Chronic Keratitis Research Articles

Simplified medial canthoplasty: Technique and early postoperative complications in 601 dogs (1180 eyes).

To present a novel modified medial canthoplasty (MCP) technique, the application in 601 dogs (1180 eyes), and a review of the early postoperative complications related to the technique. Macroblepharon and nasal entropion is a common presentation in many brachycephalic dog breeds promoting chronic keratitis. The previously described MCP techniques limit the medial shortening of the eyelids to the location of the lacrimal puncta. A novel technique was developed allowing for a more extensive eyelid shortening nasally. The modification of the here described technique includes the longitudinal splitting of the lacrimal canaliculi allowing for an extensive shortening of the lids beyond the lacrimal puncta. Records of 601 dogs which underwent the modified MCP were reviewed regarding breed, indications for surgery, follow-up, and early postoperative surgical complications. Descriptive statistics were applied. Six hundred one dogs (1180 eyes) were included in this study. Twenty-four different breeds underwent the simplified MCP with the Pug (n = 403) being the most represented breed. Indications were macropalpebral fissure, medial entropion, pigmentary keratitis, trichiasis by haired caruncle, strabismus after globe prolapse, and facial nerve paralysis. The overall complication rate was 1.01% (12/1180) and consisted of wound dehiscence 0.59% (7/1180), corneal ulceration caused by suture material 0.25% (3/1180), and wound infection (2/1180). None of the 601 operated dogs developed serious complications related to the surgical technique. The simplified MCP is a novel technique with a very low complication rate.

Strigid herpesvirus-1 as a differential for chronic keratitis in owls

An adult free-ranging great horned owl was referred for evaluation of chronic ulcerative keratitis in the left eye that had been treated for several months. In vivo confocal microscopy confirmed that the corneal lesion was an inactive scar, and histopathology and molecular testing of a proliferative palpebral conjunctival lesion in the same eye confirmed infection with strigid herpesvirus- 1. Resolution of the conjunctivitis occurred following the biopsy and the owl was released. Four months later the owl re-presented with presumed rodenticide poisoning, and there was no evidence of recurrence of ocular disease.

Early-onset Chronic Keratitis as the First Presenting Component of Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1): A Case Report and Review of the Literature

Early-onset Chronic Keratitis as the First Presenting Component of Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1): A Case Report and Review of the Literature

Опыт применения новых технологий оптической когерентной томографии в диагностике заболеваний роговицы у собак и кошек

In the article we present the results of the clinical study of cornea optical coherence tomography (OCT) in cats and dogs, performed by the authors during complex diagnostics of various keratophathies, such as: endothelial corneal dystrophy, pigmentary keratitis, chronic keratoconjunctivitis, chronic herpetic keratitis, ulcerative keratitis, corneal injuries, cats’ corneal sequestration, chronic keratitis complications of glaucoma. Normal cornea OCT scans characteristics for cats and dogs are given. OCT scans of various corneal pathologies in cats and dogs are presented and the identified pathological changes are described. Corneal OCT scan results of animals after keratoplasty operations with the use of various grafts forms have a great clinical interest. The results of the current clinical study suggest that corneal OCT in cats and dogs is highly informative and promising method of additional diagnosis of severe keratopathies, especially in cases of weak effectiveness of traditional drug therapy regimens, as well as before performing keratoplasty and in its postoperative period.

The long‐term outcomes of standing superficial keratectomy as the sole treatment of corneal B‐cell lymphoma in five horses in the UK: Clinical, histopathology, immunohistochemical and molecular findings

SummaryThis case report describes five horses with solitary corneal B‐cell lymphoma treated with superficial keratectomy as a sole treatment and their long‐term follow‐up. All five cases had a presumed clinical diagnosis of immune‐mediated keratitis (IMMK) which was initially responsive to immunosuppressive or immunomodulatory treatment. Between 6 and 71 months from the start of clinical disease, these cases became refractory to treatment. All five horses underwent superficial keratectomy under standing sedation and regional anaesthesia. A focal superficial keratectomy was performed in one horse to remove the affected area, and in the remaining four horses, the superficial cornea was removed in its entirety. Histopathology, immunohistochemistry (IHC) and polymerase chain reaction for antigen receptor rearrangements (PARR testing) were performed on all five keratectomy specimens. The histopathological and immunohistochemical findings indicated a florid stromal infiltrate of mitotically active, intermediate to large B‐lymphocytes amidst a variable background of chronic keratitis. In three of the five cases, the lymphocytes displayed prominent epitheliotropism. PARR testing confirmed rearrangements of, specifically, IGH2, IGH3 and KDE, indicating B‐cell clonal expansion consistent with B‐cell lymphoma. There has been no local recurrence in any of the five horses over 24–84 months of follow‐up and no clinical evidence of multicentric lymphoma. No adjunctive treatment was given post‐keratectomy and all eyes have remained comfortable and off treatment. Results of this report show that standing superficial keratectomy is a viable diagnostic tool and a long‐term treatment option for diffuse intermediate to large corneal B‐cell lymphoma.

