Toluidine blue 1% eye drop versus optical coherence tomography for margin delimitation of ocular surface squamous neoplasia.

PURPOSE: To compare the use of toluidine blue 1% eye drops with anterior segment optical coherence tomography (OCT) for the determination of tumour margins in patients with ocular surface squamous neoplasia (OSSN). METHODS: The study was conducted from July 2020 to June 2021 at the Ocular Oncology department at the Federal University of São Paulo, Brazil. Slit-lamp photographs after toluidine blue staining and OCT of the anterior segment were taken on the same day from patients with OSSN. Photographs and OCT images were analyzed quantitatively using the software ImageJ and IMAGEnet®, respectively. The agreement between techniques was evaluated qualitatively through the Bland-Altman graph and quantitatively through intraclass correlation (ICC). RESULTS: A total of 21 participants (71.43% males) with a clinical diagnosis of OSSN were included in the study. The average + SD diameter along the chosen axes was 4.43 ± 2.08 mm with OCT of 4.37 ± 2.03 mm with toluidine blue, a difference not statistically significant (p = 0.2891). The Bland-Altman analysis indicated a good qualitative agreement between the methods, with all cases inserted within the limits of agreement from -0.3217 to 0.4268. The ICC quantitative analysis showed an almost perfect agreement of 99.57% (95%CI: 98.96-99.83%; p < 0.001). CONCLUSIONS: Our findings showed that OCT and toluidine eye drops are equivalent in determining margins for tumour measurements, which is particularly relevant in low-income settings where anterior segment OCT is not available. The use of toluidine blue 1% could be an useful alternative to quantify the size of the tumour, help to monitor tumour growth, and outline margins for surgical planning.

Ocular Biomechanics and Glaucoma.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. Corneal biomechanics have an important role in managing patients with glaucoma. While evidence suggests that patients with thin and stiffer corneas have a higher risk of developing glaucoma, it also influences the accurate measurement of intraocular pressure. We reviewed the pertinent literature to help increase our understanding of the biomechanics of the cornea and other ocular structures and how they can help optimize clinical and surgical treatments, taking into consideration individual variabilities, improve the diagnosis of suspected patients, and help monitor the response to treatment.

COVID-19-related Ocular Hypertension Secondary to Anterior Uveitis as Part of a Multisystemic Inflammatory Syndrome.

It is the consensus of the medical community that ocular complications associated with Coronavirus Disease 2019 (COVID-19) are mild, self-limiting, and there are no reports to date of a sight-threatening event. We report a patient with a systemic inflammatory syndrome in the context of COVID-19, with ophthalmological (uveitis), dermatological (erythema and skin nodules), and cardiovascular (edema) manifestations. The anterior uveitis led to an increase in the intraocular pressure that failed to respond to clinical treatment and prompted a surgical intervention to save the vision. To the best of our knowledge, this is the first report of a COVID-19-related ocular hypertension. Timely surgical intervention was key to save the vision in the patient's only eye.

Largest case series of Latin American eyelid tumors over 13-Years from a single center in Sao Paulo, Brazil.

PURPOSE: Malignant lesions of the eyelid are the most common eye cancers. Although rarely lethal, late diagnosis can lead to serious visual morbidity. Definitive diagnosis of neoplastic lesions is pathological. Indications and types of eyelid lesions in a single high-volume ophthalmic reference center in Sao Paulo, Brazil, were analyzed. METHODS: The surgical pathological reports of patients who underwent eye removal procedures between January 2000 and December 2012 were retrieved from the electronic database of the Ophthalmology Department and retrospectively reviewed. Data regarding the final anatomopathological diagnosis, sex, and age were analyzed via the χ2 test with Yates' correction. RESULTS: Of the 1,113 eyelid tumors resected over the 13-year study period, 324 (29%) lesions were malignant. The most prevalent lesions were basal cell, squamous cell, and sebaceous gland carcinomas. The median ages of patients (females, n=165, 51%; males, n=159, 49%) with a diagnosis of basal cell, squamous cell, and sebaceous gland carcinomas were 65, 75, and 70 years, respectively. CONCLUSION: This is the largest retrospective cohort analysis of eyelid tumors in a Latin American population. These findings are in agreement with those from large centers in other countries and regions.

