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PURPOSE: This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography. METHODS: This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts reliability (calibration) and resolution (boldness) and were compared between local (Indian) and external (non-Indian) experts. RESULTS: Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40). CONCLUSION: Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.

OBJECTIVES: The aim of this study was to retrospectively evaluate the signalment, treatment, surgical technique and outcomes for feline symblepharon. METHODS: A retrospective medical record review and standardized grading of clinical descriptions and photographs was undertaken. RESULTS: Forty kittens (54 eyes) aged 3-46 weeks had symblepharon of five types in various combinations: eyelid deformation (24 kittens; 32 eyes); ankyloblepharon (four kittens; four eyes); conjunctiva-to-conjunctiva (11 kittens; 12 eyes); third eyelid-to-conjunctiva (24 kittens; 29 eyes); and corneoconjunctival adhesions (14 kittens; 16 eyes). At initial presentation, 23 (43%) eyes were affected by one type of symblepharon, 25 (46%) eyes by two types and six (11%) eyes by three types; 11 (20%) corneas were ulcerated. Twenty-four (44%) eyes of 18 (45%) kittens were managed medically. Surgery was performed under general anesthesia/sedation (30 occasions) or topical anesthesia (21 occasions) on 30 (56%) eyes of 22 kittens; 12 eyes (40%) underwent multiple surgeries. Four techniques were commonly employed: separation of conjunctival-to-conjunctival adhesions ± eyelid margins (14 eyes); resection of third eyelid adhesions ± temporary tacking of the third eyelid (modified Arlts pterygium technique; 18 eyes); en bloc resection of the third eyelid (two eyes); and separation of corneoconjunctival adhesions (14 eyes). Median duration of follow-up was 55 days (range 1-1051). Median symblepharon grade in kittens treated surgically improved for all types except corneoconjunctival symblepharon. Median symblepharon grade in kittens receiving medical management remained the same or improved. Corneoconjunctival symblepharon opacity decreased for eyes treated surgically but increased for eyes treated medically. Three eyes were enucleated due to complications of corneoconjunctival symblepharon. At final presentation, symblepharon persisted in 46 (85%) eyes; however, menace response was evident in 13/16 eyes an

During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis.

During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis.

Objectives: To study the treatment outcomes of intrastromal voriconazole injections in patients with resistant mycotic keratitis in terms of clinical characteristics and associated risk factors for treatment success. Methods: We retrospectively reviewed 70 medical records at a tertiary referral center in Northeastern Thailand from November 2015 to January 2020. The patients had fungal keratitis resistant to topical antifungal eye drops, with or without systemic antifungal therapy, and underwent intrastromal voriconazole injection. The recorded data included demographic information, possible risk factors, microbiological studies, clinical findings, procedures, clinical outcomes, and complications of the injections. Results: Of the 70 patients, 15.2% showed improvement, while the others required therapeutic penetrating keratoplasty (TPK) or evisceration. The mean size of the ulcer was 4.84 mm. Ulcer < 4 mm and the presence of hypopyon were associated with treatment failure (p=0.015 and p=0.003, respectively). Vegetative materials were the most common risk factor. Fusarium species were isolated from 57.1% of the identified organisms. The most common complications were new corneal infiltrations and hyphemas. Conclusions: Intrastromal voriconazole injection reduces the need for therapeutic penetrating keratoplasty or evisceration, as approximately one-sixth of patients with non-healing fungal keratitis responded to it.

Objectives: To study the treatment outcomes of intrastromal voriconazole injections in patients with resistant mycotic keratitis in terms of clinical characteristics and associated risk factors for treatment success. Methods: We retrospectively reviewed 70 medical records at a tertiary referral center in Northeastern Thailand from November 2015 to January 2020. The patients had fungal keratitis resistant to topical antifungal eye drops, with or without systemic antifungal therapy, and underwent intrastromal voriconazole injection. The recorded data included demographic information, possible risk factors, microbiological studies, clinical findings, procedures, clinical outcomes, and complications of the injections. Results: Of the 70 patients, 15.2% showed improvement, while the others required therapeutic penetrating keratoplasty (TPK) or evisceration. The mean size of the ulcer was 4.84 mm. Ulcer < 4 mm and the presence of hypopyon were associated with treatment failure (p=0.015 and p=0.003, respectively). Vegetative materials were the most common risk factor. Fusarium species were isolated from 57.1% of the identified organisms. The most common complications were new corneal infiltrations and hyphemas. Conclusions: Intrastromal voriconazole injection reduces the need for therapeutic penetrating keratoplasty or evisceration, as approximately one-sixth of patients with non-healing fungal keratitis responded to it.

PurposeTo develop and evaluate an automated, portable algorithm to differentiate active corneal ulcers from healed scars using only external photographs.DesignA convolutional neural network was trained and tested using photographs of corneal ulcers and scars.ParticipantsDe-identified photographs of corneal ulcers were obtained from the Steroids for Corneal Ulcers Trial (SCUT), Mycotic Ulcer Treatment Trial (MUTT), and Byers Eye Institute at Stanford University.MethodsPhotographs of corneal ulcers (n = 1313) and scars (n = 1132) from the SCUT and MUTT were used to train a convolutional neural network (CNN). The CNN was tested on 2 different patient populations from eye clinics in India (n = 200) and the Byers Eye Institute at Stanford University (n = 101). Accuracy was evaluated against gold standard clinical classifications. Feature importances for the trained model were visualized using gradient-weighted class activation mapping.Main outcome measuresAccuracy of the CNN was assessed via F1 score. The area under the receiver operating characteristic (ROC) curve (AUC) was used to measure the precision-recall trade-off.ResultsThe CNN correctly classified 115 of 123 active ulcers and 65 of 77 scars in patients with corneal ulcer from India (F1 score, 92.0% [95% confidence interval (CI), 88.2%-95.8%]; sensitivity, 93.5% [95% CI, 89.1%-97.9%]; specificity, 84.42% [95% CI, 79.42%-89.42%]; ROC: AUC, 0.9731). The CNN correctly classified 43 of 55 active ulcers and 42 of 46 scars in patients with corneal ulcers from Northern California (F1 score, 84.3% [95% CI, 77.2%-91.4%]; sensitivity, 78.2% [95% CI, 67.3%-89.1%]; specificity, 91.3% [95% CI, 85.8%-96.8%]; ROC: AUC, 0.9474). The CNN visualizations correlated with clinically relevant features such as corneal infiltrate, hypopyon, and conjunctival injection.ConclusionsThe CNN classified corneal ulcers and scars with high accuracy and generalized to patient populations outside of its training data. The CNN f

