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Corneal infections in the 21st century
  1. Hon Shing Ong,
  2. Melanie C Corbett
  1. Department of Corneal and Ocular Surface Disease, The Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Hon Shing Ong, The Western Eye Hospital, Imperial College Healthcare NHS Trust, 153–173 Marylebone Road, London NW1 5QH, UK; honshing{at}gmail.com

Abstract

Ninety years ago, the first issue of the Postgraduate Medical Journal published a review of an article written by Mr Robert Lindsay-Rea, a consultant ophthalmic surgeon in the Western Ophthalmic Hospital and an oculist in the West End Hospital for Nervous Diseases, entitled “A preliminary report on the treatment of keratitis”. Today, microbial keratitis remains an important cause of avoidable visual impairment in the world. The aetiology of microbial keratitis has changed greatly over the past century due to the discovery of antibiotics, improvement in sanitation and education, the rising trend of contact lens wear and increased air travel. Significant advances have also been made in our understanding and management of this important disorder. This article highlights some of these changes and discusses the current management and research.

  • Infection
  • Keratitis
  • Microbial
  • Treatment
  • Advancement
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Introduction

The cornea is the transparent avascular structure of the front of eye. It is an important component of the human optical system, contributing about two-thirds of its total refractive power. Any change in shape or optical transparency of the cornea can result in visual loss.

Ninety years ago in 1925, in the first issue of the Postgraduate Medical Journal, a review of an article written by Mr Robert Lindsay-Rea (1881–1971) entitled “A preliminary report on the treatment of keratitis” was published.1 ,2 Mr Lindsay-Rea was a consultant ophthalmic surgeon in the Western Ophthalmic Hospital (currently the Western Eye Hospital, Imperial College Healthcare NHS Trust) and an oculist in the West End Hospital for Nervous Diseases.3 A summary of his report is shown in box 1.

Box 1

Summary of article “A preliminary report on the treatment of keratitis” by Mr Robert Lindsay-Rea.2

Mr Robert Lindsay-Rea based his article on his observation and study of 91 patients.2 He discussed the treatment of interstitial keratitis caused by syphilis, highlighting the fact that many forms of syphilitic disease presented after an attack of interstitial keratitis. He recorded that the minimum time needed for an eye to regain 6/6 vision after onset of an attack was 4 months, but recovery for some patients could take over a year. The treatment regime he described entailed 8–12 injections of Novarsenobillon followed by mercury and iodides, or mercury alone in children. Novarsenobillon (neoarsphenamine or neosalvarsan) is a derivative of Salvarsan (arsphenamine), an organoarsenic compound introduced in the 1910s.4 It was the first effective treatment for syphilis.5 ,6 By dividing patients into three groups according to whether they received prompt treatment, delayed treatment or no treatment, he illustrated the importance of prompt treatment to better visual outcome.

Keratitis is a non-specific clinical term describing inflammation of the cornea. It can result in a change in its structure and a reduction in its transparency. It can range from mild superficial punctate erosions to more significant corneal ulceration, neovascularisation, scarring or thinning. The commonest cause of keratitis is corneal infection. Corneal infection (or infectious keratitis) is one of the leading causes of preventable blindness in both the developing and developed world today.7 Infectious or microbial keratitis can be caused by a range of pathogens including bacteria, fungi and protozoa. Herpetic eye disease is also an important cause of viral keratitis, but this is a distinct entity which is not covered in this review.

Over the past 90 years, much has changed in the epidemiology, aetiology and management of keratitis. The advancement in diagnostic tools and the development of effective treatment for microbial keratitis has resulted in an overall improvement in visual outcome. With a focus on infectious aetiology in the adult population, this review highlights some of these changes and discusses the current management and research which guides our treatment of such patients who attend the Western Eye Hospital today.

