Extensive Chorio-retinal Damage Due to Dirofilaria Repens- Report of a Case.

Purpose: To report a case of ocular dirofilariasis causing extensive chorio-retinal damage.Method: Surgical removal of the worm and identification of the same by microscopic examinationand polymerase chain reaction.Results: The worm was identified as Dirofilaria repens.Conclusion: Ocular dirofilariasis is an arthropod borne parasitic infestation affecting the subconjunctival tissue and anterior chamber. Vitreous involvement in Dirofilaria is very rare. Dirofilaria repens can cause extensive chorio-retinal damage resembling diffuse unilateralsubacute neuroretinitis.

Case Report: Acute Vision Loss in a Young Returning Traveler with Dengue Fever.

Ocular complications are rare in patients with dengue fever, but may cause permanent loss of vision. We present the case of a 29-year-old German woman who developed severe acute vision loss because of dengue-associated maculopathy after traveling to Vietnam and Cambodia. Initially, the optical coherence tomography showed detachment of the retinal pigment epithelium, a central shift in the retinal pigmentation and intraretinal cysts. The patient was hospitalized and treated with a short course of intravenous prednisolone. Vision improved, and the patient showed full recovery at 9 months after the onset. This case highlights the importance of awareness and adequate management for ocular involvement in patients with dengue fever, including travelers.

Suspected ocular toxocariasis and macular heterotopia.

We report a case of an asymptomatic Caucasian male who attended our clinic for a routine check-up and macular heterotopia associated with lesions compatible with ocular toxocariasis were found.

Central Nervous System Virus Infection in African Children with Cerebral Malaria.

We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056-1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection.

Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria.

BACKGROUND: Our prior study findings suggest that Plasmodium falciparum is the cause of disease in both malaria retinopathy-positive (RP) and most retinopathy-negative (RN) cerebral malaria (CM), and that absence of retinopathy and decreased disease severity in RN CM may be due to shorter duration of illness, lower parasite biomass, and decreased var gene expression in RN compared to RP CM. In the present study, we assessed the pathophysiology of RP and RN CM. METHODS: We compared markers of systemic and central nervous system inflammation, oxidative stress, neuronal injury, systemic endothelial activation, angiogenesis, and platelet activation in Ugandan children with RP (n = 167) or RN (n = 87) CM. RESULTS: RP children had higher plasma C-reactive protein (P = .013), ferritin and erythropoietin (both P < .001) levels, an elevated cerebrospinal fluid (CSF):plasma albumin ratio (P < .001), and higher CSF tau protein levels (P = .049) than RN children. Levels of plasma and CSF proinflammatory and anti-inflammatory cytokines and oxidative stress markers did not differ between RP and RN children. RN children had higher plasma levels of endothelin 1 (P = .003), platelet-derived growth factor (P = .012), and platelet factor 4 (P = .034). CONCLUSIONS: RP and RN CM may represent different phases of CM. RN CM may be driven by early vasospasm and platelet activation, whereas the more advanced RP CM is associated with greater inflammation, increased erythropoietic drive, blood-brain barrier breakdown, and neuronal injury, each of which may contribute to greater disease severity.

[Retinal manifestations of neuro-malaria or "malarial retinopathy" in Yaoundé]. / Atteintes rétiniennes du neuro-paludisme ou « rétinopathie paludique ¼ à Yaoundé.

AIM: Contribute to the improvement of diagnostic and prognostic approaches to treating children with neuro-malaria in Yaoundé. PATIENTS AND METHOD: A prospective and analytical study carried out in 2 hospitals of Yaoundé from October 2015 to March 2016. All patients aged 3 months to 15 years hospitalized for neuro-malaria in one of the 2 hospitals benefited from a fundus examination. The variables studied were: age, sex, Glasgow or Blantyre score, fundus examination and parasitaemia. For statistical analysis, we used the software R 3.3.0, Chi2, exact of Fisher or Kolmogorov-Smirnov tests with a significance P<5%. RESULTS: Out of the 178 children hospitalized during the study period, 44 had neuro-malaria (24.71%) and 26 (46 diseased eyes) among them presented retinal lesions at a frequency of 14.60%. The mean age was 5.54±3.49 years with a sex ratio of 1.09. The under 5-years-old were the most affected with 31 (70.45%) cases. The fundus lesions of 26 (59.09%) were retinal hemorrhages in 24 (54.54%), retinal whitening and vessel discoloration in 8 (18.18%) respectively. Papillary edema was associated in 4 (9.09%). Macular involvement was noted in 9 cases. These lesions were correlated with age, depth of coma, duration, and clinical course. The rate of parasitaemia did not affect their occurrence. CONCLUSION: Retinal lesions are frequent and serious during neuro-malaria in our environment, especially in children under five. They must therefore be an emphasis in the systematic exam to rule it out for a better prognostic evaluation and a fast and adequate multidisciplinary management.

