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Seminario-Vidal L, Kroshinsky D, Malachowski SJ, Sun J, Markova A, Beachkofsky TM, Kaffenberger BH, Ergen EN, Mauskar M, Bridges A, Calhoun C, Cardones AR, Chen ST, Chodosh J, Cotliar J, Davis MDP, DeNiro KL, Dominguez AR, Eljure-Téllez J, Femia A, Fox LP, Guda A, Mitchell C, Mostaghimi A, Ortega-Loayza AG, Owen C, Pasieka H, Rahnama-Moghadam S, Saeed HN, Saunderson RB, Shanbhag S, Sharon VR, Strowd L, Venkatesh S, Wanat KA, Wetter DA, Worswick S, Micheletti RG. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol 2020;82(6):1553-1567.Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.
Singh RB, Ichhpujani P, Thakur S, Jindal S. Promising therapeutic drug delivery systems for glaucoma: a comprehensive review. Ther Adv Ophthalmol 2020;12:2515841420905740.Abstract
The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.
Shanbhag SS, Hall L, Chodosh J, Saeed HN. Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2020;18(3):517-522.Abstract
PURPOSE: To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera® device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up ≥ 3 months after discharge were included. RESULTS: Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was ≥20/40 in 87% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78% of eyes (43/55) and 58% of eyes (32/55) respectively. CONCLUSIONS: Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM.
Enayati S, Chang K, Achour H, Cho K-S, Xu F, Guo S, Z Enayati K, Xie J, Zhao E, Turunen T, Sehic A, Lu L, Utheim TP, Chen DF. Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential. Cells 2020;9(3)Abstract
Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as (cone-rod homeobox) and , as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 × 10 ( = 1.78 × 10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.
Busch C, Okada M, Zur D, Fraser-Bell S, Rodríguez-Valdés PJ, Cebeci Z, Lupidi M, Fung AT, Gabrielle P-H, Giancipoli E, Chaikitmongkol V, Laíns I, Santos AR, Kunavisarut P, Sala-Puigdollers A, Chhablani J, Ozimek M, Hilely A, Degenhardt V, Loewenstein A, Iglicki M, Rehak M, Rehak M. Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity. Acta Ophthalmol 2020;98(7):e801-e806.Abstract
PURPOSE: To investigate clinical baseline characteristics and optical coherence tomography biomarkers predicting visual loss during observation in eyes with diabetic macular oedema (DMO) and good baseline visual acuity (VA). METHODS: A sub-analysis of a 12-month, retrospective study, including patients with baseline VA ≤0.1 logMAR (≥20/25 Snellen) and centre-involving DMO. The primary outcome measure was the correlation between baseline characteristics and VA loss ≥10 letters during follow-up. RESULTS: A total of 249 eyes were included in the initial study, of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment at baseline. Visual acuity (VA) loss ≥10 letters occurred in 21.8% (observed cohort) and in 24.3% (treated cohort), respectively. Within observed eyes, presence of hyperreflective foci [HRF; odds ratio (OR): 3.18, p = 0.046], and disorganization of inner retina layers (DRIL; OR: 2.71, p = 0.026) were associated with a higher risk of VA loss ≥10 letters. In observed eyes with a combined presence of HRF, DRIL and ellipsoid zone (EZ) disruption, the risk of VA loss was further increased (OR: 3.86, p = 0.034). In eyes with combined presence of DRIL, HRF and EZ disruption, risk of VA loss was 46.7% (7/15 eyes) in the observed cohort, and 26.3% (5/19 eyes) in the treated cohort (p = 0.26). CONCLUSION: Patients with DMO and good baseline VA, managed by observation, are of increased risk for VA loss if DRIL, HRF and EZ disruption are present at baseline. Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss at 12 months.
