Pediatric uveitis accounts for 5-10% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause chronic damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or non-infectious in etiology. The etiology of non-infectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, it's treatment, and it's complications on the child and the child's family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.
BACKGROUND/AIM: To investigate the prevalence, causes and risk factors of visual impairment (VI) among the elderly in 'home for the aged' in Hyderabad, India. METHODS: Individuals aged ≥60 years were recruited from 41 'homes for the aged'. All participants had complete eye examinations including presenting visual acuity, refraction, slit-lamp examination, intraocular pressure measurement and fundus imaging by trained clinicians. VI was defined as presenting visual acuity worse than 6/18 in the better eye. Multivariate logistic regression was used to determine the risk factors associated with VI. RESULTS: 1512 elderly residents from 41 homes for the aged were enumerated, of whom 1182 (78.1%) were examined. The mean age of examined participants was 75.0 years (SD 8.8 years; range: 60-108 years); 35.4% of those examined were men. The prevalence of VI was 30.1% (95% CI 27.5 to 32.8). The leading cause of VI was cataract (46.3%, n=165), followed by uncorrected refractive error (27.0%, n=96), posterior capsular opacification (14.9%, n=53) and posterior segment disease (6.5%, n=23). Overall, 88.2% of the VI was either treatable or correctable. In multiple logistic regression, those aged 80 years and older (OR: 1.7, p<0.01), living in 'free' homes (OR: 1.5, p<0.01) and who were immobile/bedridden (OR: 3.02, p<0.01) had significantly higher odds of VI. Gender was not associated with VI. CONCLUSIONS: VI was common and largely avoidable in residents of 'homes for the aged' in Hyderabad, India. Screening for vision loss in 'homes for aged' and the provision of appropriate services should become routine practice to achieve the goal of healthy ageing in India.
Mucins are a family of high molecular weight, heavily-glycosylated proteins produced by wet epithelial tissues, including the ocular surface epithelia. Densely-packed O-linked glycan chains added post-translationally confer the biophysical properties of hydration, lubrication, anti-adhesion and repulsion. Membrane-associated mucins (MAMs) are the distinguishing components of the mucosal glycocalyx. At the ocular surface, MAMs maintain wetness, lubricate the blink, stabilize the tear film, and create a physical barrier to the outside world. In addition, it is increasingly appreciated that MAMs function as cell surface receptors that transduce information from the outside to the inside of the cell. Recently, our team published a comprehensive review/perspectives article for molecular scientists on ocular surface MAMs, including previously unpublished data and analyses on two new genes MUC21 and MUC22, new MAM functions and new biological roles, comparing human and mouse (PMID: 31493487). The current article is a refocus for the audience of The Ocular Surface. First, we update the gene and protein information in a more concise form, and include a new section on glycosylation. Next, we discuss biological roles, with some new sections and further updating from our previous review. Finally, we provide a new chapter on MAM involvement in ocular surface disease. We end this with discussion of an emerging mechanism responsible for damage to the epithelia and their mucosal glycocalyces: the unfolded protein response (UPR). The UPR offers a novel target for therapeutic intervention.
Importance: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, Setting, and Participants: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main Outcomes and Measures: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56  years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, -1.0 to 1.9 letters]; P = .47). Conclusions and Relevance: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333.
We are currently experiencing a deadly novel viral pandemic with no efficacious, readily available anti-viral therapies to SARS-CoV-2. Viruses will hijack host cellular machinery, including metabolic processes. Here, I provide theory and evidence for targeting the host de novo purine synthetic pathway for broad spectrum anti-viral drug development as well as the pursuit of basic science to mitigate the risks of future novel viral outbreaks.
