Publications by authors named "Alejandra de-la-Torre"

50 Publications

Ocular Cicatricial Pemphigoid, Sjögren's Syndrome, and Hashimoto's Thyroiditis as a Multiple Autoimmune Syndrome: A case report.

Eur J Ophthalmol 2021 Feb 18:1120672121996637. Epub 2021 Feb 18.

Research Group in Neurosciences NeURos, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.

Purpose: To present a rare and novel association of Ocular Cicatricial Pemphigoid, Sjögren's Syndrome, and Hashimoto's Thyroiditis as a Multiple Autoimmune Syndrome.

Case Report: A 43-year-old Colombian female, presented with corneal ulcers, associated with trichiasis. At the ophthalmological examination forniceal shortening OU and symblepharon OD was found. Conjunctival biopsy was performed, evidencing linear deposition of IgG and IgA antibodies along the basement membrane of the conjunctiva, confirming Ocular Cicatricial Pemphigoid diagnosis. After 12 years, the patient presented constitutional symptoms, xerostomia, and worsening of xerophthalmia. Laboratory tests showed positive Anti-TG, Anti-TPO, Anti-Ro, and Anti-La antibodies, and salivary gland biopsy was consistent with Sjögren's Syndrome. Due to these findings, Hashimoto's Thyroiditis and Sjögren's Syndrome were diagnosed, defining a Multiple Autoimmune Syndrome.

Conclusion: A novel association of Multiple Autoimmune Syndrome is presented in this case. Ophthalmologists and other specialists involved in the evaluation and treatment of patients with autoimmune diseases, should be aware of this clinical presentation. A multidisciplinary approach in this condition is important for optimum treatment instauration and follow-up, in order to prevent complications.
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http://dx.doi.org/10.1177/1120672121996637DOI Listing
February 2021

Ocular Co-infection with and in an Immunocompetent Patient - A Case Report.

Ocul Immunol Inflamm 2021 Feb 5:1-5. Epub 2021 Feb 5.

NeURos Research Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario , Bogotá, Colombia.

: To report a case of ocular co-infection with and in an immunocompetent woman. : Retrospective observational case report. : A 61-year-old woman presented with decreased vision and floaters in the right eye of 1-month duration. Ocular examination revealed panuveitis with a large yellowish-white retinochoroiditis lesion adjacent to a chorioretinal scar. Investigations showed positive Mantoux test, QuantiFERON TB test, and HRCT chest suggestive of active pulmonary tuberculosis. Serology revealed raised IgG anti antibody. Vitreous aspirate was positive for and genome by polymerase chain reaction and showed high IgG and IgM antibodies. She was treated with anti toxoplasmic and antitubercular therapy along with oral corticosteroid and therapeutic vitrectomy. : Ocular tuberculosis and toxoplasmosis can not only mimic each other but also present as co-infection in rare cases.
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http://dx.doi.org/10.1080/09273948.2020.1849738DOI Listing
February 2021

Referral Process in Patients with Uveitis: A Challenge in the Health System.

Clin Ophthalmol 2021 6;15:1-10. Epub 2021 Jan 6.

Research Group in Neuroscience NeURos, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.

Purpose: To describe the evaluation and referral process from a group of patients with uveitis presented at a specialized uveitis center in Bogotá, Colombia.

Methods: An observational descriptive cross-sectional study was performed. After applying the selection criteria, 315 clinical records were recovered. Univariate and bivariate analyses were used, reporting proportions, means and standard deviations.

Results: The mean age of the sample was 45.23 years old and 63.8% of them were females. Patients were mostly referred by retina specialists, general ophthalmologists, rheumatologists, and cornea specialists. Meantime between the first ocular symptom and uveitis specialist evaluation was 2.08 years. Patients had been previously evaluated by a mean of 1.9 ophthalmologists. In 79.9% of patients, inflammation was recognized by the remittent; however, only 4.7% of patients were correctly graded according to SUN classification. At first time consultation with the uvea specialist, 52.1% of the patients arrived with an adequate infectious panel, 58.1% with an adequate rheumatologic panel, 11.6% with aqueous humor PCR study, 65.1% with an initial etiological diagnosis, 34.9% with inadequate topical treatment, and 59.6% with inadequate systemic treatment. The mean time to reach a diagnosis by the uvea specialist was 5.27 weeks (0.10 years). A diagnostic coincidence was not reached in 58.7% of the cases.

Conclusion: The referral process to uveitis specialists is complex but highly relevant for those who suffer from this pathology. Health professionals must be aware of the standardized classification of the disease, the appropriate treatment according to the classification, and early referral to the uveologist with adequate laboratory tests.
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http://dx.doi.org/10.2147/OPTH.S287766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797337PMC
January 2021

A white circular-spot pattern of iridian atrophy associated with Varicella-zoster virus and Toxoplasma gondii coinfection: a case report.

BMC Ophthalmol 2020 Dec 7;20(1):479. Epub 2020 Dec 7.

NeURos Research Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63 C 69, Bogotá, Colombia.

Background: We report a case of white circular spots of iridian atrophy, which we will call "polka dots" pattern, as a rare ophthalmological finding associated with uveitis secondary to varicella-zoster virus and Toxoplasma gondii coinfection in a male patient in Bogotá, Colombia.

