Microsporidial Keratitis Research Articles

Advances in clinical diagnosis and treatment of microsporidial keratitis

Microsporidia, a unicellular eukaryotic microorganism, poses a risk of infecting the eyes, precipitating microsporidia keratitis (MK). This condition typically manifests in two forms: microsporidian keratoconjunctivitis (MKC) or stromal keratitis (MSK). While MKC often resolves spontaneously, it can progress to MSK, a vision-threatening condition that, in severe instances, may lead to corneal perforation. Epidemiological studies reveal that MK is prevalent in Southeast Asia, particularly during the rainy season. Diagnosis encompasses a range of methods, including corneal scraping for microbiological analysis, PCR testing, and advanced imaging techniques such as AS-OCT and IVCM. Therapeutic approaches vary, with MKC typically managed through local and systemic drug therapy, while MSK may necessitate more aggressive interventions, including corneal transplantation. In China, MK case reports are scarce, and physicians still grapple with a lack of comprehensive understanding regarding its clinical presentation, diagnostic strategies, and treatment options. This deficit can lead to missed or misdiagnoses, as well as overtreatment. Consequently, this review endeavors to comprehensively outline the epidemiology, etiology, clinical features, diagnostic modalities, and therapeutic interventions for MK, thereby offering valuable insights and guidance for clinical practice.

Microsporidial stromal keratitis: treatment outcomes, clinical manifestations, confocal microscopy and histopathology findings: a retrospective observational study

ObjectiveMicrosporidial stromal keratitis (MSK) is an uncommon disease. Only several case series have been reported. We aimed to describe the clinical manifestations, histopathology and treatment outcomes of MSK.Methods and analysisRetrospective...

Seasonal and Temporal Trends of Infectious Keratitis in Northern Vietnam.

The epidemiology of corneal ulcers in Vietnam has not been well characterized. In this report, we reviewed retrospectively the microbiological data of patients with a clinical diagnosis of corneal ulcer at the microbiology laboratory of Vietnam National Eye Hospital from January 1, 2010 to March 31, 2023. We observed a seasonal pattern for fungal and microsporidial keratitis, with an annual peak in November, and an inverse relationship between fungal keratitis and inclement weather. The November peak coincided with one of the major harvesting seasons in Vietnam. We also observed increasing numbers of microsporidial and Acanthamoeba keratitis cases in recent years. Knowledge of these trends are helpful in guiding empirical treatment of corneal infections and preventing corneal blindness.

Microsporidial Stromal Keratitis: A Rare Entity in Central Europe

Recent data analyses account for corneal opacities as the fifth leading cause of blindness worldwide [1], with infectious keratitis being the most common condition [2], [3]. Microsporidia are obligate intracellular, spore-forming fungi that may cause such infectious keratitis. Their ubiquitous presence in the environment leads to frequent human exposure [4], although the exact pathogenesis of keratitis remains unclear. Direct inoculation with contaminated water, food, soil, and ocular trauma has been postulated [5], [6]. There are two different corneal manifestations of microsporidial keratitis: multifocal epithelial keratitis, which mainly affects immunosuppressed patients as in human immunodeficiency virus (HIV), and stromal keratitis, largely seen among immunocompetent individuals [7]. The disease entity is endemic in Asian countries and has rarely been reported in Europe [8]. We describe a case of histopathologically confirmed stromal microsporidial keratitis diagnosed at a tertiary care hospital in Switzerland.

Microsporidia-Associated Anterior Uveitis After Keratoconjunctivitis.

The aim of this study was to describe the clinical features and management of uveitis associated with microsporidial keratoconjunctivitis (MKC). The medical records of clinically diagnosed or microbiologically proven patients with MKC between July 2016 and August 2021 were reviewed. Patients with documented evidence of keratic precipitates (KPs) or anterior chamber cells were analyzed for their demography, clinical features, and treatment. Patients with microsporidial stromal keratitis and herpes simplex virus keratouveitis were excluded from the study. Of the 2212 patients reviewed within the study period 171 of 172 eyes (7.7%) had documented evidence of KPs and/or anterior chamber cells. The patients' mean age was 43.8 ± 13.8 years, and there were more men (n = 120). The mean duration of appearance of KPs was 6.9 ± 5.5 days, and 28% (n = 48 of 171) appeared on the day of presentation. Superficial punctate keratitis was central and diffuse in 48 and 49 patients, respectively. The treatment was either lubricant alone (45.3%; 78 eyes) or combined with topical steroids (54.7%; 94 eyes). The mean duration of the resolution was longer in the "corticosteroid" than "no corticosteroid" group: KPs: 15.3 ± 6.5 days versus 12.3 ± 5.8 days ( P = 0.007) and superficial punctate keratitises: 15.4 ± 9.4 days versus 11.7 ± 6.2 days ( P = 0.01). The presenting visual acuity with a pinhole was 0.26 ± 0.26 (logMAR) and it improved to 0.03 ± 0.07 on resolution ( P < 0.0001, paired t test). Uveitis after MKC is a self-limiting entity that often resolves without corticosteroid. One must exercise caution in using steroids in the presence of active corneal lesions.

