesh Coll Phys Surg 2017; 35(1): 36-42

Background: This article aims to describe histopathologic high risk tumor characteristics in our patient population of retinoblastoma. It is based on consensus criteria for definitions of choroidal and optic nerve invasion as outlined in The International RetinoblastomaStaging Working Group (IRSWG) 2009.Materials and Methods: Fifty histopathologically diagnosed cases of retinoblastoma were archived from records of Pathology department during years 2004 to 2014. Re-evaluation of slides to identify choroidal and optic nerve invasion as per IRSWG along with Pathologic tumor staging was done. Data were entered into Microsoft excel sheets and results expressed in percentages. Department of Ophthalmology was consulted for recurrence of Retinoblastoma.Results: Among fifty cases, Choroidal invasion was absent in 62% cases. Minimal invasion (<3mm) was seen in 18% cases, massive (>3mm) in 14% cases and extra ocular involvement in 6% cases. The optic nerve was free of tumor in more than three forth of the cases (78%). Prelaminar and retro laminar involvement of optic nerve was observed in 6% and 10% cases respectively. Intraocular spread of tumor was observed in 6% of cases. The cut margin of optic nerve was involved in 42% while it was free of tumor in 58% of cases. Significant number of tumours were pathologically classified as pT1 (58%) followed by pT2a (22%). pT3a and pT4b were found in 6% each and pT3b and pT4a were found in 4% each. Recurrence was observed in two cases of PT3a and one of pT4b.Conclusion: We conclude identifying low percentages of high risk charateristics in a retrospective histologic experience with Retinoblastoma. Recurrence observed in two tumours staged pT3a sheds light on prognostic significance of reporting massive choroidal invasion despite free cut margin. These observations call for routine practice of standardized histopathologic reporting and processing of enucleated eye samples at our tertiary care centre.Journal of Pathology of Nepal (2015) Vol. 5, 723-726

Abstract Abstract 1773 The outcomes of MCL patients have improved in recent years secondary to a better understanding of the biology of this disease, but also with the development of novel therapeutic agents and treatment modalities of this largely incurable subtype of aggressive lymphoma. The spectrum of clinical behavior observed in MCL patients suggests differences exist at the molecular level that impact clinical outcomes. Previously accepted biomarkers of response need to be re-evaluated in the post-rituximab and/or HDC-ASCS era to confirm their continued validity. We retrospectively studied the impact of pathological and additional cytogenetic abnormalities besides the t(11;14)(q13;q32) at the time of diagnosis in MCL patients treated at our institution in an attempt to identify potential prognostic biomarkers for this disease. Using the Roswell Park Cancer Institute (RPCI) tumor registry and NHL databases, MCL patients treated at RPCI between 2000 and 2009 were identified. MCL diagnosis was confirmed by our Pathology Department and required Bcl-1 (Cyclin-D1) overexpression or t(11;14)(q13;q32) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), respectively. All available demographic, clinical (stage, IPI score, MIPI score, performance status, front- and second-line treatment), and pathologic data (blastoid vs. non-blastoid features, Ki67%, CD5 expression) were recorded and analyzed. Differences in response rate to front-line treatment, PFS and OS were compared between different pathological subsets of homogenously treated patients. The final analysis was restricted to 58 MCL patients (M:41/F:17) that received rituximab- and anthracycline-based multi-agent chemotherapy (R+CHOP=34, R+HyperCVAD-like =24) in the front-line setting. Majority of the patients were Caucasian, had an ECOG PS of 0–1, and their median age was 63 yrs (range 43–92). Stage III or IV disease at diagnosis was present in 92% of the cases, 85% had extra nodal site(s) of disease, and 33% had B-symptoms. At the completion of the front-line chemo-immunotherapy, 50% of the patients achieved a complete remission (CR), and 29% a partial remission (PR). Only 52% underwent HDC-ASCS in first remission. In accordance with prior reports, the IPI and MIPI score correlated with clinical outcomes (i.e. PFS and OS). In addition, the blastoid variant of MCL at the time of original diagnosis (40% of cohort) correlated with poor prognosis. Blastoid MCL patients had a statistically significant shorter median PFS (13 vs. 31.7 months, P=0.009) and OS (19.1 vs. 57 months, P=0.004) than patients with non-blastoid MCL. Moreover, the inferior clinical outcome of blastoid MCL was not influenced by the IPI score, MIPI score or the use of HDC-ASCS in first remission. Ki67 index of >40% (58% of studied cases) was associated with blastoid variant and with worse prognosis. The median OS but not the PFS was longer in MCL patients with a Ki67< 40% (not reached) than in MCL with Ki67 >40% (19.1 months, P= .016). In an attempt to identify additional genetic abnormalities seen in the blastoid variant that would explain the inferior prognosis, we analyzed by FISH diagnostic bone marrow and peripheral blood samples available from a selected group of 10 patients for additional molecular cytogenetic changes. Secondary cytogenetic aberrations, which included deletions of 17p (P53), 13q (RB and D13S25), and 9p (CDKN2A), were observed in 8 of 10 patients studied. Loss of P53 was restricted to blastoid MCL cases only (5 patients); two of these patients had a higher karyotypic complexity including both del(9p), and del(13q) in addition to 17p deletion. Multiple abnormalities were seen in 5/8 patients. ATM deletion was rarely seen (1/10 patients) and MYC rearrangement was not observed. In summary our data suggest that blastoid MCL have inferior clinical outcomes in terms of PFS and OS despite aggressive chemo-immunotherapy and HDC-ASCS. It is unclear if blastoid MCL represents a different clinical entity separate from non-blastoid MCL variants or is the result of the acquisition of additional genetic abnormalities leading to clonal evolution. Additional ongoing cytogenetic analysis will be presented at the annual meeting. Disclosures: Hernandez-Ilizaliturri: Genmab: Research Funding.