Corneal infections in the early 20th century

From the published literature in the early 1900s it was evident that suppurative keratitis (now more commonly known as microbial keratitis or corneal ulceration) was difficult to manage.8 ,9 Notable publications from this time period include Nathaniel Bishop Harman's book published in 1919. The book describes ‘serpiginous corneal ulcers’, a severe form of suppurative keratitis characterised by ulcers with swollen raised edges and sinuous curved outlines, extensive infiltration and hypopyon with or without corneal perforation.10 This would often be associated with severe pain, photophobia and congestion of the eye. Harman also observed that chronic sepsis of the lacrimal sac frequently occurred, and the literature highlighted the importance of examining the lacrimal system for discharge when patients presented with corneal ulcers.8 ,10

Aetiology

Serpiginous ulcers generally occurred in elderly people, often following a corneal abrasion, and had a tendency to steadily progress.10 In addition, most cases (particularly those not associated with injury) occurred in poor ill-nourished patients. Other listed causes of serpiginous ulcers in this publication included “purulent disease of the conjunctiva, trachoma, acneiform ulcers, ulcers from exposure following orbicularis paresis, exophthalmic goitre or coma, and trophic ulcers following pathology of the first division of the fifth cranial nerve”. Acneiform ulcers are now recognised as rosacea keratitis, a form of inflammatory keratitis associated with acne rosacea. Orbicularis paresis refers to facial palsy resulting in lagophthalmos, and exophthalmic goitre refers to the proptosis associated with thyroid eye disease. Coma, at the time, was often due to typhoid or meningitis. Trophic ulcers (now more commonly known as neurotrophic ulcers) resulted from loss of corneal sensation (supplied by the V1 division of the trigeminal nerve). The most frequent cause was secondary to herpetic keratitis.

The common causative organisms for serpiginous ulcers were reported to be Pneumococcus, Staphylococcus and Morax–Axenfeld bacillus (now known as Moraxella lacunata).8 ,10

Treatment and management

In the absence of antibiotics, medical treatments used in the early 20th century were mainly antiseptics or disinfectants. For ulcers in the early stages, the recommended treatment was frequent use of warm boric acid, perchloride of mercury or yellow oxide of mercury. Zinc sulfate 0.5% drops were recommended for Moraxella infections10 and optochin (ethylhydrocupreine) for Pneumococcus.9 For more severe ulcers the endorsed treatment was direct chemical cautery with potent antiseptics and disinfectants such as trichloroacetic acid, nitric acid, iodine, pure phenol (carbolic acid) or lysol (chlorophenol).9 ,10

In cases where discharge from the lacrimal system was present, it was suggested that the lower punctum should be dilated and the lacrimal sac washed frequently with antiseptic lotions.10 If there was any obstruction, either the cannaliculus was to be split open or the lacrimal sac needed to be excised.8 ,10 For trophic ulcers and ulcers resulting from exposure, stitching of the eyelids at the inner and outer canthi with copious Vaseline lubrication was recommended to avoid losing the eye.

For ulcers that progressed despite medical treatment, it was proposed that the edge of the ulcer could be cauterised with galvano or fine-pointed thermal cautery. Radium radiation therapy was also suggested as an effective adjunctive treatment for severe corneal ulcers.11 For advanced non-healing ulcers, opening of the anterior chamber using techniques such as a Guthrie–Saemisch incision or ‘delimiting keratotomy’ were thought to be necessary in order to relieve tension off the cornea and allow an “influx of a new supply of lymph, containing antibodies from the limbus”.9 Pus in the anterior chamber was drawn out through the incision using forceps. Atropine or eserine were used to dilate or constrict the pupil, thereby reducing iris prolapse. The wounds were opened daily until healing was complete (usually 5–8 days). Despite being a radical procedure then, keratotomy was thought to be an effective therapeutic measure in severe ulcers. Sanford R Gifford, an ophthalmic surgeon, wrote the following statement in his report: “I have never been sorry for having done it, however, in a serpent ulcer, and in the early days, when it was not a routine procedure, have often been sorry for having postponed it”. He also stated that: “The scar of the incision, though made in clear cornea, is insignificant compared to that made by the ulcer in its otherwise almost inevitable advance”.9

Corneal infections in the 21st century

In the early 20th century there was limited understanding of infectious keratitis, and recommended treatments were based mainly on anecdotal case reports from individual ophthalmologists. Presently, in the 21st century, significant advances have been made in our understanding and management of this important disorder. However, despite these advances, severe microbial keratitis remains clinically challenging and an important cause of avoidable visual impairment today.12

Epidemiology

Microbial keratitis is still associated with the potential for significant permanent visual loss and the need for hospital admission and surgical intervention in both developing and developed nations.13 ,14 The true prevalence of microbial keratitis is unknown; estimated prevalence varies between 6.3 per 100 000 and 710 per 100 000, depending on the study population.12 ,15 ,16 The WHO estimated corneal ulcers to be responsible for 1.5–2.0 million new cases of monocular blindness every year.17 This is likely to be a conservative estimate due to under-reporting.

