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 Table of Contents    
REVIEW ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 83-85  

Recent trends: Medical management of infectious keratitis


Department of Ophthalmology, Regional Institute of Ophthalmology, Pt.B.D. Sharma, PGIMS, Rohtak, Haryana, India

Date of Web Publication24-Jun-2015

Correspondence Address:
Dr. Sneha Solanki
C-103, Hextex Commune, Sector-43, Gurgaon, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-620X.159104

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   Abstract 

This review article highlights the newer diagnostic modalities and approaches in the medical management of infectious keratitis. A Medline literature search conducted to March 2014 has been included. Recent studies or publications were selected from international indexed journals using suitable key words. Development of specular microscopy and polymerase chain reaction (PCR) has a promising role as diagnostic modalities in infectious keratitis, especially in refractory cases. Previously fortified antibiotics have been the mainstay of treatment for bacterial keratitis. Recently, the advent of fourth-generation fluoroquinolones monotherapy has shown promising results in the management of bacterial keratitis. Corneal collagen cross-linking is being considered in the refractory cases. Topical natamycin and amphotericin B should be considered as the first choice anti-fungal agents in suspected filamentous or yeast infection respectively. Voriconazole and newer routes of administration such as intrastromal and intracameral injection of conventional anti-fungal agents have demonstrated a positive clinical response. Ganciclovir is a newer anti-viral agent with promising results in herpes simplex keratitis. Thus, introduction of newer diagnostic modalities and collagen cross-linking along with fourth-generation fluoroquinolones and newer azoles have a promising role in the management of infectious keratitis.

Keywords: Corneal ulcer, collagen cross-linking with riboflavin therapy, fourth generation fluoroquinolones, Infectious keratitis,


How to cite this article:
Solanki S, Rathi M, Khanduja S, Dhull C S, Sachdeva S, Phogat J. Recent trends: Medical management of infectious keratitis. Oman J Ophthalmol 2015;8:83-5

How to cite this URL:
Solanki S, Rathi M, Khanduja S, Dhull C S, Sachdeva S, Phogat J. Recent trends: Medical management of infectious keratitis. Oman J Ophthalmol [serial online] 2015 [cited 2020 Apr 4];8:83-5. Available from: http://www.ojoonline.org/text.asp?2015/8/2/83/159104


   Introduction Top


Until date, infectious keratitis poses a diagnostic dilemma due to the varied presentation and visual morbidity if adequate control measures are not instituted in time.

Although the conventional causes are categorized into a variety of pathogens such as bacteriae, fungi, viruses and protozoae, confusion in the etiological diagnosis superadded with the problem of increasing resistance to the older anti-microbials often leads to a delay in the initiation of appropriate treatment. This has led the researchers to develop newer diagnostic and treatment modalities. Over the past few years, ophthalmologists worldwide have witnessed changing trends in the diagnostic techniques such as polymerase chain reaction (PCR) and confocal microscopy, as well as treatment strategies such as usage of ultraviolet light and newer antimicrobials. [1]

All these medical advancements have widened the scope of improvement of refractory cases of infectious keratitis. It is, therefore, essential to update our knowledge regarding the diagnosis and management of infectious keratitis.


   Diagnosis Top


Although a detailed history along with presenting clinical features usually suffice in identifying the causative agent but it is highly recommended to thoroughly investigate the type of causative organism by combining the conventional diagnostic techniques of smear and culture with the newer diagnostic tools like confocal microscopy, PCR or genetic fingerprinting by pulsed field gel electrophoresis [2] after taking the corneal scrapings from the base and the edge of the ulcer.