PurposeThe purpose of this article was to evaluate the impact of sample collection order on the diagnostic yield of metagenomic deep sequencing (MDS) for determining the causative pathogen in infectious keratitis.MethodsWe performed a cross-sectional diagnostic test evaluation among subjects with infectious keratitis at Aravind Eye Hospital in Madurai, India. All subjects underwent corneal scrapings of the affected eye to obtain potassium hydroxide smear, Gram stain, bacterial culture, and fungal culture, in this order. The order of MDS specimen collection relative to smear and culture samples was randomized and served as the primary predictor. Outcomes included the normalized copy number of pathogenic RNA detected by MDS, the proportion of MDS samples that were diagnostic, and the agreement of MDS results with cultures.ResultsMDS samples from 46 subjects with corneal ulcers were evaluated. MDS was positive in 33 subjects (76%) and had 74% overall agreement with culture results. There was no association between order of MDS sample collection and normalized copy number of genetic material detected (P = 0.62) or the likelihood of MDS positivity (P = 0.46). However, the likelihood of agreement between MDS and cultures decreased when MDS corneal swabs were collected after other diagnostic corneal scrapings (P = 0.05).ConclusionsThe overall yield of MDS for detecting the cause of infectious keratitis was not affected by sample collection order. However, diagnostic agreement between MDS and cultures decreased when MDS samples were collected after other specimens. Additional investigation is warranted to determine whether this represents increased sensitivity of MDS compared with cultures or higher susceptibility to contaminants.

PurposeDevelop computer vision models for image-based differentiation of bacterial and fungal corneal ulcers and compare their performance against human experts.DesignCross-sectional comparison of diagnostic performance.ParticipantsPatients with acute, culture-proven bacterial or fungal keratitis from 4 centers in South India.MethodsFive convolutional neural networks (CNNs) were trained using images from handheld cameras collected from patients with culture-proven corneal ulcers in South India recruited as part of clinical trials conducted between 2006 and 2015. Their performance was evaluated on 2 hold-out test sets (1 single center and 1 multicenter) from South India. Twelve local expert cornea specialists performed remote interpretation of the images in the multicenter test set to enable direct comparison against CNN performance.Main outcome measuresArea under the receiver operating characteristic curve (AUC) individually and for each group collectively (i.e., CNN ensemble and human ensemble).ResultsThe best-performing CNN architecture was MobileNet, which attained an AUC of 0.86 on the single-center test set (other CNNs range, 0.68-0.84) and 0.83 on the multicenter test set (other CNNs range, 0.75-0.83). Expert human AUCs on the multicenter test set ranged from 0.42 to 0.79. The CNN ensemble achieved a statistically significantly higher AUC (0.84) than the human ensemble (0.76; P < 0.01). CNNs showed relatively higher accuracy for fungal (81%) versus bacterial (75%) ulcers, whereas humans showed relatively higher accuracy for bacterial (88%) versus fungal (56%) ulcers. An ensemble of the best-performing CNN and best-performing human achieved the highest AUC of 0.87, although this was not statistically significantly higher than the best CNN (0.83; P = 0.17) or best human (0.79; P = 0.09).ConclusionsComputer vision models achieved superhuman performance in identifying the underlying infectious cause of corneal ulcers compared with cornea specialists.

BackgroundCorneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.MethodsA cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.FindingsWe assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control gro

PurposeTo determine whether a community health worker (CHW) program increases referrals to local eye care providers and ultimately reduces the incidence of corneal ulcers.DesignCluster-randomized trial performed from 2014 to 2017 in rural South India.MethodsThis was a community-based study that included all inhabitants of 42 rural South Indian communities. CHWs were trained to diagnose corneal abrasions and assist participants in seeking care at a local vision center. Given the nature of the intervention, the trial was not masked. The main outcome measure was incident corneal ulcer, defined as an active infiltrate or evidence of a new opacity, as assessed by means of penlight examination during an annual door-to-door census.ResultsTwenty-one study clusters were randomized to the CHW intervention and 21 to no intervention. Vision centers diagnosed 195 corneal abrasions from the intervention clusters during the 2-year study (rate, 223 per 100,000 person-years; 95% CI, 28-1743) and 62 from the control clusters (rate, 62 per 100,000 person-years; 95% CI, 8-496; incidence rate ratio, 3.57; 95% CI, 2.01-6.35; P < .001). The estimated incidence of corneal ulceration during the study period was 60 per 100,000 person-years (95% CI, 25-141) in the intervention group and 32 per 100,000 person-years (95% CI, 13-80) in the control group (incidence rate ratio, 1.86; 95% CI, 0.5-6.4; P = .32).ConclusionsA CHW program resulted in 3.5 times more referrals to local eye care providers for corneal abrasions, but no difference could be detected in the incidence of corneal ulceration. CHW programs provide a mechanism for increasing referrals to eye hospitals.Trial registrationClinicalTrials.gov ID: NCT02284698.

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

PURPOSE: To determine if smartphone photography could be a useful adjunct to blindness prevalence surveys by providing an accurate diagnosis of corneal opacity. METHODS: A total of 174 patients with infectious keratitis who had undergone corneal culturing over the past 5 years were enrolled in a diagnostic accuracy study at an eye hospital in South India. Both eyes had an ophthalmologist-performed slit lamp examination, followed by anterior segment photography with a handheld digital single lens reflex (SLR) camera and a smartphone camera coupled to an external attachment that provided magnification and illumination. The diagnostic accuracy of photography was assessed relative to slit lamp examination. RESULTS: In total, 90 of 174 enrolled participants had a corneal opacity in the cultured eye and no opacity in the contralateral eye, and did not have a penetrating keratoplasty or missing photographs. Relative to slit lamp examination, the sensitivity of corneal opacity diagnosis was 68% (95%CI 58-77%) using the smartphones default settings and 59% (95%CI 49-69%) using the SLR, and the specificity was 97% (95%CI 93-100%) for the smartphone and 97% (95%CI 92-100%) for the SLR. The sensitivity of smartphone-based corneal opacity diagnosis was higher for larger scars (81% for opacities 2 mm in diameter or larger), more visually significant scars (100% for eyes with visual acuity worse than 20/400), and more recent scars (85% for eyes cultured in the past 12 months). CONCLUSION: The diagnostic performance of a smartphone coupled to an external attachment, while somewhat variable, demonstrated high specificity and high sensitivity for all but the smallest opacities.