Case Presentation: We present de case of a 53-year-old Colombian male patient with a diagnosis of anterior uveitis in his left eye due to varicella-zoster virus and Toxoplasma gondii coinfection documented by polymerase chain reaction analysis. He presented with multiple areas of superficial white circular spots of iridian atrophy in 360º, some with deeper atrophy where the stroma fibers were visualized and only a small punctate defect of transillumination was evident. This rare pattern of iridian atrophy has not been previously described in cases of uveitis in the literature.

Conclusions: This is the first case reporting the findings of superficial "polka dots" pattern iridian atrophy in 360° secondary to anterior uveitis due to the coinfection of a virus and a parasite. The identification of similar clinical cases may lead to early initiation of systemic treatment in these patients.
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http://dx.doi.org/10.1186/s12886-020-01748-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720502PMC
December 2020

High Prevalence of Abnormal Ocular Surface Tests in a Healthy Pediatric Population.

Clin Ophthalmol 2020 22;14:3427-3438. Epub 2020 Oct 22.

Research Group in Neurosciences NeURos. Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.

Purpose: To describe ocular surface characteristics and tests' results in a healthy pediatric population.

Methods: We performed a cross-sectional study with 60 healthy children, obtaining consent, OSDI and screen use survey and conducting ocular surface tests. Statistical univariate analysis for categorical and quantitative variables was made. To describe the correlation of the results in both eyes, we used a model of random effects. To characterize the possible profiles of device use, we applied the mixed-cluster methodology.

Results: Sixty healthy children between 7 and 17 years old were evaluated. Girl's proportion was 41.6%. Mean Ocular Surface Disease Index Score was 9.98±8.49 points. Daily screen time was 5.59±2.77 hours and the most popular screen was the smartphone. Mean results (with standard deviations or confidence intervals) of ocular surface tests were blink frequency while reading on paper, 6.8±5.68 times per minute; blink frequency while reading on screen, 8.7±7.14 times per minute; tear meniscus height, 0.19[0.18-0.2] mm; non-invasive tear break-up time, 12.44[10.99-13.9] seconds; nasal conjunctival redness, 0.86[0.77-0.94]; temporal conjunctival redness, 0.96[0.87-1.04]; tear osmolarity, 299.3[295.14-303.45] mmol; and Schirmer test, 23.73[21.28-26.18] mm. Lid margin was irregular in three eyes; 44.7% had thin lipid layer; lissamine green staining was positive in 70.8%; fluorescein staining was positive in 47.4%; 36.64% exhibited partial meibomian gland loss.

Conclusion: Considering the scarcity of specific pediatric values of ocular surface tests, we performed a clinical investigation involving the complete pool of ocular surface tests in children. Although healthy children were included in this study, we found that all the participants had at least one abnormal result and 33.33% had dry eye disease diagnosis, according to the TFOS DEWS II. It would be relevant to carry out further multicentric studies to compare our ocular surface tests' results with other groups of children.
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http://dx.doi.org/10.2147/OPTH.S266261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588271PMC
October 2020

Reply: Anterior Uveitis Due to Intracameral Moxifloxacin: A Case Report.

Ocul Immunol Inflamm 2020 Sep 25:1-2. Epub 2020 Sep 25.

NeURos Research Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario , Bogotá, Colombia.

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http://dx.doi.org/10.1080/09273948.2020.1805986DOI Listing
September 2020

Ocular Toxoplasmosis in Africa: A Narrative Review of the Literature.

Ocul Immunol Inflamm 2020 Sep 25:1-6. Epub 2020 Sep 25.

Grupo de Investigación en Neurociencia (Neuros), Escuela de Medicina y Ciencias de La Salud, Universidad Del Rosario , Bogotá, Colombia.

Purpose: To present a narrative review about ocular toxoplasmosis epidemiology, disease burden and prevalent African parasitic strains.

Methods: An initial search for MeSH terms was conducted with a posterior advanced search in two electronic databases. Full text reading was performed.

Results: Animal African studies have identified type II, type III, Africa 1, and Africa 3 strains. Seroprevalence varies from 6.4% to 74.5%. Nevertheless, there is a scarcity of epidemiology and serotyping information about ocular toxoplasmosis. African studies have demonstrated that uveitis patients present high frequencies of ocular toxoplasmosis. There is a lack of studies describing specific clinical characteristics, which can be related, to environmental and socioeconomic factors, parasite serotype and genotype, and genetic susceptibility of the host.

Conclusion: As has more virulent strains in the Southern hemisphere, it is relevant to determine African strain types and the correlation between the infecting strains and the clinical manifestations.
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http://dx.doi.org/10.1080/09273948.2020.1801761DOI Listing
September 2020

Prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in thyroid eye disease: a systematic review of the literature.

Syst Rev 2020 09 1;9(1):201. Epub 2020 Sep 1.

Research Group in Neurosciences NeURos, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63C 69, Bogotá, Colombia.

Background: Thyroid eye disease is an autoimmune disorder of the orbital retrobulbar tissue commonly associated with dysthyroid status. The most frequent condition is hyperthyroidism, although it is also present in hypothyroid and euthyroid patients. The prevalence of thyroid conditions in patients with thyroid eye disease had been previously evaluated; however, there is no consensus on a global prevalence. The study aims to estimate the prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in patients with TED, through a systematic review of literature.