Early and middle childhood developmental, cognitive, and psychiatric outcomes of Malawian children affected by retinopathy positive cerebral malaria.

The objective is to determine the short -and long-term developmental, cognitive, and psychiatric effects of retinopathy positive cerebral malaria (CM-R) among young children in a prospective study assessing them around the onset of disease and again 2 years at preschool and again at school age. In total, 109 children were recruited from the Queen Elizabeth Central Hospital in Blantyre, Malawi, (N = 49) with CM-R and non-malaria controls  (N = 60). Children were assessed for overall motor, language, and social skills using the Malawi Developmental Assessment Tool (MDAT) at preschool age. At school age, the same children were then given the Kaufman Assessment Battery for Children, second edition (KABC-II), which assessed global cognitive performancememory, and learning; as well as the Test of Variables of Attention (TOVA), which assessed attention. The Achenbach Child Development Checklist (CBCL) was administered at both time points to assess emotional and behavioral patterns. Controls scored significantly better on all KABC-II global domains as well as on the mental processing index than their CM-R group counterparts, but showed no performance differences in the TOVA and CBCL assessments at school age, or in the MDAT and CBCL assessments at preschool age. The MDAT total score was significantly correlated with the KABC-II sequential processing, learning, and mental processing index among CM-R survivors but not among controls. Persisting neurocognitive effects of CM can be captured with the KABC-II at school age. The MDAT at preschool age is correlated with the KABC-II among CM-R survivors and can be used to capture early emerging developmental deficits due to CM-R.

Confrontation with a live subretinal parasite.

BACKGROUND: Parasitic infestation of the eyes are a major cause of ocular diseases across the globe. Filarial and filarial-like nematodes top the list of the nematodes that affect the eye. CASE: A rare case of live sub retinal worm is reported in a 25 years old apparently healthy young male. The case presented with unilateral loss of vision and floaters in the affected eye. Upon examination a live subfoveal worm was identified with continuous wriggling movements and diffuse retinal edema. The worm was removed surgically and sent for parasitological examination. OBSERVATION: The worm was identified microscopically as Loa Loa. However detailed histopathological examination could not be incorporated. The patient's vision improved to 6/12 (0.30 Log MAR) from the initial presentation of 3/60 (1.30 Log MAR) after three months follow-up. CONCLUSION: The rare sub retinal live worm presents a challenge in management. The management depends upon the location and viability of the parasite. Surgical management is aimed at worm removal and vision preservation.

Automated Detection of Malarial Retinopathy in Retinal Fundus Images obtained in Clinical Settings.

Cerebral malaria (CM) is a life-threatening clinical syndrome associated with 5-10% of malarial infection cases, most prevalent in Africa. About 23% of cerebral malaria cases are misdiagnosed as false positives, leading to inappropriate treatment and loss of lives. Malarial retinopathy (MR) is a retinal manifestation of CM that presents with a highly specific set of lesions. The detection of MR can reduce the false positive diagnosis of CM and alert physicians to investigate for other possible causes of the clinical symptoms and apply a more appropriate clinical intervention of underlying diseases. In order to facilitate easily accessible and affordable means of MR detection, we have developed an automated software system that detects the retinal lesions specific to MR, whitening and hemorrhages, using retinal color fundus images. The individual lesion detection algorithms were combined into an MR detection model using partial least square classifier. The classifier model was trained and tested on retinal image dataset obtained from 64 patients presenting with clinical signs of CM (44 with MR, 20 without MR). The MR detection model yielded specificity of 92% and sensitivity of 68%, with an AUC of 0.82. The proposed MR detection system demonstrates potential for broad screening of MR and can be integrated with a low-cost and portable retinal camera, to provide a bed-side tool for confirming CM diagnosis.

