Macular Star, Optic Disc Swelling, and Lethargy in a Child.

A 13-year-old girl with a 7-day history of painless vision loss and central scotoma in her left eye was referred to the hospital. Dilated fundus examination revealed a bilateral sectorial macular star that was more extended in the left eye and some faint, small, tan-yellow dots were observed at the level of the retinal pigment epithelium in the posterior pole. What would you do next?

Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina.

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

Risk factors for failure after primary vitrectomy with no scleral buckling for rhegmatogenous retinal detachment / Fatores de risco para falha de tratamento após vitrectomia primária sem retinopexia com introflexão escleral

ABSTRACT Objective To assess pre-operative conditions that could influence primary anatomical success rate in a cohort of patients with rhegmatogenous retinal detachments (RRD) treated with primary vitrectomy and no scleral buckling. Methods A retrospective analysis was performed in a group of patients that underwent primary pars plana vitrectomy with gas tamponade and without scleral buckling for RRD between 2014 and 2019, with a minimum follow-up of 4 months. Results 305 eyes of 301 patients were included; 59.01% eyes were phakic, 39.01% were pseudophakic and 1.96% aphakic. 13.11% of patients had proliferative vitreoretinopathy grade B and 3.28% proliferative vitreoretinopathy grade C at the time of diagnosis while 83.61% had proliferative vitreoretinopathy grade 0 or A. 53.1% had superior breaks, 15.4% inferior breaks and 31.5% a combination of both. Primary success rate was obtained in 90.82% of eyes (95%CI 87.58-94.06). 9.18% of eyes (95%CI 5.94-12.42) re-detached. In 3.27% the cause of re-detachment was proliferative vitreoretinopathy, and in the remaining 5.90% because of a new or a missed break, the leakage of a previously treated break, or an area of shallow peripheral detachment with no detectable break. Of 181 phakic eyes, 10.49% re-detached, whereas in over 126 aphakic or pseudophakic eyes 7.75% re-detached (p=0.42). 16.39% eyes of the entire cohort had preoperative grade B or C proliferative vitreoretinopathy, whereas 32.14% of re-detached eyes had preoperative grade B or C proliferative vitreoretinopathy (95%CI 17.29-46.99; p=0.02). Th eyes that re-detached after the first surgery had a mean of 2.5 (95%CI 1.86-3.13) retinal tears, against a mean of 1.87 (95%CI 1.73-2.00) retinal tears of those that did not re-detach after the first surgery (p=0.02). Conclusion We found location of breaks and lens status to be independent factors not related to a lower single operation success rate, whereas the number or size of breaks and preoperative proliferative vitreoretinopathy stages B or C were independent factors related to a higher likelihood of re-detachment.

RESUMO Objetivo Avaliar condições pré-operatórias que poderiam influenciar a taxa de sucesso anatômico primário em uma coorte de pacientes com descolamento de retina regmatogênico tratada com vitrectomia primária e sem introflexão escleral. Métodos Foi realizada uma análise retrospectiva em um grupo de pacientes submetidos a vitrectomia primária pars plana com tamponamento gasoso e sem introflexão escleral por desprendimento de retina regmatogênico entre os anos 2014 e 2019, com monitoramento mínimo de 4 meses. Resultados Foram incluídos 305 olhos de 301 pacientes; 59,01% dos olhos eram fáquicos, 39,01% eram pseudofáquicos, e 1,96% era afáquico; 13,11% dos pacientes tinham vitreorretinopatia proliferativa grau B, e 3,28%, vitreorretinopatia proliferativa grau C no momento do diagnóstico, enquanto 83,61% tinham vitreorretinopatia proliferativa grau 0 ou A; 53,1% tinham rasgaduras superiores; 15,4%, rasgaduras inferiores e 31,5%, uma combinação de ambas. A taxa de sucesso primário foi obtida em 90,82% dos olhos (IC95% 87,58-94,06); 9,18% dos olhos (IC95% 5,94-12,42) se redestacaram. Em 3,27%, a causa do redescolamento foi vitreorretinopatia proliferativa e, nos 5,90% restantes, por causa de uma ruptura nova ou perdida, o vazamento de uma ruptura previamente tratada, ou uma área de descolamento periférico superficial sem ruptura detectável. Dos 181 olhos fáticos, 10,49% redestacaram-se, enquanto em mais de 126 olhos afáquicos ou pseudofáquicos 7,75% redestacaram-se (p=0,42); 16,39% dos olhos de toda a coorte tinham vitreorretinopatia proliferativa pré-operatória grau B ou C, enquanto 32,14% dos olhos redescolados tinham vitreorretinopatia proliferativa pré-operatória grau B ou C (IC95% 17,29-46,99) (p=0,02). Os olhos que se redescolaram após a primeira cirurgia tiveram média de 2,5 (IC95% 1,86-3,13) lágrimas retinianas, contra uma média de 1,87 (IC95% 1,73-2,00) lágrima retiniana daqueles que não se redestacaram após a primeira cirurgia. (p=0,02). Conclusão A localização das rasgaduras e o status da lente são fatores independentes não relacionados a uma menor taxa de sucesso da operação, enquanto o número ou o tamanho das rasgaduras e estágios vitreorretinopatia proliferativa pré-operatórios B ou C foram fatores independentes relacionados a uma maior probabilidade de redescolamento.