Aetiology

Update

In the 21st century, improvement in diagnostic techniques means that we can now identify most of the organisms that can cause corneal infections. We now know that, in addition to bacteria, different microorganisms including fungi and protozoa (Acanthamoeba) can cause microbial keratitis. Over the last century, factors that have influenced our study of the aetiology of microbial keratitis include the discovery of antibiotics, better sanitation and education, and increased air travel. With the discovery of penicillin, syphilitic keratitis as described by Lindsay-Rea is now rare. Due to improved sanitation and health promotion, new cases of trachoma are also rare in the UK.

Large variation exists in the prevalence of microorganisms in different geographical locations due to differences in demographic factors, predisposing risk factors, socioeconomic conditions and climate.18 Awareness of the microbial prevalence in different geographical regions is now increasingly important for ophthalmologists treating microbial keratitis, given the rise in international travel and migration. In addition, local protocols for diagnosing and treating microbial keratitis need to be reviewed regularly as the profile of organisms, drug sensitivities and resistance evolve.

Risk factors for microbial keratitis that have remained unchanged since the 1900s include a history of trauma, ocular surface disease and corneal exposure due to neurological deficits or thyroid eye disease. Additionally, today, iatrogenic risk factors such as ophthalmic surgery and the use of topical steroids are well recognised.19–21

The widespread use of contact lenses since the 1970s has also introduced an important risk factor for microbial keratitis. Contact lens-associated microbial keratitis was rare before the 1970s but, since the 1990s, contact lens wear has become the most important risk factor for all forms of microbial keratitis in developed nations, accounting for 55–65% of diagnosed cases.19–21 While suppurative keratitis was more commonly encountered in the elderly population in the early 20th century, keratitis associated with contact lens wear often affects healthy young individuals. Among contact lens wearers, specific risk factors for developing microbial keratitis include soft contact lenses, cosmetic contact lenses, overnight wear (especially extended wear contact lenses), poor hygiene (infrequent lens disinfection, infrequent lens case cleaning, not washing hands), swimming or showering in lenses, number of days of wear per week, internet purchase of contact lenses, smoking, self-reported poor general health, diabetes mellitus and high socioeconomic class.19 ,22–25

Bacterial keratitis

Today, bacterial keratitis remains the most common cause of microbial keratitis in temperate countries such as the UK, accounting for over 90% of cases.18 ,22 ,26 The remaining cases are caused by fungi (yeast, moulds and microsporidia) and Acanthamoeba.22 ,26

Bacteria commonly multiply in contact lens cases where they are protected from disinfection by bacterial biofilm. Pseudomonas species account for the majority of cases of contact lens-related bacterial keratitis. Other common Gram-negative bacteria include Serratia marcescens and Enterobacteriaceae. They often present with rapidly progressive stromal infiltrates, suppuration and, if left untreated, may result in corneal necrosis, thinning and perforation. The common Gram-positive cocci causing corneal infections include Staphylococcus and Streptococcus species, many of which are commensals of the nasal mucosa, skin, conjunctiva and the upper respiratory tract. Other less common causes of bacterial keratitis include atypical (non-tuberculous) Mycobacterium and Nocardia species. Microbial keratitis due to atypical mycobacteria is associated with ocular surgery, especially photorefractive corneal surgery. Nocardia species are Gram-positive bacteria often associated with trauma involving soil or vegetable matter.

Fungal keratitis

Fungal keratitis can be caused by filamentary fungi (eg, Fusarium, Aspergillus) or yeasts (eg, Candida). Fungus is an important cause of microbial keratitis in tropical countries18 ,27–30 whereas, in the developed world, it largely occurs in eyes with a poor ocular surface, immunosuppression (including treatment with long-term topical steroids) or contact lens wear. In the tropics, the associated risk factor is often agricultural trauma. Conversely, the prevalence of Acanthamoeba in these countries is low.27 ,31

East India is reported to have the highest proportion of corneal infections attributable to fungi (67%) worldwide.28 Most of these reported cases were caused by Aspergillus (60% of fungal cultures). The highest proportion of fungal keratitis due to Fusarium was reported in a study from Hyderabad (73% of fungal cultures).29 Keratitis due to Candida, on the other hand, often occurs in patients who are immunosuppressed or in eyes with a poor ocular surface. Another fungal organism that is emerging as a cause of fungal keratitis in tropical Asian countries is microsporidia.30 ,32 Risk factors for microsporidia include soil exposure, contact lens wear and topical steroid use.

