Diagnosis and Management Protocol of Acute Corneal Ulcer

International Journal of Health Sciences and Research Vol.10; Issue: 3; March 2020 Website: www.ijhsr.org Review Article ISSN: 2249-9571

Vaishal P Kenia1, Raj V Kenia2, Onkar H Pirdankar3

1Kenia Eye Hospital, Mumbai 2Kenia Foundation, Mumbai 3Kenia Medical and Research Foundation, Mumbai

Corresponding Author: Onkar H Pirdankar

ABSTRACT

Corneal ulceration is one of the leading causes of corneal blindness. Various pathogens are responsible for corneal ulceration. Accurate and quick diagnosis and prompt treatment is a key to improve clinical and visual outcomes in cases of corneal ulceration. However there are no specific guidelines or protocols are available for managing the corneal ulcers. Sometimes even an experienced clinician struggle to predict the course of the disease in most of the cases. Here we make an attempt to provide an overview on diagnostic approach and management protocol of acute corneal ulcer.

Key words: Acute corneal ulcer, corneal ulceration, corneal blindness

INTRODUCTION parasitic (Acanthamoeba).Whereas the non- Corneal ulceration is one of the infectious causes are autoimmune, major ocular emergencies causing ocular neurotrophic, toxic, allergic keratitis, morbidity. It is considered a leading cause chemical burns, keratitis secondary to of corneal blindness especially in the entropion, trichiasis, blepharitis, developing countries. It has been estimated lagophthalmos. that globally, corneal ulceration with ocular Infectious causes of corneal trauma are resulting in 1.5 -2 million cases ulceration vary based on geographic of corneal blindness annually 1. It affects location. The common microorganism are males more than the females, can be seen at Fusarium species, Pseudomonas aeruginosa, any age and mostly the patients belong to a Aspergillus spp., S. Pneumoniae, low socio-economic strata 2,3. In developing Staphylococcus Spp. Fungal organisms are countries like India, the major reason for common in Countries like India, China. In corneal ulcer is ocular trauma whereas in other countries such as Philippines, Taiwan, the developed countries, the most common Thailand and Singapore bacterial organisms reason is contact lens wear. such as Pseudomonas aeruginosa is Etiology and Epidemiology: common. Table 1 describes the common The causes of a corneal ulcer can be microorganisms, by counties 4. infections like bacteria, viruses, fungi or

Common organism Total IND CH SG PH JP TH KR TW Bacterial 38.0% 38.3% 15.3% 41.3% 53.2% 47.8% 50.5% 42.8% 61.8% Fungal 32.7 45.6% 30.2% 0.7% 27.0% 6.3% 9.1% 10.0% 8.2% Parasitic 2.4 2.1% 0.9% 1.3% 5.7% 5.0% 4.0% 1.2% 6.9% Viral 12.6% 6.9% 46.2% 7.0% 2.0% 16.6% 6.1% 6.0% 8.2% Infectious 14.5% 7.1% 4.4% 49.7% 12.1% 24.3% 30.3% 40.0% 15.0% Keratitis (Not Specified)