Methods: We conducted a systematic review of the literature following the PRISMA guidelines, in MEDLINE, COCHRANE, EMBASE, Science Direct, and LILACS databases. Inclusion criteria were primary studies of patients with a diagnosis of thyroid eye disease made by an ophthalmologist or with diagnosis criteria, with measurement of thyroid function (TSH, T3, and free T4), and diagnosis of the primary thyroid condition. A quality assessment was made through the Joanna Briggs Institute Quality tools. Finally, we extracted relevant details about the design, the results, and the prevalence of thyroid disorders in thyroid eye disease.

Results: The initial search revealed 916 studies, of which finally thirteen met inclusion criteria. Six studies were performed in Europe (Germany, Wales, and Spain), five in Asia (Iran, South Korea, Japan, and Singapore), one in North America (USA), and one in Africa (Ghana). The global prevalence, in patients of thyroid eye disease, was 10.36% for hypothyroidism, 7.9% for euthyroidism, and 86.2% for hyperthyroidism.

Conclusions: Professionals should be aware that thyroid eye disease can be present in patients with a normal thyroid function. The assessment for these patients is based on orbital images; serum TSH, T3, and free T4; antibody levels as thyrotropin receptor antibodies; and thyroperoxidase levels. Additionally, we want to encourage research in this field in other regions of the world such as Latin America.

Systematic Review Registration: PROSPERO ID CRD42020107167.
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http://dx.doi.org/10.1186/s13643-020-01459-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465839PMC
September 2020

Serotyping, host genes and cytokines response in human ocular toxoplasmosis.

Microb Pathog 2020 Nov 27;148:104465. Epub 2020 Aug 27.

GEPAMOL, Centro de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Universidad del Quindío, Armenia (Quindio), Colombia. Electronic address:

In human ocular toxoplasmosis, serotype is related with greater severity. We analyzed Toxoplasma GRA6 serotype in 23 patients with ocular toxoplasmosis (13 confirmed, two co-infections- and eight unconfirmed cases) and 20 individuals chronically infected with Toxoplasma but without ocular involvement. In patients with ocular toxoplasmosis, we also studied host gene polymorphisms related to immune response (IL-1β; IL-1α; IL-10; IFN-γ; TNF-α, IL-12), IL-17R, TLR-9, and P2RX7. Additionally, eight patients were studied for the production of TNFα, IL1-β, IFN-γ and IL-10 by their peripheral leukocytes after ex vivo stimulation with soluble Toxoplasma antigens. There were no differences in the distribution of serotypes (GRA6-I versus GRA6 non-I) between infected individuals with- or without ocular involvement. Seropositivity for GRA6-I was associated with higher number of retinal lesions and higher levels of IL-1β. Two polymorphisms were associated with specific clinical manifestations of ocular toxoplasmosis: IL-10 -819 C/T with bilateral lesions and IL-12 + 169,774 A/C with synechia. Higher levels of IL-10 were found in patients with the allele G/G at the polymorphic region IL-10 -1082. People with a GRA6 I serotype and possessing the allele G/G at the polymorphic region TNFα-857 suffered from an increased number of retinal lesions. We found a positive association between host cytokine genes polymorphisms and GRA6 serotypes correlated with specific clinical manifestations and immune response in ocular toxoplasmosis.
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http://dx.doi.org/10.1016/j.micpath.2020.104465DOI Listing
November 2020

Allergy against Steroids in Ocular Inflammation.

Ocul Immunol Inflamm 2020 Jul 9:1-6. Epub 2020 Jul 9.

Research Group in Neurosciences NeURos. Escuela De Medicina Y Ciencias De La Salud, Universidad Del Rosario , Bogotá, Colombia.

Allergy to steroids is an uncommon and harmful condition that leads to a decrease in treatment options and increase in morbidity due to the suboptimal disease control. It can manifest as an immediate response or a delay manifestation. Worsening of underlying condition and not treatment response can indicate corticosteroids hypersensitivity as well. Despite its low prevalence, all clinicians should be aware of this condition and know the treatment options. This narrative review attempts to update information about corticosteroid allergy and we present a case of a patient with the diagnosis of Vogt Koyanagi Harada Syndrome with a history of steroids allergy, as an example, to integrate this information to the ocular inflammation field.
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http://dx.doi.org/10.1080/09273948.2020.1766511DOI Listing
July 2020

Pathophysiological Mechanisms of Cognitive Impairment and Neurodegeneration by Infection.

Brain Sci 2020 Jun 12;10(6). Epub 2020 Jun 12.

GI en Neurociencias-NeURos, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá 111221, Colombia.

is an obligate intracellular parasite considered one of the most successful pathogens in the world, owing to its ability to produce long-lasting infections and to persist in the central nervous system (CNS) in most warm-blooded animals, including humans. This parasite has a preference to invade neurons and affect the functioning of glial cells. This could lead to neurological and behavioral changes associated with cognitive impairment. Although several studies in humans and animal models have reported controversial results about the relationship between toxoplasmosis and the onset of dementia as a causal factor, two recent meta-analyses have shown a relative association with Alzheimer's disease (AD). AD is characterized by amyloid-β (Aβ) peptide accumulation, neurofibrillary tangles, and neuroinflammation. Different authors have found that toxoplasmosis may affect Aβ production in brain areas linked with memory functioning, and can induce a central immune response and neurotransmitter imbalance, which in turn, affect the nervous system microenvironment. In contrast, other studies have revealed a reduction of Aβ plaques and hyperphosphorylated tau protein formation in animal models, which might cause some protective effects. The aim of this article is to summarize and review the newest data in regard to different pathophysiological mechanisms of cerebral toxoplasmosis and their relationship with the development of AD and cognitive impairment. All these associations should be investigated further through clinical and experimental studies.
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http://dx.doi.org/10.3390/brainsci10060369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349234PMC
June 2020

Anterior Uveitis Due to Intracameral Moxifloxacin: A Case Report.