Largest case series of Latin American eyelid tumors over 13-Years from a single center in Sao Paulo, Brazil / A maior série de casos de tumores de pálpebra na América Latina ao longo de 13 anos de um único centro em São Paulo, Brasil

ABSTRACT Purpose: Malignant lesions of the eyelid are the most common eye cancers. Although rarely lethal, late diagnosis can lead to serious visual morbidity. Definitive diagnosis of neoplastic lesions is pathological. Indications and types of eyelid lesions in a single high-volume ophthalmic reference center in Sao Paulo, Brazil, were analyzed. Methods: The surgical pathological reports of patients who underwent eye removal procedures between January 2000 and December 2012 were retrieved from the electronic database of the Ophthalmology Department and retrospectively reviewed. Data regarding the final anatomopathological diagnosis, sex, and age were analyzed via the χ2 test with Yates' correction. Results: Of the 1,113 eyelid tumors resected over the 13-year study period, 324 (29%) lesions were malignant. The most prevalent lesions were basal cell, squamous cell, and sebaceous gland carcinomas. The median ages of patients (females, n=165, 51%; males, n=159, 49%) with a diagnosis of basal cell, squamous cell, and sebaceous gland carcinomas were 65, 75, and 70 years, respectively. Conclusion: This is the largest retrospective cohort analysis of eyelid tumors in a Latin American population. These findings are in agreement with those from large centers in other countries and regions.

RESUMO Objetivo: As lesões malignas de pálpebras são os cânceres oftalmológicos mais frequentes. Embora raramente letal, o diagnóstico tardio pode levar a diversas complicações severas e a uma alta taxa de morbidade visual. O diagnóstico definitivo de lesões neoplásicas é patológico. No presente estudo, revisamos casos de um único centro de referência oftalmológica de maior volume em São Paulo, Brasil. Métodos: Avaliação retrospectiva de todos os tumores palpebrais operados entre os anos de 2000 e 2012 no Departamento de Oftalmologia. Dados incluindo diagnóstico anatomopatológico final, sexo e idade - foram analisados através do método χ2 YATES. Resultados: Dentre os 1.113 tumores palpebrais ressecados no período de estudo de 13 anos, 324 (29%) dos pacientes com lesões únicas eram malignas. A lesão mais prevalente foi Carcinoma Basocelular (CBC), seguido por carcinoma espinocelular (CEC) e carcinoma de células sebáceas (CCS). A média da idade dos pacientes com diagnóstico de CBC, CCS e CEC foi 65, 75 e 70 respectivamente distribuídos entre 165 (51%) mulheres e 159 (49%) homens. Conclusão: Essa é a maior análise de coorte retrospectivo de tumores palpebrais da América Latina. Nossos achados estão de acordo com outros grandes centros de outros países e continentes.

Outcomes of primary endoresection for choroidal melanoma.

PURPOSE: To review long time treatment results in patients with small or medium sized choroidal melanoma who underwent surgical tumor endoresection as a primary treatment when plaque radiotherapy was unable and patients declined enucleation. MATERIALS AND METHODS: Patients were evaluated for best corrected visual acuity (BCVA), and underwent biomicroscopy, indirect ophthalmoscopy, retinography and ultrasound as well as the usual systemic workup. Study inclusion required the absence of scleral invasion or metastasis and an anterior margin not exceeding the pars plana or the ciliary body. Surgery consisted of a clear lens phacoemulsification with a PC-IOL, and a 23-gauge pars plana vitrectomy with anterior vitreous shave, lesional choroidal endodiathermy, followed by 23-gauge probe tumor endoresection and continuous endolaser. Patients were followed at post-operative 1 day, 1 week, 1, 3, and 6 months and then every 6 months with a complete ophthalmological exam including ultrasound biomicroscopy and systemic follow-up at 3, 6 and every 6 months thereafter. RESULTS: Fourteen patients with choroidal melanoma were included the study. Pre-operative BCVA ranged from 20/20 to hand motion (HM): 20/20 (n = 2); 20/60 (n = 1); and HM (n = 10). Pathological analysis confirmed the diagnosis of uveal melanoma in all cases. Mean follow-up was 54.5 months (45-66 months) with a final BCVA ranging from 20/60 to HM: 20/60 (n = 1); 20/60 to 20/200 (n = 10); and HM (n = 2). The eye retention rate in our study was 100%. No intraocular recurrence was observed. One patient died 12 months after surgery from metastatic disease. CONCLUSION: Endoresection appears to be an acceptable alternative to enucleation for the treatment of posteriorly-localized uveal melanoma, with excellent local control and eye salvage rates.