International Journal of Health Sciences and Research (www.ijhsr.org) 69 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Table 1 describes common organism found response is less aggressive and slow in Asian countries (IND-India, Ch- China, compared to bacteria. Fungus secretes SG- Singapore, PH- Philippines, JP- Japan, proteolytic enzymes and fungal antigens and TH-Thailand, KR- South Korea, TW- toxins which facilitates their deeper stromal Taiwan) penetration and breach the descemets membrane and thereby reach anterior Pathogenesis: chamber where it forms fungus-exudate-iris Bacterial: mass covering the pupillary area. 5 Bacterial corneal ulcers are results Viral: from the penetration of bacteria after a In viral ulcer, the virus reaches the cornea breach in the corneal epithelial barrier from within via terminal branches of except organisms like gonococcus can ophthalmic division of the trigeminal nerve. penetrate an intact epithelium to cause ulcer. It has been postulated that in case of herpes Factors predisposing the epithelium like simplex there is an involvement of the sub corneal edema, prolonged contact lens basal nerves which results in epithelial usage, dry eyes, and trauma make it swelling whereas in case of herpes zoster vulnerable to corneal infection. The most there is an involvement of deep stromal common microorganism is Pseudomonas nerves. So without epithelial breach the Aeruginosa which utilizes glycocaluxto virus reaches the eye via nerve endings and adhere to epithelium and then invades into the inflammation of nerve causes the stroma through breach in epithelial. neurogenic pain. The virus actively Inflammatory cells (PMNs) reach the site of replicates in corneal epithelium. The virus corneal breach from the tears and limbal in the epithelium form raised lesion forming vessels which releases cytokines and superficial punctate keratitis and then interleukins resulting in progressive slough to form large epithelial defect and invasion of cornea and increase in size of eventually stromal ulceration. the ulcer. Phagocytosis of the organism Parasites such as acanthamoeba: releases the free radicals and proteolytic Acanthamoeba keratitis is most commonly enzymes leading to necrosis and sloughing associated with soft contact lens use, Once it of the epithelium, bowman’s membrane and is adherent to the contact lens, it survives in stroma. In addition, process is facilitated by the space between the contact lens and the proteases and exotoxin that are produced by ocular surface and later gets attached to the multiplying bacteria and endotoxin that are glycoproteins on the corneal villi. The produced by organisms after their death. microtrauma to the corneal epithelial The endotoxins are polysaccharides within surface due to contact lens use promotes the the cell wall of gram negative bacteria and entry of the organism into the epithelium, are responsible for ring infiltrates. 3,4 the invade Bowman's layer and enter the Fungal: stroma. The infection then moves along the Fungus are classified as yeast, filamentous corneal nerves, produces acute septated, pigmented and non-pigmented and inflammation and radial deposits (radial filamentous without septae. In the tropical keratoneuritis). The acute inflammation countries, the commonest fungus is produces metalloproteases that digests filamentous like Aspergillus, Fusarium, in collagen fibrils and allows deeper temperate countries yeast fungus like penetration into the stroma. As the disease candida is common. Fungal pathogens also progresses, it may penetrate the anterior enter the cornea after an epithelial breach, chamber and can cause endophthalmitis. following trauma or foreign body in the Symptoms: 6,7 form of vegetative material or soil particles  Reduced visual acuity, and after invasion incite a host  Tearing, inflammatory response. The inflammatory  Discharge,

International Journal of Health Sciences and Research (www.ijhsr.org) 70 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

 Redness are the common symptoms long-term use of ocular medications (topical presented by the patients. steroids, Anti-glaucoma medications),  Pain (Disproportionate pain can be seen contact lens wear (age of contact lens and in Herpes and Acanthamoeba. Fungal lens cleaning solution), and previous ocular ulcers are quieter whereas pseudomonas infections is important as all these factors are fast growing) alter the ocular surface milieu and promote  Diagnostic Approach: microbial invasion of the cornea in the absence of trauma. Similarly, systemic Careful History: diseases such as diabetes, rheumatoid It is very important to keep in mind arthritis, hepatitis, auto-immune diseases the TRIAD of ocular trauma, Lowered and their therapy, tuberculosis, malignancy immune status (either the ocular surface or impair the natural immune status of an the individual as a whole) or extremely individual and predisposes to opportunistic virulent organisms that penetrate the intact infections, unusual microbes, fungi or ocular surface. A corneal ulcer cannot viruses. develop in a healthy individual with a Thorough Slit lamp Biomicroscopy: healthy ocular surface, in the absence of A thorough slit lamp examination is ocular trauma. In this respect, a detailed useful to evaluate the clinical signs may be history focussed on finding the cause of an helpful to confirm the probable diagnosis. ulcer in the patient is very important so as to Figure 1 briefly describes the diagnostic ensure an appropriate management. A approach for acute corneal ulcer. history of ocular trauma, ocular surgery,

Diagnostic Approach with Corneal Ulcers Patients

Presentation: History Reduced Visual acuity, tearing, discharge, redness, Pain (disproportionate in case of Herpes and Acanthamoeba)

Risk Factors: External: Corneal trauma, Contact Lens (CL) wear, contaminated CL solution Ocular Factors: Ocular surface and adnexal disorders, Dacryocystitis, corneal epithelial disease Systemic Factors: Long term steroid use, diabetes Mellitus, Kidney Failure, HIV