Microsporidial Keratitis - First Case Series of a Rare Pathogen in the Wake of Flood Disasters of 2022 in Pakistan.

The recent monsoon rains in Pakistan were unprecedented and caused flooding all over Pakistan, especially in Sindh and Balochistan. Following this national disaster, various water-borne and contagious diseases started erupting all over the country. In such a calamity-struck city of Jacobabad, we started receiving cases with a peculiar set of ocular complaints mimicking viral keratoconjunctivitis. Failure to respond to traditional treatment and the unique appearance of these corneal opacities led to a rare diagnosis of Microsporidial Keratoconjunctivitis, which was later confirmed by microscopy and staining of corneal scrapings of the most affected case. In line with published literature, all cases were treated with topical fluoroquinolone and topical anti-fungal therapy, following which the disease was cleared within a week. The disease has seen an upward trend the world over, especially among Asia. To the best of our knowledge, no such cases have been reported in Pakistan as yet. In this case series, we highlightthe strong correlation of emergence of microsporidial keratitis in patients following exposure to pooled water bodies after the monsoon rainy season and floods. Moreover, this report will help create awareness in eye professionals regarding the prevention, timely diagnosis and treatment of these rare and emerging cases. Key Words: Keratitis, Spores, Water-borne diseases, Microsporidia.

Microsporidial Keratitis First Case Series of a Rare Pathogen in the Wake of Flood Disasters of 2022 in Pakistan

Microsporidial Keratitis First Case Series of a Rare Pathogen in the Wake of Flood Disasters of 2022 in Pakistan

Chlorhexidine in the treatment of microsporidial stromal keratitis and the effect of host immunity: A case series and literature review.

Microsporidial stromal keratitis is an increasingly well-known vision-threatening disease. A large proportion of cases are initially misdiagnosed as herpes simplex keratitis and treated with topical steroids. In most of such cases, medical treatment failed, and corneal transplantation was required. This study reported the results of 0.02% topical chlorhexidine used to treat three cases of microsporidial stromal keratitis and reviewed the literature on the outcomes of microsporidial stromal keratitis treatment. In the first case, histopathology of a specimen from penetrating keratoplasty (PK) revealed severe chronic inflammation involving the entire stromal layer but no microorganism activity after the application of topical chlorhexidine for 10 months. The second case exhibited complete resolution of keratitis after topical chlorhexidine. The patient in the third case did not respond to medical treatment, and therapeutic PK was performed. Histopathological examination revealed numerous microsporidial spores that had colonized in the mid and deep stroma, where few inflammatory cells were observed. These findings explain the variable microsporidial susceptibility to chlorhexidine, suggesting the crucial role of host immunity. In cases of host immunity, topical chlorhexidine may represent a promising option for the treatment of microsporidial stromal keratitis.

Microsporidia-induced stromal keratitis: a new cause of presumed immune stromal (interstitial) keratitis

Background and objectiveTo describe the clinical features, diagnosis and management of immune stromal keratitis/interstitial keratitis (IK) associated with microsporidial epithelial keratitis.MethodsBetween October 2020 and January 2021, medical records of IK...

Successful medical management of bilateral microsporidial stromal keratitis

An 81-year-old gentleman with a vague history of dust falling into the eyes presented with a white lesion in the left eye for 5 months. Both eyes showed two foci of central dense stromal infiltrates with keratic precipitates. Suspecting herpes simplex virus (HSV) keratouveitis, topical steroids, and antiviral eye ointment were started. A month later, he developed unilateral microsporidial keratoconjunctivitis with persistent bilateral deep stromal keratitis. The corneal scrapings revealed microsporidial spores on 10% Potassium hydroxide (KOH)with Calcofluor White Stain. Topical 1% voriconazole eye drops for 4 months in the right eye, a combination of 1% voriconazole and Natamycin eye drops for 9 months in the left eye and oral albendazole 400 mg twice daily for 3 weeks resulted in complete resolution. There were no recurrences over 1 year. We present a literature review of the medical management of microsporidial stromal keratitis highlighting our case with bilateral disease successfully managed medically with antifungal therapy.