Ocul Immunol Inflamm 2020 May 29:1-4. Epub 2020 May 29.

NeURos Research Group, Escuela De Medicina Y Ciencias De La Salud, Universidad Del Rosario , Bogotá, Colombia.

Purpose: To report a case of a drug-induced anterior uveitis secondary to the use of intracameral moxifloxacin.

Case Report: A 64-year-old Colombian male patient presented with severe ocular pain and photophobia in his left eye 15 days after cataract surgery. In the ophthalmology and glaucoma specialist evaluation, pigment dispersion in the anterior chamber and camerular angle, severe anterior segment inflammation, and elevated intraocular pressure were observed. Poor response to treatment for a suspected viral origin and exclusion of other possible etiologies, led to the conclusion of intracameral moxifloxacin induced anterior uveitis.

Conclusion And Importance: We present the second published case worldwide about anterior uveitis secondary to intracameral moxifloxacin, which may rarely cause hypertensive uveitis that may be confused with viral uveitis. This provides evidence on the importance of postoperative follow-up by the surgeon for an early referral and treatment of these cases.
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http://dx.doi.org/10.1080/09273948.2020.1757120DOI Listing
May 2020

Ophthalmological treatment of early-onset sarcoidosis/Blau syndrome in a Colombian child: A case report.

Am J Ophthalmol Case Rep 2020 Jun 18;18:100714. Epub 2020 Apr 18.

NeURos Research Group. Escuela de Medicina y Ciencias de La Salud, Universidad Del Rosario, Carrera 24 # 63 C 69, Bogotá, Colombia.

Purpose: To report the ophthalmological approach of a patient with Blau syndrome (BS) in Colombia.

Observations: We describe a 9-year-old Colombian boy with sporadic BS due to a nucleotide-binding oligomerization domain containing 2 (NOD2) mutation, who presented with joint and dermatologic symptoms. He was referred to the uveitis service with a single functional eye, due to retinal detachment in the other eye. Despite treatment with corticosteroids, methotrexate, and adalimumab, the patient continued to exhibit progressive disease.

Conclusion: BS-related uveitis is characterized by severe ocular morbidity. Appropriate interdisciplinary treatment is necessary for the correct identification and management of the disease, considering the inherent difficulty in its diagnosis due to its diverse clinical manifestations. The severity of BS-related uveitis in this report highlights the need for more effective therapies.
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http://dx.doi.org/10.1016/j.ajoc.2020.100714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178324PMC
June 2020

Severe acute multi-systemic failure with bilateral ocular toxoplasmosis in immunocompetent patients from urban settings in Colombia: Case reports.

Am J Ophthalmol Case Rep 2020 Jun 13;18:100661. Epub 2020 Mar 13.

Fundación Oftalmológica Nacional, Uveitis and Retina Services, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Cl. 50 #13 - 50, Bogotá, Colombia.

Propose: To report two cases of severe acute multi-systemic failure with bilateral ocular toxoplasmosis in immunocompetent patients from urban settings in Colombia.

Observations: We report two immunocompetent male patients aged 44- and 67-years-old who, despite not having visited the Amazonian region in Colombia, had severe bilateral posterior uveitis and extensive-bilateral macular lesions and multiple organ failure that required admission to an intensive care unit. was positive by PCR assay in vitreous humor samples. Patients were treated with intravitreal clindamycin and dexamethasone in addition to systemic treatment with trimethoprim-sulfamethoxazole. In both patients, infection by atypical strains was confirmed; in one case by serotyping and in another one by genotyping (ROP 18 virulent allele). After 2 and 4 months of treatment respectively, the patients showed improvement of the posterior uveitis and its systemic manifestations. However, there was no significant visual acuity improvement due to bilateral extensive macular involvement.

Conclusions And Importance: Clinicians should be aware that toxoplasmosis originating from South America could be associated with severe acute multisystemic and intraocular bilateral involvement, even in patients with no history of exposure to jungle environments.
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http://dx.doi.org/10.1016/j.ajoc.2020.100661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078491PMC
June 2020

Disease of the Year 2019: Ocular Toxoplasmosis in HIV-infected Patients.

Ocul Immunol Inflamm 2020 Oct 12;28(7):1031-1039. Epub 2020 Mar 12.

Gepamol. Centro de Investigaciones Biomédicas, Universidad del Quindío , Armenia, Q, Colombia.

Ocular toxoplasmosis (OT) may be an initial manifestation of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected patients. OT has different clinical manifestations and can mimic other intraocular infections. Clinical findings may show single or multifocal retinochoroidal lesions or panuveitis. Atypical presentations are associated with extensive uni- or bilateral areas of retinal necrosis. OT lesions not associated with preexisting retinochoroidal scars are usually due to acquired rather than congenital infection. When CD4+ T cell counts are <100 c/uL, vitritis is frequently mild. Isolated anterior uveitis has been reported in single cases. Positive immunoglobulin M (IgM) antibodies are rare but their presence can support the diagnosis. As atypical presentations of OT are common, anterior chamber puncture for multiplex polymerase chain reaction amplification of infectious DNA should be considered, as early diagnosis and treatment can prevent massive tissue destruction and preserve vision. This review provides an overview of OT in HIV-infected patients.
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http://dx.doi.org/10.1080/09273948.2020.1735450DOI Listing
October 2020

Bilateral corneal perforation and iris prolapse as a complication non-peripheral ulcerative keratitis in a patient with fulminant granulomatosis with polyangiitis: a case report.