Purpose: To describe a case of retinopathy as onset manifestation of chronic myeloid leukemia (CML), successfully treated with leukapheresis and medical therapy. Methods: A 28-year-old male patient presented complaining painless acute visual impairment in his right eye (RE). He reported moderate asthenia and episodes of night sweats during the previous month. His past medical history was unremarkable. BCVA at presentation was 20/80 in RE and 20/32 in left eye (LE). Fundus examination revealed venous congestion, diffuse Roth spots, and whitish macular infiltrates in both eyes. OCT showed hyperreflective foveal infiltrates, in both eyes. Blood test showed markedly elevated white blood cells (WBCs) count (430 × 103/mm3). Clinical-instrumental examination revealed hepatosplenomegaly. These features were consistent with CML. The patient was treated with leukapheresis and nilotinib. Results: After 2 weeks of treatment, the WBCs count dropped (71 × 103/mm3), and the patient reported subjective improvement of symptoms. At 1-month follow-up, BCVA and retinopathy signs were improved in both eyes. OCT showed the almost complete resolution of foveal infiltrates with ellipsoid zone focal defects. At 4-months follow-up, we observed complete resolution of retinopathy. BCVA was 20/32 in RE and 20/25 in LE. OCT showed the persistence of ellipsoid zone focal defects in RE and complete anatomical restoration in LE. At 6-months follow-up, the patient was clinically well and his WBCs count was normal. Conclusion: In our case, the CML-related retinopathy represented the onset sign of the underlying systemic pathology, leading to proper management and treatment, with hematological normalization and resolution of the retinopathy.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite successful ocular treatment, about 50% of patients succumb to metastatic dissemination, which occurs haematogenously and mainly affects the liver. On the basis of clinical, histopathological and genetic features of the primary tumour it is possible to predict if the individual patient is at high risk (HR) or low risk (LR) of developing metastases. However, the mechanisms responsible for the development of metastatic disease in UM are still largely unknown; therefore no adjuvant treatment is currently offered to HR patients to prevent development of fatal disease. As the time to discovery of clinically detectable metastases can range from months to decades, a secreted biomarker(s) that could be routinely tested in blood is much needed. The scope of the work presented in this thesis was to use proteomics as a tool to identify potential novel, UM-specific biomarkers. Moreover, the proteomic data acquired would complement genomic and transcriptomic information already generated by the Liverpool Ocular Oncology Research Group, with the ultimate aim of increasing our understanding of UM development and dissemination. The aim of Chapter 2’s project was to compare the proteome of UM tissue samples at HR versus LR of developing metastatic disease using isobaric tags for relative and absolute quantitation (iTRAQ) labelling and mass spectrometry (MS). The quantification of proteins in our samples, proteomic analysis and further validation by immunohistochemistry has led to the identification of two novel prognostic and potentially therapeutic target, S100A6 and the tumour suppressor PDCD4. In Chapter 3 we focused on proteins released in the conditioned medium (secretome) of short-term cultures of HR and LR UM cells, as well as normal melanocytes. Using a label-free quantitative proteomic approach, almost 2000 proteins were identified and quantified, with more than 30% of these identified as secreted and/or previously described in exosomes. Using these data, an 18-protein signature able to discriminate between HR and LR UM was identified. Further validation will be necessary in secretome samples and in the peripheral blood of UM patients, but this has the potential of being translated into a clinically useful assay to detect early development of metastatic disease. As reported in Chapter 4, we also conducted a pilot clinical study on circulating tumour cells (CTC) in UM, using the CellSearch® platform with the novel melanoma kit to enumerate CTC in the peripheral blood of UM patients at LR, HR or with overt metastatic disease. CTC were detected in metastatic and HR tumours and were not present in LR UM, however, the number of CTC detected varied widely, calling into question the clinical value of using this platform in UM patients. The research detailed in Chapter 5 had a direct clinical value, as it addressed the procedures undertaken during the acquisition and processing of prognostic biopsies from UM tumours treated conservatively. The modifications introduced led to a significant improvement of the success rate of such prognostic biopsies for risk stratification, which is essential for clinical management, follow-up and research purposes. In conclusion, the work conducted throughout this PhD has provided further insight into the molecular characteristics that can differentiate between HR and LR UM, identifying novel potential biomarkers that will need validation in the clinical setting.

