Very High-Frequency Ultrasonography Signs in Bilateral Acute Choroidal Effusion Associated with Systemic Sulphonamide Medications: 2 Cases.

Sulphonamides are commonly used in medicine for several purposes; however, they can lead to significant adverse effects, including idiosyncratic reactions and choroidal detachment corresponding to a forward rotation of the iris-lens diaphragm; this could also evolve into acute transient myopia with possible acute angle closure glaucoma. The risk of such reactions to sulphonamides is approximately 3%. In our communication, we have reported on 2 cases involving patients who suffered choroidal detachments after starting sulphonamide treatments and who were diagnosed with the help of ultrasound biomicroscopy. Patient 1 was an 87-year-old male with bilateral pseudophakia who developed an acute change in vision in both eyes after he started taking chlorthalidone, a classic thiazide diuretic antihypertensive that is characterized by having a sulpha-based group. Patient 2 was a 42-year-old female who developed dramatic visual loss after beginning a new treatment (topiramate) for weight loss. We were able to successfully detect the choroidal detachments in these patients with ultrasound biomicroscopy, which aided us in quickly diagnosing the condition. Subsequently, the drugs were immediately discontinued, and appropriate treatment was administered resulting in the full recovery of both patients.

Diagnosis and long-term monitoring of adenomas of the ciliary body epithelium by ultrasound biomicroscopy.

INTRODUCTION: The natural course of adenomas of the ciliary-body epithelium (ACE) is uncertain, due to their low incidence and their frequent initial surgical management.Their differential diagnosis with amelanotic melanoma or metastasis is challenging and diagnostic biopsies require sufficient tissue and highly specialized pathologists. Ultrasound biomicroscopy offers high resolution images and clear sonographic signs suggestive of ACE allowing a more precise differential diagnosis and therefore, a more conservative initial attitude. METHODS: Descriptive, retrospective, non-comparative study of consecutive cases of ACE observed between October 2003 and December 2019 in a reference unit in ocular oncology of a tertiary hospital. Patients were studied on a quarterly basis the first year and, subsequently, every 6 months with a complete ophthalmological exam and ultrasound biomicroscopy with the platform Aviso linear scanning 50 MHz probe (Quantel Medical, Clermont-Ferrand, France). RESULTS: Three ACE were analysed for a median of 3 years (interquartile range: 2.5-5.5 years). Clinical features include a whitish-to-brown spherical mass, with engorged superficial vessels. Ultrasound biomicroscopy shows an oval-spherical shape, medium-to-high echogenicity, low acoustic attenuation, regular internal structure, and respect for the neighboring structures. By their clinical-ultrasonographic characteristics, one was considered an adenoma of the pigmented ciliary-body epithelium (browner and hyperechogenic) and two were classified as adenomas of the non-pigmented ciliary epithelium (whitish appearance and medium-echogenicity). CONCLUSION: Ultrasound biomicroscopy allows a reasonable clinicalsonographic suspicion of ACE. An initial conservative management is proposed as a safer option for stable, mildly symptomatic patients, avoiding aggressive sight threatening treatments.

Blood Biomarkers of Uveal Melanoma: Current Perspectives.

The detection of metastases in patients with a diagnosis of uveal melanoma (UM) is a controversial issue. While only 1% of the patients have detectable metastases at the time of diagnosis, up to 30% of them will develop liver metastases within 5 years of treatment. UM spreads hematogenously, therefore, blood biomarkers may be helpful for prognosis and monitoring the disease progression. Despite the great progress achieved thanks to the genetic analysis of UM biopsies, this is an invasive technique and is limited by the heterogeneity of the tumor. The present review considers the current understanding in the field regarding biomarkers for the diagnosis and prognosis of UM and its metastasis, primarily to the liver. General covered topics include non-conventional markers such as proteins previously identified in cutaneous melanoma and UM cell lines, circulating tumor cells, microRNAs (miRNA), and circulating DNA, and how each may be critical in the development of novel blood biomarkers for UM.

Effects of internal limiting membrane peeling during vitrectomy for macula-off primary rhegmatogenous retinal detachment.