Visual loss as the initial manifestation of an ignored disseminated prostate cancer: A case report.

Purpose: To present a rare case of advanced disseminated prostate cancer with bilateral visual loss as the initial manifestation of the disease. Observations: A 55-year-old man referring progressive visual blurring for the last 6 months and painless severe bilateral visual loss in the last 7 days prior to our consultation, associated with a bilateral optic disc swelling and leptomeningeal metastases from a previously ignored prostate carcinoma is presented. Rapid improvement of visual acuity and involution of leptomeningeal metastasis was observed after initiation of the specific oncologic treatment. Conclusions and importance: Bilateral visual loss may be the initial manifestation of leptomeningeal carcinomatosis from an ignored prostate cancer. Prompt diagnosis is crucial in order to improve the quality of life of a critically ill patient with a disseminated prostate cancer.

ROP Screening Tool Assessment and Validation in a Third-Level Hospital in Argentina: A Pilot Study.

PURPOSE: To evaluate whether a mathematical tool that predicts severe retinopathy of prematurity (ROP) using clinical parameters at 6 weeks of life (ROPScore calculator smartphone application; PABEX Corporation) can be useful to predict severe ROP in a population of premature infants in Argentina. METHODS: In this retrospective study, data from the clinical records of all premature infants examined between 2012 and 2018 in the ophthalmology department of a public third-level hospital in Córdoba, Argentina, were obtained. ROPScore screening was applied using a Microsoft Excel spreadsheet (Microsoft Corporation). The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of the algorithm were analyzed. RESULTS: Between 2012 and 2018, a total of 2,894 pre-term infants were examined and 411 met the inclusion criteria, of whom 34% (n = 139) presented some form of ROP and 6% (n = 25) developed severe forms that required treatment. The sensitivity of the algorithm for any ROP and severe ROP was 100%. The PPV and NPV were 35.64% and 100%, respectively, for any ROP and 9.88% and 100% for severe ROP. CONCLUSIONS: One-time only calculation of the ROPScore algorithm could identify severe cases after validation, reducing the number of screened infants by 38% in infants with a birth weight of 1,500 g or less or a gestational age of 32 weeks or younger. [J Pediatr Ophthalmol Strabismus. 2021;58(1):55-61.].

Optimizing optical coherence tomography and histopathology correlation in retinal imaging.

OBJECTIVE: To develop a methodology to correlate optical coherence tomography (OCT) images and histopathological sections from the same eye. Part 1: To determine the best fixative for optimal OCT and histopathological analysis in post-mortem eyes. Part 2: A protocol is proposed to correlate histopathological features and OCT scans from the same post-mortem eyes. DESIGN: Experimental study. PARTICIPANTS: Part 1: Twenty-three rabbit eyes and 14 post-mortem human eyes. Part 2: Nineteen post-mortem human eyes. METHODS: Part 1: Six different fixatives were tested, and specimens were evaluated on 4 criteria: globe shape, structure opacification, retinal detachment, and nuclear details. Part 2: Based on the findings from Part 1, fixed human eyes were imaged using OCT. Orientation-controlled histopathological processing was performed to obtain serial tissue sections from paraffin embedded tissue, which were matched to corresponding OCT images. RESULTS: Part 1: Of the 6 fixatives, 2% glutaraldehyde and Davidson's solution met the proposed criteria in rabbit eyes. Of these, glutaraldehyde showed similar results in human eyes and was selected for Part 2. Part 2: Using anatomical landmarks, cross-sectional histopathological sections in the same orientation as the OCT images were correlated to their corresponding OCT images. Retinal lesions such as a macular hole, an epiretinal membrane, and the presence of drusen were easily correlated, proving the reliability of our methodology. Moreover, the photoreceptor's inner/outer junction was correlated to a hyperreflective band on OCT. CONCLUSIONS: A standardized protocol was developed to correlate OCT images and histopathological findings by generating serial cross-sections of the retina, which can be used to better understand otherwise ambiguous OCT findings.