Purpose: To describe the effectiveness and safety of nicergoline in patients with epithelial corneal defect or corneal ulcer due to neurotrophic keratitis. Methods: A prospective case series review was performed in 14 patients (14 eyes) with neurotrophic keratopathy who started treatment with nicergoline as an off-label prescription from January to November of 2020. Patients with a epithelial defect or corneal ulcer due to neurotrophic keratitis were treated with 10 mg of oral nicergoline twice daily. Results/Serial cases: Complete corneal healing was observed in 10 (71.4%) of the 14 patients after 25.6 ± 26.60 days (range 7-90) with nicergoline. In three (21.5%) patients the wound healing was not achieved (all of them with autoimmune disease), and one patient (7.1%) was lost to follow-up. Eleven patients (79%) were females; the average age at consultation was 69 years (44-96). The mean time between diagnosis and the starting of nicergoline was 10.92 ± 8.85 days (0-28). No adverse effects of nicergoline were observed in any subject. Conclusion: Nicergoline as an adjunctive treatment for neurotrophic keratitis showed a potential use in the healing of epithelial defect with a good tolerance in real-life clinical practice. Introduction

Infectious bovine keratoconjunctivitis (IBK) is a painful ocular disease in cattle that is characterized by the presence of a corneal ulcer and production losses. A common industry practice is to cover an affected eye with a piece of cloth to reduce exposure to face flies and ultraviolet light with the goal of alleviating pain, accelerating healing, and reducing spread. To study the efficacy of eye patches in the treatment of IBK, a group of 216 clinically normal Angus crossbred steers were followed between April and August 2019 and evaluated weekly for the development of IBK. Eyes of cattle that developed IBK were enrolled with a blocked randomization scheme based on ulcer severity score to receive either an eye patch (treatment group) or no eye patch (control group). All treatment and control group animals received parenteral antimicrobial and nonsteroidal anti-inflammatory treatments and were housed in a pasture separated from the rest of the cohort for a maximum of 28 d or until clinical cure. Corneal ulcer areas were measured, and body weights were recorded twice weekly for steers in the treatment and control groups. Weights of all steers in the cohort were recorded three times during the trial period. The primary outcome, rate of corneal ulcer healing, was higher (P = 0.001) for lesions in eyes receiving an eye patch as determined by a linear mixed model that controlled for ulcer severity score at enrollment and previous IBK in the opposite eye. Median corneal ulcer healing time was 10 (IQR [Interquartile range] 7-17) d for patched eyes vs. 14 (IQR 7-21) d for unpatched eyes. In a Cox proportional hazards model adjusted for severity score at diagnosis, the hazard ratio for ulcer healing was 1.62 (95% CI: 1.02-2.56, P = 0.042) for eyes that received a patch compared to eyes that did not. Among all 216 steers in the cohort, those that were diagnosed with IBK had a numerically higher average daily gain (ADG) (0.45 [±SE 0.01] kg) vs. those that were not (0.42 [±SE

Introducción: Las úlceras corneales son una de las patologías oftalmológicas más frecuentes en nuestra sociedad, bien asociadas a traumatismos externos, infecciones por diversidad de bacterias, hongos, virus o protozoos o por lo que es la causa más frecuente en ambientes industrializados como el nuestro, el uso de lentes de contacto, en la mayor parte de los casos, inadecuado. Los malos hábitos higiénicos y de cuidado de las lentes de contacto dan lugar a la aparición de pequeños traumatismos en la córnea que en su mayoría se infectan por bacterias, ocasionando lagrimeo, inyección conjuntival, disminución de la agudeza visual, enrojecimiento o dolor. Dependiendo también estos síntomas del agente causal y de los antecedentes oftalmológicos del paciente. Su diagnóstico se basa en el estudio mediante lampara de hendidura y tinción con fluoresceína con el fin de localizar el daño en el epitelio corneal y en el cultivo de muestras obtenidas del raspado corneal, del líquido de preservación de la funda de las lentes de contacto y de las propias lentes. Una vez aislado el germen causal, el tratamiento consiste en la aplicación de colirios antibióticos fortificados, midriáticos ciclopléjicos, hipotensores oculares y desbridamiento en los casos en los que sea necesario. En algunas ocasiones aparecen secuelas tras la curación de la patología como la pérdida de visión o cicatrices en el epitelio corneal. Objetivo: Identificar las posibles diferencias etiológicas, clínicas, de tratamiento y pronosticas de las ulceras corneales asociadas al uso de lentes de contacto. Material y métodos: Se trata de una revisión bibliográfica de la literatura existente, mediante la búsqueda en distintas bases de datos. Resultados y discusión: Tras la revisión, se han encontrado diversos resultados. En relación con las úlceras corneales asociadas a lentes de contacto, con la bibliografía revisada, se ha podido concluir que el uso de lentes de contacto supone un factor de riesgo para el desarrollo d, Introdución: As úlceras corneais son unha das patoloxías oftalmolóxicas máis frecuentes na nosa sociedade, ben asociadas a traumatismos externos, infeccións por diversidade de bacterias, fungos, virus ou protozoos ou polo que é a causa máis frecuente en ambientes industrializados como o noso, o uso de lentes de contacto, na maior parte dos casos, inadecuado. Os malos hábitos hixiénicos e de coidado das lentes de contacto dan lugar á aparición de pequenos traumatismos na córnea que na súa maioría inféctanse por bacterias, ocasionando lagrimeo, inxección conxuntival, diminución da agudeza visual, enroxecimiento ou dor. Dependendo tamén estes síntomas do axente causal e dos antecedentes oftalmolóxicos do paciente. O seu diagnóstico baséase no estudo mediante lámpada de fenda e tinción con fluoresceína co fin de localizar o dano no epitelio corneal e no cultivo de mostras obtidas do raspado corneal, do líquido de preservación de fúnda das lentes de contacto e das propias lentes. Unha vez illado o xerme causal, o tratamento consiste na aplicación de colirios antibióticos fortificados, midriáticos ciclopléxicos, hipotensores oculares e desbridamento nos casos nos que sexa necesario. Nalgunhas ocasións aparecen secuelas tras a curación da patoloxía como a perda de visión ou cicatrices no epitelio corneal. Obxectivo: Identificar as posibles diferenzas etiolóxicas, clínicas, de tratamento e pronósticas das úlceras corneais asociadas ao uso de lentes de contacto. Material e métodos: Trátase dunha revisión bibliográfica da literatura existente, mediante a procura en distintas bases de datos. Resultados e discusión: Tras a revisión, atopáronse diversos resultados. En relación coas úlceras corneais asociadas a lentes de contacto, coa bibliografía revisada, púidose concluír que o uso de lentes de contacto supón un factor de risco para o desenvolvemento de úlceras infecciosas debido ós cambios que o seu uso provoca na córnea. Como axentes etiolóxicos destacaron a Pseudomona aerugi, Introduction: Corneal ulcers are one of the most frequent ophthalmological pathologies in our society, either associated with external trauma, infections due to a diversity of bacteria, fungi, viruses or protozoa, or for what is the most frequent cause in industrialized environments like ours, the use contact lens, in most cases, inappropriately. Poor hygiene and contact lens care habits lead to the appearance of small traumas in the cornea that are mostly infected by bacteria, causing tearing, conjunctival injection, decreased visual acuity, redness, or pain. These symptoms also depend on the causative agent and the patient's ophthalmological history. Its diagnosis is based on the study by means of a slit lamp and fluorescein staining to locate the damage in the corneal epithelium and on the culture of samples obtained from corneal scraping, the preservation liquid from the contact lens sheath and of the lenses themselves. Once the causative germ has been isolated, treatment consists of the application of fortified antibiotic eye drops, cycloplegic mydriatics, ocular hypotensive and debridement when necessary. On some occasions, sequelae appear after the healing of the pathology, such as loss of vision or scars in the corneal epithelium. Objetive: Identify the possible etiological, clinical, treatment and prognostic differences of corneal ulcers associated with the use of contact lenses. Materials and methodology: the paper in based on a bibliographic review of the existing literature, trough the research in several databases. Results and discussion: Upon review, various results have been found. In relation to corneal ulcers associated with contact lenses, with the reviewed bibliography, it has been possible to conclude that the use of contact lenses is a risk factor for the development of infectious ulcers due to the changes that its use causes in the cornea. As etiological agents, Pseudomonas aeruginosa and Acanthamoeba spp stood out, being, respectively, the mos