A non-invasive, high-resolution technique of in vivo confocal microscopy of the cornea can be considered a diagnostic aid to help in making a rapid and accurate diagnosis of acanthamoeba or fungal infection while the results from other modalities are still awaited. [3] It has its limitation in diagnosing bacteria and microsporidium, which are too minute to be resolved by this technique. [4]

Polymerase chain reaction is a highly sensitive and rapid technique to identify pathogens by extraction and amplification from small quantities of DNA [5] and it seems to be a good adjunct to the conventional diagnostic techniques in refractory cases especially fungal and acanthamoeba infections where delay in the diagnosis of the pathogen worsens the ocular outcome of treatment. Limited availability of this modality limits its usage in the present scenario. [6] PCR high-resolution melting analysis is a recently introduced diagnostic strategy based on real-time and discriminates among the various varieties of fungi. [7]


   Treatment Protocols Based on Causative Organism Top


Bacterial keratitis

Antibiotics

Topical route: Broad spectrum antibiotics demonstrating adequate coverage against both Gram-positive and Gram-negative pathogens should be started as the first line of treatment. The usual protocol is to start a combination therapy of topical fortified antibiotics (cefazolin 5% and tobramycin or gentamicin 1.4%) therapy aggressively on half-hourly basis all through 24 h to enhance the therapeutic levels of drugs thereby bringing the infection under control. Frequency should be reduced based on the clinical response. There is no indication for the use of oral antibiotics unless scleritis or endophalmitis are suspected. [1]

Fourth generation fluoroquinolone monotherapy (eg: Gatifloxacin or moxifloxacin) is a good alternative to the conventional therapy and has demonstrated encouraging results, documented by meta-analysis and randomized controlled trials where both forms of treatment have shown comparable results in terms of efficacy and safety. [8],[9]

Fluoroquinolones demonstrate added advantages over fortified antibiotics in terms of better stability, longer shelf life and epitheliotoxicity, with the added advantage of not requiring refrigeration. [1]

Among the fluoroquinolones, the fourth generation (gatifloxacin and moxifloxacin) demonstrate the superiority over older generations (ciprofloxacin, ofloxacin) in terms of better coverage against both Gram-positive and Gram-negative microbes with no resistance documented until date. [10] Moxifloxacin has got the highest aqueous humour penetration, followed by gatifloxacin, with ciprofloxacin having the least penetration into the aqueous humour. [11]

Although fluoroquinolones can be recommended as the first line of treatment with promising results, the response to treatment should be closely monitored and changed according to the clinical response and culture results. The topical therapy may further be modified according to the results of in vitro bacterial sensitivity.

Subconjunctival route is no longer advisable for routine management of corneal infections [12] as it is associated with various ocular side-effects such as pain, redness, patient apprehension, risk of globe perforation and failure to provide enhanced corneal levels of antibiotic compared with drops.

Steroids

The use of topical steroids in infectious keratitis was analyzed in the multicentric, randomized clinical trial steroids in corneal ulcer trial (SCUT). Topical steroids, when used as an adjunctive treatment under antibiotic cover, do not provide any added benefit as proved by a SCUT. [1],[13]

Corneal collagen cross linking

It uses ultraviolet: A light activated riboflavin to strengthen the corneal tissue. This technique has been recently introduced as a treatment modality especially in the healing of refractory cases of infectious keratitis and has shown promising results. A meta-analysis conducted by Alio et al. has very well documented the role of collagen cross-linking (CXL) in infectious keratitis. They observed that the use of CXL hastened the epithelialisation, decreased the need for keratoplasty and reduced corneal melting. [14]

Fungal keratitis

Antifugal therapy

Natamycin 5% suspension is considered to be the first choice among anti-fungal agents in cases of filamentary fungal keratitis. [15] In cases refractory to the conventional natamycin therapy, Voriconazole (broad spectrum azole), available as topical 0.1% or 1% drops or tablet (200 mg) can be used as an alternative to treat filamentous fungi corneal infection with oral administration having shown good ocular penetration. [16],[17],[18] The mycotic ulcer treatment trial (MUTT) has demonstrated the superiority of natamycin over voriconazole in terms of better visual acuity outcomes and a lower rate of perforation. MUTT was a randomized, multi-centric trial where 368 patients were randomly distributed for topical natamycin and voriconazole therapy. Patients in the natamycin group reported better visual outcomes and fewer rates of perforation thereby reducing the need for therapeutic keratoplasty. [15] Topical amphotericin-B 0.015% therapy should be instituted in cases where yeast infection is suspected.