Slit Lamp Biomicroscopy Infiltrate Features Severity Factors Bacterial ulcer: Necrotic stroma, purulent discharge and hypopyon • Size of infiltrate (<2mm or >2mm) Fungal Ulcer: Stromal Infiltrate with feathery borders • Location of Infiltrate (central Versus peripheral) Viral Ulcer: Dendritic pattern with progressive geographic and Amoeboid • Depth of Infiltrate (<50% or > 50%) configuration • Involving limbus, sclera Acanthamoba Ulcer: Stromal infliltrates with ring shaped configuration and • Associated with AC reaction hypopyon • Hypopyon

Initial Medical treatment Approach  Severe ulcers need intense therapy and follow ups  Anti fungal and Acanthamoeba treatment after smear report and strong clinical judgement

Laboratory Investigation Conventional Superficial Scraping and Culture Corneal Biopsy and Deep Stromal Confocal Microscopy Culture Smear: Giemstain, KOH, Calcoflour White, For Deep Infiltrate For Acanthamoeba and Fungal Reduced AFB stain eg Nocardia Infection Culture: Blood Agar, Sabouraud agar, Special Non nutrient Agar with E. Coli Figure 1: Diagnostic Approach with Corneal Ulcers Patients

International Journal of Health Sciences and Research (www.ijhsr.org) 71 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Slit lamp examination starts with: 1. Eyelid assessment for Blepharitis, meibomian glands dysfunction, ectropian/ entropian, lagophthalmos. 2. Eyelashes assessment for trichiasis/ distichiasis 3. Lacrimal apparatus system assessment for punctal abnormalities, dacryocystitis 4. Conjunctiva assessment for discharge, inflammation, foreign body, papillae, follicle, cicatrization, symblepharon, pseudomembrane, filtering bleb, tube errosion 5. Sclera assessment for any nodule, Figure 2: Post RK bacterial ulcer (S. Aureus) (Image from Vaishal P Kenia) thinning 6. Cornea assessment for epithelial defects, punctate keratopathy, stromal edema, ulceration, thinning, perforation, infiltrate characteristics (size, shape, location, depth), foreign body, sign of previous corneal surgeries. Fluorescein or rose Bengal staining allow clinicians to identify some organism or underlying cause. For example in cases of viral infections dendritic ulcers are stained with fluorescein and rose Bengal stain. 7. Anterior chamber assessment for presence of any inflammation, look for cells and flare, hypopyon, hyphema Figure 3: Iron foreign body induced gram negative bacterial corneal ulcer in a diabetic case (Image from Vaishal P Kenia) Signs: 6,7 Although there are no specific signs to identify the responsible organisms, a careful slit lamp assessment with clinical experience help reach probable diagnosis. Various factors such as size, shape, location of Infiltrate, involvement of limbus, sclera, associated with AC reaction and hypopyon gives information about how aggressive the infection is. Bacterial: Gram positive infection (Figure 2):

 Localized infiltrate with distinct borders Figure 4: Fungal ulcer with feathery margin with satellite  Minimal stromal haze lesion (Image from Vaishal P Kenia) Gram negative infection (Figure 3): Fungal:  Dense stromal suppuration/ Ring  Dry raised slough, with a dried Infiltrate appearance of surrounding cornea which  Hazy surrounding cornea with a ground is clear. glass appearance.  Stromal infiltrate with feathery edges,

International Journal of Health Sciences and Research (www.ijhsr.org) 72 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

 Satellite lesions and thick endothelial  Hyopopyon is also a common finding in exudates, (Figure 4) acanthamoba.  Sometimes presents with ring infiltrate  In late cases radial keratoneuritis can  Hypopyon usually forms which is also be noted and can be identified as convex upwards and may wax and whitish outline of the corneal nerves 6,7. wane.

Viral:  Viral ulcers can result from herpes simplex or herpes zoster infections  Viral ulcer can be seen in the form of dendritic pattern (linear branching) due to central desquamation.  The end of the branches manifest a characteristically swollen appearance.  It generally gets stained with

