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Taketani Y, Marmalidou A, Dohlman TH, Singh RB, Amouzegar A, Chauhan SK, Chen Y, Dana R. Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor. Am J Pathol 2020;190(9):1859-1866.Abstract
Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.
Hayashi T, Yasutsugu I, Shimizu T, Kuroki T, Kobashigawa Y, Iijima Y, Yuda K. Pars plana vitrectomy combined with penetrating keratoplasty and transscleral-sutured intraocular lens implantation in complex eyes: a case series. BMC Ophthalmol 2020;20(1):369.Abstract
BACKGROUND: The aim of this study was to evaluate the clinical outcomes of pars plana vitrectomy (PPV) combined with penetrating keratoplasty (PKP) and transscleral-sutured intraocular lens (IOL) implantation (IOL-suture) in complex eyes. METHODS: In this prospective, consecutive interventional case series, patients who underwent PKP combined with PPV and IOL implantation from July 2014 to March 2018 at Yokohama Minami Kyosai Hospital were enrolled. The postoperative best corrected visual acuity (BCVA) (converted to logarithm of the minimal angle of resolution [logMAR] units), intraocular pressure (IOP, mmHg), endothelial cell density (ECD, cells/mm), graft survival, complications, astigmatism, and spherical equivalent (dioptres [D]) were evaluated. RESULTS: This study included 11 eyes of 11 patients (three females and eight males; mean age, 61.8 ± 13.9 years) with an injury (n = 6) or bullous keratopathy (n = 5). The BCVA significantly improved from 1.50 ± 0.66 logMAR preoperatively to 0.78 ± 0.59 logMAR (p < 0.001) postoperatively. The baseline ECD significantly decreased from 2396 ± 238 cells/mm preoperatively to 1132 ± 323 cells/mm (p < 0.001) postoperatively. Despite two rejection episodes, graft survival rates were 100%. The mean follow-up period was 38.0 ± 20.5 months. Two patients required combined glaucoma surgery, and three patients underwent subsequent glaucoma surgery. Postoperative astigmatism and spherical equivalent were 3.9 ± 3.2 D and 0.29 ± 2.18 D, respectively. CONCLUSION: The combination of PKP, PPV, and IOL-suture implantation could be a safe and effective approach for eyes requiring anterior segment surgery; however, these eyes are associated with a higher incidence of glaucoma surgery.
Harris JM, Han IC, Sachdeva MM, Zhang AY, Zebardast N. Post-operative intracranial gas migration with optic nerve infiltration and atrophy following retinal detachment repair. Am J Ophthalmol Case Rep 2020;20:100920.Abstract
Purpose: To report a patient with post-operative gas migration into the optic nerve and lateral ventricles after retinal detachment repair. Observations: A 78-year-old pseudophakic man developed a temporal visual field cut in his non-operative, right eye 3 weeks after repair of a recurrent, shallow, macula-involving retinal detachment with perfluoropropane intraocular gas in the left eye. Visual acuity in the right eye measured 20/40, and static perimetry demonstrated temporal visual field loss that respected the vertical midline. Dilated fundus examination of the right eye was unrevealing for any retinal cause, raising suspicion for an intracranial etiology. An urgent CT scan of the brain demonstrated gas in all segments of the left optic nerve and lateral ventricles, consistent with intracranial gas migration along the optic nerve. Given the absence of systemic neurologic symptoms, cautious observation was advised on consultation with neuroradiology and neurosurgery, and follow-up CT scan 1 week later showed resolution of the intracranial gas. By 10-weeks post-operatively, vision returned to 20/20 in the right eye with persistent temporal field loss, and the left eye was hand motions (20/70 pre-operatively) with evidence of optic nerve atrophy and severe cupping. Conclusions: Intracranial gas migration is a rare complication of retinaldetachment repair with intraocular gas and may occur in the setting of structural defects of the optic nerve and high post-operative intraocular pressure. Clinicians should be alert to this rare but serious complication, which can cause neurologic symptoms and result in vision loss in both the operative and non-operative eyes.
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.
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.

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