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Carreno-Galeano JT, Dohlman TH, Kim S, Yin J, Dana R. A Review of Ocular Graft-versus-Host Disease: Pathophysiology, Clinical Presentation and Management. Ocul Immunol Inflamm 2021;:1-10.Abstract
Graft-versus-host disease is a common complication following allogeneic hematopoetic stem cell transplantation that can affect multiple organ systems, including the eyes. Ocular GVHD (oGVHD) is characterized by a T cell-mediated immune response that leads to immune cell infiltration and inflammation of ocular structures, including the lacrimal glands, eyelids, cornea and conjunctiva. oGVHD has a significant negative impact on visual function and quality of life and successful management requires a multi-disciplinary approach with frequent monitoring. Here, we review the pathophysiology and clinical presentation of oGVHD, along with current therapeutic strategies based on our clinical experience and the reported literature.
Kaseke C, Park RJ, Singh NK, Koundakjian D, Bashirova A, Garcia Beltran WF, Takou Mbah OC, Ma J, Senjobe F, Urbach JM, Nathan A, Rossin EJ, Tano-Menka R, Khatri A, Piechocka-Trocha A, Waring MT, Birnbaum ME, Baker BM, Carrington M, Walker BD, Gaiha GD. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV. Cell Rep 2021;36(2):109378.Abstract
Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.
Chen Y, Yang Y-C, Tang L-Y, Ge Q-M, Shi W-Q, Su T, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma. Cancer Manag Res 2021;13:5835-5843.Abstract
Objective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. Results: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.
Elhusseiny AM, Bishop K, Staffa SJ, Zurakowski D, Hunter DG, Mantagos IS. Virtual reality prototype for binocular therapy in older children and adults with amblyopia. J AAPOS 2021;Abstract
PURPOSE: To evaluate the best-corrected visual acuity and stereoacuity gains in children >7 years of age and adults with unilateral amblyopia treated with a prototype virtual reality-based binocular amblyopia therapy. METHODS: In this randomized, double masked, cross-in clinical trial, patients at Boston Children's Hospital with unilateral anisometropic and/or strabismic amblyopia and history of prior amblyopia treatment failure were randomized to either a full-treatment group (8 weeks of binocular treatment using therapeutic software application in virtual reality headset) or a sham-crossover group (4 weeks of sham treatment followed by 4 weeks of binocular treatment). Amblyopic eye visual acuity and stereoacuity were evaluated at 4, 8, and 16 weeks' follow-up. RESULTS: The study cohort included 20 participants (10 females), with a median age of 9 years (range, 7-38 years). In the full-treatment group (11 patients), the mean amblyopic eye logMAR visual acuity at 16 weeks was 0.49 ± 0.26, compared with 0.47 ± 0.20 at baseline. In the sham-crossover group, it was 0.51 ± 0.18 at 16 weeks, compared with 0.53 ± 0.21 at baseline. Stereoacuity (log arcsec) was significantly improved, from 7.3 ± 2 at baseline to 6.6 ± 2.3 at 8 weeks (P < 0.001) and 6.7 ± 2.6 at 16 weeks (P < 0.001). No significant adverse events (diplopia, asthenopia, or worsening strabismus) were noted in either group. CONCLUSIONS: Although the virtual reality-based prototype for binocular amblyopia therapy did not significantly improve visual acuity in the amblyopic eyes of older children and adults, stereoacuity did significantly improve compared with baseline; improvements were clinically minute. However, larger studies are required to confirm the results.