fluorescence. Figure 6 Ring Infiltrate in Acanthamoeba (Image from Garg  Anterior stromal infiltrate appear under P., Rao, G., 1999)8 the ulcer but resolves spontaneously.  Corneal sensation is reduced. B. Microsporadia:  Progressive centrifugal enlargement  Characterized by raised epithelial lesion may result in larger epithelial defect and deep stromal keratitis. with a geographical and amoeboid Identification of causative organism configuration. (Figure 5) underlying the disease is important for successful treatment and it requires laboratory investigations. Microscopic examination and cultures is a considered as a gold standard for the accurate diagnosis. Laboratory investigations allow for direct visualization of microorganism in material and help understand the inoculation of material under appropriate conditions to allow multiplication of microorganism. Microbiological Culture and Light Microscopy:8,9 Traditionally clinicians were heavily Figure 5 showing three phases of lesions: epithelial dots (9 o'clock), dendritic pattern (6 o'clock) and a geographic epithelial dependent on light microscopes, corneal keratitis (12–2 o'clock), suggesting herpes simplex virus epithelial smears and cultures. Conventional smear keratitis.(Image From Gurav P et al 2015 9) and culture for bacteria, fungus and Parasitic Acanthamoeba can be prepare by scraping A. Acantamoeba: the base and leading edge of the corneal  Acanthamoba keratitis can be contact ulcer using flame sterilized Kimura spatula lens or non contact lens related or sterile surgical blade no 15 on Bard Parker Handle. Every scraping can be use  Characterized by epithelial irregularities, for direct microscopic examination, culture corneal edema, with single or multiple and antibiotic susceptibility testing. These stromal infliltrates which has classic scraping are immediately placed on glass ring shaped configuration (Figure 6) slides for light microscopy and agar plates  However diffuse and satellite infiltrates for culture (Blood agar, chocolate agar, are also common. Potato dextrose agar (PDA), Sabouraud agar

International Journal of Health Sciences and Research (www.ijhsr.org) 73 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer etc). The slides for light microscopy are With advancement in technology, direct stained with 10% potassium hydroxide or visualization of pathogens within the gram stain or Giemsa stain to aid in the patients cornea is possible. In Vivo confocal visualization of fungal filament, bacterial or microscopy is non invasive technique Acantamoeba cyst growth respectively. available in clinical settings. To best of our Special staining such as modified Ziehl knowledge there are presently two Neelsen for nocardia, microsporadia and modalities available for clinical use are KOH or calcoflour white staining for scanning slit IVCM (Confoscan, Nidek acanthaomeba and fungus can be use. For Technology, Fremont, CA) and laser culture the agar plates are inoculated at 25- scanning IVCM (HRT3 with Rostock 27degree C for 7 days in case of (PDA) corneal module, Heidelberg Engineering, whereas in case of other media it is Heidelberg, Germany). On confocal inoculated at 35-37 degree C (2 days for microscopy acanthamoeba cyst can be blood agar) and microorganism growth is identified as double walled ovoid bodies and assessed on daily basis. Cultures of contact fungal bodies were seen as bright linear lens, lens case and contact lens solution can filamentous structures with bright borders also be done in case of contact lens wearers. that appear as parallel lines (double walled linear bodies)10 Corneal Biopsy and deep Stromal Treatment protocols Culture technique: In majority of the cases the infection Corneal biopsy is indicated if the is resolved without any acute surgical need. infiltrate is located in the mid or deep However surgical intervention is required stroma with overlying uninvolved tissues. irrespective of infection is resolved or not Corneal biopsy can be performed at the slit resolved 2.Initiation of treatment is based on lamp biomicroscope or operating clinical judgement, smear report and the microscope. After instillation of topical treatment is modified according to culture anaesthetic, a small trephine or blade is used report and clinical response. It has also been to excise a small piece of stromal tissue at reported that use of topical cortico steroid is the edge of the infiltrate which can be sent controversial hence they are best avoided. for culture as well as histopathology. Medical Treatment: Antimicrobial Susceptibility: 9 Antibiotic, antifungal or antiviral Antimicrobial susceptible testing of eye drops are the treatments of choice the isolates is performed by Kirby Buaer however Antifungal and Acanthamoeba Disk Diffusion method using ciprofloxacin therapy started only after microbiological (5 µg), ofloxacin (5 µg), gatifloxacin (5 µg), evidences, in most cases. The line of tobramycin (10 µg), chloramphenicol (30 medical treatment and the route of treatment µg), amikacin (30 µg), gentamicin (10 µg), is decided based on the depth, size and moxifloxacin (5 µg) as per Clinical and location of infiltrates. Central infiltrate Laboratory Standards Institute Guidelines. would require more aggressive treatment as Disk diffusion method assesses antibiotic compared to peripheral, superficial<2mm sensitivity of bacteria. It uses antibiotic infiltrate. Deep intrastromal infiltrate would discs to evaluate the extent to which require intrastromal injections as it gives bacteria are affected by those antibiotics. good drug availability at deeper layer. Antibiotic susceptibility does not Bacterial Keratitis: necessarily directly reflex clinical Topical antibiotics (Monotherapy) susceptibility. can be in given in cases of superficial Confocal Microscopy: peripheral infiltrates< 2mm. For deep Confocal microscopy has played a crucial stromal involvement or an infiltrate larger role in the diagnosis of microbial keratitis, than 2 mm with extensive suppuration a fungal and acanthamoba keratitis 8,10,11. loading dose every 5-15 minutes followed