Objectives Eyelid pathology A differential for the red eye Eyeball pathology Eye emergencies Diabetic eye diseases

The emergence of clinical metagenomics as an unbiased, hypothesis-free approach to diagnostic testing is set to fundamentally alter the way infectious diseases are detected. Long envisioned as the solution to the limitations of culture-based conventional microbiology, next generation sequencing methods will soon mature, and our attention will inevitably turn to how they can be applied to areas of medicine which need it most urgently. In ophthalmology, the demand for this technology is particularly pressing for the care of infectious corneal ulcers, where current diagnostic tests may fail to identify a causative organism in over half of cases. However, the optimism found in the budding discourse surrounding clinical metagenomics belies the reality that clinicians and scientists will soon be inundated by oppressive volumes of sequencing data, much of which will be foreign and unfamiliar. Therefore, our success in translating clinical metagenomics is likely to hinge on how we make sense of these data, and understanding its implications for the interpretation and implementation of sequencing into routine clinical care. In this consortium-led review, we provide an outline of these data-related issues and how they may be used to inform technical workflows, with the hope that we may edge closer to realizing the potential of clinical metagenomics for this important unmet need.

Introduction: corneal ulcers have not been characterized in the General Teaching Hospital “Dr. Agostinho Neto” from Guantanamo.Objective: to characterize the corneal ulcer in patients treated in the Ophthalmology Service of this hospital in the period from January 2014 to July 2019.Method: a descriptive, retrospective and longitudinal study was carried out with 40 patients. The variables were studied: sex, age, origin, occupation, risk factors, etiology, treatment and complications of this type of ulcer and the modifications of visual acuity according to the treatment applied to them.Results: 75.0% of the patients were male who were 65 years of age or older (47.5%), came from rural areas (72.5%) and carried out agricultural activities (45.0%). Corneal trauma was the most usual risk factor (25.0%). In 47.5% the ulcer was of fungal etiology. 100% received drug treatment, especially with fortified antibiotic eye drops (25.0%). Surgical treatment was applied to 27.5%, the most common technique was the conjunctival lining (15.0%). Visual acuity improved in 75.0% of patients after treatment.Conclusions: in the General Teaching Hospital “Dr. Agostinho Neto” corneal ulcer is not a health problem, but it does determine the visual acuity of affected patients, in which the fungal etiology and the need for the use of fortified eye drops are more common., Introdução: as úlceras de córnea não foram caracterizadas no Hospital Geral de Ensino “Dr. Agostinho Neto ”de Guantánamo.Objetivo: caracterizar a úlcera de córnea nos pacientes atendidos no Serviço de Oftalmologia deste hospital no período de janeiro de 2014 a julho de 2019.Método: estudo descritivo, retrospectivo e longitudinal, realizado com 40 pacientes. As variáveis estudadas foram: sexo, idade, procedência, ocupação, fatores de risco, etiologia, tratamento e complicações desse tipo de úlcera e as modificações da acuidade visual de acordo com o tratamento a elas aplicado.Resultados: 75,0% dos pacientes eram homens com 65 anos ou mais (47,5%), procedentes de áreas rurais (72,5%) e realizando atividades agrícolas (45,0%). O trauma corneano foi o fator de risco mais comum (25,0%). Em 47,5%, a úlcera era de etiologia fúngica. 100% receberam tratamento medicamentoso, especialmente com colírios antibióticos fortificados (25,0%). O tratamento cirúrgico foi aplicado em 27,5%, a técnica mais comum foi o revestimento conjuntival (15,0%). A acuidade visual melhorou em 75,0% dos pacientes após o tratamento.Conclusões: no Hospital Geral de Ensino “Dr. A úlcera de córnea de Agostinho Neto não é um problema de saúde, mas determina a acuidade visual dos pacientes afetados, nos quais a etiologia fúngica e a necessidade do uso de colírios fortificados são mais comuns., Introducción: las úlceras corneales no se han caracterizado en el Hospital General Docente “Dr. Agostinho Neto” de Guantánamo.Objetivo: caracterizar la úlcera corneal en pacientes atendidos en el Servicio de Oftalmología de este hospital en el período de enero 2014 a julio 2019.Método: se realizó un estudio descriptivo, retrospectivo y longitudinal con 40 pacientes. Se estudiaron las variables: sexo, edad, procedencia, ocupación, factores de riesgo, etiología, tratamiento y complicaciones de este tipo de úlcera y las modificaciones de la agudeza visual de acuerdo al tratamiento que se les aplicó.Resultados: el 75,0 % de los pacientes fue del sexo masculino que tenían 65 o más años de edad (47,5 %), procedían de áreas rurales (72,5 %) y realizaban actividades agrícolas (45,0 %). El trauma corneal fue el factor de riesgo más usual (25,0 %). En el 47,5 % la úlcera fue de etiología micótica. El 100 % recibió tratamiento farmacológico, sobre todo con colirio antibiótico fortificado (25,0 %). Se le aplicó tratamiento quirúrgico al 27,5 %, la técnica más común fue el recubrimiento conjuntival (15,0 %). La agudeza visual mejoró en el 75,0 % de los pacientes luego del tratamiento.Conclusiones: en el Hospital General Docente “Dr. Agostinho Neto” la úlcera corneal no es un problema de salud, pero sí determina la agudeza visual de los pacientes afectados, en los que es más común la etiología micótica y la necesidad del uso de colirios fortificados.

ObjectiveTo investigate the effect of topically applied proparacaine on bacterial and fungal culture results and to compare cytologic and culture results in patients with ulcerative keratitis.ProcedureCorneal samples were collected from 33 dogs, 19 horses, and 12 cats with spontaneously arising ulcerative keratitis. Samples for bacterial (dogs, cats, horses) and fungal (horses) cultures were collected prior to and following application of 0.5% proparacaine or saline. All patients then received a topical anesthetic, and samples were collected for cytology. Frequency of cultivatable bacteria before (Swab 1) and after (Swab 2) application of proparacaine or saline was compared using Fisher's exact test. Homogeneity of culture and cytology results was assessed using McNemar's test.ResultsNo difference was detected in number of animals from which bacteria were isolated from Swab 1 or Swab 2 for proparacaine (21/37 and 17/37, respectively) or saline (10/27 and 12/27, respectively). Small numbers prevented analysis of fungal culture results in horses between Swab 1 and Swab 2 for proparacaine (2/12 and 1/12, respectively) or saline (both, 1/8). Bacteria were isolated from 10 of 20 horses and detected cytologically in 3 of these; fungi were isolated from 3 of 20 horses and detected cytologically in 2 of these. Bacteria were detected more frequently using culture (31/64) than cytology (19/64).ConclusionProparacaine did not significantly alter bacterial or fungal culture results in cats, dogs, or horses; however, clinical significance warrants investigation. Culture and cytology provided complementary data; both should be performed to maximize organism detection in patients with ulcerative keratitis.