Anesi SD, Eggenschwiler L, Ferrara M, Artornsombudh P, Walsh M, Foster SC. Reliability of Conjunctival Biopsy for Diagnosis of Ocular Mucous Membrane Pemphigoid: Redetermination of the Standard for Diagnosis and Outcomes of Previously Biopsy-Negative Patients. Ocul Immunol Inflamm 2020;:1-8.Abstract
: To demonstrate the reliability of conjunctival biopsy analyzed by direct immunofluorescence (DIF) and supplemented with avidin-biotin complex immunoperoxidase (ABC) in diagnosing oMMP, and report therapy response in biopsy-positive patients, particularly when previously biopsy-negative elsewhere.: Retrospective outcomes review of 136 consecutive patients after conjunctival biopsy for suspected oMMP.: Among 136 patients, 66% were diagnosed with oMMP by DIF and 13% via supplemental ABC immunoperoxidase. Sensitivity increased from 79.6% with DIF to 95.6% with supplemental ABC. Among 57 biopsy-positive patients, 77% were in remission at 1-year follow-up and 88% after 2 years. Of 34 previous biopsy-negative but now biopsy-positive patients with a 2-year follow-up, 91% achieved remission, including all 16 diagnosed via DIF and ABC.: Conjunctival biopsy analyzed by histopathology and DIF supplemented by ABC has high reliability for diagnosing oMMP and is a useful tool to use before starting long-term immunomodulatory therapy in a patient with suspected oMMP.
Ashraf M, Shokrollahi S, Salongcay RP, Aiello LP, Silva PS. Diabetic retinopathy and ultrawide field imaging. Semin Ophthalmol 2020;35(1):56-65.Abstract
The introduction of ultrawide field imaging has allowed the visualization of approximately 82% of the total retinal area compared to only 30% using 7-standard field Early Treatment Diabetic Retinopathy (ETDRS) photography. This substantially wider field of view, while useful in many retinal vascular diseases, is particularly important in diabetic retinopathy where eyes with predominantly peripheral lesions or PPL have been shown to have significantly greater progression rates compared to eyes without PPL. In telemedicine settings, ultrawide field imaging has substantially reduced image ungradable rates and increased rate of disease identification allowing care to be delivered more effectively. Furthermore, the use of ultrawide field fluorescein angiography allows the visualization of significantly more diabetic retinal lesions and allows more accurate quantification of total retinal nonperfusion, with potential implications in the management of diabetic retinopathy and diabetic macular edema. The focus of this paper is to review the current role of ultrawide field imaging in diabetic retinopathy and its possible future role in innovations for retinal image analysis such as artificial intelligence and vessel caliber measurements.
Habib LA, Wolkow N, Cohen L, Ma L, Yoon MK, Lee NG. Pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease. Am J Ophthalmol Case Rep 2020;18:100623.Abstract
Purpose: Pyoderma gangrenosum (PG) of the eyelid can be difficult to diagnosis and may mimic other, more common pathologies, thereby delaying proper treatment and management. PG may be associated with systemic disorders that have significant comorbidities. Observations: The authors present two cases of pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease. Conclusions and importance: This case series highlights the importance of early recognition of eyelid pyoderma gangrenosum to avoid local and systemic comorbidities with timely and appropriate management.
Kang JH, VoPham T, Laden F, Rosner BA, Wirostko B, Ritch R, Wiggs JL, Qureshi A, Nan H, Pasquale LR. Cohort Study of Non-melanoma Skin Cancer and the Risk of Exfoliation Glaucoma. J Glaucoma 2020;Abstract
PRECIS: In a cohort study of 120,307 participants with 25+ years of follow-up, a history of non-melanoma skin cancer was associated with a 40% higher exfoliation glaucoma risk. PURPOSE: To evaluate the relationship between non-melanoma skin cancer (a marker of ultraviolet radiation exposure) and exfoliation glaucoma (XFG). METHODS: We performed a cohort study of US women (n=79,102; 1980-2014) and men (n=41,205; 1986-2014), aged 40+ years and at risk for glaucoma who reported eye exams. From 1984 (women)/1988 (men), we asked about basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) history separately; in prior years, we asked about any non-melanoma skin cancer history in a single question. SCC was confirmed with histopathology reports while BCC and any early (<1984/<1988) non-melanoma skin cancer history was self-reported. Incident XFG cases (362 women and 83 men) were confirmed with medical records. Using pooled data, we estimated multivariable-adjusted relative risks (MVRR; 95% confidence intervals [CIs]) with Cox proportional hazards models that were stratified by age (in months), 2-year time period at risk and average lifetime residential latitude. RESULTS: In multivariable-adjusted analyses, we observed a 40% higher XFG risk with any non-melanoma skin cancer history (MVRR=1.40; 95% CI=1.08,1.82); the association was observed even with 4 and 8 year lags in non-melanoma skin cancer history. Also, the non-melanoma skin cancer association was stronger in younger (<65▒y; MVRR=2.56; 95% CI=1.62,4.05) versus older participants (≥65▒y; MVRR=1.25; 95% CI=0.94,1.66; p for interaction=0.01) and those living in northern latitudes (≥42° north; MVRR=1.92; 95% CI=1.28,2.88) versus more southern latitudes (<42° north; MVRR=1.19; 95% CI=0.86,1.66; p for interaction=0.04). CONCLUSIONS: Non-melanoma skin cancer was associated with higher XFG risk, particularly among younger participants and those living in Northern US.