BACKGROUND: Vision screenings of a school-based program were conducted in state-mandated grades (pre-kindergarten [pre-K] or kindergarten [K], 1st and 8th grade), and nonmandated grades (2nd to 7th). METHODS: During school years 2016-19, 51,593 pre-K to 8th grade students from 123 Baltimore City Public Schools underwent vision screenings, with 85% of the schools qualifying for Free and Reduced Price Meals. Assessments included distance visual acuity, Spot photoscreening, stereopsis, and cover testing. Screening failures were analyzed by grade using aggregate data. Failure rates for mandated and nonmandated grades were compared using a logistic regression model, and visual acuity distributions were analyzed using individual data. RESULTS: Over the 3-year period, 17,414 (34%) of students failed vision screening. Failure rates by grade ranged from 28% to 38%. Children in kindergarten and 3rd grade and higher were statistically more likely to fail screening than those in 1st grade. Reduced visual acuity was the most common reason for failure (91%). Failure rates were significantly higher in nonmandated grades than in state-mandated testing grades (34.7% vs 32.5% [P < 0.001]). Mean visual acuity of all students who failed vision screening was 20/50 in the worse-seeing eye and was 20/40 in the better-seeing eye. CONCLUSIONS: One-third of students failed vision screening. High screening failure rates across all grades suggest that screening in select grade levels, as currently mandated in Maryland schools, is inadequate for detecting vision problems in the low-income communities served by this program.
Minkus CL, Pistilli M, Dreger KA, Fitzgerald TD, Payal AR, Begum H, Kaçmaz OR, Jabs DA, Nussenblatt RB, Rosenbaum JT, Levy-Clarke GA, Sen NH, Suhler EB, Thorne JE, Bhatt NP, Foster SC, Buchanich JM, Kempen JH, for Group SITED (SITE) CSR. Risk of Cataract in Intermediate Uveitis. Am J Ophthalmol 2021;Abstract
PURPOSE: To determine the incidence of and predictive factors for cataract in intermediate uveitis. DESIGN: Retrospective cohort study METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at five participating United States tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-à-vis inflammatory status. RESULTS: Among 2,190 eyes of 1,302 patients with intermediate uveitis the cumulative incidence of cataract formation was 7.6% by one year (95% CI=6.2-9.1%), increasing to 36.6% by ten years (95% CI=31.2-41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (HR=2.68, 95% CI=2.00-3.59, p<0.001), and in eyes with epiretinal membrane formation (HR=1.54, 95% CI=1.15-2.07, p=0.004). Higher dose corticosteroid therapy was associated with significantly higher incidence of cataract, especially time-updated use of topical corticosteroids ≥2 times/day or ≥4 periocular corticosteroid injections. Low dose corticosteroid medications (oral prednisone 7.5mg daily or less, or topical corticosteroid drops <2 times/day) were not associated with increased cataract risk. CONCLUSIONS: Our study found that the incidence of clinically important cataract in intermediate uveitis is moderate. The risk is higher with markers of severity, and with higher doses of corticosteroid medications, the latter being potentially modifiable.
BACKGROUND: Over 2 billion people suffer from vision impairment or blindness globally, and access to validated visual measurement tools in imperative in accurately describing and managing the burden of eye disease. The present study applies contemporary psychometric validation techniques to the widely used 33-item Indian Visual Function Questionnaire (IND-VFQ-33). METHODS: We first estimated the polychoric correlation between each pair of items. Next, an unrotated and oblique Promax rotated factor analysis, item response theory (IRT, using a graded response model (GRM)), and differential item functioning (DIF) testing were applied to the IND-VFQ-33. We subsequently propose a validated IND-VFQ-33 questionnaire after psychometric testing, data reduction, and adjustment. RESULTS: Exploratory unrotated factor analysis identified two factors; one with a particularly high eigenvalue (18.1) and a second with a lower eigenvalue still above our threshold (1.1). A subsequent oblique Promax factor rotation was undertaken for a 2-factor solution, revealing two moderately correlated factors (+ 0.68) with clinically discrete item loadings onto either Factor 1 (21 items; collectively labelled "daily activities") or Factor 2 (5 items; collectively labelled "bright lights"). IRT confirmed high item discrimination for all remaining items with good separation between difficulty thresholds. We found significant DIF on depression for six items in Factor 1 (all uniform DIF, except item 21 (non-uniform DIF) with no substantive difference in beta thresholds for any item and no substantive difference in expected individual or sum score, by depression at baseline. For Factor 2, only one item demonstrated significant uniform DIF on gender, similarly without major differences in beta thresholds or expected total score between gender at baseline. Consequently, no further item recalibration or reduction was undertaken after IRT and DIF analysis. CONCLUSION: Applying IRT and DIF validation techniques to the IND-VFQ-33 identified 2 discrete factors with 26 uniquely-loading items, clinically representative of difficulty performing daily activities and experiencing difficulty due to bright lights/glare respectively. The proposed modified scale may be useful in evaluating symptomatic disease progression or response to treatment in an Indian population.
