Corneal infection

image of how fungal filaments appear on confocal microscopy. Jaya Chidabaram

Caption: How fungal filaments appear on confocal microscopy. Jaya Chidabaram

 

Microbial keratitis (MK) is a major cause of sight loss, which is associated with considerable morbidity In temperate regions the large majority of infections are caused by bacteria. In contrast, tropical regions fungal infections occur more frequently. There are major challenges in preventing, diagnosing and treating corneal infections.

Investigating how to improve outcome in severe corneal ulceration in India

Despite adequate antimicrobial therapy, severe corneal inflammation often progresses, resulting in corneal necrosis, thinning and perforation. In tropical climates, fungal infection can account for more than half of all corneal ulcers and can be difficult to manage. Although the pathophysiology of this process has not been investigated in detail, it is likely that proteases (such as matrix metallopeptidases) that are produced by the inflammatory cell infiltrate as well as the pathogenic organism may play a role in corneal destruction.

Initial diagnosis of the causative organism in MK can be a challenge. In specialised ocular microbiology laboratories, microbial culture is often only positive in up to 70% of cases. Laser scanning in vivo confocal microscopy (IVCM) offers a high-resolution method of direct visualization of many pathogenic organisms as well as the host cellular responses over time.

In this study conducted with colleagues at Aravind Eye Hospital in Tamil Nadu, South India, we investigated the diagnosis and pathophysiology of severe MK in a setting with high incidence of disease. To ascertain the genes and pathways involved in pathophysiology, transcriptome analysis was done to compare bacterial and fungal corneal ulcer tissue (excised from patients at corneal transplantation) with non-infected normal cadaver cornea. A prospective observational cohort study was conducted to follow a cohort of approximately 250 severe MK patients over a 3 week period from time of presentation in order to identify predictors of clinical progression. Corneal scrape specimens obtained from this cohort were used to evaluate gene expression changes in these patients and to validate transcriptome results. Finally, IVCM was evaluated in this cohort for its diagnostic accuracy in severe ulcers, as well as its utility in monitoring disease progression or resolution.

Microbial Keratitis in East Africa

Microbial keratitis has been particularly understudies in Sub-Saharan Africa. Studies are underway to investigate the pattern and causes on MK in Tanzanian and Uganda. This involves defining the microbiology, resistance patterns and risk factors. We are also investigating the use of traditional eye medicines and the contribution these make to this disease.

We would like to thank the Wellcome Trust for funding this research.

Selected publications

  • M.J.Burton, J.Pithuwa, E.Okello,I.Afwamba, J.J.Onyango, F.Oates, C.Chevallier and A.B.Hall. Microbial keratitis in East Africa: why are the outcomes so poor? Ophthalmic Epidemiology, 2011; 18 (4): 158-163. Abstract here.
  • M.J. Burton. Corneal Blindness – prevention, treatment and rehabilitation. Journal of Community Eye Health2009; 22: 33-5. Link here.

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