Pundlik S, Baliutaviciute V, Moharrer M, Bowers AR, Luo G. Home-Use Evaluation of a Wearable Collision Warning Device for Individuals With Severe Vision Impairments: A Randomized Clinical Trial. JAMA Ophthalmol 2021;139(9):998-1005.Abstract
Importance: There is scant rigorous evidence about the real-world mobility benefit of electronic mobility aids. Objective: To evaluate the effect of a collision warning device on the number of contacts experienced by blind and visually impaired people in their daily mobility. Design, Setting, and Participants: In this double-masked randomized clinical trial, participants used a collision warning device during their daily mobility over a period of 4 weeks. A volunteer sample of 31 independently mobile individuals with severe visual impairments, including total blindness and peripheral visual field restrictions, who used a long cane or guide dog as their habitual mobility aid completed the study. The study was conducted from January 2018 to December 2019. Interventions: The device automatically detected collision hazards using a chest-mounted video camera. It randomly switched between 2 modes: active mode (intervention condition), where it provided alerts for detected collision threats via 2 vibrotactile wristbands, and silent mode (control condition), where the device still detected collisions but did not provide any warnings to the user. Scene videos along with the collision warning information were recorded by the device. Potential collisions detected by the device were reviewed and scored, including contacts with the hazards, by 2 independent reviewers. Participants and reviewers were masked to the device operation mode. Main Outcomes and Measures: Rate of contacts per 100 hazards per hour, compared between the 2 device modes within each participant. Modified intention-to-treat analysis was used. Results: Of the 31 included participants, 18 (58%) were male, and the median (range) age was 61 (25-73) years. A total of 19 participants (61%) had a visual acuity (VA) of light perception or worse, and 28 (90%) reported a long cane as their habitual mobility aid. The median (interquartile range) number of contacts was lower in the active mode compared with silent mode (9.3 [6.6-14.9] vs 13.8 [6.9-24.3]; difference, 4.5; 95% CI, 1.5-10.7; P < .001). Controlling for demographic characteristics, presence of VA better than light perception, and fall history, the rate of contacts significantly reduced in the active mode compared with the silent mode (β = 0.63; 95% CI, 0.54-0.73; P < .001). Conclusions and Relevance: In this study involving 31 visually impaired participants, the collision warnings were associated with a reduced rate of contacts with obstacles in daily mobility, indicating the potential of the device to augment habitual mobility aids. Trial Registration: ClinicalTrials.gov Identifier: NCT03057496.
Bouffard MA, M Mallery R, Liao YJ, Torun N. Variation in Evolving Optic Neuritis. J Neuroophthalmol 2021;41(4):476-479.Abstract
BACKGROUND: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. METHODS: Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. RESULTS: Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. CONCLUSIONS: This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.
Zhu R-L, Fang Y, Yu H-H, Chen DF, Yang L, Cho K-S. Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice. Neural Regen Res 2021;16(7):1317-1322.Abstract
Müller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2'-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.
Patel S, Yuan A, Pineda R. Acute Benign Paroxysmal Positional Vertigo After Endothelial Keratoplasty-A Unique Cause of Postoperative Nausea and Headache. Cornea 2021;40(7):926-929.Abstract
PURPOSE: To describe a case of new-onset benign paroxysmal positional vertigo (BPPV) after uncomplicated Descemet stripping automated endothelial keratoplasty. METHODS: Case report and review of literature. RESULTS: A 61-year-old woman with a history of steroid-induced glaucoma and penetrating keratoplasty for Fuchs endothelial dystrophy, and no history of BPPV or other vertigo, underwent Descemet stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure. On the third postoperative day, she developed acute spinning vertigo, nausea, and headache on sitting up after 3 days of strict supine positioning. Her ophthalmic examination was benign, with no evidence of a pupillary block, and she was diagnosed by an otologist with BPPV. Her symptoms resolved after 1 week without further intervention. CONCLUSIONS: BPPV is a benign but rare complication of nonotologic surgery and has not been previously reported with ophthalmic surgery. The overlap in symptomatology between BPPV and other serious and potentially vision-threatening causes of postoperative nausea and headache, such as pupillary block glaucoma, makes this a relevant etiology to consider in the spectrum of postendothelial keratoplasty complications.
Maleki A, Look-Why S, Asgari S, Manhapra A, Gomez S, Foster SC. Acquired Vitelliform-Like Lesion in Uveitis: A case-series. Ocul Immunol Inflamm 2021;:1-10.Abstract
PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.