Desprendimiento del epitelio pigmentario de la retina en la retinopatía por malaria / Detachment of retinal pigment epithelium in retinopathy due to malaria

CASO CLÍNICO: Varón de 45 años de edad, acude diagnosticado de paludismo con afectación neurológica. Dos meses más tarde refiere metamorfopsia en el ojo izquierdo. En el fondo de ojo se aprecia retinopatía palúdica bilateral, observándose en la tomografía de coherencia óptica (OCT) macular un desprendimiento del epitelio pigmentario (DEP) parafoveal en el ojo izquierdo. Se inicia tratamiento específico antipalúdico, evidenciándose desaparición de la retinopatía. DISCUSIÓN: El Plasmodium falciparum es responsable de la retinopatía en el paludismo neurológico. Debiéndose realizar en estos pacientes una exploración fundoscópica y OCT macular porque está asociado a una mortalidad mayor cuando existe afectación retiniana

CASE REPORT: A 45-year-old man was diagnosed with malaria with neurological involvement. Two months later he referred metamorphopsia in the left eye. Malarial retinopathy was observed in the fundus examination. The Optic Coherence Tomography (OCT) of the macula showed parafoveal pigment epithelium detachment (DEP). Specific anti-malarial treatment was initiated, with the disappearance of the retinopathy being observed. DISCUSSION: Plasmodium falciparum is responsible for the retinopathy in neurological malaria. A funduscopic examination and macular OCT should be performed in these patients, as it is associated with a higher mortality when there is a retinal involvement

Spatial statistical modelling of capillary non-perfusion in the retina.

Manual grading of lesions in retinal images is relevant to clinical management and clinical trials, but it is time-consuming and expensive. Furthermore, it collects only limited information - such as lesion size or frequency. The spatial distribution of lesions is ignored, even though it may contribute to the overall clinical assessment of disease severity, and correspond to microvascular and physiological topography. Capillary non-perfusion (CNP) lesions are central to the pathogenesis of major causes of vision loss. Here we propose a novel method to analyse CNP using spatial statistical modelling. This quantifies the percentage of CNP-pixels in each of 48 sectors and then characterises the spatial distribution with goniometric functions. We applied our spatial approach to a set of images from patients with malarial retinopathy, and found it compares favourably with the raw percentage of CNP-pixels and also with manual grading. Furthermore, we were able to quantify a biological characteristic of macular CNP in malaria that had previously only been described subjectively: clustering at the temporal raphe. Microvascular location is likely to be biologically relevant to many diseases, and so our spatial approach may be applicable to a diverse range of pathological features in the retina and other organs.

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system.

BACKGROUND: Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome. In this context, the present work has been performed to investigate which possible electrophysiological and neurochemistry alterations could be involved in the CM pathology. METHODS: Experimental CM was induced in Plasmodium berghei-infected male and female C57Bl/6 mice. The survival and neurological symptoms of CM were registered. Brains and retina were assayed for TNF levels and NOS2 expression. Electroretinography measurements were recorded to assessed a- and b-wave amplitudes and neurochemicals changes were evaluated by determination of glutamate and glutathione levels by HPLC. RESULTS: Susceptible C57Bl/6 mice infected with ≈ 106 parasitized red blood cells (P. berghei ANKA strain), showed a low parasitaemia, with evident clinical signs as: respiratory failure, ataxia, hemiplegia, and coma followed by animal death. In parallel to the clinical characterization of CM, the retinal electrophysiological analysis showed an intense decrease of a- and-b-wave amplitude associated to cone photoreceptor response only at the 7 days post-infection. Neurochemical results demonstrated that the disease led to a decrease in the glutathione levels with 2 days post inoculation. It was also demonstrated that the increase in the glutathione levels during the infection was followed by the increase in the 3H-glutamate uptake rate (4 and 7 days post-infection), suggesting that CM condition causes an up-regulation of the transporters systems. Furthermore, these findings also highlighted that the electrophysiological and neurochemical alterations occurs in a manner independent on the establishment of an inflammatory response, once tumour necrosis factor levels and inducible nitric oxide synthase expression were altered only in the cerebral tissue but not in the retina. CONCLUSIONS: In summary, these findings indicate for the first time that CM induces neurochemical and electrophysiological impairment in the mice retinal tissue, in a TNF-independent manner.