Evaluating the presence of Toxoplasma gondii in peripheral blood of patients with diverse forms of uveitis.

The purpose of this study was to evaluate the presence of Toxoplasmosis gondii in samples of peripheral blood from patients with varying etiologies of uveitis. Whole blood from patients with different forms of uveitis was tested for the presence of T. gondii using real-time PCR targeting the well-characterized 529 bp fragment. Extracted DNA was both frozen. Thirty-one patients were included in the current study and grouped as follows: acute toxoplasmosis (n = 10); toxoplasmic retinal scars (n = 9); non-infectious etiologies of uveitis (n = 6); and IgG negative for toxoplasmosis (n = 6). In total, only two patients were shown to have circulating T. gondii in peripheral blood; both of these patients were IgG positive for toxoplasmosis, were receiving immunosuppressive therapy for autoimmune uveitis, and had no clinical features of toxoplasmosis. T. gondii was identified in peripheral blood of some immunosuppressed patients. No other patients, including those with acute toxoplasmosis, had circulating parasites in peripheral blood.

Immunohistochemical Analysis of PDGFR-α, PDGFR-ß and c-Abl in Retinoblastoma: Potential Therapeutic Targets.

BACKGROUND: Our laboratory previously reported that imatinib mesylate (IM) has an inhibitory effect on two retinoblastoma (Rb) cell lines in vitro. AIMS: The purpose of this project was to determine the immunoexpression of platelet-derived growth factor receptor (PDGFR)-α, PDGFR-ß and c-Abl in 61 human samples of Rb to determine if IM-sensitive receptors are present. Additionally, this paper seeks to establish a correlation between the expression of PDGFR, c-Abl and the histopathological prognosis. METHODS: Sixty-one paraffin-embedded Rbs were collected from the Henry C. Witelson Ocular Pathology Registry. PDGFR-α, PDGFR-ß and c-Abl immunostaining was performed according to the protocol provided by Ventana Medical System Inc. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve. RESULTS: Overall, c-Abl expression was identified in 50 out of 61 specimens (81.97%), PDGFR-α was identified in 20 out of 60 specimens (33.33%) and PDGFR-ß expression was identified in 57 out of 61 specimens (93.44%). Histopathological prognosis was not correlated with immunoreactivity except in the case of PDGFR-ß. CONCLUSIONS: Rb is a cancer that expresses PDGFR-α, PDGFR-ß and c-Abl, which are known targets of IM. These markers may be responsible for the documented therapeutic effect of IM on Rb cell lines.

Expression of the metastasis suppressor BRMS1 in uveal melanoma.

AIMS: To determine the expression of breast metastasis suppressor 1 (BRMS1) in human uveal melanoma (UM) tissues and cell lines. In addition, we intend to establish a possible association between BRMS1 expression and the presence of metastatic disease. METHODS: Thirty-one formalin-fixed paraffin-embedded tissues from enucleated eyes of patients with UM were immunostained. Clinical-pathological data were obtained, including age, tumour location, largest dimension, cell type, and occurrence of metastasis. The expression of BRMS1 mRNA in four human UM cell lines was determined by real-time reverse transcriptase polymerase chain reaction, and protein expression was assessed by immunocytochemistry and western blot. The association between BRMS1 immunostaining and location, largest tumour dimension, and tumour cell type was determined using the correlation coefficient test. The association between BRMS1 immunostaining and the incidence of metastasis was assessed using Kaplan-Meier analysis. RESULTS: Of the 31 cases of UM, 24 (77.42%) stained positive and seven (22.58%) negative for BRMS1. From the positively stained tumours, 21 (87.50%) showed cytoplasmatic staining. Macrophages were usually positive when present in the tumour and staining intensity was generally higher than in UM cells. BRMS1 mRNA was present in all four human UM cell lines, as well as cytoplasmatic immunoexpression of BRMS1. Immunoblotting showed variable BRMS1 protein levels between the different cell lines. No statistically significant correlation was found between BRMS1 protein expression and survival (P = 0.69), tumour cell type (P = 0.68), largest tumour dimension (P = 0.75), and tumour location (P = 0.11). CONCLUSIONS: BRMS1 is expressed in UM both at the mRNA and protein level; however, neither was associated with any of the prognosticor outcome parameters that we tested.

