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Indian Journal of Medical Microbiology, Vol. 28, No. 2, April-June, 2010, pp. 91-94 Editorial Ocular infections: Research in India S Sharma L. V. Prasad Eye Institute, Patia, Bhubaneswar - 751 024, India Correspondence Address: L. V. Prasad Eye Institute, Patia, Bhubaneswar - 751 024, India, savitri@lvpei.org Date of Submission: 22-Mar-2010 Code Number: mb10031 PMID: 20404450 DOI: 10.4103/0255-0857.62481 Analogous to many other infections, Indian population is vulnerable to infections of the eye by virtue of subtropical climate. Any part of the eye may be infected by bacteria, fungi, parasites, or viruses. The external ocular surface acquires a microbial flora at birth and some of the commensals may become resident flora in the conjunctiva and lids and have a potential to turn into pathogens. Apart from the resident flora any micro-organism from the environment can form a transient flora in the eye and given an opportunity invades the ocular tissues. While the anterior segment is infected by direct invasion from the anterior route, blood-borne infections may reach the posterior segment of the eye. Even what may be considered a minor infection elsewhere in the body can be "fatal" to the eye in terms of visual compromise. Corneal opacity resulting from a small ulcer in the centre of the cornea or a trivial penetrating injury to the eye can lead to blindness or loss of the eye. In a population-based study at L.V. Prasad Eye Institute (Andhra Pradesh Eye Disease Study) which sampled 11,786 rural and urban subjects with complete eye examination, the prevalence of blindness was 1.84% which was close to the national blindness data, and 8.6% among these had corneal blindness due to possible infection. [1] Thus, eye care forms one of the major commitments among the medical fraternity in India. India is a home to several government and private ophthalmology institutions that are among the best in the world. While providing superb patient care laced with first class technology, these institutions focus on research in eye diseases prevalent in Indian patients. Eye infections rank foremost in the areas of research and most appropriately many of these institutions can boast of highly advanced microbiology laboratory facilities dedicated to investigation of eye infections. A PubMed search showed more than 800 articles published by Indian researchers in the field of diagnosis, aetiopathogenesis, and management of eye infections. Research emanating from these laboratories is of high impact value that is evident from the account given below. It may be noted that the description below is brief and limited for the lack of space and gives only a bird's eye view of research in India pertaining to eye infections. Infections of the ocular adnexa, ocular surface, and orbit Conjunctivitis may be caused by several groups of organisms including bacteria, Chlamydia, viruses, fungi, helminths, and protozoa. Acute bacterial conjunctivitis may be acute papillary, hyperacute purulent, or acute membranous conjunctivitis. Most common causes of purulent conjunctivitis are Neisseria (ophthalmia neonatorum) or Staphylococcus infection. Concomitant with urethritis N. gonorroheae can cause bilateral purulent conjunctivitis with or without corneal involvement in adults. Bacterial conjunctivitis may also be caused by S. pneumoniae, H. influenzae, and Group A Streptococcus. Acute or chronic inflammation of the conjunctiva may also be caused by viruses, Chlamydia, and parasites. Several studies published from Sankar Nethralaya, Chennai, have shown the prevalence of Chlamydia trachomatis as endemic in India. [2],[3] Polymerase chain reaction (PCR) for cryptic plasmid of C. trachomatis has been described by the group. Isolated fungal infections of the conjunctiva are rare. Microsporidia have been recently described as common cause of keratoconjunctivitis in Eastern part of India. [4] Seasonal outbreaks of adenoviral conjunctivitis are known to occur in India, and nested PCR for detection of DNA coding hexon protein was described by Dalapathy et al. that has resulted in the development of a widely used diagnostic kit for adenoviral infections. [5] An epidemic of hemorrhagic conjunctivitis in and around Delhi was investigated at the RP Centre for Ophthalmic Sciences, AIIMS, and confirmed to be due to Enterovirus 70 in 1996. [6] Microbial keratitis is a common, potentially sight-threatening ocular infection that may be caused by bacteria, fungi, viruses, or parasites. The relative frequency of different bacteria as causative agents in keratitis may vary geographically. Pneumococcal keratitis is commonly associated with chronic dacryocystitis. [7] Staphylococcus species continue to be the predominant cause of bacterial keratitis and in several reports Staphylococcus epidermidis or coagulase negative staphylococci (CONS) is the leading cause. [8],[9] Pseudomonas species is reported to be the most commonly isolated organism in keratitis associated with daily or extended wear soft contact lenses. [10] Corneal ulcers caused by Bacillus species are rare and the largest series (19 eyes