The newer antifungal voriconazole when given through intrastromal injection achieves high tissue concentrations, but at the same time increases the risk of perforation. [19]

Addition of oral antifungal treatment (fluconazole, voriconazole or itraconazole tablets) is indicated whenever there is an evidence of deep corneal invasion, intraocular spread or spread to the limbus.

Acanthamoeba keratitis

The diagnosis requires a high index of suspicion. A typical history of contact lens usage or swimming is the risk factors which aid in its diagnosis. Treatment is aimed toward killing the resistant amoebic cysts as opposed to the sensitive trophozoites. Chlorhexidine (0.02% or 0.2%) and polyhexamethylene biguanide (0.02% and 0.6%) should be initiated as the empiric therapy [20],[21] against trophozoites and cysts. Since these drops are not available commercially, they need to be procured from tertiary care ophthalmic institutes on request. Prolonged use even after the clinical resolution of the infection is advocated to prevent the occurrence of relapses. Although dual therapy with a second agent such as hexamidine or brolene is common, there is no published trial data to support this strategy. Oral non-steroidal agents (e.g. Flurbiprofen 50 mg TDS) can help control pain and immunosuppressive agents should be considered if there is an associated scleritis. [22]

Viral keratitis

Antiviral therapy

Antivirals have been in use for the treatment of herpetic keratitis for over two decades. The drugs commonly employed are idoxuridine, iododesoxycytidine, vidarabine, trifluridine, acyclovir and ganciclovir. In a recent multicentric trial ganciclovir 0.15% gel was found equivalent to 3% Acyclovir for the treatment of viral keratitis. Thery also observed that local tolerance of ganciclovir was better than that with acyclovir, particularly with regard to blurring and stinging after installation. [23]

Progressive disease

Microbial keratitis with negative initial culture reports, not responding to the conventional treatment is a challenge for an ophthalmologist. Fungal and acanthaoemba infection further add to the seriousness of the disease process as they are usually compounded with difficulty in the diagnosis with a high rate of false negative culture results along with greater ocular morbidity. A typically unusual history should raise the suspicion against unusual pathogens (e.g. mycobacterium, nocardia), particularly if there has been laser refractive surgery or foreign travel. A repeat culture onto selective media like Lowenstein Jensen medium, Sabouraud Dextrose Agar and non-nutrient agar should be done to determine the aetiological agent. A corneal biopsy (for culture and histopathology) would be required in those cases where the infection is deep seated in the cornea. The diagnosis can further be confirmed on confocal microscopy examination or tissue for PCR examination.


   Conclusion Top


Management of infectious keratitis has evolved over the past decades with the advent of newer and improved rapid diagnostic modalities such as PCR and Confocal microscopy. These can detect the causative microorganism more efficiently and rapidly than conventional culture techniques. Newer drugs with an increased efficacy and less resistance have led to a decrease in the rates of blinding complications. Variability in the individual responses should provide us with the urge to find better treatment options. Continuous ongoing research will definitely provide better options in the future.

 
   References Top

1.
Gokhale NS. Medical management approach to infectious keratitis. Indian J Ophthalmol 2008;56:215-20.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Gupta N, Tandon R. Investigative modalities in infectious keratitis. Indian J Ophthalmol 2008;56:209-13.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Chew SJ, Beuerman RW, Assouline M, Kaufman HE, Barron BA, Hill JM. Early diagnosis of infectious keratitis with in vivo real time confocal microscopy. CLAO J 1992;18:197-201.  Back to cited text no. 3
    
4.
McHir ST, Burton M. Moorfields Eye Hospital NHS Foundation Trust. Microbial Keratitis. The Royal College of Ophthalmologists, Focus. Autumn; 2013.  Back to cited text no. 4
    