Acanthamoeba keratitis

Acanthamoeba keratitis was first reported in 1973.33 Between 1973 and 1981, fewer than 10 cases were reported. In 1988, a review of CDC Division of Parasitic Disease laboratory log books identified 208 unique cases of Acanthamoeba keratitis, 85% of which occurred in contact lens wearers.34 This dramatic increase in the incidence of Acanthamoeba keratitis between 1985 and 1988 was attributed to the increasing popularity of soft contact lens use, improved awareness among clinicians and improved diagnostic techniques.35

Worldwide, there is a marked difference in the reported incidence of Acanthamoeba keratitis within different countries. This ranges from as low as 0.15 per million in the USA to as high as 1.4 per million in the UK. Acanthamoeba keratitis accounts for 1–1.4% of cases of microbial keratitis in India27 ,36 compared with 4% of cases in countries where contact lens wear is more common.37 Besides differences in contact lens use, such worldwide variation in incidence has been explained by differences in the types of contact lenses used, accessibility to contact lens care systems, prevalence of Acanthamoeba contamination in water and swimming pools and the availability of diagnostic techniques.38 ,39 The higher incidence of Acanthamoeba keratitis in the UK has been attributed to the use of tank-fed water supply in homes and the presence of limescale in hard water.40–42

Pathophysiology

As Harman observed in the early 1900s, most pathogens are unable to invade a structurally intact corneal epithelium.10 Corneal infections often occur when there is a breach in the integrity of the corneal epithelium due to trauma, contact lens wear or surgery, allowing microorganisms to enter, ulcerate and multiply. Left untreated, infections can progress from the corneal epithelium into the deeper corneal stroma, which is an ideal medium for microbial growth. In addition to the pathogenicity of microorganisms, immune mechanisms are important in the progression of corneal ulcers. Any insult to the cornea triggers a cascade of events that can result in further damage to the corneal tissue.16 Immune cellular pathways, inflammatory mediators and proteases can impede healing and even perpetuate corneal destruction, leading to tissue loss. This can result in corneal thinning and perforation.

Diagnosis

As noted even in the early literature, patients with microbial keratitis often present with an acute onset of pain, photophobia, conjunctival injection (redness) and varying degrees of visual loss depending on the severity and location of corneal involvement. A targeted history should aim to identify risk factors relevant today.

The slit lamp, invented in 1911, remains one of the most important diagnostic instruments used by ophthalmologists today. Significant improvements have been made in the last century, affording better illumination and magnification.43 During examination, the size, location, depth and shape of corneal infiltrates should be recorded. An epithelial defect can be detected with fluorescein stain and measured. There is often inflammatory activity in the anterior chamber and, if severe, a hypopyon may be present (figure 1). The eyelids, tear film, conjunctiva and cornea of both eyes should be examined for predisposing factors such as poor lid closure (lagophthalmos), lid margin inflammation (blepharitis), dry eyes or impaired corneal sensation. Complications such as corneal thinning, vascularisation and perforation should also be noted if present.

Figure 1

Pseudomonas keratitis with a large corneal infiltrate (top arrow), hypopyon (bottom arrow) and associated corneal thinning.

Infections with atypical organisms may have a less acute presentation. Feathery or serrated infiltrates and satellite lesions may suggest a fungal cause (figure 2). Acanthamoeba keratitis is typified by the presence of perineural infiltrates, dendritiform lesions and, later, ring infiltrates (figure 3). Lesions can look like dendritic ulcers of herpes simplex and thus a diagnosis of herpes simplex infection in a contact lens wearer should not be made until Acanthamoeba keratitis has been excluded. Polymicrobial infections causing microbial keratitis can make diagnosis and management difficult.

Figure 2

Fungal keratitis in a contact lens wearer. (A) Pre-treatment: infiltrate with irregular feathery margins (arrow) (B) Post-treatment with voriconazole drops: resolved infiltrate with residual corneal scarring.

Figure 3

Perineural infiltrates in the cornea of a contact lens wearer who had acanthamoeba keratitis.