Health Risk in Hot Springs: A Literature Review

Natural hot spring is one of the recreational water. The public used it for recreation, relaxation, and therapy. The water quality should meet standards, such as free from microorganisms to prevent the onset of health complaints. This paper aimed to identify the pathogenic microorganisms and recreational water illness in natural hot spring users from worldwide studies. Method: This systematic review analysis use PRISMA Protocol as a guide to provide this article and PEO Framework to specified the criteria. Various database used to find those article is NCBI, Google Scholar, and Science Direct. In total of 10 eligible articles to analyse from 2010 -2020. Discussion: The result showed that hot spring users experienced health complaints after using hot springs contaminated with pathogenic microorganisms. The microorganisms identified were Naegleria spp, Naegleria fowleri, Legionella pneumophila, Vittaforma corneae, Mycobacterium avium-intracellulare Complex (MAC), Pseudomonas aeruginosa, and Mycobacterium phocaicum. Recreation water illnesses identified were Primary Amebic Meningoencephalitis (PAM), Legionella pneumonia, Pseudomonas foliculitis, Pseudomonas mastitis, Microsporidial keratitis, Hot tub lung (HTL), and P. aeruginosa pneumonia. Besides the water quality, age, comorbid, and frequency of visiting hot springs were risk factors of recreational water illness. Conclusion: The onset of recreational water illness in users of hot springs was influenced by the quality of water microbiology and age.

Microsporidial Stromal Keratitis: Epidemiological Features, Slit-Lamp Biomicroscopic Characteristics, and Therapy.

Microsporidial stromal keratitis is a rare form of infectious keratitis, with only 7 cases reported in the United States to date. This study was performed to evaluate risk factors, clinical features, and response to therapy. A retrospective review of the medical records of all patients diagnosed with microsporidial stromal keratitis seen in the practices of the authors between 1999 and 2020 was performed. Diagnosis was determined by cytology or histopathology in corneal specimens. Risk factors, presence or absence of distinctive clinical features, and response to medical and surgical therapies were recorded. Nine patients-7M:2F, aged 7 to 99 years-with microsporidial stromal keratitis were identified. Exposures to recreational water and hymenopteran insect bites, both epidemiologically linked risk factors for systemic microsporidial infection, were identified in our patients. Presence of stromal edema with features of disciform keratitis and a distinctive granular keratitis were observed in 6 of 9 and 5 of 9 patients, respectively. Poor response to medical therapy was noted. Penetrating keratoplasty was effective in curing the infection. Final visual acuity was 20/40 or better in 6 of 9 patients. In patients with slowly progressive keratitis, history of exposure to recreational water or hymenopteran insects should be sought. In patients with corneal edema consistent with disciform keratitis, with evolution to a granular keratitis, microsporidia should be considered in the differential diagnosis. In cases of established microsporidial stromal keratitis, penetrating keratoplasty should be considered if prompt response to medical therapy is not noted.

Microsporidial stromal keratitis: an uncommon etiology of bilateral simultaneous corneal infection

We report three cases of bilateral microsporidial keratitis, which is an unusual presentation. All three patients presented with bilateral, simultaneous, asymmetrical, deep stromal corneal infiltrates with symptoms ranging from 5 to 12 months. Predisposing factors were noted in two of three patients. Corneal scrapings for microbiology and histopathology of corneal tissue revealed microsporidial spores from both eyes of all patients. There was no response to medical therapy and all underwent bilateral corneal transplantation. Case one additionally had recurrences in the graft and underwent repeat keratoplasties and eventually keratoprosthesis. Microsporidial stromal keratitis is a possible cause of keratitis in cases of very long-standing, indolent, culture-negative, deep stromal corneal infiltrates. So far, this infection has been reported as unilateral; however, we report these cases of bilateral infection, which is rare. Corneal transplantation is the preferred line of management due to lack of response to medical therapy.

A Narrative Review of Microsporidial Infections of the Cornea.