J Ophthalmic Inflamm Infect 2020 Jan 10;10(1). Epub 2020 Jan 10.

NeURos Research Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63, C 69, Bogotá, Colombia.

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http://dx.doi.org/10.1186/s12348-020-0195-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954162PMC
January 2020

Influence of Two Major Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection.

Front Cell Infect Microbiol 2019 4;9:413. Epub 2019 Dec 4.

Grupo de Estudio en Parasitología Molecular (GEPAMOL), Facultad de Ciencias de la Salud, Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia.

ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-γ, IL-10, and IL-1β levels in supernatants from PBMCs cultures infected with tachyzoites of the wild-type RH strain or with knock-out mutants of the and encoding genes (RHΔ and RHΔ). Cytokine secretion was compared between PBMCs obtained from seronegative individuals ( = 10), with those with chronic asymptomatic ( = 8), or ocular infection ( = 12). We also evaluated if polymorphisms in the genes encoding for -γ, β, Toll-like receptor 9 (), and purinoreceptor influenced the production of the encoded proteins after stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RHΔ, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1β was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-γ production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response.
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http://dx.doi.org/10.3389/fcimb.2019.00413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904310PMC
August 2020

Mutant GNLY is linked to Stevens-Johnson syndrome and toxic epidermal necrolysis.

Hum Genet 2019 Dec 14;138(11-12):1267-1274. Epub 2019 Oct 14.

Center For Research in Genetics and Genomics (CIGGUR), GENIUROS Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 No. 63C-69, Bogotá, DC, 112111, Colombia.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to drugs. Granulysin (GNLY) plays a key role in keratinocyte apoptosis during SJS/TEN pathophysiology. To determine if GNLY-encoding mutations might be related to the protein's functional disturbances, contributing to SJS/TEN pathogenesis, we performed direct sequencing of GNLY's coding region in a group of 19 Colombian SJS/TEN patients. A GNLY genetic screening was implemented in a group of 249 healthy individuals. We identified the c.11G > A heterozygous sequence variant in a TEN case, which creates a premature termination codon (PTC) (p.Trp4Ter). We show that a mutant protein is synthesised, possibly due to a PTC-readthrough mechanism. Functional assays demonstrated that the mutant protein was abnormally located in the nuclear compartment, potentially leading to a toxic effect. Our results argue in favour of GNLY non-synonymous sequence variants contributing to SJS/TEN pathophysiology, thereby constituting a promising, clinically useful molecular biomarker.
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http://dx.doi.org/10.1007/s00439-019-02066-wDOI Listing
December 2019

Ocular findings in Fabry disease in Colombian patients

Biomedica 2019 09 1;39(3):434-439. Epub 2019 Sep 1.

Grupo de Investigación en Oftalmología, Escuela Superior de Oftalmología, Instituto Barraquer de América, Bogotá, D.C., Colombia.

Fabry disease is a rare X-linked disorder caused by an alpha-galactosidase enzyme deficiency, which leads to a progressive lysosomal glycosphingolipids accumulation, mainly globotriaosylceramide, in multiple organism tissues including the eye. This case series describes the first ophthalmological Colombian report of Fabry disease highlighting the importance of ocular signs as markers of the disease, useful in diagnosis and treatment to avoid long-term complications that lead to a morbi-mortality increment. We describe five cases of Fabry disease from Bogotá, Colombia, including a complete clinical history, ophthalmologic, optometric examination, and photographs. We found that all patients had refractive defects and that in all cases corneal verticillata pattern was found. Four patients presented with posterior capsule lens brown-beige deposits and four patients had conjunctival and retinal tortuous vessels. A complete ophthalmologic examination is important for prompt diagnosis, which is key to starting a multidisciplinary treatment and reducing morbi-mortality.
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http://dx.doi.org/10.7705/biomedica.3841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357367PMC
September 2019

Nodular Necrotizing-Scleritis Associated with Epstein-Barr Virus Infection: A Case Report.

Ocul Immunol Inflamm 2020 May 27;28(4):556-558. Epub 2019 Sep 27.

Neuroscience Research Group-NeURos, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario , Bogotá, Colombia.

Purpose: To report a case of necrotizing scleritis associated with Epstein-Barr virus (EBV) infection.

Case Report: A 68-year-old woman with a history of scleral ulcer, perforation, and scleral graft, with initial negative studies for infectious processes and autoimmune systemic-diseases consulted our service for a second opinion after 2 years of treatment without improvement. She presented severe conjunctival and scleral hyperemia, vascular tortuosity in 360°, areas of scleral thinning and an elevated lesion of nodular appearance. EBV serologic antibody IgG titers were strongly positive and IgM titers were borderline. A scleral biopsy showed granulation tissue with severe inflammation without the presence of tumor cells; PCR was positive for EBV. The patient was treated with antiviral therapy with resolution of the scleritis.