To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a Cochet-Bonnet esthesiometer. Naïve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 ×) and neovascularization (2.6 × ; p < 0.05). At 7 dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p < 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3 dpi epitheliopathy was significantly larger in the Hd group (23.59% vs. 3.44%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in naïve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p < 0.05). Leukocyte density showed a gradual increase over time from 1 to 7 dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3 dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with naïve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41 mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7 dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.
Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.
PURPOSE: To review the published literature assessing the efficacy and safety of in-office probing compared with facility-based probing to treat congenital nasolacrimal duct obstruction (NLDO). METHODS: Literature searches were conducted in March 2020 in the PubMed database with no date restrictions and limited to studies published in English and in the Cochrane Library database with no restrictions. The combined searches yielded 281 citations. Of these, 21 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Four articles were rated level I, 2 articles were rated level II, and 15 articles were rated level III. RESULTS: Treatments consisted of observation, in-office nasolacrimal probing, or facility-based nasolacrimal probing. Success rates and complications or recurrences were recorded from 1 week to 6 months after surgery. Complete resolution of symptoms after surgery ranged from 66% to 95.6% for office-based procedures versus 50% to 97.7% for facility-based procedures. Level I evidence indicated that 66% of cases spontaneously resolved after 6 months of observation in infants between 6 and 10 months of age. Success rates for in-office probing were lower for bilateral than for unilateral NLDO (67% vs. 82%), whereas success rates were high in both unilateral (83%) and bilateral (82%) patients who underwent facility-based probing after 6 months of observation. Cost data did not indicate a definitive cost savings of either treatment method ($562 for in-office vs. $701 for facility-based, depending on cost models predicting spontaneous resolution rates at different ages). No serious adverse events with treatment or anesthesia were reported for either treatment method. CONCLUSIONS: Evidence supports the efficacy and safety of both in-office and facility-based surgery for congenital NLDO. However, treating bilateral NLDO in a facility setting may be better. Because a significant percentage of children achieved resolution spontaneously before 12 months of age, deferring treatment until 12 to 18 months of age is a reasonable option. Additional research may address symptom burden on families and the impact of anesthesia and emotional trauma of nonsedated office probings on patients and may explore further the cost of treatment for each treatment method.
