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Ocular Adverse Events following Yellow Fever Vaccination: A Case Series
Abstract
Purpose: To describe four cases of ocular adverse events resembling intraocular inflammatory and non-inflammatory conditions following yellow fever vaccination (YFV) during a recent yellow fever (YF) outbreak in Brazil.
Methods: Charts of patients diagnosed with ocular adverse events after YFV between January 2017 and January 2019 at two tertiary referral centers in Brazil.
Results: Four patients (two adults and two children) are reported. Case 1 presented with typical findings of central serous chorioretinopathy which resolved spontaneously; case 2 was diagnosed with acute Vogt-Koyanagi-Harada disease; cases 3 and 4 had bilateral diffuse retinal vasculitis. In the absence of infectious and noninfectious disorders, the temporal association between stand-alone YFV and onset of ocular symptoms within 15 days was interpreted as evidence of causation.
Conclusions: Clinicians should be aware of the wide spectrum of possible ocular adverse reactions to stand-alone YFV.
... After conducting a comprehensive review, a total of 51 reported cases (involving 61 patients), spanning from 1978 to 2023, have been associated with uveitis following various vaccinations (Table 1), including 4 case reports (5 patients) related to hepatitis B virus (HBV) vaccination [28][29][30][31]; 7 case reports (8 patients) related to human papillomavirus (HPV) vaccination [21][22][23][32][33][34][35]; 16 cases (18 patients) regarding uveitis after influenza vaccination [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]; 3 cases (4 patients) related to measles-mumps-rubella (MMR) vaccination [52][53][54]; 12 cases (16 patients) related to varicella zoster virus (VZV) vaccination [24][25][26][27][55][56][57][58][59][60][61][62]; 4 cases (5 patients) for yellow fever [63][64][65][66]; one each for hepatitis A virus (HAV) [67] and rabies virus vaccination [68]; and 3 case reports involving mixed vaccine administrations [69][70][71]. ...
... Based on the site of infection, this study included 11 cases of anterior uveitis [27,35,37,45,52,54,56,58,63], 1 case of intermediate uveitis [63], 8 cases of posterior uveitis [21,22,27,28,32,42], 3 cases of uveitis involving both anterior and intermediate segments [27,55,64], 1 case of anterior and posterior uveitis [38], and 7 cases of pan-uveitis [23,34,40,43,48,53]. Distinct types of uveitis, such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE) [36,41,46,47,57], Vogt-Koyanagi-Harada syndrome (VKH) [31,39,49,51,65,66], multiple evanescent white dot syndrome (MEWDS) [30,33,50,[67][68][69][70], acute retinal necrosis (ARN) [24][25][26]59,61,62], and uveitis sarcoidosis [60] were also included. Most patients presented with bilateral involvement (bilateral:unilateral = 36:25), and left eye involvement was more common among patients with unilateral involvement (left:right = 16:9). ...
... Although rarely reported as a uveitis trigger, the yellow fever vaccine, a live attenuated vaccine, has been associated with autoimmune disorders such as neuromyelitis optica spectrum disorder [119]. Only four reports (involving five patients) were included [64][65][66][67], with an average age of 34.4 years and a male-to-female ratio of 3:2. All patients developed symptoms within 3 weeks post-vaccination and initially presented with systemic manifestations. ...
The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.
... Vaccines were shown in few case reports to trigger the development of VKH, namely, influenza, yellow fever, hepatitis B and BCG vaccines [19][20][21][22][23][24]. Recently, Papasavvas and Herbort [25] described a patient who suffered from VKH reactivation 6 weeks after the second dose of a BNT162b2 COVID-19 vaccine, while treated with infliximab infusions every 10 weeks. ...
... A recent publication [28] assessed the risk of vaccine-associated uveitis (VAU) following SARS-CoV-2 vaccination using the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Pereima et al. [23] Kim [22] Gallagher et al. [24] Papasavvas et al. [25] Saraceno et al. [27] Koong et al. [ Pereima et al. [23] Kim [22] Gallagher et al. [24] Papasavvas et al. [25] Saraceno et al. [27] Koong et al. [26] Time to full visual acuity recovery [29] and Wang et al. [30] reported that 90.96 and 74% of their cohort, respectively, had anterior uveitis. Analysis of the largest adverse event global database suggested that VAU was primarily diagnosed after first dose and within first week following vaccination. ...
