The cultures were positive in Fungi was the most common infectious agent isolated in culture Contrary to previous reports, fungi were the most common etiological organism in the causation of infectious keratitis in children in our study population. Fusarium was the most common fungal species isolated.
This data were similar to that obtained from adult patients with infectious keratitis in the region.
This data are extremely valuable, since it may be a common practice in primary and secondary centres to start empirical treatment in young children since they may not be cooperative for microbiological investigations. In such instances, the findings from our study need to be kept in mind while initiating therapy. Different risk factors have been ascribed to fungal keratitis.
Broadly, the yeasts are thought to be associated with systemic immunosuppression while filamentous fungi often are associated with persons involved in agrarian activities. Historically, it was believed that Fusarium was a virulent organism. In fact, in his classic article on the principles of management of oculomycosis, Jones reported that Fusarium solani was far more destructive than Aspergillus. Immediately, many questions come to mind: Did something happen during these 40 years that Aspergillus became more virulent than Fusarium? Does the virulence of these fungal pathogens differ in different geographic regions?
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These are critical questions to ponder about, especially, in the context of Aspergillus being the most common etiological organism amongst the Northern and Eastern regions of India, while Fusarium is reported to be the most common organism in the Western and the Southern part of the country. In our mind, the concept of considering that each genera of fungi having a specific virulence pattern is overly simplistic.
Five years later, we performed a prospective study to see whether the risk factors have changed. Older age and male gender were more associated with poor vision. This study threw up an interesting observation that pigmentation of a corneal ulcer can be a prognostic factor for poor visual outcomes. This was interesting since earlier studies had hypothesized that pigmentation induces low virulence and less severe inflammation.
Corneal ulcers are a devastating economic problem for patients and their families. Despite the high-cost implications, they do not attract as much attention as other ocular conditions including cataracts, refractive errors, and childhood blindness. The relatively young age of the patient, the disproportionately poor socioeconomic background from where they come from and the associated loss of man years of economic productivity takes a big economic toll. Added to this is the important factor, that even in the best of the scenario of the ulcer healing, the visual rehabilitation is not optimal.
In a bid to estimate the costs of treating corneal ulcers at a tertiary eye care center from a patient's perspective, we performed a prospective cohort study in involving around patients accessing the center in a defined period. The mean follow-up duration was The costs to the patient to receive appropriate care for corneal ulcers in this population was higher than the average monthly wage for this group of individuals at that point of time. It has to be kept in mind that at least a third of the total patients would have ended up with impaired vision.
Hence, it is very important to concentrate on a preventive strategy to combat corneal infections. Even though we are often taught the characteristic descriptions ascribed to fungal and bacterial ulcers, it is often difficult to diagnose them in real life without the help of microbiology. In the initial stages of corneal ulceration, the ulcer morphology may have these distinct characteristics, but things become confusing when the ulcer increases in size and intensity [ Fig.
Unfortunately, the patients present to the clinicians in a fairly late stage. We undertook a study to determine whether established cornea specialists could predict the organism based on the clinical manifestation of the corneal ulcer.http://gohu-takarabune.com/policy/localizar-antenas/zowi-rastrear-um-numero.php
Aravind eye hospital case study analysis
Fifteen cornea specialists from the Proctor Foundation, USA and the Aravind Eye care system assessed the photographs and were asked to predict the most likely causative organism. Even though, they were able to do this slightly better than chance, it was very clear, that with all their clinical experience, they could not be very certain about the organism. More specific categorization led to even poorer clinical distinction. However, the saving grace was that the presence of an irregular feathery border was very clearly identified as that caused by a fungus [ Fig.
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Although certain clinical signs of infectious keratitis may be associated with a bacterial or fungal etiology, this study highlights the importance of obtaining appropriate microbiological testing during the initial clinical examination. Both KOH [ Fig. This importance may be more relevant in the Indian context, where fungi and bacteria cause corneal ulcers almost in equal proportions and empirical regimen is not a recommended mode of initiating treatment.
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Advanced corneal ulcer. Clinical examination alone will not be enough to make the diagnosis.
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- Fungal Keratitis is a Big Public Health Problem.
Fungal keratitis is known to be a more prolonged and severe disease than bacterial keratitis. Our department conducted two large well-designed prospective clinical trials, namely, the SCUT for patients with bacterial keratitis and MUTT for patients with fungal keratitis. This unique scenario enabled us to compare clinical outcomes in ulcers due to bacteria and fungus using data collected from two similarly structured prospective trials. When the data were compared between the two studies, it was found that fungal keratitis had nearly five times as many corneal perforations, and longer healing times.