OBJECTIVE: To identify factors that contribute to missed cataract surgery follow-up visits, with an emphasis on socioeconomic and demographic factors. METHODS: In this retrospective cohort study, patients who underwent cataract extraction by phacoemulsification at Massachusetts Eye and Ear between 1 January and 31 December 2014 were reviewed. Second eye cases, remote and international patients, patients with foreign insurance and combined cataract cases were excluded. RESULTS: A total of 1931 cases were reviewed and 1089 cases, corresponding to 3267 scheduled postoperative visits, were included. Of these visits, 157 (4.8%) were missed. Three (0.3%) postoperative day 1, 40 (3.7%) postoperative week 1 and 114 (10.5%) postoperative month 1 visits were missed. Age<30 years (adjusted OR (aOR)=8.2, 95% CI 1.9 to 35.2) and ≥90 years (aOR=5.7, 95% CI 2.0 to 15.6) compared with patients aged 70-79 years, estimated travel time of >2 hours (aOR=3.2, 95% CI 1.4 to 7.4), smokers (aOR=2.7, 95% CI 1.6 to 4.8) and complications identified up to the postoperative visit (aOR=1.4, 95% CI 1.0 to 2.1) predicted a higher rate of missed visits. Ocular comorbidities (aOR=0.7, 95% CI 0.5 to 1.0) and previous visit best-corrected visual acuity (BCVA) of 20/50-20/80 (aOR=0.4, 95% CI 0.3 to 0.7) and 20/90-20/200 (aOR=0.4, 95% CI 0.2 to 0.9), compared with BCVA at the previous visit of 20/40 or better, predicted a lower rate of missed visits. Gender, race/ethnicity, language, education, income, insurance, alcohol use and season of the year were not associated with missed visits. CONCLUSIONS: Medical factors and demographic characteristics, including patient age and distance from the hospital, are associated with missed follow-up visits in cataract surgery. Additional studies are needed to identify disparities in cataract postoperative care that are population-specific. This information can contribute to the implementation of policies and interventions for addressing them.
OBJECTIVE: There are unmet needs for refractive correction in the pediatric population, especially in high-poverty communities. We reported the impact of refractive correction on vision outcomes over a 2-year follow-up in the Baltimore Reading and Eye Disease Study. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students of second and third grades who were prescribed glasses during baseline assessment. METHODS: We conducted baseline eye exams in 12 Baltimore public schools during the fall of school year 2014-15 with follow-up visits in the spring of school year 2014-15 (first follow-up) and school year 2015-16 (second follow-up). Visual acuity (VA) was measured at distance and near with correction. Refractive status was determined based on the eye with the larger refractive error and categorized as myopia, hyperopia, and astigmatism. MAIN OUTCOME MEASURES: VA in better-seeing and worse-seeing eye at first and second follow-up, and acuity improvement from baseline. RESULTS: In the 206 students (84% African American) who completed the first follow-up, both distance (from 0.14 ± 0.20 to 0.05 ± 0.10 logMAR) and near presenting VA (from 0.08 ± 0.16 to 0.03 ± 0.06 logMAR) improved from the baseline assessment; children with more severe hyperopia showed improvement in near VA by 0.05 ± 0.16 logMAR. Children who were prescribed glasses through a school-based research study had improved vision, which was sustained into the following school year. CONCLUSIONS: Many second and third graders in Baltimore Schools needed refractive correction and benefited from provision of glasses with sustained vision improvement over the 2-year observation.
Immune checkpoint inhibitors (ICIs) have revolutionized the field of oncology by modulating the immune cell-cancer cell interaction and thereby promoting immune system disinhibition in order to target several types of malignancies. There are three classes of immune checkpoint inhibitors (ICIs): anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1), and anti-programmed cell death ligand-1 (PD-L1).It is not uncommon for physicians across all specialties to encounter a patient with a history of malignancy and ICI exposure, necessitating familiarity with their potential complications. In this review article, we discuss the most common immune-related adverse events (irAEs) pertaining to the central and peripheral nervous systems and their potential afferent and efferent neuro-ophthalmic manifestations. Early recognition and treatment of these irAEs, and discontinuation of the offending ICI are all critical steps to prevent morbidity and mortality.