... A recent publication [28] assessed the risk of vaccine-associated uveitis (VAU) following SARS-CoV-2 vaccination using the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Pereima et al. [23] Kim [22] Gallagher et al. [24] Papasavvas et al. [25] Saraceno et al. [27] Koong et al. [ Pereima et al. [23] Kim [22] Gallagher et al. [24] Papasavvas et al. [25] Saraceno et al. [27] Koong et al. [26] Time to full visual acuity recovery [29] and Wang et al. [30] reported that 90.96 and 74% of their cohort, respectively, had anterior uveitis. Analysis of the largest adverse event global database suggested that VAU was primarily diagnosed after first dose and within first week following vaccination. ...
Purpose
To report the occurrence of posterior ocular adverse events following the administration of the BNT162b2 mRNA vaccine against SARS-CoV-2.
Methods
A retrospective consecutive case series, in which the medical files of patients presenting with ocular adverse events within 30 days of the vaccine inoculation, were analyzed.
Results
Four patients (2 females) were included in the study. The diagnoses included: posterior scleritis, paracentral acute middle maculopathy, herpes panuveitis, and Vogt–Koyanagi–Harada (VKH)-like uveitis. Three of the patients had no relevant ocular history, but the patient who developed scleritis was in remission without medical therapy for four years, until the flare-up, which occurred one day after the vaccine. All patients improved with treatment.
Conclusion
Though a causal relationship cannot be definitively established, the temporal relationship suggests a possible link between the COVID-19 vaccine and the posterior ocular complications. The benefits of vaccination clearly outweigh the potential adverse effects; however, ophthalmologists should be aware of the potential for vaccine-associated uveitis.
... 2 VKH is strongly associated with the HLA-DR4/HLA-DRB1*04 alleles, although this association varies across different ethnic groups. 2 Left untreated, VKH can lead to complications such as glaucoma, cataract, choroidal neovascularization, or retinal atrophy. 3 Only a few cases of VKH following vaccinations have been reported worldwide, [4][5][6][7][8][9][10][11][12][13][14] and this report seeks to add to the literature on this subject. ...
... Only a few cases of VKH following vaccinations have been documented globally, namely after the yellow fever, 8,9 Bacillus Calmette-Guérin, 7 hepatitis B virus (HBV), 9 and SARS-CoV-2 10-14 vaccines. These reports suggest a short time interval of less than two weeks between vaccination and onset of symptoms, which is in keeping with our patient's presentation. ...
Purpose
To report a case of Vogt–Koyanagi–Harada (VKH) disease following influenza vaccination.
Observations
A 30-year-old Filipino male developed bilateral pain, redness, photophobia, floaters, headache and tinnitus 2 days after receiving the annual influenza vaccine. He presented to the emergency department 5 days after symptom onset. His past medical and ocular history was unremarkable. His best-corrected distance visual acuity (BCVA) was 20/100 in the right eye (OD) and 20/150 in the left eye (OS). Slit-lamp examination revealed fine keratic precipitates and 1+ anterior chamber cells in both eyes (OU). Dilated fundus examination revealed 1+ vitreous cells with trace haze and multiple serous retinal detachments OU. Magnetic resonance imaging (MRI) of the brain and chest X-ray were unremarkable. Serologic testing was negative for infectious, inflammatory and neoplastic causes. The patient tested positive for HLA-DR4. A diagnosis of acute Vogt-Koyanagi-Harada disease was made and high-dose oral prednisone, intravitreal triamcinolone acetonide and mycophenolate mofetil were needed to achieve quiescence. At 6 months follow-up, our patient remains in remission with no active intraocular inflammation or subretinal fluid. His BCVA has improved to 20/50 OD and 20/30 OS.
Conclusion and importance
The annual influenza vaccine may be a trigger for onset or recurrence of VKH in genetically susceptible individuals.
... [2,3] VKH or VKH-like diseases have been previously reported with vaccination against influenza, yellow fever, hepatitis B virus, and Bacillus Calmette-Guerin. [41][42][43][44] Some viral antigens may mimic self-proteins that specific HLA-class II molecules can detect, leading to the induction of an inflammatory autoimmune response. The role of cytomegalovirus in etiopathogenesis has been illustrated by Sugita et al. [45,46] However, the exact pathophysiology underlying such associations remain unknown. ...
Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis associated with multisystem involvement, is a T-cell-mediated autoimmune disorder in which cytotoxic T-cell target melanocytes in genetically susceptible individuals. Recently, there has been an increase in literature on the new onset of uveitis and reactivation of previously diagnosed cases of uveitis following Covid-19 vaccinations. It has been postulated that Covid-19 vaccines can lead to an immunomodulatory change resulting in an autoimmune phenomenon in the recipients. VKH following COVID-19 infection was reported in four patients and a total of 46 patients developing VKH or VKH-like disease following COVID-19 vaccinations. There are reports of four patients who had been recovering or recovered from VKH after receiving the first dosage of the vaccine and developed worsening of ocular inflammation after receiving the second dose of the vaccine.