Microsporidia are a rare and commonly misdiagnosed cause of corneal infection, accounting for approximately 0.4% of cases of microbial keratitis in some populations. Ocular microsporidiosis most often presents as either microsporidial keratoconjunctivitis (MKC) or microsporidial stromal keratitis (MSK). Though these two clinical entities exhibit similar symptomology, they are distinguished from one another by the time course for disease progression, findings on slit-lamp examination, and response to medical therapy. This review summarizes the current literature on the etiology and clinical presentation of microsporidial infections of the cornea and highlights ongoing developments in available diagnostic modalities and treatment regimens.

Microsporidial stromal keratitis: characterisation of clinical features, ultrastructural study by electron microscopy and efficacy of different surgical modalities

AimsTo report the clinical manifestations, ultrastructure and evaluate the efficacy of therapeutic lamellarkeratectomy (TLK) and penetrating keratoplasty (PK) for microsporidial stromal keratitis (MSK).MethodsFourteen MSK cases between 2009 and 2018 were...

Molecular identification of microsporidian species in patients with epithelial keratitis.

Introduction. Ocular microsporidiosis is a significant emerging infectious disease reported in immunocompromised patients and immunocompetent persons throughout the world.Aim. To identify the pathogens responsible for human keratitis, via corneal scrapings.Methodology. Thirty-three hospitalized patients with epithelial keratitis were examined using staining and DNA sequencing. DNA was extracted from corneal samples and the small-subunit ribosomal RNA gene was amplified by polymerase chain reaction (PCR) and sequenced.Results. Twenty-one samples were positive by staining while PCR generated amplicons in 18 cases. Of the 18 sequences, 16 were identical with, or very similar to, those of Vittaforma corneae (99-100 % similarity) and the remaining two sequences were similar to that of unidentified Microsporidium species deposited in the GenBank.Conclusion. This study has reconfirmed that V. corneae causes epithelial keratitis in humans and that a newly detected Microsporidium species is also involved in microsporidial keratitis as one of the emerging pathogens in Thailand. Ophthalomologists should be aware of microsporidial keratitis in people from Thailand and those from neighbouring countries.

Demographic and clinical profile of microspodial keratitis in North India: an underreported entity.

Ocular microsporidiosis was first described in immunocompromised subjects but recent reports have also shown cases in immunocompetent hosts. The database of existing clinical studies is very limited. The aim of present study was to analyse demographic profile, clinical features, microbiological profile, treatment and outcome of ocular microsporidiosis in northern India. The present study was carried out in the Department of Medical Parasitology, Advanced Eye Center, Postgraduate Institute of Medical Education and Research, and Bharat Vikas Parishad Charitable trust, Chandigarh. A total of 250 patients during year 2013-17 and suspected of microsporidial keratitis (either clinically or after exclusion of bacterial, viral or fungal agents). Corneal scraping were taken and subjected for various staining methods and PCR. 8 patients of microsporidial keratitis were confirmed, based on positivity by at least any two of the above mentioned techniques. None of the patients had history of contact lens wear or exposure to swimming pool. All these patients were systemically healthy and HIV serology was negative except one had history of diabetes mellitus. This study is a reminder to clinicians that when multifocal diffuse epithelial keratitis and culture-negative keratoconjunctivitis not responding to medical therapy, regardless of immune status are found in patients with symptoms suggesting an infectious keratitis, microsporidial keratoconjunctivitis should be included in the differential diagnosis.

Microsporidial keratitis retrospectively diagnosed by ultrastructural study of formalin-fixed paraffin-embedded corneal tissue: a case report