Muus C, Luecken MD, Eraslan G, Sikkema L, Waghray A, Heimberg G, Kobayashi Y, Vaishnav ED, Subramanian A, Smillie C, Jagadeesh KA, Duong ET, Fiskin E, Triglia ET, Ansari M, Cai P, Lin B, Buchanan J, Chen S, Shu J, Haber AL, Chung H, Montoro DT, Adams T, Aliee H, Allon SJ, Andrusivova Z, Angelidis I, Ashenberg O, Bassler K, Bécavin C, Benhar I, Bergenstråhle J, Bergenstråhle L, Bolt L, Braun E, Bui LT, Callori S, Chaffin M, Chichelnitskiy E, Chiou J, Conlon TM, Cuoco MS, Cuomo ASE, Deprez M, Duclos G, Fine D, Fischer DS, Ghazanfar S, Gillich A, Giotti B, Gould J, Guo M, Gutierrez AJ, Habermann AC, Harvey T, He P, Hou X, Hu L, Hu Y, Jaiswal A, Ji L, Jiang P, Kapellos TS, Kuo CS, Larsson L, Leney-Greene MA, Lim K, Litviňuková M, Ludwig LS, Lukassen S, Luo W, Maatz H, Madissoon E, Mamanova L, Manakongtreecheep K, Leroy S, Mayr CH, Mbano IM, McAdams AM, Nabhan AN, Nyquist SK, Penland L, Poirion OB, Poli S, Qi CC, Queen R, Reichart D, Rosas I, Schupp JC, Shea CV, Shi X, Sinha R, Sit RV, Slowikowski K, Slyper M, Smith NP, Sountoulidis A, Strunz M, Sullivan TB, Sun D, Talavera-López C, Tan P, Tantivit J, Travaglini KJ, Tucker NR, Vernon KA, Wadsworth MH, Waldman J, Wang X, Xu K, Yan W, Zhao W, Ziegler CGK, Ziegler CGK, Ziegler CGK. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med 2021;27(3):546-559.Abstract
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2TMPRSS2 cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
PURPOSE: Retinoschisis (RS), rhegmatogenous retinal detachment (RRD) and combined RS retinal detachment (RSRD) may resemble clinically and pose a diagnostic challenge. This study investigates the role of the fundus autofluorescence (AF) in differentiating RS, RRD and RSRD. METHODS: Fundus AF changes of 34 eyes diagnosed with RRD, 30 eyes with RS and 12 eyes with RSRD were retrospectively analysed. Ultra-widefield AF (UW-AF) image intensities obtained with the Optomap 200Tx were interpreted as hypo-, hyper- and isoautofluorescent or a mixed pattern with hypo- and hyperautofluorescence over and at the posterior margin (PM) of RRD, RS and RSRD. RESULTS: All RS eyes revealed isoautofluorescence over the area of RS, and nine eyes (30%) showed hypoautofluorescent PM. Among RRD, acute (≤2 weeks) and chronic (>2 weeks) RRD demonstrated distinct AF characteristics. Sixty-two per cent of RRD eyes had acute RRD. From those, 16 eyes (76%) demonstrated hypoautofluorescence over the detached area and 19 (90%) eyes with hyperautofluorescent PM. Sixty-two per cent of chronic RRD eyes demonstrated isoautofluorecence over the detached area. Eight RSRD eyes (67%) revealed hyperautofluorescence in the detached area. The positive predictive value (PPV) for hypoautofluorescence over the area of subretinal fluid (SRF) in RRD was 95%. The PPV for hyperautofluorescence over the area of SRF in RSRD was 100% and for isoautofluorescence for schitic area in RSRD and RS was 76%. CONCLUSION: The UW-AF can be a useful non-invasive adjuvant tool to distinguish between RRD, RS and RSRD. Hypo- or hyperautofluorescence over the area of interest and hyperautofluorescent PM indicates the presence of SRF.
PURPOSE: To describe two cases of catastrophic, bilateral retinal vascular occlusion following intravitreal (IVT) bevacizumab injection. METHODS: Case series. Main outcome measures included clinical and fluorescein angiography (FA) findings. RESULTS: Case 1 - A 65-year-old woman with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST) syndrome developed acute, severe, bilateral visual loss two weeks following bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and FA revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2 - An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left then right eye approximately three weeks following IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. FA showed diffuse venous leakage. Extensive testing revealed an elevated anti-nuclear antibody and mildly elevated anti-cardiolipin antibody. CONCLUSION: Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion following treatment with IVT bevacizumab. The moderate to severe intraocular inflammation in both cases, and the contralateral involvement following unilateral IVT injection in Case 2, suggest a possible delayed immune-mediated mechanism.
BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.
PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.