PURPOSE:: To determine the effectiveness of internal limiting membrane peeling during vitrectomy for macula-off primary rhegmatogenous retinal detachment in the prevention of postoperative epiretinal membrane formation and achievement of good visual outcomes and to identify preoperative and intraoperative risk factors for epiretinal membrane formation. METHODS:: We retrospectively analyzed data from 62 eyes of 62 consecutive patients with macula-off primary rhegmatogenous retinal detachment who underwent vitrectomy with (n = 30) or without (n = 32) internal limiting membrane peeling between January 2014 and March 2016 and were followed up for at least 12 months. The effects of internal limiting membrane peeling on visual outcomes and postoperative recovery of the macular structure were determined. We subsequently divided patients into an epiretinal membrane group and a non-epiretinal membrane group and assessed the effects of various preoperative and intraoperative factors on postoperative epiretinal membrane formation. RESULTS:: Postoperative epiretinal membrane developed in 10 patients in the no internal limiting membrane peeling group and three patients in the internal limiting membrane peeling group. Postoperative visual acuity significantly improved in both groups. Epiretinal membrane formation was found to be correlated with a higher number of retinal breaks. CONCLUSION:: Our results suggest that internal limiting membrane peeling during macula-off primary rhegmatogenous retinal detachment surgery can reduce the occurrence of postoperative epiretinal membrane, is safe, and results in favorable visual outcomes.

In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops.

PURPOSE: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops. METHODS: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1®), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made. RESULTS: Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops. CONCLUSIONS: In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene® for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments.

Evaluation of the in vitro ocular toxicity of the fortified antibiotic eye drops prepared at the Hospital Pharmacy Departments / Evaluación de la toxicidad ocular in vitro de los colirios fortificados antibióticos elaborados en los Servicios de Farmacia Hospitalaria

The use of parenteral antibiotic eye drop formulations with non-marketed compositions or concentrations, commonly called fortified antibiotic eye drops, is a common practice in Ophthalmology in the hospital setting. The aim of this study was to evaluate the in vitro ocular toxicity of the main fortified antibiotic eye drops prepared in the Hospital Pharmacy Departments. We have conducted an in vitro experimental study in order to test the toxicity of gentamicin, amikacin, cefazolin, ceftazidime, vancomycin, colistimethate sodium and imipenem-cilastatin eye drops; their cytotoxicity and acute tissue irritation have been evaluated. Cell-based assays were performed on human stromal keratocytes, using a cell-based impedance biosensor system [xCELLigence Real-Time System Cell Analyzer (RTCA)], and the Hen’s Egg Test for the ocular irritation tests. All the eye drops, except for vancomycin and imipenem, have shown a cytotoxic effect dependent on concentration and time; higher concentrations and longer exposure times will cause a steeper decline in the population of stromal keratocytes. Vancomycin showed a major initial cytotoxic effect, which was reverted over time; and imipenem appeared as a non-toxic compound for stromal cells. The eye drops with the highest irritating effect on the ocular surface were gentamicin and vancomycin. Those antibiotic eye drops prepared at the Hospital Pharmacy Departments included in this study were considered as compounds potentially cytotoxic for the ocular surface; this toxicity was dependent on the concentration used (AU)

El uso de reformulaciones de antibióticos parenterales en forma de colirios de composición o concentraciones no comercializadas, comúnmente denominados colirios antibióticos reforzados, es una práctica habitual en oftalmología a nivel hospitalario. El objetivo del presente trabajo ha consistido en evaluar la toxicidad ocular in vitro de los principales colirios antibióticos reforzados elaborados en los Servicios de Farmacia Hospitalaria. Hemos realizado un estudio experimental in vitro para evaluar la toxicidad de los colirios de gentamicina, amikacina, cefazolina, ceftazidima, vancomicina, colistimetato de sodio e imipenem-cilastatina en el que se ha evaluado su citotoxicidad y la irritación tisular aguda. Los ensayos celulares se realizan sobre queratocitos estromales humanos, mediante la utilización de un sistema biosensor de impedancia celular [(xCELLigence Real-Time System Cell Analyzer (RTCA)] y los ensayos de irritación ocular mediante el ensayo Hen´s Egg Test. Todos los colirios, excepto vancomicina e imipenem, han mostrado un efecto citotóxico de concentración y tiempo dependiente, siendo las concentraciones más altas y los tiempos más prolongados los que provocan un descenso más pronunciado en la población de queratocitos estromales. La vancomicina muestra un importante efecto citotóxico inicial que revierte con el transcurso del tiempo y el imipenem se muestra como un compuesto no tóxico para las células estromales. Los compuestos con mayor efecto irritante para la superficie ocular son la gentamicina y la vancomicina. Los colirios antiinfecciosos elaborados en los Servicios de Farmacia Hospitalaria estudiados se muestran como compuestos potencialmente citotóxicos para la superficie ocular, siendo esta toxicidad dependiente de la concentración utilizada (AU)

Evaluation of the in vitro ocular toxicity of the fortified antibiotic eye drops prepared at the Hospital Pharmacy Departments.

