Minocycline-induced blue sclera and skin hyperpigmentation

A 73-year-old man presented to the emergency department with lethargy and influenza-like symptoms. Incidentally, prominent blue sclera and blue-grey skin discolouration to the periorbital skin, pinnae, neck, upper and lower limbs, hands, feet, fingernails and toenails were noted. His general practitioner (GP) had previously ceased amiodarone, believing it to be the causative agent. A literature search confirms the side effects were likely due to minocycline, which the patient had been taking for 10 years. Long-term minocycline use is associated with scleral and skin hyperpigmentation, with no apparent adverse effect on ocular structure or function. The pigmentation may reverse with cessation of minocycline, or it may be permanent. Amiodarone may also cause skin hyperpigmentation, but scleral pigmentation is not a known association. This case report explores the side effect profiles of these two drugs, and highlights the potential for confusion regarding causative agents when used concurrently.

DABCO-Customized Nanoemulsions: Characterization, Cell Viability and Genotoxicity in Retinal Pigmented Epithelium and Microglia Cells

Quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and of quinuclidine surfactants were used to develop oil-in-water nanoemulsions with the purpose of selecting the best long-term stable nanoemulsion for the ocular administration of triamcinolone acetonide (TA). The combination of the best physicochemical properties (i.e., mean droplet size, polydispersity index, zeta potential, osmolality, viscoelastic properties, surface tension) was considered, together with the cell viability assays in ARPE-19 and HMC3 cell lines. Surfactants with cationic properties have been used to tailor the nanoemulsions’ surface for site-specific delivery of drugs to the ocular structure for the delivery of TA. They are tailored for the eye because they have cationic properties that interact with the anionic surface of the eye.

Intra-population differences of apolipoproteins in the aqueous humor

Background Evidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH’s small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG). Methods AH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure. Results A total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG. Conclusions The intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.

Multi-view convolutional neural networks for automated ocular structure and tumor segmentation in retinoblastoma

In retinoblastoma, accurate segmentation of ocular structure and tumor tissue is important when working towards personalized treatment. This retrospective study serves to evaluate the performance of multi-view convolutional neural networks (MV-CNNs) for automated eye and tumor segmentation on MRI in retinoblastoma patients. Forty retinoblastoma and 20 healthy-eyes from 30 patients were included in a train/test (N = 29 retinoblastoma-, 17 healthy-eyes) and independent validation (N = 11 retinoblastoma-, 3 healthy-eyes) set. Imaging was done using 3.0 T Fast Imaging Employing Steady-state Acquisition (FIESTA), T2-weighted and contrast-enhanced T1-weighted sequences. Sclera, vitreous humour, lens, retinal detachment and tumor were manually delineated on FIESTA images to serve as a reference standard. Volumetric and spatial performance were assessed by calculating intra-class correlation (ICC) and dice similarity coefficient (DSC). Additionally, the effects of multi-scale, sequences and data augmentation were explored. Optimal performance was obtained by using a three-level pyramid MV-CNN with FIESTA, T2 and T1c sequences and data augmentation. Eye and tumor volumetric ICC were 0.997 and 0.996, respectively. Median [Interquartile range] DSC for eye, sclera, vitreous, lens, retinal detachment and tumor were 0.965 [0.950–0.975], 0.847 [0.782–0.893], 0.975 [0.930–0.986], 0.909 [0.847–0.951], 0.828 [0.458–0.962] and 0.914 [0.852–0.958], respectively. MV-CNN can be used to obtain accurate ocular structure and tumor segmentations in retinoblastoma.

Ocular Findings and Visual Function in Children Examined during the Zika Health Brigade in the US Virgin Islands, March 2018

Among children born with laboratory-confirmed Zika virus (ZIKV) infection, visual impairment (VI) can occur despite normal ocular structure. The objective of this report is to describe ocular findings and visual function among children examined during the Department of Health Zika Health Brigade (ZHB) in the United States Virgin Islands in March 2018. This analysis is based on a retrospective chart review of children eligible to participate in the ZHB (i.e., part of the US Zika Pregnancy and Infant Registry) and who were examined by ophthalmologists. Eighty-eight children attended the ZHB. This report includes 81 children [48 (59.3%) males] whose charts were located [average gestational age = 37.6 weeks (range: 27.6–41.3) and average adjusted age at examination = 9.1 months (range: 0.9–21.9)]. Of those examined, 5/81 (6.2%) had microcephaly at birth, 2/81 (2.5%) had a structural eye abnormality, and 19/72 (26.4%) had VI. Among children with normal ocular structure and neurologic examination, 13/51 (25.5%) had VI. Despite a low incidence of abnormal ocular structure and microcephaly, about a quarter of children examined had VI. Our findings emphasize that ophthalmological examinations should be performed in all children with suspicion for antenatal ZIKV infection, even children with normal ocular structure and neurologic examination.