... Moreover, the development of CSC has been reported after vaccination for influenza, yellow fever, anthrax, and smallpox. [18][19][20][21] Recently, CSC formation by COVID-19 mRNA vaccine has been reported. 22 Herein, we present the development of CSC after the first dose of Sinopharm (Beijing Institute of Biological Products, Sinopharm, Beijing, China) vaccination, an inactivated whole-virus vaccine. ...
Purpose: To report unilateral acute‐onset central serous chorioretinopathy (CSC) following vaccination with inactivated coronavirus disease 2019 (COVID-19) vaccine in a healthy patient.
Methods: Case report and review of literature.
Results: A 39‐year‐old male was referred with sudden‐onset, painless, unilateral blurred vision in the right eye. His first dose of the Sinopharm vaccine was injected 2 days before. A complete ocular examination revealed central subretinal fluid (SRF) accumulation in favor of CSC in the right eye. Systemic workup disclosed no previous COVID‐19 infection or any systemic involvement. After 3 weeks, SRF decreased remarkably without treatment.
Conclusions: It is proposed that CSC development can be an ocular adverse effect of COVID‐19 vaccination, although it is infrequent. Ophthalmologists should be aware of the possible association between COVID‐19 vaccination and ocular adverse effects, but vaccination is the best effectual measure against COVID‐19.
... 18 Vaccine-associated CSCR has also been reported in the past with the vaccines against smallpox, influenza, yellow fever and anthrax. 2,19,20 CSCR associated with mRNA vaccines showed elevated serum cortisol levels. Raised serum cortisol level is a common association found with CSCR. ...
Corona virus disease-19 (COVID-19) vaccines have been approved for emergency use. Ocular adverse effects following the vaccines have been reported.
Purpose
To report an unique case of recurrent central serous chorioretinopathy following both doses of COVID-19 vaccine.
Observations
A 40-year-old male presented with blurring of vision in the left eye during 2 days following COVISHIELD™ (Serum Institute of India). He had a previous history of central serous chorioretinopathy in the right eye 2 years back and was treated with micropulse laser. Ocular examination showed a best corrected visual acuity of 20/20 right eye and 20/60 left eye. Fundus evaluation of left eye showed central serous chorioretinopathy. Spectral domain optical coherence tomography of the left eye revealed neurosensory detachment. Fundus fluorescein angiography of the left eye showed multiple window defects and ink-blot appearance in the macula. Oral eplerenone 50mg once a day for a month showed significant reduction in the subretinal fluid. Patient developed central serous chorioretinopathy in the left eye 3 days after 2nd dose of COVISHIELD™.
Conclusion and Importance
CSCR following vaccination may be a temporal event. In our patient it occurred following the vaccination. This is the first case of a recurrent CSCR after either dose of COVID-19 vaccination. Ocular symptoms after vaccination warrant a thorough eye evaluation.
... Vaccination-induced cranial nerve palsies have previously been reported following the influenza, hepatitis B, smallpox, and MMR vaccines [124][125][126][127][128][129][130]. While the exact mechanism has not been elucidated, vaccine-induced cranial nerve palsies are believed to be due to immune-mediated damage resulting in demyelination or vascular compromise resulting in reduced blood flow [130,131]. Given the aforementioned links between vaccination and vascular compromise as well as autoimmune phenomena, it is likely that these underlie the development of ocular motility disorders following COVID-19 vaccination. ...
Vaccination efforts as a mitigation strategy in the corona virus disease 2019 (COVID-19) pandemic are fully underway. A vital component of understanding the optimal clinical use of these vaccines is a thorough investigation of adverse events following vaccination. To date, some limited reports and reviews have discussed ocular adverse events following COVID-19 vaccination, but a systematic review detailing these reports with manifestations and clinical courses as well as proposed mechanisms has yet to be published. This comprehensive review one-year into vaccination efforts against COVID-19 is meant to furnish sound understanding for ophthalmologists and primary care physicians based on the existing body of clinical data. We discuss manifestations categorized into one of the following: eyelid, orbit, uveitis, retina, vascular, neuro-ophthalmology, ocular motility disorders, and other.
... Few studies have reported vein and artery retinal occlusion, uveitis, acute idiopathic maculopathy, acute macular neuroretinopathy, Vogt-Koyanagi-Harada disease, and multiple evanescent white dot syndrome after administration of different vaccines, such as those for B hepatitis, yellow fever, smallpox, Influenza, Neisseria meningitidis, and Herpes Zoster (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) . ...