International Journal of Health Sciences and Research (www.ijhsr.org) 74 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer by frequent applications such as every hour involves limbus and sclera. Role of is recommended. In case of monotherapy, corticosteroid in treating the bacterial ulcer Levofloxacin 1.5% is preferred over is controversial. The SCUT treatment study Gatifloxacin and Moxifloxacin due to found no benefit of concurrent topical emerging resistance with Gatifloxacin and corticosteroid therapy using prednisolone Moxifloxacin and easier availability of sodium phosphate 1% in conjunction with Levofloxacin. In cases of large or visually broad spectrum topical antibiotics. A significant infiltrate or severe infection in pervious study have reported no benefits of the presence of a hypopyon, topical fortified corticosteroids in managing corneal scars antibiotics is preferred. Systemic antibiotics 12.Table 2 describes the various antibacterial are rarely required, however they can be drugs. considered in severe cases where infection

Table 2 describes the various antibacterial drugs. Gram Positive Cocci Gram Negative Cocci Gram Positive Bacilli Gram Negative Bacilli Regular antibiotic Regular Antibiotics Regular Antibiotics Amikacin Regular antibiotic Cefazolin Ceftriaxone Fluoroquinolone Fluoroquinolone 4th Generation Fluoroquinolone Ceftazidime Clarithromycin F. Tobramycin Higher antibiotics Fluoroquinolone Higher antibiotics Vancomycin Amikacin Linezolid Ceftazidime Piperacillin Meropenam Colistin

Fungal Keratitis: Fungal ulcers are difficult to treat since the diagnosis is delayed. Mycotic ulcer treatment trial (MUTT) I compared natamycin and voriconazole revealed that Natamycin had showed significant clinical improvement as compared to voriconazole. MUTT II compared oral voriconazole and oral placebo which did report benefits of oral voriconazole in treating Fusarium Ulcer. Steroids are contraindicated in fungal ulcers. Subconjuctival antifungals should be avoided since they result in severe pain and induce tissue necrosis to some extent. Since Intrastromal Voriconazole has a good penetrating capacity it can be considered to treat deep and larger ulcers. Intrastromal Voriconalzole can be used as an adjunct to Natamycin in eyes not responding to topical natamycin13,14.Table 3 describes Antifungal drugs6,7. Figure 7 describes the algorithm for managing severe bacterial keratitis.

Figure 7: Algorithm for Managing Severe Bacterial Keratitis

International Journal of Health Sciences and Research (www.ijhsr.org) 75 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Table 3 describes Antifungal drugs Causes of Medical treatment failure Polyenes Pyrimidines Imidazoles e.g. Nystatin, e.g. Flucytosine e.g. Clotrimazole  Wrong diagnosis Amphotericin B Miconazole Natamycin Ketoconazole  Resistance to Antibiotic especially Fluconazole (Ciprofloxacin, moxifloxacin etc.) Itraconazole  Non compliance from patients

