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Prichula J, Van Tyne D, Schwartzman J, Sant'Anna FH, Pereira RI, da Cunha GR, Tavares M, Lebreton F, Frazzon J, d'Azevedo PA, Seixas A, Frazzon APG, Gilmore MS. Enterococci from Wild Magellanic Penguins (Spheniscus magellanicus) as an Indicator of Marine Ecosystem Health and Human Impact. Appl Environ Microbiol 2020;86(19)Abstract
Enterococci are commensals that proliferated as animals crawled ashore hundreds of millions of years ago. They are also leading causes of multidrug-resistant hospital-acquired infections. While most studies are driven by clinical interest, comparatively little is known about enterococci in the wild or the effect of human activity on them. Pharmaceutical pollution and runoff from other human activities are encroaching widely into natural habitats. To assess their reach into remote habitats, we investigated the identity, genetic relatedness, and presence of specific traits among 172 enterococcal isolates from wild Magellanic penguins. Four enterococcal species, 18 lineage groups, and different colonization patterns were identified. One lineage, sequence type 475 (ST475), was isolated from three different penguins, making it of special interest. Its genome was compared to those of other sequence types (ST116 and ST242) recovered from Magellanic penguins, as well as to an existing phylogeny of isolated from diverse origins over the past 100 years. No penguin-derived strains were closely related to dominant clinical lineages. Most possessed intact CRISPR defenses, few mobile elements, and antibiotic resistances limited to those intrinsic to the species and lacked pathogenic features conveyed by mobile elements. Interestingly, plasmids were identified in penguin isolates that also had been reported for other marine mammals. Enterococci isolated from penguins showed limited anthropogenic impact, indicating that they are likely representative of those naturally circulating in the ecosystem inhabited by the penguins. These findings establish an important baseline for detecting the encroachment of human activity into remote planetary environments. Enterococci are host-associated microbes that have an unusually broad range, from the built hospital environment to the guts of insects and other animals in remote locations. Despite their occurrence in the guts of animals for hundreds of millions of years, we know little about the properties that confer this range or how anthropogenic activities may be introducing new selective forces. Magellanic penguins live at the periphery of human habitation. It was of interest to examine enterococci from these animals for the presence of antibiotic resistance and other markers reflective of anthropogenic selection. Diverse enterococcal lineages found discount the existence of a single well-adapted intrinsic penguin-specific species. Instead, they appear to be influenced by a carnivorous lifestyle and enterococci present in the coastal sea life consumed. These results indicate that currently, the penguin habitat remains relatively free of pollutants that select for adaptation to human-derived stressors.
Kempen JH, Abashawl A, Suga HK, Nigussie Difabachew M, Kempen CJ, Tesfaye Debele M, Menkir AA, Assefa MT, Asfaw EH, Habtegabriel LB, Sitotaw Addisie Y, Nilles EJ, Longenecker JC. SARS-CoV-2 Serosurvey in Addis Ababa, Ethiopia. Am J Trop Med Hyg 2020;103(5):2022-2023.Abstract
In a serosurvey of asymptomatic people from the general population recruited from a clinical laboratory in May 2020 in Addis Ababa, Ethiopia, three of 99 persons tested positive for SARS-CoV-2 IgG (3.0%, 95% binomial exact confidence interval: 0.6-8.6%). Taking into account pretest probability and the sampling scheme, the range of plausible population prevalence values was approximately 1.0-8.4%. These results suggest that a larger number of people have been infected than the counts detected by surveillance to date; nevertheless, the results suggest the large majority of the general population in Addis Ababa currently is susceptible to COVID-19.