Purpose:
The primary purpose of this study was to assess vascular retinal findings temporally related to COVID-19 vaccination. With greater information regarding all possible future adverse events, we hope to understand the real dimension and relevance of what was presented.
Methods:
Eleven patients with visual complaints after COVID-19 vaccination were enrolled. Data on the following were included: age, sex, vaccine, time of symptom onset, systemic findings, medical history, best-corrected visual acuity, and ocular findings by slit-lamp biomicroscopy as well as multimodal retinal imaging (color fundus, red-free photography, spectral-domain optical coherence tomography, optical coherence tomography angiography, and fluorescein-angiography). Inclusion criteria were the presence of ophthalmologic signs within 30 days after the first or second dose of any COVID-19 vaccine.
Results:
Of 11 patients, five had arterial occlusion (45.4%), four had venous occlusion (36.4%), and two (18.2%) had nonspecific vascular alterations suggestive of retinal ischemia such as cotton-wool spots. The mean age was 57 (SD = 16; range: 27-84) years. The mean time of symptoms onset was 10 (SD = 5.4; range: 3-16) days. Nine patients were female (81.8%). Systemic risk factors were observed in 36.4% of patients. Two patients had both neurological and visual symptoms, with arterial occlusion. Overall, 36.4% patients had COVID-19 in the previous year. Seven patients (63.6%) received ChAdOx1 nCoV-19 (AZD1222) vaccine.
Conclusions:
Our data suggest that retinal events temporally related to COVID-19 vaccination are possible but are very rare. The relationship of these events with post-COVID-19 vaccination warrants further attention to derive a meaningful conclusion.
... 11 While no cases of mRNA COVID-19 vaccine associated CSR have been reported to date, CSR has been associated with vaccinations against influenza, yellow fever, anthrax and smallpox. [12][13][14][15] Still, these cases are rare. In fact, a search of the terms "central serous", "central serous retinopathy", "central serous chorioretinopathy" and "CSR" across all vaccine products by all vaccine manufacturers yielded no results from 1990 to date using the U.S. Centers for Disease Control and Prevention's Vaccine Adverse Event Reporting System. ...
Purpose: We report the case of a 33-year-old male who presented with unilateral central serous retinopathy three days after the injection of a COVID-19 vaccine. Observations: A 33-year-old healthy Hispanic male referred to the ophthalmology service due to blurry vision and metamorphopsia in the right eye without any flashes, floaters, eye redness or pain. The patient reported that 69 hours prior to presentation he received the first dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. He denied any past ocular history or pertinent medical history. He does not take any medicines and denies stressful factors in his life. The clinical examination and imaging tests were consistent with central serous reti-nopathy that resolved in three months. Conclusions and importance: This is the first report of an ocular complication potentially associated with a COVID-19 vaccination. Our case contributes information of a side effect potentially related to this new vaccine.
... 11 While no cases of mRNA COVID-19 vaccine associated CSR have been reported to date, CSR has been associated with vaccinations against influenza, yellow fever, anthrax and smallpox. [12][13][14][15] Still, these cases are rare. In fact, a search of the terms "central serous", "central serous retinopathy", "central serous chorioretinopathy" and "CSR" across all vaccine products by all vaccine manufacturers yielded no results from 1990 to date using the U.S. Centers for Disease Control and Prevention's Vaccine Adverse Event Reporting System. ...
Purpose
We report the case of a 33-year-old male who presented with unilateral central serous retinopathy three days after the injection of a COVID-19 vaccine.
Observations
A 33-year-old healthy Hispanic male referred to the ophthalmology service due to blurry vision and metamorphopsia in the right eye without any flashes, floaters, eye redness or pain. The patient reported that 69 hours prior to presentation he received the first dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. He denied any past ocular history or pertinent medical history. He does not take any medicines and denies stressful factors in his life. The clinical examination and imaging tests were consistent with central serous retinopathy that resolved in three months.
Conclusions and importance
This is the first report of an ocular complication potentially associated with a COVID-19 vaccination. Our case contributes information of a side effect potentially related to this new vaccine.
Purpose:
To provide an overview of pre-selected emerging arboviruses (arthropod-borne viruses) that cause ocular inflammation in humans.
Methods:
A comprehensive review of the literature published between 1997 and 2023 was conducted in PubMed database. We describe current insights into epidemiology, systemic and ocular manifestations, diagnosis, treatment, and prognosis of arboviral diseases including West Nile fever, Dengue fever, Chikungunya, Rift Valley fever, Zika, and Yellow fever.