Recently, confocal microscopy has proved to be very useful as an adjuvant noninvasive tool to aid in the diagnosis of microbial keratitis [ Fig. We performed a study to determine the diagnostic accuracy of in vivo confocal microscopy IVCM using Heidelberg retinal tomograph 3 for moderate-to-severe microbial keratitis.
All consecutive moderate to severe corneal ulcers were scanned by the laser scanning IVCM. The study was performed by five graders who were masked to clinical features and microbiology. The main outcome measures were sensitivity, specificity, and positive and negative predictive values of IVCM compared with those of a reference standard of positive culture.
IVCM had an overall pooled 5 graders sensitivity of The agreement between the graders was good for definite fungus k 0. We concluded that laser scanning IVCM performed with experienced confocal graders has high sensitivity and test reproducibility for detecting fungal filaments.
This imaging modality was particularly useful for detecting organisms in deep ulcers where culture and light microscopy results were inconclusive. In vivo confocal microscopy showing fungal hyphae with different branching patterns. Our next step was to see whether the confocal microscopy could distinguish different fungal species with confidence. This was important since we had shown that the clinical outcomes in fungal keratitis vary between Fusarium and Aspergillus and moreover, these two different genera respond differentially to different antifungal drugs.
Previous studies had postulated that the branching patterns of fungi as seen in IVCM images of keratitis could be used to differentiate fungal species. In our study of 68 patients of Fusarium keratitis and 30 patients of Aspergillus keratitis, it was found that the mean branch angle for Fusarium species was No adventitious sporulation was detected in Fusarium species ulcers. Dichotomous branching was also not unique and was seen in seven cases of Aspergillus keratitis and 4 cases of Fusarium keratitis. There was very little difference in the branching angle of Fusarium and Aspergillus species.
For a disease of such magnitude and a potential to cause profound morbidity, research publications in the area of drug trials in fungal keratitis are far and few in between. In fact, we published the first-ever randomized control trial in the field of fungal keratitis as late as This drug was very popular in the United Kingdom and was widely used especially in Moorfields. Interestingly, two earlier case studies from India had talked about the efficacy of this drug.
The endpoint was kept at 4 weeks. This study concluded that Econazole and Natamycin were comparable in the treatment of filamentary fungal keratitis. While we were doing this clinical trial, a thought struck us whether the concurrent use of both these drugs would prove additive. The rationale behind this thought was that Natamycin and Econazole have two different modes of action. While Natamycin binds preferentially to ergosterol on the fungal plasma membrane and causes localized membrane disruptions by altering membrane permeability, Econazole exhibits antifungal activity by inhibiting fungal cell membrane synthesis.
With this thought in mind, we designed a prospective study to see for the efficacy of using this combination study. This was compared with a historical control from our previous study performed using a similar protocol. At around this time, isolated case reports on the benefits of Voriconazole started appearing in the world literature.
In vitro susceptibility studies performed in our microbiology laboratory revealed a superior profile for Voriconazole,[ 20 ] and this finding again was reiterated in another of our studies 2 years later as well. We decided then to perform a randomized clinical trial to compare the efficacy of the new drug Voriconazole with that of the existing gold standard Natamycin in the treatment of fungal keratitis.
One of the things, we learnt early on in our career in ophthalmic research is to perform pilot or exploratory studies around our hypothesis. These pilot studies expose the teething difficulties and fallacies in our hypothesis and can be used to modify and refine the protocol before embarking on the main study.
Interestingly we chose to consider visual acuity as the most important outcome for this study, which was a novel idea since almost all previous studies including our previous trials had considered epithelial healing and nonprogression of stromal infiltration as the primary endpoint. We did not think that the epithelial healing was the optimal primary outcome for this study because one of our interventions was epithelial debridement and also because the epithelium can heal despite an active underlying corneal infiltrate in fungal keratitis.
Our pilot study was performed on patients who were randomized to receive either topical Voriconazole or Natamycin. Since anecdotal reports personal communication suggested that clinicians believe that a therapeutic re-scraping would help in the treatment of fungal keratitis, we randomized a part of this study group to undergo a repeat therapeutic scraping at 1 week.
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Aravind Eye Hospital, Madurai, India PPT | Hospital | Patient
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