Acanthamoeba Keratitis: Surgical treatment A combination of propamidine isethionate Surgical treatment depends on various (Brolene) 0.1% and polyhexamethylene factors such as size, location and causes of biguanide 0.02% can be prescribed in initial the ulcer. stage. A combination of brolene and Corneal Gluing to manage perforations: neomycin or monotherapy with For managing corneal perforations chlorhexidine also gives good results. less than 2mm cyanoacrylate glue is Steroid should be avoided however in case applied. Healing of the cornea occurs as of deep vascularisation steroids and fibrovascular tissue grows under the glue cysticidal agents combination can be used. and dislodges the glue. If the perforation is Oral Miltefosine can be considered as larger than 2mm then either a tenon patch or adjunctive treatment for Acanthamoeba multilayer amniotic membrane graft is keratitis 15. Table 4 describes Antiameoboid 6,7 considered. It has been reported that drugs . Gunderson flap have also been use to treat perforation however it was found to be non Table 4 describes Antiameoboid drugs 16 Anticeptic Biocides Aminoglycosides Diamidines effective. Chlorhexidine Neomycin Dibromopropamidine Amniotic membrane transplant (AMT): PHMB Paromomycin Hexamidine AMT can provide structural support Viral Keratitis: in areas of corneal ulceration. The use of a Usually, about 50% of active epithelial single layered AMT may be sufficient to lesions heal spontaneously without treat ulcers lacking depth and significant treatment. The cure rate of antiviral therapy stromal thinning however non effective in cases of deep ulcers and multilayered AMT is 95%. In most of the cases healing occur 16,17 by day 10. After healing has occurred can be considered .It has been reported that AMT is also efficacious in treating medication should be quickly tapered and 18 discontinued by day 14. Steroids are neurotrophic Ulcer contraindicated in viral ulcers. Table 5 DALK using the big bubble describes the anti viral drugs 6,7. technique seems to be effective and safe in the treatment of deep fungal as well Table 5 describes anti viral drug Acanthamoeba keratitis unresponsive to Topical Systemic medication19. Also, therapeutic Keratoplasty Acyclovir 3% ointment Oral Acyclovir 400mg Ganciclovir 0.15% Gel Famciclovir 500mg have shown good results in Acanthamoeba Trifluorothymidine 1% drop Valacyclovir 1gm keratitis 17. Penetrating keratoplasty (PKP) Valganciclovir 900mg is performed in advance cases where

medical treatment fails or perforation too Supplementary treatment: large to treat by other options 2,7,16,20 Cylcoplegic agents such as atropine Novel treatment approaches sulphate 1%, homatropine 1%, or Topical Povidone-Iodine 1.25% has cyclopentolate 1% can be prescribe for three shown to be as effective as topical times a day to reduce the ciliary spasm and antibiotics for bacterial keratitis21. Collagen produce mydriasis, thus help relieve pain shields or contact lenses soaked in and prevent the formation of synechiae. antibiotics are used in some cases which Glaucomatous drug can be prescribed to may enhance the drug delivery. Nano drug lower the IOP.

International Journal of Health Sciences and Research (www.ijhsr.org) 76 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer particles as it has better penetration and diagnosis and treatment. Sultan Qaboos drug availability. Univ Med J. 2009;9(2):184-195. Newer treatments such as 6. Fleiszig SM, Evans DJ. The Pathogenesis of photoactivated chromophore for infectious bacterial keratitis: studies with keratitis -corneal collagen cross-linking Pseudomonas Aeruginosa. Clin Exp Optom. 2002;85(5):271-278. (PACK-CXL)22,23 have been used in therapy 7. Kuriakose T, Thomas PA. Keratomycotic resistant cases of melting corneas and also malignant glaucoma. Indian J Ophthalmol. in novel cases of bacterial keratitis. It has 1991;39(3):118-121. been reported that Dresden protocol 8. Garg P, Rao GN. Corneal ulcer: Diagnosis technique is found be efficacious by and management. J Community Eye Heal. damaging the DNA and RNA in microbes 1999;12(30):21-23. and thus help in improving and reducing 9. Prakash G, Avadhani K, Srivastava D. The inflammatory response to bacteria. Pack three faces of herpes simplex epithelial CXL has a very good healing rate in cases keratitis: A steroid-induced situation. BMJ of bacteria as compared to fungal. However Case Rep. 2015;2015(12):2014-2015. it works better in superficial infiltrate and 10. Chidambaram JD, Prajna N V., Larke NL, et al. Prospective Study of the Diagnostic future work is required to explore its use in Accuracy of the In Vivo Laser Scanning other cases with consideration of treatment Confocal Microscope for Severe Microbial parameters as well as pathogen types. Keratitis. Ophthalmology. 2016;123(11): Prevention 2285-2293. Since it is vision threatening condition, it is 11. Motukupally SR, Singh A, Garg P, Sharma important to increase awareness about eye S. Microbial Keratitis Due to Aeromonas care. Many causes of corneal ulcers can be Species at a Tertiary Eye Care Center in prevented by using protective eye wear Southern India. Asia-Pacific J Ophthalmol. during travelling or work. Educating the 2014;3(5):294-298. patients about care and maintenance of 12. Kumar R, Andrea C, Pedram H. Current contact lens can help prevent ulcers related State of In Vivo Confocal Microscopy in Management of Microbial Keratitis. Semin to contact lens wear. Ophthalmol. 2010;25(5-6):166-170.