Results:
Arboviruses refer to a group of ribonucleic acid viruses transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. They mostly circulate in tropical and subtropical zones and pose important public health challenges worldwide because of rising incidence, expanding geographic range, and occurrence of prominent outbreaks as a result of climate change, travel, and globalization. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or non-specific, but they may include serious, potentially disabling or life-threatening complications. A wide spectrum of ophthalmic manifestations has been described including conjunctival involvement, anterior uveitis, intermediate uveitis, various forms of posterior uveitis, maculopathy, optic neuropathy, and other neuro-ophthalmic manifestations. Diagnosis of arboviral diseases is confirmed with either real time polymerase chain reaction or serology. Management involves supportive care as there are currently no specific antiviral drug options. Corticosteroids are often used for the treatment of associated ocular inflammation. Most patients have a good visual prognosis, but there may be permanent visual impairment due to ocular structural complications in some. Community-based integrated mosquito management programs and personal protection measures against mosquito bites are the best ways to prevent human infection and disease.
Conclusion:
Emerging arboviral diseases should be considered in the differential diagnosis of ocular inflammatory conditions in patients living in or returning from endemic regions. Early clinical consideration followed by confirmatory testing can limit or prevent unnecessary treatments for non-arboviral causes of ocular inflammation. Prevention of these infections is crucial.
Uveitis maybe induced by the use of various medications known as drug-induced uveitis (DIU), though rare it is an important cause of uveitis which one needs to be aware of. The drugs may be administered through any route including systemic, topical, and intravitreal. Ocular inflammation can be in the form of anterior, intermediate, posterior or pan uveitis, and rarely may present as episcleritis and scleritis. Identification of drug as the offending agent of uveitis is important as many a times stopping the drug may help recover the uveitis or the concomitant use of corticosteroids. An extensive literature review was done using the Pubmed. An overview of DIU is provided as it is important for us to be aware of this clinical entity.
Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts.
Background:
With increasing incidence of yellow fever, mass campaign vaccinations are underway and little ophthalmological alterations have been reported in literature, specially regarding non-combined vaccines.
Case presentation:
We report the case of a patient with no previous ocular or systemic diseases whom received a single dose of yellow fever vaccination and developed haematological, hepatic and renal alterations progressing with a later onset bilateral asymmetric diffuse uveitis. Ophthalmological findings included fine keratic precipitates scattered throughout the cornea and mild vitritis. Multimodal evaluation showed subtle puntiform choriocapillaris changes with decreased vascular density associated. The patient had a good visual outcome after mild oral prednisone dose, but the image findings have not presented remission.
Conclusions:
Clinicians should be aware of clinical and subclinical ocular manifestations such as subtle puntiform choriocapillaris changes as possible vaccine-related adverse events with potential to impact vision.
We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.
Introduction:
To describe the characteristics, diagnosis, and treatment of the first documented case of Vogt-Koyanagi-Harada (VKH) disease following BCG vaccination (Patient 1) and the first documented case of both VKH disease and tuberculosis (Patient 2). Two patients were diagnosed with VKH disease and monitored using fundus photography, fundus autofluorescence, fluorescein angiography (FA), spectral-domain optical coherence tomography, and enhanced depth imaging optical coherence tomography (EDI-OCT).
Case description:
A 39-year-old patient (Patient 1) had bilateral granulomatous anterior uveitis and serous retinal detachment. FA showed multiple punctuate hyperfluorescent lesions and multilobular pools of dye. EDI-OCT revealed serous retinal detachment, subretinal septa, and cystoid spaces. A 40-year-old woman (Patient 2) presented with a 3-week history of decreased vision, headache and tinnitus. Fundus examination showed bilateral disc swelling with serous retinal detachment and retinal folds. She had been diagnosed with tuberculosis. EDI-OCT showed fluctuation of the internal limiting membrane (ILM), retinal folds, retinal pigment epithelial (RPE)-Bruch membrane undulation, choroidal folds, serous retinal detachment. Both of the patients received high dosage of steroid treatment during the diagnosis. A fast recovery in VKH symptoms was observed following the treatment.
Discussion and evaluation:
Immunological mechanisms and dysregulation of the immune system may play a significant role in the association between VKH disease and BCG.
Conclusions:
EDI-OCT imaging demonstrated structural changes in the photoreceptor layer, RPE-Bruch membrane, choroid, outer retina, ILM in acute VKH.