of 17 patients) has been described from India. [11] Nocardia species have been linked with bacterial keratitis, most cases being caused by Nocardia asteroides. However, they remain a rare cause of corneal ulceration. While primary tuberculous keratitis is extremely rare, infections of the cornea have been reportedly caused by atypical mycobacteria including Mycobacterium fortuitum, M. chelonae, M. gordonae, and M. avium-intracellulare. Recently, popularized keratorefractive surgery, excimer laser photorefractive keratectomy (PRK), and excimer laser in-situ keratomilieusis (LASIK) have resulted in disastrous bacterial keratitis cases. [12] Overall, the incidence of fungal keratitis is low in temperate climates, while higher incidence is reported from Southern United States and tropical regions of the world including India. [13] Prevalent species vary from one geographical area to the other. Extensive studies have been conducted at Joseph Eye Hospital, Thiruchirapalli, and an excellent review article has been published. [14] Conventional direct smear examination methods are reported to be highly sensitive for the diagnosis of fungal keratitis; however, nearly 9-14% of the fungal isolates may be non-sporulating requiring PCR-based DNA sequencing for identification. Targeting ITS region for this purpose, exotic, heretofore unknown, species of fungi such as Glomerella cingulata, Thielavia tortuosa, Macrophomina phaseolina, etc have been reported from fungal keratitis. [15] Free living protozoa such as Acanthamoeba spp. have been described to be associated with microbial keratitis in India since 1987 and from the large number of literature that is available, the central message from India is occurrence of the disease in association with trauma rather than contact lens wear. [16] Nevertheless, PCR-based sequencing targeting 18S rDNA has shown the prevalence of T4 sequence type in India, which is similar to those reported from contact lens patients from Western countries. Microsporidia group of organisms, that reside somewhere between fungi and parasites phylogenetically, have considerable importance in ocular infections in India and large case series have been published. A series of microsporidial stromal keratitis reported from L.V. Prasad Eye Institute, Hyderabad, has shown that these cases mimic viral keratitis clinically and are often misdiagnosed. [17] Diagnosis using conventional microbiological staining procedures and PCR has been described by Indian investigators. Extensive work related to viral keratitis associated with herpes simplex virus and varicella zoster virus have been done and multiplex PCR have been developed for the diagnosis of these infections. [18],[19] Scleritis is a rare condition. It is usually non-infectious; however, it may be associated with bacterial (Pseudomonas spp., S. aureus, Nocardia spp., atypical mycobacteria) or fungal (Aspergillus spp.) infection. Infectious scleritis may be after trauma (accident, surgery), endophthalmitis, or an extension of a corneal infection. [20] Orbital cellulitis, commonly seen in children, is a retroseptal infection of the extraocular orbital contents presenting with pain, lid edema, proptosis, and diplopia. The organisms associated with orbital cellulitis are derived from the sinuses and may consist of aerobic and anaerobic bacteria. Streptococcus pneumoniae, S. aureus, and Haemophilus influenzae are the most common organisms causing orbital cellulitis. Botryomycosis, a chronic bacterial granulomatous disease of skin and subcutaneous tissue caused by an encapsulated variety of Staphylococcus, may involve the orbit. Fungi belonging to various genera such as Aspergillus, [21] Mucor, Rhizopus, Sporothrix, Bipolaris, etc. have been reported. An extensive review on orbital tuberculosis has been published from India [22] apart from several case reports. Periorbital necrotizing fascitis is a rare but potentially fatal infection commonly caused by S. pyogenes and S. aureus. Unlike neck and scalp, necrotizing fascitis in periorbital and midfacial tissues may lack obvious preceding trauma. A series of 18 cases of histomorphologic and/or culture-proven zygomycotic necrotizing fascitis from Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, comprised 15(83%) cases of immunocompetent patients with precedent trauma in 14(77%). [23] Interestingly, out of eight microbiologically proven cases, five were Apophyses spp. and two had coexistent Aspergillus and Candida spp. This report highlighted the importance of fungus as an aetiological agent in necrotizing fascitis, in a largely immunocompetent subgroup of patients from India. Intraocular infections Infections of the uveal tract (iris, ciliary body, and choroid) may be exogenous (corneal ulcer, trauma, surgery) or endogenous from a contiguous structure (sinuses, orbital abscess, cellulitis) or haematogenous. Micro-organisms from any of the groups, bacteria, fungus, virus or parasite, either directly or indirectly, may be involved in uveitis. Ocular manifestations of infection by Mycobacterium tuberculosis include acute or chronic granulomatous iridocyclitis, iris nodules, multifocal choroiditis and chronic tuberculomas. Acute tuberculous endophthalmitis is rare. Lepromatous leprosy may be associated with insidious or acute exudative iridocyclitis. Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, and Aspergillus fumigatus are some of the fungi associated with choroiditis and chorioretinitis. C. albicans may be associated with endogenous endophthalmitis, the risk factors for which include prior antibiotic therapy, prior surgery, diabetes mellitus, alcoholism, etc. The review article on ocular leptospirosis by Rathinam SR sums up the large volume of work done on this unique form of uveitis from Aravind Eye Hospital, Madurai. [24] Pioneering work has been published from India on ocular manifestations of human immunodeficiency virus infection which in major part includes uveitis, choroiditis, and retinitis. [25] Long time contentious aetiopathogenesis of Eales' disease has been put to rest by overwhelming evidence in favour of mycobacteria. [26] Infection of the vitreous compartment along with retinal and uveal coats of the eye constitutes endophthalmitis. It may be exogenous, involving intraocular surgery or following penetrating injury to the eye. Organisms causing acute endophthalmitis include gram positive and gram negative bacteria. Some of the organisms associated with acute endophthalmitis are S. pneumoniae, P. aeruginosa, S. aureus, members of Enterobacteriaceae, enterococci, etc. Causes of chronic endophthalmitis include coagulase negative staphylococci, Propionibacterium acnes, Propionibacterium arachnia, Corynebacterium spp., Aspergillus spp., etc. Intraocular infection within 6 weeks of the causative event is termed acute endophthalmitis. Postoperative endophthalmitis can occur after any intraocular surgery, though numerically most infections are seen following cataract surgery, for the obvious reason that cataract surgeries outnumber other intraocular surgeries. Endophthalmitis is a rare complication of cataract surgery and the current worldwide incidence is less than 0.1%. India is on par with rest of the world with a recent large study from Aravind Eye hospital reporting 0.09% incidence in a high volume surgery set up. [27] The microbiological diagnosis of endophthalmitis is usually based on microscopy and culture of the microorganisms from anterior chamber fluid and/or vitreous (tap or biopsy) fluid. Smears made from these samples may be examined immediately after staining with Gram or Giemsa stain for infecting pathogens. Calcofluor white may be used when a fungal aetiology is suspected. Although smear examination is a rapid method, its sensitivity is low. [28] Bacillus spp. and fungi are most commonly associated with posttraumatic endophthalmitis though other organisms may be found. [29] Endogenous endophthalmitis can arise from colonized intravenous lines or contaminated syringes used by drug addicts. Indian investigators have published a data on all types of infective endophthalmitis. Recently one of the largest series in the world has been published on fungal endophthalmitis. [30] Contaminated intravenous infusion have been reported from India to be associated with Aspergillus endophthalmitis which should serve the purpose of raising the standards of quality control in pharmaceutical industry. [31] Despite application of best of microbiological techniques and immediate processing of samples, the sensitivity of conventional methods to detect organisms in vitreous fluid ranges from 25 to 60%. Molecular methods have a great role to play in improving this sensitivity. Eubacterial PCR based on 16S rDNA, panfungal PCR based on 28S rDNA, ITS 1, ITS 4, etc. with or without sequencing have all been used by various Indian investigators. These publications have contributed enormously to the knowledge of intraocular infections of different origin. Highly sensitive molecular techniques in various forms are being employed for the diagnosis of intraocular infections. Quantitative PCR using real-time PCR and loop-mediated isothermal amplification (LAMP) assays have added extraordinary dimensions to the diagnosis of intraocular infections. [32] Conclusions A complete account of Indian contribution to the world literature in the field of eye infections is beyond the scope of this editorial; however, attempt has been made to include some of the important ones in the foregoing description of eye infections commonly seen in India. Premier ophthalmology institutions in the country can be proud of world class microbiology laboratories completely devoted to diagnosis and research in the field of eye infections. Government of India has supported several of these research projects through various funding agencies and the latest has been the support of council for scientific and industrial research (CSIR) for the development of a DNA macrochip for the diagnosis of eye infections, the first of its kind in the world. A country with high prevalence of eye infections, it is only fitting that India should focus on finding the best diagnostic methods and treatment strategies for the rest of the world to follow. References
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