BackgroundThe utility of formalin-fixed paraffin-embedded (FFPE) corneal tissue specimens for retrospective diagnosis of microsporidial keratitis was evaluated by transmission electron microscopy (TEM) analysis and the possible second case of microsporidial keratitis after Descemet stripping automated endothelial keratoplasty (DSAEK) was described.Case presentationA 68-year-old man presented with multiple crystalline opacities in the corneal stroma that progressed extremely slowly after DSAEK. Fungiflora Y staining of corneal scrapings from the affected regions revealed an oval microorganism. Topical voriconazole administration was ineffective and penetrating keratoplasty was performed. Histological and molecular analyses were carried out on the excised cornea. Ziehl–Neelsen staining revealed an acid-fast, oval organism that was visible by ultraviolet illumination after Fungiflora Y and Uvitex 2B staining, whereas periodic acid-Schiff and Grocott’s staining did not yield any significant findings. Microsporidium was detected by TEM of FFPE tissue. Nosema or Vittaforma sp. was suspected as the causative microorganism by PCR of FFPE tissue and by the fact that those species are known to cause eye infection. The corneal graft has maintained transparency at 1 year and half postoperatively.ConclusionsThis is the first known case of microsporidial keratitis diagnosed retrospectively by molecular and ultrastructural study of FFPE tissue, and the possible second case of microsporidial keratitis after DSAEK. Microsporidial keratitis should be considered when corneal opacity refractory to conventionally known therapy would occur after DSAEK. Our findings suggest that more microsporidial keratitis cases than have been reported to date can be identified by TEM or PCR examination of FFPE corneal specimens.

Efficacy of fumagillin bicyclohexylamine on experimental corneal neovascularization in rat model.

Fumagillin has been previously used to treat corneal microsporidial keratitis and also identified as an angiogenesis inhibitor. This study aimed to evaluate efficacy of fumagillin bicyclohexylamine on the rat model of corneal neovascularization induced by silver nitrate cauterization. Twenty-four Albino Wistar rats (n = 24) were divided into three groups. Following silver nitrate-induced corneal injury, eyes in Group 1 received one drop of 5mg/mL topical fumagillin bicyclohexylamine four times daily for 10days. Group 2 received subconjunctival injection of 0.1mL fumagillin bicyclohexylamine (2.5mg/mL) on day 1 and day 5. Group 3 received artificial tears and lubricants four times daily for 10days as control. On day 10, animals were sacrificed. Corneal specimens were obtained and prepared to assess vascular endothelial growth factor (VEGF-C) levels and corneal angiogenic microvessel density. There was no significant difference in VEGF-C levels between the groups (P = 0.994). Assessment of angiogenic microvessel density for peripheral corneal zone also did not reveal significant difference between the groups (P = 0.113). However, mean vascular density in Group 1 and Group 2 was significantly higher for both midperipheral and central corneal zones in comparison with Group 3 (P = 0.003, P = 0.015). Previously proved to be effective for treatment of microsporidial keratitis in humans, topical and subconjunctival concentration or dosing of fumagillin bicyclohexylamine failed to reduce corneal neovascularization induced by silver nitrate in this study. Further studies comparing different concentrations and dosing may detect inhibitory effects of fumagillin on corneal neovascularization without inducing toxicity.

Surveillance of Vittaforma corneae in hot springs by a small-volume procedure

Vittaforma corneae is an obligate intracellular fungus and can cause human ocular microsporidiosis. Although accumulating reports of V. corneae causing keratoconjunctivitis in both healthy and immunocompromised persons have been published, little is known about the organism's occurrence in aquatic environments. Limitations in detection sensitivity have meant a large sampling volume is required to detect the pathogen up to now, which is problematic. A recent study in Taiwan has shown that some individuals suffering from microsporidial keratitis (MK) were infected after exposure to the pathogen at a hot spring. As a consequence of this, a survey and analysis of environmental V. corneae present in hot springs became an urgent need. In this study, sixty water samples from six hot spring recreation areas around Taiwan were analyzed. One liter of water from each sample site was filtered to harvest the fungi. The positive samples were detected using a modified nested PCR approach followed by sequencing using specific SSU rRNA gene primer pairs for V. corneae. In total fifteen V. corneae-like isolates were identified (25.0% of sites). Among them, six isolates, which were collected from recreational areas B, C and D, were highly similar to known V. corneae keratitis strains from Taiwan and other countries. Furthermore, five isolates, which were collected from recreation areas A, C, E and F, were very similar to Vittaforma-like diarrhea strains isolated in Portugal. Cold spring water tubs and public foot bath pools had the highest detection rate (50%), suggesting that hot springs might be contaminated via untreated water sources. Comparing the detection rate across different regions of Taiwan, Taitung, which is in the east of the island, gave the highest positive rate (37.5%). Statistical analysis showed that outdoor/soil exposure and a high heterotrophic plate count (HPC) were risk factors for the occurrence of V. corneae. Our findings provide empirical evidence supporting the need for proper control and regulations at hot spring recreational waters in order to avoid health risks from this pathogen. Finally, we have developed a small volume procedure for detecting V. corneae in water samples and this has proved to be very useful.