Yousefi S, Elze T, Pasquale LR, Saeedi O, Wang M, Shen LQ, Wellik SR, De Moraes CG, Myers JS, Boland MV. Monitoring Glaucomatous Functional Loss Using an Artificial Intelligence-Enabled Dashboard. Ophthalmology 2020;127(9):1170-1178.Abstract
PURPOSE: To develop an artificial intelligence (AI) dashboard for monitoring glaucomatous functional loss. DESIGN: Retrospective, cross-sectional, longitudinal cohort study. PARTICIPANTS: Of 31 591 visual fields (VFs) on 8077 subjects, 13 231 VFs from the most recent visit of each patient were included to develop the AI dashboard. Longitudinal VFs from 287 eyes with glaucoma were used to validate the models. METHOD: We entered VF data from the most recent visit of glaucomatous and nonglaucomatous patients into a "pipeline" that included principal component analysis (PCA), manifold learning, and unsupervised clustering to identify eyes with similar global, hemifield, and local patterns of VF loss. We visualized the results on a map, which we refer to as an "AI-enabled glaucoma dashboard." We used density-based clustering and the VF decomposition method called "archetypal analysis" to annotate the dashboard. Finally, we used 2 separate benchmark datasets-one representing "likely nonprogression" and the other representing "likely progression"-to validate the dashboard and assess its ability to portray functional change over time in glaucoma. MAIN OUTCOME MEASURES: The severity and extent of functional loss and characteristic patterns of VF loss in patients with glaucoma. RESULTS: After building the dashboard, we identified 32 nonoverlapping clusters. Each cluster on the dashboard corresponded to a particular global functional severity, an extent of VF loss into different hemifields, and characteristic local patterns of VF loss. By using 2 independent benchmark datasets and a definition of stability as trajectories not passing through over 2 clusters in a left or downward direction, the specificity for detecting "likely nonprogression" was 94% and the sensitivity for detecting "likely progression" was 77%. CONCLUSIONS: The AI-enabled glaucoma dashboard, developed using a large VF dataset containing a broad spectrum of visual deficit types, has the potential to provide clinicians with a user-friendly tool for determination of the severity of glaucomatous vision deficit, the spatial extent of the damage, and a means for monitoring the disease progression.
Milman T, Jakobiec FA, Lally SE, Shields JA, Shields CL, Eagle RC. Lacrimal Gland Hamartoma (Formerly Termed Dacryoadenoma). Am J Ophthalmol 2020;217:189-197.Abstract
PURPOSE: Since the original description of "dacryadenoma" by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. DESIGN: Retrospective observational case series. METHODS: Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. RESULTS: Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%). CONCLUSION: Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.
Jamali A, Hu K, Sendra VG, Blanco T, Lopez MJ, Ortiz G, Qazi Y, Zheng L, Turhan A, Harris DL, Hamrah P. Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis. Cell Rep 2020;32(9):108099.Abstract
The presence and potential functions of resident plasmacytoid dendritic cells (pDCs) in peripheral tissues is unclear. We report that pDCs constitutively populate naïve corneas and are increased during sterile injuries or acute herpes simplex virus 1 (HSV-1) keratitis. Their local depletion leads to severe clinical disease, nerve loss, viral dissemination to the trigeminal ganglion and draining lymph nodes, and mortality, while their local adoptive transfer limits disease. pDCs are the main source of HSV-1-induced IFN-α in the corneal stroma through TLR9, and they prevent re-programming of regulatory T cells (Tregs) to effector ex-Tregs. Clinical signs of infection are observed in pDC-depleted corneas, but not in pDC-sufficient corneas, following low-dose HSV-1 inoculation, suggesting their critical role in corneal antiviral immunity. Our findings demonstrate a vital role for corneal pDCs in the control of local viral infections.
Dutta Majumder P, Marchese A, Pichi F, Garg I, Agarwal A. An update on autoimmune retinopathy. Indian J Ophthalmol 2020;68(9):1829-1837.Abstract
Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.
Yu G, Seto BK, Yamada K, Zeng K, Arroyo JG. Combined Pneumatic and Enzymatic Vitreolysis for Severe Cases of Vitreomacular Traction. Retin Cases Brief Rep 2020;Abstract
PURPOSE: To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT). METHODS: We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis (PV) who then received an additional ocriplasmin injection while their gas bubble from PV was still present between February 2015 to February 2019. VMT release was confirmed using spectral domain optical coherence tomography (OCT). RESULTS: Four out of 5 patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to PV, patient characteristics included broad adhesion diameter (>1500 μm, n=1), presence of epiretinal membrane (n=2), age > 65 years (n=4), and pseudophakia (n=1). Visual acuity (VA) improved by 3 or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an ETDRS chart but not in those whose vision was already fairly good (i.e. VA > 20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes. CONCLUSION: Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.