An unusual orbital tumor in an adult: Granuloma annulare.

PURPOSE: Granuloma annulare (GA) is a rare clinical entity that does not classically arise from the peri-orbital area in adults. The purpose of this case report is to present a 69-year-old female with GA of the orbit. As well, the pathological and immunohistochemical features of these tumors will be discussed. OBSERVATIONS: One case of GA of the orbit was identified from a tertiary ophthalmology referral centre. Clinical and histopathological features of the case were reviewed. Other cases of GA were also retrieved from the literature and addressed in this report. CONCLUSION AND IMPORTANCE: Granuloma annulare is a rare orbital lesion in adults. It is known to typically arise on the hands and feet of children. This lesion must be distinguished from necrobiotic xanthogranuloma (NXG), which is a progressive peri-orbital dermatosis seen in middle age men and women. GA is thought to be a benign, often self-resolving condition, whereas NXG tends to be linked to other systemic conditions and may have a poorer prognosis.Differentiating this rare orbital tumor from necrobitotic xanthogranuloma (NXG) is essential, as both a systemic work-up and follow-up must be appropriately arranged. A comprehensive description of pathognomonic microscopic features of GA and NXG is reviewed to achieve the correct diagnosis.

Removing Subjective Post-Mortem Grading from Posterior Capsular Opacification: A New Automated Detector Opacification Software, ADOS.

Purpose/aim: Posterior capsular opacification (PCO) is the leading complication following cataract surgery. However, PCO grading methods vary between studies and rely on subjective scoring methods; hence, they are prone to error. Therefore, software that reduces subjectivity and enhances reproducibility is needed. The aim of the study was to evaluate the reproducibility and objectivity of a novel automated custom-designed PCO detection software. MATERIALS AND METHODS: In total, 165 fixed eyes with intraocular lenses were sectioned to obtain a Miyake Apple view (MAV) image. The capsular bag (CB) with the in situ IOL was removed and imaged using the Olympus DSX110 stereoscope. Central, peripheral, and Soemmering's ring area (SRA) and intensity (SRI) were graded by two ophthalmologists using a scale of 0-4. Software was developed to detect PCO, and these values were correlated with subjective scoring. RESULTS: Intra-observer agreement for MAV and CB images ranged from poor to moderate, with very good agreement for SRI (k = 0.88, 0.86, respectively). Agreement between graders was fair to good (k = 0.31-0.77). Miyake Apple view and capsular bag images showed good correlation; central PCO showed the least correlation for both evaluators (k = 0.29, 0.72). Subjective average grading versus software correlation demonstrated very good correlation for intensity and good for area (r = 0.85, 0.61). Reproducibility of the methodology resulted in good to very good correlation. CONCLUSIONS: Software correlates with previous scoring methods and is a reliable and reproducible system. Moreover, the capsular bag view, as opposed to the Miyake Apple view, allows visualization of the capsular bag directly and avoids overlapping structures (vitreous, cornea) that may interfere with proper PCO quantification.

Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma.

Programmed cell death-1/ligand (PD-1/PD-L1) interaction negatively regulates T cell activity. PD-L1 expression in tumor cells, antigen-presenting cells, and lymphocytes of the tumor microenvironment is associated with response to treatment with PD-1/PD-L1 inhibitors, but there is still debate on the cutoff value that correlates with responders. In uveal melanoma (UM), 40% of patients will develop liver metastases and, amongst them, 90% will succumb to their disease. The aim of this study was to analyze PD-L1 expression as a prognostic marker and as a possible therapeutic target for UM. Sixty-seven enucleated eyes from UM patients with relevant clinical information were analyzed. Univariate and multivariate analysis were used to evaluate association of PD-L1 with survival. PD-L1 expression was positive relatively to tumor cells, immune cells, and the tumor and tumor-infiltrating immune cell group scoring in 46, 34 and 55% of the cases, respectively. On univariate analysis, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with a longer metastasis-free survival (P = 0.04 and P = 0.007). However, on multivariate analysis, only the tumor and tumor-infiltrating immune cell group positivity was associated with longer metastasis-free survival (P = 0.01). Furthermore, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with decreased tumor-infiltrating lymphocytes (P = 0.02). PD-L1, when expressed in uveal melanoma, is associated with better patient outcome and decreased tumor-infiltrating lymphocytes. These results support the consideration of anti-PD-1/PD-L1 therapy in uveal melanoma. To determine the best cutoff value, further studies from patients enrolled in clinical trials treated with PD-1/PD-L1 inhibitors are necessary.