Tashbayev B, Utheim TP, Utheim ØA, Ræder S, Jensen JL, Yazdani M, Lagali N, Vitelli V, Dartt DA, Chen X. Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease. Sci Rep 2020;10(1):5542.Abstract
The prevalence of dry eye disease is high worldwide and poses a great burden on patients' daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (>308 mOsm/L, >316 mOsm/L, and inter-eye difference >8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.
Lu SY, Rong SS, Wu Z, Huang C, Matsushita K, Ng TK, Leung CKS, Kawashima R, Usui S, Tam POS, Tsujikawa M, Young AL, Zhang M, Wiggs JL, Nishida K, Tham CC, Pang CP, Chen LJ. Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese. Clin Exp Ophthalmol 2020;48(5):658-665.Abstract
BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.
Horton MB, Brady CJ, Cavallerano J, Abramoff M, Barker G, Chiang MF, Crockett CH, Garg S, Karth P, Liu Y, Newman CD, Rathi S, Sheth V, Silva P, Stebbins K, Zimmer-Galler I. Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition. Telemed J E Health 2020;26(4):495-543.Abstract
Contributors The following document and appendices represent the third edition of the . These guidelines were developed by the Diabetic Retinopathy Telehealth Practice Guidelines Working Group. This working group consisted of a large number of subject matter experts in clinical applications for telehealth in ophthalmology. The editorial committee consisted of Mark B. Horton, OD, MD, who served as working group chair and Christopher J. Brady, MD, MHS, and Jerry Cavallerano, OD, PhD, who served as cochairs. The writing committees were separated into seven different categories. They are as follows: 1.Clinical/operational: Jerry Cavallerano, OD, PhD (Chair), Gail Barker, PhD, MBA, Christopher J. Brady, MD, MHS, Yao Liu, MD, MS, Siddarth Rathi, MD, MBA, Veeral Sheth, MD, MBA, Paolo Silva, MD, and Ingrid Zimmer-Galler, MD. 2.Equipment: Veeral Sheth, MD (Chair), Mark B. Horton, OD, MD, Siddarth Rathi, MD, MBA, Paolo Silva, MD, and Kristen Stebbins, MSPH. 3.Quality assurance: Mark B. Horton, OD, MD (Chair), Seema Garg, MD, PhD, Yao Liu, MD, MS, and Ingrid Zimmer-Galler, MD. 4.Glaucoma: Yao Liu, MD, MS (Chair) and Siddarth Rathi, MD, MBA. 5.Retinopathy of prematurity: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 6.Age-related macular degeneration: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 7.Autonomous and computer assisted detection, classification and diagnosis of diabetic retinopathy: Michael Abramoff, MD, PhD (Chair), Michael F. Chiang, MD, and Paolo Silva, MD.
Muhammad F, Wang D, McDonald T, Walsh M, Drenen K, Montieth A, Foster SC, Lee DJ. TIGIT A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis. J Autoimmun 2020;111:102441.Abstract
Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre reporter mouse, we identify FoxP3 and 'exFoxP3' cells, show FoxP3 and not exFoxP3 cells are suppressive. We further show FoxP3 cells express TIGIT, and are induced through A2Ar in healthy volunteers, but not patients with autoimmune disease. Furthermore, we show Tregs emerge in the target tissue at the onset of autoimmune disease in an A2Ar-dependent manner. In summary, we identify a novel subset of TIGIT Tregs that are induced through stimulation of the A2Ar.
Guan J-T, Li X-X, Peng D-W, Zhang W-M, Qu J, Lu F, D'Amato RJ, Chi Z-L. MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A. Front Pharmacol 2020;11:276.Abstract
Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.

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