Our ability to identify causative microorganisms has advanced considerably since the early 20th century. Culture techniques have been refined, immunological and nucleic acid-based identification methods such as the polymerase chain reaction (PCR) have been developed and more sophisticated microscopes are available.

In today's practice, corneal scrapes are taken wherever possible to help identify the causative organism. A needle bevel or equivalent is used to take tissue from the edge and base of the ulcer. These samples should be placed on glass slides and also spread directly on agar plates. They are sent to the microbiology laboratory for microscopy (Gram stain), culture and sensitivity testing.44 Contact lenses, cases, cleaning solutions and corneal sutures should also be sent if these are available. In cases where a diagnosis of Acanthamoeba keratitis is considered, an epithelial biopsy should be taken and plated on non-nutrient agar. This is seeded with Escherichia coli in the laboratory, on which the amoeba feed. PCR has proved more sensitive than microscopy and culture for the molecular diagnosis of bacterial, fungal and amoebic infections. It was developed in 1985 and is gaining popularity today as a routine technique for identifying microorganisms in microbial keratitis.45–50

In vivo confocal microscopy of the cornea was first used clinically in the late 1980s.51 In experienced hands, it is a useful adjunctive tool for the detection of Acanthamoeba or fungi, achieving approximately 80% specificity and 50% sensitivity.52 In Acanthamoeba keratitis, cysts showing double walls and internal structures can be observed even deep in the corneal stroma. Filaments or hyphae are seen in fungal infections.

Treatment and management

Early aggressive treatment of microbial keratitis is important to improve visual outcomes. This observation was made by ophthalmologists 90 years ago, even before the introduction of antibiotics.53 The basic principles underlying the treatment of microbial keratitis are the same today as in the early 20th century and include: (1) eradication of pathogens; (2) addressing risk factors; and (3) limitation of tissue damage and promotion of wound healing.

Eradication of pathogens

Since the introduction of penicillin during World War II and the subsequent development of a vast range of broad-spectrum antimicrobial agents, antibiotic treatment has been a central part of the management of patients with microbial keratitis. It is also responsible for improved visual outcomes in these patients.

Bacterial keratitis

If clinical features are typical of a bacterial keratitis, initial empirical treatment should be with a topical broad-spectrum antibiotic which covers both Gram-positive and Gram-negative organisms. Commonly, first-line treatment would include the use of fluoroquinolones (eg, ofloxacin 0.3%, levofloxacin 0.5%, moxifloxacin 0.5%).54 In severe cases, dual therapy with a cephalosporin (eg, cefuroxime 5% or ceftazidime 5%) can be used. Precise combinations are determined by local sensitivities. Initial treatment should be intensive (hourly application for the first 5–7 days) to achieve maximum therapeutic tissue concentration and control of the infection (sterilisation phase).44 Empirical therapy may be modified when results of laboratory sensitivities become available. After the initial sterilisation phase, depending on clinical response, topical antibiotic treatment may be reduced to allow healing of the corneal ulcer. Systemic antibiotics are often not needed unless there is corneal perforation, bacterial scleritis or endophthalmitis.

Fungal keratitis

At the diagnosis of fungal keratitis, any prior use of steroid drops should be discontinued. This is unless the patient has had a corneal transplant, where steroids are continued to avoid graft rejection. Empirical treatment for fungal keratitis depends on whether the fungus in question is a mould (filamentous) or yeast. Treatment of filamentary fungal keratitis includes natamycin 5%, econazole 1%, voriconazole 1% or chlorhexidine 0.2%.55–58 Treatment of yeasts (eg, Candida keratitis) includes amphotericin 0.15% or econazole 1%. Like bacterial keratitis, the initial treatment should be intensive, then reduced according to clinical response. Treatment duration for fungal infections is often prolonged (eg, 6 months) and should be continued beyond complete healing of the corneal ulcer. Systemic antifungal treatments (eg, voriconazole) should be started for peripheral, deep or invasive ulcers. Injection of voriconazole directly into the corneal stroma has been reported to increase the tissue concentration in deep lesions.