Vogt-Koyanagi-Harada disease (VKHD) is a rare granulomatous inflammatory disease that affects pigmented structures, such as eye, inner ear, meninges, skin and hair. This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. The absence of ocular trauma or previous intraocular surgery sets VKHD appart from sympathetic ophthalmia, its main differential diagnosis. The disease has an acute onset of bilateral blurred vision with hyperemia preceded by flu-like symptoms. The acute uveitic stage is characterized by a diffuse choroiditis with serous retinal detachment and optic disc hyperemia and edema. Fluorescein angiography in this phase demonstrates multiple early hyperfluorescent points. After the acute uveitic stage, ocular and integumentary system pigmentary changes may appear. Ocular findings may be accompanied by lymphocytic meningitis, hearing impairment and/or tinnitus in a variable proportion of patients. Prompt diagnosis followed by early, aggressive and long-term treatment with high-dose corticosteroids is most often ensued by good visual outcomes. However, some patients may experience chronic uveal inflammation with functional eye deterioration. The current review discusses the general features of VKHD, including epidemiology, classification into categories, differential diagnosis and current therapeutic approaches.
The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.
The mechanisms of immune response following yellow fever (YF-17DD) vaccination are still poorly understood. In this study, we have performed a longitudinal investigation (days 0, 7, 15 and 30) to characterize the cytokine profile of innate and adaptive immunity following YF-17DD first-time vaccination. Data from non-stimulated cultures demonstrated a prominent participation of the innate immunity with increased frequency of TNF-α(+) neutrophils and IFN-γ(+) NK-cells at day 7 besides TNF-α(+) monocytes at day 7, day 15 and day 30. Increased frequency of IL-10(+) monocytes was observed at day 15 and day 30, and decreased percentage of IL-4(+) NK-cells were detected at day 7, day 15 and day 30. Time-dependent and oscillating cytokine pattern was observed in CD4(+) T-cells, with low percentage of IL-12(+), IL-4(+) and IL-10(+) cells at day 7 and increased frequency of TNF-α(+) cells at day 15 besides IFN-γ(+) and IL-5(+) cells at day 15 and day 30. Later changes with increased percentage of IL-12(+) and IL-5(+)CD8(+) T-cells were observed at day 30. Increased frequency of IL-10(+) B-cells was observed at day 15, when seroconversion was detected in all vaccinees. The overall cytokine analysis of non-stimulated leukocytes showed a transient shift towards a pro-inflammatory profile at day 7, mainly due to changes in the innate immunity, which draws back toward a mixed/regulatory pattern at day 15 and day 30. The changes induced by the in vitro YF-17DD vaccine-stimulation were mainly observed at day 0 and day 7 (before seroconversion) with minor changes at day 15 and day 30 (after seroconversion). These data support the hypothesis that a complex network with mixed pro/anti-inflammatory cytokine profile is associated with the establishment of the protective immunity following YF-17DD primo-vaccination, free of adverse events.
As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings.
Background: Recent upsurges in yellow fever outbreaks are increasing the demand for yellow fever vaccine, while enormously straining global vaccine supply. Fractional dose yellow fever vaccination is being considered as a dose-sparing strategy to address current vaccine shortages. This systematic review and meta-analysis aimed to assess the effects of fractional dose yellow fever vaccination, in comparison with those of standard dose vaccination.
Methods: We registered this systematic review on the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42018084214), developed the protocol in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) and synthesised the evidence in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). We stratified meta-analyses by vaccine dose.
Results: We retrieved 2524 records from the literature search, eleven of them potentially eligible. From these studies, we included eight eligible trials, with a total of 2371 participants. Seroconversion rates at four-five weeks following vaccination were similar between participants who received standard doses and participants who received fractional doses containing one-third (547 participants: risk ratio [RR] 1.02, 95% confidence interval [CI] 1.00 to 1.04), one-fifth (155 participants: RR 1.00, 95% CI 0.98 to 1.03), one-tenth (890 participants: RR 0.99, 95% CI 0.96 to 1.01), and one-fiftieth (661 participants: RR 0.97, 95% CI 0.92 to 1.02) of the standard dose. However, the rates of seroconversion were substantially lower among participants who received fractional doses containing one-hundredth and lower fractions of the standard dose. Immunogenicity similarly persisted 8-10 years following both fractional and standard dose vaccination. Minor adverse events following vaccination did not differ across doses, and no serious adverse events were reported in any study arm.
Conclusions: These findings support the use of fractional dosing as a strategy for mitigating vaccine shortages. The strategy should be specifically considered for individuals who are young, immunocompetent and well nourished.
Keywords: Yellow fever, vaccination, fractional dose, dose-sparing, immunogenicity, safety.
Purpose: To report the manifestation of Vogt–Koyanagi–Harada-like disease (VKH) following yellow fever vaccination.
Methods: Case report.
