Agrawal R, Testi I, Bodaghi B, Barisani-Asenbauer T, McCluskey P, Agarwal A, Kempen JH, Gupta A, Smith JR, De Smet MD, Yuen YS, Mahajan S, Kon OM, Nguyen QD, Pavesio C, Gupta V, Gupta V. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis. Ophthalmology 2021;128(2):277-287.Abstract
TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.
Sobrin L, Yu Y, Li A, Kempen JH, Hubbard RA, VanderBeek BL. Angiotensin Converting Enzyme-Inhibitors and Incidence of Non-infectious Uveitis in a Large Healthcare Claims Database. Ophthalmic Epidemiol 2021;:1-6.Abstract
: To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). Patients in a large healthcare claims database who initiated ACE-I (n = 695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n = 354,295). A second comparison was also made between patients who initiated ACE-I (n = 505,958) and those who initiated beta-blockers (BB, n = 538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR = 0.95, 95% Confidence Interval (CI): 0.85-1.07, = .41] or secondary outcome [HR = 0.96, 95% CI: 0.86-1.07, = .44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. Our results suggest there is no evidence that ACE-I have a protective effect on NIU.
Burton MJ, Ramke J, Marques AP, Bourne RRA, Congdon N, Jones I, Ah Tong BAM, Arunga S, Bachani D, Bascaran C, Bastawrous A, Blanchet K, Braithwaite T, Buchan JC, Cairns J, Cama A, Chagunda M, Chuluunkhuu C, Cooper A, Crofts-Lawrence J, Dean WH, Denniston AK, Ehrlich JR, Emerson PM, Evans JR, Frick KD, Friedman DS, Furtado JM, Gichangi MM, Gichuhi S, Gilbert SS, Gurung R, Habtamu E, Holland P, Jonas JB, Keane PA, Keay L, Khanna RC, Khaw PT, Kuper H, Kyari F, Lansingh VC, Mactaggart I, Mafwiri MM, Mathenge W, McCormick I, Morjaria P, Mowatt L, Muirhead D, Murthy GVS, Mwangi N, Patel DB, Peto T, Qureshi BM, Salomão SR, Sarah V, Shilio BR, Solomon AW, Swenor BK, Taylor HR, Wang N, Webson A, West SK, Wong TY, Wormald R, Yasmin S, Yusufu M, Silva JC, Resnikoff S, Ravilla T, Gilbert CE, Foster A, Faal HB. The Lancet Global Health Commission on Global Eye Health: vision beyond 2020. Lancet Glob Health 2021;9(4):e489-e551.
Rossin EJ, Sobrin L, Kim LA. Single-cell RNA sequencing: An overview for the ophthalmologist. Semin Ophthalmol 2021;36(4):191-197.Abstract
Understanding the molecular composition of pathogenic tissues is a critical step in understanding the pathophysiology of disease and designing therapeutics. First described in 2009, single cell RNA sequencing (scRNAseq) is a methodology whereby thousands of cells are simultaneously isolated into individual micro-environments that can be altered experimentally and the genome-wide RNA expression of each cell is captured. It has undergone significant technological improvement over the last decade and gained tremendous popularity. scRNAseq is an improvement over prior pooled RNA analyses which cannot identify the cellular composition and heterogeneity of a tissue of interest. This new approach offers new opportunity for new discovery, as tissue samples can now be sub-categorized into groups of cell types based on genome-wide gene expression in an unbiased fashion. As ophthalmologists, we are uniquely positioned to obtain pathologic samples from the eye for further study. ScRNAseq has already been applied in ophthalmology to characterize retinal tissue, and it may offer the key to understanding various pathological processes in the future.
Hellgren G, Lundgren P, Pivodic A, Löfqvist C, Nilsson AK, Ley D, Sävman K, Smith LE, Hellström A. Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP. Neonatology 2021;:1-10.Abstract
INTRODUCTION: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. METHODS: Data for 78 infants born at gestational age (GA) <28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. RESULTS: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05-0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001). CONCLUSION: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.
Chang EK, Gupta S, Chachanidze M, Miller JB, Chang TC, Solá-Del Valle DA. Combined pars plana glaucoma drainage device placement and vitrectomy using a vitrectomy sclerotomy site for tube placement: a case series. BMC Ophthalmol 2021;21(1):106.Abstract
PURPOSE: The purpose of this study is to report the safety and efficacy of pars plana glaucoma drainage devices with pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement in patients with refractory glaucoma. METHODS: Retrospective case series of 28 eyes of 28 patients who underwent combined pars plana glaucoma drainage device and pars plana vitrectomy between November 2016 and September 2019 at Massachusetts Eye and Ear. Main outcome measures were intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity, and complications. Statistical tests were performed with R and included Kaplan-Meier analyses, Wilcoxon paired signed-rank tests, and Fisher tests. RESULTS: Mean IOP decreased from 22.8 mmHg to 11.8 mmHg at 1.5 years (p = 0.002), and mean medication burden decreased from 4.3 to 2.1 at 1.5 years (p = 0.004). Both IOP and medication burden were significantly lower at all follow-up time points. The probability of achieving 5 < IOP ≤ 18 mmHg with at least 20% IOP reduction from preoperative levels was 86.4% at 1 year and 59.8% at 1.5 years. At their last visit, three eyes (10.7%) achieved complete success with IOP reduction as above without medications, and 14 eyes (50.0%) achieved qualified success with medications. Hypotony was observed in 1 eye (3.6%) prior to 3 months postoperatively and 0 eyes after 3 months. Visual acuity was unchanged or improved in 23 eyes (82.1%) at their last follow-up. Two patients had a visual acuity decrease of > 2 lines. Two eyes required subsequent pars plana vitrectomies for tube obstruction, and one eye had transient hypotony. CONCLUSIONS: The results of pars plana glaucoma drainage device and pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement are promising, resulting in significant IOP and medication-burden reductions through postoperative year 1.5 without additional risk of postoperative complications. Inserting glaucoma drainage devices into an existing vitrectomy sclerotomy site may potentially save surgical time by obviating the need to create another sclerotomy for tube placement and suture one of the vitrectomy ports.