13. Srinivasan M, Mascarenhas J, Rajaraman R, REFERENCES et al. The Steroids for Corneal Ulcers Trial 1. Whitcher JP, Srinivasan M, Upadhyay MP. (SCUT): secondary 12- month clinical Corneal blindness: A global perspective. outcomes of a randomized controlled trial. Bull World Health Organ. 2001;79(3):214- Am J Ophthalmol. 2014;157(2):327-333. 221. 14. Sharma N, Agarwal P, Sinha R, Titiyal JS, 2. Vaddavalli PK, Garg P, Sharma S, Sangwan Velpandian T, Vajpayee RB. Evaluation of VS, Rao GN, Thomas R. Role of Confocal intrastromal voriconazole injection in Microscopy in the Diagnosis of Fungal and recalcitrant deep fungal keratitis: Case Acanthamoeba. Ophthalmology. 2011; series. Br J Ophthalmol. 2011;95(12):1735- 118(1):29-35. 1737. 3. Sharma S, Garg P, Rao GN. Patient 15. Sharma N, Chacko J, Velpandian T, et al. characteristics, diagnosis, and treatment of Comparative evaluation of topical versus non-contact lens related Acanthamoeba intrastromal voriconazole as an adjunct to keratitis. Br J Ophthalmol. 2000;84(10): natamycin in recalcitrant fungal keratitis. 1103-1108. Ophthalmology. 2013;120(4):677-681. 4. Khor WB, Prajna VN, Garg P, et al. The 16. Aichelburg AC, Walochnik J, Assadian O, Asia Cornea Society Infectious Keratitis et al. Successful treatment of disseminated Study: A Prospective Multicenter Study of Acanthamoeba sp. infection with Infectious Keratitis in Asia. Am J miltefosine. Emerg Infect Dis. 2008;14(11): Ophthalmol. 2018;195:161-170. 1743-1746. 5. Al-Mujaini A, Al-Kharusi N, Thakral A, 17. Tuli S, Gray M. Surgical management of Wali UK. Bacterial keratitis: Perspective on corneal infections. Curr Opin Ophthalmol. epidemiology, Clinico-Pathogenesis, 2016;27(4):340-347.

International Journal of Health Sciences and Research (www.ijhsr.org) 77 Vol.10; Issue: 3; March 2020 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

18. De Craene S, Knoeri J, Georgeon C, 22. Isenberg SJ, Apt L, Valenton M, et al. Kestelyn P, Borderie VM. Assessment of Prospective, Randomized Clinical Trial of Confocal Microscopy for the Diagnosis of Povidone-Iodine 1.25% Solution Versus Polymerase Chain Reaction–Positive Topical Antibiotics for Treatment of Acanthamoeba Keratitis: A Case-Control Bacterial Keratitis. Am J Ophthalmol. 2017; Study. Ophthalmology. 2018;125(2):161- 176:244-253. 168. 23. Hafezi F, Bradley Randleman J. PACK- 19. Chen HJ, Pires RTF, Tseng SCG. Amniotic CXL: Defining CXL for infectious keratitis. membrane transplantation for severe J Refract Surg. 2014;30(7):438-439. neurotrophic corneal ulcers. Br J 24. Tabibian D, Mazzotta C, Hafezi F. PACK- Ophthalmol. 2000;84(8):826-833. CXL: Corneal cross-linking in infectious 20. Gao H, Song P, Echegaray JJ, et al. Big keratitis. Eye Vis. 2016;3(1):1-5. bubble deep anterior lamellar keratoplasty for management of deep fungal keratitis. J How to cite this article: Kenia VP, Kenia RV, Ophthalmol. 2014;2014(July 2011):1-9. Pirdankar OH. Diagnosis and management 21. Jamali H, Gholampour AR. Indications and protocol of acute corneal ulcer. Int J Health Sci Surgical Techniques for Corneal Res. 2020; 10(3):69-78. Transplantation at a Tertiary Referral Center. J Ophtha. 2019;14(2):125-130.

******

International Journal of Health Sciences and Research (www.ijhsr.org) 78 Vol.10; Issue: 3; March 2020