Results: A 34-year-old immunocompetent male had tinnitus, headache, and decreased vision after a booster dose of yellow fever vaccine. Visual acuity was 20/100 in the right eye and 20/80 in the left, with serous retinal detachment (SRD) and choroidal thickening identified on clinical examination and multimodal imaging. Lumbar puncture revealed pleocytosis and an increased protein content, but extensive investigations ruled out infectious/neurological diseases. Pulse intravenous methylprednisolone was given, followed by a tapering regimen of high-dose oral prednisone. Azathioprine was started early, 3 weeks after initiation of oral steroids. Intraocular inflammation and SRD rapidly resolved, with visual acuity reaching 20/20 in both eyes, after 3 weeks. No recurrence of intraocular inflammation or sign of depigmentation was so far noticed, at 2 years of follow-up.
Conclusion: Yellow fever vaccine may be a possible trigger for VKH.
Purpose: To describe two cases of anterior and intermediate uveitis following yellow fever vaccination with fractional dose.
Methods: Case report.
Results: Case 1: A 35 year-old healthy woman presented with unilateral anterior uveitis 10 days after the yellow fever vaccination. Testing excluded infectious and rheumatic diseases and the episode was fully recovered after a short course of topical treatment. Case 2: A 21 year-old previously healthy woman presented with blurred vision in the left eye (OS) 14 days after the yellow fever vaccination. The ophthalmic examination of the OS revealed intermediated uveitis. Testing excluded infectious and neurological diseases. After six weeks of treatment with oral prednisone, the ocular inflammation had resolved.
Conclusion: Physicians should be aware of the possibility of eye inflammation following the yellow fever vaccination.
Purpose: To report a case of Vogt–Koyanagi–Harada (VKH) disease associated with hepatitis B vaccination.
Methods: Case report.
Results: A 43-year-old Caucasian male presented with a three-week history of blurry vision, pain, photophobia, and redness in both eyes. Three days prior to the onset of symptoms, he had received the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid lesions in the posterior pole, choroidal thickening, and serous macular detachment. Targeted laboratory investigations were negative for infectious or autoimmune markers. After treatment with oral corticosteroids, the patient had resolution of symptoms with near-total recovery of visual function. The patient later reported systemic findings of hearing loss, tinnitus, and integumentary changes. A diagnosis of VKH disease was made and inflammation was managed with oral corticosteroids followed by methotrexate for long-term disease control.
Conclusions: VKH disease is an inflammatory condition primarily affecting the choroid, retinal pigment epithelium, and outer retina. The underlying etiology is unclear, but it can be associated with a viral prodrome suggesting an infectious trigger in a genetically susceptible individual. Our case suggests that hepatitis B vaccination may trigger a similar inflammatory response.
Introduction: The yellow fever vaccine is a live attenuated virus vaccine that is considered one of the most efficient vaccines produced to date. The original 17D strain generated the substrains 17D-204 and 17DD, which are used for the current production of vaccines against yellow fever. The 17D-204 and 17DD substrains present subtle differences in their nucleotide compositions, which can potentially lead to variations in immunogenicity and reactogenicity. We will address the main changes in the immune responses induced by the 17D-204 and 17DD yellow fever vaccines and report similarities and differences between these vaccines in cellular and humoral immunity . This is a relevant issue in view of the re-emergence of yellow fever in Uganda in 2016 and in Brazil in the beginning of 2017.
Areas covered: This article will be divided into 8 sections that will analyze the innate immune response, adaptive immune response, humoral response, production of cytokines, immunity in children, immunity in the elderly, gene expression and adverse reactions.
Expert commentary: The 17D-204 and 17DD yellow fever vaccines present similar immunogenicity, with strong activation of the cellular and humoral immune responses. Additionally, both vaccines have similar adverse effects, which are mostly mild and thus are considered safe.
Central serous chorioretinopathy (CSC) is a common idiopathic retinal disease characterized by central vision loss from serous detachment of the neurosensory retina, serous pigment epithelial detachments, and leakage of fluid through the retinal pigment epithelium into the sub-retinal space. The concept of an association between exogenous glucocorticoid use and CSC is widely accepted among ophthalmologists. Here we review the evidence for and against such an association. This evidence includes two large, case-control studies that found strong associations, and a smaller, population-based study that found no association. We conclude that the preponderance of the literature on this topic supports the existence of an association. Both exogenous and endogenous glucocorticoids have been implicated. Although a mechanism and a causal relationship remain to be established, the association deserves broader recognition among physicians who prescribe glucocorticoids.
Purpose:
To describe a case of small retinal vessel vasculopathy postvaccination.
Methods:
We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed.
Results:
Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary plexus.