Conclusions: EBV although rare, should be considered as a differential diagnosis in patients with necrotizing scleritis with no improvement to conventional therapy.
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http://dx.doi.org/10.1080/09273948.2019.1611877DOI Listing
May 2020

Antibiotic treatment for ocular toxoplasmosis: a systematic review and meta-analysis: study protocol.

Syst Rev 2019 06 20;8(1):146. Epub 2019 Jun 20.

NeURos research group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63 C 69, Bogotá, Colombia.

Background: Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, leading to visual impairment in a high proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual impairment by reducing the size of the retinochoroidal scar, the risk of recurrence, and the severity and duration of acute symptoms. Although OT is a very common cause of infectious posterior uveitis, its treatment remains controversial. Through our systematic review and meta-analysis, we aim to provide the best possible evidence-based information on the safety and effectiveness of the different antibiotic regimes for OT.

Methods: This systematic review protocol has been developed based on PRISMA-P guidelines for reporting systematic reviews evaluating health care interventions. We will include all published and unpublished randomized controlled trials (RCTs) comparing different antibiotics used for the treatment of OT. We will consider changes in visual acuity, number of recurrences, improvement or worsening of ocular inflammation, size of lesion, and adverse effects as our outcomes. Screening, data extraction, and quality assessment will be undertaken by two reviewers with disagreements resolved through discussion. Studies that compared antibiotics with placebo will be excluded. The reviews will be assessed for quality and relevance. We will assess the risk of bias in five domains according to Cochrane group's tool. The type of data will dictate measures of treatment effect. We will use a random-effects model to calculate our meta-analysis, as eligible studies represent clinically varied populations of participants.

Discussion: The strength of our study will lie in the exhaustive and systematic nature of the literature search, as well as in its methods for assessing quality and analyzing RCT data. Considering the controversial efficacy of the treatment for OT, our study will contribute to improving the existing evidence on the effectiveness of different antibiotics. Future studies may be conducted to increase physicians' awareness of antibiotic therapies, improving the health of patients with OT.

Systematic Review Registration: PROSPERO CRD42018085468.
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http://dx.doi.org/10.1186/s13643-019-1067-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587239PMC
June 2019

Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans-A Review of the Literature.

Medicina (Kaunas) 2019 Jun 17;55(6). Epub 2019 Jun 17.

Neuroscience Research Group (NeurUROS), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, 11121, Colombia.

Glaucoma is a common complex disease that leads to irreversible blindness worldwide. Even though preclinical studies showed that lowering intraocular pressure (IOP) could prevent retinal ganglion cells loss, clinical evidence suggests that lessening IOP does not prevent glaucoma progression in all patients. Glaucoma is also becoming more prevalent in the elderly population, showing that age is a recognized major risk factor. Indeed, recent findings suggest that age-related tissue alterations contribute to the development of glaucoma and have encouraged exploration for new treatment approaches. In this review, we provide information on the most frequently used experimental models of glaucoma and describe their advantages and limitations. Additionally, we describe diverse animal models of glaucoma that can be potentially used in translational medicine and aid an efficient shift to the clinic. Experimental animal models have helped to understand the mechanisms of formation and evacuation of aqueous humor, and the maintenance of homeostasis of intra-ocular pressure. However, the transfer of pre-clinical results obtained from animal studies into clinical trials may be difficult since the type of study does not only depend on the type of therapy to be performed, but also on a series of factors observed both in the experimental period and the period of transfer to clinical application. Conclusions: Knowing the exact characteristics of each glaucoma experimental model could help to diminish inconveniences related to the process of the translation of results into clinical application in humans.
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http://dx.doi.org/10.3390/medicina55060280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630440PMC
June 2019

Uveitis and Multiple Sclerosis: Potential Common Causal Mutations.

Mol Neurobiol 2019 Dec 3;56(12):8008-8017. Epub 2019 Jun 3.

Grupo de Investigación en Psiquiatría (GIPSI), Departamento de Psiquiatría, Instituto de Investigaciones Medicas (IIM), Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.

Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has been associated with systemic autoimmune disorders, specifically with multiple sclerosis (MS). This article reports a rare three-generation family with several members affected by IU (four siblings) and comorbid MS (two siblings fulfilling MS diagnostic criteria and a third sibling presenting some neurological symptoms). Based on the clinical findings, we captured and sequenced whole exomes of seven pedigree members (affected and unaffected). Using a recessive model of transmission with full penetrance, we applied genetic linkage analysis to define minimal critical regions (MCRs) in suggestive or nominal regions of linkage. In these MCRs, we defined functional (some pathogenic), novel, and rare mutations that segregated as homozygous in affected and heterozygous in unaffected family members. The genes harboring these mutations, including DGKI, TNFRSF10A, GNGT1, CPAMD8, and BAFF, which are expressed in both eye and brain tissues and/or are related to autoimmune diseases, provide new avenues to evaluate the inherited causes of these devastating autoimmune conditions.
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http://dx.doi.org/10.1007/s12035-019-1630-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834745PMC
December 2019

Type I ROP16 regulates retinal inflammatory responses during ocular toxoplasmosis.

PLoS One 2019 22;14(3):e0214310. Epub 2019 Mar 22.

Institut de Parasitologie et Pathologie Tropicale, EA, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.