Hypoxia-inducible factor-1α and its role in the proliferation of retinoblastoma cells.

In order to better understand the role of HIF-1α in the proliferation of the retinoblastoma cells, a siRNA knockdown of HIF-1α followed by a proliferation assay was performed. Further sequencing was then carried out in order to assess knockdown efficiency and expression of HIF-1α. Upregulation of HIF-1α gene expression in CoCl2-treated retinoblastoma cells was demonstrated via melting curve analysis from PCR tests and was further analyzed using western blot and densitometry analysis. Reduction of HIF-1α expression in retinoblastoma, post HIF-1α knockdown, was observed after siRNA transfection into Y-79 cells. Knockdown of HIF-1α resulted in a significant decrease in proliferation thereby demonstrating that HIF-1α is involved in promoting survival and proliferation in retinoblastoma cells. Stabilization of HIF-1α in retinoblastoma cells using CoCl2 was unsuccessful.

Rapid growth of an orbital hemangiopericytoma with atypical histopathological findings.

Hemangiopericytoma is a rare vascular tumor that originates from pericytes. The orbit is a rare location for this particular tumor, and corresponds to 0.8% to 3% of all primary orbital tumors. We report a case of a hemangiopericytoma in a 45-year-old man that had an unusual presentation, as a rapidly growing mass in the anterior right inferior orbit. Given that there are no clinical or radiological signs pathognomonic of this tumor, a careful histopathological examination is necessary to confirm the diagnosis. In our case, it presented also with unusual histopathological findings. The clinical features, radiological findings, differential diagnosis and treatment of this challenging entity are reviewed in this case report.

Local chemotherapeutic agents for the treatment of ocular malignancies.

We critically analyze available peer-reviewed literature, including clinical trials and case reports, on local ocular cancer treatments. Recent innovations in many areas of ocular oncology have introduced promising new therapies, but, for the most part, the optimal treatment of ocular malignancies remains elusive.

Expression of the Metastasis Suppressor KAI1 in Uveal Melanoma.

Introduction. Uveal melanoma (UM) is an intraocular tumor that leads to metastatic disease in approximately 50% of afflicted patients. There is no efficacious treatment for metastatic disease in this cancer. Identification of markers that can offer prognostic and therapeutic value is a major focus in this field at present. KAI1 is a metastasis suppressor gene that has been reported to play a role in various human malignancies, although it has not previously been evaluated in UM. Purpose. To investigate the expression of KAI1 in UM and its potential value as a prognostic marker. Materials and Methods. 18 cases of human primary UM were collected and immunostained for KAI1 expression. A pathologist evaluated staining intensity and distribution semiquantitatively. Each case was categorized as group 1 (low staining) or group 2 (high staining). Results. In group 2, two of the 12 cases presented with metastasis. Conversely, in group 1, five out of 6 cases had metastasis. The mean follow-up of patients who did not develop metastasis was 81.81 months (median: 75 months) versus 42.14 months (median: 44 months) for patients with metastasis. Conclusions. KAI1 is a promising candidate marker that may offer prognostic value in UM; it may also represent a therapeutic target in metastatic disease.

Expression of SIRT1 and DBC1 in Developing and Adult Retinas.