Conclusion:
We describe a case of small artery occlusion in a previously healthy patient, 4 days after vaccination against N. meningitidis and yellow fever. Fluorescein angiography yielded greater diagnostic value than OCTA for evaluating the occlusion, whereas spectral domain optical coherence tomography angiography enabled better visualization of capillary dropout and layer-specific assessment. Further research is required to determine whether vaccination in general, or directed specifically at N. meningitidis or yellow fever, is associated with small vessel vasculopathy and the underlying pathogenesis.
A 20-year-old white woman presented with bilateral acute visual loss (visual acuity: 20/60), panuveitis, and exudative retinal detachments 3 weeks after a second dose of quadrivalent human papillomavirus (HPV4) vaccine. She was treated with oral prednisolone for 6 weeks and responded rapidly. By week 4, vision had normalized and clinical signs resolved. Uveitis after HPV4 vaccination has been reported in two cases. Although the differential diagnosis includes Harada disease, temporal correlation with HPV4 and definitive response to a short course of treatment implicate the vaccine in this case. Vaccine-induced uveitis is rare and difficult to distinguish from coincidental autoimmune disease.
[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:967–970.]
Introduction:
Drug-induced uveitis is a well described but often overlooked and/or misdiagnosed adverse reaction to medication. There are an increasing number of medications that have been related to the onset of intraocular inflammation. Identification of these inciting agents may decisively help the diagnostic algorithm involving new cases of uveitis.
Areas covered:
This review intends to be an updated comprehensive, practical guide for practitioners regarding the main drugs that have been associated with uveitis. A classification proposed by Naranjo et al. in 1981 for establishing potential causality is applied examining possible mechanisms of action. A guide for clinicians about the rationale of these observations when dealing with patients with uveitis is provided.
Expert opinion:
Several agents with different routes of administration (systemic, topical and/or intraocular) may cause intraocular inflammation. The mechanism behind ocular inflammation is frequently unknown. Clinicians should be aware of the potential drug effect to optimize diagnosis and management of such patients.
Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in cascades, this means that steroid treatment can block expression of the subsequent cytokines. The blocked cytokine activity does not depend on a reduced cytokine receptor expression; in fact available in vitro investigations show that while the cytokine expression is blunted, its receptor is upregulated. The cellular studies presented here may represent the maximum potential of steroids to modulate cytokine expression in human mononuclear cells. It remains to be determined by clinical-experimental studies how effective cytokine modulation can be achieved in situ in inflamed bowel by systemic or by topical steroid therapy. Such studies may also answer whether a blocked cytokine production/action is the key or just a secondary mechanism behind the unique efficacy of steroids in active inflammatory bowel disease.
Vaccinations are preventive measures against serious infections. In relation to the number of vaccinations per year, the incidence of severe complications is extremely low.
Two weeks after vaccinations against hepatitis A, hepatitis B and yellow fever in preparation for a trip to Africa a 21-year-old woman experienced an acute and irreversible loss of vision to 0,05 and nasal visual field defect in the left eye. Whereas vision acuity did not recover the scotoma disappeared within 6 weeks. Cerebrospinal fluid showed a lymphocytic pleocytosis. Oligoglonale bands were absent. Pathological parameters were not presented in the serum. The MRI showed a hyperintense thickening of optic nerve,as well as a hyperintense focus in right temporal side using the T(2)W-Sequence.
Only few cases have been reported with neurological complications, such as encephalitis, following vaccinations each of the above mentioned. As no other causes for the inflammation were found, the optic nerve involvement must have been caused by the vaccination. Which of the three vaccinations caused encephalitis can not be classified.
To report a case of multiple evanescent white dot syndrome (MEWDS) following simultaneous hepatitis-A virus (HAV) and yellow fever (YF) vaccination.
Review of the clinical, laboratory, photographic, and angiographic records of a patient suffering from MEWDS.
A healthy 50-year-old woman presented with rapidly progressive left-eye visual loss, associated with photopsias and a para-central scotoma, one week after receiving simultaneous HAV and YF vaccination. Both anterior segments and right-eye fundus were unremarkable. Fundus examination of the left-eye disclosed papillitis with multiple, small, white, outer-retinal lesions. Angiographic tests were pathognomonic for MEWDS. Perimetry revealed left-eye blind spot enlargement. Initial inflammatory/infectious work-up was negative. Signs and symptoms resolved spontaneously within 6 weeks, with concomitant normalization of ancillary exams.
The clinical presentation and the benign course were consistent with the diagnosis of MEWDS. No other aetiopathogenic factor than simultaneous HAV and YF immunization was identified, suggesting an autoimmune basis for MEWDS in predisposed patients.
Epidemiological update yellow fever situation summary in the Americas
- Paho
Paho. Epidemiological update yellow fever situation summary in the
Americas; 2019. http://www.paho.org. Accessed February 22, 2019.