Saddala MS, Lennikov A, Mukwaya A, Yang X, Tang S, Huang H. Data mining and network analysis reveals C-X-C chemokine receptor type 5 is involved in the pathophysiology of age-related macular degeneration. J Biomol Struct Dyn 2021;:1-10.Abstract
Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology model of CXCR5 and structural assessment analysis were performed. Data and text mining were then performed to identify AMD-related risk genes and their interaction with CXCR5 using statistical and mathematical algorithms. Sequence alignment and phylogenetic tree analysis revealed that human CXCR5 was highly similar (85.4839%) to the rabbit. The least similarity (33.871%) was found to be in zebrafish compared to the other species. The CXCR5 model structural assessment and secondary structure analysis exhibited an excellent model. Network analysis revealed that IL10, TNF, ICAM1, CXCL1, CXCL8, APP, TLR4, SELL, C3, IL17A and CCR2 were the most connected genes CXCR5. These findings suggest that CXCR5 signaling may regulate the biological function of RPE and modulate AMD pathophysiology via GPCR signaling and interacting with identified AMD risk genes. In summary, the data presented here provide novel and crucial insights into the molecular mechanisms of CXCR5 involvement in AMD.Communicated by Ramaswamy H. Sarma.
Yoon MK, Habib LA. Spheno-Orbital Dermoid Masquerading as Recurrent Orbital Abscess. Ophthalmic Plast Reconstr Surg 2021;37(6):e213-e215.Abstract
A 10-month-old girl presented with eyelid edema and erythema that did not improve with systemic antibiotics. Due to a lack of improvement, MRI was performed to avoid ionizing radiation from CT. An orbital abscess was recognized and drained. However, the abscess recurred 2 times. CT scan was performed and a tract in the sphenoid bone helped to diagnose a congenital dural sinus tract with dermoid. Definitive surgery was performed with neurosurgery to remove the entire tract including cutaneous connection. CT scan proved critical to diagnosis and should be considered in infants in select cases despite the concern for ionizing radiation in this vulnerable age group.
Elhusseiny AM, Jabroun M, Rajabi F, Gonzalez E, Alkharashi M. A novel variant in the TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. Eur J Ophthalmol 2021;:11206721211027415.Abstract
PURPOSE: To report a case of 16-month-old boy with a novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. OBSERVATION: A 16-month-old otherwise healthy boy was referred to Boston Children's Hospital for evaluation of strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, and limited left eye elevation in both adduction and abduction. Full cycloplegic hyperopic correction of +3.50 diopters (D) over both eyes was given to the patient. Over several months, refraction of the right eye showed progressive myopia (-6.00 D) with new onset iris heterochromia. Fundus examination showed there was a large area of chorioretinal atrophy with abrupt ending of the blood vessels; anterior to the ora serrata there were diffuse vitreous bands and veils that reached the lens anteriorly in direct contact with the lenticular opacity. A novel heterozygous nonsense likely pathogenic variant was identified in the TSPAN12 gene (NM_012338.3) c.315T>A (p.Cys105Ter) confirming the diagnosis of FEVR. CONCLUSION AND IMPORTANCE: Asymmetric FEVR rarely present with unilateral axial myopia however association with acquired heterochromia and cataract has never been reported. We report a case of FEVR caused by a novel TSPAN12 likely pathogenic nonsense variant presenting as unilateral progressive myopia, acquired heterochromia, and pediatric cataract.
Yu K, Guo Y, Ge Q-M, Su T, Shi W-Q, Zhang L-J, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study. Sci Rep 2021;11(1):12943.Abstract
This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P < 0.0001). The ReHo values of the middle frontal gyrus and dorsolateral superior frontal gyrus were correlated to disease duration (P < 0.05). Symptoms of ocular surface injury in DE patients are associated with dysfunction in specific brain regions, which may underlie the cognitive impairment, psychiatric symptoms, and depressive mood observed in DE patients. The decreased ReHo values of some brain gyri in this study may provide a reference for clinical diagnosis and determination of treatment efficacy.

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