Antimicrobial Resistance and Biofilm Formation by Staphylococcus aureus Isolated From Ocular Infections

Background: Untreated staphylococcal ocular infections may cause injuries in the ocular structure and lead to visual impairments, lesions in the anatomical ocular surface, and blindness. The aim of the study was to describe the characteristic of 90 Staphylococcus aureus (SA) strains from hospital and community treated ocular infections with a special emphasis on ability of biofilm formation and drug resistance. The biofilm formation was carried out using the Congo red agar (CRA) method applying Congo red dye. Studies have demonstrated that the CRA method is simple, fast, and repeatable and that modifications of some components can easily increase its accuracy. Methods: Biofilm formation was examined by the method with CRA test. On CRA, slime-producing strains formed black colonies, whereas nonproducing strains developed red colonies in 6 kinds of colors, from very red to very black: very red, red, burgundy, almost black, black, and very black. Antimicrobial susceptibility testing was performed by disc diffusion or the E-test method according to the current guidelines of the EUCAST. The MRSA, and MLSB phenotypes were detected. Polymerase chain reaction (PCR) was used to detect the mecA, and mupA genes. Erythromycin resistance genes (ermA, ermB, ermC, and msr) were detected by multiplex PCR. Results: A positive result of the CRA test was accomplished in 66.2% cases; significantly more often in hospital strains (73.4% vs 45.4%; OR, 3.3; 55% CI, 1.2–9.3). Moreover, 73.4% isolates were fully susceptible. In hospitalized patients, the level of resistance to at least 1 antimicrobial category has been identified as 40.9%, and this rate was 27.2% in outpatients. Among the tested strains, 5 (6.0%) had the resistance phenotype MRSA and 22 (26.5%) the resistance phenotype MLSB; 4 strains manifested both mechanisms; erythromycin resistance was 25.3% in those resistant to fluoroquinolones. Resistance to fluoroquinolones was 5 times more often found in ambulatory patients. All of the tested isolates were vancomycin sensitive. Conclusions: Biofilm formation is an important risk factor for developmental staphylococcal hospital-acquired ocular infections. Our results prove that hospital strains have demonstrated much greater biofilm-forming ability than nonhospital strains. Studies indicate the high efficacy of chloramphenicol and fluoroquinolones treatments, as well as the need to implement new solutions due to the aforementioned bacteria’s high resistance to neomycin and anatomic barriers difficulties.Disclosures: NoneFunding: None

An Assay System to Evaluate Riboflavin/UV-A Corneal Phototherapy Efficacy in a Porcine Corneal Organ Culture Model

The purpose of this study was to investigate the response of porcine corneal organ cultures to riboflavin/UV-A phototherapy in the injury healing of induced lesions. A porcine corneal organ culture model was established. Corneal alterations in the stroma were evaluated using an assay system, based on an automated image analysis method able to (i) localize the holes and gaps within the stroma and (ii) measure the brightness values in these patches. The analysis has been performed by dividing the corneal section in 24 regions of interest (ROIs) and integrating the data analysis with a “multi-aspect approach.” Three group of corneas were analyzed: healthy, injured, and injured-and-treated. Our study revealed a significant effect of the riboflavin/UV-A phototherapy in the injury healing of porcine corneas after induced lesions. The injured corneas had significant differences of brightness values in comparison to treated (p < 0.00) and healthy (p < 0.001) corneas, whereas the treated and healthy corneas showed no significant difference (p = 0.995). Riboflavin/UV-A phototherapy shows a significant effect in restoring the brightness values of damaged corneas to the values of healthy corneas, suggesting treatment restores the injury healing of corneas after lesions. Our assay system may be compared to clinical diagnostic methods, such as optical coherence tomography (OCT) imaging, for in vivo damaged ocular structure investigations.