CASE SERIES SUMMARY:Described are 13 cats diagnosed with deep ulcerative keratitis and successfully managed medically without grafting procedures. Typical treatment involved frequent topical application of serum and antibiotics (usually a fluoroquinolone and a cephalosporin). Seven cats also received systemic antibiotics. Analgesia was achieved using various combinations of topical atropine and systemic buprenorphine, robenacoxib or corticosteroids. Six cats were hospitalized for a median (range) period of 2.5 (1-8) days, typically because of frequent medication administration. Median (range) follow-up time was 41.5 (9-103) days. Median (range) number of recheck examinations was 4 (2-6). Median (range) time to corneal re-epithelialization was 21 (9-103) days. Median (range) topical antibiotic course was 29.5 (16-103) days. Median (range) duration of Elizabethan collar use was 28 (13-73) days. At the time of writing, no further recheck examinations were recommended for 10 cats; median (range) time between initial to final examinations in these cats was 35 (20-103) days. All cats retained the affected globes and were apparently comfortable and visual at the latest recheck examination. RELEVANCE AND NOVEL INFORMATION:These cases reveal that aggressive medical management is highly successful in select cats with deep ulcerative keratitis, and can result in a cosmetically acceptable, apparently comfortable and visual globe. However, therapy is intensive with frequent administration of multiple topical and sometimes systemic medications, and requires multiple veterinary visits over many weeks. Referral to a veterinary ophthalmologist for consideration of surgical stabilization is recommended, as not all cases may be amenable to the medical therapy described here.

Antimicrobial resistance is globally on the rise, and this makes bacterial infections increasingly difficult to treat. The opportunistic pathogen Pseudomonas aeruginosa naturally has a plethora of resistance mechanisms to counteract the action of antibiotics and disinfectants. The evolutionary ability to acquire antimicrobial resistance genes has been widely reported. However, the mechanism of antimicrobial resistance in ocular isolates of P. aeruginosa is underrepresented in literature. This thesis aimed to investigate antimicrobial resistance mechanisms in ocular isolates of P. aeruginosa using genomic approaches.Whole genome sequences were obtained using Illumina® MiSeq® from a collection of 22 isolates which included seven Indian and six Australian isolates from the cornea of microbial keratitis cases and nine Australian isolates from the lungs of cystic fibrosis patients. Antimicrobial susceptibilities to antibiotics and contact lens disinfectants were assessed using broth microdilution methods. Bioinformatics analyses were performed to examine the accessory genome, population phylogenetics, acquired resistance genes, virulence genes and single nucleotide polymorphisms in chromosomal resistance genes. Real-time qPCR was performed to measure the expression of genes associated with beta-lactam resistance. The complete genome of an Indian keratitis isolate was obtained using the MinION long read sequencing platform (Oxford Nanopore Technology®). The accessory genome of the 22 strains was estimated to be 12-26% of the total genome and a larger accessory genome was associated with strains isolated from the corneal infections. Phylogenetic analysis showed that the P. aeruginosa isolates clustered into two major groups with 62% of the keratitis isolates in the same group. Furthermore, keratitis isolates predominantly carried the exoU gene, which encodes cytotoxic factor and carriage of this gene was associated with higher resistance to fluoroquinolones and beta-lactam

ObjectiveTo investigate the effect of topically applied proparacaine on bacterial and fungal culture results and to compare cytologic and culture results in patients with ulcerative keratitis.ProcedureCorneal samples were collected from 33 dogs, 19 horses, and 12 cats with spontaneously arising ulcerative keratitis. Samples for bacterial (dogs, cats, horses) and fungal (horses) cultures were collected prior to and following application of 0.5% proparacaine or saline. All patients then received a topical anesthetic, and samples were collected for cytology. Frequency of cultivatable bacteria before (Swab 1) and after (Swab 2) application of proparacaine or saline was compared using Fisher's exact test. Homogeneity of culture and cytology results was assessed using McNemar's test.ResultsNo difference was detected in number of animals from which bacteria were isolated from Swab 1 or Swab 2 for proparacaine (21/37 and 17/37, respectively) or saline (10/27 and 12/27, respectively). Small numbers prevented analysis of fungal culture results in horses between Swab 1 and Swab 2 for proparacaine (2/12 and 1/12, respectively) or saline (both, 1/8). Bacteria were isolated from 10 of 20 horses and detected cytologically in 3 of these; fungi were isolated from 3 of 20 horses and detected cytologically in 2 of these. Bacteria were detected more frequently using culture (31/64) than cytology (19/64).ConclusionProparacaine did not significantly alter bacterial or fungal culture results in cats, dogs, or horses; however, clinical significance warrants investigation. Culture and cytology provided complementary data; both should be performed to maximize organism detection in patients with ulcerative keratitis.

CASE SERIES SUMMARY:Described are 13 cats diagnosed with deep ulcerative keratitis and successfully managed medically without grafting procedures. Typical treatment involved frequent topical application of serum and antibiotics (usually a fluoroquinolone and a cephalosporin). Seven cats also received systemic antibiotics. Analgesia was achieved using various combinations of topical atropine and systemic buprenorphine, robenacoxib or corticosteroids. Six cats were hospitalized for a median (range) period of 2.5 (1-8) days, typically because of frequent medication administration. Median (range) follow-up time was 41.5 (9-103) days. Median (range) number of recheck examinations was 4 (2-6). Median (range) time to corneal re-epithelialization was 21 (9-103) days. Median (range) topical antibiotic course was 29.5 (16-103) days. Median (range) duration of Elizabethan collar use was 28 (13-73) days. At the time of writing, no further recheck examinations were recommended for 10 cats; median (range) time between initial to final examinations in these cats was 35 (20-103) days. All cats retained the affected globes and were apparently comfortable and visual at the latest recheck examination. RELEVANCE AND NOVEL INFORMATION:These cases reveal that aggressive medical management is highly successful in select cats with deep ulcerative keratitis, and can result in a cosmetically acceptable, apparently comfortable and visual globe. However, therapy is intensive with frequent administration of multiple topical and sometimes systemic medications, and requires multiple veterinary visits over many weeks. Referral to a veterinary ophthalmologist for consideration of surgical stabilization is recommended, as not all cases may be amenable to the medical therapy described here.