Nystagmus is a disorder of eye movement characterised by irregular, uncontrolled and repetitive eye movements. It can occur in a broad spectrum of clinical situations and diseases or it may occur in isolation and an inherited disorder. Surprisingly little is known about the underlying mechanisms of ocular-motor control. Similarly, the pathophysiological mechanisms underpinning nystagmus is also poorly understood. By studying pedigrees in whom nystagmus seems to be inherited as an isolated trait (Congenital Idiopathic Nystagmus), it may be possible to identify some of the genetic causes of this disorder and subsequently understand the pathophysiology. This thesis describes a molecular genetic study of congenital nystagmus. A clinical phenotyping study is followed by linkage analysis and positional cloning. A novel nystagmus gene is investigated in a large cohort of Congenital Idiopathic Nystagmus (CIN) patients and X-inactivation studies are performed. Subsequently, cell culture and RT-PCR work is performed to study expression of this gene. Additionally a pedigree with an atypical congenital nystagmus disorder is investigated and a new mutation within a known cerebellar disease gene is identified. This work contributed to the identification of the first gene for Congenital Idiopathic Nystagmus (CIN). The first detailed temporal expression study of the FRMD7 nystagmus gene was also performed in this study which has directed further studies into the pathogenesis of CIN. Identification of a new mutation in the CACNA1A gene in a pedigree with nystagmus and subtle cerebellar signs has lead to the consideration of this gene in patients who present to hospital with isolated atypical nystagmus.

Despite the association of neuronal cell loss with a wide range of neurodegenerative disorders, the mechanisms leading to this cell death remain poorly understood. In this thesis I have investigated these mechanisms and tested whether they represent viable targets for therapeutic intervention. The adult mouse retinal explant is a popular model of axotomy-induced neuronal degeneration but has been limited by the lack of morphometric data. Since dendritic pruning is well-evidenced to precede cell loss in neurodegenerative diseases, including glaucoma and Alzheimer’s disease, I investigated whether the quantification of dendritic morphology of retinal ganglion cells in the retinal explant could be used as a more sensitive measure of neuronal health after axotomy. I report here that retinal ganglion cell dendrite loss precedes cell loss by at least 7 days and that this retraction is substantially retarded following treatment with brain-derived neurotrophic factor applied at the time of explantation. Perhaps most importantly, I demonstrate for the first time in this model that delayed application of brain-derived neurotrophic factor significantly protects against dendritic retraction of retinal ganglion cells. The work outlined in this thesis thus supports the targeting of dendritic outgrowth and/or synaptic connectivity for the treatment of neurodegenerative disorders.

Ten experiments examined the way that automatic processing of the visual perspectives and eye gaze of others affects adults‘ perception and encoding of the social world. I investigated the amount of flexibility that automatic visual perspective computation accommodates. Experiments 1, 2, and 3 demonstrate that automatic visual perspective-computation shows some flexibility for enumerating and representing perspective contents. Experiments 4 and 5 further indicate that automatic visual perspective-taking allows selection of relevant perspective information. I also examined whether observing others‘ eye gaze affects adults‘ visual working memory encoding. Experiments 6, 7, and 8 indicate that agents‘ object-oriented gaze does not lead to more efficient encoding of agent and object information. Experiments 9 and 10 demonstrate that observing others‘ participant-oriented gaze disrupts visual working memory encoding. I argue that although adults have minimal conscious control over the activation of visual perspective-computation and processing of participantoriented gaze, the efficient mindreading system shows some flexibility.