Elhusseiny AM, Gore C, Sadiq MAA, Dagi LR, Kazlas M, Hunter DG. Self-grading effect of inferior oblique myectomy and recession. J AAPOS 2020;Abstract
PURPOSE: To evaluate the outcomes of inferior oblique (IO) weakening surgery, whether recession or myectomy, and to assess the dose-response relationship and correlation with angle of preoperative hypertropia. METHODS: The medical records of all patients with vertical deviation in primary gaze who underwent unilateral IO-weakening surgery, either recession or myectomy, at Boston Children's Hospital over an 8-year period with a minimum postoperative follow-up of 1 month were reviewed retrospectively. Outcome measures were effect of IO weakening surgery on vertical deviation in primary gaze and its correlation with the preoperative angle of hyperdeviation. Secondary outcomes included resolution of abnormal head posture, reduction of ocular torsion, and postoperative under- and overcorrection RESULTS: A total of 94 patients were identified (mean age at surgery, 29.3 ± 19.8 years; range, 1-69). The mean postoperative follow-up period was 17.2 ± 15 months. IO recession was performed in 30 patients; IO myectomy, in 64. Surgical success in primary position was achieved in 72 patients (77%), with resolution of anomalous preoperative head posture in 93%. The mean effect on alignment in primary position was 11.3 ± 6.8. The response to IO-weakening surgery was strongly correlated with the preoperative hyperdeviation for both recession (R = 0.53) and myectomy (R = 0.87). CONCLUSIONS: As with other types of strabismus surgery, IO weakening has a "self-grading" contribution, in which the surgical effect strongly correlates with the magnitude of preoperative deviation. A large range of vertical misalignment can be corrected with the same surgical approach.
Narayanan D, Wallstrom G, Rodriguez J, Welch D, Chapin M, Arrigg P, Patil R, Abelson M. Early Ophthalmic Changes in Macula Does Not Correlate with Visual Function. Clin Ophthalmol 2020;14:2571-2576.Abstract
Purpose: Early detection and treatment of age-related macular degeneration require a clear understanding of the early progress of the disease. The purpose of this study was to investigate whether minimal macular ophthalmoscopic changes corresponded to changes in visual function. Methods: Color macular photos from a group of older subjects who were classified as grade 0 on AREDS simplified grading were further evaluated by a retinal specialist using 5x magnification for possible minimal macular anomalies. Group 0-A ( = 15) were defined as subjects with no visible macular anomalies while Group 0-B ( = 19) comprised subjects for whom minimal macular mottling, pigment changes or very small drusen (< 63 µm) were observed in the study eye. All subjects had best VA of 20/25 or better and had no evidence of other retinal diseases in the study eye. All subjects underwent a series of visual function tests such as standard ETDRS VA, low luminance ETDRS VA, Pelli-Robson contrast sensitivity, variable contrast flicker (VCF) sensitivity, and reading speed (words per minute, wpm) using both MNRead and low luminance reading on a tablet. Results: There was no significant difference between the mean age between the two groups (74.8 ± 5.2 years for 0-A vs 74.5 ± 4.4 for 0-B, = 0.82). None of the visual function tests identified any significant difference between the two groups. Mean ETDRS VA was 0.0 ± 0.11 for 0-A subjects and 0.08 ± 0.12 for 0-B ( = 0.063). Mean Pelli-Robson log contrast sensitivity was 1.75 ± 0.29 for 0-A and 1.78 ± 0.17 for the 0-B group ( = 0.73). VCF threshold was 0.47 ± 0.25 for 0-A and 0.43 ± 0.22 for 0-B ( = 0.64). Reading speed using MNRead was 214 ± 47.4 wpm for 0-A and 210 ± 64.7 for 0-B ( = 0.85). Low luminance tablet reading speed was 137 ± 71.8 wpm for 0-A and 151 ± 39.4 (0-B) ( = 0.49). Conclusion: A panel of psychophysical tests did not demonstrate significant differences between subjects with and without minimal macular changes.