Acanthamoeba keratitis

Acanthamoeba exists in two forms: cysts and trophozoites. Acanthamoebic cysts are more resistant to treatment than trophozoites. Thus, anti-amoebic treatment involves the use of cysticidal drugs.39 Failure to eradicate viable cysts may result in recurrence of disease when treatment intensity is reduced. A typical treatment regime is the use of combination antiseptic therapy such as polyhexamethylene biguanide 0.02% or chlorhexidine 0.2% with a diamidine such as hexamidine 0.1% or propamidine 0.1% (Brolene). Early intensive therapy is needed to treat susceptible organisms before maturation of cysts. Drop frequency is then reduced after 5–7 days due to the risk of corneal epithelial toxicity. The average duration of medical therapy is 6 months to ensure destruction of any organisms emerging from cysts.59 Recent studies have shown that antifungal drugs (eg, voriconazole and natamycin)60 and β-blockers (eg, propanolol) may also have anti-amoebic properties.61

Addressing risk factors

Methods for addressing risk factors are still similar to those described by Harman in the early 1900s. These include addressing problems with the eyelids and lacrimal system, lubricants for exposure keratopathy and tarsorrhaphy for lagophthalmos and non-healing neurotrophic ulcers. Botulinum toxin, first used in the 1970s as a treatment for strabismus, is now also commonly used on the levator palpebrae muscle as an alternative to tarsorrhaphy.62

Limitation of tissue damage and promoting wound healing

Corticosteroids

The use of corticosteroids after antibiotics is another significant advancement in medicine in the last century. When combined with appropriate antimicrobial therapy, steroids have been shown to be safe and effective in the treatment of bacterial keratitis to decrease inflammation and corneal scarring.63 ,64 As steroids reduce the host immune response without appropriate antimicrobial therapy, their non-judicious use can worsen fungal and herpetic infections.15 ,44 Corticosteroids should thus only be started in patients with microbial keratitis when microscopy or cultures have excluded a fungal infection.

Progressive keratitis

The management of microbial keratitis can be challenging, especially if the disease continues to progress and initial diagnostic tests have been equivocal.65 The possibility of poor compliance with treatment should be assessed and, if in doubt, patients should be admitted for treatment. Atypical organisms (eg, Mycobacterium, Nocardia, microsporidia) should be considered if there is a history of foreign travel, trauma from soil or vegetation or laser refractive surgery. In non-responsive cases, culture and sensitivities should be checked and there may be a need for re-culture on selective media. Corneal biopsy may also be required. Some patients with fungal or amoebic infections continue to progress despite appropriate therapy.65 The reasons for this are often unclear.

Surgical management

With our current understanding of the pathophysiology of microbial keratitis and the development of antimicrobials, surgery now plays a much lesser role in the management of uncomplicated microbial keratitis. Corneal gluing and tectonic grafts are employed when there is corneal perforation after the sterilisation phase is complete. In refractory cases of fungal keratitis, therapeutic keratoplasty (corneal transplant) may be considered to debulk the infection. However, there is a high risk of recurrence of infection in the graft. In gonoccocal keratitis, superficial keratectomy may be required to debride necrotic tissue to promote healing. In the last decade, collagen cross-linking has also been proposed to have antimicrobial effects.66 Ultraviolet light is applied with riboflavin to stiffen the corneal stroma, but the results remain controversial. Techniques such as the Guthrie–Saemisch incision or delimiting keratotomy are now obsolete.

Conclusion

Since the time of Mr Lindsay-Rea and Mr Bishop Harman 90 years ago, there have been significant changes in our understanding and treatment of corneal infections. Today, diagnosis of microbial keratitis is more precise and antibiotics offer effective treatment. Patients who might have lost their vision in the past can, with prompt diagnosis and targeted treatment, expect a good visual outcome.

Nevertheless, similarities still exist in the principles of their management. Some of our ‘new’ treatments, such as antiseptics to treat acanthamoebic keratitis in the absence of more specific agents and proposals to use ultraviolet radiation in collagen cross-linking, also draw parallels with treatments used in the early 1900s.

For the future, we need to continue ongoing efforts on public education and reduction of potential risk factors. Well-conducted trials to evaluate the efficacy and safety of new antimicrobial treatments in keratitis will also continue to facilitate the development of better evidence-based protocols.

Main messages

  • Significant advances have been made in the understanding and management of microbial keratitis over the past 90 years.

  • The basic principles underlying the treatment of microbial keratitis are the same today as in the early 20th century: eradicate infection then promote healing.