Ocular toxoplasmosis (OT), mostly retinochorioditis, is a major feature of infection with the protozoan parasite Toxoplasma gondii. The pathophysiology of this infection is still largely elusive; especially mouse models are not yet well developed. In contrast, numerous in vitro studies showed the highly Toxoplasma strain dependent nature of the host-parasite interactions. Some distinct polymorphic virulence factors were characterized, notably the rhoptry protein ROP16. Here, we studied the strain-dependent pathophysiology in our OT mouse model. Besides of two wild type strains of the canonical I (RH, virulent) and II (PRU, avirulent) types, we used genetically engineered parasites, RHΔROP16 and PRU ROP16-I, expressing the type I allele of this virulence factor. We analyzed retinal integrity, parasite proliferation and retinal expression of cytokines. PRU parasites behaved much more virulently in the presence of a type I ROP16. In contrast, knockout of ROP16 in the RH strain led to a decrease of intraocular proliferation, but no difference in retinal pathology. Cytokine quantification in aqueous humor showed strong production of Th1 and inflammatory markers following infection with the two strains containing the ROP16-I allele. In strong contrast, immunofluorescence images showed that actual expression of most cytokines in retinal cells is rapidly suppressed by type I strain infection, with or without the involvement of its homologous ROP16 allele. This demonstrates the particular immune privileged situation of the retina, which is also revealed by the fact that parasite proliferation is nearly exclusively observed outside the retina. In summary, we further developed a promising OT mouse model and demonstrated the specific pathology in retinal tissues.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430381PMC
December 2019

Coinfections and differential diagnosis in immunocompetent patients with uveitis of infectious origin.

BMC Infect Dis 2019 Jan 25;19(1):91. Epub 2019 Jan 25.

GEPAMOL, Centro de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Universidad del Quindío, Armenia, Colombia.

Background: Making a definite diagnosis of infectious uveitis is a challenging task because many other infectious, and non-infectious uveitis, may have similar non-specific symptoms and overlapping clinical appearances. Co-infections in immunocompetent patients are not frequently proved with traditional serologic-diagnostic tools.

Methods: Descriptive transversal study, in a Uveitis Service of an Ophthalmology Reference Center, in Bogotá, Colombia, from July 2014 to February 2016. Aqueous humor (AH) and/or vitreous fluid, blood and serum samples were collected from consecutive patients suspected of having infectious uveitis. The diagnosis of ocular toxoplasmosis (OT) was confirmed by the Goldmann-Witmer coefficient (GWC) and by polymerase chain reaction (PCR). Differential diagnosis by PCR in AH was done for viral origin such as Cytomegalovirus (CMV), Herpes simplex virus type 1 (HSV1), Herpes simplex virus type 2 (HSV2), Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and Mycobacterium tuberculosis.

Results: In 66 Colombian patients with uveitis of presumed infectious origin: 22 (33.3%) were confirmed as OT, 16 (24.2%) as undetermined OT, five (7.5%) as co-infections and 23 (34.8%) as other uveitis. Toxoplasma coinfection with M. tuberculosis was identified in one case by PCR and in four cases with HSV by GWC. The initial clinical diagnosis changed, after laboratory examination, in 21 cases (31.8%).

Conclusions: Clinical diagnosis can be changed by laboratory examination in a significant proportion of cases of uveitis. Diagnosis of OT should combine the use of PCR and GWC to reach the maximum of confirmation of cases. The use of multiple laboratory methods is necessary to identify co-infections and viral infections that can mimic OT in immunocompetent patients.
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http://dx.doi.org/10.1186/s12879-018-3613-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347798PMC
January 2019

Visual Features in Alzheimer's Disease: From Basic Mechanisms to Clinical Overview.

Neural Plast 2018 14;2018:2941783. Epub 2018 Oct 14.

Grupo de Investigación en Neurociencias (NeURos), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It compromises patients' daily activities owing to progressive cognitive deterioration, which has elevated direct and indirect costs. Although AD has several risk factors, aging is considered the most important. Unfortunately, clinical diagnosis is usually performed at an advanced disease stage when dementia is established, making implementation of successful therapeutic interventions difficult. Current biomarkers tend to be expensive, insufficient, or invasive, raising the need for novel, improved tools aimed at early disease detection. AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (A), and neurofibrillary tangles of hyperphosphorylated tau protein. The visual system and central nervous system share many functional components. Thus, it is plausible that damage induced by A, tau, and neuroinflammation may be observed in visual components such as the retina, even at an early disease stage. This underscores the importance of implementing ophthalmological examinations, less invasive and expensive than other biomarkers, as useful measures to assess disease progression and severity in individuals with or at risk of AD. Here, we review functional and morphological changes of the retina and visual pathway in AD from pathophysiological and clinical perspectives.
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http://dx.doi.org/10.1155/2018/2941783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204169PMC
January 2019

Virus-Induced Anterior Uveitis (VIAU) in Immunocompromised Patients.

Ocul Immunol Inflamm 2018 ;26(5):807-817

a Grupo de Investigación en Neurociencias (NeURos), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario , Bogotá , Colombia.

Purpose: To describe the clinical characteristics, diagnosis, and treatment of VIAU in immunocompromised patients.

Methods: A critical review of literature was performed.