High Inflammatory Infiltrate Correlates With Poor Symptomatic Improvement After Surgical Treatment for Superior Limbic Keratoconjunctivitis.

PURPOSE: Superior limbic keratoconjunctivitis (SLK) is a chronic and recurrent condition of unknown etiology. It is often managed conservatively, but there is a high rate of success with surgical management for severe or recalcitrant cases. The purpose of this article is to describe and analyze clinicopathological features of patients with SLK who underwent surgical treatment and their association with the clinical outcome. METHODS: A total of 22 eyes from 18 patients who underwent surgical SLK management were retrospectively analyzed. Clinicopathological data were collected including details of follow-up and patient satisfaction (n = 15). Moreover, 12 cases had specimens available for review of histopathologic findings and COX-2 expression analysis by immunohistochemistry. RESULTS: From a clinical perspective, 66.7% of the SLK eyes had nonmechanical factors contributing to SLK, and 66.7% of eyes demonstrated significant symptomatic improvement after surgery. Histopathological analysis of all the lesions showed acanthosis and goblet cell loss. Unexpectedly, in 93% of the eyes, dilated lymphatic vessels were found. Furthermore, a high inflammatory infiltrate correlated with minimal symptomatic improvements (P = 0.013). Moreover, COX-2 expression was higher in patients with SLK than in a normal conjunctiva (P = 0.001). CONCLUSIONS: In this study, the most common systemic association with SLK was the patient's autoimmune status. Histopathological evaluation revealed that high inflammatory infiltration in the biopsy might be predictive of minimal symptomatic improvement with surgical management. Finally, the higher COX-2 expression in patients with SLK compared with that in individuals with a normal conjunctiva supports the use of anti-COX-2 drugs as a possible therapeutic target.

HER2 Overexpression in Retinoblastoma: A Potential Therapeutic Target?

BACKGROUND: Retinoblastoma (RB) is the most common primary intraocular malignancy. Current therapies are associated with high morbidity in the short- and long-term. Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein detected in 15-30% of breast cancers, but it has also been described in other malignancies. Recently, it has been claimed that a truncated version of this protein is expressed in RB, responsive to directed therapies in vitro. We scored HER2 overexpression in RB tissue samples and discussed its potential clinical utility. METHODS: HER2 overexpression was investigated using immunohistochemistry; the overexpression was evaluated with a score ranging from 0 to 3+ according to the membranous staining pattern in archival formalin-fixed, paraffin-embedded RBs. RESULTS: A total of 60 RB cases and a RB cell line (Y79) were considered. The mean age at enucleation was 31.6 ± 31.5 months. The mean time from diagnosis to enucleation was 11.8 ± 11.2 months (range 1-44). Five (8%) cases were multifocal. HER2 overexpression was negative in all RB cases (49 cases scored 0 and 11 scored 1+) and in the Y79 cell line. CONCLUSIONS: Overall, we were not able to demonstrate the overexpression of HER2. Further studies should clarify and better elucidate the potential role of HER2-targeted therapies in RB.

Myopia as a risk factor for subsequent retinal tears in the course of a symptomatic posterior vitreous detachment.