The use of parenteral antibiotic eye drop formulations with non-marketed compositions or concentrations, commonly called fortified antibiotic eye drops, is a common practice in Ophthalmology in the hospital setting. The aim of this study was to evaluate the in vitro ocular toxicity of the main fortified antibiotic eye drops prepared in the Hospital Pharmacy Departments. We have conducted an in vitro experimental study in order to test the toxicity of gentamicin, amikacin, cefazolin, ceftazidime, vancomycin, colistimethate sodium and imipenem-cilastatin eye drops; their cytotoxicity and acute tissue irritation have been evaluated. Cell-based assays were performed on human stromal keratocytes, using a cell-based impedance biosensor system [xCELLigence Real-Time System Cell Analyzer (RTCA)], and the Hen's Egg Test for the ocular irritation tests. All the eye drops, except for vancomycin and imipenem, have shown a cytotoxic effect dependent on concentration and time; higher concentrations and longer exposure times will cause a steeper decline in the population of stromal keratocytes. Vancomycin showed a major initial cytotoxic effect, which was reverted over time; and imipenem appeared as a non-toxic compound for stromal cells. The eye drops with the highest irritating effect on the ocular surface were gentamicin and vancomycin. Those antibiotic eye drops prepared at the Hospital Pharmacy Departments included in this study were considered as compounds potentially cytotoxic for the ocular surface; this toxicity was dependent on the concentration used.

El uso de reformulaciones de antibioticos parenterales en forma de colirios de composicion o concentraciones no comercializadas, comunmente denominados colirios antibioticos reforzados, es una practica habitual en oftalmologia a nivel hospitalario. El objetivo del presente trabajo ha consistido en evaluar la toxicidad ocular in vitro de los principales colirios antibioticos reforzados elaborados en los Servicios de Farmacia Hospitalaria. Hemos realizado un estudio experimental in vitro para evaluar la toxicidad de los colirios de gentamicina, amikacina, cefazolina, ceftazidima, vancomicina, colistimetato de sodio e imipenem- cilastatina en el que se ha evaluado su citotoxicidad y la irritacion tisular aguda. Los ensayos celulares se realizan sobre queratocitos estromales humanos, mediante la utilizacion de un sistema biosensor de impedancia celular [(xCELLigence Real- Time System Cell Analyzer (RTCA)] y los ensayos de irritacion ocular mediante el ensayo Hen/s Egg Test. Todos los colirios, excepto vancomicina e imipenem, han mostrado un efecto citotoxico de concentracion y tiempo dependiente, siendo las concentraciones mas altas y los tiempos mas prolongados los que provocan un descenso mas pronunciado en la poblacion de queratocitos estromales. La vancomicina muestra un importante efecto citotoxico inicial que revierte con el transcurso del tiempo y el imipenem se muestra como un compuesto no toxico para las celulas estromales. Los compuestos con mayor efecto irritante para la superficie ocular son la gentamicina y la vancomicina. Los colirios antiinfecciosos elaborados en los Servicios de Farmacia Hospitalaria estudiados se muestran como compuestos potencialmente citotoxicos para la superficie ocular, siendo esta toxicidad dependiente de la concentracion utilizada.

Ocular safety comparison of non-steroidal anti-inflammatory eye drops used in pseudophakic cystoid macular edema prevention.

Non-steroidal anti-inflammatory drug (NSAID) eye drops are widely used to treat ocular inflammatory conditions related to ophthalmic surgical procedures, such as pseudophakic cystoid macular edema, and they have been used for off-label treatments. The most commonly used NSAIDs are diclofenac and ketorolac and the new molecules bromfenac and nepafenac have also been used. We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. This study also included classic cell viability tests (WST-1(®) and AlamarBlue(®)), wound healing assay, Hen's Egg Test and an ex vivo histopathological assay. NSAIDs were shown to have important cytotoxicities and to retard the healing response. Furthermore, the new eye drops containing bromfenac and nepafenac were more cytotoxic than the more classical eye drops. Nevertheless, no immuno-histochemical changes or acute irritation processes were observed after the administration of any eye drops tested. Due to cytotoxicity and the total absence of discomfort and observable injuries after the administration of these drugs, significant corneal alterations, such as corneal melts, can develop without any previous warning signs of toxicity.