Sirtuin 1 (SIRT1) is a deacetylase that can regulate various biological processes via repression of transcription. Its activity has been linked to the differentiation of neural progenitor cells, although little is known about its function during retinal development. The study described herein was undertaken to evaluate the expression of SIRT1 and its innate inhibitor, DBC1, in retinal tissues and progenitor cells. We found both SIRT1 and DBC1 to be widely expressed in mouse and human retinas, with subtle differences in subcellular distribution of each protein. We further demonstrate that nuclear-localized SIRT1 is only seen in human-derived retinal progenitor cells and not in adult retinas, suggesting that this nuclear localization may be important in retinal development. Moreover, we observed cytoplasmic DBC1 in a subset of progenitor cells as well as in mature ganglion cells, indicating that the progenitor cell subset, which was comprised predominantly of small cells, may represent a population of ganglion cell precursors. Collectively, the data presented in this study provide support for SIRT1 and DBC1 as regulators of retinal development and normal retinal physiology.

A histopathologic review of undiagnosed neoplasms in 205 evisceration specimens.

PURPOSE: Evisceration and enucleation are 2 ophthalmic surgeries used to treat blind and painful eyes. The benefits of evisceration over enucleation are many but this procedure is contraindicated in cases of a suspected intra-ocular mass. Given the lack of such studies in the literature, our aim was to review a large sample of eviscerated specimens to document the prevalence of unexpected neoplasms. METHODS: During the study period (1994-2011), 13,591 human ophthalmic specimens were received at the Henry C. Witelson Ophthalmic Pathology Laboratory and Registry. Of those, 205 were evisceration specimens. Histopathologic reports were reviewed to retrieve relevant clinical information that included clinical diagnosis, age, gender, laterality, and final histopathologic diagnosis. RESULTS: The total number of unexpected neoplasms was 4 (1.95%) including 2 (0.97%) malignancies: necrotic melanoma (1), ciliary body adenoma (1), iris nevus (1), and spindle cell melanoma (1). All the other remaining eyes had histopathologic findings that were consistent with the underlying diagnosis. CONCLUSIONS: With proper pre-operative evaluation, including history, ophthalmologic examination, and imaging studies, the rate of unexpected neoplasms in evisceration specimens were low. Evisceration is a simpler and cheaper procedure when compared with enucleation, and our results corroborate its safety, whenever indicated to treat blind and/or painful eyes.

Clinical and histopathological features of orbital granular cell tumor: case report.

A 53 year-old woman presented with a slowly progressive, painless proptosis OS. Computed tomography disclosed a round, homogeneous, well-delimited lesion in the inferior-temporal orbit. The tumor was composed of round cells with eosinophilic granular cytoplasm. Some of the cells had larger eosinophilic granules surrounded by a clear halo; known as pustulo-ovoid bodies of Milian or Bangle bodies. The diagnosis of a granular cell tumor was then established and confirmed by immunohistochemistry. Granular cell tumors are uncommon benign soft tissue neoplasms that have a predilection for the head and neck region. Awareness of the typical histopathological features is crucial for the correct diagnosis.

Clinical and histopathological features of orbital granular cell tumor: case report / Características clínicas e histopatológicas de tumor de células granulares da órbita: relato de caso

A 53 year-old woman presented with a slowly progressive, painless proptosis OS. Computed tomography disclosed a round, homogeneous, well-delimited lesion in the inferior-temporal orbit. The tumor was composed of round cells with eosinophilic granular cytoplasm. Some of the cells had larger eosinophilic granules surrounded by a clear halo; known as pustulo-ovoid bodies of Milian or Bangle bodies. The diagnosis of a granular cell tumor was then established and confirmed by immunohistochemistry. Granular cell tumors are uncommon benign soft tissue neoplasms that have a predilection for the head and neck region. Awareness of the typical histopathological features is crucial for the correct diagnosis.

Mulher de 53 anos apresentou proptose lentamente progressiva no olho esquerdo. Tomografia computadorizada mostrou uma lesão na região temporal inferior da órbita esquerda, bem delimitada, arredondada, homogênea. O tumor era composto de células com citoplasma granular eosinofilico. Algumas das células possuíam grandes grânulos eosinofílicos circundados por um halo claro, conhecidos como corpos ovoides-pustulares de Milian or corpos de Bangle. O diagnóstico de tumor de células granulares foi estabelecido, confirmado pela imuno-histoquímica. Tumor de células granulares são neoplasias incomuns com predileção da região da cabeça e pescoço. O conhecimento das características histopatológicas típicas são cruciais para o correto diagnóstico.