Research with animal models of Pseudomonas aeruginosa keratitis has shown that use of a topical corticosteroid alone against an established infection can significantly increase the number of colonizing bacteria or worsen clinical disease. Moreover, retrospective analysis has suggested that corticosteroid use in humans is associated with an increased risk of keratitis in eyes with pre-existing disease. Thus, while corticosteroids are often used to reduce ocular inflammation in the absence of infection, the risk of opportunistic infection remains a concern. However, the effect of corticosteroids on the intrinsic barrier function of uninfected corneas is unknown. Here, we tested if short-term topical corticosteroid treatment of an uninfected murine cornea would increase susceptibility to P. aeruginosa colonization or infection after epithelial injury. Topical prednisolone acetate (1%) was administered to one eye of C57BL/6 mice three times a day for 3 days; control eyes were treated with sterile PBS. Prior to inoculation with a cytotoxic P. aeruginosa corneal isolate strain 6206, corneas were subject to superficial-injury by tissue paper blotting, or scratch-injured followed by 12 h of healing. Previously we have shown that blotting renders mouse corneas susceptible to P. aeruginosa adhesion, but not infection, while 12 h healing reduces susceptibility to infection after scratching. Corneas were evaluated at 48 h for bacterial colonization and microbial keratitis (MK). To monitor impact on wound healing, corneal integrity was examined by fluorescein staining immediately after scarification and after 12 h healing. For both the tissue paper blotting and scratch-injury models, there was no significant difference in P. aeruginosa colonization at 48 h between corticosteroid-pretreated eyes and controls. With the blotting model, one case of MK was observed in a control (PBS-pretreated) cornea; none in corticosteroid-pretreated corneas. With the 12 h healing model, MK occurre

OBJECTIVE:(a) To evaluate the epidemiology of equine eosinophilic keratoconjunctivitis (EK) in the western United States, (b) to ascertain the efficacy of keratectomy and diamond burr debridement vs medical management alone, (c) to determine the efficacy of various medical therapies, and (d) to further characterize the histopathologic findings of the disease in horses. ANIMALS STUDIED:Twenty-nine horses (47 eyes) diagnosed with EK from 1993 to 2017. PROCEDURE:Retrospective medical record review; owner questionnaire. RESULTS:Average age of presentation was 11 ± 4 years. Warmbloods were significantly overrepresented (P = 0.024). Twenty horses were treated with medical therapy alone, five were treated with superficial lamellar keratectomy, and four were treated with diamond burr debridement. Follow-up data were available for 38 eyes of 23 horses. Median time to resolution for horses treated with either superficial keratectomy or diamond burr debridement (62 days) was not statistically significantly different from those that underwent medical therapy alone (46 days; P = 0.33). Eyes treated with topical steroids had a statistically significant longer median time to resolution (61 days) compared to those that did not receive topical steroid (44 days; P = 0.023). Common histopathologic findings in keratectomy samples included the presence of eosinophils, vascularization, and an eosinophilic membrane spanning areas of ulceration. CONCLUSION:In this population, time to EK resolution was similar for horses treated with medical and surgical management. The use of topical steroids was associated with a prolonged time to resolution. Keratectomy samples from horses with EK had similar findings to those reported in other species.

Introduction: Endophthalmitis is a severe inflammation of the eyeball; its most prevalent form being postoperative exogenous. Currently, there are few reported cases of exogenous post-traumatic infectious endophthalmitis caused by a mycotic agent; besides, there is a risk factor in its evolution, such as type 2 diabetes mellitus. Objective: To describe the nosological characteristics of post-traumatic endophthalmitis. Methods: A descriptive observational study was carried out as a case report, which complied with the ethical principles of the Helsinki Declaration and the Resolution 8430 of 1993. Results: A male patient of 51 years of age (rural origin, occupation: farmer) attends the emergency medical service of the Hospital Universitario de Santander, reporting ocular pain in the right eye (RE) with a history of blunt trauma (stone). Far visual acuity in RE with 0.1 LogMAR does not improve, with a diagnosis of a) blunt ocular trauma, b) corneal ulcer in RE of Fusarium etiology, c) advanced mycotic endophthalmitis in RE, d) secondary glaucoma in RE, e) type 2 diabetes mellitus de novo. After 13 days of evolution and follow-up of the patient, enucleation + implant + canthoplasty was proposed. Conclusions: adequate interdisciplinary management with complementary examinations contributes to an accurate and timely diagnosis., Introducción: la endoftalmitis es una inflamación severa del globo ocular; su mayor prevalencia es la exógena posquirúrgica; actualmente se evidencian pocos casos reportados por endoftalmitis infecciosa exógena postraumática por agente micótico; además, se tiene un factor de riesgo en su evolución, como lo es la diabetes mellitus tipo 2. Objetivo: describir las características nosológicas de la endoftalmitis postraumática. Métodos: se realizó un estudio observacional descriptivo tipo reporte de caso, que acogió los principios éticos de la declaración de Helsinki y la Resolución 8430 de 1993. Resultados: paciente masculino de 51 años de edad, de procedencia rural, ocupación agricultor; asiste al servicio médico de urgencias del Hospital Univeristario de Santander refiriendo dolor ocular OD con antecedentes de trauma contundente (piedra). AV VL con cartilla LogMAR OD 1.0, no mejora, con diagnóstico de: a) trauma ocular contundente, b) úlcera corneal OD de etiología micótica Fusarium, c) endoftalmitis micótica avanzada en OD, d) glaucoma secundario OD, e) diabetes mellitus tipo 2 de novo. Luego de 13 días de evolución y seguimiento del paciente, se plantea enucleación + implante + cantoplastia. Conclusiones: el adecuado manejo interdisciplinario con exámenes complementarios contribuye a un diagnóstico certero y oportuno.

Background: The corneal ulcer of mycotic etiology caused by Lasiodiplodia theobromae is an infrequent pathology with less than 50 cases of ocular infection by this pathogen reported in the literature.Objective: To present a case of a rare pathology, make a brief literature review, and discuss the chosen treatment that was favorable.Study design: Case reportCase summary: We present the case of a patient treated at the Hospital Universitario de Santander (HUS) during the years 2015 - 2017 with a history of ocular trauma with plant material who developed fungal corneal ulcer by Lasiodiplodia theobromae, which was confirmed using microbiological analysis of the corneal smear. Treatment with a combination of antifungals was established with a satisfactory final resultConclusion: L. theobromae is an opportunistic pathogen. The importance of early diagnosis in these cases, which requires a high index of suspicion in patients with plant trauma, with the identification of the etiological agent lies in avoiding or minimizing irreversible consequences through the establishment of an opportune treatment., Introducción: La úlcera corneal de etiología micótica por Lasiodiplodia theobromae es una patología infrecuente con menos de 50 casos de infección ocular por este patógeno reportados en la literatura.Objetivo: Dar a conocer un caso de una patología poco frecuente, haciendo una breve revisión de la literatura, y discutiendo el tratamiento elegido que resultó favorable.Diseño del estudio: Reporte de casoResumen del caso: Se presenta el caso de un paciente atendido en el Hospital Universitario de Santander (HUS) durante los años 2015 - 2017 con antecedente de trauma ocular con material vegetal quien desarrolla úlcera corneal micótica por Lasiodiplodia theobromae, que se confirmó usando análisis microbiológico del frotis corneal. Se instauró tratamiento con una combinación de antimicóticos con un resultado final satisfactorioConclusión: L. theobromae es un patógeno oportunista. La importancia del diagnóstico precoz en estos casos, que requiere un alto índice de sospecha en pacientes con trauma vegetal, con la identificación del agente etiológico radica en evitar o minimizar consecuencias irreversibles mediante la instauración de un tratamiento oportuno.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