BACKGROUND: Retinal tears complicating the course of a posterior vitreous detachment (PVD) may be unique or multiple, and when multiple they may occur simultaneously or subsequently at different moments in the evolution of a PVD. The purpose of our study was to analyze the prevalence of subsequent retinal tears (SRT) in patients with a PVD, and to identify possible risk factors for SRT. METHODS: One hundred and seventy six eyes in 165 consecutive patients that presented one or more retinal tears in the evolution of a symptomatic PVD, with a minimum follow-up of 12 months, were retrospectively evaluated. The primary outcome measure was to characterize the clinical features associated with SRT formation against those eyes with non-subsequent retinal tear (NSRT-retinal tear/s diagnosed at initial examination) formation. For that purpose, this cohort of patients was divided into two different groups: group 1 included eyes presenting one or multiple retinal tears only at initial examination (NSRT), and group 2 eyes that progressed to a further retinal tear/s (SRT) during follow-up. RESULTS: Group 1 comprised 154 eyes from 145 patients, 48.7% males and 51.3% females with a mean age of 56.9 ± 14.0 years (range = 15-89); 17.2% of patients had a previous retinal tear or retinal detachment in the fellow eye; mean number of retinal tears per eye 1.42 ± 0.8 (range = 1-5); 20.8% presented bilateral retinal tears; 59.1% were myopic eyes (p < 0.05). Group 2 comprised 22 eyes from 20 patients; mean age was 53.3 ± 13.6 years (range = 30-69); 63.6% were male (p = 0.13), and 7 patients (31.8%) had a history of SRT or retinal detachment in the fellow eye (p = 0.13). The mean number of retinal tears per eye was 1.36 ± 0.5 (range = 1-2); bilateral retinal tears were noted in 18.2% of eyes; 86.4% were myopic eyes (p = 0.01); 81.8% occurred within a 120 days-period following diagnosis of the first retinal tear. CONCLUSIONS: Multiple retinal tears may be diagnosed in the evolution of a PVD. SRT are most frequently observed in myopic patients, and are usually symptomatic. Follow-up must extend for at least 4 months after the initial symptoms.

Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model.

BACKGROUND: Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD. METHODS: Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines. RESULTS: A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions. CONCLUSIONS: Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.

Evaluation of nicotinamide as an anti-inflammatory and anti-angiogenic agent in uveal melanoma cell lines.

PURPOSE:: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. METHODS:: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. RESULTS:: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. CONCLUSIONS:: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy.

Climatic droplet keratopathy (CDK) is an acquired degenerative disease predominantly affecting males over 40 years old. It results in progressive corneal opacities usually affecting both eyes. CDK is multifactorial and its etiology remains unknown. Our recent findings are consistent with CDK pathology being driven by environmental factors with oxidative stress playing an important role (e.g.,, contributing to lipid peroxidation) rather than climate factors. The changes in corneal lipid composition affected by environmental factors remain understudied. The purpose of this study was to systematically investigate phospholipids profile (phosphatidylcholine [PC] and phosphatidylserine [PS]) in corneas from CDK patients using tandem mass spectrometry. Samples from CDK areas and from non-affected areas were obtained from patients diagnosed with CDK who underwent cataract surgery, were subjected to lipid extraction using a modified Bligh and Dyer method; protein concentrations were determined using the Bradford's method. Lipids were identified and subjected to ratiometric quantification using TSQ Quantum Access Max triple quadrupole mass spectrometer, using appropriate class specific lipid standards. All phospholipid classes showed lower total amounts in affected areas compared to control areas from CDK's corneas. Comparative profiles of two phospholipid classes (PC, PS) between CDK areas and control areas showed several common species between them. We also found a few unique lipids that were absent in CDK areas compared to controls and vice versa. Lower amount of phospholipids in CDK areas compared to control areas could be attributed to the lipid peroxidation in the affected corneal regions as a consequence of increased oxidative stress. J. Cell. Biochem. 118: 3920-3931, 2017. © 2017 Wiley Periodicals, Inc.

Evaluation of nicotinamide as an anti-inflammatory and anti-angiogenic agent in uveal melanoma cell lines / Avaliação da nicotinamida como agente anti-inflamatório e anti-angiogênico em linhas celulares de melanoma uveal

ABSTRACT Purpose: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. Methods: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. Results: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. Conclusions: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