VanderVeen DK, Drews-Botsch CD, Nizam A, Bothun ED, Wilson LB, Wilson EM, Lambert SR, Lambert SR. Outcomes of Secondary Intraocular Lens Implantation in the Infant Aphakia Treatment Study. J Cataract Refract Surg 2020;Abstract
PURPOSE: To report outcomes of secondary intraocular lens (IOL) implantation in the Infant Aphakia Treatment Study (IATS) SETTING:: Multicenter clinical practice DESIGN:: Secondary analysis of patients enrolled in a randomized clinical trial METHODS:: Details regarding all secondary IOL surgeries conducted in children enrolled in the IATS were compiled. We evaluated visual outcomes, refractive outcomes, and adverse events at age 10 ½ years. Comparisons were made to eyes that remained aphakic and to eyes randomized to primary IOL placement. RESULTS: 55/57 patients randomized to aphakia with contact lens correction were seen for the 10 ½ year study visit; 24/55 eyes (44%) had secondary IOL surgery. Median age at IOL surgery was 5.4 years (range 1.7 to 10.3 years). Mean absolute prediction error was 1.0 ± 0.7D. At age 10 ½ years, the median log MAR VA was 0.9 (range 0.2 to 1.7), similar to VA in the 31 eyes still aphakic (0.8, range 0.1 to 2.9); the number of eyes with stable or improved VA scores between the 4 ½ and 10 ½ year study visits was also similar (78% secondary IOL eyes, 84% aphakic eyes). For eyes undergoing IOL implantation after the 4.5 year study visit (n=22), the mean refraction at age 10 ½ years was -3.2 ±2.7D (range -9.9D to 1.1D), compared to -5.5 ±6.6 D (n=53, range -26.5 to 3.0D) in eyes with primary IOL (p=0.03). CONCLUSIONS: Delayed IOL implantation allows a more predictable refractive outcome at age 10 ½ years, though the range of refractive error is still large.
Daniel S, Renwick M, Chau VQ, Datta S, Maddineni P, Zode G, Wade EM, Robertson SP, Petroll MW, Hulleman JD. Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity. J Mol Med (Berl) 2020;98(11):1639-1656.Abstract
Fibulin-3 (F3) is an extracellular matrix glycoprotein found in basement membranes across the body. An autosomal dominant R345W mutation in F3 causes a macular dystrophy resembling dry age-related macular degeneration (AMD), whereas genetic removal of wild-type (WT) F3 protects mice from sub-retinal pigment epithelium (RPE) deposit formation. These observations suggest that F3 is a protein which can regulate pathogenic sub-RPE deposit formation in the eye. Yet the precise role of WT F3 within the eye is still largely unknown. We found that F3 is expressed throughout the mouse eye (cornea, trabecular meshwork (TM) ring, neural retina, RPE/choroid, and optic nerve). We next performed a thorough structural and functional characterization of each of these tissues in WT and homozygous (F3) knockout mice. The corneal stroma in F3 mice progressively thins beginning at 2 months, and the development of corneal opacity and vascularization starts at 9 months, which worsens with age. However, in all other tissues (TM, neural retina, RPE, and optic nerve), gross structural anatomy and functionality were similar across WT and F3 mice when evaluated using SD-OCT, histological analyses, electron microscopy, scotopic electroretinogram, optokinetic response, and axonal anterograde transport. The lack of noticeable retinal abnormalities in F3 mice was confirmed in a human patient with biallelic loss-of-function mutations in F3. These data suggest that (i) F3 is important for maintaining the structural integrity of the cornea, (ii) absence of F3 does not affect the structure or function of any other ocular tissue in which it is expressed, and (iii) targeted silencing of F3 in the retina and/or RPE will likely be well-tolerated, serving as a safe therapeutic strategy for reducing sub-RPE deposit formation in disease. KEY MESSAGES: • Fibulins are expressed throughout the body at varying levels. • Fibulin-3 has a tissue-specific pattern of expression within the eye. • Lack of fibulin-3 leads to structural deformities in the cornea. • The retina and RPE remain structurally and functionally healthy in the absence of fibulin-3 in both mice and humans.

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