OBJECTIVE:To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. DESIGN:Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. METHODS:Study Participants: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). INTERVENTION:Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. MAIN OUTCOME MEASURES:TPK button culture positivity. RESULTS:A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90-0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32-4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16-51.70; P = .003). CONCLUSIONS:There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

PurposeUnderstanding the spectrum of pathogens in a given geographic region is important when deciding on empiric antibiotic therapy. In this study, we evaluate the spectrum of bacterial organisms cultured from corneal samples and their antibiotic sensitivities to guide initial treatment of keratitis.MethodsWe performed a retrospective case review of cultures from suspected infectious keratitis cases at the Francis I. Proctor Foundation, University of California, San Francisco, from 1996 through 2015. Logistic regression models were used to assess the risk of culturing methicillin-resistant Staphylococcus aureus (MRSA) from ulcers over time and the association between the year cultured and moxifloxacin resistance.ResultsA total of 522 of 2203 (23.7%) cultures grew bacterial organisms believed to be the etiology of infection, with available antibiotic sensitivity data. Of these, 338 (65.3%) grew gram-positive organisms with the most common being methicillin-sensitive Staphylococcus aureus (20.1%, N = 105). One hundred eighty (34.7%) grew gram-negative species with Pseudomonas aeruginosa as the most prevalent organism (10.9%, N = 57). There was 1.13 increased odds of culturing MRSA for each 1-year increase in the culture date (P = 0.01) and 1.26 increased odds of culturing an organism resistant to moxifloxacin with each 1-year increase in the culture date after controlling for the infectious organism (P < 0.001).ConclusionsGram-positive organisms are the most commonly identified etiology of microbial keratitis in this series. Approximately 35% of cultured organisms had variable susceptibility to moxifloxacin, and resistance seems to be increasing over time. The risk of culturing MRSA increased over time.

PURPOSE:To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment. DESIGN:Secondary analysis of randomized clinical trial data. METHODS:We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics. SUBJECTS:Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal). MAIN OUTCOME MEASURES:The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization. RESULTS:Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P = .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3 months (P = .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (-0.24 mm1; P = .45) or time to re-epithelialization (hazard ratio = .81; P = .31). CONCLUSIONS:Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management.

Background The integrity of the ocular surface and the transparency of the cornea is crucial to obtain a good visual acuity a requirement to actively participate in both social and professional environments. The homeostasis of the ocular surface is constantly endangered by microbes and by intrinsic factors with negative influence on wound healing. Furthermore, widespread use of contact lenses obtain a risk of corneal infection even resulting in corneal perforation and loss of the eye. Current therapies include topical and systemic antibiotics and antimycotics, often applied in an in-ward setting.Patients/Materials and Methods Some microbes can be therapy-resistent or-refractory and therefore cause a deterioration of the clinical aspect. In this study, the effects of cold plasma treatment of corneal ulcers on reduction of microbial load in vitro, in tissue ex vivo and in a therapy-refractory ulcer.Results In vitro, ex vivo and in the patientmicrobial load could be reduced or the clinical findings improved.Conclusions Plasma medicine and its disinfective properties could open a novel approach to treat microbial infections of the cornea. The can result in reduced treatment times, a faster demission of the patients and overall in a reduction of health care costs.

Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (

ImportanceIdentifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high-risk patients, particularly in resource-poor settings.ObjectiveTo determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK).Design, setting, and participantsThis is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015. Participants had a baseline visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or a placebo (all participants received topical voriconazole, 1%). After 39 participants (16.3%) were enrolled, topical natamycin, 5%, was also added.Main outcomes and measuresThe primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK.ResultsThe mean (SD) age at enrollment was 49 (13) years, 104 participants (43.3%) were women, and all were of Southeast Asian descent. The presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing TPK (95% CI, 1.18-4.40; P = .01). Study participants whose infiltrate involved the posterior one-third had a 71.4% risk of developing corneal perforation and/or needing TPK. For each 1-mm increase in the geometric mean of the infiltrate, there was 1.37 (95% CI, 1.12-1.67; P = .002) increased odds of developing perforation and/or needing TPK. Other clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism and duration of symptoms, and demographic characteristics, such as sex and occupation, were not significant predictors in the multivariable regression analysis.Conclusions and releva

PurposeTo determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I).DesignSecondary analysis from a multicenter, double-masked, randomized clinical trial.Methodssetting: Multiple hospital sites of the Aravind Eye Care System, India.Study populationPatients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 reexamined 6 days after initiation of treatment.InterventionCorneal scraping and cultures were obtained from study participants at day 6 after enrollment.Main outcome measuresWe assessed 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation, and re-epithelialization rates stratified by culture positivity at day 6.ResultsOf the 323 patients with smear-positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured 6 days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 logMAR; 95% confidence interval [CI]: 0.24-0.44; P < .001), had larger 3-month scar size (0.39 mm; 95% CI: 0.06-0.73; P = .02), were more likely to perforate or require therapeutic penetrating keratoplasty (odds ratio: 6.27; 95% CI: 2.73-14.40; P < .001), and were slower to re-epithelialize (hazard ratio: 0.33; 95% CI: 0.21-0.50; P < .001) than those with a negative 6-day culture result.ConclusionsEarly microbiological cure on culture is a predictor of clinical response to treatment.

The Steroids for Corneal Ulcers Trial (SCUT) was a multicenter, international study of bacterial keratitis in which 101 Pseudomonas aeruginosa infections were treated. Twenty-two of 101 P. aeruginosa isolates collected had a colony morphology characteristic of a loss-of-function mutation in lasR, the gene encoding a quorum-sensing master regulator. Ulcers caused by these 22 strains were associated with larger areas of corneal opacification, worse vision, and a lower rate of vision recovery in response to treatment than ulcers caused by the other isolates. The lasR sequences from these isolates each contained one of three nonsynonymous substitutions, and these strains were deficient in production of LasR-regulated protease and rhamnolipids. Replacement of lasR with either of the two most common lasR alleles from the SCUT isolates was sufficient to decrease protease and rhamnolipid production in PA14. Loss of LasR function is associated with increased production of CupA fimbriae, and the LasR-defective isolates exhibited higher production of CupA fimbriae than LasR-intact isolates. Strains with the same lasR mutation were of the same multilocus sequence type, suggesting that LasR-deficient, environmental P. aeruginosa strains were endemic to the area, and infections caused by these strains were associated with worse patient outcomes in the SCUT study. (This study has been registered at ClinicalTrials.gov under registration no. NCT00324168.) IMPORTANCE The LasR transcription factor is an important regulator of quorum sensing in P. aeruginosa and positively controls multiple virulence-associated pathways. The emergence of strains with lasR loss-of-function alleles in chronic disease is well described and is thought to represent a specific adaptation to the host environment. However, the prevalence and virulence of these strains in acute infections remain unclear. This report describes observations revealing that lasR mutants were common among isolates from a large, mult