Detecting ultrasonographic hollowness in small choroidal melanocytic tumors using 10 MHz and 20 MHz ultrasonography: a comparative study.

BACKGROUND: The purpose of this work was to compare the detection of ultrasonographic hollowness (UH), as a risk sign for evolution from small choroidal melanocytic tumors (SCMT) to uveal melanoma (UM), between conventional ultrasonography (standardized 8 MHz ultrasonography and B-mode 10 MHz ultrasonography) and high-resolution 20 MHz ultrasonography. METHODS: Fifty SCMTs from 50 eyes were included in this work. In all cases, ultrasonographic studies were performed using: 8 MHz standardized A-mode, 10 MHz B-mode, and posterior pole 20 MHz B-mode. Comparison between the presence and the absence of UH were carried out between the ultrasonographic images. RESULTS: There were no statistically significant differences between the SCMT dimensions obtained using the 8-10 and 20 MHz techniques. UH was detected in 12 and 20 cases by means of ten and 20 MHz probes respectively. The difference between these proportions was statistically different from zero (McNemar test, p-value = 0.008). Cases without UH by 20 MHz have lower height values than cases with UH. However, these differences were not found by 10 MHz ultrasonography. By receiver operating characteristic (ROC) study, specificity was better by 20 MHz than 10 MHz ultrasonography when the value of tumor height as marker for UH was studied. CONCLUSIONS: UH is easier to detect by 20 MHz than by 10 MHz ultrasonography. This ultrasonographic sign appears to be correlated with the height of the tumor. Thus, we believe UH estimation by 20 MHz ultrasonography could be used as a significant predictive factor for SCMT growth.

Cyclodextrin-polysaccharide-based, in situ-gelled system for ocular antifungal delivery.

Fluconazole was studied with two different hydrophilic cyclodextrins (hydroxypropyl-ß-cyclodextrin (HPBCD) and sulfobutyl ether-ß-cyclodextrin (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole-HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural polysaccharides gellan gum and κ-carrageenan. This system showed good bioadhesive properties and effective control of fluconazole release.

Vasoproliferative tumors of ocular fundus: ultrasonographic characteristics.

The aim of this work is to describe ultrasonographic features in vasoproliferative tumors of ocular fundus (VPTOF). The charts of eight patients were retrospectively studied. Clinical data obtained by complete ophthalmologic examination and ultrasonographic findings were analyzed. Nodular masses affecting either the retina alone or the retina and the choroid were found. The surface contour of the tumor was regular in 5 and irregular in 3 cases. In dimensions, the mean (+/- SD) major base was 7.14 +/- 2.56 mm, minor base 6.74 +/- 2.48 mm, and height 2.38 +/- 1.26 mm. Internal structure was always solid and irregular, while reflectivity was mostly medium, and high in 6 eyes. Kappa angle was not present in any case. No signs of vascularity were detected. According to the results, it is suggested that ultrasonographic examination be performed along with ophthalmoscopy on differential diagnosis of VPTOF.

Ultrasonographic findings in circumscribed choroidal hemangioma after photodynamic therapy.

Circumscribed choroidal hemangioma (CCH) is a benign and relatively rare tumor located posteriorly to the equator. The most frequently associated clinical finding is an exudative retinal detachment (ERD). The aim of this work is to describe ultrasonographic findings in eyes diagnosed with CCH + ERD after photodynamic therapy (PDT). Five eyes of five patients diagnosed with CCH (2 men and 3 women; 3 right eyes and 2 left eyes; mean age 50.6 (range 42-63) years) were referred to the Unit of Ocular Oncology. All cases were selected for PDT since all of them showed a macula-off ERD and hence poor visual acuity. The PDT protocol consisted of verteporfin 6 mg/m2 body surface area and exposure to laser light dose at 689 nm at an intensity of 600 mW/cm2 (1 to 3 sessions depending on the persistence of ERD). Ultrasonographic examination was performed by use of the I3-ABD System (posterior segment 10 MHz B-scan and 8 MHz standardized diagnostic A-scan probes, Innovative Imaging Inc., Sacramento, CA, USA). Ultrasonographic findings recorded on the first examination were consistent with those previously described for CCH in the literature. Dimensions of the tumors were very similar in all cases. However, after PDT we detected significant reduction of the height of the tumor and increased reflectivity, without changes in internal structure. Moreover, we detected retinal reattachment in all cases and therefore a slight improvement in visual acuity. Significant changes in ultrasonographic findings can be found after PDT for CCH.