Retinal integrity in human babesiosis: a pilot study.

BACKGROUND: Prior case reports and animal studies have reported on potential ophthalmologic complications of babesiosis, but this issue has not previously been addressed in a cohort of patients with babesiosis. This cross-sectional descriptive pilot study evaluated the retinas of patients with acute babesiosis to determine if retinal abnormalities are a feature of the disease. METHODS: We screened all patients admitted to Yale New Haven Hospital with laboratory confirmed babesiosis during the summer of 2023 and obtained informed consent. Patients were interviewed and underwent pupil dilation and a retinal examination using an indirect ophthalmoscope. Demographic and clinical information were obtained by questionnaire and through chart review. RESULTS: Ten patients underwent retinal eye exams with results that were generally unremarkable. No study patients showed any signs of retinal inflammation, infection, retinal bleeding, retinal tears, or abnormal vessel formation that could be attributed to infection. CONCLUSION: This small study did not find evidence of retinopathy in patients with babesiosis. Further studies with larger populations, repeated exams, and long term follow up will further elucidate the potential small vessel complications of human babesiosis.

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.

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.

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.

Myxobolus axelrodi n. sp. (Myxosporea: Myxobolidae) a parasite infecting the brain and retinas of the cardinal tetra Paracheirodon axelrodi (Teleostei: Characidae).

An investigation of mortalities in a group of cardinal tetras Paracheirodon axelrodi Meyers, 1936, a popular ornamental fish, revealed myxozoan parasites in ventricles of the brains in 3/10 fish and the ocular retina of a fourth. Parasite impacts were unclear, as additional histopathological findings were present, including bacterial dermatitis and meningitis. Ethanol-preserved specimens pooled from multiple fish were used for morphological characterization of myxospores. Elongate, teardrop myxospores were 20.5 ± 0.7-µm (mean ± SD; range = 19.0-21.8 µm) long, 6.6 ± 0.5-µm (5.7-7.9 µm) wide, and 5.1 ± 0.4-µm (4.8-5.9 µm) thick (valvular width). Two, unequally sized, apical, pyriform polar capsules were in the same plane as the sutural ridge. The larger measured 9.9 ± 0.8-µm (8.0-11.2 µm) long and 3.8 ± 0.3-µm (3.2-4.8 µm) wide. The smaller was 4.1 ± 0.3-µm (3.5-4.5 µm) long and 2.0 ± 0.1-µm (1.8-2.3 µm) wide. Identical 1912 bp 18S rRNA sequences were obtained from two pooled spore samples from tetra brains, which did not match any sequences in the NCBI nr/nt database. Phylogenetically, these parasites grouped loosely within a clade containing Myxobolus spp. from other South American characins and Unicauda spp. from siluriform catfish. Myxospores shared some morphological similarities with Myxobolus inaequus from the unrelated glass knifefish (Order: Gymnotiformes), but were genetically divergent (<85 % similarity) from other myxozoan parasites of South American characins and shared few morphological features or tissue predilection sites. Based on host and tissue tropism, spore morphology, and 18S rRNA sequencing, we report this isolate as a previously unknown species, Myxobolus axelrodi n. sp.

Retinal changes in visceral leishmaniasis by retinal photography.

BACKGROUND: In visceral leishmaniasis (VL), retinal changes have previously been noted but not described in detail and their clinical and pathological significance are unknown. A prospective observational study was undertaken in Mymensingh, Bangladesh aiming to describe in detail visible changes in the retina in unselected patients with VL. METHODS: Patients underwent assessment of visual function, indirect and direct ophthalmoscopy and portable retinal photography. The photographs were assessed by masked observers including assessment for vessel tortuosity using a semi-automated system. RESULTS: 30 patients with VL were enrolled, of whom 6 (20%) had abnormalities. These included 5 with focal retinal whitening, 2 with cotton wool spots, 2 with haemorrhages, as well as increased vessel tortuosity. Visual function was preserved. CONCLUSIONS: These changes suggest a previously unrecognized retinal vasculopathy. An inflammatory aetiology is plausible such as a subclinical retinal vasculitis, possibly with altered local microvascular autoregulation, and warrants further investigation.

Toxocara optic neuropathy after ingestion of raw meat products.