Patterns of Corneal Disorders in Corneal Button Specimens: Descriptive Study in a Tertiary Referral Hospital in Bahrain

Introduction: Corneal injuries and disorders are among the commonest clinical scenarios that are encountered in the ophthalmology clinical practice. Penetrating Keratoplasty (PKP) surgeries count for the most frequent efficient surgical management of diseased corneas. The latter are usually sent as button specimens for histopathology examination for further describing the pattern of the corneal disorders. Aims and Objectives: The aims of this study are to discuss the rate of Penetrating Keratoplasty (PKP) surgeries in SMC in 6 years interval (2016-2022) along with to determine the most common histopathological and microbiological diagnosis of corneal specimens from Penetrating Keratoplasty (PKP) and to study the clinical spectrum with age and sex distribution of corneal disorders in Bahrain alongside correlation with the comorbidities and the pathological diagnosis. Patients and Methods: It is a retrospective analysis of one-hundred and one histopathology reports of corneal button specimens at Salmaniya medical complex during the last 6 years (1-1-2016 till 31-3-2022). Medical records, surgical notes and histopathology reports of patients were retrieved from ISEHA system. Statistical analysis was done using Microsoft Excel 2019. Results: Corneal scarring (44%) was the most common pathological diagnosis, followed by Keratoconus (KC) (15%), acute keratitis (14%), degeneration (9%), chronic keratitis with fibrosis (5%), decompensated cornea and failed graft (5%), pseudophakic bullous keratopathy (3%) and herpetic keratitis (3%). There was Bahraini nationality (98%) and male preponderance (66%). The most common age group affected was 70–79 years with the median age of 51.5 year. Conclusion: Our study shows the importance of determining the most common histological diagnoses of corneal button specimens along with the correlation of the latter with the age, gender, surgical complications and systemic comorbidities. Knowing the exact pathology of the diseased cornea would assist in providing the proper post-operative management and to avoid possible elements that could promote complications.

Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India.

To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population. Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management. Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3-16 μg/mL, amphotericin B: 1-8 μg/mL, voriconazole: 0.5-1.5 μg/mL, itraconazole: 0.5-12 μg/mL, posaconazole: 0.094-1.5 μg/mL. MIC against Aspergillus flavus was natamycin: 8-32 μg/mL, amphotericin B: 0.5-16 μg/mL, voriconazole: 0.025-4 μg/mL, itraconazole: 0.125-8 μg/mL, posaconazole: 0.047-0.25 μg/mL; against Aspergillus niger isolates, to natamycin was 6 μg/mL (n=1), amphotericin B 8-12 μg/mL (n = 3), voriconazole: 0.125-0.19 μg/mL (n = 3), itraconazole: 0.38-0.75 μg/mL, posaconazole: 0.064-0.19 μg/mL and against Aspergillus fumigatus (n = 1), was natamycin4 μg/mL, amphotericin B - 8 μg/mL, voriconazole 0.25 μg/mL, itraconazole 1 μg/mL, and posaconazole 0.19 μg/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5-16 μg/mL, amphotericin B: 0.5-8 μg/mL, voriconazole: 0.19-3 μg/mL, itraconazole: 0.125 μg/mL, posaconazole: 0.125-0.5 μg/mL and against susceptible Curvularia was natamycin 0.75-4 μg/mL, amphotericin B 0.5-1 μg/mL, voriconazole 0.125-0.19 μg/mL, itraconazole 0.047-0.094 μg/mL, posaconazole 0.047-0.094 μg/mL. MIC against Mucor spp.+ Rhizopus spp. (n = 1) was natamycin: 8 μg/mL, amphotericin B: 0.75 μg/mL, posaconazole: 1.5 μg/mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 μg/mL, posaconazole: 0.094 μg/mL. MIC against Penicillium (n=1) was natamycin: 8 μg/mL, voriconazole: 0.25 μg/mL, itraconazole: 0.5 μg/mL, and Posaconazole: 0.125 μg/mL. Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates.