RESUMO Objetivo: Acredita-se que a nicotinamida (NIC) seja capaz de diminuir a angiogênese induzida pelo fator de crescimento endotelial vascular (VEGF). Investigar os efeitos da nicotinamida sobre a secreção de citocinas pró-angiogênicas e pró-inflamatórias em linhagens de células de melanoma uveal humano (UM). Métodos: Duas linhagens de células humanas de UM (92,1 e OCM-1) foram tratadas com NIC (10 mmol/L) ou apenas com meio de cultura por 48 horas. O sobrenadante das culturas obtido após a administração de nicotinamida foi comparado com o sobrenadante das culturas controle quanto à expressão de 20 fatores pró-angiogênicos e pró-inflamatórios, pela técnica de enzyme-linked immunosorbent assay (ELISA). Resultados: Sete citocinas pró-angiogênicas foram detectadas nas condições de controle em ambas as linhagens de células de UM. O tratamento com nicotinamida promoveu uma redução significativa da secreção das seguintes citocinas angiogênicas: Angiogenina, ANG2, EGF e VEGF-A em células 92.1; bFGF em células OCM-1; PIGF em ambas as linhagens celulares. Quanto às proteínas pró-inflamatórias, a expressão de MCP-1 e IL-8 foi significativamente reduzida com a administração de nicotinamida em relação às culturas de células que não receberam o tratamento. Conclusões: Nicotinamida apresenta propriedades anti-inflamatórias e anti-angiogênicas em modelo experimental in vitro. Tais efeitos sugerem a possibilidade de utilizar esta substância na quimioprevenção do UM. Entretanto, estudos com modelos experimentais in vivo são necessários para melhor avaliar o benefício do tratamento do UM com nicotinamida.

Endophthalmitis Prophylaxis in Cataract Surgery: Overview of Current Practice Patterns Around the World.

BACKGROUND: Acute-onset postoperative endophthalmitis after cataract surgery remains a rare but important cause of visual loss. There is no global consensus regarding the optimal strategies for prophylaxis of endophthalmitis and practices vary substantially around the world, especially with respect to the use of intracameral antibiotics. The European Society of Cataract & Refractive Surgeons in a randomized clinical trial (2007) reported an approximately 5-fold reduction in endophthalmitis rates associated with the use of intracameral cefuroxime. Despite this report, the use of intracameral antibiotics has not been universally adopted. METHODS: Various endophthalmitis prophylaxis patterns around the world (including the United States, Canada, Australia/New Zealand, Japan, China, India, Indonesia, South Africa, Argentina, Russia, Sweden and Mexico) are compared. Each contributing author was asked to provide similar information, including endophthalmitis rates based on published studies, current practice patterns, and in some cases original survey data. Various methods were used to obtain this information, including literature reviews, expert commentary, and some new survey data not previously published. RESULTS: Many different practice patterns were reported from around the world, specifically with respect to the use of intracameral antibiotics. CONCLUSION: There is no worldwide consensus regarding endophthalmitis prophylaxis with cataract surgery.

Epithelial Inclusion Cyst in Conjunctival Melanoma.

Conjunctival melanoma is the second most common conjunctival malignancy. Its differential diagnosis with other conjunctival melanocytic neoplasms is inherently difficult. The presence of epithelial cysts is a useful feature in conjunctival tumors and favors a benign lesion. Herein 2 cases of conjunctival melanoma with cysts are presented. To the best of our knowledge, this is the first series of conjunctival melanoma with epithelial inclusion cysts. This series emphasizes the importance of considering several malignant features when reviewing conjunctival melanocytic lesions, as malignancy can exist even in the presence of epithelial inclusion cysts.

The eye and the skin in endocrine metabolic diseases.

The eye and skin may offer critical clues to the diagnosis of a varied spectrum of metabolic diseases from endocrine origin and their different stages of severity, such as diabetes mellitus and Graves disease. On the other hand, such entities may compromise the eye and visual function severely, and awareness of these possible associations is an important step in their diagnosis and management. A large number of less common endocrine diseases may also have significant ocular/visual or skin involvement. Often the etiologic relationship between the endocrine metabolic disease and the ocular compromise is unknown, but diverse pathogenetic mechanisms may act through a common pathologic pathway producing ocular damage, as occur in diabetic retinopathy. This review emphasizes the ocular and skin manifestations of different metabolic diseases of endocrine origin.

The eye and the skin in nonendocrine metabolic disorders.

As metabolism is controlled by the input of genes and the environment, metabolic disorders result from some disturbance in the interaction between genes and environmental factors. Many metabolic disorders consist in congenital enzyme deficiencies, also known as "inborn errors of metabolism," that may be disabling or cause severe illness and death and are predominantly inherited in an autosomal recessive fashion. The deposit in cells and tissues of storage substances from errors in metabolic processes may produce a wide variety of disorders affecting different organs and functions, with different degrees of severity, and often present around the time of birth or early childhood. Distinctive ocular and skin manifestations accompany many metabolic diseases and may provide clues for their diagnosis and evolution.