PURPOSE: To report Toxocara optic neuropathy in five men with histories of ingestion of raw meat, liver, or blood. CASE REPORT: Five men in their 30s to 60s presented with unilateral visual disturbance. All five had a history of ingesting raw meat, liver, or blood products. All five men presented with optic disc edema and three also showed granulomatous infiltration of the retina. With Goldmann or Humphrey visual field testing, two patients showed central scotomas and two exhibited arcuate defects. Serum eosinophil count and total IgE were elevated in four patients. Serum enzyme-linked immunosorbent assay testing was positive for Toxocara canis IgG in all five cases. CONCLUSIONS: This report shows the variable clinical presentations of Toxocara optic neuropathy and the importance of questioning for a history of eating raw meat and blood products as a risk factor.

Single nucleotide polymorphisms in the interferon gamma gene are associated with distinct types of retinochoroidal scar lesions presumably caused by Toxoplasma gondii infection.

The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ gene ( IFNG ) with different types of retinal scar lesions presumably caused by toxoplasmosis were investigated in a cross-sectional population-based genetic study. Ten SNPs were investigated and after Bonferroni correction, only the associations between SNPs rs2069718 and rs3181035 with retinal/retinochoroidal scar lesions type A (most severe scar lesions) and C (least severe scar lesions), respectively, remained significant. The associations of two different IFNG SNPs with two different types of retinal lesions attributable to toxoplasmosis support the hypothesis that different inflammatory mechanisms underlie the development of these lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear cells stimulated with Toxoplasma gondii antigens was also investigated. The association between SNP rs2069718 and type A scar lesions revealed that differential IFN-γ levels are correlated with distinct genotypes. However, no correlation was observed with IFN-γ secretion levels and the SNP rs3181035 , which was significantly associated with type C scar lesions. Our findings strongly suggest that immunogenetic studies of individuals with congenital or postnatally acquired infection are needed to better understand the role of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis.

[Ocular toxocariasis--case report]. / TOXOCAROZA OCULARA (PREZENTARE DE CAZ).

Ocular Toxocariasis is a parasitosis caused by Toxocara catis/canis larvae localized in the eye. The most frequent clinical manifestations are the central retinal granuloma, peripheral retinal granuloma and chronic endophthalmitis. Secondary complications due to the presence of parasite in the posterior segment of the eye may have significant consequences on visual function. We present the case of a 23 years old patient, admitted for progressive decrease of the right eye BCVA during the last 6 months. After performing clinical examination and serological tests we established the diagnosis of ocular Toxocariasis. The patient presented a particular form of the disease consisting in the presence of both a central retinal granuloma and a peripheral one. We performed 23G pars plana vitrectomy and membrane peeling. VA improved as soon as the first month after surgery.

Vitreal, retinal, and choroidal findings in active and scarred toxoplasmosis lesions: a prospective study by spectral-domain optical coherence tomography.

BACKGROUND: The aim of our study was to investigate vitreal, retinal, and choroidal morphologic changes in active and scarred toxoplasmosis lesions using spectral-domain optical coherence tomography (SD-OCT). METHODS: In this prospective study, 19 eyes of 15 consecutive patients with ocular toxoplasmosis were included. Complete ophthalmologic examination and SD-OCT were done at the initial visit and during follow-up. Retina and choroid SD-OCT protocols directed to macular area and lesions observed on clinical examination were used. RESULTS: Seventeen active lesions and 56 retinochoroidal scars were studied. In the acute phase, disruption, thickening, and hyper-reflectivity of the neurosensory retina with photoreceptor (PR) interruption and retinal pigment epithelial (RPE) elevation were found. The choroid became thickened and hyporeflective. During follow-up, neurosensory retinal layers thinning and disorganization, PR interruption, and RPE elevation and/or atrophy were demonstrated. The choroid returned to normal thickness and became more hyperreflective. Five active lesions presented with hyperreflective oval deposits within the vitreoretinal interface, adjacent to or far away from the lesions. During follow-up, the deposits became smaller, entered into the inner retina layers and faded with time until complete resolution. Multiple hyperreflective dots in the vitreous cavity, compatible with vitritis, and posterior hyaloid thickening were demonstrated in the acute phase, with complete resolution and detachment of the posterior hyaloid during follow-up. Four types of scars were specified according to outer retina-choroid interface changes; atrophic, elevated, deep, and combined (atrophic & elevated). Epiretinal membrane segments were found over active and scarred lesions. CONCLUSIONS: SD-OCT imaging showed toxoplasmic retinochoroidal lesions and scars to be complex and characterized acutely by thickening and disorganization of both the retina and underlying choroid, and following scar formation by varying degrees of thinning, often in conjunction with irregularity of the outer retinal layers.

Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study*.

OBJECTIVE: To investigate the relationship among the angiopoietin-Tie-2 system, retinopathy, and mortality in children with cerebral malaria. DESIGN: A case-control study of retinopathy-positive vs. retinopathy-negative children with clinically defined cerebral malaria. SETTING: Queen Elizabeth Central Hospital in Blantyre, Malawi. SUBJECTS: One hundred fifty-five children presenting with severe malaria and meeting a strict definition of clinical cerebral malaria (Blantyre Coma Score ≤ 2, Plasmodium falciparum parasitemia, no other identifiable cause for coma) were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory parameters were recorded at admission and funduscopic examinations were performed. Admission levels of angiopoietin-1, angiopoietin-2, and a soluble version of their cognate receptor were measured by enzyme-linked immunosorbent assay. We show that angiopoietin-1 levels are decreased and angiopoietin-2 and soluble Tie-2 levels are increased in children with cerebral malaria who had retinopathy compared with those who did not. Angiopoietin-2 and soluble Tie-2 were independent predictors of retinopathy (adjusted odds ratio [95% CI], angiopoietin-2, 4.3 [1.3-14.6], p = .019; soluble Tie-2, 9.7 [2.1-45.8], p = .004). Angiopoietin-2 and soluble Tie-2 were positively correlated with the number of hemorrhages, the severity or retinal whitening, and the extent of capillary whitening observed on funduscopic examination (p < .05 after adjustment for multiple comparisons). Angiopoietin-2 and soluble Tie-2 levels were elevated in children with cerebral malaria who subsequently died and angiopoetin-2 was an independent predictor of death (adjusted odds ratio: 3.9 [1.2-12.7], p = .024). When combined with clinical parameters, angiopoetin-2 improved prediction of mortality using logistic regression models and classification trees. CONCLUSIONS: These results provide insights into mechanisms of endothelial activation in cerebral malaria and indicate that the angiopoietin-Tie-2 axis is associated with retinopathy and mortality in pediatric cerebral malaria.

Clinical characteristics of ocular toxocariasis in Eastern China.

PURPOSE: To explore the clinical characteristics of patients with ocular toxocariasis in eastern China. METHODS: The medical records of 35 cases of ocular toxocariasis in Fudan University Eye & ENT Hospital between May 2009 and April 2011 were retrospectively reviewed and analyzed. UBM, RetCam or fundus imaging, and high-frequency or conventional ultrasonography were performed in these patients. RESULTS: The mean patient age in our series of ocular toxocariasis was 11.86 ± 8.80 years. There were 28 children and seven adults, the majority residing in a rural area (88.57%). All cases were classified into three clinical subtypes: granuloma in the peripheral retina (60% of cases); granuloma in the posterior pole (28.57% of cases); and vitreous inflammation mimicking chronic endophthalmitis (5.71% of cases). We also identified an additional subtype with unique clinical features that we termed "combined type" presenting in 5.71% of our patients. This subtype exhibited granulomas in both the posterior pole and peripheral retina. RetCam fundus imaging was able to identify granulomas in the posterior and peripheral subtypes, 100% and 80.95% of cases respectively. Moreover, UBM combined with conventional ultrasonography identified granulomas in 95% of the peripheral subtype cases and in 100% of the posterior pole subtype cases. CONCLUSIONS: This is the first ocular toxocariasis series described in Chinese patients. Compared with reports from developed countries, the ocular features in our series were more severe and complicated, presenting with poorer visual acuity and a high rate of retinal detachment (45.7%). The application of RetCam and UBM during examination in ocular toxocariasis can provide valuable information in determining the severity of disease and features important in considering surgical procedures in such patients.

Imported intraocular gnathostomiasis with subretinal tracks confirmed by western blot assay.

We report a case of intraocular gnathostomiasis diagnosed by western blot assay in a patient with subretinal tracks. A 15-year-old male patient complained of blurred vision in the right eye, lasting for 2 weeks. Eight months earlier, he had traveled to Vietnam for 1 week and ate raw wild boar meat and lobster. His best-corrected visual acuity was 20/20 in both eyes and anterior chamber examination revealed no abnormalities. Fundus examination showed subretinal tracks in the right eye. Fluorescein angiography and indocyanine green angiography showed linear hyperfluorescence of the subretinal lesion observed on fundus in the right eye. Ultrasound examination revealed no abnormalities. Blood tests indicated mild eosinophilia (7.5%), and there was no abnormality found by systemic examinations. Two years later, the patient visited our department again for ophthalmologic evaluation. Visual acuity remained 20/20 in both eyes and the subretinal tracks in the right eye had not changed since the previous examination. Serologic examination was performed to provide a more accurate diagnosis, and the patient's serum reacted strongly to the Gnathostoma nipponicum antigen by western blot assay, which led to a diagnosis of intraocular gnathostomiasis. This is the first reported case of intraocular gnathostomiasis with subretinal tracks confirmed serologically using western blot in Korea.

Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria.

OBJECTIVE: To assess children with retinopathy-positive cerebral malaria (CM) for neurocognitive sequelae. METHODS: Participants were selected from an ongoing exposure-control study. Eighty-three Malawian children averaging 4.4 years of age and diagnosed with retinopathy-positive CM were compared to 95 controls. Each child was classified as delayed or not using age-based norms for the Malawi Developmental Assessment Tool (MDAT) for developmental delay on the total scale and for the domains of gross motor, fine motor, language and social skills. Groups were also compared on the Achenbach Child Behaviour Checklist (CBCL) (1.5-5 years). RESULTS: Children with retinopathy-positive CM were delayed, relative to the comparison group, on MDAT total development (P = 0.028; odds ratio or OR = 2.13), with the greatest effects on language development (P = 0.003; OR = 4.93). The two groups did not differ significantly on the Achenbach CBCL internalizing and externalizing symptoms total scores. Stepwise regression demonstrated that coma duration, seizures while in hospital, platelet count and lactate level on admission were predictive of assessment outcomes for the children with retinopathy-positive CM. CONCLUSIONS: Children who suffer retinopathy-positive CM at preschool age are at greater risk of developmental delay, particularly with respect to language development. This confirms previous retrospective study findings with school-age children evaluated years after acute illness. The MDAT and the Achenbach CBCL proved sensitive to clinical indicators of severity of malarial illness.

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.

Retinopathy in severe malaria in Ghanaian children--overlap between fundus changes in cerebral and non-cerebral malaria.

BACKGROUND: In malaria-endemic areas, reliably establishing parasitaemia for diagnosis of malaria can be difficult. A retinopathy with some features unique to severe malaria with a predictive value on prognosis, has been described. Detection of this retinopathy could be a useful diagnostic tool. This study was designed to determine the diagnostic usefulness of retinopathy on ophthalmoscopy in severe malaria syndromes: Cerebral malaria (CM) and non-cerebral severe malaria (non-CM), i.e. malaria with respiratory distress (RD) and malaria with severe anaemia (SA), in Ghanaian children. Secondly, to determine any association between retinopathy and the occurrence of convulsions in patients with CM. METHODS AND SUBJECTS: A cross-sectional study of consecutive patients on admission with severe malaria who were assessed for retinal signs, at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, from July to August 2002 was done. All children had dilated-fundus examination by direct and indirect ophthalmoscopy. RESULTS: Fifty-eight children aged between six months and nine years were recruited. Twenty six(45%) had CM, 22 with convulsion; 26(45%) had SA and six(10%) had RD.Any retinopathy was seen in: CM 19(73%), SA 14(54%), RD 3(50.0%), CM with convulsion 15(68%) and CM without convulsion 4(100%). Comparison between CM versus non-CM groups showed a significant risk relationship between retinal whitening and CM(OR = 11.0, CI = 2.2- 56.1, p = 0.001). There was no significant association with papilloedema(OR = 0.9, CI = 0.3 - 3.0, p = 0.9), macular whitening(OR = 1.6, CI = 0.5 - 4.8, p = 0.4), macular haemorrhage(OR = 0.28, CI = 0.03 - 2.7 p = 0.2), retinal haemorrhage(OR = 1.9, CI = 0.6 - 5.6, p = 0.3), vessel abnormality(OR = 1.9, CI = 0.6 - 6.1, p = 0.3) and cotton wool spots(OR not calculated, p = 0.08).Tortuous and engorged retinal veins, not previously described as a feature of CM, was the most common vascular abnormality(15/58 = 26%) and was detected even in the absence of papilloedema. CONCLUSION: Retinal whitening, a sign suggestive of retinal ischaemia, was significantly more common in CM than in non-CM syndromes. However, the high prevalence of any retinopathy in the latter suggests that the brain and the retina may be suffering from ischaemia in both CM and non-CM.

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.