Freitag SK, Yen MT. Reply. Ophthalmology 2021;128(6):e29-e30.
Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, Ong JS, Hewitt AW, Segrè AV, Rouhana JM, Hamel AR, Igo RP, Choquet H, Qassim A, Josyula NS, Cooke Bailey JN, Bonnemaijer PWM, Iglesias A, Siggs OM, Young TL, Vitart V, Thiadens AAHJ, Karjalainen J, Uebe S, Melles RB, Nair SK, Luben R, Simcoe M, Amersinghe N, Cree AJ, Hohn R, Poplawski A, Chen LJ, Rong S-S, Aung T, Vithana EN, Vithana EN, Vithana EN, Vithana EN, Vithana EN, and Consortium UKBEV, and Consortium UKBEV, and Consortium UKBEV, Tamiya G, Shiga Y, Yamamoto M, Nakazawa T, Currant H, Birney E, Wang X, Auton A, Lupton MK, Martin NG, Ashaye A, Olawoye O, Williams SE, Akafo S, Ramsay M, Hashimoto K, Kamatani Y, Akiyama M, Momozawa Y, Foster PJ, Khaw PT, Morgan JE, Strouthidis NG, Kraft P, Kang JH, Pang CP, Pasutto F, Mitchell P, Lotery AJ, Palotie A, van Duijn C, Haines JL, Hammond C, Pasquale LR, Klaver CCW, Hauser M, Khor CC, Mackey DA, Kubo M, Cheng C-Y, Craig JE, Macgregor S, Wiggs JL. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat Commun 2021;12(1):1258.Abstract
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Hu S-L, Shi W-Q, Su T, Ge Q-M, Li Q-Y, Li B, Liang R-B, Zhu P-W, Shao Y. Surgical correction of recurrent epiblepharon in Chinese children using modified skin re-draping epicanthoplasty. Int J Ophthalmol 2021;14(2):217-222.Abstract
AIM: To evaluate the clinical efficacy of the modified skin re-draping epicanthoplasty procedure for correction of recurrent lower lid epiblepharon in Chinese children. METHODS: From 2016 to 2018, 18 children (10 males and 8 females, average age 6.2±1.7y; 30 eyes) with recurrent epiblepharon who attended Beijing Children's Hospital were included in the study. All the children had undergone lower eyelid surgery for epiblepharon. Surgical design included using an additional incision along the upper palpebral margin, to avoid vertical scarring on the upper lid. The re-draping method was used to correct recurrent epiblepharon. Follow-up ranged from 3 to 24mo. Postoperative surgical outcomes, complications, and subjective satisfaction were evaluated. RESULTS: Complete correction of cilia touching the cornea was observed in all patients during an average follow-up of 7.1mo. No "dog ears" or obvious scars were formed after surgery. All parents were satisfied with the cosmetic results and none complained. Mean astigmatism decreased from 2.39±0.79 diopter (D) preoperatively to 2.19±0.79 D at 6mo after surgery; however, the difference was not significant. Best-corrected visual acuity improved, although the change in mean visual acuity was not significant. No recurrence occurred during the follow-up period. CONCLUSION: This surgical modified skin re-draping technique is effective and highly satisfactory for correction of recurrent epiblepharon. The approach is characterized by a simple design, a straightforward procedure, inconspicuous scarring, and good postoperative appearance.
Styliadis C, Leung R, Özcan S, Moulton EA, Pang E, Taylor MJ, Papadelis C. Atypical spatiotemporal activation of cerebellar lobules during emotional face processing in adolescents with autism. Hum Brain Mapp 2021;42(7):2099-2114.Abstract
Autism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.
Singh RB, Khera T, Ly V, Saini C, Cho W, Shergill S, Singh KP, Agarwal A. Ocular complications of perioperative anesthesia: a review. Graefes Arch Clin Exp Ophthalmol 2021;259(8):2069-2083.Abstract
Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.
Moein H-R, Sendra VG, Jamali A, Kheirkhah A, Harris DL, Hamrah P. Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis. Sci Rep 2021;11(1):4267.Abstract
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.
Agrawal R, Testi I, Mahajan S, Yuen YS, Agarwal A, Kon OM, Barisani-Asenbauer T, Kempen JH, Gupta A, Jabs DA, Smith JR, Nguyen QD, Pavesio C, Gupta V, Gupta V. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis. Ophthalmology 2021;128(2):266-276.Abstract
TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.