The Steroids for Corneal Ulcers Trial (SCUT) was a multicenter, international study of bacterial keratitis in which 101 Pseudomonas aeruginosa infections were treated. Twenty-two of 101 P. aeruginosa isolates collected had a colony morphology characteristic of a loss-of-function mutation in lasR, the gene encoding a quorum-sensing master regulator. Ulcers caused by these 22 strains were associated with larger areas of corneal opacification, worse vision, and a lower rate of vision recovery in response to treatment than ulcers caused by the other isolates. The lasR sequences from these isolates each contained one of three nonsynonymous substitutions, and these strains were deficient in production of LasR-regulated protease and rhamnolipids. Replacement of lasR with either of the two most common lasR alleles from the SCUT isolates was sufficient to decrease protease and rhamnolipid production in PA14. Loss of LasR function is associated with increased production of CupA fimbriae, and the LasR-defective isolates exhibited higher production of CupA fimbriae than LasR-intact isolates. Strains with the same lasR mutation were of the same multilocus sequence type, suggesting that LasR-deficient, environmental P. aeruginosa strains were endemic to the area, and infections caused by these strains were associated with worse patient outcomes in the SCUT study. (This study has been registered at ClinicalTrials.gov under registration no. NCT00324168.) IMPORTANCE The LasR transcription factor is an important regulator of quorum sensing in P. aeruginosa and positively controls multiple virulence-associated pathways. The emergence of strains with lasR loss-of-function alleles in chronic disease is well described and is thought to represent a specific adaptation to the host environment. However, the prevalence and virulence of these strains in acute infections remain unclear. This report describes observations revealing that lasR mutants were common among isolates fro

Background/aimsThe Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis.MethodsThe Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations.Results323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm.ConclusionsMonocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority.Trial registration numberClinicaltrials.gov Identifier: NCT00996736.

Purpose of reviewTopical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis.Recent findingsJudicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers.SummarySeveral randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.

BackgroundTo determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial.DesignNon-pre-specified subgroup analysis of a randomized controlled trial in a tertiary hospital.ParticipantsThree hundred twenty-three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400.MethodsThe Mycotic Ulcer Treatment Trial I was a randomized, double-masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated.Main outcome measuresThree-month visual acuity (primary), 3-month infiltrate or scar size, corneal perforation and/or transplant and re-epithelialization time.ResultsOf the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3-month visual acuity (P = 0.006), larger 3-month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001).ConclusionsFungal keratitis that is smear-positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre.

ObjectiveTo compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.Design, setting, and participantsThe Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis.InterventionsStudy participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%.Main outcomes and measuresThe primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use.ResultsA total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup anal

ImportanceThe development of multiple triazole resistance in pathogenic filamentous fungi has become an increasing clinical concern and has been shown to increase the risk for treatment failure.ObjectiveTo determine whether antifungal resistance increased during the Mycotic Ulcer Treatment Trial I (MUTT I), as measured by minimum inhibitory concentrations (MICs) in baseline cultures.Design, setting, and participantsThis secondary analysis of a double-masked, multicenter, randomized clinical trial included patients with culture- or smear-positive filamentous fungal corneal ulcer and a baseline visual acuity of 20/40 to 20/400. Culture-positive samples with susceptibility testing were included in this analysis. The patients were treated at multiple locations of the Aravind Eye Care Hospital system in South India. Data were collected from April 3, 2010, to December 31, 2011, and analyzed from July 15 to September 1, 2015.InterventionsCorneal smears and cultures were obtained from all study participants at baseline. Susceptibility testing was performed for each culture-positive specimen.Main outcomes and measuresMinimum inhibitory concentration of voriconazole and natamycin in baseline cultures.ResultsOf 323 participants with smear-positive specimens (183 men [56.7%]; 140 women [43.3%]; median [interquartile range] age, 47 [38-56] years), fungal-positive cultures were obtained for 256 (79.3%). The MIC data were available for 221 of 323 participants (68.4%), because 35 samples had no growth during susceptibility testing. A 2.14-fold increase per year (95% CI, 1.13-4.56; P = .02) in voriconazole MICs after controlling for the infectious organism was found. This association was not found when looking at natamycin MICs of baseline cultures after controlling for the infectious organism (1.26; 95% CI, 0.13-12.55; P = .85).Conclusions and relevanceSusceptibility to voriconazole appeared to decrease during the relatively short enrollment period of the clinical trial. This decre

ImportanceGiven the limitations in health care resources, quality-of-life measures for interventions have gained importance.ObjectiveTo determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire.Design, setting, and participantsSecondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3).InterventionsStudy participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%.Main outcomes and measuresSubscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months.ResultsA total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52).Conclusions and releva

ImportanceGiven the limitations in health care resources, quality-of-life measures for interventions have gained importance.ObjectiveTo determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire.Design, setting, and participantsSecondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3).InterventionsStudy participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%.Main outcomes and measuresSubscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months.ResultsA total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52).Conclusions and releva

ObjectiveTo assess the trends in microbiological organisms identified from corneal scrapings from patients with infectious keratitis at a tertiary care medical centre in South India.MethodsWe reviewed the records of the microbiology laboratory at Aravind Eye Hospital in Madurai, India, from 2002 until 2012. We identified the microbiological causes of all corneal ulcers from the culture and smear results, and assessed for trends in bacterial and fungal keratitis over time.ResultsOf 23 897 corneal patients with ulcer with a corneal smear from 2002 to 2012 a fungal organism was identified in 34.3%, a bacterial organism in 24.7% and no organism in 38.3%. During this period, the annual number of keratitis cases due to bacteria decreased from 677 to 412, and the annual number due to fungus increased from 609 to 863. In analyses accounting for the total number of outpatients seen each year, the decline in number of smears positive for bacteria was statistically significant (p<0.001) but the increase in the number positive for fungus was not (p=0.73). The relative frequency of individual bacterial or fungal organisms remained relatively stable over this time.ConclusionsAt a tertiary eye care centre in South India, there has been a reduction in the numbers of smear-positive bacterial keratitis over the past 11 years. This decline likely reflects economic development in India and increased access to antibiotics.

Interleukin 17A (IL-17) production by peripheral blood neutrophils was examined in patients with fungal keratitis and in uninfected individuals in southern India, which has high levels of airborne Aspergillus and Fusarium conidia. Il17a gene expression and intracellular IL-17 were detected in all groups, although levels were significantly elevated in neutrophils from patients with keratitis. There were no significant differences in plasma IL-17 and IL-23 between patients with keratitis and uninfected individuals; however, combined data from all groups showed a correlation between the percentage IL-17 producing neutrophils and plasma IL-23, and between plasma IL-17 and IL-6 and IL-23.