5.
Bagyalakshmi R, Therese KL, Madhavan HN. Application of semi-nested polymerase chain reaction targeting internal transcribed spacer region for rapid detection of panfungal genome directly from ocular specimens. Indian J Ophthalmol 2007;55:261-5.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
6.
Tananuvat N, Salakthuantee K, Vanittanakom N, Pongpom M, Ausayakhun S. Prospective comparison between conventional microbial work-up vs PCR in the diagnosis of fungal keratitis. Eye (Lond) 2012;26:1337-43.  Back to cited text no. 6
    
7.
Borderie V, Laroche L, Chaumeil C. New strategy for rapid diagnosis and characterization of fungal infections: The example of corneal scrapings. PLoS One 2012;7:e37660. Available from: http://www.plosone.org [Last accessed on 2014 May 15].  Back to cited text no. 7
    
8.
Hanet MS, Jamart J, Chaves AP. Fluoroquinolones or fortified antibiotics for treating bacterial keratitis: Systematic review and meta-analysis of comparative studies. Can J Ophthalmol 2012;47:493-9.  Back to cited text no. 8
    
9.
McLeod SD, LaBree LD, Tayyanipour R, Flowers CW, Lee PP, McDonnell PJ. The importance of initial management in the treatment of severe infectious corneal ulcers. Ophthalmology 1995;102:1943-8.  Back to cited text no. 9
    
10.
Scoper SV. Review of third-and fourth-generation fluoroquinolones in ophthalmology: In-vitro and in-vivo efficacy. Adv Ther 2008;25:979-94.  Back to cited text no. 10
    
11.
Solomon R, Donnenfeld ED, Perry HD, Snyder RW, Nedrud C, Stein J, et al. Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5%, and ciprofloxacin 0.3% into the aqueous humor. Ophthalmology 2005;112:466-9.  Back to cited text no. 11
    
12.
Baum J, Barza M. Topical vs subconjunctival treatment of bacterial corneal ulcers. Ophthalmology 1979;87:710-6.  Back to cited text no. 12
    
13.
Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, et al. Corticosteroids for bacterial keratitis: The Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol 2012;130:143-50.  Back to cited text no. 13
    
14.
Alio JL, Abbouda A, Valle DD, Del Castillo JM, Fernandez JA. Corneal cross linking and infectious keratitis: A systematic review with a meta-analysis of reported cases. J Ophthalmic Inflamm Infect 2013;3:47.  Back to cited text no. 14
    
15.
Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, et al. The mycotic ulcer treatment trial: A randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol 2013;131:422-9.  Back to cited text no. 15
    
16.
Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ. Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol 2007;143:151-3.  Back to cited text no. 16
    
17.
Jhanji V, Sharma N, Mannan R, Titiyal JS, Vajpayee RB. Management of tunnel fungal infection with voriconazole. J Cataract Refract Surg 2007;33:915-7.  Back to cited text no. 17
    
18.
Hariprasad SM, Mieler WF, Holz ER, Gao H, Kim JE, Chi J, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 2004;122:42-7.  Back to cited text no. 18
    
19.
Sharma N, Chacko J, Velpandian T, Titiyal JS, Sinha R, Satpathy G, et al. Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology 2013;120:677-81.  Back to cited text no. 19
    
20.
Elder MJ, Kilvington S, Dart JK. A clinicopathologic study of in vitro sensitivity testing and Acanthamoeba keratitis. Invest Ophthalmol Vis Sci 1994;35:1059-64.  Back to cited text no. 20
    
21.
Hay J, Kirkness CM, Seal DV, Wright P. Drug resistance and Acanthamoeba keratitis: The quest for alternative antiprotozoal chemotherapy. Eye (Lond) 1994;8:555-63.  Back to cited text no. 21
    
22.
Bacon AS, Frazer DG, Dart JK, Matheson M, Ficker LA, Wright P. A review of 72 consecutive cases of Acanthamoeba keratitis, 1984-1992. Eye (Lond) 1993;7:719-25.  Back to cited text no. 22
    
23.
Colin J. Ganciclovir ophthalmic gel, 0.15%: A valuable tool for treating ocular herpes. Clin Ophthalmol 2007;1:441-53.  Back to cited text no. 23
    




 

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