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Memorias del Instituto de Investigaciones en Ciencias de la Salud
On-line version ISSN 1812-9528
Mem. Inst. Investig. Cienc. Salud vol.17 no.1 Asunción Apr. 2019
https://doi.org/10.18004/mem.iics/1812-9528/2019.017(01)03-005
Articles
Keratitis and the challenge of being in the middle of the road
1Fundación Visión, Asunción, Paraguay
The cornea is a transparent and immunologically privileged organ, due to its lack of blood vessels and the layout and distribution of collagen fibers. It is cleverly defended by physical barriers like the corneal epithelium, the turnover and composition of the tear film and finally, the external protection from the environment obtained from the eyelid. The cornea has five layers, including a 5-7 cell thick epithelium, stroma and endothelium, with support layers separating the stroma from the other two layers. An infection of the cornea by bacteria, fungi or protozoa is referred to as keratitis1, a sight-threatening condition that can lead to perforation, or an extension of the infection like endophthalmitis. In fact, the most serious complication of keratitis can be blindness that is caused by corneal scarring.
Corneal blindness is one of the five main causes of blindness worldwide2and although it affects lower income countries, this epidemic has three different faces. In lower income countries2, the epidemic is inversely related to healthcare access. Higher income countries have a direct relationship between contact lens use and keratitis incidence3. Middle income countries like Paraguay are affected by both ends of this spectrum.
Keratitis can be classified by its underlying cause (infectious vs. non-infectious). The most common types of infectious keratitis are bacterial and fungal; whereas non-infectious include immunologic, exposure and allergic keratitis as well as others4.
Risk factors5include contact lens use, corneal trauma or abrasion, immunocompromise, autoimmune disease, ocular surface and anatomical conditions, previous herpetic disease, exposure to contaminated water and previous eye surgery.
Typically, a patient will present complaining of eye pain, redness, secretions, progressive visual loss and light intolerance. Bacterial keratitis has the unwelcome characteristic of having a rapid progression, where a complete tissue destruction can occur in less than 48 hours and often occurs in 24 h6.
Careful questioning will reveal the presence of one or more risk factors, especially contact lens use or ocular trauma. Although milder signs cannot be seen easily without adequate equipment and are missed by non-specialists; physical examination using the ophthalmological lamp will reveal an inflammation of the corneal tissues and in some cases epithelial breaking which confirms the diagnosis.
Corneal scrapings should be obtained for microscopy (Gram and Giemsa stainings), cultures (blood agar and chocolate agar plates) and antibiotics sensitivity; other stainings and culture mediums can be obtained if deemed necessary. Ideally, these samples and cultures should be obtained before starting antibiotic therapy. This is sometimes impossible because by the time patients get to an ophthalmologist, they have already received treatment from others. However, it is still convenient to obtain samples as soon as possible and in some cases, it is necessary to suspend the treatment in order to identify the underlying cause and susceptibility to achieve a successful treatment. Although stainings, microscopy and cultures are still the gold standard for diagnosis, and they are widely recognized as highly specific, even consistently, their sensibility still remains unsatisfactory.
Molecular techniques are being used to complement traditional methods. Polymerase Chain Reaction (PCR) for suspected viral infections is becoming more common, although assay specifications can vary widely. Both Quantitative and Multiplex PCR are being tested, but remain out of reach for many and badly standardized for others. Next Generation Sequencing (NGS) refers to newer methods of DNA determination and the two methods being explored the most for Keratitis are Sequencing by Ligation (SBL) and Sequencing by Synthesis (SBS). They overcome one of PCR’s main limitations as they not require a priori knowledge of what pathogen should be investigated. Although promising, availability and standardization of these molecular methods are the major holdbacks in order to achieve a consensus of when and how to use them.
Regarding treatment of keratitis, the consequences of erroneous or delayed treatment are visually devastating. Treatment is often delayed in impoverished conditions because of lack of access, whereas, being used to mild eye discomfort delays seeking help among contact lenses users. Self-medication for keratitis is common and usually insufficient for the clinical case. This has resulted in increased antibiotic resistance, and once again, lower income countries double the prevalence of some resistant strains (53-61%, coagulase negative Staphylococcus spp. resistant to moxifloxacin)7when compared with higher income countries (26-35%)8,9. Finally, the treatment needs to be adjusted not only by etiology, but by the visual risk level and antibiotic susceptibility; which makes treatment complex and requires qualified personnel.
Current treatment standard includes antibiotics, oral analgesics, and support measures that may include agents that paralyze the iris temporarily to alleviate light induced pain. The use of corticosteroids remains controversial.
In Paraguay, a 13-year retrospective study10 described the demographic profile of 660 patients, the etiology of their keratitis and found that most patients had self-medicated and delayed seeking medical help by at least one week. In our current issue, Ku et al. describe their prospective findings of a two-year period. Little has changed telling us that a better job needs to be done in educating the public about self-medication and the need of seeking timely help.
In conclusion, diagnosis and treatment of keratitis remain a challenge. Middle income countries like Paraguay face an increased epidemic driven by an increase in contact lens users and the limitation of care for rural communities. The delay in treatment and self-medication need to be better addressed to make progress.
REFERENCIAS BIBLIOGRÁFICAS
1. Barnes S, Hallak J, Pavan-Langston D, Azar D. Microbial Keratitis. En: Dolin R, Blaser MJ, Bennett J. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases (8th Edition). Philadelphia: Elsevier; 2015. [ Links ]
2. O’Brien KS, Lietman TM, Keenan JD, Whitcher JP. Microbial keratitis: a community eye health approach. Community Eye Health. 2015;28(89):1-2 [ Links ]
3. Kraig Scot Bower, Frank S. Hwang. BMJ Best Practice Keratitis. BMJ Best Practice. [Online] February 2019. https://bestpractice.bmj.com/topics/en-gb/561. [ Links ]
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5. Stapleton F, Naduvilath T, Keay L, Radford C, Dart J, Edwards K, et al. Risk factors and causative organisms in microbial keratitis in daily disposable contact lens wear. PLoS One [Internet]. 16 de agosto de 2017 [citado 10 de abril de 2019];12(8). Disponible en: Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558933/ [ Links ]
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7. Lalitha P, Manoharan G, Karpagam R, Prajna NV, Srinivasan M, Mascarenhas J, et al. Trends in antibiotic resistance in bacterial keratitis isolates from South India. British Journal of Ophthalmology. febrero de 2017;101(2):108-1. [ Links ]
8. Ni N, Nam EM, Hammersmith KM, Nagra PK, Azari AA, Leiby BE, et al. Seasonal, geographic, and antimicrobial resistance patterns in microbial keratitis: 4-year experience in eastern Pennsylvania. Cornea. marzo de 2015;34(3):296-302. [ Links ]
9. Peng MY, Cevallos V, McLeod SD, Lietman TM, Rose-Nussbaumer J. Bacterial Keratitis: Isolated Organisms and Antibiotic Resistance Patterns in San Francisco. Cornea . enero de 2018;37(1):84-7. [ Links ]
10. Laspina F, Samudio M, Cibils D, Christopher N Ta, Fariña N, Sanabria R, et al. Epidemiological characteristics of microbiological results on patients with infectious corneal ulcers: a 13-year survey in Paraguay. Graefe's Archive for Clinical and Experimental Ophthalmology, 2004; 242: 204-9. [ Links ]