Results: Diagnosis and treatment of VIAU in immunocompromised patients may be a challenge due to atypical clinical-courses, severe presentations, and more frequent recurrences. A conclusive diagnosis can be made by aqueous-humour PCR-analysis. Visual prognosis depends on early diagnosis and prompt treatment. Frequent ocular examinations are recommended in HIV patients with CD-4-counts below 100 in order to rule out opportunistic ocular coinfections. It is essential to bear in mind the potential side-effects of therapeutic interventions and consider the possibility of Immune Recovery Uveitis (IRU) in eyes with treated viral retinitis after the initiation of HAART.

Conclusions: Early diagnosis and treatment of VIAU in immunocompromised patients can be achieved with high suspicion, recognizing clinical features, and obtaining specimens for molecular diagnostic testing in order to avoid usually severe ocular morbidity.
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http://dx.doi.org/10.1080/09273948.2018.1483519DOI Listing
September 2018

Polymerase chain reaction (PCR) in ocular and ganglionar toxoplasmosis and the effect of therapeutics for prevention of ocular involvement in South American setting.

Acta Trop 2018 Aug 31;184:83-87. Epub 2018 Jan 31.

Grupo de Estudio en Parasitología Molecular (GEPAMOL), Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia; Grupo de Investigación en Neurociencias (NeURos), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia. Electronic address:

Introduction: Cases of toxoplasmosis present in South America tend to be more severe than that found in other continents. Here, we present our clinical experience of ocular and ganglionar toxoplasmosis in the use of PCR, and of the treatment to prevent ocular involvement.

Methodology: Retrospective analysis of clinical charts of patients with ocular and lymphadenitic toxoplasmosis at the parasitology and tropical medicine consultation in the "Universidad del Quindio" in Colombia. In total, 91 records of cases with ocular toxoplasmosis and 17 with lymphadenitis that underwent PCR analysis for B1 repeated sequence in blood, were compared to the results of 104 people with chronic asymptomatic toxoplasmosis. In addition, 41 clinical records were included from patients with confirmed toxoplasmic lymphadenitis: 10 untreated, 6 that begun treatment after four months of symptoms, and 25 that were treated during the first four months of symptoms and had a follow-up during at least one year.

Results: Patients with ocular toxoplasmosis or lymphadenitis had a higher probability of PCR positivity in peripheral blood than chronic asymptomatic people. There were no cases of retinochoroiditis in 25 patients with toxoplasmic lymphadenitis treated before 4 months of symptoms and followed during at least 12 months. In four out of ten untreated cases, new lesions of retinochoroiditis presented after the symptoms of lymphadenitis.

Conclusions: Toxoplasmosisin South America exhibits different clinical behavior and this influences the laboratory results as well as the need for treatment in the case of lymphadenitis. Clinicians should be aware of the geographical origin of the infection in order to adopt different therapeutic and diagnostic approaches.
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http://dx.doi.org/10.1016/j.actatropica.2018.01.013DOI Listing
August 2018

Vogt-Koyanagi-Harada Syndrome in a Group of Patients in Two Ophthalmology Referral Centers in Bogotá, Colombia.

Ocul Immunol Inflamm 2018 14;26(7):1123-1127. Epub 2017 Sep 14.

a Fundación Oftalmológica Nacional (FUNDONAL), Uveitis Service, Bogotá, Columbia.

Purpose: To describe the clinical presentation of Vogt-Koyanagi-Harada (VKH) syndrome in a group of patients in Colombia.

Methods: Retrospective review of 2638 medical records of patients with uveitis in two centers during 17 years.

Results: A total of 25 patients with uveitis were diagnosed with VKH syndrome (0.95%), 23 patients were included in the data analysis (0.87%), 78.3% females, and mean age of diagnosis was 37 years (SD ± 29). Main complaints: blurred vision (87%), headaches (47.8%), tinnitus (26.1%), and hearing impairments (21.7%). Ophthalmic findings: bilateral serous retinal detachment (73.9%) and non-granulomatous uveitis (52.3%). Most of the patients were diagnosed with probable disease (56.5%). Mean duration of follow-up was 14 months; disease relapse was encountered in 26% of patients despite treatment.

Conclusion: Patients in Colombia with VKH had clinical features similar to those reported in other Hispanic populations, except for the non-granulomatous uveitis. This disease may be considered as having variation of clinical manifestations across population groups.
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http://dx.doi.org/10.1080/09273948.2017.1341536DOI Listing
December 2018

Bilateral Iris Depigmentation and Ocular Hypotony as End-Stage Manifestations of Untreated Vogt-Koyanagi-Harada Disease.

Ocul Immunol Inflamm 2018 26;26(7):1101-1106. Epub 2017 May 26.

c Ophthalmology Department , School of Medicine, CES University , Medellín , Colombia.

Purpose: To describe severe bilateral iris depigmentation and persistent ocular hypotony as end-stage manifestations of untreated Vogt-Koyanagi-Harada disease.

Methods: We present the clinical findings and diagnostic studies performed for three patients with bilateral iris depigmentation.

Results: Vogt-Koyanagi-Harada disease in late recurrent stage was diagnosed in three patients with bilateral severe iris depigmentation and persistent ocular hypotony.

Conclusions: Early diagnosis and treatment of inflammation are crucial factors in the clinical outcome of Vogt-Koyanagi-Harada disease. When left undiagnosed and untreated from early stages, severe iris depigmentation and ocular hypotony, uncommon manifestations of this disease, can develop.
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http://dx.doi.org/10.1080/09273948.2017.1320411DOI Listing
December 2018