Malarial retinopathy in adult: a case report.

Although widely reported in children, the malarial retinopathy has rarely been described in adults. We observed a case in the department of ophthalmology at the pediatric and gynecology-obstetrics Yaoundé Hospital. The diagnosis revealing a decrease in visual acuity was confirmed by thorough ophthalmological and biological assessments. The basic treatment by quinine therapy was conclusive. The authors point out the need to consider this diagnosis in case of any decrease in visual acuity in febrile context for any adult living or recently having stayed in endemic areas.

Subretinal echinococcosis: a case report.

BACKGROUND: Echinococcosis is a dangerous zoonotic parasitic disease. Ocular echinococcosis is very rare, especially the hydatid cysts in subretinal space. We present a case of subretinal echinococcosis and management. CASE PRESENTATION: A 37-year-old man with subretinal echinococcosis who developed panuveitis and visual impairment. The patient lives on agriculture and animal husbandry, which made him susceptible to parasitic infection. He had severe panuveitis and blurred vision on arrival at hospital. According to his ocular examination and systemic review, the subretinal echinococcosis diagnosis was made. The patient received pars plana lensectomy and pars plana vitrectomy. The lesion underneath his retina was removed, and histopathology examination confirmed the subretinal echinococcosis diagnosis. CONCLUSIONS: Echinococcosis is a dangerous zoonotic parasitic disease in pastoral areas. Ocular echinococcosis is usually secondary to systemic infection. Although the incidence is rare, the disease could lead to destructive visual function impairment.

Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria.

BACKGROUND: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent a completely different disease process or a subgroup within the spectrum of CM remains an important question in malaria. In the current study, we use newly designed primer sets with the best coverage to date in a large cohort of children with SM to determine the role of var genes in malaria disease severity and especially CM as discriminated by retinopathy. METHODS: We performed qRT-PCR targeting the different subsets of these var genes on samples from Ugandan children with CM (n = 98, of whom 50 had malarial retinopathy [RP] and 47 did not [RN]), severe malarial anemia (SMA, n = 47), and asymptomatic parasitemia (AP, n = 14). The primers used in this study were designed based on var sequences from 226 Illumina whole genome sequenced P. falciparum field isolates. RESULTS: Increasing severity of illness was associated with increasing levels of endothelial protein C receptor (EPCR)-binding PfEMP1. EPCR-binding PfEMP1 transcript levels were highest in children with combined CM and SMA and then decreased by level of disease severity: RP CM > RN CM > SMA > AP. CONCLUSIONS: The study findings indicate that PfEMP1 binding to EPCR is important in the pathogenesis of SM, including RN CM, and suggest that increased expression of EPCR-binding PfEMP1 is associated with progressively more severe disease. Agents that block EPCR-binding of PfEMP1 could provide novel interventions to prevent or decrease disease severity in malaria.

Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: Cohort Description and Baseline Results.

Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The Cognitive Outcomes and Psychiatric symptoms of retinopathy-positive CM (COPS) cohort is the first large (N = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures semi-annually for up to 5 years. We report baseline characteristics of the cohort and outcomes at 1 month. At enrollment, CM cases were more likely to come from families with fewer socioeconomic resources and to have health characteristics that increase risk for malaria. In children younger than 5 years, cases were delayed in motor, language, and social development by approximately 6 months, compared with controls. More significant delays occurred in those with MRI abnormalities at the 1-month follow-up visit. There were no differences between cases and controls in inhibitory self-control, nor in cognitive function in children ≥ 5 years of age. The latter finding may be related to the smaller sample size, case-control imbalance in socioeconomic status, or the use of cognitive and behavioral assessments that are less culturally appropriate to this population. Continued follow-up will help determine predictors of long-term outcomes.