A Patient With Recurrent Immune Stromal Keratitis and Adherence Challenges.

Herpes simplex keratitis (HSK) is a common yet potentially blinding condition caused by a primary or reactivated herpetic infection of the cornea. Immune stromal keratitis (ISK), a type of HSK, is classified by a cellular and neovascularization infiltration of the cornea, and patients with ISK may experience low-grade chronic keratitis for years. A 52-year-old man presented to the eye clinic complaining of a watery and itchy right eye with mildly blurred vision. With consultation from a corneal specialist, the patient was given the presumptive diagnosis of ISK in the right eye based on the unilateral corneal presentation and lack of corneal sensitivity. ISK presents unilaterally with decreased or absent corneal sensitivity and nonspecific symptoms. It should be at the top of the list in the differential diagnosis in any patient with unilateral corneal edema, opacification, or neovascularization, and the patient should be started on oral antiviral therapy.

Crioterapia después de queratectomía por carcinoma de células escamosas en un perro: Reporte de caso

Ocular neoplasms represent a growing part of the veterinary ophthalmic routine. Squamous cell carcinoma (SCC) is described as rare in dogs, but it has been on the increase due to different etiologies. The presence of chronic keratitis and exposure to ultraviolet radiation are some of these factors. In the present study, the objective was to report cryotherapy, a technique that was effective in the treatment of squamous cell carcinoma (SCC). A 13-year-old mixed-breed dog was seen at a veterinary center in Londrina-PR, with a neoformation in the right eye. Ophthalmic examination revealed no other changes. Direct and consensual pupillary reflexes were present and intraocular pressure was 12 mmHg. Slit lamp bio-microscopy was performed, which showed increased corneal thickness and superficial corneal vascularization with neoformation infiltrating the epithelium and small part of the stroma. On that account, the diagnosis of SCC was made which led to the decision to remove the neoplasm. Thus, a lamellar keratectomy was performed associated with the cryotherapy technique, through temporary tarsorrhaphy. The suspicion of carcinoma is based on the macroscopic morphological basis of the lesion and its location, but the definitive diagnosis is made through histopathology with microscopic examination of the injured tissue. It may be concluded that through clinical history, described etiologies and histopathological examination are essential for the diagnosis of SCC.

Corynebacterium jeikeium as an Unusual Cause of Keratitis: A Case Report From a Tertiary Care Hospital in Chhattisgarh, India

Bacterial keratitis is a serious, potentially sight-threatening complication in neglected cases of corneal trauma. Few bacteria and fungi are implicated in the pathogenesis of bacterial keratitis after trauma; however, keratitis by an opportunistic organism is rare. We report here a case of keratitis caused by Corynebacterium jeikeium (C. jeikeium) after accidental trauma with rice grains. The patient presented to us with chronic keratitis, which responded to 5% fortified vancomycin eye drops after microbiological investigation and drug sensitivity.

PRODUCTION AND APPLICATION OF ANGIOSTATINS FOR THE TREATMENT OF OCULAR NEOVASCULAR DISEASES

Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial cells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with aberrant neovascularization. The aim of the present paper was to summarize available information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special emphasis was made on the laboratory approaches of production of different angiostatin isoforms, as well as comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins have been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological conditions induced by traumas, chemical burns, previous surgery, chronic contact lens wear, autoimmune diseases, keratitis and viral infections (herpes, COVID-19), corneal graft rejection, etc. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND treatment illustrates a vivid example of upcoming revolution in local gene therapy. Further comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatinbased intervention modalities for treating ocular neovascularization.