  • Early aggressive treatment of microbial keratitis is important to improve visual outcomes.

  • Contact lens wear is currently the most important risk factor for microbial keratitis in developed nations.

  • Public education in infection risks associated with contact lens use, such as poor contact lens hygiene or long duration of wear, is important in the prevention of microbial keratitis.

  • Keratitis caused by atypical organisms (eg, fungus and Acanthamoeba) must be considered in patients with suggestive clinical presentations or a poor response to initial antibiotic treatment.

Current research questions

  • How can the management of fungal and Acanthamoeba keratitis be improved by facilitating the host response or developing new cidal agents?

  • What is the role of collagen cross-linking in the management of corneal infections?

  • How can wound healing after infective keratitis be modified to reduce the long-term sequelae such as corneal scarring and irregularity, which have a lasting impact on vision?

Key references

  • Dart JK, Radford C, Minassian D, et al. Risk factors for microbial keratitis with contemporary contact lenses. Ophthalmology 2008;115:1647–54.

  • Dart JK, Saw VP, Kilvington S. Acanthamoeba keratitis: diagnosis and treatment update 2009. Am J Ophthalmol 2009;148:487–99.

  • Allan DS, Dart JKG. Strategies for the management of microbial keratitis. Br J Ophthalmol 1995;79:777–86.

  • Prajna NV, Krishnan T, Mascarenhas J, et al. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol 2013;131:422–9.

  • Srinivasan M, Mascarenhas J, Rajaraman R, et al. Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol 2012;130:143–50.

Self assessment questions

Please answer true (T) or false (F) to the below statements.

  • The cornea contributes up to one third of the refractive power of the human optical system

  • In a normal human eye, the cornea is an avascular structure

  • Loss of vision can result from changes in shape or optic transparency of the cornea

  • Infections of the cornea is an important cause of keratitis

  • Corneal neovascularisation, thinning, perforation and scarring are potential complications of microbial keratitis

  • Infection of the cornea is no longer an important cause of blindness in the world today

  • Over the past decade, the clinical symptoms and signs of bacterial keratitis have changed

  • In the developed countries today, the majority of microbial keratitis occurs in the elderly or patients who are immunocompromised

  • Many risk factors for developing microbial keratitis seen in the early 1900s are still important and should be considered when managing patients with the condition today

  • Keratitis is an important cause of visual loss in developed countries

  • In developed countries such as the United Kingdom, the majority of microbial keratitis cases are caused by bacteria

  • Trachoma is a leading cause of blindness in the world

  • With the discovery of penicillin, syphilitic keratitis is now rare

  • Contact lens wear is now the most important risk factor for developing microbial keratitis in developed countries

  • Compared to patients who wear soft contact lenses, the risk of microbial keratitis is higher in those who wear rigid contact lenses

  • Large variation exists in the prevalence of micro-organisms in different geographical locations

  • Atypical organisms (e.g. fungii) are rare causes of microbial keratitis in developed countries

  • Acanthamoeba keratitis in the United Kingdom has been attributed to the use of tank-fed water supply in homes and the presence of lime scale in hard water

  • Clinical presentation of microbial keratitis caused by atypical organisms (e.g. acanthamoeba) are often similar to those caused by bacteria

  • Nocardia are gram-negative bacteria associated with soil or vegetable matter

  • Compared to the early 20th century, similarities still exist in the principles of management of microbial keratitis today

  • Local protocols for diagnosing and treating microbial keratitis need to be reviewed regularly as the profile of organisms, drug sensitivities and resistance evolve

  • Confocal microscopy is a useful adjunctive tool for the detection of acanthamoeba or fungi in the management of microbial keratitis

  • At the diagnosis of fungal keratitis, topical steroids should be added to reduce inflammation and scarring

  • Techniques such as the Guthrie-Saemisch incision or delimiting keratotomy should be performed in cases of severe microbial keratitis

Answers

  1. A (F); B (T); C (T); D (T); E (T)

  2. A (F); B (F); C (F); D (T); E (T)

  3. A (T); B (T); C (T); D (T); E (F)

  4. A (T); B (F); C (T); D (F); E (F)

  5. A (T); B (T); C (T); D (F); E (F)

References

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Footnotes

  • Contributors HSO: literature search, writing of article, critical revision and final approval of article. MCC: writing of article, critical revision and final approval of article.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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