Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela

IMPORTANCE The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed. OBJECTIVE To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. DESIGN, SETTING, AND PARTICIPANTS This prospective case series included 43 patients from 2 ophthalmic centers in Colombia and Venezuela who underwent evaluation from October 1, 2015, through June 30, 2016, and were clinically diagnosed with congenital Zika syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native American. INTERVENTIONS Ophthalmic and systemic evaluations and serologic testing were performed on all infants. Patients underwent external ocular examination and dilated ophthalmoscopy. Serologic testing ruled out toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus. MAIN OUTCOMES AND MEASURES Ophthalmic manifestations of congenital Zika syndrome. RESULTS Of the 43 patients included in this series (28 female and 15 male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all the children had no ophthalmic findings and did not report ocular symptoms during pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve findings included hypoplasia with the double-ring sign, pallor, and increased cup-disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%). Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had a combination of lesions in the posterior pole. Five patients (12%) were diagnosed with congenital glaucoma, characterized by the clinical triad of epiphora, photophobia, and blepharospasm; increased intraocular pressure; corneal clouding at birth; and buphthalmos. These data reveal that 12%(95%CI, 5%-24%) of cases of congenital Zika with microcephaly had anterior segment abnormalities and 88%(95%CI, 76%-94%) had important macular and optic nerve abnormalities. The visual sequelae of these ophthalmic manifestations remain unknown. CONCLUSIONS AND RELEVANCE Congenital Zika syndrome in the current study had severe ocular abnormalities, and all patients had bilateral involvement. Ocular findings were focal macular pigment mottling, chorioretinal atrophy with a predilection for the macular area, congenital glaucoma and optical nerve hypoplasia, and optic disc abnormalities. Ophthalmic examination is recommended in patients with congenital Zika syndrome

Non-congenital severe ocular complications of Zika virus infection

In 2016, during a major Zika virus (ZIKV) outbreak in Maracaibo, Venezuela, a 49-year-old woman and an unrelated 4-year-old boy developed bilateral optic neuritis 2–3 weeks after presenting an acute febrile illness characterized by low-grade fever, rash and myalgia [1]. Both patients presented sudden, painless bilateral loss of vision with no corneal or uveal abnormalities. Fundoscopic examination revealed oedema of the optic nerve and optic disc pallor. Optical coherence tomography confirmed bilateral optic nerve head swelling in the case of the adult, but it was not carried out in the child. Automated perimetry performed in the adult revealed bilateral diffuse visual field loss. Magnetic resonance imaging of the brain in both cases was unremarkable. Both patients were diagnosed with bilateral optic neuritis of possible infectious or parainfectious origin. Differential diagnoses that were considered and subsequently discarded included arteritic and non-arteritic ischaemic optic neuropathy, and brain disorders such as multiple sclerosis and brain tumours. Both patients were seropositive for anti-ZIKV IgG and seronegative for anti-ZIKV IgM. In addition, both patients were positive for anti-dengue virus (DENV) IgG for all four DENV serotypes. Management included intravenous methylprednisolone for 3 days, followed by oral prednisolone for 11 days. Although the patients presented a modest improvement in their vision, they continued to have visual impairment after several months of follow-up [1]

Optic neuropathy and congenital glaucoma associated with probable Zika virus infection in Venezuelan patients

Introduction: Although the current Zika virus (ZIKV) epidemic is a major public health concern, most reports have focused on congenital ZIKV syndrome, its most devastating manifestation. Severe ocular complications associated with ZIKV infections and possible pathogenetic factors are rarely described. Here, we describe three Venezuelan patients who developed severe ocular manifestations following ZIKV infections. We also analyse their serological response to ZIKV and dengue virus (DENV). Case presentation: One adult with bilateral optic neuritis, a child of 4 years of age with retrobulbar neuritis [corrected]. and a newborn with bilateral congenital glaucoma had a recent history of an acute exanthematous infection consistent with ZIKV infection. The results of ELISA tests indicated that all patients were seropositive for ZIKV and four DENV serotypes. Conclusion: Patients with ZIKV infection can develop severe ocular complications. Anti-DENV antibodies from previous infections could play a role in the pathogenesis of these complications. Well-designed epidemiological studies are urgently needed to measure the risk of ZIKV ocular complications and confirm whether they are associated with the presence of anti-flaviviral antibodies

Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure: Findings from the Maracaibo Aging Study

Purpose—To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. Design—Observational cross-sectional study. Participants—A subset (n=93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants — who were at least 40 years of age — had measurements for optical tomography coherence, visual field tests, 24-hour BP, office BP, and intraocular pressureHg. Methods—Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to drops in nocturnal BP. Main Outcome Measures—Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and visual field defects. Results—The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 50 (27.0%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme drops in nighttime systolic and diastolic BP (\u3e20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio=19.78 and 5.55, respectively). Conclusions—In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme drops in nocturnal BP in individuals at high risk of glaucoma are warranted

Correlates of condom use in a sample of MSM in Ecuador

BACKGROUND: In Ecuador, the prevalence of HIV in the general population is approximately 0.3%. However, up to 17% prevalence has been reported among specific groups of homosexual and bisexual men. The objective of this study is to explore correlates of condom use among men who have sex with men (MSM) across eight cities in Ecuador. METHODS: A cross-sectional survey design was used. A questionnaire including variables on sexual behaviour, demographics, and socio-economic characteristics was distributed to a sample of MSM in eight Ecuadorian cities. RESULTS: Information was obtained for 2,594 MSM across the eight cities. The largest subcategory of self-identification was active bisexuals (35%), followed by those who described themselves as "hombrados" (masculine gays, 22%). The mean age was 25 years, and the majority were unmarried (78%), with a median of 10 years of schooling (IQR 7 – 12). Regarding condom use, 55% of those interviewed had unprotected penetrative sex with each of their last three partners, and almost 25% had never used a condom. The most important correlates of condom use were single status, high life-skills rating, and high socio-economic status (RP 5.45, 95% CI 4.26 – 6.37; RP 1.84, 95% CI 1.79 – 1.86, and RP 1.20, 95% CI 1.01 – 1.31, respectively). CONCLUSION: Our data illustrate the urgent need for targeted HIV-prevention programs for MSM populations in Ecuador. MSM have the highest HIV prevalence in the country, and condom use is extremely low. It is imperative that prevention strategies be re-evaluated and re-prioritized to more effectively respond to the Ecuadorian epidemic

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Pseudotumoral and Multiple Retinal Pigment Epithelium Proliferation in Vogt-Koyanagi-Harada Disease

We report a case of pseudotumoral retinal pigment epithelium (RPE) proliferation in Vogt-Koyanagi-Harada (VKH) disease, in a 50-year-old female who presented with a juxtapapillary and peripheral subretinal hyperpigmented lesions in the left eye and “sunset glow fundus,” hyperpigmented striae, and multiple atrophic chorioretinal spots in the periphery. The darkly pigmented exuberant larger subretinal mass extended to the periphery with associated subretinal fibrosis. This patient demonstrated the entire clinical presentation of VKH disease, which tends to course with a chronic, bilateral, granulomatous panuveitis and exudative retinal detachment associated with poliosis, vitiligo, alopecia, and central nervous system and auditory signs. Our case is unique for the presence of exuberant, pseudotumoral RPE proliferation at the juxtapapillary region and peripheral area. Although this complication has rarely been reported, a high index of suspicion is warranted for early diagnosis and avoids unnecessary treatments of a pseudotumor