MOOREN’S ULCER

Mooren's ulcer is chronic ulcerative keratitis that is generally painful, progressive starting peripherally and progressing in a circular and centralized manner, either unilateral or bilateral without scleritis and without systemic disease. Mooren's ulcer mostly idiopathic. Mooren's ulcer was divided into three type which is unilateral, bilateral progressive and bilateral indolent. Initial treatment for Mooren's ulcer consists of topical corticosteroids. If corticosteroids do not control inflammation, excision of the limbal conjunctiva can be performed. This case report describes the diagnosis and management of a case of mooren's ulcer without an obvious cause. This topic is important to discuss and requires prompt and adequate management because one of the complications is perforation which can lead to blindness.

Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses

BackgroundDistichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait.ResultsA genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10− 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10− 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder.ConclusionsThis study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance.

Delayed-onset Bilateral Peripheral Posterior Interstitial Keratitis Associated with Epstein-Barr Virus-Induced Infectious Mononucleosis

ABSTRACT Introduction Epstein-Barr Virus (EBV) has been previously reported to cause rare occurrence of mostly epithelial and nummular keratitis. We hereby report two patients developing bilateral peripheral deep interstitial keratitis following EBV-related infectious mononucleosis (IM). Description of cases Two female adolescents presented with findings of chronic relapsing posterior interstitial keratitis with neovascularisation mostly located in the superior and inferior peripheral cornea, in absence of signs of anterior uveitis. The disease presented months after the occurrence of IM. Other etiologies of interstitial keratitis were excluded. EBV DNA could not be detected in the aqueous humor of both patients. The patients responded promptly to topical corticosteroids, with multiple recurrences reported in one case. Conclusion EBV-induced IM can cause bilateral peripheral interstitial keratitis with delayed onset. Progressive relapsing course of the keratitis can be observed.

The use of tear ferning test in cats for evaluation of ocular surface

BackgroundThe tear film is a trilaminar fluid composed mainly of lipids, electrolytes, proteins and water. It is responsible for lubrication, nutrition and protection against microbial and toxic agents. Disruption of any these components may weaken the ocular surface, making it more susceptible to disease. Increasing evidence suggests that qualitative tear film deficiencies are an important predisposing factor or cause of some of the most common and challenging ocular diseases in cats, including conjunctivitis, corneal ulcer, spontaneous chronic corneal epithelial defects (SCCED), pigmentary keratitis, corneal sequestrum and dry eye syndrome. The aim of this study was to describe the tear ferning test in healthy cats and to compare the results by using two grading scales for humans. Tear samples were collected using Schirmer tear test (STT) strips from 60 healthy cats, and, after centrifuging the strips to obtain the samples, the aliquot was placed on clean microscope glass until it dried and the tear ferning patterns were observed under a polarized light microscope and classified according to the Rolando and Masmali grading scales.ResultsFerning patterns in the lower grades showed full crystallization with high density, without gaps between the ferns and branches, forming several nuclei that were easily distinguished. According to the Rolando scale, 50% (60/120), 46.6% (56/120) and 3.4% (4/120) of eyes showed type I, II and III patterns, respectively. According to the Masmali scale, 15% (18/120), 56.6% (68/120 eyes) and 28.4% (34/120) of eyes showed grade 0, 1 and 2 patterns, respectively. No difference was observed between the right and left eyes for both Rolando (P = 0.225) and Masmali (P = 0.683) scales.ConclusionsThe tear ferning test is a qualitative test that can be used in cats as a complementary evaluation of the ocular surface. While the Rolando scale showed an increased prevalence of types I and II, the Masmali scale showed an increased prevalence of grades 1 and 2. This can be attributed to the species-specific differences between human and feline tear film. So Masmali grade 2 can be considered a normal tear pattern for the species, because all the cats used in study were clinically healthy. For this reason, future complementary studies are necessary for comparing healthy eyes and eyes with different ocular surface disease in cats. Both scales can be feasible options for grading tear crystallization in cats, but as Rolando scale included 96.6% of the samples in the 2 types that are considered normal for humans, we think that this scale seemed to be more precise to classify crystallization pattern in cats. The crystallization patterns observed in this study can form the basis for standardizing ocular surface parameters in cats.