Non-congenital severe ocular complications of Zika virus infection

International audienceIn 2016, during a major Zika virus (ZIKV) outbreak in Maracaibo, Venezuela, a 49-year-old woman and an unrelated 4-year-old boy developed bilateral optic neuritis 2-3 weeks after presenting an acute febrile illness characterized by low-grade fever, rash and myalgia [1]. Both patients presented sudden, painless bilateral loss of vision with no corneal or uveal abnormalities. Fundoscopic examination revealed oedema of the optic nerve and optic disc pallor. Optical coherence tomography confirmed bilateral optic nerve head swelling in the case of the adult, but it was not carried out in the child. Automated perimetry performed in the adult revealed bilateral diffuse visual field loss. Magnetic resonance imaging of the brain in both cases was unremarkable. Both patients were diagnosed with bilateral optic neuritis of possible infectious or parainfectious origin. Differential diagnoses that were considered and subsequently discarded included arteritic and non-arteritic ischaemic optic neuropathy, and brain disorders such as multiple sclerosis and brain tumours. Both patients were seropositive for anti-ZIKV IgG and seronegative for anti-ZIKV IgM. In addition, both patients were positive for anti-dengue virus (DENV) IgG for all four DENV serotypes. Management included intravenous methylprednisolone for 3 days, followed by oral prednisolone for 11 days. Although the patients presented a modest improvement in their vision, they continued to have visual impairment after several months of follow-up [1]. DISCUSSION Correct Answer: 4. These complications can lead to permanent visual impairment. ZIKV is a mosquito-borne RNA virus belonging to the genus Flavivirus of the family Flaviviridae [2]. The classical QUESTION Which of the following statements is accurate about non-congenital severe ocular complications of Zika virus (ZIKV) infection? ANSWER OPTIONS 1. They are unique to ZIKV infection and readily distinguish-able from complications caused by other flaviviruses. 2. Serious ocular complications are related to the severity of the acute exanthematous illness. 3. The diagnosis can be conclusively established by detecting anti-Zika IgM and/or IgG in the patient's serum. 4. These complications can lead to permanent visual impairment. 5. There is specific treatment for ocular manifestations caused by ZIKV infection. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. 1 clinical picture of ZIKV infection includes fever, exanthema, headache and conjunctivitis. The most common non-congenital, ocular manifestation of ZIKV infection is a self-limiting conjunctivitis. Serious ocular complications have been reported for other arboviruses, such as DENV [3-20], chikungunya virus [21-24], West Nile virus [25-39] and Rift Valley fever virus [9-11, 40] (Table 1). To date, there is no specific ocular lesion that is pathognomonic for ZIKV infection [41-45]. Non-congenital ocular complications are infrequent, but serious, consequences of ZIKV and other arboviral infections. The complications may appear at the end of the acute febrile illness, but more commonly occur within 2 weeks to 1 month after the onset of symptoms. There is no evidence to suggest that serious ocular complications correlate with the severity of the acute febrile illness. One study, however, found that the white cell count and serum albumin are significant predictors of ocular complications of DENV [46]. Serological testing for arboviral diseases should be performed in all patients with ocular complications and a recent history of acute febrile exanthematous infection, who live, or have travelled to, endemic regions. The presence of IgM to ZIKV strongly suggests that the ocular manifestation is associated with this virus. A causative aetiology, however, can only be established by documenting the presence of the virus in body fluids, either by cell culture or by PCR. It should be noted that other viruses, such as herpes simplex virus and human immunodeficiency virus, can also cause retinal damage and optic neuritis. Furthermore, as in the cases presented here, the diagnosis is complicated by cross-reactivity among flaviviruses, and by the co-circulation of arboviruses. Most patients with ocular complications of arboviral infections recover completely. Nevertheless, physicians should be aware that a small percentage of patients have permanent damage with long-life visual impairment. There is no specific or established treatment for optic neuritis caused by any arboviral infection. Systemic steroids may be used to reduce inflammation and resulting ischae-mia. Corticosteroids have been used in combination with acyclovir to treat chikungunya-associated optic neuritis, but efficacy has not been proven [47]

Heritability of Ocular Traits in Hispanics

Purpose: The burden of glaucoma disease among Hispanics is significantly higher than in their white counterparts. It remains unclear to what extent these differences are determined by genetic factors in Hispanics. We therefore examined a highly inbred family population-based cohort in Venezuela to estimate the proportion of genetic contribution of ocular traits relevant to glaucoma disease. Methods: A subset of 67 participants ≥40y from the Maracaibo Aging Study (MAS) with family pedigree were randomly included. The papillary retinal nerve fiber layer (RNFL) and macular thickness were measured with Spectralis Domain-OCT. Heritability analyses (h2, expressed as %) were performed using the variance components approach as implemented in the software package Sequential Oligogenic Linkage Analysis Routines. A likelihood ratio test was used to test whether the heritability of a given phenotype was significantly (P Results: Heritability estimates were significant for 13 out of 62 ocular traits analyzed. Total RNFL thickness (h2=0.79, P=0.007 for right eye and h2=0.72, P=0.026 for left eye), as well as thickness of the right eye superior (h2=0.60, P2=0.82, P2=0.86, P2=0.71; P Conclusions: Several heritability estimates were in the moderate to high range, suggesting this highly inbred cohort may provide insight into the molecular basis of the intermediate ocular traits, which in turn may explain underlying causes of glaucoma