Lipofilling of the upper eyelid to treat paralytic lagophthalmos

Lagophthalmos is one of the most unpleasant and dangerous conditions that affect patients with facial palsy. The lack of ocular protection leads to corneal problems (such as conjunctival infections, acute and chronic keratitis, corneal ulcerations, and blindness). A dynamic reanimation of blinking eyelids is the therapeutic gold standard. However, success is not guaranteed with these dynamic techniques; even if results are good, blinking is usually restored within a year of the initial operation. Procedures that act more rapidly and have a higher success rate are needed. We proposed that lipofilling of the upper eyelid would improve eye closure, exploit the advantages of using autologous fat, and avoid the risks of exposure or migration associated with loading the lid with gold. Between 2012 and September 2018, we did upper eyelid lipofilling procedures for 75 patients with unilateral facial palsy. The main favourable result of lipofilling of the upper lid was the immediate improvement in corneal discomfort. Everybody described a partial to total increase in corneal comfort postoperatively. In the treatment of paralytic lagophthalmos, lipofilling of the upper eyelid produces favourable aesthetic and functional results, ocular health is restored, and the patients' quality of life is improved.

Conjunctival Papillomas and Corneal Squamous Cell Carcinomas After Long-term Ciclosporin Treatment in Four Brachycephalic Dogs with Chronic Keratitis

Conjunctival Papillomas and Corneal Squamous Cell Carcinomas After Long-term Ciclosporin Treatment in Four Brachycephalic Dogs with Chronic Keratitis

Mystery eye: Human adenovirus and the enigma of epidemic keratoconjunctivitis.

Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to the specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden.

A treatment protocol for minimizing duration and complications of adenoviral epidemic keratoconjunctivitis.

PURPOSE:The purpose of the study was to assess the treatment protocol of topical 2.5% Povidone-Iodine (PovI) and 0.1% fluorometholone (FluM) for Adenoviral Epidemic keratoconjunctivitis (EKC) in reducing the duration and severity of the disease as compared to conventional treatment. This was a retrospective case–control study.MATERIALS AND METHODS:Cases were defined as patients with EKC receiving the treatment protocol and conjunctival swab taken for polymerase chain reaction. Controls were defined as similar patients receiving conventional treatment protocol. Forty-one cases and 35 controls were identified for analysis. Cases were treated with a protocol using 2.5% povidone-iodine eye drops and 0.1% FluM eye drops. Controls received conventional treatment until resolution of signs and symptoms. Both the groups were followed up for 1 month. Data collected were analyzed for effect of the two treatment protocols on the duration of EKC, rate of recovery, and incidence of complications.RESULTS:The treatment protocol was significantly better than conventional treatment protocol in achieving cure (P = 0.002) with large effect size. The proportion of cases achieving cure was significantly higher with treatment protocol (64% vs. 11% at 5 days, P < 0.001) by 5 days. There was a significant reduction of the subepithelial infiltrates (SEI) incidence group (10% vs. 57%, P < 0.001). There were no SEI at 1 month in the treatment group (0% vs. 31%).CONCLUSION:Treatment protocol used in our study can significantly reduce the severity and duration of EKC. It can prevent chronic keratitis in majority of cases. Since povidone-iodine is nonspecific and virucidal for adenovirus, this therapy can be used for other types of adenoviral conjunctivitis.

Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia

The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis. Acanthamoeba can also cause chronic keratitis and both Balamuthia and Acanthamoeba can cause skin and systemic infections. There are minimal drug development pipelines for these pathogens despite a lack of available treatment regimens and high fatality rates. To identify anti-amebic drugs, we screened 159 compounds from a high-value repurposed library against trophozoites of the three amebae. Our efforts identified 38 compounds with activity against at least one ameba. Multiple drugs that bind the ATP-binding pocket of mTOR and PI3K are active, highlighting these compounds as important inhibitors of these parasites. Importantly, 24 active compounds have progressed at least to phase II clinical studies and overall 15 compounds were active against all three amebae. Based on central nervous system (CNS) penetration or exceptional potency against one amebic species, we identified sixteen priority compounds for the treatment of meningoencephalitis caused by these pathogens. The top five compounds are (i) plicamycin, active against all three free-living amebae and previously U.S. Food and Drug Administration (FDA) approved, (ii) TG02, active against all three amebae, (iii and iv) FDA-approved panobinostat and FDA orphan drug lestaurtinib, both highly potent against Naegleria, and (v) GDC-0084, a CNS penetrant mTOR inhibitor, active against at least two of the three amebae. These results set the stage for further investigation of these clinically advanced compounds for treatment of infections caused by the free-living amebae, including treatment of the highly fatal meningoencephalitis.